Case report: Reversible brain atrophy with low titer anti-amphiphysin antibodies related to gastric adenocarcinoma.

Amphiphysin (AMPH) autoimmunity is associated with a variety of neurological complications, including encephalitis, peripheral neuropathy, myelopathy, and cerebellar syndrome. Its diagnosis is based on clinical neurological deficits and the presence of serum anti-AMPH antibodies. Active immunotherapy, such as intravenous immunoglobulins, steroids, and other immunosuppressive therapies, has been reported to be effective in most patients. However, the extent of recovery varies depending on the case. Herein, we report the case of a 75-year-old woman with semi-rapidly progressive systemic tremors, visual hallucinations, and irritability. Upon hospitalization, she developed a mild fever and cognitive impairment. Brain magnetic resonance imaging (MRI) showed semi-rapidly progressive diffuse cerebral atrophy (DCA) over 3 months, while no clear abnormal intensities were observed. The nerve conduction study revealed sensory and motor neuropathy in the limbs. The fixed tissue-based assay (TBA) failed to detect antineuronal antibodies; however, based on commercial immunoblots, the presence of anti-AMPH antibodies was suspected. Therefore, serum immunoprecipitation was performed, which confirmed the presence of anti-AMPH antibodies. The patient also had gastric adenocarcinoma. High-dose methylprednisolone, and intravenous immunoglobulin were administered and tumor resection was performed, resulting in resolution of the cognitive impairment and improvement in the DCA on the post-treatment MRI. After immunotherapy and tumor resection, the patient's serum was analyzed using immunoprecipitation, which showed a decrease in the level of anti-AMPH antibodies. This case is noteworthy because the DCA showed improvement after immunotherapy and tumor resection. Additionally, this case demonstrates that negative TBA with positive commercial immunoblots do not necessarily indicate false positive results.

Natural History of Spinocerebellar Ataxia Type 31: a 4-Year Prospective Study.

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.

"Gliomatosis encephali" as a novel category of brain tumors by the first autopsy case report of gliomatosis cerebelli.

Gliomatosis cerebri is a rare diffuse glioma that is neither mass-forming nor necrotic, and does not disrupt existing structures. Gliomatosis occurring in the cerebellum is known as gliomatosis cerebelli, and only three such cases examined by biopsy have been reported. Here we describe the first autopsy findings of a patient who was diagnosed as having gliomatosis in the cerebellum. Neuropathological examination identified the tumor cells as being positive for glial fibrillary acidic protein, vimentin and nestin, with atypical nuclei that were cashew-nut- or dishcloth-gourd-shaped. These tumor cells were dense in the right cerebellum, but also spread broadly throughout the brain including the left cerebrum and optic nerve. Mitotic figures were frequently seen in the cerebellum, brain stem and cerebrum. Scherer's secondary structures were evident not only in the cerebellum but also the cerebrum. No necrosis, microvascular proliferation or destruction of anatomical structures was detected in the whole brain. Differences in the origin of the tumors of the gliomatoses cerbri and cerebelli suggests these tumors are different types of brain tumors. Thus the findings support that the gliomatosis cerebelli is a novel type of brain tumor classification. Furthermore, by the similarities of the histological features among the tumors, it appears appropriate to establish a novel category of "gliomatosis encephali" which includes both gliomatosis cerebri and gliomatosis cerebelli.

Renal cholesterol embolism: analysis of two spontaneous autopsy cases.

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.

Direct pericardial involvement of non-small cell lung cancer rapidly developing pericardial constriction.

A 71-year-old male, who had been followed up after being treated with chemo-radiotherapy for non-small cell lung cancer (adenocarcinoma), rapidly developed dyspnea and mild fever. Radiographs showed left pleural effusion and cardiomegaly, and echocardiographic examination revealed echo-free space, suggesting a pericardial effusion. The patient was treated conservatively without any surgical procedures such as pericardiocentesis. Disappearance of the echo-free space was followed by development of pericardial constriction within two months. At post-mortem examination, a direct extension to the pericardium from the primary lesion of the right upper lobe through the mediastinum was observed. The rapid development of pericardial constriction is extremely rare in patients with malignant pericarditis.

Pulmonary sarcoidosis with associated bloody pleurisy.

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. Serum angiotensin-II-converting enzyme and 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, some nodules 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.

Progressive supranuclear palsy with asymmetric tau pathology presenting with unilateral limb dystonia.

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.