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Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently emerging autoimmune disease of the central nervous system (CNS); GFAP astrocytopathy is characterized by optic neuritis and meningoencephalomyelitis. We report the case of a 55-year-old man, otherwise healthy, who presented with isolated headaches for three months, without other features of meningoencephalitis or myelitis. His neurological examination and fundoscopy were unremarkable. Gadolinium-enhanced brain MRI demonstrated increased T2 hyperintensity within the right sub-lenticular basal ganglia, with additional leptomeningeal enhancement along the bilateral perisylvian regions and mesial temporal lobes. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, matching oligoclonal bands, and a negative infectious and cytological workup. Cell-based assays for anti-aquaporin-4, anti-myelin oligodendrocyte glycoprotein, autoimmune encephalitis panel, and vasculitis workup were all negative, except for CSF positivity for GFAP α antibody. Oncological screening, including CT of the chest, abdomen, pelvis, and scrotal US, was unremarkable. Immunotherapy with high-dose intravenous steroids for five days and subsequent single four-weekly doses resulted in the resolution of both clinical and radiographic features, with a maintained status 24 months after onset. This case highlights isolated headache and basal ganglia, mesial temporal lobe involvement as a rare presentation of autoimmune GFAP astrocytopathy.
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Despite convergent evidence that upwards of 50% of patients with MS transition from a relapsing to progressive phase within 20 years of disease onset, and the recent acknowledgement of the commonality of progression independent of relapses, there remains no consensus regarding the nature and timing of a discussion about the possibility of a secondary progressive phase with relapsing-remitting MS patients. Some neurologists prefer to conduct this at the inaugural visit to provide more information about disease behaviour and potential planning that might entail, while others may defer any discussion about this phase, as there is no clear consensus for it and it can be a sensitive topic, with concern that too early a discussion could worsen anxiety and discourage or delay decisions regarding disease modifying treatments. Furthermore, it is unknown at onset which patients will transition to a progressive phenotype. This review and opinion paper will outline some of the opportunities and challenges associated with such a disclosure, and attempt to provide a balanced, patient-centred approach to address this delicate topic.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Progressão da Doença , RecidivaRESUMO
Multiple sclerosis (MS) most commonly presents in young adults, although 3-5% of patients develop MS prior to the age of 18 years. The new and comprehensive consensus for the management of MS in Saudi Arabia includes recommendations for the management of MS and other CNS inflammatory demyelinating disorders in pediatric and adolescent patients. This article summarizes the key recommendations for the diagnosis and management of these disorders in young patients. Pediatric and adult populations with MS differ in their presentation and clinical course. Careful differential diagnosis is important to exclude alternative diagnoses such as acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica spectrum disorders (NMOSD). The diagnosis of MS in a pediatric/adolescent patient is based on the 2017 McDonald diagnostic criteria, as in adults, once the possibility of ADEM or NMOSD has been ruled out. Few data are available from randomized trials to support the use of a specific disease-modifying therapy (DMT) in this population. Interferons and glatiramer acetate are preferred initial choices for DMTs based on observational evidence, with the requirement of a switch to a more effective DMT if breakthrough MS activity occurs.
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Encefalomielite Aguda Disseminada , Esclerose Múltipla , Neuromielite Óptica , Adolescente , Criança , Humanos , Consenso , Acetato de Glatiramer/uso terapêutico , Interferons/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/terapia , Neuromielite Óptica/epidemiologia , Arábia SauditaRESUMO
This article focuses on the diagnosis and management of neuromyelitis optica spectrum disorder (NMOSD). NMOSD is an autoimmune, demyelinating condition characterized by inflammation of the optic nerve and/or the spinal cord, with symptoms that can range from mild impairment of movement to paralysis. The newly approved diagnostic criteria have improved the accuracy of NMOSD diagnosis. The management of NMOSD is under major revolution due to the many new therapeutic options. The role of the antibodies directed at aquaporin-4 (AQP4) has materialized as a biomarker for NMOSD. Several new treatments that target variable aspects in immunopathology such as IL-6, complement, or depletion of B cells are emerging. The management of AQP4-negative patients remains challenging.
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Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Biomarcadores , Consenso , Humanos , Interleucina-6 , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/terapia , Arábia SauditaRESUMO
OBJECTIVES: To report demographic and clinical data on 98 myasthenia gravis (MG) patients, seen over 5 years (January 2014-December 2018). METHODS: This was a retrospective, observational cohort study carried out at 3 hospitals in Bahrain. MG was classified into ocular or generalized types. We subdivided MG into early-onset (EOMG, ≤ 49 years) or late-onset (LOMG, > 49 years). Demographic and clinical data were recorded. The data was entered and analyzed using SPSS version 26.0. RESULTS: 61.2% were females. The mean age at onset was 43.8±17.7 years in males and 43.1±15.7 years in females. 72.4% had EOMG. A pure ocular presentation was most common (51%). Limb weakness was more prevalent in AChR-positive patients. The MuSK group had more severe presentation. 57.1% of patients were AChR-positive, 3.1% MuSK-positive, and 39.8% double-seronegative. Generalized disease onset was more likely with AChR. Abnormal CT chest was seen in 24/69 (35%) including thymic hyperplasia, thymoma, and thymic atrophy. Pathology findings were thymic hyperplasia (55.0%), thymoma (30%), thymolipoma (10%), and normal thymus (5%). Treatment outcomes were favorable. CONCLUSION: The present study revealed that MG was more common in females, with similar age at onset between males and females. The majority of patients had EOMG with ocular disease and AChR positivity. The clinical outcomes were favorable. Following a standardized protocol for MG diagnosis and workup is recommended.
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Miastenia Gravis , Neoplasias do Timo , Idade de Início , Autoanticorpos , Barein/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Blood pressure (BP) changes during alemtuzumab infusions are poorly understood. The aim of this study was to examine BP changes during alemtuzumab infusions in persons with multiple sclerosis (PwMS). METHODS: This was a retrospective cohort review of systolic (S) and diastolic (D) BP in PwMS receiving alemtuzumab. RESULTS: Thirty-one patients were identified; 22 (64.5%) were women. Mean age and disease duration were 35.2 ± 7.1 and 9.2 ± 5.4 years, respectively. There was no history of hypertension or vascular events. Mean baseline SBP was 119.8 ± 15.1 mmHg, 118.8 ± 14.3 mmHg and 106.5 ± 6.1 mmHg whilst mean DBP was 75.3 ± 9.2 mmHg, 74.1 ± 12.4 mmHg and 69.2 ± 4.3 mmHg at doses 1, 6 and 9, respectively. During the first cycle, SBP increased by 19.2 ± 9.4 mmHg, with comparable percentage increases over the five infusions (16%, 22%, 17%, 11%, 13%, respectively). DBP increased by 6.2 ± 3.8 mmHg with similar percentage increases over the five infusions (8.4%, 11.5%, 5.5%, 7%, 3%). For the second cycle, SBP increased by 16.9 ± 3.2 mmHg, with similar increases over the 3 days (12%, 15%, 17%). DBP increased by 5.4 ± 4.2 mmHg (11%, 9%, 12.8%). The third cycle demonstrated increased mean and percentage of SBP and DBP by 8.9 ± 2.3 mmHg (10%, 70%, 11.8%) and 4.2 ± 1.9 mmHg (3%, 2%, 6.5%), respectively. Collectively, for 31 patients, in the first cycle, mean SBP increased from 119.8 ± 15.1 mmHg to 138.8 ± 13 mmHg (p Ë 0.001), whilst mean DBP increased from 74.5 ± 9.2 mmHg to 79.2 ± 9.1 mmHg (p = 0.007). Overall, 17 (54.8%) patients had increasing BP by ≥20% and nine (29%) had increasing BP by ≥20 mmHg from baseline. CONCLUSIONS: This demonstrates significant increases in BP during alemtuzumab infusions in PwMS.
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Hipertensão , Esclerose Múltipla , Alemtuzumab , Pressão Sanguínea , Feminino , Humanos , Esclerose Múltipla/tratamento farmacológico , Estudos RetrospectivosRESUMO
Introduction: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-related disease was initially described as a subtype of neuromyelitis optica spectrum disorder (NMOSD) with antibodies against MOG. However, it has recently been described as a separate disease entity with clinical and radiological features that overlap those of multiple sclerosis (MS) and NMOSD; the clinical features of this disease phenotype remain undetermined. We herein report the clinical presentation of nine MOG-IgG-positive patients, not all of whom fulfill the NMOSD criteria, in order to highlight the features and challenges of this condition. Method: We retrospectively reviewed the records of the London (Ontario) MS clinic to identify patients diagnosed with positive MOG antibodies based on the 2015 NMOSD consensus criteria. Result: Nine patients were identified, all Caucasian. Seven (78%) were female, and the median age of onset was 41 years (range, 28-69 years); the median Expanded Disability Status Scale score at onset was 3.0 (range, 2.0-4.0). A monophasic course was noted in two (22.2%) patients, while the median number of relapse events was 3 (range 2-5) in 77.8% of the patients. Optic neuritis and transverse myelitis contributed equally as initial manifestations in three individuals (33%), while brainstem relapse was reported in two individuals (22%). The brain magnetic resonance imaging findings were compatible with McDonald's 2010 dissemination in space criteria in three cases (33%). Short myelitis and an (H)-sign were each documented in one patient. Conclusion: The phenotypes of MOG Ab-positive cases exhibited overlapping features with MS and NMOSD. This finding highlights the importance of screening for anti-MOG in individuals with demyelinating symptoms, in consideration of the possibility of false-positive MOG Ab results.
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OBJECTIVE: To describe the clinical and radiological characteristics of neuromyelitis optica spectrum disorders (NMOSD) patients from the Arabian Gulf relative to anti-aquaporin 4 antibody serostatus. METHODS: Retrospective multicentre study of hospital records of patients diagnosed with NMOSD based on 2015 International Panel on NMOSD Diagnosis (IPND) consensus criteria. RESULTS: One hundred forty four patients were evaluated, 64.3% were anti-AQP4 antibody positive. Mean age at onset and disease duration were 31±12 and 7⯱â¯6 years respectively. Patients were predominantly female (4.7:1). Overall; relapsing course (80%) was more common than monophasic (20%). Optic neuritis was the most frequent presentation (48.6%), regardless of serostatus. The proportion of patients (54.3%) with visual acuity of ≤ 0.1 was higher in the seropositive group (pâ¯=â¯0.018). Primary presenting symptoms of transverse myelitis (TM) were observed in 29% of patients, and were the most significant correlate of hospitalization (p<0.001). Relative to anti-APQ4 serostatus, there were no significant differences in terms of age of onset, course, relapse rates or efficacy outcomes except for oligoclonal bands (OCB), which were more often present in seronegative patients (40% vs.22.5%; pâ¯=â¯0.054). Irrespective of serostatus, several disease modifying therapies were instituted including steroids or immunosuppressives, mostly, rituximab and azathioprine in the cohort irrespective of serostatus. The use of rituximab resulted in reduction in disease activity. CONCLUSION: This is the first descriptive NMOSD cohort in the Arabian Gulf region. Seropositive patients were more prevalent with female predominance. Relapsing course was more common than monophasic. However, anti-AQP4 serostatus did not impact disease duration, relapse rate or therapeutic effectiveness. These findings offer new insights into natural history of NMOSD in patients of the Arabian Gulf and allow comparison with patient populations in different World regions.
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Imunoglobulina G/uso terapêutico , Glicoproteína Mielina-Oligodendrócito/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite Óptica/tratamento farmacológico , Sistema de Registros , Acuidade Visual/efeitos dos fármacosRESUMO
Immune reconstitution therapy (IRT) is an emerging management concept for multiple sclerosis, whereby a short course of treatment provides long-lasting suppression of disease activity. "Cladribine tablets 10 mg" refers to a total cumulative dose of cladribine given over 2 years (henceforth referred to as cladribine tablets 3.5 mg/kg); it is a relatively new treatment option that is hypothesised to act as an IRT acting preferentially on the adaptive immune system. A randomised, 2-year, placebo-controlled trial (CLARITY) showed that treatment with cladribine tablets reduced indices of disease activity (relapses, lesions on magnetic resonance images, disability progression) and that this effect outlasted the pharmacologic effect of the treatment on the immune system (mainly a reduction in circulating B and T cells, with little effect on components of the innate immune system such as monocytes). CLARITY Extension, a 2-year extension to this trial, demonstrated durable efficacy, also in patients who received the standard 2-year course of cladribine tablets 3.5 mg/kg and were re-randomised to placebo for a further 2 years. Relative risk reductions for relapse rate with cladribine tablets 3.5 mg/kg were similar for patients with or without prior high disease activity. Reductions in disability progression with cladribine tablets 3.5 mg/kg were higher in patients with prior high relapse rates with or without prior treatment non-response. In this review, we describe the therapeutic profile of cladribine tablets 3.5 mg/kg and provide practical information on initiating this treatment option in the most appropriate patients.
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Neuromyelitis optica spectrum disorders (NMOSD) have been studied in different ethnic groups, including Asians, African-Americans, and Caucasians. Demonstrating the clinical features among diverse communities is important to understand the variable disease phenotypes, which will lead to further classification and better clinical management. Testing for antibody against aquaporin-4 (AQP4), the most common target antigen in NMOSD, is not available in many countries and tests use different methods, with variable sensitivity. With negative antibody results, the diagnosis of NMOSD becomes challenging and may affect the outcomes of patients with NMOSD. There are no adequate studies that assess NMOSD cohorts in the Arabian Gulf region, despite the increasing number of diagnosed cases. It is worth assessing NMOSD cohorts in the Arabian Gulf population to study the natural history of disease and to establish an epidemiological background for future perspectives. Various challenges to implement such a mission are outlined, including disease rarity, overlapping presenting symptoms and signs, which posed the issue of mimickers in the differential diagnosis, lack of specialized clinics, absence of highly sensitive testing methods for diagnosis, and the indefinite agreement on the negative AQP4 NMOSD criteria. Collaborative efforts started to take a place among many experts in the region to establish a registry of NMOSD patients for better perception of the disease pattern.
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OBJECTIVE: Diagnostic criteria from 2002 classify transverse myelitis (TM) as idiopathic or disease associated but predate the discovery of aquaporin-4 (AQP4)-immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which associate with TM. Prior incidence estimates of idiopathic TM (ITM) range from 1 to 6.2 per 1 million. We sought to determine whether the population-based incidence and prevalence of ITM were reduced by testing patients with ITM for AQP4/MOG-IgG and reclassifying seropositive cases as having disease-associated TM. METHODS: For this observational study, we retrospectively identified all cases of incident (January 1, 2003-December 31, 2016) and prevalent (December 31, 2016) ITM in Olmsted County (85% white) by using the Rochester Epidemiology Project medical records linkage system. ITM was defined by the 2002 Transverse MyelitisConsortium Working Group diagnostic criteria. Available sera were tested for AQP4-IgG and MOG-IgG. RESULTS: Twenty-four patients (incident 22, prevalent 17) initially met 2002 ITM criteria (longitudinally extensive TM [LETM] 6). Sera were tested for AQP4-IgG in 22 of 24 (92%) and MOG-IgG in 21 of 24 (88%). Three seropositive cases (AQP4-IgG 2, MOG-IgG 1) were identified and reclassified as having disease-associated TM, accounting for 14% of total incident and 12% of total prevalent cases. AQP4-IgG and MOG-IgG seropositive cases represented 50% (3 of 6) of idiopathic LETM. After reclassification of seropositive patients, the final ITM incidence was 8.6 per 1,000,000 and prevalence was 7.9 per 100,000. Three cases of ITM (14%) subsequently fulfilled multiple sclerosis criteria within the study period. CONCLUSIONS: The availability of AQP4-IgG and MOG-IgG modestly reduced ITM incidence and prevalence, which remained higher than previously reported in this predominantly white population. Incorporation of these biomarkers into future revisions of TM diagnostic criteria should be considered.
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Aquaporina 4/imunologia , Autoanticorpos/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Mielite Transversa/epidemiologia , Adulto , Idoso , Feminino , Humanos , Imunoglobulina G/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Mielite Transversa/classificação , Mielite Transversa/imunologia , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
Importance: Recognizing the characteristics of myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) myelitis is essential for early accurate diagnosis and treatment. Objective: To evaluate the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4-IgG (AQP4-IgG) and multiple sclerosis (MS). Design, Setting, and Participants: We retrospectively identified 199 MOG-IgG-positive Mayo Clinic patients from January 1, 2000, through December 31, 2017, through our neuroimmunology laboratory. Fifty-four patients met inclusion criteria of (1) clinical myelitis; (2) MOG-IgG positivity; and (3) medical records available. We excluded 145 patients without documented myelitis. Myelitis of AQP4-IgG (n = 46) and MS (n = 26) were used for comparison. Main Outcomes and Measures: Outcome variables included modified Rankin score and need for gait aid. A neuroradiologist analyzed spine magnetic resonance imaging of patients with MOG-IgG and control patients blinded to diagnosis. Results: Of 54 included patients with MOG-IgG myelitis, the median age was 25 years (range, 3-73 years) and 24 were women (44%). Isolated transverse myelitis was the initial manifestation in 29 patients (54%), and 10 (19%) were initially diagnosed as having viral/postviral acute flaccid myelitis. Cerebrospinal fluid-elevated oligoclonal bands occurred in 1 of 38 (3%). At final follow-up (median, 24 months; range, 2-120 months), 32 patients (59%) had developed 1 or more relapses of optic neuritis (n = 31); transverse myelitis (n = 7); or acute disseminated encephalomyelitis (n = 1). Clinical features favoring MOG-IgG myelitis vs AQP4-IgG or MS myelitis included prodromal symptoms and concurrent acute disseminated encephalomyelitis. Magnetic resonance imaging features favoring MOG-IgG over AQP4-IgG or MS myelitis were T2-signal abnormality confined to gray matter (sagittal line and axial H sign) and lack of enhancement. Longitudinally extensive T2 lesions were of similar frequency in MOG-IgG and AQP4-IgG myelitis (37 of 47 [79%] vs 28 of 34 [82%]; P = .52) but not found in MS. Multiple spinal cord lesions and conus involvement were more frequent with MOG-IgG than AQP4-IgG but not different from MS. Wheelchair dependence at myelitis nadir occurred in one-third of patients with MOG-IgG and AQP4-IgG but never with MS, although patients with MOG-IgG myelitis recovered better than those with AQP4-IgG. Conclusions and Relevance: Myelitis is an early manifestation of MOG-IgG-related disease and may have a clinical phenotype of acute flaccid myelitis. We identified a variety of clinical and magnetic resonance imaging features that may help clinicians identify those at risk in whom MOG-IgG should be tested.
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Glicoproteína Mielina-Oligodendrócito/imunologia , Mielite Transversa/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neuromielite Óptica/diagnóstico , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Criança , Pré-Escolar , Encefalomielite Aguda Disseminada/diagnóstico , Encefalomielite Aguda Disseminada/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Mielite Transversa/imunologia , Recidiva Local de Neoplasia/complicações , Neuromielite Óptica/imunologia , Prognóstico , Adulto JovemRESUMO
OBJECTIVE: To define the frequency, duration, and severity of intractable nausea, vomiting, or hiccups in aquaporin-4-immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and propose diagnostic criteria and a severity scale for area postrema syndrome (APS). METHODS: An International NMOSD database was interrogated for frequency of APS. Patients with AQP4-IgG-positive NMOSD completed an APS symptom questionnaire. Nausea and vomiting severity was derived from the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score. The diagnostic criteria, severity scale, and immunotherapy response was applied to a prospective validation cohort of patients from multiple centers. RESULTS: Analysis of an international database for AQP4-IgG-seropositive NMOSD (n = 430) revealed a high prevalence of isolated APS attacks (onset 7.1%-10.3%; subsequent 9.4%-14.5%) across continents. For 100 patients with 157 episodes of APS, nausea (n = 127, 81%) lasted for a median of 14 days (range 2-365), vomiting (113, 72%) with a median of 5 episodes/d (2-40) lasted 1-20 minutes, and hiccups (102, 65%) lasted a median of 14 days (2-365). Symptoms consistently and completely resolved following immunotherapy. Data were used to propose APS diagnostic criteria and repurpose PUQE score (hiccups severity grade based on symptom duration). The clinical utility was demonstrated in a prospective validation cohort. CONCLUSION: Isolated APS attacks are frequently encountered both at onset and during the NMOSD course. The diagnostic criteria proposed here will assist clinicians in recognizing APS. Diagnosis of an APS attack earlier than 48 hours is possible if a dorsal medulla lesion is detected. Accurate diagnosis and evaluation of APS attack severity will assist in outcome measurement in NMOSD clinical trials.
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Aquaporina 4/imunologia , Área Postrema/patologia , Imunoglobulina G/sangue , Neuromielite Óptica , Adolescente , Adulto , Idoso , Área Postrema/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Imunoterapia , Cooperação Internacional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/terapia , Inquéritos e Questionários , Vômito/etiologia , Adulto JovemRESUMO
Transnasal sphenopalatine ganglion block is emerging as is an attractive and effective treatment modality for acute migraine headaches, cluster headache, trigeminal neuralgia, and several other conditions. We assessed the efficacy and safety of this treatment using the Sphenocath® device. 55 patients with acute migraine headaches underwent this procedure, receiving 2 ml of 2% lidocaine in each nostril. Pain numeric rating scale (baseline, 15 minutes, 2 hours, and 24 hours) and patient global impression of change (2 hours and 24 hours after treatment) were recorded. The majority of patients became headache-free at 15 minutes, 2 hours, and 24 hours after procedure (70.9%, 78.2%, and 70.4%, resp.). The rate of headache relief (50% or more reduction in headache intensity) was 27.3% at 15 minutes, 20% at 2 hours, and 22.2% at 24 hours. The mean pain numeric rating scale decreased significantly at 15 minutes, 2 hours, and 24 hours, respectively. Most patients rated the results as very good or good. The procedure was well-tolerated with few adverse events. This treatment is emerging as an effective and safe option for management of acute migraine attacks.
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BACKGROUND: Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. METHODS: A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]). RESULTS: Patients were categorized as: demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13), cancer (n=11), neuromyelitis optica (n=10) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86% clinical sensitivity/77% specificity. CONCLUSIONS: cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.
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Cadeias kappa de Imunoglobulina/líquido cefalorraquidiano , Cadeias lambda de Imunoglobulina/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Bandas Oligoclonais/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Lactente , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Sensibilidade e Especificidade , Adulto JovemRESUMO
Neuromyelitis optica spectrum disorders (NMOSD) predominantly affect women who are of childbearing age. Understanding the interactions between pregnancy and NMOSD is important for clinical management. Aquaporin-4 (AQP4), the most common target antigen in NMOSD, is expressed on placenta in early pregnancy. A variety of immune and cytokine changes in pregnancy may impact pregnancy outcomes in NMOSD patients. Relapses continue during pregnancy and increase in frequency postpartum. Preeclampsia and fetal loss are more frequent in NMOSD than in controls. Transfer of AQP4-immunoglobulin G (IgG) from mother to baby occurs but appears not to cause disease. Several treatment options are relatively safe and mitigate the risk of relapse during pregnancy and postpartum. For patients with active NMOSD, it may be advisable to continue immunotherapy during pregnancy.