Central Nervous System Involvement in ANCA-Associated Vasculitis: What Neurologists Need to Know

Objective: To provide a comprehensive review of the central nervous system (CNS) involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including the pathogenesis, clinical manifestations, ancillary investigations, differential diagnosis, and treatment. Particular emphasis is placed on the clinical spectrum and diagnostic testing of AAV.Recent Findings: AAV is a pauci-immune small-vessel vasculitis characterized by neutrophil-mediated vasculitis and granulomatousis. Hypertrophic pachymeninges is the most frequent CNS presentation. Cerebrovascular events, hypophysitis, posterior reversible encephalopathy syndrome (PRES) or isolated mass lesions may occur as well. Spinal cord is rarely involved. In addition, ear, nose and throat (ENT), kidney and lung involvement often accompany or precede the CNS manifestations. Positive ANCA testing is highly suggestive of the diagnosis, with each ANCA serotype representing different groups of AAV patients. Pathological evidence is the gold standard but not necessary. Once diagnosed, prompt initiation of induction therapy, including steroid and other immunosuppressants, can greatly mitigate the disease progression.Conclusions and Relevance: Early recognition of AAV as the underlying cause for various CNS disorders is important for neurologists. Ancillary investigations especially the ANCA testing can provide useful information for diagnosis. Future studies are needed to better delineate the clinical spectrum of CNS involvement in AAV and the utility of ANCA serotype to classify those patients.Evidence Review: We searched Pubmed for relevant case reports, case series, original research and reviews in English published between Sep 1st, 2001 and Sep 1st, 2018. The following search terms were used alone or in various combinations: “ANCA,” “proteinase 3/PR3-ANCA,” “myeloperoxidase/MPO-ANCA,” “ANCA-associated vasculitis,” “Wegener's granulomatosis,” “microscopic polyangiitis,” “Central nervous system,” “brain” and “spinal cord”. All articles identified were full-text papers

Application of MRI Post-processing in Presurgical Evaluation of Non-lesional Cingulate Epilepsy

Background and Purpose: Surgical management of patients with cingulate epilepsy (CE) is highly challenging, especially when the MRI is non-lesional. We aimed to use a voxel-based MRI post-processing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle epileptogenic lesions in CE, thereby improving surgical evaluation of patients with CE with non-lesional MRI by visual inspection.Methods: Included in this retrospective study were 9 patients with CE (6 with negative 3T MRI and 3 with subtly lesional 3T MRI) who underwent surgery and became seizure-free or had marked seizure improvement with at least 1-year follow-up. MRI post-processing was applied to pre-surgical T1-weighted volumetric sequence using MAP. The MAP finding was then coregistered and compared with other non-invasive imaging tests (FDG-PET, SPECT and MEG), intracranial EEG ictal onset, surgery location and histopathology.Results: Single MAP+ abnormalities were found in 6 patients, including 3 patients with negative MRI, and 3 patients with subtly lesional MRI. Out of these 6 MAP+ patients, 4 patients became seizure-free after complete resection of the MAP+ abnormalities; 2 patients didn't become seizure-free following laser ablation that only partially overlapped with the MAP+ abnormalities. All MAP+ foci were concordant with intracranial EEG ictal onset (when performed). The localization value of FDG-PET, SPECT and MEG was limited in this cohort. FCD was identified in all patients' surgical pathology except for two cases of laser ablation with no tissue available.Conclusion: MAP provided helpful information for identifying subtle epileptogenic abnormalities in patients with non-lesional cingulate epilepsy. MRI postprocessing should be considered to add to the presurgical evaluation test battery of non-lesional cingulate epilepsy

PHF5A is a potential diagnostic, prognostic, and immunological biomarker in pan-cancer

Abstract Studying the molecular mechanisms and regulatory functions of genes is crucial for exploring new approaches and tactics in cancer therapy. Studies have shown that the aberrant expression of PHF5A in tumors is linked to the origin and advancement of multiple cancers. However, its role in diagnosis, prognosis, and immunological prediction has not been comprehensively investigated in a pan-cancer analysis. Using several bioinformatic tools, we conducted a systematic examination of the potential carcinogenesis of PHF5A in various tumors from multiple aspects. Our analysis indicated that PHF5A expression varied between normal and tumor tissues and was linked to clinical diagnosis and prognosis in various cancers. The results confirmed a notable variation in the levels of PHF5A promoter methylation among several types of primary tumor and normal tissues and methylation of the PHF5A promoter played a guiding role in prognosis in some cancers. According to our findings, PHF5A played a critical role in tumor immunity and it might be an excellent target for anticancer immunotherapy. To sum up, PHF5A can be used in pan-cancer diagnostics, prognostics, and immunotherapy

Central pontine myelinolysis in a patient with epilepsia partialis continua and hyperglycaemic hyperosmolar state

Central pontine myelinolysis (CPM) is a demyelinating disorder, which is associated most commonly with the rapid correction of hyponatraemia and other abrupt changes in physiological osmotic conditions. This includes the treatment of hyperosmolar hyperglycaemia in diabetes mellitus (DM) sufferers. Herein, we report a case of CPM in a 55-y-old patient with new-onset DM who presented with partial focal seizures and a sudden-onset right-sided hemiplegia. Magnetic resonance imaging revealed a lesion in the central pons. The patient responded to glucose control and antiepileptic medication, and achieved a recovery of limb function within 17 d of admission. CPM occurred in this patient before the correction of hyperglycaemic hyperosmolar state, and a disturbance in his initial electrolytes was not found. This report is the first documented case of long-term hyperglycaemic hyperosmolar state leading to CPM, and highlights that CPM can present as an isolated hemiplegia. </jats:p

Ketogenic dietary therapy in adult status epilepticus: current progress and clinical application

AbstractStatus epilepticus (SE) is a common fatal neurological disease with high morbidity and mortality. Even if a large proportion of patients might be relieved from anti-seizure medications, sedatives and anesthetics, some still remain out of control. The ketogenic dietary (KD) has been proven useful in patients refractory to medications and/or who have failed to respond to surgical intervention. Recently, KD has shown beneficial therapeutic effects in children with SE, but studies in adults have rarely been reported. In this paper, we review the efficacy and utility of KD in adult SE patients and highlight its application for clinical reference and management.</jats:p