Cortical Basal Ganglionic Degeneration
Author: Anna M Barrett, MD; Chief Editor: Selim R Benbadis, MD more...
Author: Anna M Barrett, MD; Chief Editor: Selim R Benbadis, MD more...
Updated: Feb 19, 2010
Cortical
basal ganglionic degeneration (CBGD), a sporadic neurodegenerative
tauopathy, 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[26] or
primary progressive apraxia in patients who had no prominent
movement disorders earlier in their lives.
Background
Data on incidence and prevalence of this disorder are still being collected. Clinical reports have multiplied geometrically in the last 20 years, suggesting either that clinical evaluation has become more sensitive or that the syndrome is appearing more frequently. It is estimated to account for about 5% of cases of parkinsonism seen in clinics that specialize in movement disorders, or 0.62-0.92 per 100,000 per year, with an estimated prevalence of 4.9-7.3 per 100,000.
This is a progressive neurodegenerative disorder with increasing levels of disability and loss of independence. Individuals with CBGD do not usually die of the disorder itself but of complications of the bedridden state, such as aspiration pneumonia and infections, within 10 years of onset.
No racial predilection is known.
CBDG may be more common in women.
Typically, CBGD presents between the ages of 60 and 80. No pathologically confirmed case of CBGD has ever been published with onset before 45 years, but the author of this chapter personally reviewed medical records for a man who died with pathologically confirmed CBGD whose first symptoms occurred at age 41.
Boeve et al proposed the following clinical diagnostic criteria for cortical basal ganglionic degeneration (CBGD):[3]
Insidious onset and progressive course
No identifiable alternative cause (stroke, tumor, etc)
Cortical dysfunction including at least 1 of the following:
Focal or asymmetric ideomotor apraxia[37] : Disorder of skilled, learned, purposeful movement; this is one of the few disorders in which limb apraxia can appear in the history (ie, patients are often aware of the apraxia).
Alien limb ("My hand/leg has a mind of its own.")
Cortical (parietal) sensory loss
Visual or tactile neglect
Constructional apraxia
Focal or asymmetric myoclonus
Apraxia of speech or nonfluent aphasia[35]
Extrapyramidal dysfunction, including at least 1 of the following:
Focal or asymmetric appendicular rigidity (unresponsive to levodopa)[37]
Focal or asymmetric appendicular dystonia
In some cases, associated depression and postural instability
Unusual presentations, for example, primary progressive aphasia and progressive buccofacial apraxia
Prominent delusions or hallucinations (not related to levodopa): These suggest that the patient does not have CBGD; they are more characteristic of diffuse Lewy body disease.
Limb apraxia: Patients must make errors beyond using a body part as a tool (eg, using fingers as scissor blades). Errors often suggest ideomotor or limb-kinetic apraxia.
Other mental abnormalities include the following:
Amnesia
Generally, no "cognitive" abnormalities (eg, right-left disorientation, naming difficulty, acalculia), but rather "frontal-executive" deficits (eg, distractibility, perseveration, loss of judgment, motor planning deficit even on the less motor-impaired side)
Eye movements: These can be impaired, with restricted horizontal movements as well as upgaze; restricted downgaze is suggestive of progressive supranuclear palsy.
Dystonia: This is not purely action induced.
Myoclonus: Myoclonus must spread beyond fingers if stimulus sensitive.
Rigidity: This must be elicited easily without reinforcement.
No resting tremor is present.
No autonomic disturbance is present.
Cortical sensory loss: Loss of graphesthesia (ability to identify a letter drawn in the hand or on the finger) can be a sensitive test.
The cause of CBGD is unknown.
Case reports suggest that a familial predisposition may exist in some individuals with this disorder.
Because of the clinical and pathologic relationships between CBGD, progressive supranuclear palsy, and Pick disease, interest in this disease has focused on chromosome arm 17q markers. At this point, however, no definite relationship between genetic markers in this region and CBGD has been demonstrated.
Limb apraxia and eye movement abnormalities appear to be highly associated with left cortical structural change.
Frontal Lobe Syndromes (Primary Progressive Aphasia and Primary Progressive Apraxia)
Parkinson Disease
On first evaluation, discontinue anticholinergics or other medications that impair attention and memory. Discontinue any medications that may cause parkinsonism. Start vitamin E if the patient has memory loss. Consider empiric treatment of depression and initiate a trial of levodopa/carbidopa (Sinemet) if rigidity and movement disorder are disabling. Institute a plan for titration of this medication to an appropriate level before declaring the patient to be a "levodopa/carbidopa failure." Consider botulinum toxin injections if the patient has painful limb dystonia. Obtain an EEG if the patient has polymyoclonus or rapid decline. Refer to occupational, physical, and speech therapists, as needed, for gait and safety evaluation, assistive devices, and an exercise program to maintain endurance and strength.
On second evaluation, treat any systemic conditions identified on serologic testing. Discontinue Sinemet if ineffective, and begin empiric trial of second- or third-line dopaminergic agent or consider treatment with clonazepam for myoclonus. Consider a spinal tap if any symptoms suggestive of CNS Whipple disease are present; discuss this possibility with the patient and family. Refer the patient to a geriatric nurse practitioner, case manager, or other dementia resource persons when available. Share reading material on CBGD and dementia with the patient and family. Coordinate consultation with a behavioral neurologist or movement disorder specialist if the family desires.
On third evaluation, treat any systemic conditions further identified, perform spinal tap, and consider brain biopsy if the diagnosis is still in doubt or if the family or patient may benefit. Consider further adjustment of dopaminergic therapies depending upon clinical response.
Unfortunately, no treatment trials of medication for CBGD have been completed to date; thus, no regimen is reported to be highly effective in slowing or reversing its motor or cognitive symptoms.[17] Medications for Parkinson disease, including anticholinergics, levodopa, and dopamine agonists, may improve symptoms to some extent in many patients and usually are tried at some point during the course of the disease.
These agents are dopamine receptor agonists.
This agent, approved for the treatment of Alzheimer disease in the US, has both dopaminergic and neuroprotective properties. N-methyl-D-aspartate (NMDA) antagonist. Although no published evidence can be currently identified to support its use in CBGD, theoretically this agent might slow the progression of the disorder, or improve motor function.
Unresponsiveness to this medication supports diagnosis of CBGD; thus, an empiric trial, titrated to high dose (many advocate minimum 4 g daily), is recommended in every patient.
Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist. Stimulates dopamine receptors in corpus striatum.
Approximately 28% absorbed from GI tract and metabolized in liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine.
Initiate at low dosage; slowly increase dosage to individualize therapy. Maintain levodopa dosage during introductory period.
Assess dosage titration every 2 wk. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.
Often not helpful but a trial probably worthwhile for patients with disabling rigidity.
Nonergot dopamine agonist with specificity to D2 dopamine receptor but has also been shown to bind to D3 and D4 receptors and may stimulate dopamine activity on nerves of striatum and substantia nigra. Often not very helpful, but trial worthwhile.
Unknown mechanism of action; may release dopamine from dopaminergic terminals.
No studies demonstrate that therapy with neuroprotective drugs slows the course of CBGD. However, such therapy does affect the course of other neurodegenerative dementias; therefore, neuroprotective agents generally are offered empirically.
Might protect polyunsaturated fatty acids in membranes from attack by free radicals.
Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.
Numerous studies suggest neuroprotective effect in preventing or slowing course of dementia of Alzheimer type.
Useful for the management of myoclonus. By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.
Reduced disabling myoclonus in 23% patients in one trial. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.
Botulinum toxin can inhibit transmission of impulses in neuromuscular tissue.
Useful in reducing excessive, abnormal muscular contractions. Binds to receptor sites on motor nerve terminals and after uptake inhibits release of acetylcholine, blocking transmission of impulses in neuromuscular tissue.
Re-examine patients 7-14 d after administering initial dose to assess for satisfactory response.
Increase doses twofold over previously administered dose for patients who experience incomplete paralysis of target muscle. Doses of 200-300 units usually administered; maximum safe dose believed to be 400 units.