Objective: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. Methods: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). Results: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrastenhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. Conclusion: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS.
We report the case of a 9-year-old girl admitted with fever, headache, and a cerebrospinal fluid lymphocytic pleocytosis. Polymerase chain reaction was positive for human herpes virus 6. She subsequently developed ataxia and bilateral loss of vision. Magnetic resonance imaging (MRI) showed bilateral optic nerve lesions with extension to optic chiasm and a short-segment myelitis. Serologic studies were positive for Borrelia burgdorferi IgM. Anti-aquaporin 4 antibody was negative and anti-myelin oligodendrocyte glycoprotein antibody (MOG) positive. After intravenous methylprednisolone, ceftriaxone, and intravenous immunoglobulin, her vision slowly recovered. The patient was discharged with only mild visual acuity loss, 1 month after admission. Brain MRI was repeated later and was normal and MOG assay became negative. In our view, this patient suffered from a postinfectious, anti-MOG-mediated, spinal cord and optic nerve demyelination. Borrelia burgdorferi infection is associated with neurologic manifestations in up to 15% of cases.1 Optic neuritis related with Lyme borreliosis has been reported infrequently and there is uncertainty about the validity of the diagnosis in many cases.2 Neurologic manifestations associated with human herpes virus 6 (HHV6) infection are usually febrile seizures in infants and encephalitis in immunosuppressed patients. 3Optic neuritis may have multiple causes, including infection and several autoimmune diseases, such as multiple sclerosis, acute disseminated encephalomyelitis, or neuromyelitis optica spectrum disorders.We describe a case of one female adolescent with antimyelin oligodendrocyte glycoprotein (MOG)-positive optic neuritis and myelitis. She had a positive polymerase chain reaction for HHV6 in cerebrospinal fluid and positive enzyme-linked immunosorbent assay and Western blot for Borrelia burgdorferi in serum. We propose that our case expands the spectrum of the association between infection and immunemediated MOG demyelination. Case ReportA previously healthy 9-year-old girl of African descent living in the Azores Islands was admitted to her local hospital with a 6-day history of a febrile illness, headache, and somnolence, previously treated with amoxicillin-clavulanic acid without resolution of symptoms. She had no history of recent travel. Her white blood cell count was 16340/mL (80% neutrophils) and c-reactive protein 0.88 mg/dL. Cerebrospinal fluid examination revealed a cell count of 95 cells/mL, with lymphocytic predominance and elevated protein (66 mg/dL). Polymerase chain reaction in the cerebrospinal fluid was positive for HHV6 and negative for Borrelia burgdorferi, and no serologic tests were performed regarding HHV6. Four days later, she presented with gait imbalance, abdominal pain, and dysuria. Neurologic examination was positive for gait ataxia with a positive Romberg sign. She underwent treatment with a 21-day course of ganciclovir (10 mg/kg/d) and was discharged on the 26th day after admission with a normal physical examination. Brain
Introduction: Some patients with epilepsy identify weather as a typical seizure trigger. However, it is yet to be confirmed. Thus, we aimed to evaluate possible relationships between daily meteorological conditions and the daily incidence of seizures. Methods: This was a retrospective single center study that included adult patients who were admitted to the emergency room of a tertiary hospital in Lisbon, with a seizure, between January and December 2015. The influence of temperature, atmospheric pressure, relative humidity, wind, precipitation, sunlight duration, and the seasons on seizure frequency was evaluated. Results: Three hundred seven seizure episodes were included (from 286 patients) in a total of 365 days, 117 (38.1%) first unprovoked seizures and 190 (61.9%) with previous seizure episodes. There were 82 days with higher incidence of seizures (≥2) and 171 days without seizures. We found a statistical significant relation between lower ambient temperatures, higher atmospheric pressure, and higher maximum humidity with days with two or more seizures. We also found a statistically significant higher incidence of seizures in the winter days (p-value: 0.001) and in days with lower daylight duration (10.8 vs. 12.7 h; p-value: 0.0001). With the exception of humidity, these findings remained true when analyzing the subgroup of patients with previous seizures, but there was no significant difference in the subgroup of first unprovoked seizures. Conclusions: Our results support the possible influence of the weather on seizure frequency in the overall admissions of the emergency department of a tertiary hospital. In particular, these findings suggest that winter conditions, such as, lower ambient temperatures, higher atmospheric pressure, higher humidity, and reduced sunlight exposure, may have impact in the occurrence of higher incidence of seizures in patients with epilepsy.
In this real-world audit, fingolimod appeared to be effective after first-line treatment failure in reducing disease activity and progression of disability throughout the observational period and may be an effective option after natalizumab. Fingolimod was well tolerated with low rates of discontinuation and adverse events.
Background Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). Objectives To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. Methods Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. Results Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. Conclusions Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.
Parvovirus B19 (PB19) is a common, widespread, small, single-stranded DNA virus which has been linked with a broad spectrum of clinical illnesses, including a variety of neurological complications such as encephalitis, meningitis, myelitis, stroke, cerebellar ataxia, and neuropathy. The authors describe a case of PB19 infection associated with hemolytic anemia and cranial polyneuropathy involving the second and third cranial nerves in a 23-year-old immunocompetent woman. The diagnosis of acute PB19 infection was established with detection of positive DNA and anti-PB19 IgM antibodies in blood samples. Antiganglioside antibody studies were performed and serum anti-GD1b IgG was strongly positive. Further investigation was normal or negative, excluding other infectious or autoimmune disorders. The patient was initially treated with a 5-day course of intravenous immunoglobulin (IGIV). Because of incomplete neurological recovery, methylprednisolone was also administered 7 days after IGIV therapy initiation. Complete resolution of clinical symptoms was observed 3 months after disease onset at follow-up visit, despite the persistence of PB19 DNA and anti-PB19 IgM antibodies in serum 5 months after the initial presentation. Our report provides evidence that PB19 could affect both the central and peripheral nervous system, possibly by triggering an autoimmune mechanism that leads to autoantibody production.
Objectives The aim of this study was to evaluate postmarketing dimethyl fumarate (DMF) safety and effectiveness in a real-world population with relapsing-remitting multiple sclerosis (RRMS). Methods This was a retrospective, single-center study with RRMS patients treated with DMF. Demographic, clinical, and imagiological characteristics were analyzed, including annualized relapse rate (ARR), Expanded Disability Status Scale, “No Evidence of Disease Activity 3,” previous treatment, adverse events, treatment duration, and reason for discontinuation. We investigated which baseline variables were associated with clinical and radiological outcomes. Results We included 176 patients (70.4% females) with a median on-treatment follow-up time of 25.5 months. In total, 139 patients received prior disease-modifying therapies, and 37 were treatment-naive. Annualized relapse rate decreased by 77.1% in the total population (P < 0.001) and also decreased in the naive, tolerability switch, and efficacy switch groups by 95.8%, 56.7%, and 76.6% (P < 0.001). No Evidence of Disease Activity 3 status after 12 months of DMF treatment was maintained in 69.2% patients. Thirty patients (17%) discontinued treatment because of adverse drug reactions, and 21 (11.9%) because of lack of effectiveness. The occurrence of first relapse during follow-up was associated with higher ARR in the year before DMF start (hazard ratio, 4.833; P < 0.001) and prior exposure to multiple sclerosis treatments (tolerability and efficacy switchers). Conclusions In this real-world audit, DMF appeared to be effective and safe for RRMS. Additionally, the study suggested that naive patients strongly benefit from DMF, and DMF also improves ARR in patients who switched from injectable therapies due to tolerability and efficacy issues.
Objectives: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up.Methods: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021.Results: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects. Conclusion:Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.
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