Parinaud's syndrome – A rare presentation of clinically isolated syndrome

We present a 26 year old Pakistani lady with first presentation of a demyelinating event, presenting as Parinaud's syndrome. The video demonstrates a convergence–retraction nystagmus on upgaze and failure of accommodation, and her brain imaging confirms a corresponding pre-tectal contrast enhancing T2 hyperintense lesion suggestive of demyelination. A review of the literature is presented

Putative Biomarkers of Neuro-restoration in the CNS

The aim of this work was to investigate putative biomarkers of neuronal plasticity and repair in the central nervous system. The effects of different disease processes, such as inflammation, demyelination and neurodegeneration were explored. We developed and validated ELISA-based assays for the quantification of neural cell adhesion molecule (NCAM) and growth-associated protein (GAP)-43, two known facilitators of neuronal outgrowth in the nervous system. NCAM isoforms in biological samples were characterised using mass spectrometry. Soluble NCAM was measured in in-vitro and in-vivo models of inflammation/demyelination and neurodegeneration, and across different neurological disorders in the CSF to understand the impact of inflammation and axonal loss on its levels. Recombinant GAP-43 was produced using baculovirus technology and purified in appreciable amounts for use in a new ELISA. Soluble GAP-43 levels were quantified across different neurological disorders in the CSF. Values for CSF NCAM and GAP-43 were correlated with clinical outcome measures. CSF NCAM demonstrated a restricted pattern of expression compared to that of serum whilst GAP-43 is almost exclusively expressed in the CSF, indicating that these biomarkers are intrathecally synthesised. CSF NCAM and GAP-43 levels were lower in neurological disorders with prominent axonal injury; multiple sclerosis, movement disorders, motor neurone disease, Alzheimer’s disease and meningitis. In vitro neuronal cell culture model and in vivo experimental autoimmune encephalomyelitis studies demonstrate that CSF NCAM correlates well with disease progression in multiple sclerosis. A similar relationship was not found with CSF GAP-43. In conclusion, the adult CNS may possess the intrinsic capacity to repair, but this capacity may be dramatically reduced in disease states. Measuring this process may be important in understanding neuronal repair and plasticity

Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement

Líquido cefalorraquídeo; Consenso; Esclerosis múltipleLíquid cefaloraquidi; Consens; Esclerosi múltipleCerebrospinal fluid; Consensus; Multiple sclerosisCerebrospinal fluid (CSF) analysis is of utmost importance for diagnosis and differential diagnosis of patients with suspected multiple sclerosis (MS). Evidence of intrathecal immunoglobulin G (IgG) synthesis proves the inflammatory nature of the disease, increases diagnostic certainty and substitutes for dissemination in time according to current diagnostic criteria. The gold standard to determine intrathecal IgG synthesis is the detection of CSF-restricted oligoclonal bands (OCBs). However, advances in laboratory methods brought up κ-free light chains (FLCs) as a new biomarker, which are produced in excess over intact immunoglobulins and accumulate in CSF in the case of central nervous system-derived inflammation. Overwhelming evidence showed a high diagnostic accuracy of intrathecal κ-FLC synthesis in MS with sensitivity and specificity of approximately 90% similar to OCB. κ-FLCs have advantages as its detection is fast, easy, cost-effective, reliable, rater-independent and returning quantitative results which might also improve the value of predicting MS disease activity. An international panel of experts in MS and CSF diagnostics developed a consensus of all participants. Six recommendations are given for establishing standard CSF evaluation in patients suspected of having MS. The panel recommended to include intrathecal κ-FLC synthesis in the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis

A cell-based assay for the detection of neutralizing antibodies against alemtuzumab.

Aim: The humanized anti-CD52 monoclonal antibody alemtuzumab depletes lymphocytes and is currently used to treat relapsing multiple sclerosis. During treatment, anti-alemtuzumab antibodies may develop and reduce effective lymphocyte depletion in future treatment cycles. Results: Alemtuzumab-Alexa Fluor 488 conjugate binding to the CHO-CD52 cell surface was inhibited by anti-alemtuzumab antibodies. Conclusion: In this proof-of-concept study, a CHO-CD52 cell line has been developed and used to detect the presence of anti-alemtuzumab neutralizing antibodies. This platform provides the basis of an assay for routine screening of serum for neutralizing antibodies from patients treated with alemtuzumab

A rare presentation of atypical demyelination: tumefactive multiple sclerosis causing Gerstmann's syndrome

r. KS has been supported by a Higher Education Funding Council for England (HEFCE) Clinical Senior Lectureshi

Anaesthetic management of people with multiple sclerosis.

There is a lack of published guidelines on the management of patients with multiple sclerosis (MS) undergoing procedures that require anaesthesia and respective advice is largely based on retrospective studies or case reports. The aim of this paper is to provide recommendations for anaesthetists and neurologists for the management of patients with MS requiring anaesthesia. This review covers issues related to the anaesthetic management of patients with MS, with a focus on preoperative assessment, choice of anaesthetic techniques and agents, side-effects of drugs used during anaesthesia and their potential impact on the disease evolution, drug interactions that may occur, and the need to use monitoring devices. A systematic PubMed research was performed to retrieve relevant articles

Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis

Background: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses. Methods: Eighty-six acute ON cases were randomized to receive phenytoin (4–6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL). Results: Sixty-four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo – phenytoin was −44 pg/ml at 3 months (P = 0.019) and −27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and −1.6 pg/ml at 6 months (P = 0.766). Conclusions: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized