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The evolution of neuromyelitis optica spectrum disorder (NMOSD) from a rare, incurable and misunderstood disease with almost universally poor outcomes to its present state in just over a decade is unprecedented in neurology and possibly in medicine. Our knowledge of NMOSD biology has led to the recognition of wider phenotypes, new disease mechanisms, and thus clinical trials of new and effective treatments. This article aims to update readers on the recent developments in NMOSD with particular emphasis on clinical advances, the 2015 diagnostic criteria, biomarkers, imaging, and therapeutic interventions.

Background. Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood. Methods. We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging–based temporal lobe volume. Results. Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P = .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P = .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%; P = .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P = .012) and a positive correlation with serum IL-1α level (P = .0003) and CSF IL-1β level (P = .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P = .007) and CSF specimens from all patients (P = .016); the IL-10 level correlated inversely with BBB permeability (P = .005). Conclusions. A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis.

The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values.

A 48-year-old man presented with numbness in fingers and diplopia 1 week after a flu-like illness. He made a full recovery but 8 years later developed progressive and disabling sensory ataxia. He had superimposed acute flare-ups with numbness, double vision and ptosis, all following infections. A blood test showed antidisialosyl antibodies including GD1b, GD3, GT1b and GQ1b in keeping with the diagnosis of chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and antidisialosyl antibodies (CANOMAD). Initial treatment with monthly courses of intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days every 4 weeks helped temporarily but there were marked disabling fluctuations of symptoms. With IVIg 0.6 g/kg/day weekly his symptoms are stable. He remains mobile and has no eye symptoms without need for any other medication. This case demonstrates that weekly IVIg infusions instead of one 5-day course monthly may be able to avoid fluctuations of symptoms in CANOMAD.

There is evidence that apolipoprotein E (apoE) and amyloid β-protein (Aβ), which are implicated in the pathology of chronic neurodegenerative disorders, are involved in the response of the brain to acute injury; however, human in vivo evidence is sparse. We conducted a prospective observational study to determine the magnitude and time-course of alterations in cerebrospinal fluid (CSF) apoE and Aβ concentrations after traumatic brain injury (TBI), and the relationship of these changes to severity of injury and clinical outcome. Enzyme linked immunosorbant assay(ELISA) was used to assay apoE, Aβ 1-40 and Aβ 1-42 in serial CSF samples from 13 patients with TBI and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. There was a significant decrease in CSF apoE (p < 0.001) and Aβ (p< 0.001) after TBI contrasting the observed elevation in CSF S100B (p < 0.001) and tau (p < 0.001) concentration. There was significant correlation (r = 0.67, p = 0.01) between injury severity and the decrease in Aβ 1-40 concentration after TBI. In vivo, changes in apoE and Aβ concentration occur after TBI and may be important in the response of the human brain to injury.

The APOE ϵ4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Post-mortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p< 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p<0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury where in view of previous data, it may have a protective role.