Discussing Challenges in Diagnosis of Tuberculous Meningitis and Neurosarcoidosis.

Isolated chronic granulomatous meningitis remains a diagnostic challenge for the physician. Symptoms are often nonspecific and ancillary tests have low-sensitivity rates, which may delay targeted treatment and lead to increased morbidity and mortality. Here, we discuss the challenges in diagnosing and treating patients with chronic meningitis by reporting two cases of previously healthy patients who presented with granulomatous meningitis on brain biopsy.

Encephalopathies Associated With Severe COVID-19 Present Neurovascular Unit Alterations Without Evidence for Strong Neuroinflammation.

OBJECTIVE: Coronavirus disease (COVID-19) has been associated with a large variety of neurologic disorders. However, the mechanisms underlying these neurologic complications remain elusive. In this study, we aimed at determining whether neurologic symptoms were caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) direct infection or by either systemic or local proinflammatory mediators. METHODS: In this cross-sectional study, we checked for SARS-CoV-2 RNA by quantitative reverse transcription PCR, SARS-CoV-2-specific antibodies, and 49 cytokines/chemokines/growth factors (by Luminex) in the CSF +/- sera of a cohort of 22 COVID-19 patients with neurologic presentation and 55 neurologic control patients (inflammatory neurologic disorder [IND], noninflammatory neurologic disorder, and MS). RESULTS: We detected anti-SARS-CoV-2 immunoglobulin G in patients with severe COVID-19 with signs of intrathecal synthesis for some of them. Of the 4 categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines, and growth factors. By contrast, patients with COVID-19 did not present overall upregulation of inflammatory mediators in the CSF. However, patients with severe COVID-19 (intensive care unit patients) exhibited higher concentrations of CCL2, CXCL8, and vascular endothelium growth factor A (VEGF-A) in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated albumin ratio and correlated with the increase of peripheral inflammation (serum hepatocyte growth factor [HGF] and CXCL10). CONCLUSIONS: Our results do not indicate active replication of SARS-CoV-2 in the CSF or signs of massive inflammation in the CSF compartment but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.

[Recent Advances in Neurology]. / Neurologie.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease.

L'année 2020 a vu d'importantes avancées dans le domaine des biomarqueurs sanguins pour le diagnostic biologique de la maladie d'Alzheimer. Plusieurs études permettent de mieux définir la prise en charge de l'épilepsie chez la femme en âge de procréer et de l'état de mal épileptique. Les nouvelles recommandations suisses pour la prise en charge préhospitalière de l'AVC aigu sont en cours de publication, tout comme de nouvelles cibles pour leur prévention secondaire. De nombreuses avancées concernant la prise en charge des Neuromyelitis Optica Spectrum Disorder ont été publiées. Divers tableaux neurologiques (centraux et périphériques) liés à la pandémie de Covid-19 ont été décrits. Plusieurs études ont permis de confirmer l'efficacité des nouveaux traitements de la migraine (notamment les anti-Calcitonin Gene-Related Peptide). Enfin, de nouvelles thérapies pharmacologiques sont disponibles pour la maladie de Parkinson.

Genotype-phenotype correlations in a large series of patients with muscle type CPT II deficiency.

OBJECTIVES: The adult or 'muscular' form of carnitine-palmitoyl-transferase II (CPT II) deficiency presents with recurrent rhabdomyolytic episodes and myoglobinuria, usually triggered by prolonged exercise. The aim of this study was to investigate a large series of patients in order to provide genotype-phenotype correlations. METHODS: Our muscle tissue bank was surveyed for patients showing attacks of rhabdomyolysis with myoglobinuria. After exclusion of cases affected with toxic myoglobinuria, McArdle's disease and Becker muscular dystrophy, over 100 patients were selected for isotope-exchange radioenzymatic assay of CPT enzyme activity in muscle, and 25 cases resulted to be defective. Acylcarnitine profile was performed in five patients using tandem mass spectrometry. Mutations in the CPT2 gene were identified using DNA sequencing. RESULTS: Although the clinical features were rather homogeneous, some patients presented life-threatening events (acute renal failure) and muscle weakness, and low levels of residual CPT activity. The typical acylcarnitine profile found in mutant patients confirmed its value as a screening method for further diagnostic investigations. We found a high frequency of the common p.Ser113Leu mutation, the recurrence of the rare p.Arg631Cys mutation in a genetic isolate in Southern Italy, and identified four novel mutations. In some affected patients only one mutant allele was found, suggesting either incomplete mutation detection or the possibility they are symptomatic carriers. DISCUSSION: Null mutations and homozygous mutations were frequently associated with a more severe phenotype and biochemical defect. The identification of symptomatic obligate heterozygous carriers might suggest that additional epigenetic or environmental factors may contribute to determine the phenotype.