Cerebrospinal Fluid Removal for Idiopathic Intracranial Hypertension: Less Cerebrospinal Fluid Is Best.

BACKGROUND: Although lumbar punctures (LPs) are used for diagnostic evaluation in idiopathic intracranial hypertension (IIH), they can also provide relief from IIH-associated headache. Conversely, low-pressure headache secondary to LP can be debilitating. Low-volume cerebrospinal fluid (CSF) removal to a "high-normal" closing pressure (CP), approximately 18-20 cm H2O, may result in relief of IIH-associated headache with a lowered frequency of post-LP headache. METHODS: We conducted a single-center retrospective analysis from 2011 to 2016 of patients who underwent fluoroscopic LPs aiming for high-normal CPs. Inclusion criteria were as follows: 1) pre-existing diagnosis of IIH, or opening pressure (OP) and clinical findings diagnostic for IIH; 2) height and weight recorded within 1 year; 3) documented LP data parameters; and 4) one week post-LP follow-up documenting whether headache was worse, unchanged, or better. RESULTS: One hundred forty-six patients met the inclusion criteria. Mean age was 34.9 years ± 11.0, and mean body mass index was 39.2 kg/m ± 10.5. Mean volume removed was 9.7 mL ± 4.6. The mean CP was 17.9 cm H2O ±2.7. The mean pressure change (OP-CP) per volume removed was 1.50 cm H2O/mL ±0.6. Headache symptoms at follow-up were improved in 64% (80/125) of patients, worse in 26% (33/125), and unchanged in 10% (12/125). Eleven patients were headache-free, and 11 patients required hospital care for post-LP headache. CONCLUSIONS: Low-volume CSF removal to approximately 18 cm H2O resulted in relief of IIH-associated headache in most patients and a low incidence of post-LP headache. Although clinically variable, these data suggest that for every 1 mL of CSF removed, the CP decreases approximately 1.5 cm H2O.

Review of Phase III Clinical Trials Outcomes in Patients with Secondary Progressive Multiple Sclerosis.

OBJECTIVE: Few satisfyingly effective treatments exist for patients with Secondary Progressive Multiple Sclerosis (SPMS). Our goal in conducting this review is to highlight clinical outcomes and study design, which may be applied to future phase III clinical trials for patients with SPMS. METHODS: A review of the available literature of phase III clinical trials since 1990 that specifically studied patients with SPMS. PubMed and ClinicalTrials.org were searched using appropriate terms. RESULTS: Expanded Disability Status Scale (EDSS) was most often used as an outcome measure, with time to confirmed disability progression at three months being used most often. Components of the Multiple Sclerosis Functional Composite (MSFC) were the next most frequent primary outcome measure used. Patient Reported Outcomes (PROs) were frequently used as secondary outcome measures with specific PROs more successful than others. MRI measures related to brain parenchymal volume have recently started to be used in phase III clinical trials. CONCLUSIONS: Some successful trials may have been related to patient selection for less inflammatory disease, which confounds the comparison between successful trials. Time to confirmed disability at three months or changes in composite MSFC are reasonable primary outcome measures to use in future SPMS trials with a suggestion that the MSFC may be more sensitive to progressive disease changes. PROs and MRI measures following brain parenchymal volume are reasonable secondary outcome measures to incorporate into future phase III trials in SPMS.

A New England COVID-19 Registry of Patients With CNS Demyelinating Disease: A Pilot Analysis.

BACKGROUND AND OBJECTIVES: We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic. METHODS: A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization. RESULTS: Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support. DISCUSSION: The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.