Treatment and outcomes of non-aneurysmal perimesencephalic subarachnoid haemorrhage: A 5 year retrospective study in a tertiary care centre.

PURPOSE: Perimesencephalic Subarachnoid Haemorrhage (PMSAH) is an uncommon type of SAH. Severity of PMSAH can be graded by the presence of blood in the Sylvian fissure. No study compares the outcomes from PMSAH with blood present or absent in the Sylvian fissure. Furthermore, the use of Nimodipine lacks evidence base in PMSAH. We investigated whether continuing Nimodipine to 21 days in PMSAH with or without blood in the Sylvian fissure made any significant difference to patient outcome. METHODS: Retrospective study of 93 cases admitted to tertiary centre from 2016 to 2020. We compared prevalence of cases with blood in Sylvian fissure, and analysed outcomes including complications and changes to patient modified rankin scale (MRS). We also audited use of Nimodipine in these cases and analysed whether Nimodipine made any significant difference in preventing complications. RESULTS: 91 % of PMSAH were grade 1, 24 cases (26 %) had blood in the Sylvian fissure. Sylvian fissure positive (Sylvian-positive) cases were statistically significantly more likely to have higher rates of complication compared to Sylvian fissure negative (Sylvian-negative) cases. Our centre stopped Nimodipine 56 % of the time in Sylvian-negative cases and 45 % of the time in Sylvian-positive cases. There was no statistically significant difference in outcomes when Nimodipine was continued to 21 days or ceased after negative angiogram; this result extended to both Sylvian-positive and Sylvian-negative subgroups when directly comparing Sylvian-positive cases with each other and Sylvian-negative cases likewise. DISCUSSION: Sylvian-positive cases have a significantly higher rate of complication, as well as an increase in MRS. This may be because of the inflammatory properties of haemoglobin in the subarachnoid space post-bleed. Furthermore, acknowledging the limitations of our retrospective data, we did not find a statistically significant difference in continuing Nimodipine to 21 days with relation to PMSAH outcomes in all subgroups.

IDH mutation in glioma: new insights and promises for the future.

IMPORTANCE: Over the past 4 years, our understanding of gliomagenesis and the practice of neuro-oncology have been radically changed by the discovery of mutations involving the isocitrate dehydrogenase (IDH) enzymes. IDH mutation has been found to be an inciting event in gliomagenesis and to have a profound effect on the molecular and genetic route of oncogenic progression and on clinical outcome. OBJECTIVES: To review the role of IDH enzymes in normal physiology and describe aberrations in the IDH pathway that are associated with gliomagenesis, to review recent work examining the effect of IDH-targeted therapy in cancers harboring IDH mutation, and to determine how this work has expanded our understanding of the role of IDH in the development and progression of glioma. EVIDENCE REVIEW: A systematic review of the literature dating from 2008, when IDH mutation was discovered to be clinically significant in glioma, to 2013 was performed using the PubMed database. The following search terms were used: IDH, IDH1, IDH2, and isocitrate dehydrogenase, in conjunction with glioma or leukemia. The search was limited to articles published in English. Further hand searching was performed using a review of the pertinent references from the identified publications. All identified original articles were investigated for content and critiqued by Z.T. and S.D. FINDINGS: IDH mutation is an early event in gliomagenesis and has significant implications for glioma progression and tumor behavior. Early evidence suggests that IDH may be a therapeutic target in IDH-mutant gliomas. CONCLUSIONS AND RELEVANCE: IDH mutation is a central and defining event in the development and progression of glioma and may be a key target for future therapies for these types of neoplasms.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: report on a case with morphometric studies.

Two previously distinct leukodystrophies, pigmentary orthochromatic leukodystrophy and hereditary diffuse leukoencephalopathy with spheroids, have recently been interpreted as variants of the same disease, adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP). We report a sporadic case of a 56-year-old male with ALSP presenting as frontotemporal dementia behavioral variant (FTD-bv). He had a history of depression and developed socially inappropriate behaviors consistent with FTD-bv. His first neurological exam was normal, but he developed new symptoms in the next 1.5 years: executive functional difficulties, anosognosia, urinary incontinence, epilepsy, extrapyramidal syndrome, severe gait disturbance, dysarthria, dysphagia and mutism. He died of pneumonia 20 months after initial presentation. MRI revealed increased T2-FLAIR signal in periventricular white matter and corpus callosum atrophy. Histology showed extensive demyelination of the centrum semiovale, most severe in frontal and temporal lobes, sparing U-fibers. There was no cortical neuronal loss, but selective loss of thalamic neurons. Histopathological hallmarks were cortical neuronal ballooning, white matter orthochromasia, pigmented macrophages, oligodendroglial loss, and axonal spheroids, some myelinated and some vacuolated. Morphometric studies for myelin, spheroids, oligodendrocytes and astrocytes showed that: 1) spheroids were most abundant in areas of partial demyelination rather than areas of extensive demyelination, being absent in normal appearing areas, 2) oligodendrocyte loss only occurred in regions of extensive demyelination and not in partial demyelination, and 3) there was no statistically significant change in number of astrocytes. There were also many more spheroids than physiologically expected in the gracile and cuneate nuclei. These findings suggest that the formation of spheroids is an early-stage event in disease progression. *These authors contributed equally to this work.

Enteric alpha-synuclein expression is increased in Parkinson's disease but not Alzheimer's disease.

BACKGROUND AND OBJECTIVE: Alpha-synuclein (α-Syn) is immunohistochemically detectable in enteric neurons in some subjects. We determined its age distribution in the general autopsy population and in an age-matched subset investigated differences with Parkinson's (PD) and Alzheimer's diseases (AD). METHODS: Archival autopsy samples of colon from 95 cases (77 general population, 10 PD, and 8 AD) were immunostained with monoclonal antibody KM51. α-Syn detectability was semiquantitatively graded 1 to 3. RESULTS: α-Syn was detectable in 52% of the general population, and its level of expression did not change between ages 40 and 91. All PD subjects were α-Syn positive, with higher prevalence (P = 0.001) and grade (P = 0.003) than age-matched controls. AD subjects were no more likely to be α-Syn positive or have a higher grade than controls. CONCLUSIONS: Either PD develops selectively in the enterically α-Syn-positive population subset or PD induces this expression. Absence of increased α-Syn expression in AD points to differences in pathogenesis.