Sparing of the substantia nigra in sporadic Creutzfeldt‐Jakob disease presenting as an acute corticobasal syndrome

Sporadic Creutzfeldt-Jakob disease (sCJD) can present with a rapidly progressive corticobasal syndrome including asymmetric parkinsonism, dystonia, apraxia, and alien limb phenomena.1–4 Loss of substantia nigra dopaminergic neurons is a requirement for the pathological diagnosis of corticobasal degeneration (CBD). 5 Whether these neurons also degenerate in sCJD with acute corticobasal presentation is currently unknown. Here, we have examined the integrity of the nigrostriatal tract in a pathologically confirmed case of sCJD presenting with an acute corticobasal syndrome. A 74-year-old right-handed man with arterial hypertension and type 2 diabetes mellitus presented to the emergency ward with a 3-week history of progressive clumsiness, stiffness and posturing of his left arm and deterioration of his vision. During the last week before admission, his gait had become slow and stooped, and he had developed speech and swallowing difficulties. According to the referring general practitioner, his mental status was still intact. There was no history of neurological diseases in his family. On examination, the patient was alert and oriented to time and place and had good insight into his medical problem. Speech was comprehensible though unclear and extremely slow. The patient was able to distinguish light from darkness, but was otherwise blind. Pupillary reflexes to light were preserved. Extensive testing of cognitive functions was difficult due to the slowness of speech and the visual deficit, but there was no obvious memory or language impairment. The patient had a tendency to deviate his head and gaze to the right. Facial expression was markedly reduced. There were blepharospasms. There was a striking dystonic flexion posture and action myoclonus of the left arm and occasional levitation of the right arm. Ideomotor apraxia was marked in the left hand and mild in the right hand. There was rigidity in the four limbs, especially on the left side. Strength and sensation were normal. Tendon reflexes were increased bilaterally, with a Babinski sign on the left. There was no tremor or ataxia. Gait was profoundly hypokinetic, with short steps, stooped posture, prominent freezing, and postural instability. Over the next few weeks, the patient developed anarthria, generalized dystonia and myoclonus, and incontinence. The patient died of pneumonia 4 weeks after admission. T2and diffusion-weighted MRI on the day of admission revealed normal appearance of the basal ganglia and bilateral hyperintensity of the parietal and occipital cortex, especially on the right side (Fig. 1A). EEGs showed generalized triphasic complexes. Routine blood, urine, and CSF investigations for infectious, inflammatory, toxic, or metabolic causes were negative. CSF 14–3-3 protein was positive. Seven days after admission, Tc-ECD SPECT scan showed pronounced hypoperfusion over the occipital, parietal, and lateral temporal cortex of the right hemisphere and, to a lesser extent, the left parietal cortex (Fig. 1B). Semiquantitative I-FP-CIT SPECT imaging of the dopamine transporter showed normal striatal I-FP-CIT binding compared with published results from 27 patients with essential tremor6 (Fig. 1C). Upon pathological examination, the brain weighed 1,300 g. Macroscopic inspection of the brain showed generalized atrophy of the cerebral cortex and normal pigmentation of the substantia nigra. Microscopy revealed widespread spongiform changes and gliosis in the cerebral (especially occipital) cortex (Fig. 1D), caudate nucleus, putamen (Fig. 1E), and the molecular layer of the cerebellar cortex, as well as synaptic-type abnormal prion protein (PrP) deposits in these areas.7 Remarkably, none of these pathological abnormalities were found in the substantia nigra (Fig. 1F). Although the asymmetric dystonia, myoclonus, parkinsonism, apraxia, and levitation of this patient were reminiscent of CBD, the rapid disease progression and the cortical visual deficit strongly suggested the diagnosis of CJD, which was supported by MRI, EEG, and CSF 14–3-3 analysis and confirmed by neuropathological examination. Histological abnormalities of the substantia nigra are considered uncommon in the more typical form of CJD presenting as a rapidly progressive dementing illness.8,9 Whether relative sparing of the nigrostriatal tract also occurs in CJD with acute corticobasal presentation has not been addressed before. Unexpectedly, antemortem FP-CIT SPECT imaging and postmortem histological examination revealed remarkable preservation of nigral dopaminergic neurons in our patient, despite the clinical similarities with CBD, a disease in which nigrostriatal cell loss is an invariable pathological feature.5 The striking neuropathological changes in caudate and putamen suggest the possibility that the patient’s parkinsonism may have been caused by dysfunction of the nigrostriatal system at the postsynaptic level. Alternatively, the parkinsonian features may have been due to degeneration of other neuronal circuits. Interestingly, Boeve and colleagues reported a case of CJD with corticobasal presentation and a much more chronic disease course (4 years). 10 Neuropathological examination of their case showed sparing of the substantia nigra, as in our patient. However, in contrast to our case, the striatum was also prePublished online 29 May 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.2157