Lethal Complications of Meningiomas: A Case Series.

Background: Meningiomas are the most prevalent type of primary intracranial tumor in adults, comprising nearly one-third of all intracranial tumors. They are typically benign, slow-growing, and asymptomatic but may cause neurological symptoms as they expand due to mass effect. Classification is determined by World Health Organization (WHO) grades 1 to 3 following pathological examination corresponding to benign, atypical, and anaplastic (malignant), respectively, reflecting their rate of growth and risk of recurrence. The vast majority are WHO grade 1 and their slow growth permits timely presentation for elective resection; however, meningiomas in vulnerable locations and coexisting morbidities can result in sudden death. Objectives: We present a series of four adult patients with meningiomas which resulted in death, including a case of fatal seizure, midline hemorrhagic meningioma, postresection meningitis, and compression of the cerebellum. Research design: Retrospective review of the authors' cases was conducted. Available pathology, medical, and autopsy records including gross images were reviewed in each case. The inclusion criteria were adult patients (>18 years old) and that the cause of death had to include meningioma. Subjects: The four patients included a 61-year-old male, an 84-year-old female, a 62-year-old male, and a 37-year-old female. Measures: Qualitative; autopsy reports describing cause of death and pathology report findings including gross and microscopic analysis. Conclusions: Meningiomas are often benign in nature but can rarely result in death. Size and location of the tumor and risk factors are contributory. Autopsy examination can be instrumental in identifying the cause and mechanism of deaths associated with meningiomas.

Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) can leave patients with memory impairments that may not recover fully. Molecular mechanisms are poorly understood, and no treatment is available. The sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channel plays an important role in acute central nervous system injury. We evaluated upregulation of Sur1-Trpm4 in humans with SAH and, in rat models of SAH, we examined Sur1-Trpm4 upregulation, its role in barrier dysfunction and neuroinflammation, and its consequences on spatial learning. METHODS: We used Förster resonance energy transfer to detect coassociated Sur1 and Trpm4 in human autopsy brains with SAH. We studied rat models of SAH involving filament puncture of the internal carotid artery or injection of blood into the subarachnoid space of the entorhinal cortex. In rats, we used Förster resonance energy transfer and coimmunoprecipitation to detect coassociated Sur1 and Trpm4, we measured immunoglobulin G extravasation and tumor necrosis α overexpression as measures of barrier dysfunction and neuroinflammation, and we assessed spatial learning and memory on days 7 to 19. RESULTS: Sur1-Trpm4 channels were upregulated in humans and rats with SAH. In rats, inhibiting Sur1 using antisense or the selective Sur1 inhibitor glibenclamide reduced SAH-induced immunoglobulin G extravasation and tumor necrosis α overexpression. In models with entorhinal SAH, rats treated with glibenclamide for 7 days after SAH exhibited better platform search strategies and better performance on incremental and rapid spatial learning than vehicle-treated controls. CONCLUSIONS: Sur1-Trpm4 channels are upregulated in humans and rats with SAH. Channel inhibition with glibenclamide may reduce neuroinflammation and the severity of cognitive deficits after SAH.

Sudden unexpected death in lymphocytic hypophysitis.

Lymphocytic hypophysitis is an unusual inflammatory condition of the pituitary gland, classically seen in females during the peripartum periods. The clinical presentation is varied and depends on hormonal deficiencies and pathophysiological effects on the target organs. Although involvement of the neurohypophysis and secondary diabetes insipidus are rare, progression to multiple organ endocrinopathies is common. Pathologically, the condition is characterized by lymphocytic infiltration of the hypophysis with occasional involvement of the thyroid and adrenal glands. Here, we present the case of a 23-year-old woman diagnosed at autopsy with lymphocytic hypophysitis, with concomitant infiltrates in the thyroid gland and adrenal medulla, who died suddenly and unexpectedly with no other apparent cause of death. This case stresses the importance of greater awareness of the entity, and prompt treatment. Moreover, although the precise mechanism of death is unclear, this case raises the possibility of endocrine dysfunction as a contributing factor to sudden death and emphasizes the need to routinely sample the pituitary gland in young women with sudden unexpected death and no apparent cause.