Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls.

INTRODUCTION: Several CSF biomarkers of neuronal injury have been studied in people living with HIV. At this time, the most useful is the light subunit of the neurofilament protein (NFL). This major structural component of myelinated axons is essential to maintain axonal caliber and to facilitate effective nerve conduction. CSF concentrations of NFL provide a sensitive marker of CNS injury in a number of neurological diseases, including HIV-related neuronal injury. Areas Covered: In this review, the authors describe CSF NFL concentrations across the spectrum of HIV-infection, from its early acute phase to severe immunosuppression, with and without neurological conditions, and with and without antiretroviral treatment (n = 516). Furthermore, in order to provide more precise estimates of age-related upper limits of CSF NFL concentrations, the authors present data from a large number (n = 359) of HIV-negative controls. Expert Commentary: Recently a new ultrasensitive diagnostic assay for quantification of NFL in plasma has been developed, providing a convenient way to assess neuronal damage without having to perform a lumbar puncture. This review also considers our current knowledge of plasma NFL in HIV CNS infection.

Analyzing the efficacy of frequent sodium checks during hypertonic saline infusion after elective brain tumor surgery.

OBJECTIVE: To assess the utility of frequent sodium checks (every 6h) in patients receiving hypertonic saline (HS) after elective brain tumor surgeries. PATIENTS AND METHODS: A single-institution retrospective review of patients having undergone elective craniotomies for brain tumors and treated with postoperative continuous intravenous infusions of 3% HS was performed. Changes in serum sodium values were analyzed at different time points. The rates of <12.5, 25, and 50cc/h infusions were also examined. Healthcare cost analysis was performed by extrapolating our cohort to the total number of craniotomies performed in the United States. RESULTS: No significant differences among sodium values checked between 0 to 4, 4-6, 6-8, 8-10, and >10h were observed (P=.64). In addition, no differences in serum sodium values among the rates of <12.5, 25, and 50cc/h were found (P=.30). No patients developed symptoms of acute hypernatremia. CONCLUSIONS: Serum sodium values did not significantly change more than 10h after infusion of HS. Further studies are needed to determine the optimal frequency of routine sodium checks to increase the quality of care and decrease healthcare costs.

Clinical and biomarker assessment of demyelinating events suggesting multiple sclerosis.

BACKGROUND: Initial demyelinating event (IDE) diagnosis and prognosis are not straightforward. OBJECTIVE: To identify potential diagnostic markers and outcome predictors of IDEs suggestive of multiple sclerosis (MS), that is, clinically isolated syndromes (CISs). METHODS: Clinically isolated syndrome cases (i.e., subjects with an IDE compatible with MS onset and no alternative explanation) with at least 1.5 years' follow-up were retrospectively identified. All cases underwent clinical, neurophysiological, MRI, and cerebrospinal fluid (CSF) assessment, including exploratory tau, 14-3-3, and cystatin C testing. CIS recovery, conversion to MS, and long-term neurological disability were used as outcome measures. Patients with neuromyelitis optica spectrum disorders, idiopathic acute transverse myelitis (IATM), Creutzfeldt-Jacob disease, and non-inflammatory/non-neurodegenerative disorders served as controls for CSF analysis. RESULTS: Forty-six CIS cases were included. Severe presentation was associated with incomplete recovery, while presence of at least 3 periventricular lesions on baseline MRI correlated with MS conversion. Initial pyramidal tract involvement, incomplete CIS recovery, and number of relapses predicted neurological disability. CSF tau, 14-3-3, and cystatin C did not correlate with any outcome measure. CIS cases had significantly lower tau and cystatin C levels compared to IATM. CONCLUSIONS: An extensive diagnostic evaluation of patients with an IDE is worthwhile to make prognostic predictions. More robust molecular biomarkers are needed.

A simple, inexpensive and easily reproducible model of spinal cord injury in mice: morphological and functional assessment.

Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance, and significantly impacts life expectancy and quality. Animal models provide a good opportunity to test therapeutic strategies in vivo. C57BL/6 mice were subjected to laminectomy at T9 and compression with a vascular clip (30g force, 1min). Two groups were analyzed: injured group (SCI, n=33) and laminectomy only (Sham, n=15). Locomotor behavior (Basso mouse scale-BMS and global mobility) was assessed weekly. Morphological analyses were performed by LM and EM. The Sham group did not show any morphofunctional alteration. All SCI animals showed flaccid paralysis 24h after injury, with subsequent improvement. The BMS score of the SCI group improved until the intermediate phase (2.037+/-1.198); the Sham animals maintained the highest BMS score (8.981+/-0.056), p<0.001 during the entire time. The locomotor speed was slower in the SCI animals (5.581+/-0.871) than in the Sham animals (15.80+/-1.166), p<0.001. Morphological analysis of the SCI group showed, in the acute phase, edema, hemorrhage, multiple cavities, fiber degeneration, cell death and demyelination. In the chronic phase we observed glial scarring, neuron death, and remyelination of spared axons by oligodendrocytes and Schwann cells. In conclusion, we established a simple, reliable, and inexpensive clip compression model in mice, with functional and morphological reproducibility and good validity. The availability of producing reliable injuries with appropriate outcome measures represents great potential for studies involving cellular mechanisms of primary injury and repair after traumatic SCI.

[Assessment of drug-related risk using expected/observed methods (standardized rate method): definition and application to pharmacovigilance]. / Evaluation du risque médicamenteux par la méthode attendu/observé: définition et utilisation en pharmacovigilance.

Indirect standardisation or the standardised rate method, consists of a comparison of the number of observed and expected cases. This method could be applied in the field of pharmacovigilance in order to investigate the potential relationship between drug exposure and the occurrence of an adverse event. It consists of the calculation of an expected number of events obtained by multiplying the exposed population by the event rate in the reference population. The comparison is made by means of a standardised mortality or incidence ratio (SMR or SIR). Three examples of this method are presented. The first example concerns central nervous system demyelinating disorders and hepatitis B vaccine, where the SIR calculated from spontaneous reports was equal to 1.05 (95% CI [0.82-1.26]). In the second example, the SMR of cardiovascular deaths related to sildenafil was significantly different from 1 (0.69, [0.43-1.08]) using data from prescription-event monitoring. In the last example, a strong association between acute leukaemia and chemotherapy in breast cancer was found (SIR 28.5, [12.3-56.2]) using exhaustive data from cancer registries. This method allows a quick and cheap risk assessment, although the quality of available data may limit validity of results. In this case, the hypothesis need to be examined by further ad-hoc clinical and pharmacoepidemiological studies.