www.perpetualcommotion.com
"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
Corticobasal Ganglionic Degeneration (CBD,
CBGD)/ Corticobasal Syndrome (CBS)
-Notes, links and comments-
-Notes, links and comments-
I have nothing to sell you but hope, and that I give you for free.
[I am constantly in the process of summarizing and condensing information I dig up. I'm creating and maintaining these pages for my own use to keep track and try to make sense of all of this information. I make it all available to the entire world because someone might be helped by it.]It is important to keep in mind that "corticobasal syndrome" (CBS) is a set symptoms. The physical or medical cause of the symptoms can not be deterimined without a brain autopsy. (Perhaps new neuroimaging techniques or tests of the cerebral spinal fluid or blood tests will some day be able to make diagnosing the cause without a brain autopsy or biopsy possible.) Apparently, between 25 and 40% of clinically diagnosed CBS turns out to be due to Alzheimer's disease (AD) pathology. Therefore, it is reasonable to try treatments known or suspected to help AD victims.
See Ideas at the bottom of this page.
You should keep in mind that we really don't know how aware of their surroundings people with CBD are. While the disease strips people of the ability to move in a purposeful way and communicate, sufferers may very well be fully able to understand conversations around them. Some caregivers claim that they can still communicate with their loved ones even after they have fallen mute by way of subtle signs, such as blinking their eyes for "yes" or not blinking for "no". I remember tears pouring out of my mother's eyes in the movement disorders neurologist's office after he gave us the diagnosis, but she couldn't say anything. A good dramatization of what things might be like for them can be found in the 1990 movie Awakenings with Robert Di Nero and Robin Williams. In the movie, the patients were only periodically aware of their surroundings. But another physician who studied the victims of this certain encephalitis they all had many years earlier claimed that the disease had not spared their higher mental functions because "the alternative would be unthinkable." I fear that with CBD, we may just be facing the unthinkable: Active minds trapped in frozen bodies. Treat them with kindness and compassion, and remember that if they have an itch, they can't even scratch it.
While we're on the topic of movies, if you have ever seen the 1964 Peter Sellers movie "Dr. Strangelove or: How I Learned to Stop Worrying and Love the Bomb", you may recognize the physical afflictions of the Strangelove character as those of CBD, a disease that was not recognized until 1968.
Names for corticobasal degeneration:
CBGD: Corticobasal
Ganglionic Degeneration, an old name for CBD, still in common
use, but not so much in medicine.
CBD: Corticobasal Degeneration, a tentative diagnosis based on symptoms and imaging, but may also be reserved for postmortem diagnosis after a brain autopsy.
CBS: Corticobasal Syndrome, a diagnosis based on symptoms and imaging
CBS-AD: The diagnosis after brain autopsy that finds Alzhemer's disease pathology.
CBS-CBD: The diagnosis after brain autopsy that find "classic" CBD disease pathology.
Corticodentatonigral Degeneration with Neuronal Achromasia: As first described by Rebeiz et al (1968)
Rebeitz-Kolodny-Richardson Syndrome: An obsolete term for CBD.
Corticonigral degeneration: An obsolete term for CBD. Also, "corticonigral degeneration with nuclear achromasia"
CBD: Corticobasal Degeneration, a tentative diagnosis based on symptoms and imaging, but may also be reserved for postmortem diagnosis after a brain autopsy.
CBS: Corticobasal Syndrome, a diagnosis based on symptoms and imaging
CBS-AD: The diagnosis after brain autopsy that finds Alzhemer's disease pathology.
CBS-CBD: The diagnosis after brain autopsy that find "classic" CBD disease pathology.
Corticodentatonigral Degeneration with Neuronal Achromasia: As first described by Rebeiz et al (1968)
Rebeitz-Kolodny-Richardson Syndrome: An obsolete term for CBD.
Corticonigral degeneration: An obsolete term for CBD. Also, "corticonigral degeneration with nuclear achromasia"
CBS-AD vs. CBS-CBD:
There are two known causes of CBS
at the cellular level. In about 25% of the cases, the
pathology is very similar to Alzheimer's disease. Another
###% has CBD characteristics.
CBS Symptoms:
Note: Symptoms can have many
root causes. The presence of these symptoms does not mean
a person has CBS, but rather that the presence of the disease
should be entertained.
Parkinsonism (rigidity, slow
movements, postural instability):
Both motor and cognitive dysfunction
Asymmetry of symptoms (worse on one side of the body)
Cortical dysfunction
Problems with walking eventually occur in almost all
Family history of dementia or parkinsonism is rare (there are rare cases in whom a hereditary process may be at play)
Gradual progression (reported stepwise progression esp. after short seizure events)
Seizures (rare?)
Age of onset and survival time:
akinesia (difficulty initiating
and performing movements, and movements are reduced in speed
and size)
rigidity (muscle stiffness)
tremor
disequilibrium (unsteadiness, falling)
Dopaminergic medical therapy fails (Parkinson's disease medicine
are not effective)rigidity (muscle stiffness)
tremor
disequilibrium (unsteadiness, falling)
Both motor and cognitive dysfunction
Asymmetry of symptoms (worse on one side of the body)
Cortical dysfunction
apraxia (poor coordination of
the arms or legs)
"alien limb" phenomenon (tendency for the arm “to act as if it has a mind of its own”, e.g. Dr. Strangelove)
cortical sensory loss (numbness or odd sensations)
aphasia (poor comprehension and/or expression of language)
myoclonus (quick jerks) Stimulus sensitive (e.g. flicking the patients fingers)
. It frequently has a myoclonic (jerky) component. Stimulus sensitive myoclonus can be seen. The rigidity .
Basal ganglia dysfunction"alien limb" phenomenon (tendency for the arm “to act as if it has a mind of its own”, e.g. Dr. Strangelove)
cortical sensory loss (numbness or odd sensations)
aphasia (poor comprehension and/or expression of language)
myoclonus (quick jerks) Stimulus sensitive (e.g. flicking the patients fingers)
. It frequently has a myoclonic (jerky) component. Stimulus sensitive myoclonus can be seen. The rigidity .
bradykinesia (Slowness of
movement)
rigidity (stiffness in a limb, muscle stiffness) may be extreme and associated pain is common
dystonia (fixed muscle contractions, also including blepharospasm)
tremor (shaking) typically an action tremor that improves at rest
Memory impairment and/or personality/behavioral changes (some
patients)rigidity (stiffness in a limb, muscle stiffness) may be extreme and associated pain is common
dystonia (fixed muscle contractions, also including blepharospasm)
tremor (shaking) typically an action tremor that improves at rest
Problems with walking eventually occur in almost all
Family history of dementia or parkinsonism is rare (there are rare cases in whom a hereditary process may be at play)
Gradual progression (reported stepwise progression esp. after short seizure events)
Seizures (rare?)
Age of onset and survival time:
Begins from 50 – 70 years of age,
but has been diagnosed in patients under 40.
Duration of illness from onset of symptoms to death has ranged from 3-13 years, typically 8 years
Duration of illness from onset of symptoms to death has ranged from 3-13 years, typically 8 years
Pathology:
characterized by an asymmetric
frontoparietal neuronal loss
gliosis with ballooned, achromatic cortical neurons
nigral degeneration
variable subcortical involvement
Lewy bodys and neurofibrillary tangles are absent
Neuropathological Features of CBD
Gross findings
Positive immunoreactivity of swollen, achromatic cortical neurons and axons with antibodies to phosphorylated neurofilaments
Positive immunoreactivity of subcortical and cortical neurons with antibodies to tau (corticobasal bodies; globose neurofibrillary
tangles)
Positive immunoreactivity of clusters of astrocytic processes in cortex with antibodies to tau (astrocytic plaques)
Negative immunoreactivity of swollen, achromatic neurons with antibodies to [alpha]-synuclein
Insight and memory tends to be preserved throughout most of the illness
Depression is common
gliosis with ballooned, achromatic cortical neurons
nigral degeneration
variable subcortical involvement
Lewy bodys and neurofibrillary tangles are absent
Neuropathological Features of CBD
Gross findings
Superior frontoparietal and
perirolandic cerebral cortical atrophy—asymmetric
Enlargement of lateral ventricles—asymmetric
Reduction of cerebral white matter, internal capsules, and cerebral peduncles—asymmetric
Thinning of corpus callosum
Pallor of substantia nigra
Microscopic findingsEnlargement of lateral ventricles—asymmetric
Reduction of cerebral white matter, internal capsules, and cerebral peduncles—asymmetric
Thinning of corpus callosum
Pallor of substantia nigra
Neuronal loss, gliosis and
swollen, ballooned achromatic neurons in cerebral
cortex—especially frontoparietal
Disorganization of laminar pattern of cerebral cortex in regions of heavy neuronal loss
Abnormal cerebral white matter—swollen axons, demyelination of axons, spongiform appearance of neuropil in regions of heavy
neuronal loss
Pigmented neuron loss and gliosis in substantia nigra
Variable neuronal loss and gliosis in subthalamic nucleus, globus pallidus, corpus striatum, red nucleus, claustrum, thalamus,
dentate and cerebellar roof nuclei, and scattered brain stem nuclei
Immunocytochemical findingsDisorganization of laminar pattern of cerebral cortex in regions of heavy neuronal loss
Abnormal cerebral white matter—swollen axons, demyelination of axons, spongiform appearance of neuropil in regions of heavy
neuronal loss
Pigmented neuron loss and gliosis in substantia nigra
Variable neuronal loss and gliosis in subthalamic nucleus, globus pallidus, corpus striatum, red nucleus, claustrum, thalamus,
dentate and cerebellar roof nuclei, and scattered brain stem nuclei
Positive immunoreactivity of swollen, achromatic cortical neurons and axons with antibodies to phosphorylated neurofilaments
Positive immunoreactivity of subcortical and cortical neurons with antibodies to tau (corticobasal bodies; globose neurofibrillary
tangles)
Positive immunoreactivity of clusters of astrocytic processes in cortex with antibodies to tau (astrocytic plaques)
Negative immunoreactivity of swollen, achromatic neurons with antibodies to [alpha]-synuclein
Insight and memory tends to be preserved throughout most of the illness
Depression is common
Neuroradiological imaging
characteristics:
Brain atrophy (shrinkage)
frontal and parietal cerebral
cortex
brainstem particularly substantia nigra
Cortical (outer layer of the brain)
atrophy greater for CBD than ADbrainstem particularly substantia nigra
fronto-parietal regions (located
near the center-top of the head)
Electrophysiological studies
EEG (electroencephalogram) may
show changes in brain function over time that are consistent
with the neurodegeneration
Differential diagnosis between CBD and PSP:
tau deposits (lesions) in brain
cells called "astrocytes"
CBD: deposit at the end of the
processes of the cells forming “astrocytique plaques”
PSP: deposit throughout the whole astrocyte forming “tufted astrocytes.”
type of tau proteins that aggregate in CBD are similar to those that aggregate in PSP, and both have the same genetic abnormalitiy (H1 Haplotype)
PSP: deposit throughout the whole astrocyte forming “tufted astrocytes.”
type of tau proteins that aggregate in CBD are similar to those that aggregate in PSP, and both have the same genetic abnormalitiy (H1 Haplotype)
Summaries:
Wikipedia entry:
Corticobasal degeneration (CBD) or
Corticobasal Ganglionic Degeneration (CBGD) is a rare
progressive neurodegenerative disease involving the cerebral
cortex and the basal ganglia.[1] It is characterized by marked
disorders in movement and cognitive dysfunction. Clinical
diagnosis is difficult, as symptoms of CBD are often similar to
those of other diseases, such as Parkinson's disease (PD) and
progressive supranuclear palsy (PSP). Furthermore, a definitive
diagnosis of CBD is only possible after death, as the only
absolute determinant of the disease requires the application of
neuropathology and histopathology...
http://en.wikipedia.org/wiki/Corticobasal_degeneration
http://en.wikipedia.org/wiki/Corticobasal_degeneration
Here's one of the best summaries I've come across:
Corticobasal Degeneration
Natividad P. Stover, M.D. and Ray L. Watts, M.D.
SEMINARS IN NEUROLOGY/VOLUME 21, NUMBER 1 2001
Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.
Natividad P. Stover, M.D. and Ray L. Watts, M.D.
SEMINARS IN NEUROLOGY/VOLUME 21, NUMBER 1 2001
Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.
Neuropathological
Features of CBD
Gross findings
Gross findings
Superior frontoparietal and
perirolandic cerebral cortical atrophy—asymmetric
Enlargement of lateral ventricles—asymmetric
Reduction of cerebral white matter, internal capsules, and cerebral peduncles—asymmetric
Thinning of corpus callosum
Pallor of substantia nigra
Microscopic findingsEnlargement of lateral ventricles—asymmetric
Reduction of cerebral white matter, internal capsules, and cerebral peduncles—asymmetric
Thinning of corpus callosum
Pallor of substantia nigra
Neuronal loss, gliosis and
swollen, ballooned achromatic neurons in cerebral
cortex—especially frontoparietal
Disorganization of laminar pattern of cerebral cortex in regions of heavy neuronal loss
Abnormal cerebral white matter—swollen axons, demyelination of axons, spongiform appearance of neuropil in regions of heavy
neuronal loss
Pigmented neuron loss and gliosis in substantia nigra
Variable neuronal loss and gliosis in subthalamic nucleus, globus pallidus, corpus striatum, red nucleus, claustrum, thalamus,
dentate and cerebellar roof nuclei, and scattered brain stem nuclei
Immunocytochemical findingsDisorganization of laminar pattern of cerebral cortex in regions of heavy neuronal loss
Abnormal cerebral white matter—swollen axons, demyelination of axons, spongiform appearance of neuropil in regions of heavy
neuronal loss
Pigmented neuron loss and gliosis in substantia nigra
Variable neuronal loss and gliosis in subthalamic nucleus, globus pallidus, corpus striatum, red nucleus, claustrum, thalamus,
dentate and cerebellar roof nuclei, and scattered brain stem nuclei
Positive immunoreactivity of
swollen, achromatic cortical neurons and axons with antibodies
to phosphorylated neurofilaments
Positive immunoreactivity of subcortical and cortical neurons with antibodies to tau (corticobasal bodies; globose neurofibrillary
tangles)
Positive immunoreactivity of clusters of astrocytic processes in cortex with antibodies to tau (astrocytic plaques)
Negative immunoreactivity of swollen, achromatic neurons with antibodies to [alpha]-synuclein
Positive immunoreactivity of subcortical and cortical neurons with antibodies to tau (corticobasal bodies; globose neurofibrillary
tangles)
Positive immunoreactivity of clusters of astrocytic processes in cortex with antibodies to tau (astrocytic plaques)
Negative immunoreactivity of swollen, achromatic neurons with antibodies to [alpha]-synuclein
Causes
The cause of CBD is unknown.
Several factors probably contribute to its development,
including genetics, environmental exposures, toxins and
accumulation of products of oxidative injury.
The brains of patients with CBD show cell loss and shrinkage (atrophy) in certain brain areas (frontal and parietal cerebral cortex and brainstem particularly substantia nigra). CBD is considered to be a “tauopathy” because in the affected cells of those with this disease there are clumps (aggregates) of tau, a protein normally found in cells (Figure 4) . There are differences in how the tau deposits in one type of brain cells called astrocytes in CBD and PSP. While in CBD they deposit at the end of the processes of the cells forming “astrocytique plaques”, in PSP they deposit throughout the whole astrocyte forming what is called “tufted astrocytes.” The presence of one or the other type of lesions helps making the diagnosis of these disorders.
The type of tau proteins that aggregate in CBD are similar to those that aggregate in PSP, and both have the same genetic abnormalitiy (H1 Haplotype), which is also found in less percentage in the general population, making some investigators suspect that CBD and PSP may be different forms of the same disease. However, this issue is still controversial.
http://www.litvanfoundation.com/index.php?option=com_content&task=view&id=23&Itemid=163
The brains of patients with CBD show cell loss and shrinkage (atrophy) in certain brain areas (frontal and parietal cerebral cortex and brainstem particularly substantia nigra). CBD is considered to be a “tauopathy” because in the affected cells of those with this disease there are clumps (aggregates) of tau, a protein normally found in cells (Figure 4) . There are differences in how the tau deposits in one type of brain cells called astrocytes in CBD and PSP. While in CBD they deposit at the end of the processes of the cells forming “astrocytique plaques”, in PSP they deposit throughout the whole astrocyte forming what is called “tufted astrocytes.” The presence of one or the other type of lesions helps making the diagnosis of these disorders.
The type of tau proteins that aggregate in CBD are similar to those that aggregate in PSP, and both have the same genetic abnormalitiy (H1 Haplotype), which is also found in less percentage in the general population, making some investigators suspect that CBD and PSP may be different forms of the same disease. However, this issue is still controversial.
http://www.litvanfoundation.com/index.php?option=com_content&task=view&id=23&Itemid=163
Here is a brief description of corticobasal ganglionic degeneration (CBGD):
"Corticobasal
degeneration
(CBD), also known as corticobasal ganglionic degeneration
(CBGD), was first described in the late 1960’s by Drs. Rebeiz,
Kolodny, and Richardson. Following a lengthy period with no
additional reports, several more patients were identified and
their symptoms and autopsy findings were described in the
1980’s and 1990’s. Patients typically have symptoms reflecting
dysfunction in the cerebral cortex (thus the term “cortical”
or “cortico-”) and basal ganglia (thus the terms “basal” or
“basal ganglionic”), and symptoms are usually worse on one
side of the body. Specifically, cortical dysfunction is
manifested as poor coordination of the arms or legs (apraxia),
tendency for the arm “to act as if it has a mind of its own”
(alien limb phenomenon), numbness or odd sensations (cortical
sensory loss), poor comprehension and/or expression of
language (aphasia), and quick jerks (myoclonus). Slowness of
movement (bradykinesia), stiffness in a limb (rigidity), fixed
muscle contractions such as when the fingers curl into a fist
(dystonia), and tremor are presumed to reflect basal ganglia
dysfunction. Some patients develop memory impairment and/or
personality/behavioral changes. Problems with walking
eventually occur in almost all. In our studies the duration of
illness from onset of symptoms to death has ranged from 3-13
years. The vast majority of patients do not appear to have any
family history of dementia or parkinsonism, although there are
rare cases in whom a hereditary process may be at play. The
cause of CBD is not yet known.
"This illness is frustrating to patients, their families, and the physicians who care for them. Since insight and memory tends to be preserved throughout most of their illness, depression is common and should be treated when it evolves. Physical, occupational, and speech therapy can be helpful although as the illness progresses third party payers tend to not reimburse for these services, unfortunately. Medications provide little benefit, but agents such as Sinemet are worth trying. All sleep disorders such as sleep apnea and restless legs syndrome should be evaluated and treated as improvement in quality of life for patients and their loved ones can occur."
http://www.tornadodesign.com/cbgd/boeve_updateoncbgd.htm
"This illness is frustrating to patients, their families, and the physicians who care for them. Since insight and memory tends to be preserved throughout most of their illness, depression is common and should be treated when it evolves. Physical, occupational, and speech therapy can be helpful although as the illness progresses third party payers tend to not reimburse for these services, unfortunately. Medications provide little benefit, but agents such as Sinemet are worth trying. All sleep disorders such as sleep apnea and restless legs syndrome should be evaluated and treated as improvement in quality of life for patients and their loved ones can occur."
http://www.tornadodesign.com/cbgd/boeve_updateoncbgd.htm
Corticobasal Degeneration:
Evaluation of Cortical Atrophy by Means of Hemispheric
Surface Display Generated with MR Images
"RESULTS: The extent and magnitude of cortical atrophy were larger in the group with corticobasal degeneration than in the group with Alzheimer disease. The parasagittal and paracentral regions were significantly more atrophic in patients with corticobasal degeneration than in patients with Alzheimer disease (P < .05). The mean hemispheric-to-total intracranial volume ratios were significantly smaller in the patients with corticobasal degeneration (61%) and those with Alzheimer disease (64%) than in control subjects (69%). Asymmetry of hemispheric volume was significantly larger in the group with corticobasal degeneration than in the control group.
"CONCLUSION: The extent of cortical atrophy in corticobasal degeneration is more widespread than was previously thought. Parasagittal and paracentral atrophy is a distinctive feature of corticobasal degeneration and distinguishes it from Alzheimer disease."
http://radiology.rsnajnls.org/cgi/content/full/216/1/31
"RESULTS: The extent and magnitude of cortical atrophy were larger in the group with corticobasal degeneration than in the group with Alzheimer disease. The parasagittal and paracentral regions were significantly more atrophic in patients with corticobasal degeneration than in patients with Alzheimer disease (P < .05). The mean hemispheric-to-total intracranial volume ratios were significantly smaller in the patients with corticobasal degeneration (61%) and those with Alzheimer disease (64%) than in control subjects (69%). Asymmetry of hemispheric volume was significantly larger in the group with corticobasal degeneration than in the control group.
"CONCLUSION: The extent of cortical atrophy in corticobasal degeneration is more widespread than was previously thought. Parasagittal and paracentral atrophy is a distinctive feature of corticobasal degeneration and distinguishes it from Alzheimer disease."
http://radiology.rsnajnls.org/cgi/content/full/216/1/31
Corticobasal Degeneration
Information for Patients and Caregivers
"Corticobasal degeneration (CBD) is a rare neurological disease in which parts of the brain deteriorate or degenerate. CBD is also known as corticobasal ganglionic degeneration, or CBGD...
Several regions of the brain degenerate in CBD. The cortex, or outer layer of the brain, is severely affected, especially the fronto-parietal regions, located near the center-top of the head. Other, deeper brain regions are also affected, including parts of the basal ganglia, hence the name "corticobasal" degeneration. The combined loss of brain tissue in all these areas causes the symptoms and findings seen in people with CBD."
http://www.wemove.org/cbd/
"Corticobasal degeneration (CBD) is a rare neurological disease in which parts of the brain deteriorate or degenerate. CBD is also known as corticobasal ganglionic degeneration, or CBGD...
Several regions of the brain degenerate in CBD. The cortex, or outer layer of the brain, is severely affected, especially the fronto-parietal regions, located near the center-top of the head. Other, deeper brain regions are also affected, including parts of the basal ganglia, hence the name "corticobasal" degeneration. The combined loss of brain tissue in all these areas causes the symptoms and findings seen in people with CBD."
http://www.wemove.org/cbd/
NINDS Corticobasal Degeneration
Information Page
"Corticobasal degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia. Corticobasal degeneration progresses gradually."
"There is no treatment available to slow the course of corticobasal degeneration, and the symptoms of the disease are generally resistant to therapy."
http://www.ninds.nih.gov/disorders/corticobasal_degeneration/corticobasal_degeneration.htm
"Corticobasal degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia. Corticobasal degeneration progresses gradually."
"There is no treatment available to slow the course of corticobasal degeneration, and the symptoms of the disease are generally resistant to therapy."
http://www.ninds.nih.gov/disorders/corticobasal_degeneration/corticobasal_degeneration.htm
[Perhaps there are treatments to slow the progression. See Ideas at the bottom of this page.]
Parkinson's & Parkinson's
Plus Disorders
[lots of links]
http://www.geocities.com/murraycharters/002.html
[lots of links]
http://www.geocities.com/murraycharters/002.html
Cortical Basal Ganglionic
Degeneration
"Cortical basal ganglionic degeneration (CBGD) may be considered a syndrome rather than a disease. Its defining clinical characteristics (ie, progressive dementia, parkinsonism, limb apraxia) may occur as a result of heterogenous neuropathological conditions such as Pick complex disorders (see Pick Disease), Alzheimer disease, and even rare disorders such as CNS Whipple disease and Niemann-Pick type C. Histopathologically identifiable CBGD can also present clinically as primary progressive aphasia or primary progressive apraxia in patients who had no prominent movement disorders earlier in their lives."
http://www.emedicine.com/neuro/topic77.htm
"Cortical basal ganglionic degeneration (CBGD) may be considered a syndrome rather than a disease. Its defining clinical characteristics (ie, progressive dementia, parkinsonism, limb apraxia) may occur as a result of heterogenous neuropathological conditions such as Pick complex disorders (see Pick Disease), Alzheimer disease, and even rare disorders such as CNS Whipple disease and Niemann-Pick type C. Histopathologically identifiable CBGD can also present clinically as primary progressive aphasia or primary progressive apraxia in patients who had no prominent movement disorders earlier in their lives."
http://www.emedicine.com/neuro/topic77.htm
Corticobasal Degeneration
"Corticobasal degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia."
http://healthlink.mcw.edu/article/921395030.html
"Corticobasal degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia."
http://healthlink.mcw.edu/article/921395030.html
CORTICOBASAL DEGENERATION (CBD)
Corticobasal degeneration, sometimes referred to as corticobasal ganglionic degeneration (CBGD), is a heterogeneous disease which clinically, genetically and pathologically is similar to, or overlaps with frontotemporal dementia (FTD). For this reason, CBD is considered to be part of the ‘Pick complex’ of neurodegenerative diseases"
http://memory.ucsf.edu/Education/Disease/cbd.html
Corticobasal degeneration, sometimes referred to as corticobasal ganglionic degeneration (CBGD), is a heterogeneous disease which clinically, genetically and pathologically is similar to, or overlaps with frontotemporal dementia (FTD). For this reason, CBD is considered to be part of the ‘Pick complex’ of neurodegenerative diseases"
http://memory.ucsf.edu/Education/Disease/cbd.html
Corticobasal Degeneration
"Corticobasal degeneration (CBD) is a neurodegenerative disease that was first described by Rebeiz et al., who referred to the disorder as "corticodentatonigral degeneration with neuronal achromasia." Other terms for this disease include corticonigral degeneration and cortical-basal ganglionic degeneration"
http://www.treatment-options.com/article.cfm?PubID=NE05-2-2-03&Type=Article&KeyWords=
"Corticobasal degeneration (CBD) is a neurodegenerative disease that was first described by Rebeiz et al., who referred to the disorder as "corticodentatonigral degeneration with neuronal achromasia." Other terms for this disease include corticonigral degeneration and cortical-basal ganglionic degeneration"
http://www.treatment-options.com/article.cfm?PubID=NE05-2-2-03&Type=Article&KeyWords=
The Association for Frontotemporal Dementias
Corticobasal Degeneration
Overview
"Corticobasal Degeneration (CBD) is a progressive neurological disorder that presents primarily as a movement disorder, characterized by lack of movement and muscle rigidity. Initial symptoms, which typically begin at or around age 60, may first appear on one side of the body (unilateral), but eventually affect both sides as the disease progresses. A patient with CBD may first present with language disorder, and develop the motor symptoms over time..."
http://www.ftd-picks.org/?p=diseases/corticobasaldegeneration
Corticobasal Degeneration
Overview
"Corticobasal Degeneration (CBD) is a progressive neurological disorder that presents primarily as a movement disorder, characterized by lack of movement and muscle rigidity. Initial symptoms, which typically begin at or around age 60, may first appear on one side of the body (unilateral), but eventually affect both sides as the disease progresses. A patient with CBD may first present with language disorder, and develop the motor symptoms over time..."
http://www.ftd-picks.org/?p=diseases/corticobasaldegeneration
Many researchers believe that CBD is closely related to another neurodegenerative disease called Progressive Supranuclear Palsy (PSP). Here is a good article about PSP that might contain research and ideas applicable to CBD:
Rational therapeutic
approaches to progressive supranuclear palsy
Brain 2010: 133; 1578–1590
http://brain.oxfordjournals.org/content/133/6/1578.full.pdf+html
Brain 2010: 133; 1578–1590
http://brain.oxfordjournals.org/content/133/6/1578.full.pdf+html
NINDS Corticobasal Degeneration Information Page
What is Corticobasal Degeneration?
Corticobasal degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia. Corticobasal degeneration progresses gradually. Initial symptoms, which typically begin at or around age 60, may first appear on one side of the body (unilateral), but eventually affect both sides as the disease progresses. Symptoms are similar to those found in Parkinson disease, such as poor coordination, akinesia (an absence of movements), rigidity (a resistance to imposed movement), disequilibrium (impaired balance); and limb dystonia (abnormal muscle postures). Other symptoms such as cognitive and visual-spatial impairments, apraxia (loss of the ability to make familiar, purposeful movements), hesitant and halting speech, myoclonus (muscular jerks), and dysphagia (difficulty swallowing) may also occur. An individual with corticobasal degeneration eventually becomes unable to walk.
Is there any treatment?
There is no treatment available to slow the course of corticobasal degeneration [there are new ideas that haven't been tried yet -ed.], and the symptoms of the disease are generally resistant to therapy. Drugs used to treat Parkinson disease-type symptoms do not produce any significant or sustained improvement. Clonazepam may help the myoclonus. Occupational, physical, and speech therapy can help in managing disability.
What is the prognosis?
Corticobasal degeneration usually progresses slowly over the course of 6 to 8 years. Death is generally caused by pneumonia or other complications of severe debility such as sepsis or pulmonary embolism.
What research is being done?
The NINDS supports and conducts research studies on degenerative disorders such as corticobasal degeneration. The goals of these studies are to increase scientific understanding of these disorders and to find ways to prevent, treat, and cure them.
NIH Patient Recruitment for Corticobasal Degeneration Clinical Trials
At NIH Clinical Center
Throughout the U.S. and Worldwide
Organizations
National Organization for Rare Disorders (NORD)
P.O. Box 1968
(55 Kenosia Avenue)
Danbury, CT 06813-1968
orphan@rarediseases.org
http://www.rarediseases.org
Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
Fax: 203-798-2291
WE MOVE (Worldwide Education & Awareness for Movement Disorders)
204 West 84th Street
New York, NY 10024
wemove@wemove.org
http://www.wemove.org
Tel: 212-875-8312
Fax: 212-875-8389
CUREPSP (Foundation for PSP|CBD and Related Brain Diseases)
Executive Plaza III
11350 McCormick Road, Ste. 906
Hunt Valley, MD 21031
info@curepsp.org
http://www.curepsp.org
Tel: 410-785-7004 800-457-4777
Fax: 410-785-7009
http://www.ninds.nih.gov/disorders/corticobasal_degeneration/corticobasal_degeneration.htm
Corticobasal degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia. Corticobasal degeneration progresses gradually. Initial symptoms, which typically begin at or around age 60, may first appear on one side of the body (unilateral), but eventually affect both sides as the disease progresses. Symptoms are similar to those found in Parkinson disease, such as poor coordination, akinesia (an absence of movements), rigidity (a resistance to imposed movement), disequilibrium (impaired balance); and limb dystonia (abnormal muscle postures). Other symptoms such as cognitive and visual-spatial impairments, apraxia (loss of the ability to make familiar, purposeful movements), hesitant and halting speech, myoclonus (muscular jerks), and dysphagia (difficulty swallowing) may also occur. An individual with corticobasal degeneration eventually becomes unable to walk.
Is there any treatment?
There is no treatment available to slow the course of corticobasal degeneration [there are new ideas that haven't been tried yet -ed.], and the symptoms of the disease are generally resistant to therapy. Drugs used to treat Parkinson disease-type symptoms do not produce any significant or sustained improvement. Clonazepam may help the myoclonus. Occupational, physical, and speech therapy can help in managing disability.
What is the prognosis?
Corticobasal degeneration usually progresses slowly over the course of 6 to 8 years. Death is generally caused by pneumonia or other complications of severe debility such as sepsis or pulmonary embolism.
What research is being done?
The NINDS supports and conducts research studies on degenerative disorders such as corticobasal degeneration. The goals of these studies are to increase scientific understanding of these disorders and to find ways to prevent, treat, and cure them.
NIH Patient Recruitment for Corticobasal Degeneration Clinical Trials
At NIH Clinical Center
Throughout the U.S. and Worldwide
Organizations
National Organization for Rare Disorders (NORD)
P.O. Box 1968
(55 Kenosia Avenue)
Danbury, CT 06813-1968
orphan@rarediseases.org
http://www.rarediseases.org
Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
Fax: 203-798-2291
WE MOVE (Worldwide Education & Awareness for Movement Disorders)
204 West 84th Street
New York, NY 10024
wemove@wemove.org
http://www.wemove.org
Tel: 212-875-8312
Fax: 212-875-8389
CUREPSP (Foundation for PSP|CBD and Related Brain Diseases)
Executive Plaza III
11350 McCormick Road, Ste. 906
Hunt Valley, MD 21031
info@curepsp.org
http://www.curepsp.org
Tel: 410-785-7004 800-457-4777
Fax: 410-785-7009
http://www.ninds.nih.gov/disorders/corticobasal_degeneration/corticobasal_degeneration.htm
Corticobasal degeneration,
sometimes referred to as corticobasal ganglionic degeneration
(CBGD), is a heterogeneous disease which clinically, genetically
and pathologically is similar to, or overlaps with
frontotemporal dementia (FTD). For this reason, CBD is
considered to be part of the ‘Pick complex’ of neurodegenerative
diseases (see FTD description).
CBD was first described in 1968 by Rebeiz and colleagues, who immediately recognized its potential relationship to FTD based on macroscopic and microscopic analyses of CBD brains. Historically, CBD patients have been diagnosed on the basis of movement problems which sometimes appear similar to Parkinson’’s disease (PD). Unlike PD, however, CBD patients typically do not respond significantly to PD medicines, such as levodopa/carbidopa (Sinemet). Also, many symptoms of CBD are not found in PD patients. For this reason CBD is often referred to as a ‘Parkinson’s-plus’ syndrome.
When a diagnosis of CBD is suspected, it is important to refer the patient to a neurologist who is experienced with this disorder. This is because the constellation of symptoms and problems experienced by affected individuals and their caregivers is unique. There have been significant advances in the understanding of CBD over the past 10 years, and as a result, improved counseling, support and symptomatic treatments are now available. We are actively involved in research to better understand the pathophysiology of CBD.
Demographics
CBD typically occurs in patients between 45 and 70. In our experience, women are affected more commonly than men. Rarely, there is a family history of dementia, psychiatric problems or a movement disorder.
Symptoms
Patients with CBD present with either a movement disorder or cognitive deficits. As the disease progresses, most patients will eventually develop both types of symptoms, often with a delay of 2-3 years.
Movement
A characteristic feature of movement symptoms in CBD is striking asymmetry of involvement. Most frequently symptoms begin insidiously in one hand or arm, less commonly in one leg. Rarely, symptoms may involve the mouth and facial muscles.
Many patients will complain initially of a subtle change in sensation or an inability to make the affected limb follow commands. This latter deficit is called apraxia and may be confused for clumsiness or weakness. There may be difficulties in completing specific tasks, such as opening a door or brushing one’s teeth or using tools, such as a can opener. When a leg is affected initially, a patient may have problems with complex movements such as dancing; or when more severe, a patient may begin to trip and fall. Some patients will experience an involuntary stiffening, twisting or contraction of the affected limb called dystonia. There may be uncontrolled jumping of the limb when it is tapped gently or when the patient is startled, called myoclonus.
Finally, CBD patients often complain that the affected limb feels like it is not a part of their body, a sensation called alien limb. Sometimes an alien limb will move on its own, in an uncontrollable way. For example, an alien hand will rise to touch the patient’s face. Alien limb phenomenon was dramatized by the actor Peter Sellers in the film Dr. Strangelove.
Movement symptoms tend to progress slowly from one side of the body to the other or from leg to arm on the same side of the body.
Cognition
Patients with CBD who present with cognitive difficulties are usually initially diagnosed with frontotemporal dementia or Alzheimer's disease. It is only after they develop movement symptoms that the diagnosis of CBD is entertained. Occasionally, a diagnosis of CBD is not apparent until a patient’s brain is examined at autopsy.
Progressive difficulty with language is a common cognitive complaint in CBD. This most commonly involves difficulty with expression of language, such as word finding difficulty or naming problems. Reading, writing and simple mathematical calculations may also be impaired.
Personality changes, inappropriate behavior, repetitive and/or compulsive activities similar to those seen in FTD (see FTD description) are also common in CBD. Short-term memory problems, such as repeating questions or misplacing objects are also common.
Many patients with the movement difficulties of CBD will also have mild cognitive problems when they are evaluated in a specialized dementia clinic.
Treatment
At this time, there is no specific treatment for CBD. Instead individual symptoms are targeted with specific medications. For example, rigidity and difficulty walking may partially respond to treatments for Parkinson’s disease. Dystonia and myoclonus may respond to muscle relaxants or anti-seizure medications. Memory and behavior problems may respond to treatments for Alzheimer's disease and/or depression.
http://memory.ucsf.edu/Education/Disease/cbd.html
Cortico-basal ganglionic degeneration (CBGD) is a complex neurobehavioural disorder characterised by insidious onset and gradually progressive cerebrocortical and extrapyramidal dysfunction.
A 52 years old male presented in May 1998 with behavioural abnormalities since November 1996 and abnormal movements since June 1997. Initially the patient had difficulty in dressing himself. Soon afterwards he had difficulty in finding his way while inside the house. Sometimes he spent the whole night outside the house, to be discovered next morning by his family members in the nearby field. In April 1997 he also developed speech abnormality. His speech gradually became incomprehensible and he would laugh or cry without any reason. He also became forgetful. He developed twisting movements of right sided fingers, wrist and forearm and neck and lower limbs. He also developed parkinsonian features and was unable to perform activities of daily living on his own. There was no history of myoclonus, seizures, motor weakness, sensory or bladder and bowel symptoms.
On examination he was restless, laughing or crying without reasons. He could follow some verbal commands but could not do so when written commands were provided. He could neither utter a comprehensible word nor write a legible letter. His cranial nerves were normal. Examination of motor system was normal except the presence of akinesia, rigidity and dystonic posturing of limbs. These were more profound on the right side. There was no tremor or ataxia. His deep tendon reflexes as well as the plantars were normal. There was gross postural instability. The rigidity and akinesia did not respond to levodopa.
Investigations revealed normal haemogram, blood glucose, renal function and liver function tests. Serum calcium, phosphorous and alkaline phosphatase were 9.6 mg/dl,3.5 mg/dl and 11KAU/L, respectively. The serum copper was 90 mgm/dl and ceruloplasmin was 30 mg/dl. Serum VDRL was nonreactive and ELISA for HIV 1 and 2 were negative. CSF examination revealed a protein content of 20 mg/dl and sugar of 68 mg/dl and was acellular. The T2 weighted images on MRI [Figure. 1] showed prominent sylvian cisterns and prominence of cortical sulci particularly in frontal and both parietal lobes, suggesting symmetrical atrophy of frontal and parietal lobes. There was no KF ring on eye examination.
The typical features of CBGD can be categorised into movement disorders (akinesia, rigidity, postural instability, limb dystonia, cortical myoclonus and postural/intention tremor) and cortical signs, such as cortical sensory loss, apraxias and the 'alien limb' phenomenon.[1],[2] The most striking features of CBGD is asymmetry of involvement which differentiates it from most other neurodegenerative disorders. Rinne et al[2] reviewed 36 patients, with mean age at onset of 60.9+9.7 years. (range : 40-76 years). In the patients reported by Riley et al, the mean age at onset was 60 years (range: 51-71 years) and men were more commonly affected than women. Riley et al[1] reported apraxia in 71% of cases of CBGD. Although they found ideational and ideomotor apraxias to occur early and were sometimes the presenting symptoms, a variety of other apraxias have also been reported in CBGD. Alien limb phenomenon is an unusual sign in neurology and its presence, in the absence of a known callosal lesion, is highly suggestive of the diagnosis of CBGD. Speech abnormalities and aphasia has been reported to occur in 21% of patients with CBGD and are considered to reflect left hemisphere cortical pathology in this disorder.[1] Involvement of right parietal cortex in CBGD gives rise to visuospatial and constructional disturbances. Personality change, impaired attention, acalculia, impaired recall and learning, concrete thinking and left-right confusion have been noted in a number of patients. Oculomotility disturbances particularly manifested by impaired convergence and vertical and horizontal gaze palsy has been noted in CBGD. This feature sometime confuse CBGD with progressive supranuclear palsy (PSP). Dementia is a late feature of CBGD and was found in 43% of patients by Riley et al.[1] The full spectrum of clinical features typically seen in CBGD can also be present in patients with Pick's disease, but the latter disorder is usually dominated by cognitive, behavioural, and language disturbances such as primary progressive aphasia. Moreover, apraxia and parkinsonism, if present, are usually late finding in Pick's disease. Pathological features in CBGD include neuronal degeneration in pre-and post-central cortical areas, degeneration of basal ganglia, including substantia nigra (SN), and presence of achromatic neural inclusion seen not only in the cortex but also in the thalamus, subthalamus nucleus, red nucleus, and SN.[4] CT scans were abnormal in 14 of the 15 patients in one series, 8 had asymmetrical parietal lobe atrophy corresponding to the most affected side, and 6 had bilateral parietal atrophy.[1] PET scans shows reduced 18(F) fluorodopa uptake in the caudate and putamen, and markedly asymmetrical cortical hypometabolism in the superior temporal and inferior parietal lobe.[5]
Our patient presented with dressing and situational apraxias as the initial symptoms. Gradually, he developed abnormalities of speech, emotional lability, loss of social inhibition etc., the features of diffuse cortical dysfunction. These features were combined with asymmetric involvement of right side with extrapyramidal features like limb dystonia, akinesia, rigidity and postural instability. Our patients did not have 'alien limb' phenomenon which is a very interesting features of CBGD. However, its absence does not exclude the diagnosis, as it was observed only in 50% of patients by Riley et al.[1] The presence of features of cortical dysfunction in the early phase of illness compounded by extrapyramidal features and the absence of oculomotility disturbances and ataxia, clearly suggest the diagnosis of CBGD in our patients. These clinical findings were corroborated by symmetrical atrophy of frontal and parietal lobes in neuroimaging studies.
1. Riley DE, Lang AE, Lewis A et al : Cortico-basal ganglionic degeneration. Neurology 1990; 40 : 1203-1212.
2. Rinne JO, Lee MS, Thompson PD et al : Cortico-basal degeneration: a clinical study of 36 cases. Brain 1994; 117 : 1183-1196.
3. Bogen JE : Split-brain syndrome. In: Handbook of clinical neurology. Vol. 1(45): Clinical Neuropsychology. Friederiks JAM, Ed. Amsterdam: Elselvier. 1985; 99-106.
4. Lippa CF, Cohen R, Smith TW et al : Primary progressive aphasia with focal neuronal achromasia. Neurology1991; 42 : 882-886.
5. Eidelberg D, Dhawan V, Moller JR et al : The metabolic landscape of cortico-basal ganglionic degeneration, regional asymmetries studies with positron emission tomography. J Neurol Neurosurg Psychiatry 1991; 54 : 856-862.
http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2000;volume=48;issue=4;spage=405;epage=6;aulast=Anand
CBD was first described in 1968 by Rebeiz and colleagues, who immediately recognized its potential relationship to FTD based on macroscopic and microscopic analyses of CBD brains. Historically, CBD patients have been diagnosed on the basis of movement problems which sometimes appear similar to Parkinson’’s disease (PD). Unlike PD, however, CBD patients typically do not respond significantly to PD medicines, such as levodopa/carbidopa (Sinemet). Also, many symptoms of CBD are not found in PD patients. For this reason CBD is often referred to as a ‘Parkinson’s-plus’ syndrome.
When a diagnosis of CBD is suspected, it is important to refer the patient to a neurologist who is experienced with this disorder. This is because the constellation of symptoms and problems experienced by affected individuals and their caregivers is unique. There have been significant advances in the understanding of CBD over the past 10 years, and as a result, improved counseling, support and symptomatic treatments are now available. We are actively involved in research to better understand the pathophysiology of CBD.
Demographics
CBD typically occurs in patients between 45 and 70. In our experience, women are affected more commonly than men. Rarely, there is a family history of dementia, psychiatric problems or a movement disorder.
Symptoms
Patients with CBD present with either a movement disorder or cognitive deficits. As the disease progresses, most patients will eventually develop both types of symptoms, often with a delay of 2-3 years.
Movement
A characteristic feature of movement symptoms in CBD is striking asymmetry of involvement. Most frequently symptoms begin insidiously in one hand or arm, less commonly in one leg. Rarely, symptoms may involve the mouth and facial muscles.
Many patients will complain initially of a subtle change in sensation or an inability to make the affected limb follow commands. This latter deficit is called apraxia and may be confused for clumsiness or weakness. There may be difficulties in completing specific tasks, such as opening a door or brushing one’s teeth or using tools, such as a can opener. When a leg is affected initially, a patient may have problems with complex movements such as dancing; or when more severe, a patient may begin to trip and fall. Some patients will experience an involuntary stiffening, twisting or contraction of the affected limb called dystonia. There may be uncontrolled jumping of the limb when it is tapped gently or when the patient is startled, called myoclonus.
Finally, CBD patients often complain that the affected limb feels like it is not a part of their body, a sensation called alien limb. Sometimes an alien limb will move on its own, in an uncontrollable way. For example, an alien hand will rise to touch the patient’s face. Alien limb phenomenon was dramatized by the actor Peter Sellers in the film Dr. Strangelove.
Movement symptoms tend to progress slowly from one side of the body to the other or from leg to arm on the same side of the body.
Cognition
Patients with CBD who present with cognitive difficulties are usually initially diagnosed with frontotemporal dementia or Alzheimer's disease. It is only after they develop movement symptoms that the diagnosis of CBD is entertained. Occasionally, a diagnosis of CBD is not apparent until a patient’s brain is examined at autopsy.
Progressive difficulty with language is a common cognitive complaint in CBD. This most commonly involves difficulty with expression of language, such as word finding difficulty or naming problems. Reading, writing and simple mathematical calculations may also be impaired.
Personality changes, inappropriate behavior, repetitive and/or compulsive activities similar to those seen in FTD (see FTD description) are also common in CBD. Short-term memory problems, such as repeating questions or misplacing objects are also common.
Many patients with the movement difficulties of CBD will also have mild cognitive problems when they are evaluated in a specialized dementia clinic.
Treatment
At this time, there is no specific treatment for CBD. Instead individual symptoms are targeted with specific medications. For example, rigidity and difficulty walking may partially respond to treatments for Parkinson’s disease. Dystonia and myoclonus may respond to muscle relaxants or anti-seizure medications. Memory and behavior problems may respond to treatments for Alzheimer's disease and/or depression.
http://memory.ucsf.edu/Education/Disease/cbd.html
Cortico-basal ganglionic degeneration (CBGD) is a complex neurobehavioural disorder characterised by insidious onset and gradually progressive cerebrocortical and extrapyramidal dysfunction.
A 52 years old male presented in May 1998 with behavioural abnormalities since November 1996 and abnormal movements since June 1997. Initially the patient had difficulty in dressing himself. Soon afterwards he had difficulty in finding his way while inside the house. Sometimes he spent the whole night outside the house, to be discovered next morning by his family members in the nearby field. In April 1997 he also developed speech abnormality. His speech gradually became incomprehensible and he would laugh or cry without any reason. He also became forgetful. He developed twisting movements of right sided fingers, wrist and forearm and neck and lower limbs. He also developed parkinsonian features and was unable to perform activities of daily living on his own. There was no history of myoclonus, seizures, motor weakness, sensory or bladder and bowel symptoms.
On examination he was restless, laughing or crying without reasons. He could follow some verbal commands but could not do so when written commands were provided. He could neither utter a comprehensible word nor write a legible letter. His cranial nerves were normal. Examination of motor system was normal except the presence of akinesia, rigidity and dystonic posturing of limbs. These were more profound on the right side. There was no tremor or ataxia. His deep tendon reflexes as well as the plantars were normal. There was gross postural instability. The rigidity and akinesia did not respond to levodopa.
Investigations revealed normal haemogram, blood glucose, renal function and liver function tests. Serum calcium, phosphorous and alkaline phosphatase were 9.6 mg/dl,3.5 mg/dl and 11KAU/L, respectively. The serum copper was 90 mgm/dl and ceruloplasmin was 30 mg/dl. Serum VDRL was nonreactive and ELISA for HIV 1 and 2 were negative. CSF examination revealed a protein content of 20 mg/dl and sugar of 68 mg/dl and was acellular. The T2 weighted images on MRI [Figure. 1] showed prominent sylvian cisterns and prominence of cortical sulci particularly in frontal and both parietal lobes, suggesting symmetrical atrophy of frontal and parietal lobes. There was no KF ring on eye examination.
The typical features of CBGD can be categorised into movement disorders (akinesia, rigidity, postural instability, limb dystonia, cortical myoclonus and postural/intention tremor) and cortical signs, such as cortical sensory loss, apraxias and the 'alien limb' phenomenon.[1],[2] The most striking features of CBGD is asymmetry of involvement which differentiates it from most other neurodegenerative disorders. Rinne et al[2] reviewed 36 patients, with mean age at onset of 60.9+9.7 years. (range : 40-76 years). In the patients reported by Riley et al, the mean age at onset was 60 years (range: 51-71 years) and men were more commonly affected than women. Riley et al[1] reported apraxia in 71% of cases of CBGD. Although they found ideational and ideomotor apraxias to occur early and were sometimes the presenting symptoms, a variety of other apraxias have also been reported in CBGD. Alien limb phenomenon is an unusual sign in neurology and its presence, in the absence of a known callosal lesion, is highly suggestive of the diagnosis of CBGD. Speech abnormalities and aphasia has been reported to occur in 21% of patients with CBGD and are considered to reflect left hemisphere cortical pathology in this disorder.[1] Involvement of right parietal cortex in CBGD gives rise to visuospatial and constructional disturbances. Personality change, impaired attention, acalculia, impaired recall and learning, concrete thinking and left-right confusion have been noted in a number of patients. Oculomotility disturbances particularly manifested by impaired convergence and vertical and horizontal gaze palsy has been noted in CBGD. This feature sometime confuse CBGD with progressive supranuclear palsy (PSP). Dementia is a late feature of CBGD and was found in 43% of patients by Riley et al.[1] The full spectrum of clinical features typically seen in CBGD can also be present in patients with Pick's disease, but the latter disorder is usually dominated by cognitive, behavioural, and language disturbances such as primary progressive aphasia. Moreover, apraxia and parkinsonism, if present, are usually late finding in Pick's disease. Pathological features in CBGD include neuronal degeneration in pre-and post-central cortical areas, degeneration of basal ganglia, including substantia nigra (SN), and presence of achromatic neural inclusion seen not only in the cortex but also in the thalamus, subthalamus nucleus, red nucleus, and SN.[4] CT scans were abnormal in 14 of the 15 patients in one series, 8 had asymmetrical parietal lobe atrophy corresponding to the most affected side, and 6 had bilateral parietal atrophy.[1] PET scans shows reduced 18(F) fluorodopa uptake in the caudate and putamen, and markedly asymmetrical cortical hypometabolism in the superior temporal and inferior parietal lobe.[5]
Our patient presented with dressing and situational apraxias as the initial symptoms. Gradually, he developed abnormalities of speech, emotional lability, loss of social inhibition etc., the features of diffuse cortical dysfunction. These features were combined with asymmetric involvement of right side with extrapyramidal features like limb dystonia, akinesia, rigidity and postural instability. Our patients did not have 'alien limb' phenomenon which is a very interesting features of CBGD. However, its absence does not exclude the diagnosis, as it was observed only in 50% of patients by Riley et al.[1] The presence of features of cortical dysfunction in the early phase of illness compounded by extrapyramidal features and the absence of oculomotility disturbances and ataxia, clearly suggest the diagnosis of CBGD in our patients. These clinical findings were corroborated by symmetrical atrophy of frontal and parietal lobes in neuroimaging studies.
1. Riley DE, Lang AE, Lewis A et al : Cortico-basal ganglionic degeneration. Neurology 1990; 40 : 1203-1212.
2. Rinne JO, Lee MS, Thompson PD et al : Cortico-basal degeneration: a clinical study of 36 cases. Brain 1994; 117 : 1183-1196.
3. Bogen JE : Split-brain syndrome. In: Handbook of clinical neurology. Vol. 1(45): Clinical Neuropsychology. Friederiks JAM, Ed. Amsterdam: Elselvier. 1985; 99-106.
4. Lippa CF, Cohen R, Smith TW et al : Primary progressive aphasia with focal neuronal achromasia. Neurology1991; 42 : 882-886.
5. Eidelberg D, Dhawan V, Moller JR et al : The metabolic landscape of cortico-basal ganglionic degeneration, regional asymmetries studies with positron emission tomography. J Neurol Neurosurg Psychiatry 1991; 54 : 856-862.
http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2000;volume=48;issue=4;spage=405;epage=6;aulast=Anand
Corticobasal ganglionic
degeneration (which we will call CBD) is a rare progressive
neurological disorder characterized by a combination of
Parkinsonism and cortical dysfunction. It is a rare sporadic
progressive disorder first reported in 1968. CBD appears to be
closely related to another, less rare, sporadic extrapyramidal
degenerative disorder named Progresive Supranuclear Palsy (PSP)
. In CBD, cognitive symptoms dominate, while in PSP, eye
movement symptoms dominate the picture.
The Parkinsonism is generally an asymetric akinetic rigid syndrome, unresponsive to levodopa, similar to that of multiple system atrophy and PSP. Eye movement abnormalities are common, as in PSP, and a supranuclear gaze palsy can be seen as in PSP. Given the genetic similarities between CBD and PSP, it seems possible that they are simply two "faces" of the same disease.
Neuroradiological imaging studies in CBD demonstrate cortical atrophy, which may be symmetrical or asymmetrical. Other cortical signs include
Alien limb phenomenon
Apraxia
Dysphasia
Cortical sensory loss
Pyramidal signs
Proposed diagnostic criteria include at least three of the following:
bradykinesia and rigidity that does not respond to levodopa
alien limb phenomena
cortical sensory signs
focal limb dystonia
action tremor
myoclonus
The "alien limb" symptom is highly specific but it is not necessary for the diagnosis. Arm levitation resembling alien limb phenomena has been reported in PSP (Barclay et al, 1999), which certainly can also show focal limb dystonia and bradykinesia. Other aspects of this picture could easily be mistaken for other neurodegenerative disease such as Alzheimer's or Picks disease, and in fact, even experienced clinicians are correct 50% of the time or less when judged by pathological criteria. Onset in the sixth or seventh decade is typical. Disease progression is quicker than in Parkinsonism but similar to that of PSP. Recently language disturbance has been documented to be frequent (Frattali et al, 2000).
Pathology.
There is neuronal loss and gliosis and swollen achromatic neurons (ballooned neurons) are found in all cortical layers, but especially so in superior frontal and parietal gyri. There is extensive loss of myelinated axons in the white matter. Scattered neuronal inclusions may be seen similar to Pick bodies. Ballooned neurons are strongly reactive for phosphorylated neurofilaments and may include the tau protein (see below)(Dickson et al, 1986). Neuronal loss and gliosis are also observed in the nuclei of the basal ganglia. Lewy bodys and neurofibrillary tangles are absent. The substantia nigra shows neuronal loss with extraneuronal melanin, gliosis and neurofibrillary inclusions, called "corticobasal bodies".
Differential Diagnosis:
CBD is difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than 50% or the time (Litvan et al, 1997). CBD and may also be impossible to differentiate from PSP or a striato-niagral type of MSA. As more cortical signs develop in later stages, the disorders below may be possible to separate. As diagnostic sensitivity is poor, neuropathological confirmation remains the gold standard. Even here, one wonders if this disorder can be defined.
Parkinsonism
PSP (progressive supranuclear palsy, related by tau)
MSA (multiple system atrophy)
Picks disease
While CBD patients have normal saccadic velocity, this may be an artifact of case definition. If PSP and CBD share the same pathologic mechanism (see below), they may simply be two different presentations of the same disease.
The cause of CBD is presently unknown but because the tau protein accumulates in this disorder, it may be related to a mutation in the tau gene. (Higgins et al, 1999). Tau is a microtubule-binding protein that is normally abundant in neurons. Other "tauopathies" include Alzheimer's disease, Picks disease, frontotemporal dementia and parkinsonism, ALS-parkinson dementia complex of Guam, and progressive supranuclear palsy (PSP) (Higgins et al, 1999). According to Di Maria et al (2000) and Houlden et al (2001), CBD shares the same tau haplotype as do PSP patients (see above), suggesting that both CBD and PSP share the same genetic background, and possibly the same pathoogic mechanism.
Conventional Treatment
CBD patients do not respond to levodopa treatment (the standard treatment for Parkinsonism). Management is based on appropriate use of appliances, prevention of medical complications, and appropriate use of nursing. Patients with CBD and caregivers should establish early on the plan regarding invasive care -- intubation, feeding tubes, as these issues are almost certain to come up in the course of the disease.
References:
Barclay CL, Bergeron C, Lang AE. Arm levitation in progressive supranuclear palsy. Neurology 1999:52:879-882
Di Maria et al. Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. Ann Neurol 2000:47:374-377
Dickson DW and others. Ballooned neurons in select neurodegenerative disease contain phosphorylated neurofilament epitopes. Acta Neuropathol 71:216-223, 1986)
Frattali CM and others. Language disturbances in corticobasal degeneration. Neurology 2000:54:990-992
Higgins JJ, Litvan I, Nee LE, Loveless BS. A lack of the R406W tau mutation in progressive supranuclear palsy and corticobasal degeneration. Neurology 1999:52:404-406
Houlden H and others. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 2001:56:1702-6.
Koller WC, Montgomery EB. Issues in the early diagnosis of Parkinson's disease. Neurology 1997:49 (Suppl 1), S10-25.
Litvan I, and others. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997:48:119-125
Riley DE, Lange AE, Lewis A, et al. Cortico-basal ganglionic degeneration. Neurology 1990;40:1203-1212
****
http://www.dizziness-and-balance.com/disorders/central/movement/corticobasal.html
The Parkinsonism is generally an asymetric akinetic rigid syndrome, unresponsive to levodopa, similar to that of multiple system atrophy and PSP. Eye movement abnormalities are common, as in PSP, and a supranuclear gaze palsy can be seen as in PSP. Given the genetic similarities between CBD and PSP, it seems possible that they are simply two "faces" of the same disease.
Neuroradiological imaging studies in CBD demonstrate cortical atrophy, which may be symmetrical or asymmetrical. Other cortical signs include
Alien limb phenomenon
Apraxia
Dysphasia
Cortical sensory loss
Pyramidal signs
Proposed diagnostic criteria include at least three of the following:
bradykinesia and rigidity that does not respond to levodopa
alien limb phenomena
cortical sensory signs
focal limb dystonia
action tremor
myoclonus
The "alien limb" symptom is highly specific but it is not necessary for the diagnosis. Arm levitation resembling alien limb phenomena has been reported in PSP (Barclay et al, 1999), which certainly can also show focal limb dystonia and bradykinesia. Other aspects of this picture could easily be mistaken for other neurodegenerative disease such as Alzheimer's or Picks disease, and in fact, even experienced clinicians are correct 50% of the time or less when judged by pathological criteria. Onset in the sixth or seventh decade is typical. Disease progression is quicker than in Parkinsonism but similar to that of PSP. Recently language disturbance has been documented to be frequent (Frattali et al, 2000).
Pathology.
There is neuronal loss and gliosis and swollen achromatic neurons (ballooned neurons) are found in all cortical layers, but especially so in superior frontal and parietal gyri. There is extensive loss of myelinated axons in the white matter. Scattered neuronal inclusions may be seen similar to Pick bodies. Ballooned neurons are strongly reactive for phosphorylated neurofilaments and may include the tau protein (see below)(Dickson et al, 1986). Neuronal loss and gliosis are also observed in the nuclei of the basal ganglia. Lewy bodys and neurofibrillary tangles are absent. The substantia nigra shows neuronal loss with extraneuronal melanin, gliosis and neurofibrillary inclusions, called "corticobasal bodies".
Differential Diagnosis:
CBD is difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than 50% or the time (Litvan et al, 1997). CBD and may also be impossible to differentiate from PSP or a striato-niagral type of MSA. As more cortical signs develop in later stages, the disorders below may be possible to separate. As diagnostic sensitivity is poor, neuropathological confirmation remains the gold standard. Even here, one wonders if this disorder can be defined.
Parkinsonism
PSP (progressive supranuclear palsy, related by tau)
MSA (multiple system atrophy)
Picks disease
While CBD patients have normal saccadic velocity, this may be an artifact of case definition. If PSP and CBD share the same pathologic mechanism (see below), they may simply be two different presentations of the same disease.
The cause of CBD is presently unknown but because the tau protein accumulates in this disorder, it may be related to a mutation in the tau gene. (Higgins et al, 1999). Tau is a microtubule-binding protein that is normally abundant in neurons. Other "tauopathies" include Alzheimer's disease, Picks disease, frontotemporal dementia and parkinsonism, ALS-parkinson dementia complex of Guam, and progressive supranuclear palsy (PSP) (Higgins et al, 1999). According to Di Maria et al (2000) and Houlden et al (2001), CBD shares the same tau haplotype as do PSP patients (see above), suggesting that both CBD and PSP share the same genetic background, and possibly the same pathoogic mechanism.
Conventional Treatment
CBD patients do not respond to levodopa treatment (the standard treatment for Parkinsonism). Management is based on appropriate use of appliances, prevention of medical complications, and appropriate use of nursing. Patients with CBD and caregivers should establish early on the plan regarding invasive care -- intubation, feeding tubes, as these issues are almost certain to come up in the course of the disease.
References:
Barclay CL, Bergeron C, Lang AE. Arm levitation in progressive supranuclear palsy. Neurology 1999:52:879-882
Di Maria et al. Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. Ann Neurol 2000:47:374-377
Dickson DW and others. Ballooned neurons in select neurodegenerative disease contain phosphorylated neurofilament epitopes. Acta Neuropathol 71:216-223, 1986)
Frattali CM and others. Language disturbances in corticobasal degeneration. Neurology 2000:54:990-992
Higgins JJ, Litvan I, Nee LE, Loveless BS. A lack of the R406W tau mutation in progressive supranuclear palsy and corticobasal degeneration. Neurology 1999:52:404-406
Houlden H and others. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 2001:56:1702-6.
Koller WC, Montgomery EB. Issues in the early diagnosis of Parkinson's disease. Neurology 1997:49 (Suppl 1), S10-25.
Litvan I, and others. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997:48:119-125
Riley DE, Lange AE, Lewis A, et al. Cortico-basal ganglionic degeneration. Neurology 1990;40:1203-1212
****
http://www.dizziness-and-balance.com/disorders/central/movement/corticobasal.html
Corticobasal
Degeneration Overview
What is corticobasal degeneration?
Corticobasal degeneration (CBD) is a rare neurological disease in which parts of the brain deteriorate or degenerate. CBD is also known as corticobasal ganglionic degeneration, or CBGD.
Several regions of the brain degenerate in CBD. The cortex, or outer layer of the brain, is severely affected, especially the fronto-parietal regions, located near the center-top of the head. Other, deeper brain regions are also affected, including parts of the basal ganglia, hence the name "corticobasal" degeneration. The combined loss of brain tissue in all these areas causes the symptoms and findings seen in people with CBD.
Causes of Corticobasal Degeneration
What causes the degeneration of brain tissue in CBD?
Unfortunately, the cause of CBD is entirely unknown. There is currently no strong evidence to suggest CBD is an inherited disease, and no other risk factors, such as toxins or infections, have been identified.
Studies of brain tissue of individuals with CBD show certain characteristic cell changes. Similar, although not identical, changes are observed in two other neurodegenerative diseases, Pick's disease and progressive supranuclear palsy. These changes, involving a brain protein called tau, have provided researchers some initial clues in their search for the causes of CBD.
Symptoms of Corticobasal Degeneration
What are the symptoms of CBD?
Symptoms of CBD usually begin after age 60. The initial symptoms of CBD are often stiffness, shakiness, jerkiness, slowness, and clumsiness, in either the upper or lower extremities. Other initial symptoms may include dysphasia (difficulty with speech generation), dysarthria (difficulty with articulation), difficulty controlling the muscles of the face and mouth, or walking and balance difficulties. Symptoms usually begin on one side of the body, and spread gradually to the other. Some patients (probably more than commonly recognized in the past) may have memory or behavioral problems as the earliest or presenting symptoms.
CBD is a progressive disease, meaning the symptoms worsen over time. Over the course of one to several years, most people with CBD gradually worsen, with symptoms progressing to involve upper and lower extremities and other body regions. Symptoms of advanced CBD include:
•parkinsonism (rigidity, slow movements, postural instability)
•tremor
•myoclonus (sudden, brief jerky movements)
•dystonia, including blepharospasm
•speech difficulty
•mild-to-moderate cognitive impairment (memory loss, difficulty planning or executing unrehearsed movements, dementia)
•sensory loss
•"alien hand/limb" phenomenon (difficulty controlling the movements of a limb, which seems to undertake movements on its own, sometimes combined with a feeling that the limb is not one's own)
Diagnosis of Corticobasal Degeneration
How is CBD diagnosed?
Early in the disease course, it is often difficult to distinguish CBD from similar neurodegenerative diseases. Diagnosis of CBD involves a careful neurological exam, combined with one or more types of laboratory evaluations. Electrophysiological studies, including an EEG (electroencephalogram), may show changes in brain function over time that are consistent with the neurodegeneration. CT or MRI scans can also be used in this way, providing images of asymmetric atrophy of the fronto-parietal regions of the brain's cortex, the regions most frequently involved in the disease.
Approaches to Treatment
How is CBD treated?
Unfortunately, there are no drugs or other therapies that can slow the progress of the disease, and very few that offer symptomatic relief. [Have they tried the things listed in the Ideas section of this page?] Tremor and myoclonus may be controlled somewhat with drugs such as clonazepam. Baclofen may help reduce rigidity somewhat. Levodopa and other dopaminergic drugs used in Parkinson's disease are rarely beneficial, but may help some CBD patients.
Physical therapy exercises may be useful to maintain range of motion of stiff joints. This may prevent pain and contracture (muscle shortening), and help maintain mobility. Occupational therapy may be used to design adaptive equipment that supports the activities of daily living, thus helping to maintain more functional independence. Speech therapy is used to improve articulation and volume.
What is the usual course of CBD?
A person with CBD will usually become immobile due to rigidity within five years of symptom onset, and may require a gastrostomy tube for feeding at some point before that. Most often, within ten years of onset, pneumonia or other bacterial infections may lead to life-threatening complications.
http://www.wemove.org/cbd/cbd.html
What is corticobasal degeneration?
Corticobasal degeneration (CBD) is a rare neurological disease in which parts of the brain deteriorate or degenerate. CBD is also known as corticobasal ganglionic degeneration, or CBGD.
Several regions of the brain degenerate in CBD. The cortex, or outer layer of the brain, is severely affected, especially the fronto-parietal regions, located near the center-top of the head. Other, deeper brain regions are also affected, including parts of the basal ganglia, hence the name "corticobasal" degeneration. The combined loss of brain tissue in all these areas causes the symptoms and findings seen in people with CBD.
Causes of Corticobasal Degeneration
What causes the degeneration of brain tissue in CBD?
Unfortunately, the cause of CBD is entirely unknown. There is currently no strong evidence to suggest CBD is an inherited disease, and no other risk factors, such as toxins or infections, have been identified.
Studies of brain tissue of individuals with CBD show certain characteristic cell changes. Similar, although not identical, changes are observed in two other neurodegenerative diseases, Pick's disease and progressive supranuclear palsy. These changes, involving a brain protein called tau, have provided researchers some initial clues in their search for the causes of CBD.
Symptoms of Corticobasal Degeneration
What are the symptoms of CBD?
Symptoms of CBD usually begin after age 60. The initial symptoms of CBD are often stiffness, shakiness, jerkiness, slowness, and clumsiness, in either the upper or lower extremities. Other initial symptoms may include dysphasia (difficulty with speech generation), dysarthria (difficulty with articulation), difficulty controlling the muscles of the face and mouth, or walking and balance difficulties. Symptoms usually begin on one side of the body, and spread gradually to the other. Some patients (probably more than commonly recognized in the past) may have memory or behavioral problems as the earliest or presenting symptoms.
CBD is a progressive disease, meaning the symptoms worsen over time. Over the course of one to several years, most people with CBD gradually worsen, with symptoms progressing to involve upper and lower extremities and other body regions. Symptoms of advanced CBD include:
•parkinsonism (rigidity, slow movements, postural instability)
•tremor
•myoclonus (sudden, brief jerky movements)
•dystonia, including blepharospasm
•speech difficulty
•mild-to-moderate cognitive impairment (memory loss, difficulty planning or executing unrehearsed movements, dementia)
•sensory loss
•"alien hand/limb" phenomenon (difficulty controlling the movements of a limb, which seems to undertake movements on its own, sometimes combined with a feeling that the limb is not one's own)
Diagnosis of Corticobasal Degeneration
How is CBD diagnosed?
Early in the disease course, it is often difficult to distinguish CBD from similar neurodegenerative diseases. Diagnosis of CBD involves a careful neurological exam, combined with one or more types of laboratory evaluations. Electrophysiological studies, including an EEG (electroencephalogram), may show changes in brain function over time that are consistent with the neurodegeneration. CT or MRI scans can also be used in this way, providing images of asymmetric atrophy of the fronto-parietal regions of the brain's cortex, the regions most frequently involved in the disease.
Approaches to Treatment
How is CBD treated?
Unfortunately, there are no drugs or other therapies that can slow the progress of the disease, and very few that offer symptomatic relief. [Have they tried the things listed in the Ideas section of this page?] Tremor and myoclonus may be controlled somewhat with drugs such as clonazepam. Baclofen may help reduce rigidity somewhat. Levodopa and other dopaminergic drugs used in Parkinson's disease are rarely beneficial, but may help some CBD patients.
Physical therapy exercises may be useful to maintain range of motion of stiff joints. This may prevent pain and contracture (muscle shortening), and help maintain mobility. Occupational therapy may be used to design adaptive equipment that supports the activities of daily living, thus helping to maintain more functional independence. Speech therapy is used to improve articulation and volume.
What is the usual course of CBD?
A person with CBD will usually become immobile due to rigidity within five years of symptom onset, and may require a gastrostomy tube for feeding at some point before that. Most often, within ten years of onset, pneumonia or other bacterial infections may lead to life-threatening complications.
http://www.wemove.org/cbd/cbd.html
Cortical-basal ganglionic
degeneration (CBGD), or corticobasal degeneration typically
begins from 50 – 70 years of age. Mean survival is about 8
years. Its distinctive features are an asymmetric
levodopa-resistant akinetic-rigid syndrome associated with
"cortical" features such as apraxia, cortical sensory loss, and
alien limb phenomenon. General cognitive function had been
thought to be preserved.
This "classical" description emphasizing a parietal/perceptual-motor presentation may be biased because the cases mainly originate from movement disorder centers. Features of speech disturbances or dementia had been thought to represent the minority of cases. In a recent review by Grimes et al. only 4 of 13 pathologically proven patients had a prior clinical diagnosis of CBGD. It appears now that dementia can be a prominent feature of advanced disease and may be the most common feature. Aphasia can be seen in over 50% of patients. Depression is common. Apathy, social withdrawal, bizarre behavior, hypersexuality irritability, and anarthria have been described.
Parkinsonian signs including unilateral limb rigidity (79%), bradykinesia (71%), postural instability (45%) and apraxia are found in almost all patients. Dystonic posturing of the arm and hand is common (43%). Tremor when present is typically an action tremor that improves at rest. It frequently has a myoclonic (jerky) component. Stimulus sensitive myoclonus can be seen. The rigidity may be extreme and associated pain is common.
With progression cortical sensory deficits, pyramidal tract dysfunction, dysarthria, dysphagia and other symptoms emerge or worsen. Alien limb phenomena develop in 50% of cases. It may be as simple as levitation of a limb. Magnetic apraxia (approach behavior with groping and manipulation) is a sign of CBGD. Described eye movement abnormalities include saccadic pursuit, difficulty initiating saccades, and rarely supranuclear palsy.
CBGD, like PSP is a disorder of the tau protein (a tauopathy). It seems now that it has significant overlap with the frontotemporal dementias (FTD), parkinsonism associated with chromosome 17 (FTDP-17), primary progressive aphasia (PPA), Pick's disease, and PSP.
General References On Clinical Features of Parkinsonisms
*Handbook of Clinical Neurology Vol 49 Extrapyramidal disorders: Vinken, Bruyn, Klawans eds. Elsevier Science publishers 1996
Movement Disorders a Comprehensive Survey;: Weiner, Lang A. eds. Futura publishing company 1989
Neurodegenerative Diseases, Calne, D., eds. W.B. Saunders Company 1994
Parkinson's Disease and Movement Disorders, Jankovic, Tolosa ,eds. Urban & Scharzenberg 1988
References for criteria in the diagnosis of Parkinsonism
CBGD
D. A. Grimes, A. E. Lang MD, FRCPC, C. B. Bergeron Dementia as the most common presentation of cortical-basal ganglionic degeneration Neurology Volume 53 Number 9 December 10, 1999
http://www.cmdg.org/Movement_/Parkinsons_Plus/CBGD/cbgd.htm
This "classical" description emphasizing a parietal/perceptual-motor presentation may be biased because the cases mainly originate from movement disorder centers. Features of speech disturbances or dementia had been thought to represent the minority of cases. In a recent review by Grimes et al. only 4 of 13 pathologically proven patients had a prior clinical diagnosis of CBGD. It appears now that dementia can be a prominent feature of advanced disease and may be the most common feature. Aphasia can be seen in over 50% of patients. Depression is common. Apathy, social withdrawal, bizarre behavior, hypersexuality irritability, and anarthria have been described.
Parkinsonian signs including unilateral limb rigidity (79%), bradykinesia (71%), postural instability (45%) and apraxia are found in almost all patients. Dystonic posturing of the arm and hand is common (43%). Tremor when present is typically an action tremor that improves at rest. It frequently has a myoclonic (jerky) component. Stimulus sensitive myoclonus can be seen. The rigidity may be extreme and associated pain is common.
With progression cortical sensory deficits, pyramidal tract dysfunction, dysarthria, dysphagia and other symptoms emerge or worsen. Alien limb phenomena develop in 50% of cases. It may be as simple as levitation of a limb. Magnetic apraxia (approach behavior with groping and manipulation) is a sign of CBGD. Described eye movement abnormalities include saccadic pursuit, difficulty initiating saccades, and rarely supranuclear palsy.
CBGD, like PSP is a disorder of the tau protein (a tauopathy). It seems now that it has significant overlap with the frontotemporal dementias (FTD), parkinsonism associated with chromosome 17 (FTDP-17), primary progressive aphasia (PPA), Pick's disease, and PSP.
General References On Clinical Features of Parkinsonisms
*Handbook of Clinical Neurology Vol 49 Extrapyramidal disorders: Vinken, Bruyn, Klawans eds. Elsevier Science publishers 1996
Movement Disorders a Comprehensive Survey;: Weiner, Lang A. eds. Futura publishing company 1989
Neurodegenerative Diseases, Calne, D., eds. W.B. Saunders Company 1994
Parkinson's Disease and Movement Disorders, Jankovic, Tolosa ,eds. Urban & Scharzenberg 1988
References for criteria in the diagnosis of Parkinsonism
CBGD
D. A. Grimes, A. E. Lang MD, FRCPC, C. B. Bergeron Dementia as the most common presentation of cortical-basal ganglionic degeneration Neurology Volume 53 Number 9 December 10, 1999
http://www.cmdg.org/Movement_/Parkinsons_Plus/CBGD/cbgd.htm
Corticobasal
Ganglionic Degeneration With Balint's Syndrome
Mario F. Mendez, M.D., Ph.D.
Received May 20, 1999; revised August 20, 1999; accepted November 19, 1999. From the Departments of Neurology and Psychiatry, UCLA School of Medicine
ABSTRACT
Corticobasal ganglionic degeneration (CBGD) is a neurodegenerative dementia characterized by asymmetric parkinsonism, ideomotor apraxia, myoclonus, dystonia, and the alien hand syndrome. This report describes a patient with CBGD who developed Balint's syndrome with simultanagnosia, oculomotor apraxia, and optic ataxia.
Key Words: Balint's Syndrome • Corticobasal Ganglionic Degeneration • Dystonia
Corticobasal ganglionic degeneration (CBGD) is a progressive neurodegenerative disorder involving both cortical and basal ganglionic dysfunction. The main features of CBGD are movement disorders and dementia.1,2 It is not widely appreciated that CBGD can also produce prominent visuospatial difficulties.
Balint's syndrome is a complex visuospatial disorder. It includes the inability to integrate complex visual scenes (simultanagnosia); the inability to accurately direct hand or other movements by visual guidance (optic ataxia); and reduced or inaccurate voluntary eye movements to visual stimuli (oculomotor apraxia).3,4 This triad results in a dramatic impairment in the ability to explore visual space. This case report expands the clinical spectrum of CBGD to include Balint's syndrome.
http://neuro.psychiatryonline.org/cgi/content/full/12/2/273
Mario F. Mendez, M.D., Ph.D.
Received May 20, 1999; revised August 20, 1999; accepted November 19, 1999. From the Departments of Neurology and Psychiatry, UCLA School of Medicine
ABSTRACT
Corticobasal ganglionic degeneration (CBGD) is a neurodegenerative dementia characterized by asymmetric parkinsonism, ideomotor apraxia, myoclonus, dystonia, and the alien hand syndrome. This report describes a patient with CBGD who developed Balint's syndrome with simultanagnosia, oculomotor apraxia, and optic ataxia.
Key Words: Balint's Syndrome • Corticobasal Ganglionic Degeneration • Dystonia
Corticobasal ganglionic degeneration (CBGD) is a progressive neurodegenerative disorder involving both cortical and basal ganglionic dysfunction. The main features of CBGD are movement disorders and dementia.1,2 It is not widely appreciated that CBGD can also produce prominent visuospatial difficulties.
Balint's syndrome is a complex visuospatial disorder. It includes the inability to integrate complex visual scenes (simultanagnosia); the inability to accurately direct hand or other movements by visual guidance (optic ataxia); and reduced or inaccurate voluntary eye movements to visual stimuli (oculomotor apraxia).3,4 This triad results in a dramatic impairment in the ability to explore visual space. This case report expands the clinical spectrum of CBGD to include Balint's syndrome.
http://neuro.psychiatryonline.org/cgi/content/full/12/2/273
[Neuroprotection
and neurodegenerative parkinsonian syndromes] [Article
in French]
Destée A.
Clinique neurologique, EA 2683 MENRT, CHU de Lille. adestee@chru-lille.fr
Rev Neurol (Paris). 2003 May;159(5 Pt 2):3S93-104.[Article in French]
Abstract
The diffuse nature of the lesions in neurodegenerative parkinsonian syndromes explains the inefficacy of symptomatic treatments and the potential interest of neuroprotector treatments that could slow down or even prevent neuron degeneration in structures involved in the degenerative processes. As these syndromes share preferential degeneration of the substantia nigra with Parkinson's disease it is logical to hypothesize that the same mechanisms of neuron death are involved. The responsibility of an exotoxin, with a mechanism of action that would be similar to that of MPTP and/or rotenone, appears to be implicated only in progressive supranuclear palsy (PSP): this is suggested by the "guadeloupean parkinsonean" syndrome. There is no evidence demonstrating an exotoxin in corticobasal degeneration (CBD), which might play an anecdotal role in rare cases of multiple system atrophy (MSA). There are rare cases of PSP, sometimes with autopsy proof, generally with autosomal dominant inheritance, but in the much larger number of sporadic cases there is an undeniable genetic susceptibility linked with certain polymorphisms of the tau protein gene. Genetic susceptibility plays a much less pronounced role in CBD. There is no argument however in favor of a genetic factor in MSA. A few arguments suggest that oxidative stress is involved in PSP and MSA, or even CBD, but no evidence of a primary effect. Perturbed mitochondrial metabolism is possible in PSP. Undeniable proof of the effect of inflammation, excitotoxicity, and apoptosis remains to be presented. We now have several compounds which could affect different phases of neurodegeneration. Identifying the precise cause of neuronal death is needed to properly choose the most effective therapeutic approach (single drug or multiple drug regimens). Therapeutic assessment should be conducted in patients with certain diagnosis. This apparently evident prerequisite does not however appear to be easy to satisfy as has been demonstrated by anatomoclinical series in PSP and MSA, and even more so in CBD. Use of international criteria does not alleviate the difficulty. Satisfactory criteria of efficacy remain to be identified. Assuming that such trials would be conclusive, there remains the question of how to implement neuroprotection in routine practice. The difficulties encountered are well known: late intervention after development of the disease in sporadic cases, ethical issues concerning preclinical screening in familial forms of the disease or in patients exposed to an exotoxin.
PMID: 12773894 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/12773894
Destée A.
Clinique neurologique, EA 2683 MENRT, CHU de Lille. adestee@chru-lille.fr
Rev Neurol (Paris). 2003 May;159(5 Pt 2):3S93-104.[Article in French]
Abstract
The diffuse nature of the lesions in neurodegenerative parkinsonian syndromes explains the inefficacy of symptomatic treatments and the potential interest of neuroprotector treatments that could slow down or even prevent neuron degeneration in structures involved in the degenerative processes. As these syndromes share preferential degeneration of the substantia nigra with Parkinson's disease it is logical to hypothesize that the same mechanisms of neuron death are involved. The responsibility of an exotoxin, with a mechanism of action that would be similar to that of MPTP and/or rotenone, appears to be implicated only in progressive supranuclear palsy (PSP): this is suggested by the "guadeloupean parkinsonean" syndrome. There is no evidence demonstrating an exotoxin in corticobasal degeneration (CBD), which might play an anecdotal role in rare cases of multiple system atrophy (MSA). There are rare cases of PSP, sometimes with autopsy proof, generally with autosomal dominant inheritance, but in the much larger number of sporadic cases there is an undeniable genetic susceptibility linked with certain polymorphisms of the tau protein gene. Genetic susceptibility plays a much less pronounced role in CBD. There is no argument however in favor of a genetic factor in MSA. A few arguments suggest that oxidative stress is involved in PSP and MSA, or even CBD, but no evidence of a primary effect. Perturbed mitochondrial metabolism is possible in PSP. Undeniable proof of the effect of inflammation, excitotoxicity, and apoptosis remains to be presented. We now have several compounds which could affect different phases of neurodegeneration. Identifying the precise cause of neuronal death is needed to properly choose the most effective therapeutic approach (single drug or multiple drug regimens). Therapeutic assessment should be conducted in patients with certain diagnosis. This apparently evident prerequisite does not however appear to be easy to satisfy as has been demonstrated by anatomoclinical series in PSP and MSA, and even more so in CBD. Use of international criteria does not alleviate the difficulty. Satisfactory criteria of efficacy remain to be identified. Assuming that such trials would be conclusive, there remains the question of how to implement neuroprotection in routine practice. The difficulties encountered are well known: late intervention after development of the disease in sporadic cases, ethical issues concerning preclinical screening in familial forms of the disease or in patients exposed to an exotoxin.
PMID: 12773894 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/12773894
Unfortuantely, the article is in French, so I don't know what the "several compounds which could affect different phases of neurodegeneration" are.
*********************************************************************************************
How often is "CBS" actually CBD?
CBS stands for "corticobasal syndrome." It's a clinical diagnosis given while someone is alive. CBD stands for "corticobasal degeneration." Many clinicians (including those at Mayo Rochester) are trying to only use the term CBD for a pathological diagnosis made on a post-mortem basis. Upon brain autopsy, someone with a clinical diagnosis of CBS can actually show evidence of something other than CBD. The diagnostic accuracy for CBD is rather poor.
Differential Diagnosis:
CBD is difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than 50% or the time (Litvan et al, 1997). CBD and may also be impossible to differentiate from PSP or a striato-niagral type of MSA. As more cortical signs develop in later stages, the disorders below may be possible to separate. As diagnostic sensitivity is poor, neuropathological confirmation remains the gold standard. Even here, one wonders if this disorder can be defined.
Litvan I, and others. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997:48:119-125
http://www.dizziness-and-balance.com/disorders/central/movement/corticobasal.html
CBD is difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than 50% or the time (Litvan et al, 1997). CBD and may also be impossible to differentiate from PSP or a striato-niagral type of MSA. As more cortical signs develop in later stages, the disorders below may be possible to separate. As diagnostic sensitivity is poor, neuropathological confirmation remains the gold standard. Even here, one wonders if this disorder can be defined.
Litvan I, and others. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997:48:119-125
http://www.dizziness-and-balance.com/disorders/central/movement/corticobasal.html
That paper was published in 1997. I have not found more recent information... yet. The diagnostic accuracy may have improved since then.
If I'm interpreting this paper correctly, Mayo Rochester researchers looked at the clinical records of 11 patients diagnosed during life with CBS but upon brain autopsy 5 had Alzheimer's Disease-- that's almost 50% folks!-- (called CBS-AD in this paper) and 6 had CBD (called CBS-CBD in this paper). Part of the clinical records includes MRI scans taken while the patients were alive. A technique called voxel-based morphometry was used to compare patterns of gray matter atrophy.
The problem I'm having with the numbers is, I don't know if the researchers left out all of those who had been diagnosed with "CBS" during life but were found to have neither CBS-AD or CBS-CBD.
The researchers found that "On direct comparisons between the two subject groups, CBS-AD showed greater loss in both temporal and inferior parietal cortices than CBS-CBD. ... In subjects presenting with CBS, prominent temporoparietal, especially posterior temporal and inferior parietal, atrophy may be a clue to the presence of underlying AD pathology."
Because this is a technique used with standard MRI scans, this approach could be utilized by all clinicians with access to a top radiologist.
Anatomical
differences between CBS-corticobasal degeneration and
CBS-Alzheimer's disease.
Mov Disord. 2010 May 4. [Epub ahead of print]
Josephs KA, Whitwell JL, Boeve BF, Knopman DS, Petersen RC, Hu WT, Parisi JE, Dickson DW, Jack CR Jr.
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
We compare patterns of gray matter loss on MRI in subjects presenting as corticobasal syndrome (CBS) with Alzheimer disease pathology (CBS-AD) to those presenting as CBS with corticobasal degeneration pathology (CBS-CBD). Voxel-based morphometry was used to compare patterns of gray matter loss in pathologically confirmed CBS-AD subjects (n = 5) and CBS-CBD subjects (n = 6) to a group of healthy controls (n = 20), and to each other. Atlas based parcellation using the automated anatomic labeling atlas was also utilized in a region-of-interest analysis to account for laterality. The CBS-AD subjects were younger at the time of scan when compared with CBS-CBD subjects (median: 60 years vs. 69; P = 0.04). After adjusting for age at time of MRI scan, the CBS-AD subjects showed loss in posterior frontal, temporal, and superior and inferior parietal lobes, while CBS-CBD showed more focal loss predominantly in the posterior frontal lobes when compared with controls. In both CBS-AD and CBS-CBD groups, there was basal ganglia volume loss, yet relative sparing of hippocampi. On direct comparisons between the two subject groups, CBS-AD showed greater loss in both temporal and inferior parietal cortices than CBS-CBD. No regions showed greater loss in the CBS-CBD group compared to the CBS-AD group. These findings persisted when laterality was taken into account. In subjects presenting with CBS, prominent temporoparietal, especially posterior temporal and inferior parietal, atrophy may be a clue to the presence of underlying AD pathology.
PMID: 20629131 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20629131
Imaging correlates of pathology in corticobasal syndrome.
Neurology. 2010 Nov 23;75(21):1879-87.
Whitwell JL, Jack CR Jr, Boeve BF, Parisi JE, Ahlskog JE, Drubach DA, Senjem ML, Knopman DS, Petersen RC, Dickson DW, Josephs KA.
Abstract
BACKGROUND: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS.
METHODS: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls.
RESULTS: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD.
CONCLUSIONS: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology.
PMID: 21098403 [PubMed]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=21098403[uid]
There is also a report from a patient of Dr. Boeve at the Mayo
Clinic in Rochester, MN that for patients with CBD-AD, there is
greater atrophy of the hippocampus
than with CBS-CBD.Mov Disord. 2010 May 4. [Epub ahead of print]
Josephs KA, Whitwell JL, Boeve BF, Knopman DS, Petersen RC, Hu WT, Parisi JE, Dickson DW, Jack CR Jr.
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
We compare patterns of gray matter loss on MRI in subjects presenting as corticobasal syndrome (CBS) with Alzheimer disease pathology (CBS-AD) to those presenting as CBS with corticobasal degeneration pathology (CBS-CBD). Voxel-based morphometry was used to compare patterns of gray matter loss in pathologically confirmed CBS-AD subjects (n = 5) and CBS-CBD subjects (n = 6) to a group of healthy controls (n = 20), and to each other. Atlas based parcellation using the automated anatomic labeling atlas was also utilized in a region-of-interest analysis to account for laterality. The CBS-AD subjects were younger at the time of scan when compared with CBS-CBD subjects (median: 60 years vs. 69; P = 0.04). After adjusting for age at time of MRI scan, the CBS-AD subjects showed loss in posterior frontal, temporal, and superior and inferior parietal lobes, while CBS-CBD showed more focal loss predominantly in the posterior frontal lobes when compared with controls. In both CBS-AD and CBS-CBD groups, there was basal ganglia volume loss, yet relative sparing of hippocampi. On direct comparisons between the two subject groups, CBS-AD showed greater loss in both temporal and inferior parietal cortices than CBS-CBD. No regions showed greater loss in the CBS-CBD group compared to the CBS-AD group. These findings persisted when laterality was taken into account. In subjects presenting with CBS, prominent temporoparietal, especially posterior temporal and inferior parietal, atrophy may be a clue to the presence of underlying AD pathology.
PMID: 20629131 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20629131
Imaging correlates of pathology in corticobasal syndrome.
Neurology. 2010 Nov 23;75(21):1879-87.
Whitwell JL, Jack CR Jr, Boeve BF, Parisi JE, Ahlskog JE, Drubach DA, Senjem ML, Knopman DS, Petersen RC, Dickson DW, Josephs KA.
Abstract
BACKGROUND: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS.
METHODS: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls.
RESULTS: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD.
CONCLUSIONS: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology.
PMID: 21098403 [PubMed]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=21098403[uid]
7 of 24 had CBD
6 of 24 had PSP
6 of 24 had AD (Alzheimer's Disease)
5 of 24 had FTLD with TDP-43
*********************************************************************************************
Ideas (...treatments for CBD, allopathic, alternative, main-stream and avant-garde)
Most articles describing the cellular level characteristics of CBD include something like the following:
"Pathology is characterized by an
asymmetric frontoparietal neuronal loss and gliosis with
ballooned, achromatic cortical neurons, nigral degeneration, and
variable subcortical involvement."
Unfortunately, few articles go further in discussing these, their possible causes, and more importantly, what can be done about them. Most authors typically give only one brief sentence.
Here is one of the better ones:
"There is neuronal loss and
gliosis and swollen achromatic neurons (ballooned neurons) are
found in all cortical layers, but especially so in superior
frontal and parietal gyri. There is extensive loss of myelinated
axons in the white matter. Scattered neuronal inclusions may be
seen similar to Pick bodies. Ballooned neurons are strongly
reactive for phosphorylated neurofilaments and may include the
tau protein (Dickson et al, 1986). Neuronal loss and gliosis are
also observed in the nuclei of the basal ganglia. Lewy bodys and
neurofibrillary tangles are absent. The substantia nigra shows
neuronal loss with extraneuronal melanin, gliosis and
neurofibrillary inclusions, called "corticobasal bodies"."
We have:
Gliosis
Ballooning of neurons
Achromatic neurons
Loss of myelinated axons
Neuronal inclusions
Gliosis
Definition:
Gliosis is a proliferation of
astrocytes in damaged areas of the central nervous system (CNS).
This proliferation usually leads to the formation of a glial
scar.
Astrocytes are relatively large
glial cells and have various functions, including accumulating
in areas where neurons have been damaged. It is the most
important histopathological sign of cns injury. Astrocytes
undergo both hypertrophy and hyperplasia. the nucleus enlarges
and becomes vesicular and nucleolus becomes prominent.
Previously scant cytoplasm expands and becomes bright pink and
irregular from which arise numerous processes (gemistocytic
astrocyte).
So, it sounds like the gliosis is a symptom of whatever the
underlying condition is that causes the neurons to become
unhealthy.Ballooning
What causes this "ballooning"? Is it the phosphorylated neurofilaments? (Does this author mean tau protein neurofilaments?) If the hyperphoshporylation of tau protein neurofilaments causes the neurons to become unhealthy and ballooned, then treating the cause of the hyperphosphorylation would be appropriate. What can cause hyperphosorylation of tau? Hypothermia due to anesthetics can do it, but the problem resolves itself when the temperature returns to normal. Could a chronically low body temperature lead to this condition? Exposure to RF energy in the typical cell phone frequency range has been shown to improve the lot of AD mouse model mice exposed to it. The reason is not known, but one thing RF energy definitely does is cause heating. So, perhaps simply elevating the temperature of the ailing neurons a little bit would prevent or revers the tau protein hyperphosphorylation.
Achromatic Neurons
Loss of myelinated axons
Neuronal Inclusions
When tau proteins are exposed to the sugar D-ribose, it tends to form "clumps". This is the same description used for the tau protein inclusions of CBD. Are they the same? Is a problem with metabolising D-ribose the cause of the clumped-up tau protein inclusions? D-ribose is used by cells to make the internal energy currency of cells called ATP (adenosine triphosphate) from the simple sugar glucose. If the neurons are having a problem making ATP, but still make plenty of D-ribose (or the D-ribose comes from some other source, but is not used), could excessive D-ribose cause "ribosylation"?
If this is so, treating the tau corruption and aggregation problem directly with chemicals (see the Tau Busters), any positive effects may be short-lived since the glucose problem would still exist, and the neurons would continue to starve for energy. If the cells can still use ketone bodies as a back up power supply, then perhaps ketogenic diets might help.
Phenothiazine-mediated
rescue of cognition in tau transgenic mice requires
neuroprotection and reduced soluble tau burden
It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function.
Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection.
Results: Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, RemberTM, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced.
Conclusions: Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model.
Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced.
Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet"because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels.
This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.
Author: John O'LearyQingyou LiPaul MarinecLaura BlairErin CongdonAmelia JohnsonUmesh JinwalJohn KorenJeffrey JonesClara KraftMelinda PetersJose AbisambraKaren DuffEdwin WeeberJason GestwickiChad Dickey
Credits/Source: Molecular Neurodegeneration 2010
PMID:
21040568 [PubMed - in process]PMCID: PMC2989315It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function.
Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection.
Results: Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, RemberTM, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced.
Conclusions: Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model.
Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced.
Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet"because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels.
This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.
Author: John O'LearyQingyou LiPaul MarinecLaura BlairErin CongdonAmelia JohnsonUmesh JinwalJohn KorenJeffrey JonesClara KraftMelinda PetersJose AbisambraKaren DuffEdwin WeeberJason GestwickiChad Dickey
Credits/Source: Molecular Neurodegeneration 2010
Full text of the article:
Molecular Neurodegeneration 2010,
5:45doi:10.1186/1750-1326-5-45
http://www.molecularneurodegeneration.com/content/5/1/45
Pub Med Central: PMCID: PMC2989315
Mol Neurodegener. 2010; 5: 45.
Published online 2010 November 1. doi: 10.1186/1750-1326-5-45.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989315/?tool=pubmed
It is
interesting to note that the degeneration tends to follow the
path of neural networks:http://www.molecularneurodegeneration.com/content/5/1/45
Pub Med Central: PMCID: PMC2989315
Mol Neurodegener. 2010; 5: 45.
Published online 2010 November 1. doi: 10.1186/1750-1326-5-45.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989315/?tool=pubmed
Neuronal
subpopulations and genetic background in tauopathies: a catch
22 story?
L. Bue´e*, A. Delacourte
Neurobiology of Aging 22 (2001) 115–118
"...these vulnerable neurons degenerate following precise pathways. Regarding encephalopathy such as PEP, it is clear that a virus follows neural networks for its propagation. It is now well established that there is also a sequential degeneration of vulnerable networks of neurons in AD and PSP. In AD, both biochemical and neuropathological studies show that NFT formation starts in the hippocampal formation (from transentorhinal to entorhinal and then hippocampus), progresses sequentially as follows anterior, inferior and medium temporal cortex, and then spreads into polymodal association areas, unimodal areas and primary and/or sensory areas..."
http://www.alzheimer-adna.com/pdf/2001/2001Bueecatch22.pdf
In mid
2009 we read that corrupted tau proteins can have
characteristics similar to the prions of "mad cow disease",
scrapie, chronic wasting disease of deer, and CJD of humans:L. Bue´e*, A. Delacourte
Neurobiology of Aging 22 (2001) 115–118
"...these vulnerable neurons degenerate following precise pathways. Regarding encephalopathy such as PEP, it is clear that a virus follows neural networks for its propagation. It is now well established that there is also a sequential degeneration of vulnerable networks of neurons in AD and PSP. In AD, both biochemical and neuropathological studies show that NFT formation starts in the hippocampal formation (from transentorhinal to entorhinal and then hippocampus), progresses sequentially as follows anterior, inferior and medium temporal cortex, and then spreads into polymodal association areas, unimodal areas and primary and/or sensory areas..."
http://www.alzheimer-adna.com/pdf/2001/2001Bueecatch22.pdf
Rogue protein
'spreads in brain'
BBC Sunday, 7 June 2009
Scientists have shown a rogue protein thought to cause Alzheimer's can spread through the brain, turning healthy tissue bad. They believe the tau protein may share characteristics with the prion proteins which cause vCJD. When injected into the brains of healthy mice it triggered formation of protein tangles linked to Alzheimer's. However, experts stressed the Nature Cell Biology study did not mean tau could be passed from person to person. Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease... Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease.
http://news.bbc.co.uk/2/hi/health/8084787.stm
BBC Sunday, 7 June 2009
Scientists have shown a rogue protein thought to cause Alzheimer's can spread through the brain, turning healthy tissue bad. They believe the tau protein may share characteristics with the prion proteins which cause vCJD. When injected into the brains of healthy mice it triggered formation of protein tangles linked to Alzheimer's. However, experts stressed the Nature Cell Biology study did not mean tau could be passed from person to person. Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease... Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease.
http://news.bbc.co.uk/2/hi/health/8084787.stm
Vulnerable Brain Region May Be Central to Progression of Alzheimer's Disease
ScienceDaily (Nov. 7, 2010)
New research is helping to unravel the events that underlie the "spread" of Alzheimer's disease (AD) throughout the brain. The research, published by Cell Press in the November 4th issue of the journal Neuron, follows disease progression from a vulnerable brain region that is affected early in the disease to interconnected brain regions that are affected in later stages... "Our findings directly support the hypothesis that AD-related dysfunction is propagated through networks of neurons, with the EC as an important hub region of early vulnerability,"...
http://www.sciencedaily.com/releases/2010/11/101103135239.htm
[Note: here seems to be a similar progression in Parkinson's disease:
How
The Pathology Of Parkinson's Disease Spreads
ScienceDaily (July 29, 2009) — Accumulation of the synaptic protein alpha-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson's and other related neurodegenerative diseases. This pathology appears to spread throughout the brain as the disease progresses. Now, researchers at the University of California, San Diego School of Medicine and Konkuk University in Seoul, South Korea, have described how this mechanism works... "The discovery of cell-to-cell transmission of this protein may explain how alpha-synuclein aggregates can pass to new, healthy cells," said first author Paula Desplats, project scientist in UC San Diego's Department of Neurosciences. "We demonstrated how alpha-synuclein is taken up by neighboring cells, including grafted neuronal precursor cells, a mechanism that may cause Lewy bodies to spread to different brain structures."... In these studies, autopsies of deceased Parkinson's patients who had received implants of therapeutic fetal neurons 11 to 16 years prior revealed that alpha-synuclein had propagated to the transplanted neurons...
http://www.sciencedaily.com/releases/2009/07/090727191914.htm]
ScienceDaily (July 29, 2009) — Accumulation of the synaptic protein alpha-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson's and other related neurodegenerative diseases. This pathology appears to spread throughout the brain as the disease progresses. Now, researchers at the University of California, San Diego School of Medicine and Konkuk University in Seoul, South Korea, have described how this mechanism works... "The discovery of cell-to-cell transmission of this protein may explain how alpha-synuclein aggregates can pass to new, healthy cells," said first author Paula Desplats, project scientist in UC San Diego's Department of Neurosciences. "We demonstrated how alpha-synuclein is taken up by neighboring cells, including grafted neuronal precursor cells, a mechanism that may cause Lewy bodies to spread to different brain structures."... In these studies, autopsies of deceased Parkinson's patients who had received implants of therapeutic fetal neurons 11 to 16 years prior revealed that alpha-synuclein had propagated to the transplanted neurons...
http://www.sciencedaily.com/releases/2009/07/090727191914.htm]
Glucose hypometabolism
See also Coconut Oil
Just as in Alzheimer's disease, glucose hypometabolism is a characteristic of CBD. Areas of the brain affected by the disease can be identified by neuro imaging techniques that look for a problem with glucose metabolism. Ketogenic diets might help. See Coconut Oil
The test called "FDG-PET" ([(18)F]-fluoro-deoxyglucose positron emission tomography) detects areas of the brain experiencing glucose hypometabolism.
Mitochondrial Dysfunction (and ATP Depletion)
This may relate to glucose hypometabolism and the production of ATP (and the use of D-ribose).
See http://health.groups.yahoo.com/group/tauopathies/message/200
There are several ideas for addressing the problem of mitochondrial dysfunction:
CoQ10
L-carnitine
Magnesium
[D-ribose (not used due to questions about safety with CBD tau corruption)]
Target: Mitochondrial dysfunction
L-carnitine
Magnesium
[D-ribose (not used due to questions about safety with CBD tau corruption)]
Target: Mitochondrial dysfunction
alpha-tocopherol
(vitamin E)
N-acetyl cysteine (NAC)
Niacinamide
Target: Mitochondrial dysfunction
[Dosage unknown. Use "Suggested Usage" from bottles for the time being.]
N-acetyl cysteine (NAC)
Niacinamide
Target: Mitochondrial dysfunction
[Dosage unknown. Use "Suggested Usage" from bottles for the time being.]
Target:
Mitochondrial
dysfunction
vitamin B6 (pyridoxine HCl) -
20mg / day
vitamin B9 (folate or folic acid) - 0.8mg (= 800 mcg.) / day
vitamin B12 (cyanocobalamin) - 0.5mg (= 500 mcg.) / day
vitamin B9 (folate or folic acid) - 0.8mg (= 800 mcg.) / day
vitamin B12 (cyanocobalamin) - 0.5mg (= 500 mcg.) / day
Target:
???
Adding medium chain triglycerides (MCTs) to the diet may be an effective work-around for one type of mitochondrial disfunction, glucose hypometabolism.
Exposure to toxins?
Could silver toxity be a cause some cases?
Case Reports: Unintentional silver intoxication following self-medication: an unusual case of corticobasal degeneration
Annals of Clinical Biochemistry
1 November 2009
Ann Clin Biochem 2009;46:520-522
doi:10.1258/acb.2009.009082
Exposure to "Agent Orange" in the military (after WWII to the mid 1970's) or the industrial version used by power utility companies to clear the brush from beneath power lines. It is rumored on some message boards that "Parkinson's Disease has been accepted by the Veteran's Administration as a disease that can be attributed to agent orange." So perhaps Agent Orange exposure is behind some cases of CBD.
Sporadic PSP-like disease has been linked to chronic consumption of plants of the Annonaceae family, in particular Annona muricata in Guadeloupe (Caparros-Lefebvre and Elbaz, 1999; Lannuzel et al., 2007), and also in other regions (Angibaud et al., 2004). (It is possible that these were sporadic cases of PSP.) Annonaceae plants contain acetogenins, which are highly lipophilic, stable and extremely potent inhibitors of complex I in vitro (Zafra-Polo et al., 1996). Annonacin, the most abundant acetogenin in A. muricata, kills neurons by ATP-depletio at nanomolar concentrations.
Other environmental lipophilic complex I [NEED DEFINITION!!!! -ed] inhibitors [Need a list of these -ed] have been studied and were found to cause decreased ATP levels, neuronal cell death and somatodendritic redistribution [NEED DEFINITION!!!! -ed] of phosphorylated tau protein from axons to the cell body in primary cultures of foetal rat striatum (Escobar-Khondiker et al., 2007; Ho¨ llerhage et al., 2009). Their potency to decrease ATP-levels correlated with their potency to induce tau redistribution, suggesting that ATP depletion is the main underlying cause of tau redistribution.
Bacterial, Viral or Prion cause?
Neurological disorders like CBD tend to follow paths through the brain, starting in one area and progressing to other connected areas. This is suspiciously like a viral or prion type progression. However, neither has been identified... yet.
Note: "Dementia" has been linked to chronic infections, such as the stomach ulcer bacteria and periadontal disease.
Update September 17, 2011: A large percentage of CBS cases turn out to be due to "Alzheimer's disease pathology". In other words, the CBS symptoms are a rare manifestation of Alzheimer's disease. There is a theory that many, if not most cases of AD are caused by an infection! Read more at The Role of Infection and Inflammation in Neurodegenerative Diseases. The big question is, by the time CBS symptoms appear, is it too late, even if the pathogen is identified and eradicated? Has too much damage already been done? I don't know, but if you are the type that is compelled to follow all leads, then you will want to explore this one.
Head Injury
See also Head/Brain Injury
Lou Gehrig may not have had Lou Gehrig's disease?
Sports Brain Trauma May Cause
Disease Mimicking ALS, Researchers Find
http://www.sciencedaily.com/releases/2010/08/100817134304.htm
http://www.sciencedaily.com/releases/2010/08/100817134304.htm
Could something similar be the initiator CBD?
Iron Metabolism
See "Iron Metabolism in Parkinsonian Syndromes"
"Irony of Iron"
CCSVI
The outlook for a therapy...
"Pharmacotherapy for CBD has
generally been of limited benefit. The treatment efforts are
focused on alleviating rigidity, dystonia, tremor, myoclonus,
neuropsychological symptoms, and other manifestations. Part of
the difficulty in designing effective pharmacotherapy for CBD is
the widespread pathological involvement of different subcortical
and cortical neuronal systems and the lack of knowledge of the
full biochemical and molecular background to explain the
pathophysiology of the various manifestations."
CORTICOBASAL DEGENERATION/STOVER, WATTS
SEMINARS IN NEUROLOGY/VOLUME 21, NUMBER 1 2001
[Note: This was the outlook of over 10 years ago!]
Some possible "Disease Modifying Agents":CORTICOBASAL DEGENERATION/STOVER, WATTS
SEMINARS IN NEUROLOGY/VOLUME 21, NUMBER 1 2001
[Note: This was the outlook of over 10 years ago!]
Substance: Coenzyme Q10 [CoQ10]
Target: Mitochondrial dysfunction
Mechanism: Complex I cofactor
Substance: Pyruvate, creatine, niacinamide
Target: Mitochondrial dysfunction
Mechanism: Multifunctional cocktail
Substance: Lithium
Target: Tau dysfunction
Mechanism: GSK-3beta inhibitors
Substance: Valproic acid
Target: Tau dysfunction
Mechanism: Aggregation inhibitors
Substance: Nypta
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Substance: Methylthioninium chloride [Methylene blue?]
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Substance: Danuvetide
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Substance: Cinnamon proanthocyanidins, cinnameldehyde
Target: Tau dysfunction, glucose metabolism
Mechanism: Microtubule stabilizers, improves glucose metabolism
Substance: Grape seed extract
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Substance: Medium Chain Triglycerides
Target: Glucose hypometabolism
Mechanism: Ketogenic diet
Some other things to look into are neurospirochetosis, B12 deficency, AFA and Colostrinin
(In the case of neurospirochetosis, the "treatment" would be some sort of effective antibiotic therapy.)
The medical establishment are quick to tell you that there's nothing they can do, but have they tried these things? If they insist that they don't or can't work, ask, "Have you tried them? Here are the research papers telling you why they could work. Where are the papers telling me why they can't?"
Why not try?
It's comforting to delude yourself into believing that there are giants out there diligently and unceasingly working for us and serving our every need. But there aren't. This must be a leftover from childhood. Some people like to believe that there is a class of wise elites who know everything and will take care of everything. There isn't. This is a leftover from the days of kings, dukes, lords and "our betters". There is education, experience, and cleverness. Cleverness is the ability to do something with the information you have. There are educated people who are not clever. There are experienced people who are not educated, but they are clever. There are clever people who are not experiened. Add to this that there are educated, experienced, clever people who are not curious. Ego is a major motivating factor in academia and this is ironic. Academia should be motived by logic and what is best for the greater good, but it is mostly concerned with pride, financial gain, and the acquisition of control. You are smarter than you think, and quite capable of looking things up, putting the pieces of the puzzel together, and coming up with ideas that the educated elite have no motivation to look for. I think that motivation is the key. It makes you curious. It makes you look. You are motivated to find answers. Are they?
Some CBD related sites:
Google Groups:
Tauopathies [Tone: open]
Yahoo Groups:
CBD_support
The Litvan Neurological Foundation, Inc. (LNRF)
http://www.litvanfoundation.com/index.php?option=com_content&task=blogcategory&id=15&Itemid=171
The Center of Excellence in
Corticobasal Degeneration
Newsletter Volume 1, Issue 1 Spring 2010
http://www.litvanfoundation.com/images/pdfs/cbd%20newsletter%201_1%20march%202010.pdf
Newsletter Volume 1, Issue 1 Spring 2010
http://www.litvanfoundation.com/images/pdfs/cbd%20newsletter%201_1%20march%202010.pdf
U.S. NATIONAL INSTITUTES OF HEALTH
National Institute on Aging
The Alzheimer's Disease Education and Referral (ADEAR) Center
Booklet - Frontotemporal Disorders: Information for Patients, Families, and Caregivers
http://www.nia.nih.gov/NR/rdonlyres/80E4FE4B-47A4-43A2-905B-8443E5759A47/0/FTDbooklet_10oct8.pdf
The following "CBGD Caregivers Report" articles are a bit dated (from about 2000), but still have good information.
CBGD Caregivers Report
Welcome to the
online version
Alan G. McIlvaine, Scottsdale, AZ.
Theresa Roberts, Long Beach, CA.
Darcy Croissant, Glenwood Springs, CO.
Anonymous
Sandra Till, UK
Robert Hall, South bend, IN.
Louise Davis, Australia
Sandra Roberts, Norfolk, VA
Judy Graham, Daughter of Dottie Powell, Shady Shores, Texas.
Alan G. McIlvaine, Scottsdale, AZ.
Theresa Roberts, Long Beach, CA.
Darcy Croissant, Glenwood Springs, CO.
Anonymous
Sandra Till, UK
Robert Hall, South bend, IN.
Louise Davis, Australia
Sandra Roberts, Norfolk, VA
Judy Graham, Daughter of Dottie Powell, Shady Shores, Texas.
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Final Thoughts
I am continually astounded and confounded by how reluctant most caretakers are to fight this disease. I am even more astonished by how many victims of CBD would rather let the disease have its way with them. It is almost as if there is an unspoken deathwish... Thanatos. Or maybe they feel that the disease has sort of consciousness and that it will be angry and revengeful at such insolence. But what it appears like is most caregivers want their charge to hurry along and get it over with, and the victims see the disease as a badge of honor that gives them some sort of macabre status among the well. Here I have listed a treasure trove of things to try, yet there just doesn't seem to be any interest. In fact, what I detect is a desire to speed the disease along and let the Grim Reaper solve all their problems. But, you are here, so you probably want to try something, even if, to be realistic, the odds of success are not so good.
I'm not saying that some researcher "out there" has the cure and is hiding it because of some nefarious plot against humanity. I'm not saying a cure or even a treatment is known. I do assert that a treatment and a cure exists, even if no one on Earth knows what it is yet. Therefore, it is reasonable, to look for it. If you do not believe a cure exists, you would be a fool to look for one.
Knowing what the outcome of doing nothing is, one might as well pursue alternative medicine, herbal remedies, and new ideas in traditional medicine. Much can be learned from trying new ideas on live people.
If you make up your mind that something does not exist, can not possibly exist, then you will not look for it, and you will be rewarded appropriately consistent with your expectations. . If you drive to a store with the unshakable firm conviction that there are no unoccupied parking spaces close to the door, you will pull into the first open spot you find. Then, only as you walk to the door will you discover, oh yeah, here's a spot, and there, and over there... Of course, there are some people who even upon seeing an empty parking spot close to the door, their conviction will be such that they will believe that they are hallucinating.
There are many ideas that have not been tried yet on people suffering with CBD. It is a very very rare disease so all but the most specialized physicians and researchers have the time, money or motivation to keep up on developments. Unlike years past, with the Internet, motivated amateurs can keep up on published research and pull together seemingly disparate pieces of information from around the world to synthesize a picture of a disease process and plans for altering it that have escaped the professionals. Since up to this point the professionals have very little to offer other than a pat on the hand and some kind words, I hope this is so.
To me, this means that you can make a real contribution by trying things to help a living person. And I think that this contribution will be much more helpful than merely donating a dead organ to science.
There have been some anecdotal reports of positive results with B12, water-soluble cinnamon extract, MCT oils, AFA and AFA extracts. Take them as leads for where to start your own inquiries.
Don't let the good-deathers get to you. There is no compassion in death. None. Zip. Zero. Nada. Only in life. Death comes in so many cruel ways. There is no need to hurry it along. If we get to decide whose life is worth living and who should die based on our judgement of their quality of life, and if they are "suffering", whoa Nelly! Watch out. I might decide that your life does not contribute, that you are suffering, and that your life is not of much use to you since it certainly isn't much use to me. Hmmm... seems that genocide stems from such elitism.
Ecclesiastes 9
1 For all this I considered in my heart even to declare all this, that the righteous, and the wise, and their works, are in the hand of God: no man knoweth either love or hatred by all that is before them. 2 All things come alike to all: there is one event to the righteous, and to the wicked; to the good and to the clean, and to the unclean; to him that sacrificeth, and to him that sacrificeth not: as is the good, so is the sinner; and he that sweareth, as he that feareth an oath. 3 This is an evil among all things that are done under the sun, that there is one event unto all: yea, also the heart of the sons of men is full of evil, and madness is in their heart while they live, and after that they go to the dead. 4 For to him that is joined to all the living there is hope: for a living dog is better than a dead lion. 5 For the living know that they shall die: but the dead know not any thing, neither have they any more a reward; for the memory of them is forgotten. 6 Also their love, and their hatred, and their envy, is now perished; neither have they any more a portion for ever in any thing that is done under the sun. 7 Go thy way, eat thy bread with joy, and drink thy wine with a merry heart; for God now accepteth thy works. 8 Let thy garments be always white; and let thy head lack no ointment. 9 Live joyfully with the wife whom thou lovest all the days of the life of thy vanity, which he hath given thee under the sun, all the days of thy vanity: for that is thy portion in this life, and in thy labour which thou takest under the sun. 10 Whatsoever thy hand findeth to do, do it with thy might; for there is no work, nor device, nor knowledge, nor wisdom, in the grave, whither thou goest. 11 I returned, and saw under the sun, that the race is not to the swift, nor the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favour to men of skill; but time and chance happeneth to them all. 12 For man also knoweth not his time: as the fishes that are taken in an evil net, and as the birds that are caught in the snare; so are the sons of men snared in an evil time, when it falleth suddenly upon them. 13 This wisdom have I seen also under the sun, and it seemed great unto me: 14 There was a little city, and few men within it; and there came a great king against it, and besieged it, and built great bulwarks against it: 15 Now there was found in it a poor wise man, and he by his wisdom delivered the city; yet no man remembered that same poor man. 16 Then said I, Wisdom is better than strength: nevertheless the poor man's wisdom is despised, and his words are not heard. 17 The words of wise men are heard in quiet more than the cry of him that ruleth among fools. 18 Wisdom is better than weapons of war: but one sinner destroyeth much good.
1 For all this I considered in my heart even to declare all this, that the righteous, and the wise, and their works, are in the hand of God: no man knoweth either love or hatred by all that is before them. 2 All things come alike to all: there is one event to the righteous, and to the wicked; to the good and to the clean, and to the unclean; to him that sacrificeth, and to him that sacrificeth not: as is the good, so is the sinner; and he that sweareth, as he that feareth an oath. 3 This is an evil among all things that are done under the sun, that there is one event unto all: yea, also the heart of the sons of men is full of evil, and madness is in their heart while they live, and after that they go to the dead. 4 For to him that is joined to all the living there is hope: for a living dog is better than a dead lion. 5 For the living know that they shall die: but the dead know not any thing, neither have they any more a reward; for the memory of them is forgotten. 6 Also their love, and their hatred, and their envy, is now perished; neither have they any more a portion for ever in any thing that is done under the sun. 7 Go thy way, eat thy bread with joy, and drink thy wine with a merry heart; for God now accepteth thy works. 8 Let thy garments be always white; and let thy head lack no ointment. 9 Live joyfully with the wife whom thou lovest all the days of the life of thy vanity, which he hath given thee under the sun, all the days of thy vanity: for that is thy portion in this life, and in thy labour which thou takest under the sun. 10 Whatsoever thy hand findeth to do, do it with thy might; for there is no work, nor device, nor knowledge, nor wisdom, in the grave, whither thou goest. 11 I returned, and saw under the sun, that the race is not to the swift, nor the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favour to men of skill; but time and chance happeneth to them all. 12 For man also knoweth not his time: as the fishes that are taken in an evil net, and as the birds that are caught in the snare; so are the sons of men snared in an evil time, when it falleth suddenly upon them. 13 This wisdom have I seen also under the sun, and it seemed great unto me: 14 There was a little city, and few men within it; and there came a great king against it, and besieged it, and built great bulwarks against it: 15 Now there was found in it a poor wise man, and he by his wisdom delivered the city; yet no man remembered that same poor man. 16 Then said I, Wisdom is better than strength: nevertheless the poor man's wisdom is despised, and his words are not heard. 17 The words of wise men are heard in quiet more than the cry of him that ruleth among fools. 18 Wisdom is better than weapons of war: but one sinner destroyeth much good.
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Home Preface Brain Failure Notes References pg. 1 References pg. 2
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Updated: November 9, 2010
Inception: November 4, 2009