Estimation of sample size in randomized controlled trials in multiple sclerosis studying annualized relapse rates: A systematic review.

BACKGROUND: In multiple sclerosis (MS) studies, the most appropriate model for the distribution of the number of relapses was shown to be the negative binomial (NB) distribution. OBJECTIVE: To determine whether the sample-size estimation (SSE) and the analysis of annualized relapse rates (ARRs) in randomized controlled trials (RCTs) were aligned and compare the SSE between normal and NB distributions. METHODS: Systematic review of phase 3 and 4 RCTs for which the primary endpoint was ARR in relapsing remitting MS published since 2008 in pre-selected major medical journals. A PubMed search was performed on 30 November 2020. We checked whether the SSE and ARR analyses were congruent. We also performed standardized (fixed α/ß, number of arms and overdispersion) SSEs using data collected from the studies. RESULTS: Twenty articles (22 studies) were selected. NB distribution (or quasi-Poisson) was used for SSE in only 7/22 studies, whereas 21/22 used it for ARR analyses. SSE relying on NB regression necessitated a smaller sample size in 21/22 of our calculations. CONCLUSION: SSE was rarely performed using the most appropriate model. However, the use of an NB model is recommended to optimize the number of included patients and to be congruent with the final analysis.

High Prevalence of Headaches During Covid-19 Infection: A Retrospective Cohort Study.

OBJECTIVES: To document the prevalence of new headaches in patients with Covid-19 infection and the potential association with other neuro-sensorial symptoms (anosmia and ageusia). The persistence of these symptoms 1 month after recovery was also documented. BACKGROUND: Headaches are a very common symptom of viral infections. Surprisingly, early Chinese studies reported a relatively low prevalence (12-15%) of headaches associated with Covid-19. METHODS: All the patients with laboratory-confirmed or chest-CT-confirmed Covid-19 infection, diagnosed between February 27th and April 15th , 2020 in the dedicated laboratory of Clermont-Ferrand University Hospital were followed for 1 month after recovery. RESULTS: A total of 139 consecutive patients (mean [SD] age, 48.5 [15.3] years; 87 women [62.6%]) were interviewed 1 month after disappearance of fever and dyspnea (semi-structured phone interview). Overall, 59.0% (82/139) of people with Covid-19 had mild disease, 36.7% (51/139) had severe disease, and 4.3% (6/139) had critical illness. Eighty-two (59.0%; 95% CI: 50.3 to 67.3) reported new headaches during the acute phase and 3.6% (5/139) had persistent headaches 1 month after fever and dyspnea remission. Anosmia and ageusia were also very common, occurring in 60.4% (84/139) and 58.3% (81/139) of the patients, respectively. These 2 symptoms persisted in 14.4% (20/139) and 11.5% (16/139) of Covid-19 patients 1 month after recovery. Headaches were neither clearly associated with anosmia, nor with ageusia, and were not associated with disease severity (ie, requiring hospitalization or intensive care unit). CONCLUSION: This specific study highlights the high prevalence of new headaches during Covid-19 infection in French patients. Further studies are needed to refine the characterization of patients with Covid-19-associated headaches.

Anti-LGI1 Encephalitis With Co-occurring IgLON5 Antibodies: Clinical Features and Human Leukocyte Antigen Haplotypes.

OBJECTIVES: Autoimmune encephalitis (AE) with antibodies against LGI1 and IgLON5 are clinically distinctive but share some particularities such as a strong association with specific human leukocyte antigen (HLA) class II alleles. METHODS: We clinically describe a patient with double positivity for LGI1 and IgLON5 antibodies. In addition, we conducted specific immunodepletion with the patient's serum and HLA typing and investigated the presence of serum IgLON5 antibodies in a cohort of 23 anti-LGI1 patients carrying the HLA predisposing for anti-IgLON5 encephalitis. RESULTS: A 70-year-old woman with a history of lymphoepithelial thymoma presented with subacute cognitive impairment and seizures. Investigations included MRI and EEG showing medial temporal involvement, increased CSF protein content, and polysomnography with REM and non-REM motor activity, along with obstructive apnea. Neural antibody testing revealed both LGI1 and IgLON5 antibodies in serum and CSF, and serum immunodepletion ruled out cross-reactivity. The patient carried DRB1*07:01 and DQA1*01:01∼DQB1*05:01, but no other IgLON5-positive case was identified in a cohort of anti-LGI1 patients carrying DQA1*01∼DQB1*05. Nearly full therapeutic response was obtained after intensified immunosuppressive treatment. DISCUSSION: We present a case of anti-LGI1 encephalitis with concomitant IgLON5 antibodies. Co-occurring IgLON5 antibodies in anti-LGI1 encephalitis are exceptional, but may appear in genetically predisposed individuals.

Whole-body reversible neuropathic pain associated with right parieto-temporal operculum single inflammatory lesion in a patient with multiple sclerosis: A case report.

BACKGROUND: The posterior insula and the medial parietal operculum (PIMO) are part of the pain network. Pain can be induced by direct stimulation of the PIMO, but the clinical consequence of lesions in this brain area is not well known. CASE REPORT: We report the case of a patient with multiple sclerosis who presented a relapse characterized by isolated widespread neuropathic pain. The MRI displayed a single new inflammatory lesion in the juxta cortical white matter of the opercular region. This lesion was extended to the parietal operculum and was associated with the pain syndrome. The patient was treated with high-dose intravenous methylprednisolone, and the pain disappeared progressively. Diffusion-tensor MRI showed that some of the fibres passing through the lesion ended in the PIMO. CONCLUSION: Based on diffusion-tensor MRI we hypothesize that the partial disconnection from afference to the PIMO can lead to widespread neuropathic pain. SIGNIFICANCE: Most of the data concerning the functional role of the PIMO come from stereoelectroencephalography in presurgical evaluation of epilepsy, or from functional imaging (PET or fMRI). There is, however, very few data on the consequences of the lesion of the PIMO. Here, we report the first case of a transient widespread pain syndrome associated to a single, small and reversible inflammatory lesion of the PIMO. Thus, this case highlights the key role of the PIMO in spatial perception of pain.