Difficulty identifying spinocerebellar ataxia 17 from preceding psychiatric symptoms


SPINOCEREBELLAR ATAXIA (SCA) with preceding psychiatric symptoms has only ever been reported for SCA17.1,2 SCA17, a rare autosomal dominant disorder, is characterized by various neurological symptoms and/or psychiatric symptoms. SCA17 with psychiatric symptoms is often diagnosed as a variety of psychiatric disorders such as schizophrenia and bipolar disorder before the onset of neurological symptoms.1 SCA17 is a polyglutamine disease caused by expanded CAG/CAA repeats in the TATA box-binding protein (TBP) gene.1 Here, we report two rare cases of undefined hereditary SCA other than SCA17 with preceding psychiatric symptoms.

A 65-year-old man had presented with hypomanic and depressive episodes on more than 10 occasions since the age of 18. He was diagnosed with bipolar disorder at the age of 45. The patient noticed progressive unsteadiness of gait from 58 years of age, with double vision and difficulties in fastening a button.

A 54-year-old man had exhibited social withdrawal since he was in high school. He complained of cenesthopathy and persecutory delusion since his 30s, and was diagnosed with schizophrenia. He complained of feeling vertigo since 47 years of age, and subsequently reported further symptoms, such as double vision, gait disturbance, dysphagia and slurred speech. There were past histories of paralytic ileus and aspiration pneumonia at 53 years of age. He had autonomic symptoms, such as mild orthostatic hypotension and severe constipation.

Both patients had limb and gait ataxia, intention tremor, saccades during slow pursuit, gaze nystagmus and convergent disturbance, and had mild rigidity only in the former patient. They had no other neurological symptoms. They had several biological relatives with SCA. The latter had relatives with progressive muscular dystrophy and schizophrenia. Brain magnetic resonance imaging indicated atrophy of the cerebellum (hemisphere and vermis) in both cases; additionally lower pons in the latter case. They were diagnosed with SCA in their late 50s. Mutation analysis failed to identify any mutations in well-known causative genes reported in Japan for SCA1, SCA2, DRPLA, SCA3 and SCA6 in the former patient. No abnormally expanded triplet repeats were identified in the TBP gene (SCA17) in both patients. Their mental state is relatively stable with medication (patient 1, paroxetine 40 mg/day and taltirelin hydrate 10 mg/day; patient 2, aripiprazole 12 mg/day), while their neurological symptoms and cerebral atrophy are gradually progressing. These patients met the diagnostic criteria for schizophrenia or bipolar disorder from DSM-IV and matched the criteria of SCA from the Japanese Ministry of Health, Labor and Welfare. Informed consent was obtained from both patients.

Because the presence of pre-existing psychiatric symptoms was consistent with SCA17,1 we suspected that these symptoms were referable to SCA17, but SCA17 was excluded in both cases on genetic analysis. SCA is a heterogeneous syndrome with similar clinical phenotypes, such as ataxia and cerebellar atrophy, and is caused by different genetic abnormalities at different chromosomal loci. Some characteristic symptoms are considered to be useful to distinguish several subtypes of SCA. This approach failed to identify the subtype of SCA in the present patients. We suggest that it is difficult to identify SCA17 on the basis of preceding psychiatric symptoms.