Isolated myxopapillary ependymoma of the fourth ventricle: case report and review of literature.

We report a case of isolated myxopapillary ependymoma (MPE) of the fourth ventricle. This is the thirteenth reported case of primary intracranial MPE and the fourth reported case of MPE originating from the fourth ventricle. We suggest that exhaustive clinical and radiological investigation of a spinal ependymoma must be undertaken in all cases of intracranial ependymoma.

Role of routine neuropathological examination for determining cause of death in sudden unexpected deaths in infancy (SUDI).

BACKGROUND: Current guidelines for the investigation of sudden unexpected death in infancy (SUDI) include full neuropathological examination with recommendations for brain fixation for 1-2 weeks. Little evidence is available regarding the yield of such examination in determining cause of death in clinical practice. This study examines the frequency of neuropathological findings determining cause of death at postmortem examination in SUDI in relation to clinical and macroscopic features. METHODS: All postmortem examinations performed for the indication of SUDI at a single specialist centre over a 14-year period were reviewed, including clinical history, macroscopic and neuropathological findings. RESULTS: 6% of postmortem examinations performed for cases of SUDI demonstrated a neuropathological cause of death; in almost all (>90%) the clinical history and/or macroscopic examination suggested the cause of death. In 2% of all cases the cause of death was determined by histological neuropathological examination, but there were no cases in which histological neuropathological examination of a macroscopically normal brain revealed the cause of death in the absence of a 'neurological history'. Macroscopic brain abnormalities and the presence of a 'neurological history' were significantly more likely to yield histological brain abnormalities (11-fold and fourfold, respectively). CONCLUSIONS: Histological neuropathological examination rarely determines the cause of death in SUDI in the absence of macroscopic abnormalities or neurological clinical history. A macroscopically abnormal brain and the presence of a clinical history of possible neurological disease or of inflicted injury are significantly more likely to be associated with significant histological brain abnormalities.

Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations.

BACKGROUND: Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a form of ALS characterized by protein deposits in motor neurons that are morphologically and tinctorially distinct from those of classic sporadic ALS. The nosologic position of this type of ALS in the molecular pathologic and genetic classification of ALS is unknown. METHODS: We identified neuropathologically 4 patients with juvenile ALS with basophilic inclusions and tested the hypothesis that specific RNA binding protein pathology may define this type of ALS. Immunohistochemical findings prompted us to sequence the fused in sarcoma (FUS) gene. RESULTS: Motor symptoms began between ages 17 and 22. Disease progression was rapid without dementia. No family history was identified. Basophilic inclusions were strongly positive for FUS protein but negative for TAR DNA binding protein 43 (TDP-43). Granular and compact FUS deposits were identified in glia and neuronal cytoplasm and nuclei. Ultrastructure of aggregates was in keeping with origin from fragmented rough endoplasmic reticulum. Sequencing of all 15 exons of the FUS gene in 3 patients revealed a novel deletion mutation (c.1554_1557delACAG) in 1 individual and the c.1574C>T (P525L) mutation in 2 others. CONCLUSION: Juvenile ALS with basophilic inclusions is a FUS proteinopathy and should be classified as ALS-FUS. The FUS c.1574C>T (P525L) and c.1554_1557delACAG mutations are associated with this distinct phenotype. The molecular genetic relationship with frontotemporal lobar degeneration with FUS pathology remains to be clarified.