Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Polypathology-associated neurodegeneration after remote head injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. TBI ranges from mild to severe and is a recognized risk factor for later neurodegenerative conditions including chronic traumatic encephalopathy (CTE), Alzheimer disease (AD) and Parkinson disease (PD). The development of CTE is typically associated with repetitive exposure to mild TBI (mTBI), while a single moderate-to-severe TBI is considered a risk factor for AD and PD. Polypathology is common, and the lines between these conditions post TBI can be somewhat blurred. The mechanisms through which TBI leads to future neurodegeneration are not well understood. Heterogeneity and distance from the injury or injuries and individual genetic and environmental factors make clinical studies difficult. We present the case of an 82-year-old man who died 4 years after developing a phenotypically mixed dementia with neuropsychiatric features and parkinsonism. He had a remote history of a severe TBI 40 years prior, following a road traffic accident which caused a large right frontal injury, requiring neurosurgical intervention. Post-mortem neuropathological examination demonstrated abnormal phosphorylated-Tau (p-Tau), beta-amyloid plaques (Aß) and α-synuclein deposition. Spatial immunohistochemical analysis demonstrated increased perivascular accumulation of p-Tau with blood-brain barrier (BBB) disruption at the site of injury, which decreased with distance from the injury site. The appearances are suggestive of initial vascular disruption with persisting BBB disruption as a driver of the pathology.

Antibody-Negative Paraneoplastic Limbic Encephalitis, Parkinsonism, Hypothermia, and Narcolepsy Associated with Endometrial Carcinoma.

BACKGROUND: We describe the clinical and neuropathological features of a patient with T-cell-mediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy-like presentation associated with endometrial carcinoma. OBJECTIVES: This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneoplastic syndromes and demonstrates the importance of investigation for occult malignancy even in the absence of paraneoplastic antibodies. METHODS: This is a case report with diagnosis confirmed at postmortem. RESULTS: Paraneoplastic antibodies were not detected. The initial improvement with immunosuppression was short lived, and postmortem neuropathological examination demonstrated encephalitis with predominant T-cell infiltration affecting the hypothalamus and extending to the brainstem, suggestive of a paraneoplastic syndrome. CONCLUSIONS: Although the possibility of a novel antibody cannot be ruled out, consideration must also be given to recent demonstration of purely T-cell-mediated neuronal destruction in the context of paraneoplastic syndromes.

Emergency anaphylaxis protocols: A cross-sectional analysis of general practice surgeries and pharmacies in both the urban and rural setting in Ireland.

BACKGROUND: The incidence of anaphylaxis appears to be increasing worldwide with cases in the community outnumbering those in the hospital setting. General practice (GP) surgeries and pharmacies, based in the community, are often the first point of contact for many patients suffering from anaphylaxis. OBJECTIVES: To determine if studied GP surgeries and pharmacies have an anaphylaxis protocol on site and have access to an anaphylaxis kit; to explore GP's and pharmacists' personal experiences with management of anaphylaxis. METHODS: A cross-sectional, questionnaire-based study was performed examining anaphylaxis protocols in a sample of general practices and pharmacies from some counties in Ireland. This consisted of a sample from rural and urban settings. The study commenced in October 2014. RESULTS: Nineteen of 24 GPs (79%) and 9 (29%) pharmacies had an anaphylaxis protocol (P < 0.001). Twenty-four (100%) GP practices and 12 pharmacies (39%) surveyed had an anaphylaxis kit on site. Twelve GPs (50%) had treated a patient with anaphylaxis in the surgery while 8 (33%) had treated a patient in the community. One pharmacist (3%) had witnessed anaphylaxis in practice. Two pharmacies and one GP had been contacted by local businesses to alert them to a case of anaphylaxis. CONCLUSION: In contrast to national and international guidelines only 79% of GPs and 29% of pharmacies in this study from Ireland had an anaphylaxis protocol onsite.