Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

Diagnostic Delay of Multiple Sclerosis in a Portuguese Population.

INTRODUCTION: Multiple sclerosis is a chronic inflammatory disease, in which a diagnostic delay could reduce the available therapeutic options. Therefore, it is important to monitor the time to diagnosis and understand factors that may potentially reduce it. The objective of this study was to determine the time between the first symptoms and the diagnosis of multiple sclerosis and which factors may contribute to a diagnostic delay. MATERIAL AND METHODS: Cross-sectional multicenter study, with retrospective data analysis, conducted in five tertiary Portuguese hospitals. Patients were consecutively selected from each local multiple sclerosis patients´ database. Sociodemographic and initial clinical data were collected through a questionnaire. Date of final diagnosis and multiple sclerosis classification was obtained from clinical files. RESULTS: A total of 285 patients were included with mean age at diagnosis of 36 years. The median time between first clinical manifestation and multiple sclerosis diagnosis was nine months (IQR 2 - 38). Diagnostic delay was associated with an older age (p < 0.001; r = 0.35), motor deficit at onset [26.5 months (IQR 4.5 - 56.5); p = 0.0005], higher number of relapses before diagnosis (p < 0.001; r = 0,626), first observation by other medical specialty [11 months (IQR 2 - 48); p < 0.001], prior alternative diagnosis [20 months (IQR 4 - 67.5); p < 0.001] and primary progressive subtype [37 months (IQR 25 - 64.5); p < 0.001]. The most significant delay occurred between the initial symptom and neurological observation. DISCUSSION: A significant delay occurred between initial symptoms and the diagnosis of multiple sclerosis, reflecting the need toincrease awareness of this entity and its diverse symptom presentation.

Introdução: A esclerose múltipla é uma doença inflamatória crónica na qual um atraso no diagnóstico poderá reduzir as opções terapêuticas, sendo importante monitorizar o tempo até ao diagnóstico e compreender os fatores que potencialmente o reduzam. Foi objetivo deste estudo determinar o tempo entre os primeiros sintomas e o diagnóstico de esclerose múltipla e quais os fatores que podem contribuir para o atraso no diagnóstico. Material e Métodos: Estudo multicêntrico transversal retrospetivo, realizado em cinco hospitais portugueses. Os doentes foram selecionados, consecutivamente, a partir de bases de dados locais. Os dados sociodemográficos e clínicos iniciais foram adquiridos através de questionário individual. A data do diagnóstico final e a classificação da esclerose múltipla foram obtidas por consulta do processo clínico. Resultados: Foram incluídos 285 doentes com média de idade ao diagnóstico de 36 anos. A mediana do tempo entre a primeira manifestação clínica e o diagnóstico foi de nove meses (IQR 2 - 38). O atraso no diagnóstico foi associado a idade avançada (p < 0,001; r = 0,35), défice motor inicial [26,5 meses (IQR 4,5 - 56,5), p = 0,0005], maior número de surtos previamente ao diagnóstico (p < 0,001; r = 0,626), primeira observação por outra especialidade médica [11 meses (IQR 2 - 48); p < 0,001], diagnóstico prévio alternativo [20 meses (IQR 4 - 67,5); p < 0,001] e esclerose múltipla primária progressiva [37 meses (IQR 25 - 64,5), p < 0,001]. O atraso mais significativo ocorreu entre o primeiro sintoma e a observação por neurologista. Discussão: Ocorreu um atraso significativo entre o primeiro sintoma e o diagnóstico de esclerose múltipla, refletindo uma necessidade de maior acuidade na identificação dos seus principais sintomas.

An unusual case of short-lasting unilateral neuralgiform headache attacks.

BACKGROUND: Short-lasting unilateral neuralgiform headaches include those with conjunctival injection and tearing and with cranial autonomic symptoms. Most frequently reported as idiopathic, there is a growing number of symptomatic cases described. CASE REPORT: A 57-year old man presented a 16-year history of right hemifacial short-lasting pain attacks accompanied by ipsilateral autonomic symptoms and simultaneous malar contractions. Brain MRI disclosed a right acoustic neuroma compressing the right facial nerve and a venous developmental anomaly perpendicular to the right facial nerve root entry zone, without lesions affecting the trigeminal nerve. He was started on lamotrigine, resulting in complete remission of pain attacks, autonomic signs and facial contractions. CONCLUSIONS: This patient presents a typical short-lasting unilateral neuralgiform headache with response to lamotrigine. The uniqueness of the case is the co-occurring malar contractions, evocative of facial nerve involvement. We speculate whether facial nerve compression renders this nerve more susceptible to triggering during a short-lasting unilateral neuralgiform headache attack.

Clinical features of hypertrophic pachymeningitis in a center survey.

BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.

Juvenile myoclonic epilepsy refractory to treatment in a tertiary referral center.

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is an epileptic syndrome often regarded as one in which seizures are relatively easy to control. Individuals with JME, however, often require lifelong therapy to remain seizure-free, and a few have refractory epilepsy. We ascertained a population with JME and characterized a subgroup with refractory epilepsy. MATERIAL AND METHODS: We audited and reviewed clinical records of individuals diagnosed with JME identified via a sample of 6600 individuals in a clinical database from a specialized epilepsy clinic at a tertiary referral center. RESULTS: We identified 240 people with a diagnosis of JME (146 females), with a mean age at seizure onset of 14.2years (SD: 4.5), and a mean age at diagnosis of 15.6years (SD: 4.9). Clinical phenotypes seen were classic JME phenotype (88%), childhood absence epilepsy evolving into JME (6%), JME with adolescent absences (4%), and JME with astatic seizures (2%). More than a quarter (28%) had a family history of epilepsy. The most commonly used antiepileptic drug (AED) was sodium valproate in 78% of individuals, followed by levetiracetam (64%) and lamotrigine (55%). In the previous year, 47.5% were seizure-free. Using the International League against Epilepsy (ILAE) definitions and considering National Institute for Health and Care Excellence (NICE)-recommended AEDs for this syndrome, 121 individuals (50.4%) were identified as having refractory epilepsy. DISCUSSION: Juvenile myoclonic epilepsy is often regarded as a benign epileptic syndrome, but in this setting, half of the individuals with JME have refractory epilepsy with only about a quarter of those seizure-free in the previous year. Despite some advances in the understanding of this syndrome, there is still much to do before we can offer all the best outcomes.

Concurrent autoimmune hepatitis in multiple sclerosis.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare and chronic inflammatory disorder associated with extrahepatic autoimmune diseases, including, infrequently, multiple sclerosis (MS). Short Reports: We report five cases of MS and AIH association. One patient developed AIH while under interferon beta-1b and the remaining while off disease-modifying therapy, although after methylprednisolone bolus in three. All presented a liver biopsy compatible with AIH. Hepatitis resolution was achieved with immunosuppressive treatment, but one patient died after a fulminant hepatitis requiring liver transplant. DISCUSSION: A thorough review of published cases supports this clear, although rare, association and a liver biopsy should be considered in AIH suspected cases.

Neurosarcoidosis according to Zajicek and Scolding criteria: 15 probable and definite cases, their treatment and outcomes.

INTRODUCTION: Neurosarcoidosis occurs in about 5% to 15% of patients with sarcoidosis. The purpose of this study was to identify and characterize a cohort of neurosarcoidosis patients and to review the largest previously reported neurosarcoidosis case series. METHODS: This retrospective study enrolled all patients with the diagnosis of probable or definitive neurosarcoidosis according to Zajicek and Scolding criteria, followed at the neurology department of a tertiary center in Portugal from January 1989 to December 2015. RESULTS: A total of 15 patients presented a diagnosis of probable or definitive neurosarcoidosis, with a mean age at time of diagnosis of 38.5years. The presenting neurologic syndrome was isolated cranial neuropathy, aseptic meningitis, myelitis, brain parenchymal lesion, myelorradiculitis and meningomyelorradiculitis. MRI study most often presented different enhancing lesions and the CSF analysis commonly revealed a lymphocytic pleocytosis and raised proteins. Thirteen patients had histopathology confirmation of systemic sarcoidosis and one preformed a spinal cord biopsy. Corticosteroids was the most often used treatment alone or in combination with immunosuppressive drugs. After a mean follow-up of 86.1months, the majority of patients fully recovered to a mRankin 0. DISCUSSION: Fully comprehension of neurosarcoidosis is still a challenge due to its rarity and limited number of large published series, which renders the epidemiological study of this disease very difficult. In this study, the thoroughly medical records review and the summarize of previous published cohorts allow to add some information in the epidemiological and clinical knowledge of this entity.

SUNCT syndrome: A cohort of 15 Portuguese patients.

BACKGROUND: In this paper, we describe a cohort of patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), a rare trigeminal autonomic headache, managed in the outpatient clinic of a tertiary hospital. METHODS: Patients were identified through review of individual records between January 1, 2008 and June 30, 2014. RESULTS: Fifteen patients were identified (eight males:seven females), with mean age at onset of 49.7 years, mean number of attacks per day of 7.5 and mean attack duration of 54.6 seconds. Pain was mostly orbital, periorbital or temporal. Cranial autonomic signs/symptoms were universally present; one patient reported ipsilateral epistaxis. Two symptomatic cases were identified and treated surgically. Most patients responded to lamotrigine, one to topiramate and another to eslicarbazepine. CONCLUSION: Our case series is among the largest reported, with findings similar to others already published, but the first to report epistaxis during SUNCT attack and response to eslicarbazepine.