Rapidly progressive ataxia during rehabilitation and a difficult road to diagnosis.

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It is important for geriatricians to remain vigilant when patients are undergoing rehabilitation. We would like to report an individual initially diagnosed with cervical myelopathy but who later developed rapidly progressive ataxia and was finally diagnosed with sporadic Creutz-feldt Jakob disease (sCJD) after extensive investigations. Typical signal changes were present only in the second set of magnetic resonance imaging (MRI) scans of the brain. A 68-year-old man presented with a 2-week history of bilateral lower limb weakness and required a cane for walking. There were no myalgia, numbness, paresthesias, or sphincter disturbances. He was initially clinically diagnosed with cervical myelopathy given the presence of brisk jerks in both lower limbs and myelopathic hand signs. During the next month of rehabilitation, he developed rapidly deteriorating truncal and limb ataxia. He then required a frame for walking. His Mini-Mental State Examination (MMSE) score was 30. Blood tests including complete blood count, liver and kidney biochemistries, thyroid function, vitamin B12, folate, fasting glucose, creatine kinase, paraneoplastic antibodies, heavy metals, and tumor markers were unremarkable. MRI of the whole spine (at ~1 month) showed narrowing of multiple levels of disc space, osteophytes, and facet joint hypertrophy but without any significant cord compression. MRI of the brain, cerebrospinal fluid (CSF) examination including microscopy and culture, nerve conduction study, electromyography, whole-body positron emission tomography computed tomography (PET-CT), and electroencephalogram (EEG) were unremarkable. MRI of the brain, repeated 2 months after the initial presentation, demonstrated hyperintense signals over the caudate nucleus and putamen on T2-weighted imaging and diffusion-weighted imaging sequences (Figure 1). EEG was subsequently repeated and showed diffuse slowing and semiperiodic biphasic and triphasic slow waves. Cerebrospinal fluid tau level was 1,180 pg/mL (normal ≤325.7 pg/mL).1 CSF 14-3-3 protein testing was not available in the hospital. The individual was diagnosed with sCJD ataxic subtype. He developed akinetic mutism and spontaneous myoclonus in both upper limbs 3 months after initial presentation. Given the expected progressive downhill course, he was offered palliative care, and he died 5 months after initial presentation. The subject met the diagnostic criteria of probable sCJD given his rapidly progressive dementia, myoclonus, akinetic mutism, and typical changes on the second set of MRI and EEG.2 According to Chinese CJD surveillance data, the median age of onset for sCJD is 61, with a male-to-female ratio of 1.25:1.3 The pathogenesis of sCJD is thought to be the loss of the proteostasis network, with conversion of normal cellular prion protein (PrPc) into abnormal scrapie PrP (PrPSc), which aggregates and replicates by template conversion of PrPc and finally results in tissue damage and symptomatic disease.4 The initial clinical presentation of cerebellar ataxia with unsteady gait posed the first diagnostic difficulty, especially in the presence of normal cognitive function. Only approximately 16.6% of sCJD in Han Chinese has first presented with cerebellar syndrome.3 The cerebellar syndrome was due to the accumulation of PrPSc in the cerebellum. It was hypothesized that such accumulation of PrPSc caused impairment in synaptic protein expression and hence synaptic loss with functional impairment.5 The initially normal brain MRI and EEG caused the second diagnostic difficulty. The sensitivity of the use of MRI with diffusion-weighted sequences in the diagnosis of sCJD along its clinical course is 96%, and the specificity is 93%.6 Age-related iron deposition may have masked the basal ganglia T2 sequence signal changes in the first set of MRI in that region.6 A second set of brain MRI should be performed if sCJD is still clinically possible. A repeat EEG may also be helpful because periodic abnormal discharges may only be captured in 70% of individuals along the clinical course.7 This subject illustrated that CJD should be considered in individuals with rapidly deteriorating ataxia in rehabilitation setting. Although CJD is not treatable, correct diagnosis allows successful palliation, which should include education of the individual and relatives of the expected rapid trajectory of the disease, with median survival of 6 months; appropriate management of symptoms such as myoclonic jerking, dysphagia, and “startle response”; and proper body management after the death of the patient.8 The individual may be able to arrange personal matters before further cognitive deterioration. Rapidly progressive ataxia should prompt consideration of CJD. Repeat MRI or EEG should be considered in the case of strong clinical suspicion of CJD even if initial imaging or EEG findings were normal. Correct diagnosis allows for successful palliation and skilled care of the individual and provision of family support. Conflict of Interest: The authors have no financial or any other personal conflict to report. Author Contributions: Study concept and design: Shea, Chan. Acquisition of subject and data: all authors. Analysis and interpretation of data: all authors. Preparation of manuscript: all authors. Critical review and approval: all authors. Sponsor's Role: None.