A Case of Subacute Progressive Cerebellar Ataxia: Brownell-Oppenheimer Variant of Sporadic Creutzfeldt-Jakob Disease
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.310104
Source of Support: None, Conflict of Interest: None
There are several clinical variants of sporadic Creutzfeldt-Jakob disease (sCJD) depending upon prominent symptom in initial stage of disease. Brownell Oppenheimer variant is relatively uncommon variant and is characterized by isolated presence of cerebellar ataxia early in the course of disease.
A 55-year-old female patient presented with progressive unsteadiness while walking of 10 weeks and progressive visual hallucination and behavioural abnormalities of 2 weeks duration. There was no history of myoclonus, hypertension, diabetes mellitus, coronary artery disease, or cerebrovascular disease.
On examination, she was euphoric, poorly attentive, disoriented with normal language function but impaired insight and judgement. Cranial nerve examinations were normal except markedly slow vertical saccades and tendency to keep head in extension position. Motor system examination was normal except abnormal rocking movement of trunk in the form of stereotypy was present. Frontal release signs were present with normal deep tendon and plantar reflex. Sensory system examination was normal. Cerebellar system examination revealed normal appendicular coordination and speech but patient had wide stance, gait ataxia and tandem walking was impaired.
Complete haemogram, liver and renal function tests, erythrocyte sedimentation rate, anti-nuclear antibodies, serum vitamin B12, thyroid function tests and anti thyroid peroxidise and thyroglobulin antibodies were within normal limits. All viral markers were negative including human immunodeficiency virus. Routine CSF analysis and EEG were normal. MRI brain showed bilateral caudate and putamen hyper-intensities well evident in DWI and FLAIR sequences characteristic of CJD [Figure 1]. Thus, the diagnosis of probable sCJD was made according to University of California–San Francisco (UCSF) 2007 criteria.
Few other conditions like Hashimoto encephalopathy, toxic-metabolic and anoxic encephalopathy, Lewy body disease, limbic and paraneoplastic encephalitis may have similar clinical presentation. These conditions were excluded by appropriate investigations and clinical evaluation as mentioned above. On follow-up at two months, the patient had relentless progression of disease and she was akinetic rigid and bed bound.
Sporadic CJD presents as four main variants – Heidenhain, cerebellar, panencephalitic and classic variants. Classic variant constitutes 60% of all cases, characterized by rapidly progressive dementia with startle myoclonus and typical EEG findings of periodic sharp waves. Motor sign are prominent including pyramidal, cerebellar and extrapyramidal signs. Heidenhain variant constitutes about 20% of all cases and its most salient feature is early visual disturbances. Panencephalitic variant accounts for approximately 10% of cases and it affects both gray and white matter and has both cortical and cerebellar symptomatology. Ataxic variant accounts for 10% of all cases of sCJD. Progressive cerebellar ataxia without presence of other typical symptoms of sCJD in initial stage of disease is hallmark of ataxic variant of sCJD also called Brownell-Oppenheimer variant. Cerebellar cortex is affected out of proportion to other gray matter in this variant and marked granule cell loss is prominent histopathological finding. Diagnosis at earlier stage can be difficult as initially it is dominated by isolated cerebellar ataxia with cognitive decline and other typical features of classic sCJD occurring late. Cooper et al. in their study of 29 cases of ataxic sCJD found that this variant constitutes 5% of all sCJD cases in United Kingdom with mean survival longer than classic sCJD. In their study, 80% of cases of these cases showed classical basal ganglia hyperintensities and 20% had normal MRI study but none had cerebellar abnormalities. Classical EEG abnormalities seen in only 10% cases as compared to two-third cases in classic sCJD. Reason behind normal EEG in this variant is that brunt of attack would be at cerebellum in initial part of disease and then on basal ganglia, thalamus and then cortex. Second, periodic sharp wave complexes which are characteristic of sCJD marks the onset of terminal stage of disease and can be absent in early stages as in our patient. Third, in the presence of movement disorder (e.g., myoclonus), EEG is most likely to be abnormal and our patient didn't have myoclonus till four months. Fourth, typical EEG findings of CJD only occurs in two-thirds of all cases.
We could not perform CSF 14-3-3 and autoantibody panel for paraneoplastic and limbic encephalitis due to financial constraint and the patient's relative did not consent for the brain biopsy.
We report this case to emphasize the prominence of cerebellar involvement in sCJD, especially in ataxic variant of sCJD. Isolated cerebellar involvement may be the only manifestation in the early part of ataxic sCJD variant and hence should be considered in differential diagnosis while approaching a case of subacute progressive cerebellar ataxia.
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