Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Gadolinium-enhanced brain lesions in multiple sclerosis relapse.

OBJECTIVE: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. METHODS: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. RESULTS: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002). CONCLUSION: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario.

Gadolinium-enhanced brain lesions in multiple sclerosis relapse / Lesiones cerebrales captantes de gadolinio en el brote de los pacientes con esclerosis múltiple

Objective: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. Methods: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. Results: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0–4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p = 0.002). Conclusion: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario. (AU)

Objetivo: Estudiar la paradoja clínico-radiológica en el brote de la esclerosis múltiple (EM) mediante el análisis de lesiones captantes de gadolinio (Gd+) en la RM cerebral antes del tratamiento con metilprednisolona (MP). Métodos: Analizamos la RM cerebral basal de 90 pacientes con EM en brote de 2 ensayos clínicos aleatorizados multicéntricos fase IV que demostraron la no inferioridad de diferentes vías y dosis de MP, realizadas antes del tratamiento con MP y en los 15 días siguientes a la aparición de los síntomas. Se analizaron el número y la localización de las lesiones Gd+. Se estudiaron las asociaciones mediante análisis univariado. Resultados: El 62% de los pacientes tenía al menos una lesión Gd+ cerebral y el 41% de los pacientes tenía 2 o más lesiones. La localización más frecuente fue la subcortical (41,4%). Se encontraron lesiones Gd+ cerebrales en el 71,4% de los pacientes con síntomas de tronco cerebral o cerebelo, en el 57,1% con síntomas medulares y en el 55,5% con neuritis óptica. El 30% de los pacientes con síntomas cerebrales no tenían lesiones Gd+ y sólo el 4,.6% de los pacientes tenían lesiones Gd+ sintomáticas. El análisis univariante mostró una correlación negativa entre la edad y el número de lesiones Gd+ (p = 0,002). Conclusiones: La mayoría de los pacientes en brote mostraron varias lesiones Gd+ en la RM cerebral, incluso cuando la manifestación clínica fue medular u óptica. Nuestros hallazgos ilustran la paradoja clínico-radiológica en el brote de la EM y apoyan el valor de la RM cerebral en este escenario. (AU)

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Shock cardiogénico en síndrome clínico aislado / Cardiogenic shock in clinically isolated syndrome

No disponible

Comparison of two high doses of oral methylprednisolone for multiple sclerosis relapses: a pilot, multicentre, randomized, double-blind, non-inferiority trial.

BACKGROUND AND PURPOSE: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. METHODS: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double-blind, multicentre, non-inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non-inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non-inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium-enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. RESULTS: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, -0.26 (-0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium-enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. CONCLUSIONS: A lesser high-dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response.

Anti-Ri-associated paraneoplastic cerebellar degeneration and breast cancer: an autopsy case study.

Several antineuronal antibodies are associated with paraneoplastic cerebellar degeneration. Anti-Ri is one of these antibodies in some cases but it is more commonly associated with paraneoplastic opsoclonus myoclonus in the context of gynecological neoplasia. Anti-Ri autoantibodies are thought to be directed against onconeural antigens, NOVA-1 and NOVA-2, that are expressed by the tumor as well as by neurons. The results of the treatment of both syndromes have been disappointing, although aggressive multimodality immunosuppressive treatments have been used. There are few cases of anti-Ri paraneoplastic cerebellar degeneration and none has been pathologically studied. We report the pathological study of a patient who died from anti-Ri-positive paraneoplastic cerebellar degeneration associated with breast cancer only confirmed at autopsy.

[Basilar artery rostral occlusion syndrome. Clinico-radiological assessment of 56 patients]. / Síndrome por oclusión rostral de la arteria basilar. Valoración clinicorradiológica de 56 pacientes.

We studied 56 patients, 30 women and 26 men ranging from 30 to 79 years of age (average age 64.5 +/- 10.4), who were admitted to our hospital between 1982 and August 1995 with clinical features compatible with occlusion at the level of the bifurcation of the basilar artery. The patients were selected following clinical and neuro-radiological criteria. All patients included in the study had two or more recent infarcts in the vertebro-basilar territory, related to involvement of the rostral region of the basilar artery. The diagnosis was confirmed by CT or MR scanning. The infarcts were in the thalamus, brain-stem, cerebellum and parieto-occipital lobe. A thalamic infarct associated with an infarct in another region was the most frequent lesion. The CT-MR findings in the 56 cases were: 29 patients presented with a unilateral thalamic infarct associated with another infarct (23 occipital, 8 parietal, 6 brain-stem and 2 cerebellum). There were eight patients with bilateral thalamic infarcts and seven with bilateral occipital infarcts. In six patients the occipital infarct was associated with another infarct at a different level (parietal or cerebellar) and six patients had cerebellar infarcts together with an infarct of the mid-brain. In 22 of the patients, lesions were found in three or more areas. The commonest clinical findings were: Motor deficit (69.6%), abnormal eye movements (44.5%), cerebellar dysfunction (42.8%), altered level of consciousness (32.1%), visual field defects (28.5%), pupil anomalies (19.6%). The most frequently associated risk factors were: Arterial hypertension (58.9%), a history of ACV (32.1%) and atrial fibrillation (21.4%). Mortality was 5.7%. In contrast to the classical descriptions, motor defecit was the commonest symptom in our series.