No abstract

Spinocerebellar ataxia type 31 (SCA31) is known as a late-onset, relatively pure cerebellar form of ataxia, but a longitudinal prospective study on the natural history of SCA31 has not been done yet. In this prospective cohort study, we enrolled 44 patients (mean ± standard deviation 73.6 ± 8.5 years) with genetically confirmed SCA31 from 10 ataxia referral centers in the Nagano area, Japan. Patients were evaluated every year for 4 years using the Scale for the Assessment and Rating of Ataxia (SARA) and the Barthel Index (BI). Of the 176 follow-up visits (91.5%), 161 were completed in this study. Five patients (11.4%) died during the follow-up period, and two patients (4.5%) were lost to follow-up. The annual progression of the SARA score was 0.8 ± 0.1 points/year and that of the BI was -2.3 ± 0.4 points/year (mean ± standard error). Shorter disease duration at baseline was associated with faster progression of the SARA score. Our study indicated the averaged clinical course of SCA31 as follows: the patients develop ataxic symptoms at 58.5 ± 10.3 years, become wheelchair bound at 79.4 ± 1.7 years, and died at 88.5 ± 0.7 years. Our prospective dataset provides important information for clinical trials of forthcoming disease-modifying therapies for cerebellar ataxia. It also represents a useful resource for SCA31 patients and their family members in genetic counseling sessions.

We report an autopsy case of a 77-year-old Japanese man with a 7-year history of progressive unilateral left limb dystonia and arm levitation. Brain computed tomography showed fronto-temporal atrophy. The patient was diagnosed as having corticobasal degeneration. Histopathologically, the cerebral cortices, especially of the parasagittal region, and subcortical nuclei revealed numerous Gallyas/tau-positive cytoplasmic inclusions characteristic of progressive supranuclear palsy (PSP). Grumose degeneration was evident in the dentate nucleus. Astrocytic plaques were not present, but a small number of ballooned neurons were found in the fronto-temporal regions. The involvement by the PSP lesions was quite asymmetric in the affected areas, including the frontal cortices, basal ganglia, red nuclei, and inferior olivary nuclei, being more prominent on the side contralateral to the side of limb dystonia. The apparent unilateral dominance of PSP pathology may be relevant to the asymmetric clinical presentation of this patient.

A 64-year-old man was admitted to our hospital complaining of non-productive cough and right chest pain. Chest radiographs showed bilateral hilar lymphadenopathy, diffuse granular nodules and right pleural effusion. Serumangiotensin-II-converting enzymeand lysozyme levels were elevated. Since thoracentesis indicated bloody pleurisy, video-assisted thoracoscopy was performed and revealed multiple white nodules on both the visceral and parietal pleura. Resected pleural biopsy specimens showed non-caseous granulomas. Furthermore, somenodules were observed to compress and involve small vessels and capillaries. The bloody pleurisy was assumed to have been derived from the rupture of small vessels that had been compressed and affected by the granuloma with sarcoidosis.

Two cases of spontaneous cholesterol embolism, which followed different clinical courses, acute and chronic renal failure, are presented and histopathological lesions are compared. Both cases were diagnosed as cholesterol embolism post-mortem. Case 1 (a 66-year-old man) had acute onset of illness with fever, leucocytosis and renal failure, diagnosed as vasculitis, and died of rupture of an abdominal aortic aneurysm. Case 2 (an 84-year-old man) had eosinophilia of unknown aetiology for 7 years with intermittent worsening of renal function and died of sepsis. Case 1 had diffuse cholesterol crystal emboli in the interlobular arteries and arterioles of the kidney, but case 2 had patchy cholesterol emboli in the interlobular arteries of the kidney. The aorta of case 1 was diffusely ulcerated, which is in contrast to that of case 2, who had limited ulceration in thoracic aorta, which might have contributed to the long duration of illness. Immunohistochemically, the number of macrophages and T cells that infiltrated around cholesterol emboli in the arteries was more in case 1 (macrophages 27.7, T cells 36.1/mm(2)) than in case 2 (2.7, 1.38/mm(2)). Focal interstitial inflammation occurred in both cases. In case 1, marked tubulitis was observed. Case 2 had rather severe atrophy of the tubules and fibrotic interstitium where mast cells were rich (31.9/mm(2)). The number of B cells and eosinophils was few in case 2 (11.35, 0.7/mm(2)) compared with case 1 (101.9, 16.15/mm(2)). These results suggest that in acute lesions of renal cholesterol embolism, macrophages and T cells accumulate around cholesterol crystals and cause tubulointerstitial inflammatory lesions with other inflammatory cells. In chronic lesions, macrophages, T cells and mast cells are the major inflammatory cells present in the interstitium.