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Objective: To explore differences in patient reported outcomes, health care resources and expenditures in persons with multiple sclerosis (pwMS) with or without access to an MS-nurse., Methodology: An observational, multicenter and cross-sectional study was conducted. Seven centers with, and twelve centers without an MS-nurse participated. The multiple sclerosis impact scale-29 (MSIS-29) was the primary outcome measure. Secondary outcome measures included: hospital anxiety and depression scale, coping measures, health-economic and disease-knowledge parameters., Results: Three hundred thirty-four pwMS were included, of which 196 had access to an MS-nurse. Mean age was 44.5 ± 11.4 and 69% were women. The median expanded disability status scale and patient determined disease steps were respectively 2.0 (IQR 2.5) and 2.5 (IQR 3). No statistical significant differences between centers with or without an MS-nurse were observed for the MSIS-29 (total) (mean ranks: 169.9 vs. 157.8; Z = -1.114; p = .253), depression (X²= 1,772, p = .412), anxiety (X²= 0.446, p = .800) or health expenditures. MS-disease knowledge was higher in patients followed in centers with an MS-nurse than in centers without (17.08(3.37) vs. 15.30(3.39), t(331) = 4.734, p < .001)., Conclusion: We did not observe clinical differences regarding HRQoL in pwMS between centers with and without an MS-nurse. Yet, we did observe a higher level of MS-specific knowledge in pwMS who had access to an MS-nurse, which may emphasize the important role of MS-nurses in educating and improving self-efficacy and adherence. Belgian registration number B300201421282., Competing Interests: Declarations. Ethics approval and consent to participate: All human experiments were performed in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). Each pwMS was informed and signed an informed consent before participation and ethics committee approval was obtained at the Antwerp University Hospital (Belgian registration number B300201421282). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background and Objectives: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS)., Methods: ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population., Results: Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed., Discussion: Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS., Classification of Evidence: This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected., Trial Registration Information: ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.

Background: Pain is reported in 66% of cancer patients with advanced disease. Adequate pain management is a cornerstone of comprehensive supportive cancer care., Purpose: The purpose of this study was to assess pain management in Oncology Units in Belgium., Methods: A descriptive research design was applied. A structured questionnaire developed by a writing committee was sent to 37 healthcare professionals in 2021. Twenty-four replied., Results: In most centers, pain management is organized through the pain clinic (91.7%), followed by a multidisciplinary team (83.3%) and the palliative care unit (75%). Eighty-seven percent use tools to assess the pain, mostly for in-patients. Pain guidelines are applied in 17 centers with the ESMO guidelines being the most often mentioned. Mild to moderate pain is managed with paracetamol, non-steroidal anti-inflammatory drugs, and tramadol. All centers handle severe pain with strong opioids, including buprenorphine and fentanyl. Only 62% are concerned about the side effects of strong opioids. In case of neuropathic pain, treatments with pregabalin, gabapentine, and tricyclic antidepressants are the most common, followed by opioids and interventional therapies for refractory neuropathic pain. Asking advice to the pain clinic, combination therapy and opioid rotation are used for patients with inadequate analgesia. Eighty to 90% of the centers have access to intraspinal and epidural techniques, respectively. An active teaching program on pain relief is offered in 66%, but only 33% of the centers do active research focused on pain management., Conclusions: This is the first survey on pain management in the Belgian centers. Surprisingly only one-third of the health professionals ask advice to the pain clinic in case of inadequate pain relief, meaning that we are far away from a multidisciplinary patient-centered approach. Therefore, the BSMO Supportive Care Task Force promotes the development of an interdisciplinary committee in every oncology unit., Competing Interests: Declarations. Ethics approval: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to assess the diagnostic management and follow-up imaging for glioma patients across Belgian hospitals by calculating process indicators., Methods: Patients with newly diagnosed glioma in Belgium (2016-2019) were selected from the Belgian Cancer Registry. The National Social Security Number served as unique patient identifier, linking the Registry to vital status and reimbursement data. Nine measurable process related to diagnosis and follow-up imaging were identified, with reformulations for 7 due to data limitations. For each indicator, technical documentation sheets, containing all required details (rationale, numerator and denominator, target, limitations, benchmarking, subgroup analyses) were developed, reviewed by a multidisciplinary expert panel, and validated in six pilot hospitals. Per indicator, patients were assigned to the most relevant hospital per indicator using allocation algorithms., Results: Results for process indicators assessing MRI use in glioma diagnosis and follow-up aligned with predefined targets (90%), except for early postoperative MRI (48.5% vs. target 90%). Mandatory reporting of the WHO performance status (89.3% vs. target 100%) and performance of full-spine (43.6% vs. target 90%) and follow-up MRI (73.5% vs. target 90%) in ependymoma were suboptimal. The largest variability across centers was noted for the indicator on early postoperative MRI., Conclusion: This calculation of process indicators identified opportunities for improvement in diagnosis and follow-up imaging for glioma patients in Belgium. Monitoring indicator results and providing individual feedback reports to the Belgian hospitals invites neuro-oncology care teams and hospital managements to reflect on their results and to take measures to continuously improve care for glioma., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 36-year-old man who sought evaluation for a persistent headache and numbness on the cheek. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.

Introduction: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). The safety profile and patient preference for conventional versus shorter ocrelizumab infusions were investigated in the ENSEMBLE PLUS study., Methods: ENSEMBLE PLUS was a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810), comparing outcomes in patients with early-stage relapsing-remitting MS receiving ocrelizumab 600 mg over the approved 3.5-h (conventional) versus 2-h (shorter) infusion. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first randomized dose (RD); the secondary endpoint included IRR frequency at subsequent RDs., Results: At first RD, the number of patients with an IRR in the conventional (101/373; 27.1%) versus shorter (107/372; 28.8%) infusion group was similar (difference, stratified estimates [95% CI]: 1.9% [- 4.4, 8.2]). Most IRRs (conventional: 99.4%; shorter: 97.7%) were mild/moderate. IRR frequency decreased over the course of RDs; three patients discontinued from the shorter infusion arm but continued with conventional infusion. Overall, > 98% of IRRs resolved without sequelae in both groups. Pre-randomization throat irritation was predictive of future throat irritation as an IRR symptom. Adverse events (AEs) and serious AEs were consistent with the known ocrelizumab safety profile. On completion of ENSEMBLE PLUS, most patients chose to remain on (95%) or switch to (80%) shorter infusion., Conclusion: ENSEMBLE PLUS demonstrates the safety and tolerability of shorter ocrelizumab infusions. Most patients remained on/switched to shorter infusion after unblinding; IRRs did not strongly influence patient decisions., Clinical Trials Registration: Substudy of ENSEMBLE (NCT03085810)., Registration: March 21, 2017., (© 2024. The Author(s).)

Background: Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate., Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods., Methods: Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite ® -Optilite (Sint-Jan Bruges hospital) and N Latex ® -BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis., Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite ® -Optilite: 7.7; N Latex ® -BNII: 4.71), κIgG index (Freelite ® -Optilite: 14.15, N Latex ® -BNII: 12.19), and CSF κFLC/IgG ratio (Freelite ® -Optilite: 2.27; N Latex ® -BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite ® -Optilite) versus 94.6% (N Latex ® -BNII) for the κFLC index, 91% (Freelite ® -Optilite) versus 92.2% (N Latex ® -BNII) for the κIgG index, and 81.3% (Freelite ® -Optilite) versus 91.4% (N Latex ® -BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite ® -Optilite and 90.5% for N Latex ® -BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite ® -Optilite: 0.924; N Latex ® -BNII: 0.962] and κIgG index (AUC Freelite ® -Optilite: 0.929; N Latex ® -BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%)., Conclusions: The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures., Competing Interests: The 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 © 2024 Dekeyser, De Kesel, Cambron, Vanopdenbosch, Van Hijfte, Vercammen and Laureys.)

Objectives: To ascertain the involvement of palliative care with neurology services in the care of people with amyotrophic lateral sclerosis (ALS) in the United Kingdom, Italy and Switzerland, in particular the collaboration with and referral from neurology, the involvement in multidisciplinary team care and in the respiratory support of ALS patients., Methods: In 2019, two online surveys were undertaken of palliative care specialists, using specialist groups of the European Academy of Neurology, European Association of Palliative Care and the Association of Palliative Medicine for Great Britain and Ireland., Results: The respondents were specialist palliative care professionals, predominantly senior doctors, involved in the care of people with ALS. As the numbers of respondents from many countries were in single figures the analysis was restricted to the United Kingdom, Italy and Switzerland. The time of involvement varied, with early involvement commonest in the UK. Barriers to referral included neurologists not referring and financial issues, particularly in Switzerland. The reluctance of patients and families to see palliative care services was reported as less than 20% in all countries. Respondents were often involved in the care of people receiving noninvasive ventilation (NIV), in all countries. and with tracheostomy ventilation (TV), particularly in Italy., Conclusions: Palliative care services are often involved in the care of people with ALS, but the extent and timing of involvement varies. The use of clinical guidelines and education on palliative care for neurology services may encourage collaboration, for the benefit of people with ALS and their families.

We describe a case of a 36-year-old woman with no psychiatric or somatic history who was presented to the emergency department with a profound change in mental status, more precisely a catatonic status and auditory hallucinations. Due to the unclear aetiology and suspicion of underlying psychiatric problems, the patient was admitted to the psychiatric ward. After discharge against medical advice, readmission was necessary due to deterioration and sudden onset of myoclonus. On further examination, acute disseminated encephalomyelitis (ADEM) was diagnosed. This case illustrates that ADEM can present itself as an initial psychiatric problem and emphasizes the importance of extensive medical clearance at presentation and continued attention for possible somatic origin, even when the initial clearance turns out to be negative.

Acetylcholine (ACh) levels are elevated in actively depressed subjects. Conversely, antagonism of either nicotinic or muscarinic ACh receptors can have antidepressant effects in humans and decrease stress-relevant behaviors in rodents. Consistent with a role for ACh in mediating maladaptive responses to stress, brain ACh levels increase in response to stressful challenges, whereas systemically blocking acetylcholinesterase (AChE, the primary ACh degradative enzyme) elicits depression-like symptoms in human subjects, and selectively blocking AChE in the hippocampus increases relevant behaviors in rodents. We used an ACh sensor to characterize stress-evoked ACh release, then used chemogenetic, optogenetic and pharmacological approaches to determine whether cholinergic inputs from the medial septum/diagonal bands of Broca (MSDBB) or ChAT-positive neurons intrinsic to the hippocampus mediate stress-relevant behaviors in mice. Chemogenetic inhibition or activation of MSDBB cholinergic neurons did not result in significant behavioral effects, while inhibition attenuated the behavioral effects of physostigmine. In contrast, optogenetic stimulation of septohippocampal terminals or selective chemogenetic activation of ChAT-positive inputs to hippocampus increased stress-related behaviors. Finally, stimulation of sparse ChAT-positive hippocampal neurons increased stress-related behaviors in one ChAT-Cre line, which were attenuated by local infusion of cholinergic antagonists. These studies suggest that ACh signaling results in maladaptive behavioral responses to stress if the balance of signaling is shifted toward increased hippocampal engagement., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Cerebral cavernous malformations of the intracanalicular optic nerve are extremely rare lesions. Only a few case reports and 1 case series have been published. We report an additional case with atypical imaging and review the existing literature with attention to time to surgery and imaging characteristics., Case Description: In a 38-year-old man with progressive visual field deficit, a lesion compressing the left optic nerve in the optic canal was diagnosed. On magnetic resonance imaging, this lesion had a homogeneous signal and was tentatively diagnosed as a meningioma. A left frontolateral craniotomy with extradural skull base approach with neuronavigation was performed for resection and definitive diagnosis of the lesion. Pathologic examination showed a lesion most consistent with a cavernous hemangioma. Follow-up magnetic resonance imaging at 6 months showed no remaining tissue or recurrence. Clinically, there was subjective and objective improvement of sight., Conclusions: A cerebral cavernous malformation should always be in the differential diagnosis of a lesion causing an optic neuropathy with visual acuity loss and visual field defect. Clinical presentation of an optic neuropathy requires medical imaging; magnetic resonance imaging is the modality of choice in the diagnosis of these lesions. The treatment of cerebral cavernous malformation is gross total resection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Alemtuzumab is a humanized IgG monoclonal antibody approved in more than 60 countries for patients with relapsing remitting multiple sclerosis (RRMS). In phase 2 and 3 clinical trials (CAMMS223 (NCT00050778), CARE-MS I (NCT00530348), and CARE-MS II (NCT00548405)), patients receiving alemtuzumab demonstrated significantly greater improvements on clinical and MRI outcomes versus SC IFNβ-1a; mild to moderate infusion-associated reactions (IARs) were the most frequently reported adverse events (AEs) associated with alemtuzumab. EMERALD (NCT02205489) was a phase 4, multicenter, multinational, single-arm study designed to assess an algorithm for the prevention and management of IARs in RRMS patients treated with alemtuzumab., Methods: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H 1 and/or H 2 antagonists or equivalent gastroprotection (proton pump inhibitors) were given 1 day before alemtuzumab infusion, 1 h prior to the infusion, and post-infusion. Methylprednisolone was given orally 1 day before infusion, 1 h prior to the infusion, and as needed post-infusion. Antipyretics were given 1 h before infusion and as needed post-infusion. Anti-emetics and normal saline were given as needed during and post-infusion., Results: Of the 61 patients screened, 58 (95.1%) were enrolled into the study. Of the 58 patients who received the first infusion of Period 1, 57 (98.3%) completed the 5 days of Course 1. A total of 54 patients received the first infusion of Period 2 and 53 completed the 3-day course. All patients (n = 58) completed the Month 6 visit and 54 the Month 12 visit. 93.1% of patients had at least one IAR (91.4% in Period 1 and 81.5% in Period 2), the majority of which were grade 1 (69.1%) or grade 2 (28.0%). The three most common IARs of headache, pyrexia, and rash occurred in 48.8%, 40.7%, and 24.1% of patients during the first course and 14.8%, 17.2%, and 5.6% of patients during the second course, respectively. The majority of IARs occurred within 6 h after the start of alemtuzumab infusion, with a peak during the first 2 h. The types and overall incidence of IARs were consistent with phase 2 and 3 trials. Frequency and distribution of rash were reduced in the EMERALD study compared with previous clinical trials. Serious IARs occurred in 15.5%, a higher rate than reported in clinical trials of alemtuzumab., Conclusion: Although most alemtuzumab-treated patients experienced IARs as in previous controlled clinical studies, there was an improvement in the frequency and distribution of alemtuzumab-associated rash, which may have been associated with this study's prophylaxis regimen., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the last few years, an increasing worldwide incidence in syphilis has been reported, mostly in the United States and Western Europe. Neurosyphilis is characterized by a wide differential diagnosis, which too often causes the disease to remain undetected for a long time. We report a case of a male patient with manic psychotic symptoms, in whom neurosyphilis was identified after elaborate diagnostic investigations. We give an overview of the disease process and correlations with psychiatric symptoms, diagnostics, screening and treatment.

Melanoma antigen genes (Mage) were first described as tumour markers. However, some of Mage are also expressed in healthy cells where their functions remain poorly understood. Here, we describe an unexpected role for one of these genes, Maged1, in the control of behaviours related to drug addiction. Mice lacking Maged1 are insensitive to the behavioural effects of cocaine as assessed by locomotor sensitization, conditioned place preference (CPP) and drug self-administration. Electrophysiological experiments in brain slices and conditional knockout mice demonstrate that Maged1 is critical for cortico-accumbal neurotransmission. Further, expression of Maged1 in the prefrontal cortex (PFC) and the amygdala, but not in dopaminergic or striatal and other GABAergic neurons, is necessary for cocaine-mediated behavioural sensitization, and its expression in the PFC is also required for cocaine-induced extracellular dopamine (DA) release in the nucleus accumbens (NAc). This work identifies Maged1 as a critical molecule involved in cellular processes and behaviours related to addiction., (© 2018 The Authors.)

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis.

Alemtuzumab (Lemtrada ® ) is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease defined by clinical or imaging features. Alemtuzumab demonstrated superior efficacy over active comparator in both treatment naive patients and those with inadequate response to prior therapy. Alemtuzumab is associated with a consistent and manageable safety and tolerability profile. Treatment with alemtuzumab for multiple sclerosis increases the risk for autoimmune adverse events including immune thrombocytopenia (ITP). Complete blood counts with differential should be obtained prior to initiation of treatment and at monthly intervals thereafter for 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP onset is confirmed, appropriate medical intervention should be promptly initiated, including immediate referral to a specialist. This paper presents the consensus of Belgian multiple sclerosis specialists and hematologists to guide the treating physician with practical recommendations.

The article Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus, written by Lambert et al., was originally published electronically on the publisher's internet portal on 27 January 2018 without open access.

Cerebral venous thrombosis is a rare complication of intracranial hypotension. We describe 3 cases in which this phenomenon occurred, as a result of a lumbar puncture or due to a spontaneous cerebrospinal fluid leak. We emphasize the importance of early detection of the intracranial hypotension syndrome, the most common clinical manifestation being orthostatic headache. It is not an innocent condition as it is associated with other potential complications such as subdural hygroma/hematoma, cranial nerve palsies, cerebellar tonsillar descent, and even brainstem manifestations. Any change in the typical features of the syndrome should lead to further investigation. Repeat cerebral imaging is important in that situation, including ruling out cerebral venous thrombosis., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)