Corticobasal Ganglionic Degeneration (CBGD)
This 73 year old man, with a history of hypertension and coronary artery disease, presented with a one-and-a-half year history of progressive inability to use his left arm, slurred speech, gait difficulty, and non-specific bladder complaints. On exam, he had slight postural hypotension, slight difficulties with arithmetic, impaired saccades, slurred speech, tremor, and dystonia, worse on the left than on the right. He also had apraxia and evidence of bilateral pyramidal tract dysfunction, again worse on the left. Pertinent negatives included lack of significant cognitive impairment, no clinical benefit to levodopa, no evidence of ataxia, and a negative family history. The differential diagnosis for progressive neurological decline in extrapyramidal, pyramidal, and cortical function, and a negative family history would include the "parkinsonism plus" syndromes. The following diseases or syndromes were considered in the differential for this patient:
Idiopathic Parkinson's disease usually begins unilaterally and our patient's symptoms of predominantly left sided rigidity, cogwheeling, and shaking were consistent with this diagnosis. However, the additional signs and symptoms of postural hypotension and cortical apraxia, as well as the lack of a response to carbidopa/levodopa, suggested a different pathological process than that occurring in idiopathic Parkinson's disease.
This patient had a history of hypertension and coronary artery disease, risk factors for cerebrovascular disease. Multiple subcortical infarcts can produce clinical syndromes which appear similar to idiopathic Parkinson's disease, progressive supranuclear palsy, and normal pressure hydrocephalus. The asymmetry of the patient's complaints and physical findings were supportive of a focal, possibly ischemic etiology. However, ideomotor apraxia would reflect a cortical localization for an infarct which was not seen on the MRI of this patient. Also, the chronic progressive nature of his symptoms, without a history of stroke or stepwise deterioration, made the diagnosis of a multi-infarct state less likely.
PSP usually presents in the seventh decade with supranuclear gaze palsy (particularly of down gaze), bradykinesia, rigidity (especially of the axial musculature), and gait unsteadiness. Our patient did have some impairment of saccades and a mild supranuclear gaze paresis. Dystonia can occur in PSP but is usually in the neck musculature. Limb dystonia has been reported in PSP, but it is rare. PSP usually presents symmetrically and our patient's complaints and findings were distinctly asymmetric.
Postural hypotension, bladder complaints, parkinsonism, and a lack of response to carbidopa/levodopa, would all be in accord with the Shy-Drager syndrome (SDS) form of MSA. However, in SDS, the symptoms are usually symmetric in onset and the cortical findings seen in our patient would be unusual.
Striatonigral degeneration (SND), another form of MSA, was included in the differential diagnosis. The dysarthria seen in our patient is often present in SND, as are the pyramidal signs such as hyperreflexia. However, the asymmetric symptoms and cortical findings would make this diagnosis less likely.
The symptoms and signs present in our patient, (unilateral limb rigidity, apraxia, dystonia, difficulty with saccades, and dysarthria), were felt to be most consistent with a diagnosis of CBGD.
The patient had slow saccades and dysmetria and prolonged latency of initiating saccades (vertically more than horizontally). Saccadic (cogwheel) pursuit was slow. A mild supranuclear gaze paresis was present, but was overcome by doll's head maneuver. These findings were not specific for any particular disorder, but were consistent with a neurodegenerative disease.
The apraxia seen in our patient was typical for CBGD. Mild ideomotor apraxia was present in the right hand with marked apraxia in the left hand which was compounded with rigidity and dystonia. Despite the patient stating that he could not get his left arm to do what he wanted it to, and needing to restrain it with his right arm, he specifically denied the subjective sensation that the arm felt foreign, as if it did not belong to him (the "alien limb" sign). Although he had some dystonia and mild proprioceptive deficits, it was not enough to account for the dramatic impairment of function in his left arm and less severely in his left leg.
Since patients with CBGD do not have autonomic complaints, our patient's mild orthostatic hypotension and non-specific bladder complaints would be atypical. It was felt that the orthostasis was related to medication and the urinary urgency to a separate process. Since the patient had previously been given carbidopa/levodopa with no apparent benefit, he was started on a trial of baclofen and will be seen in follow-up in one month.
The clinical syndrome of asymmetric parkinsonism and cortical abnormalities along with unique pathology were first reported in 1968[1] and later came to be known as corticobasal ganglionic degeneration (CBGD). Since then, there has been increasing recognition of the syndrome and two large series[2,3] have been reported. A total of 51 patients with clinical CBGD were discussed and there was pathological verification in five. The most common signs and symptoms were (in descending order): limb rigidity (100%), limb apraxia (91%), gait difficulties (89%), focal reflex myoclonus (88%), eye movement abnormalities (78%), limb dystonia (77%), pyramidal signs (73%), dysarthria (62%), cortical sensory abnormalities (55%), and the "alien limb" phenomenon (55%). Tremor, frontal lobe reflexes, and cognitive impairment are less commonly seen. Thirty-seven percent of cases had symptoms which began on the right and 63% on the left. Sixty-four percent of patients had symptoms beginning in an arm, 28% with difficulty walking, 5% with an arm and leg equally involved, and 3% with speech difficulties. The disease is steadily progressive with a mean survival of 6-7 years.
Apraxia, one of the hallmarks of CBGD, is defined as the inability to perform coordinated motor activities in the absence of weakness, comprehension deficits, or adventitious movements.
Ideomotor apraxia, or the inability to execute an action, has been divided into two types[4], one associated with left parietal damage and one with damage to the left supplementary motor area. In the parietal variety, the ability to comprehend gestures as well as to pantomime to verbal command is lost; whereas in the frontal variety, gesture comprehension is normal.
Ideational apraxia is when the entire concept of an action is lost and the subject can not even attempt it. This can be tested by having subjects perform sequential tasks like having them turn on a flashlight after given two batteries and an empty flashlight.
Buccofacial apraxia, or apraxia of activities of the mouth and face, can be tested by having the patients perform such actions as blowing out a match and licking crumbs off their lips.
A study of apraxia in the less involved limb in 10 patients with CBGD[5] showed that seven had ideomotor apraxia and none had buccofacial apraxia. Four of the seven with ideomotor apraxia had intact gestural comprehension so their apraxia was of the frontal type. The other three had more severe apraxia with ideational deficits as well as difficulties with gestural comprehension. In this study, half the patients had onset of symptoms from the left hemisphere and half from the right. All of the five with initial symptoms in the left hemisphere had apraxia in the left hand whereas only two of the five with symptoms starting in the right hemisphere exhibited apraxia in the ipsilateral hand. This is consistent with other studies in CBGD[6] and that in most right handers the "engram" for movement sequences for both hands is in the left hemisphere.[4]
The distinction of CBGD as a unique entity was established with the initial case report in 1968.[1] These authors described asymmetric convolutional atrophy of the frontal and parietal lobes macroscopically. Microscopically, they observed marked neuronal loss in the outer layers of these cortical areas and astrocytic gliosis without a significant inflammatory reaction. Most distinctive in CBGD are swollen neuronal bodies with eccentric displacement of the nucleus and lack of cytoplasmic staining. Subcortically, loss of neurons in the substantia nigra and in the subthalamic nucleus as well as in the dentate nuclei in two of three cases was identified. The swollen neuronal bodies seen in CBGD are somewhat reminiscent of the changes seen in Pick's disease, but the absence of Pick bodies and the characteristic distribution of the changes usually distinguish the two diseases.
Diagnostic tests are helpful in excluding other disorders, but the diagnosis of CBGD is ultimately clinical. CT and MRI reveal asymmetrical atrophy corresponding to the symptomatic side in about 50% of cases, whereas atrophy is symmetric in the other 50%.[2] A study of CBGD patients with PET techniques[7] showed decreased fluorodopa uptake in the basal ganglia asymmetrically as well as asymmetric decreased oxygen metabolism in the superior and posterior temporal, the inferior parietal, and occipital association cortices.
Although the clinical presentation of CBGD is fairly unique, there can be errors in the diagnosis. Cases of pathologically proven CBGD have presented with severe dementia and isolated speech disturbances[8] as well as levodopa responsive parkinsonism, ataxia, and progressive myoclonic epilepsy.[2] Alzheimer's, PSP, SND, hemiparkinsonism, and Pick's disease have also presented with the classical findings of CBGD.[9]
Treatment of CBGD has been tried but with only occasional benefit. Symptomatic medications as diverse as chlordiazepoxide, carbidopa/levodopa, propranolol, methysergide, and amantadine have all been administered, with minimal success.
Email comments: