Clinical and imaging findings of progressive supranuclear palsy with predominant cerebellar ataxia

We previously demonstrated that cerebellar ataxia may be a chief manifestation in some Japanese PSP patients, and we proposed PSP-C as a novel subtype. In this letter, we aim to describe the features of this subtype and its prevalence in Japanese and other populations. We identified 10 Japanese patients from previous reports with pathologically confirmed PSP-C (Table 1A). We also present a video of a patient with PSP-C (see Video 1), although we do not have a video of the patient in an earlier stage of the disease. Most patients were initially diagnosed with spinocerebellar degeneration (SCD) or MSA with predominant cerebellar ataxia (MSA-C). The clinical features of PSP-C are as follows: (1) predominantly affects men (8:2 men/ women); (2) mean age at onset is 67.2 6 5.6 years (range, 57– 73) and the average disease duration is 6.0 6 2.6 years (range, 3–11); (3) it presents with initial symptoms of gait disturbance associated with truncal ataxia, although 1 patient developed prominent limb ataxia; (4) falls and supranuclear gaze palsy appear within 2 years of onset (6 and 3 patients, respectively); (5) palatal or ocular-palatal-pharyngeal myoclonus may occur (2 patients); and (6) no dysautonomia occurs. We previously compared the clinical features of 4 patients with pathologically confirmed PSP-C and 11 with MSA-C and found that late onset, early falls, and supranuclear vertical gaze palsy without dysautonomia are characteristic of PSP-C. Pathological findings were consistent with the diagnosis of PSP, but the olivopontocerebellar involvement, particularly in the cerebellum, was generally more severe, and tau-positive inclusion bodies in Purkinje cells were more frequently observed. Imaging findings in PSP-C patients are as follows (Supporting Fig. 1): (1) no obvious atrophy of the cerebellum and frontal lobe during early stages; (2) in advanced stages, proportional atrophy of the cerebellum without widening of the cerebellar fissures, but with an enlarged pontocerebellar cistern and atrophy of the superior cerebellar peduncles and midbrain (hummingbird or penguin sign), and mild-to-moderate enlargement of the fourth ventricle. Abnormal intensities on MRI of the cerebellum or brainstem, including the “hot cross bun sign,” are not observed. Thus, inconspicuous cerebellar atrophy and enlargement of the pontocerebellar cistern can be used to distinguish PSP-C from SCD as the disease progresses. A differential diagnosis of PSP-C should be considered for patients with cerebellar ataxia, but no apparent cerebellar atrophy on brain MRI. We also investigated the prevalence of PSP-C in Western countries. It appears that although PSP-C exists in Western countries, it is extremely rare (Table 1B). This may be attributed to different ethnic and genetic factors involved in the development of cerebellar ataxia in Japanese and Western PSP patients. In conclusion, we demonstrate that PSP-C is a slowly progressive adult-onset disease characterized by truncal and limb ataxia, vertical supranuclear palsy, and postural instability with falls, but without dysautonomia or the hot cross bun sign on brain MRI. Although this PSP subtype is mainly observed in Japanese patients, PSP-C also occurs in Western countries. Clinical diagnostic criteria for PSP-C should be established.