Search

Background: The assessment of serum neurofilament light chain (sNfL) concentration in multiple sclerosis (MS) is a useful tool for predicting clinical outcomes and assessing treatment response. However, its use in clinical practice is still limited. We aimed to assess how measurement of sNfL influences neurologists' treatment decisions in MS., Methods: We conducted a cross-sectional, web-based study in collaboration with the Spanish Society of Neurology. Neurologists involved in MS care were presented with different simulated case scenarios of patients experiencing either their first demyelinating MS event or a relapsing-remitting MS. The primary outcome was therapeutic inertia (TI), defined as the absence of treatment initiation or intensification despite elevated sNfL levels. Nine cases were included to estimate the TI score (range 0-9, where higher values represented a higher degree of TI)., Results: A total of 116 participants were studied. Mean age (standard deviation-SD) was 41.9 (10.1) years, 53.4 % male. Seventy-eight (67.2 %) were neurologists fully dedicated to the care of demyelinating disorders. Mean (SD) TI score was 3.65 (1.01). Overall, 92.2 % of participants (n = 107) presented TI in at least 2/9 case scenarios. The lack of full dedication to MS care (p = 0.014), preference for taking risks (p = 0.008), and low willingness to adopt evidence-based innovations (p = 0.009) were associated with higher TI scores in the multivariate analysis after adjustment for confounders., Conclusion: TI was a common phenomenon among neurologists managing MS patients when faced with the decision to initiate or escalate treatment based on elevated sNfL levels. Identifying factors associated with this phenomenon may help optimize treatment decisions in MS care., Competing Interests: Declaration of competing interest Gustavo Saposnik received consulting fees from Roche Farma Spain and is supported by the University of Toronto Scientific Merit award. He also receives a modest stipend from the World Stroke Organization as the Editor in Chief of the World Stroke Academy. Enric Monreal reported receiving research grants, travel support, or honoraria for speaking engagements from Almirall, Merck, Roche, Sanofi, Bristol Myers Squibbb, Biogen, Janssen, and Novartis. Jose M García-Domínguez received honoraria as speaker, advisor and researcher from Almirall, Bristol Myers Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. Jose E Meca-Lallana received honoraria as a consultant, chairman and lecturer in meetings and participated in clinical trials and other research projects promoted by Alexion, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Lamberto Landete received honoraria for participating in advisory boards and scientific and educational activities from Almirall, Bayer, Biogen, Bristol Myers Squibb, Sanofi, Merck, Novartis, UCB, Roche, and Teva. Virginia Meca-Lallana received consulting and speaking fees from Almirall, Biogen, Genzyme, Janssen, Merck, Novartis, Roche, Terumo, Sanofi, Teva, and Bristol Myers Squibb. Luis Querol received speaker honoraria from Merck, Sanofi, Roche, Biogen, Grifols and CSL Behring; provided expert testimony for Grifols, Johnson & Johnson, Annexon Pharmaceuticals, Sanofi, Novartis, Takeda, and CSL-Behring; and received research funds from Roche, UCB, and Grifols. Eduardo Agüera received speaking honoraria from Roche, Novartis, Merck, Sanofi, and Biogen. Sergio Martínez-Yélamos received honoraria for participating on advisory boards and for collaborations as consultant and scientific communications; they also received research support as well as funding for travel and congress expenses from Roche, Biogen Idec, Novartis, TEVA, Merck, Genzyme, Sanofi, Bayer, Almirall, and Bristol Myers Squibb. Luisa M Villar reported receiving research grants and personal fees from Merck, Roche, Sanofi, Bristol Myers Squibb, Biogen, and Novartis. Ana B Caminero received courses and honoraria for her participation as speaker/meeting moderator/symposia organizer from Alter, Almirall, Bayer, Bial, Biogen, Bristol Myers Squibb, Lilly, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva, and UCB; and support to attend scientific meetings from Biogen, Bial, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Rocío Gómez-Ballesteros, Elisa Salas, Nicolas Medrano, Elena García-Arcelay, and Jorge Maurino are employees of Roche Farma Spain., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with solid tumors. However, along with their efficacy, new toxicities related to immune system activation have surfaced, some of which pose life-threatening risks. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are among the serious, albeit rare, immune-related adverse effects (irAEs) observed. Although commonly associated with hematologic malignancies and chimeric antigen receptor T cell therapies, CRS has been reported in patients treated with ICIs, with ICANS being a less documented complication. The present study presents a case report of a 76-year-old patient with resected melanoma who developed clinical symptoms of CRS and ICANS following adjuvant pembrolizumab therapy. The patient presented with neurological symptoms of weakness and encephalopathy with confusion, bradypsychia, dysarthria, tremors and visual hallucinations. Laboratory tests revealed elevated serum levels of tumor necrosis factor-alpha and interleukin-6 along with inflammatory markers, hepatic and renal dysfunction, as well as rapidly progressive normochromic-normocytic anemia. Treatment with corticosteroids led to rapid symptom resolution, albeit with subsequent symptom recurrence after tapering its dose. This case underscores the importance of recognizing and managing irAEs associated with ICIs and highlights the need for vigilant monitoring and individualized therapeutic approaches., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October., Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts., Development: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

Introduction: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals., Methods: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents., Results: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments., Conclusions: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS., (Copyright © 2021 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy., Competing Interests: LV received a research grant from Biogen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Toboso, Tejeda-Velarde, Alvarez-Lafuente, Arroyo, Hegen, Deisenhammer, Sainz de la Maza, Alvarez-Cermeño, Izquierdo, Paramo, Oliva, Casanova, Agüera-Morales, Franciotta, Gastaldi, Fernández, Urbaneja, Garcia-Dominguez, Romero, Laroni, Uccelli, Perez-Sempere, Saiz, Blanco, Galimberti, Scarpini, Espejo, Montalban, Rasche, Paul, González, Álvarez, Ramo, Caminero, Aladro, Calles, Eguía, Belenguer-Benavides, Ramió-Torrentà, Quintana, Martínez-Rodríguez, Oterino, López de Silanes, Casanova, Landete, Frederiksen, Bsteh, Mulero, Comabella, Hernández, Espiño, Prieto, Pérez, Otano, Padilla, García-Merino, Navarro, Muriel, Frossard and Villar.)

Objective: To study the long-term outcome and persistence of two patterns of cervical spinal cord abnormality in early relapsing-remitting multiple sclerosis (RRMS)., Methods: RRMS patients with a spinal cord MRI performed during the first 3 years of the disease, a control MRI 5 years later and who have been followed up at least 10 years were included. Patients were grouped according the T2 spinal cord MRI into: (A) nodular pattern, if one or more focal lesions were present; and (B) diffuse pattern, defined as a poorly demarcated high signal area. The end point was defined as the time to reach an Expanded Disability Status Score (EDSS) of 4.0., Results: Twenty-five patients were included; 12 in group A and 13 in group B. Three patients in group A and 9 in group B reached EDSS 4, in a mean time of 11 years in group A and 7 years in group B (log rank 10.3, p = 0.001). Multivariate Cox regression analysis assessing the risk of EDSS 4.0 including sex, age, number of relapses in the first 2 years, number of T2 brain lesions and spinal cord pattern showed higher risk for the diffuse pattern (hazard ratio 7.2, 95% confidence interval 1.4-36.4). Control MRI showed the persistence of the diffuse pattern in all patients, and the development of diffuse pattern in two patients with basal nodular lesions., Conclusions: The diffuse abnormality in cervical spinal cord at the beginning of the disease is persistent and predicts a worse prognosis in RRMS patients.

Observational study designed to explore the effect of demographical variables and number of relapses over the disability progression in the two first years of beta-interferon treatment for multiple sclerosis. One hundred and sixty two patients treated with beta-interferon for at least two years were included, 70.9% females, mean age 33.4 years, mean disease duration 75.1 months, mean EDSS 2.4, previous year relapse rate 1.3. Main end-point was defined as a sustained EDSS increase (1.5 if previous EDSS 0-2.0; 1.0 if previous EDSS 2.5-4.0; 0.5 if previous EDSS 4.5 or higher). 62.3% of patients presented one or more relapses and 32.7% patients reached sustained disability increase. The univariate and multivariate Cox regression analysis only showed statistical significance for the relapses in the two first years after the treatment (HR 1 relapse: 3.4, p = 0.05; HR > or = 2 relapses: 4.3, p < 0.001). The Kaplan-Meier survival analysis showed a higher probability of EDSS progression for patients with one relapse (log rank 10.9, p = 0.02) and with > or = 2 relapses (log rank 17.7, p < 0.001), with no differences between them (p = 0.38). In conclusion, patients with one or more relapses in the first two years of interferon treatment developed an earlier sustained progression of the disability.

Objective: To study if there are different patterns of clinical activity--measured by the annual exacerbation rate (AER)--among relapsing-remitting multiple sderosis (RRMS), "early" secondary multiple sclerosis (SPMS) and "late" SPMS., Methods: A prospective 5-year follow-up study in 80 MS patients has been carried out, calculating the AER and the mean expanded disability status scale (EDSS) change rate (MCR)., Results: A significant difference on the AER, among RRMS, early SPMS and late SPMS, has been found., Conclusions: The SPMS has a high clinical inflammatory activity before and during its transformation from a RRMS.

Objectives: To explore fatigue in multiple sclerosis and evaluate the specificity of three fatigue scales in this condition: the fatigue severity scale, the specific fatigue scale and the fatigue impact scale., Material and Methods: We sent out 60 questionnaires with the three scales and the quality of life scale, the Nottingham Health Profile, to patients with multiple sclerosis as clinically defined by Poser's criteria. Answers were received to 58 questionnaires and the data correlated by Sperman's correlation and the Student t test, with demographic variables (age, age of onset and sex) and clinical variables (clinical form, time the disease was present, period of time since the previous episode and Kurtzke scale (EDSS)., Results: Fatigue was present in 78% of the patients. There was correlation between fatigue severity scale and EDSS, pyramidal function, cerebellar function, the period of time the illness was present and the clinical form. We found that the specific fatigue scale is independent of EDSS. The fatigue impact scale was correlated with the EDSS apart from the questions concerning cognitive function., Conclusions: Fatigue is a common symptom of multiple sclerosis which has an independent effect on cognitive function. It is also related to involvement of the pyramidal and cerebellar systems, and depends on the degree of disability and time the disease has been present. The specific fatigue scale is a good tool for exploration of this symptom of multiple sclerosis.

Introduction: Axon pathology in multiple sclerosis is an emerging concept, not because it is unknown but because it has been forgotten. However, clinical, functional and pathological aspects have clearly shown that it is damaged at a very early stage in development of the plaque of demyelination. There is sufficient clinical, radiological and pathological evidence to permit definition of axonal damage as the central element of the pathology and clinical features of multiple sclerosis., Development and Conclusions: Throughout this article we will see how the axon is affected in multiple sclerosis, how this affects the inflammatory response and which parameters allow us to measure axonal damage and its relation to disability. Finally we will see how a new physiopathogenic concept of multiple sclerosis appears, based on the axonal lesion, and how this fits current clinico-pathological concepts better.

Introduction: Sjögren's syndrome is a chronic inflammatory condition of unknown aetiology and autoimmune pathology. The defining feature is the dry syndrome, expressed as xerophthalmia and xerostomia. Extra-glandular involvement at many other levels may also occur. Neurological involvement is not unusual. The peripheral nervous system is most frequently involved, and a predominantly sensitive symmetrical distal polyneuropathy may be the first sign of the condition. Other patterns of peripheral involvement are also associated with the syndrome. We present a case of subacute demyelinating polyradiculopathy associated with primary Sjögren's syndrome., Clinical Case: A 28 year old woman with dry syndrome presented with paraesthesia in her hands and feet, distal weakness, which had progressed proximally in the muscles of her arms and legs, and bilateral facial weakness. The condition progressed for eight weeks. When complementary tests were done, alterations typical of this condition (FR, ANA, anti-Ro and anti-La) were seen and also others typical of the dry syndrome (Schirmer's test). Therefore, in view of these findings and the clinical features, after other conditions had been ruled out, a diagnosis of primary Sjögren's syndrome was made. The type of neuropathy was determined by the clinical features, electromyography and CSF findings. Treatment with corticosteroids gave good results., Conclusions: Demyelinating polyradiculopathy is a form of peripheral nervous system involvement which is rarely seen in this disorder. In the differential diagnosis Sjögren's syndrome should be considered, an orientative history taken, autoantibodies determined and an ophthalmological examination made.

Introduction: Lacunar infarcts (LI) and deep cerebral hemorrhages (DCH) have the same localization and a vasculopathy which appears to be similar, at the level of the small perforating arteries, classically attributed to arterial hypertension (AHT)., Objectives: To compare the vascular risk factors of patients with lacunar ictus (LIc) and those with DCH, to try to determine how these may affect the appearance of one type of stroke or another., Patients and Methods: We analyzed a prospective consecutive series of patients with cerebral vascular accidents (CVA), selecting 1,540 patients in the first 1,155 with a first CVA. We recorded demographic data and the following risk factors: previous transient ischemic accident (TIA), AHT, diabetes mellitus (DM), hypercholesterolemia, ischemic cardiopathy, atrial fibrillation and the presence of silent infarcts on CT., Results: Two hundred and four patients had LIc and 163 had DCH. There was a significant dissociation between LIc and a history of TIA, DM, hypercholesterolemia and the presence of silent lacunar-type infarcts on CT. However, after multivariant analysis, DM did not continue to be an independent variable. Arterial blood pressure was found to be greater in the DCH group., Conclusions: The presence of different risk factors for LIc and DCH may be the key to understanding the mechanism which leads to one type or other of CVA.

Introduction: Multiple sclerosis (MS) is a demyelinating disorder of the CNS, of autoimmune pathology and unknown aetiology. Several theories regarding its aetiology have been suggested, although none seems to be completely convincing. Genetically predisposed persons are affected, therefore groups of MS are seen in certain families., Objectives: To describe the family links, type of illness and evolution of 12 patients from six families with two or more members diagnosed as having MS, and to evaluate any differences from the other cases recorded in our data base., Patients and Methods: We studied 12 patients diagnosed on the criteria of Poser, and with at least one first or second degree relation with MS. We compared clinical data, form of presentation and course with 127 patients recorded in the data base., Results: We describe six families: two homozygotic twins, two families in which transmission was from father to child and three families with first degree cousins affected. We found no clinical variation in the presentation, number of attacks or evolution, as compared with the other patients. Nor was there homogeneity between the familial forms of MS., Conclusions: Familial forms make up approximately 10% of the series. We do not have any data available for early diagnosis nor for prognostic significance of familial MS.

Introduction: 50% of the patients with cerebral tumours present with epileptic crises, which may be partial or generalized. The commonest partial crises have motor symptoms. These make up 30% of the simple partial crises. Partial simple crises with purely vegetative-type symptoms are very uncommon (less than 5%). They are considered to be caused by discharges in the internal regions of the temporal lobes, mainly in the limbic system. This means that it is very difficult to identify them using techniques of surface EEG., Clinical Case: We describe the case of a patient with a cerebral tumour. The initial clinical features were short episodes of generalized coldness and sweating which had been present for the previous two weeks, without any other symptoms. During a routine EEG, focal critical paroxystic activity was recorded in the right temporal region. This coincided with a clinical episode similar to those described., Conclusions: The episodes were labelled partial simple vegetative crises. In this case the EEG was crucial for diagnosis and subsequently to recommend suitable treatment. However, difficulty in recording this type of crisis with a surface EEG makes correct diagnosis of these patients very difficult, since the epileptogenic focus is deeply situated.