Glial and neuronal markers in cerebrospinal fluid in different types of multiple sclerosis.

In the present study, CSF concentrations of NFL, t-tau, p-tau, GFAP, S-100B, YKL-40, MCP-1, α-sAPP, ß-sAPP, and Aß38, Aß40, Aß42 were measured in 324 MS patients to test whether a correlation among the biomarkers exists and whether the profile of CSF biomarkers varies among the different types of MS. The CSF concentrations of NFL were significantly higher in RRMS while CSF concentrations of GFAP were higher in PPMS. CSF concentrations of NFL correlated with YKL-40 in CIS patients while CSF concentrations of GFAP correlated with YKL-40 in RRMS patients.

Esclerosi múltiple: un repte diagnòstic a pediatria / Esclerosis múltiple: un reto diagnóstico en pediatría / Multiple sclerosis: a diagnostic challenge in pediatrics

Introducció: l'esclerosi múltiple (EM) és la malaltia desmielinitzant primària del sistema nerviós central (SNC) més comuna. Sol manifestar-se amb episodis de focalitat neurològica amb curs remitentrecurrent. Entre el 2 i el 5% dels casos debuten en la infància. Es descriu un cas de malaltia primària de l'SNC suggestiu d'EM, en què es remarca la importància de fer un bon diagnòstic diferencial i es ressalten els nous criteris diag-nòstics d'EM pediàtrica. Cas clínic: nena de 12 anys que es presenta amb clínica d'una setmana d'evolució d'hipoestèsia en territori trigemi-nal esquerre i extremitat superior dreta. Herpes labial actiu. Vacunada del virus de l'hepatitis B i del virus del papil•loma humà vuit mesos abans. Estudi de neuroimatge amb ressonància magnètica nuclear (RM) cerebral que mostra lesions desmielinitzants a substància blanca en hemisferi cerebral esquerre i hemiprotuberància dreta, algunes amb signes d'activitat. Líquid cefaloraquidi (LCR) sense proteïnoràquia ni pleocitosi, amb bandes oligoclonals d'IgG de síntesi intratecal. Reacció en cadena de polimerasa (PCR) d'herpes virus en LCR negativa. El quadre clínic i les lesions de l'RM orienten al diagnòstic amb alta sospita d'EM. Comentaris: les malalties desmielinitzants de l'SNC plante-gen un ampli diagnòstic diferencial. La presència de serologies positives en sèrum orienta a una malaltia desmielinitzant com l'encefalomielitis aguda disseminada (EMAD) en què és freqüent un mecanisme postinfecciós. La neuroimatge és molt útil en el diagnòstic de les malalties desmielinitzants. Les bandes oligoclonals, els anticossos anti-AQP4/NMO (neuromielitis òptica) i els anticossos anti-MOG (mielina de l'oligodendròcit) poden ser de gran ajuda en el diagnòstic de les malalties desmielinitzants

Introducción. La esclerosis múltiple (EM) es la enfermedad desmielinizante primaria del sistema nervioso central (SNC) más común. Suele manifestarse con episodios de focalidad neurológica con curso remitente-recurrente. Entre el 2 y el 5% de los casos debutan en la infancia. Se describe un caso de enfermedad primaria del SNC sugestivo de EM, remarcando la importancia de hacer un buen diagnóstico diferencial y resaltando los nuevos criterios diagnósticos de EM pediátrica. Caso clínico. Niña de 12 años que se presenta con clínica de una semana de evolución de hipostesia en territorio trigeminal izquierdo y extremidad superior derecha. Herpes labial activo. Vacunada de virus de la hepatitis B y de virus del papiloma humano ocho meses antes. Estudio de neuroimagen con resonancia magnética nuclear (RM) cerebral que muestra lesiones desmielinizantes en sustancia blanca de hemisferio cerebral izquierdo y hemiprotuberancia derecha, algunas con signos de actividad. Líquido cefalorraquídeo (LCR) sin proteinorraquia ni pleocitosis, con bandas oligoclonales de IgG de síntesis intratecal. Reacción en cadena de polimerasa (PCR) de herpes virus en LCR negativa. El cuadro clínico y las lesiones de la RM orientan al diagnóstico con alta sospecha de EM. Comentarios. Las enfermedades desmielinizantes del SNC plantean un amplio diagnóstico diferencial. La presencia de serologías positivas en suero orienta a una enfermedad desmielinizante como la encefalomielitis aguda diseminada (EMAD), en que es frecuente un mecanismo post-infeccioso. La neuroimagen es muy útil en el diagnóstico de las enfermedades desmielinitzantes. Las bandas oligoclonales, los anticuerpos anti-AQP4/NMO (neuromielitis óptica) y los anticuerpos anti-MOG (mielina del oligodendrocito) podrían ser de gran ayuda en el diagnóstico de enfermedades desmielinizantes (AU)

Introduction. Multiple sclerosis (MS) is the most common primary demyelinating disease of the central nervous system (CNS). It usually manifests with episodes of neurological deficits that follow a relapsing-remitting course, and approximately 2-5% of the cases have an onset during childhood. We describe a case of primary demyelinating disease of the CNS suggestive of MS, we emphasize the importance of a proper differential diagnosis, and highlight the new diagnostic criteria for pediatric MS. Case report. A 12-year old girl presented with a one-week history of hypoesthesia in the left trigeminal dermatome and the right upper extremity, and active cold sores. There was history of hepatitis B and human papilloma virus immunization eight months prior. A brain magnetic resonance imaging (MRI) showed demyelinating lesions in the left hemisphere and right medulla oblongata; some of them enhanced with gadolinium. Cerebrospinal fluid (CSF) showed normal protein and absence of pleocytosis, but with oligoclonal bands of intratechal synthesis. Polymerase chain reaction for herpes virus was negative. The clinical and MRI lesions suggested the diagnosis or a primary CNS demyelinating disease, with high suspicion for MS. Comments. Demyelinating diseases of the CNS include a broad differential diagnosis. The presence of positive serology may suggest the diagnosis of acute disseminated encephalomyelitis (ADEM), which is a post-infectious process. Neuroimaging may be very useful in the diagnosis of demyelinating diseases. In addition, oligoclonal bands, anti-AQP4/NMO (neuromyelitis optica) antibodies, and anti-MOG (myelin oligodendrocyte) antibodies may be helpful in the diagnosis (AU)

MxA mRNA expression as a biomarker of interferon beta response in multiple sclerosis patients.

Myxovirus resistance protein A (MxA) is a molecule induced after interferon-ß injection. The aim of this study was to investigate whether MxA determination one year after starting interferon-ß can predict treatment response in multiple sclerosis patients. MxA mRNA expression was evaluated in blood samples obtained at baseline and at month 12. Clinical variables were prospectively recorded. A threshold of 5 was defined to establish MxA induction. On survival analysis, time to the next relapse and to EDSS progression were significantly longer in patients showing MxA induction, suggesting that MxA induction after one year may be useful to identify interferon-ß responders.

Effectiveness of natalizumab in patients with highly active relapsing remitting multiple sclerosis.

INTRODUCTION: We evaluated the effectiveness of natalizumab in patients with highly active, relapsing-remitting multiple sclerosis (HA-RRMS) to identify baseline predictors associated with freedom from disease activity. METHODS: We analyzed 70 patients treated with natalizumab and followed for at least 1 year with progression of disability of ≥1 point on the EDSS before starting therapy. We recorded freedom from clinical activity, radiological activity, and disease activity (clinical and radiological). RESULTS: The median (IQR) follow-up was 2.3 (2.0-3.8) years. Of the 52 patients who completed 2 years of treatment, 25 were free of disease activity (48.1%). The ARR decreased from a mean ± SD of 2.49 ± 0.86 at baseline to 0.47 ± 0.83 at the end of the first year (p < 0.001) and 0.34 ± 0.69 at the end of the second year (p < 0.001). The percentage of patients with gadolinium-enhanced lesions decreased from 21 at baseline to 5.7 at the end of the first year (p < 0.001) and to 5.8 during the second year (p < 0.005). Baseline EDSS ≤3.0 was significantly associated with freedom from disease activity (OR, 2.49; 95% CI, 1.24-4.99; p = 0.010). CONCLUSIONS: Natalizumab is effective in patients with HA-RRMS. Baseline EDSS ≤3.0 increases the probability of remaining disease-free in HA-RRMS treated with natalizumab.

Etiologic spectrum and prognosis of longitudinally extensive transverse myelopathies.

BACKGROUND: Patients with a first episode of longitudinal extensive transverse myelopathy (LETM) were reviewed with two objectives: to evaluate the clinical spectrum of LETM and to analyze the related clinical and laboratory variables that can be used as functional prognostic markers. METHODS: A retrospective review was conducted of clinical, radiologic and biochemical data of patients admitted for LETM between 1993 and 2011. RESULTS: Our cohort included 72 patients [median age 41 years, interquartile range (IQR) 29-61.5]. Median follow-up was 34 months (IQR 17.2-63). The modified Rankin Scale (mRS) score was ≥2 at the end of follow-up in 72.2%. The final diagnosis was idiopathic LETM in 22 patients, multiple sclerosis in 18, parainfectious disease in 11, systemic disease in 9, spinal cord infarction and neuromyelitis optica spectrum disorders in 3 patients each, and acute demyelinating encephalomyelitis, dural fistula, and tumor-related LETM in 2 patients each. Unfavorable outcome was associated with mRS ≥2 at admission [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.66] and older age (OR 1.06, 95% CI 1.01-1.11). CONCLUSION: Idiopathic LETM was the most frequent diagnosis at the end of follow-up. Older age and clinically severe disease at onset were independent prognostic factors of poorer functional recovery.

Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series.

BACKGROUND: In 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IATM. METHODS: Eighty-seven patients diagnosed with IATM between 1989 and 2011 were retrospectively reviewed. Two patients with positive neuromyelitis optica IgG serum antibodies were excluded. Epidemiological, clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85 patients were analyzed. RESULTS: Eleven (13%) patients converted to MS after a median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of symptoms was related to conversion to MS. Only 9.4% of patients with IATM were unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38-45.00) were associated with a poorer outcome (Rankin ≥ 2). CONCLUSIONS: At least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.