Multiple system atrophy with amyloid-ß-predominant Alzheimer's disease neuropathologic change.

Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency and mostly comprise primary age-related tauopathy or low levels of Alzheimer's disease-related neuropathologic change. Therefore, the concomitant presence of different misfolded proteins in the same brain region is less likely in multiple system atrophy. During the neuropathological evaluation of 21 consecutive multiple system atrophy cases, we identified four cases exhibiting an unusual discrepancy between high Thal amyloid-ß phase and low transentorhinal Braak neurofibrillary tangle stage. We mapped α-synuclein pathology, measured the size and number of glial cytoplasmic inclusions and compared the amyloid-ß peptides between multiple system atrophy and Alzheimer's disease. In addition, we performed α-synuclein seeding assay from the affected putamen samples. We performed genetic testing for APOE, MAPT, PSEN1, PSEN2 and APP. We refer to the four multiple system atrophy cases with discrepancy between amyloid-ß and tau pathology as 'amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy' to distinguish these from multiple system atrophy with primary age-related tauopathy or multiple system atrophy with typical Alzheimer's disease neuropathologic change. As most multiple system atrophy cases with mixed pathologies reported in the literature, these cases did not show a peculiar clinical or MRI profile. Three amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy cases were available for genetic testing, and all carried the APOE ɛ4 allele. The extent and severity of neuronal loss and α-synuclein pathology were not different compared with typical multiple system atrophy cases. Analysis of amyloid-ß peptides revealed more premature amyloid-ß plaques in amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy compared with Alzheimer's disease. α-Synuclein seeding amplification assay showed differences in the kinetics in two cases. This study highlights a rare mixed pathology variant of multiple system atrophy in which there is an anatomical meeting point of amyloid-ß and α-synuclein, i.e. the striatum or cerebellum. Since biomarkers are entering clinical practice, these cases will be recognized, and the clinicians have to be informed that the prognosis is not necessarily different than in pure multiple system atrophy cases but that the effect of potential α-synuclein-based therapies might be influenced by the co-presence of amyloid-ß in regions where α-synuclein also aggregates. We propose that mixed pathologies should be interpreted not only based on differences in the clinical phenotype but also on whether protein depositions regionally overlap, potentially leading to a different response to α-synuclein-targeted therapies.

Incidence, risk factors and outcomes of seizures occurring after craniotomy for primary brain tumor resection.

OBJECTIVE: To determine the incidence, risk factors and outcomes of early post-craniotomy seizures. METHODS: This was a retrospective cohort study of all patients who underwent craniotomy for primary brain tumor resection (2002-2011) and admitted postoperatively to the intensive care unit. The patients were divided into 2 groups depending on the occurrence of seizures within 7 days. RESULTS: One-hundred-ninety-three patients were studied: 35.8% had preoperative seizure history and 16.6% were on prophylactic antiepileptic drugs (AEDs). Twenty-seven (14%) patients had post-craniotomy seizures. The tumors were mostly meningiomas (63% for the post-craniotomy seizures group versus 58.1% for the other group; p=0.63) and supratentorial (92.6% for the post-craniotomy seizures versus 78.4% for the other group, p=0.09) with tumor diameter=3.7+/-1.5 versus 4.2+/-1.6 cm, (p=0.07). One (3.1%) of the 32 patients on prophylactic AEDs had post-craniotomy seizures compared with 12% of the 92 patients not receiving AEDs preoperatively (p=0.18). On multivariate analysis, predictors of post-craniotomy seizures were preoperative seizures (odds ratio, 2.62; 95% confidence interval, 1.12-6.15) and smaller tumor size <4 cm (odds ratio, 2.50; 95% confidence interval, 1.02-6.25). Post-craniotomy seizures were not associated with increased morbidity or mortality. CONCLUSION: Early seizures were common after craniotomy for primary brain tumor resection, but were not associated with worse outcomes. Preoperative seizures and smaller tumor size were independent risk factors.