Status Epilepticus as the Initial Presentation of Intravascular Lymphoma

Intravascular lymphoma (IVL) is a rare disease form of malignant lymphoma, and it is characterised by the selective growth of lymphoma cells within the lumina of vessels. Identification of this disease at an early stage is difficult because of non-specific clinical symptoms and neuroradiological findings. Most reported IVL cases are diagnosed at post-mortem following autopsy. We report the case of a patient who presented with status epilepticus (SE) as the initial manifestation of IVL. Despite the administration of anti-convulsant agents and general care the patient’s condition deteriorated rapidly after admission, culminating in death due to respiratory failure and heart failure 21 days after the onset of symptoms. Post-mortem examination revealed IVL in the brain and multiple organs. Epileptic seizures often appear during the clinical course of IVL; however, they occur most frequently at advanced stages. Diagnosis of IVL that first presents with SE is of clinical importance because the treatment and prognosis of acute SE arising from IVL are different from those of SE originating from other causes

Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model

AbstractAnticholinergics, and drugs with anticholinergic properties, are widely and frequently prescribed, especially to the elderly. It is well known that these drugs decrease cognitive function and increase the risk of dementia. Although the mechanism of anticholinergic drug-induced cognitive impairment has been assumed to be functionally reduced acetylcholine (ACh) neurotransmission, some data have indicated that anticholinergics might enhance the pathology of Alzheimer's disease. In this study, we investigated the pathological effects of anticholinergics on neurodegeneration. We chronically administered two anticholinergics, trihexyphenidyl (TP) and propiverine (PP) (the latter with less central anticholinergic action), to neurodegenerative tauopathy model mice 2 to 10months old. Furthermore, because the ACh nervous system regulates both central and peripheral inflammation, we administered TP or PP to PS19 mice in which we had artificially induced inflammation by lipopolysaccharide injection. Tau pathology, synaptic loss, and neurodegeneration in the hippocampal region, as well as tau insolubility and phosphorylation, were markedly increased in TP-treated mice and mildly increased in PP-treated mice. Furthermore, immunohistochemical analysis revealed microglial proliferation and activation. Moreover, anticholinergics increased interleukin-1β expression in both the spleen and brain of the tauopathy model mice intraperitoneally injected with lipopolysaccharide to induce systemic inflammation. Interestingly, these alterations were more strongly observed in TP-treated mice than in PP-treated mice, consistent with the level of central anticholinergic action. Anticholinergic drugs not only impair cognitive function by decreased ACh neurotransmission, but also accelerate neurodegeneration by suppressing an ACh-dependent anti-inflammatory system. Anticholinergics should be less readily prescribed to reduce the risk of dementia

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer’s disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick’s disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis