[A case suspected of dystonia with marked cerebellar atrophy with torsion dystonia of the neck and cerebellar ataxia that developed during pharmacologic schizophrenia treatment].

A 46 year-old man with schizophrenia had taken several anti-psychotic drugs since 25 years of age. From ~35 years of age, he noticed occasional neck torsion to the left, and later an ataxic gait; both symptoms gradually worsened. On admission, the patient was taking olanzapine (5 mg/day) and biperiden hydrochloride (1 mg/day) because his schizophrenia was well controlled. His parents were not consanguineous, and there was no family history of neuropsychiatric diseases. On neurological examination, he showed mild cognitive impairment, saccadic eye pursuit with horizontal gaze nystagmus, mild dysarthria, dystonic posture and movement of the neck, incoordination of both hands, and an ataxic gait. Deep tendon reflexes were normal except for the patellar tendon reflex, which was exaggerated bilaterally. Pathological reflexes were negative and there was no sign of rigidity, sensory disturbance or autonomic dysfunction. Ophthalmological examinations detected thinning of the outer macula lutea in both eyes, indicative of macular dystrophy. After admission, all anti-psychotic drugs were ceased, but his dystonia was unchanged. Levodopa and trihexyphenidyl hydrochloride were not effective. General blood, urine and cerebrospinal fluid examinations showed no abnormalities. Brain MRI showed cerebellar atrophy and bilateral symmetrical thalamic lesions without brainstem atrophy or abnormal signals in the basal ganglia. I123-IMP SPECT also revealed a decreased blood flow in the cerebellum. Genetic screening, including whole exome sequencing conducted by the Initiative on Rare and Undiagnosed Disease identified no possible disease-causing variants. The patient's dystonia worsened and choreic movements manifested on his right hand and foot. We suspected dystonia with marked cerebellar atrophy (DYTCA), but could not exclude drug-induced dystonia. Macular dystrophy and bilateral thalamic lesions on brain MRI have not been previously described in DYTCA. Whether these features might be primarily associated with dystonia or cerebellar ataxia now remains to be determined.

A novel nonsense mutation in a Japanese family with ataxia with oculomotor apraxia type 2 (AOA2).

We report a 67-year-old Japanese woman with ataxia with oculomotor apraxia type 2 (AOA2). She was born to consanguineous parents and showed a teenage onset, a slowly progressive cerebellar ataxia and sensory-motor neuropathy and an elevated level of serum alpha-fetoprotein (AFP). All of these clinical features were consistent with typical AOA2. She lacked oculomotor apraxia, as frequently observed in previously reported AOA2 patients. She was homozygous for a novel nonsense mutation, Glu385Ter (E385X), in the senataxin gene (SETX). To our knowledge, this is the fifth Japanese family with genetically confirmed AOA2. The mutations in SETX in Japanese AOA2 families are heterogeneous, except for M274I, which has been found in two unrelated families. More extensive screening by serum AFP followed by molecular genetic analysis of SETX in patients with Friedreich's ataxia-like phenotype may show that AOA2 is more common in Japan than previously thought.