Corticobasal degeneration (CBD) is a rare neurodegenerative disorder that may result in profound visual impairment. It is characterized by both cerebral cortex and basal ganglia signs. Cortical features include progressive apraxia, dementia, myoclonus, and aphasia, while basal ganglia features include akinesia, rigidity, and dystonia.
The lack of universal diagnostic criteria makes it difficult to assess the true incidence of CBD, but it is estimated to occur in 0.62 to 0.92 per 100,000 per year with possible female predilection (1). It is almost always sporadic and presents between 60 and 80 years of age. Diagnosis early in the course is often difficult, as the disorder shares many features with progressive supranuclear palsy (PSP), Parkinson disease, frontotemporal dementia, and multiple systems atrophy (MSA) (2). A distinctive feature of CBD is its marked asymmetric or unilateral onset of motor apraxia. Typically, patients develop a “useless” or “alien” limb, as well as focal apraxia, rigidity and dystonia, usually of one of the upper limbs (3). Definitive diagnosis requires histopathological analysis demonstrating atrophy in the cerebral cortex and basal ganglia corresponding to areas of tau protein accumulation (4,5). In the absence of histopathological confirmation, the term corticobasal syndrome (CBS) is used to describe the clinical presentation of CBD (5).
Impairment of visual function is rare in CBS but can be quite striking. Visual involvement generally occurs in the form of oculomotor deficits. Specifically, asymmetric visuomotor apraxia can occur without actual gaze paresis. Visual dysfunction also may result from the severe cognitive impairment leading to impairment of visuospatial processing, including simultagnosia and optic ataxia (1,6). We describe a case of CBS with profound visual deficits that was diagnosed by neuro-ophthalmologic and neuropsychometric testing.
A 60-year-old woman noted progressive difficulty with vision over the past year, characterized by difficulty reading and performing everyday household tasks. Several years earlier, she experienced worsening memory and attention deficits, which initially were attributed to Alzheimer disease. She subsequently developed increasing gait and movement abnormalities. Cognitive and motor function testing revealed both extrapyramidal and cortical deficits, and she was given a diagnosis of CBS. The remainder of her medical and surgical history was noncontributory.
During her initial encounter in the neuro-ophthalmology clinic, much of her history had to be provided by her husband, as her cognitive impairment prevented prolonged coherent speech. Both her husband and her physical therapists had noted that she had difficulty with reaching for objects, and she often missed her targets. She had great difficulty in finding objects within visual space. She denied loss of vision, photopsia, scotoma, or diplopia. There was no family history of neurodegenerative or ophthalmologic disease. The patient was alert and responsive to commands. She had experienced frequent involuntary movements of her upper body and head. Visual acuity was 20/40 in each eye. She had great difficulty in finding the Snellen chart optotypes and often made corrective head movements rather than ocular saccades. She was unable to perform color vision testing, as she was unable to locate the Isihara plates. Visual field assessment was difficult, but she appeared to have intact evoked saccades to hand motions in all fields. Pupils, external, slit-lamp, and fundus examinations were normal. While ductions and versions were intact, she had prolonged latency for saccadic movements in all directions, particularly upgaze. Her saccadic apraxia was also associated with mild saccadic dysmetria, but saccadic velocity appeared normal. Pursuit movements were also markedly and symmetrically impaired. There was no gaze preference. There was no nystagmus, but she had micro- and macro-square-wave jerks.
On neurologic examination, the patient demonstrated marked impairment with finger-to-nose tasks, felt to be secondary to optic ataxia. This deficit was more prominent with the use of her left hand or left-sided visual stimuli. The patient demonstrated profound simultagnosia in describing the Cookie-Thief drawing (used in the NIH Stroke Scale testing form). She displayed no resting tremor and had normal muscular tone. However, she had marked ideomotor apraxia. She tended to use her left hand much less than the right and was noted to exhibit an occasional tonic flexed posture of the left arm. The patient had an expressive aphasia and although her speech was intermittently fluent, she often displayed a hesitant cadence and had difficulty with certain words. She also demonstrated mild alexia, as she could only read the first sentence of the NIH Stroke Scale.
More detailed neuropsychometric testing performed earlier had revealed cognitive deficits consistent with moderate dementia, with a score of 12 (normal range: 23–30) on the mini–mental state examination and 5 (normal range: 7–10) on her word list memory tasks. Her testing was limited by expressive aphasia, and the level of her dementia may have been overestimated.
MRI of the brain revealed diffuse cortical atrophy, with some predominance in the posterior parietal regions. The patient was referred to low vision services and was advised to continue occupational and physical rehabilitation.
Our patient had clinical findings consistent with CBS and severe visuomotor dysfunction. Several features support the diagnosis of CBS, including focal ideomotor apraxia, a partial alien limb phenomenon involving the left upper extremity, and signs of moderate dementia (7–9). Consistent with her systemic manifestations, one of our patient's primary visual deficits was oculomotor apraxia.
The clinical distinction between CBS and PSP or other tauopathies is difficult to define (Table 1). A review of patients with either clinical or histopathological diagnosis of CBS-CBD revealed that only 5 of 19 patients with pathologic confirmation of CBD were correctly diagnosed with CBS during life (10). Conversely, of 21 patients who were diagnosed with CBS during life, only 5 had pathology consistent with CBD. Some have suggested that the clinical presentation typically attributed to either CBS or PSP instead be grouped in a single entity (10,11).
Likewise, distinguishing visual involvement in CBS from that found in PSP may be challenging. The visual involvement in CBS overlaps to some degree with PSP, including an apparent supranuclear ophthalmoplegia seen in both of these disease entities (12). However, in CBS, there is not a true paresis of saccades but rather prolonged saccadic latency. In PSP, saccades are slow, whereas in CBS, velocity and range of saccades remain intact (13). PSP typically affects vertical saccades, while in CBS, horizontal eye movements more often are affected. If the clinical examination is conducted hastily, prolonged saccadic latency may be mistaken for a gaze palsy and mislead the examiner to diagnose PSP.
Features of our case that are unusual for CBS include prolonged saccadic latency in upgaze and preserved horizontal saccades. There have been reports of pathologically confirmed CBD that have produced severe saccadic apraxia in upgaze (14).
Less commonly, visual involvement in CBS is due to disorders of higher processing functions of the cerebral cortex.(15) Our patient demonstrated simultagnosia, optic ataxia, and oculomotor apraxia. These are features of Balint syndrome, which results from bilateral occipital-parietal dysfunction. Tang-Wai et al (16) reported a similar case of histopathologically confirmed CBD; the patient presented with visual processing dysfunction with features of both Balint and Gerstmann syndrome (16). The presence of higher-order visual processing dysfunction has been associated with the extent of cortical involvement in CBS. Neuroimaging and postmortem examination of patients presenting with visuospatial processing deficits in CBS has revealed diffuse or focal cerebral atrophy (16). A recent series of patients with atypical parkinsonian syndromes, looking specifically at visuospatial dysfunction, found that patients with CBS tended to show more deficits compared to those with PSP or MSA (6). In this study, many patients with CBS had normal mini–mental state examinations, suggesting that the visuospatial disorders observed could not solely be attributed to general cognitive decline.
While universally accepted diagnostic criteria for CBS are lacking, the neurologic evaluation findings should include unilateral or general apraxia and dystonia and focal or generalized cortical sensory loss. Neuropsychometric testing may demonstrate additional deficits of higher cognitive function, including memory and language. Neuroimaging, while not necessarily helpful for making a diagnosis of CBD, can exclude other more treatable conditions (2,17). Prognosis is poor, as most patients die within 10 years of the onset of the symptoms secondary to severe dysphagia or complications of being immobile (18). Although there is no treatment for CBS, low vision evaluation and physical therapy may improve patient functioning.
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