Background Integrating clinical findings with neuroradiological changes is a crucial skill in neurology, particularly for diagnosis. Multiple Sclerosis (MS) lesions in the brainstem are rarely asymptomatic, leading to unique and often localised clinical syndromes. MS lesions exhibit a characteristic perivenular distribution, which in the brainstem is imprinted by the consistent topography of the penetrating veins. Objective This review provides an integrative perspective on the anatomical patterns of MS lesions in the brainstem (midbrain, pons, and medulla). It correlates specific clinical syndromes with radiological appearances, aiding in both diagnosis and functional localisation. Methods We searched the available literature using keywords related to the three brainstem sections (midbrain, pons, medulla) and eloquent anatomical locations (medial longitudinal fasciculus, cerebellar peduncle, nerve fascicle, aqueduct, area postrema), aiming to correlate specific radiological patterns of MS lesions with their consistent clinical syndromes as reported in the literature. Summary of Key Findings Brainstem MS lesions often cause irritative symptoms rather than full functional loss. Unlike other conditions, visible MS lesions on MRI rarely disappear and usually remain as silent lesions following an acute event. The consistent venous architecture creates specific radiological patterns that link to distinct clinical presentations. In contrast, inflammatory disorders like NMOSD and MOGAD cause more aggressive and extensive dysfunction. Conclusion The visual details of MS brainstem lesions reflect their close relationship to venous anatomy, which can be anticipated even when the central vein sign is not directly visualised. Recognising these specific clinical-radiological syndromes provides a unique and insightful diagnostic tool for MS, underscoring the value of strong functional and radiological-anatomical interpretation skills in clinical neurology.

To study the impact of cladribine tablets (CladT) on B cell function: kappa and lambda free light chain levels (K/L-FLC), immunoglobulin (Ig) G production including B-cell chemoattractant CXCL-13.

Recently it has been shown that treatments targeting B cells in multiple sclerosis (MS) are effective in controlling disease activity. B cells contribute to the pathogenesis of MS via antigen presentation, T cell activation, and antibody production. In the chronic progressive cladribine trial, some patients treated with cladribine had a significant decline in oligoclonal band number. However, the mode of action of cladribine tablets (CladT) on peripheral immune cells and its biological activity within the CNS remains to be determined further.The CladB study is a longitudinal prospective investigation of CladT treatment in relapsing-remitting MS (RRMS). Blood was sampled at Day 0, 1, 5, then once a week for 8 weeks, fortnightly up to 24 weeks, and once a month till 96 weeks for immune cells. This was compared to a historical cohort of alemtuzumab treated samples for one month. Paired cerebrospinal fluid (CSF) and blood were also taken at Day 0, 48 and 96 weeks after initiating CladT for Kappa and Lambda-free light chain (кFLC, λFLC) index, oligoclonal bands (OCBs), immunoglobulin indices, inflammatory mediators and neurofilament light chain (NfL). Participants also underwent clinical and magnetic resonance imaging brain assessments.Ten participants (3 male, 7 female, mean age 35.9 ± 10.5 (SD) and Expanded disability Status Scale 2.5 (range 0-6) at baseline were enrolled. B cells, in particular memory B cells, were heavily depleted by CladT. Alemtuzumab, conversely rapidly depleted both T and B cells. Although still present, reduction in OCB numbers were observed in 4/10 participants and кFLC index reduced from mean 164.5 ± 227.1 (SD) at baseline to 71.3 ± 84.7 at 48 weeks (p=0.002) and 64.4 ± 67.3 at 96 weeks (p=0.01). This coincided with reduction in IgG index [1.1 ± 0.5 (SD) at baseline, 0.8 ± 0.4 (p=0.014) at 48 weeks and 0.8 ± 0.3 (P=0.02) at 96 weeks] and CSF CXCL-13 [88.6± 68.4 (SD) pg/mL, 39.4 ± 35.2 mg/mL (p=0.037) at 48 weeks and 19.1 ± 11.7pg/ml at 96 weeks (p=0.027)]. CSF NfL levels were reduced at 48 weeks only (p=0.01).In conclusion, our study supports the view that CladT treatment works primarily by depleting memory B-cells and antibody-secreting cell precursors in RRMS leading to sustained effects on intrathecal antibody production and total IgG associated with a reduction in the B-cell chemoattractant CXCL-13 in the CSF.### Competing Interest StatementAll authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: all authors had financial support from Merck for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.### Funding StatementMerck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA, Darmstadt, Germany.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:London - Stanmore Research Ethics Committee.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAnonymised data are available from the authors upon reasonable request.

The presence of central nervous system lesions fulfilling the criteria of dissemination in space and time on MRI leads to the diagnosis of a radiologically isolated syndrome (RIS), which may be an early sign of multiple sclerosis (MS). However, some patients who do not fulfill the necessary criteria for RIS still evolve to MS, and some T2 hyperintensities that resemble demyelinating lesions may originate from mimics. In light of the recent recognition of the efficacy of disease-modifying therapy (DMT) in RIS, it is relevant to consider additional imaging features that are more specific of MS. We performed a narrative review on cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL) in patients with RIS. In previous RIS studies, the reported prevalence of CLs ranges between 20.0 and 40.0%, CVS + white matter lesions (WMLs) between 87.0 and 93.0% and PRLs between 26.7 and 63.0%. Overall, these imaging findings appear to be frequent in RIS cohorts, although not consistently taken into account in previous studies. The search for CLs, CVS + WML and PRLs in RIS patients could lead to earlier identification of patients who will evolve to MS and benefit from DMTs.

Recent studies demonstrate the efficacy of B cell-targeting therapies in managing multiple sclerosis (MS) activity, emphasizing the critical role of B cells in MS pathogenesis. CladB study aimed to quantify the temporal changes in peripheral immune cells and their activity over 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS).Ten participants (3 males, 7 females) had blood samples collected at multiple intervals (Day 0, 1, 5, then weekly for 8 weeks, biweekly for up to 24 weeks, and monthly for up to 96 weeks) for immune cell analysis, compared to a historical alemtuzumab-treated cohort. Paired cerebrospinal fluid (CSF) was also taken for various analyses, alongside clinical and brain imaging assessments.CladT depleted memory B cells, while alemtuzumab rapidly depleted T and B cells. The кFLC index decreased from 164.5 ± 227.1 to 71.3 ± 84.7 at 48 weeks (p = 0.002) and to 64.4 ± 67.3 at 96 weeks (p = 0.01). The IgG index dropped from 1.1 ± 0.5 at baseline to 0.8 ± 0.4 at 48 weeks (p = 0.014) and to 0.8 ± 0.3 at 96 weeks (p = 0.02). CSF CXCL-13 decreased from 88.6 ± 68.4 pg/mL to 39.4 ± 35.2 pg/mL at 48 weeks (p = 0.037) and 19.1 ± 11.7 pg/mL at 96 weeks (p = 0.027). CSF NfL levels were reduced at 48 weeks (p = 0.01).CladT primarily depletes memory B cells and antibody-secreting cell precursors in RRMS, leading to sustained effects on intrathecal antibody production and total IgG, and a reduction in CSF CXCL-13.

OBJECTIVES:Our objectives were to investigate the characteristics of people living with HIV who presented with new or recurrent symptoms in the context of re-emergence of cerebrospinal fluid HIV RNA escape after antiretroviral therapy (ART) modification (termed relapse of CSF HIV RNA escape). METHODS:People living with HIV-1 with known CSF HIV RNA escape were identified, with clinical and laboratory data obtained from records in a tertiary centre. CSF HIV RNA escape was defined as quantifiable CSF HIV RNA in the presence of unquantifiable plasma HIV-RNA or CSF HIV RNA greater than plasma HIV RNA in cases where plasma HIV-RNA was quantifiable. Relapse was defined as a re-emergence of CSF HIV RNA escape with new symptoms after ART therapy intensification post-initial CSF HIV RNA escape. RESULTS:Among 40 people living with HIV who presented with neurosymptomatic CSF HIV RNA, eight (20%) presented with a relapse of CSF HIV RNA escape. Symptoms on relapse included confusion (n = 2), cognitive decline (n = 2), cerebellar dysfunction (n = 2) and worsening of pre-existing seizures (n = 1). Prior to their relapse, three people underwent drug therapy modification, with two people stopping raltegravir intensification, and one person switched from tenofovir alafenamide, emtricitabine and raltegravir for a new regimen. CONCLUSIONS:People with a relapse of CSF HIV RNA escape within this cohort presented with varied symptoms similar to their initial CSF HIV RNA escape. Clinicians should be vigilant of relapse of symptoms, particularly when simplifying ART regimens in people with CSF HIV RNA escape.

There is a lack of published guidelines on the management of patients with multiple sclerosis (MS) undergoing procedures that require anaesthesia and respective advice is largely based on retrospective studies or case reports. The aim of this paper is to provide recommendations for anaesthetists and neurologists for the management of patients with MS requiring anaesthesia. This review covers issues related to the anaesthetic management of patients with MS, with a focus on preoperative assessment, choice of anaesthetic techniques and agents, side-effects of drugs used during anaesthesia and their potential impact on the disease evolution, drug interactions that may occur, and the need to use monitoring devices. A systematic PubMed research was performed to retrieve relevant articles.

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood. Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity. Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment. Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable). Results: Of n = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad. Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.

Background Cladribine is an immunotherapy for people with multiple sclerosis (pwMS). Whilst many pwMS do not require retreatment after completing a standard dosing schedule, disease activity resumes in others. Aims To investigate whether baseline characteristics, including degree of lymphocyte reduction, and total or weight-adjusted drug dose, were associated with re-emerging disease activity. Methods Demographics, clinical, laboratory and magnetic resonance imaging data of pwMS who received two courses of cladribine were extracted from the health record. To assess associations of predictor variables with time to new disease activity, a series of Cox proportional hazards models were fitted. Results Of our total cohort (n=264) 236 pwMS received two courses of cladribine. Median follow-up was 3.5 years (IQR:2.9,4.3) from the last administration. Re-emerging disease activity occurred in 57/236 (24%). Twenty-two/236 received a third course of cladribine 37 months (median;IQR:31.7,42.1), and 22/236 other immunotherapies 19 months (13.0,30.2) after their second course of cladribine, respectively. Thirteen/236 were yet to receive immunotherapy. Hazard models indicated association between re-emerging disease activity and (i) baseline MRI activity (ii) dose of cladribine administered at the second course. Conclusions Re-emerging disease activity was associated with high baseline MRI activity and low dose second treatment course.

24-year-old man presented with drowsiness, worsening cognitive impairment and a mixed movement disorder. He was adopted as a child and was reported to be independent and working one year before admission, but progressively slow and unable to self-care since. On examination, he was cognitively impaired on all domains. He had increased tone, brisk reflexes and extensor plantars. There were dysto- nia-parkinsonian features of dystonic tremor and bradykinesia, slow saccades and oculomotor apraxia, along with motor impersistence. After exclusion of chronic infections, the working diagnosis was of a neurodegenerative movement disorder. Whilst there was no overt chorea, the differentials for juvenile Huntingdon’s disease (HD) were explored, and HD ultimately confirmed on genetic testing.Learning PointsJuvenile HD patients may not have chorea but may be rigid or parkinsonian.Slow saccades are most prominent in juvenile HD patients, even early.Involuntary movements are often partially suppressible, and mild chorea is easily overlooked. Look for involuntary head turns, fidgety movements of the fingers and toes, frequent blinking and odd facial expressions.Test for motor impersistence in these individuals.Gait may appear normal but tandem walk may bring out chorea, imbalance, or other problems.katieyoganathan@gmail.com

IntroductionStrategy, evidence and anticipation should underpin workforce-planning.AimTo estimate a sustainable patient-caseload (PCL) for a full-time equivalent MS specialist neurologist (FTE-MSologist).MethodsHypothetically, an FTE-MSologist refers to 10-MSology-related programmed activities per week. We considered three service models (core, aspirational, alternative/DGH) with differing frequency, duration and content of patient consultations and monitoring. We computed the ideal number of new patients and existing patients, for each scenario, from detailed qualitative interviews with 4 MSologists at different NHS Trusts. Computations assumed all 3 scenarios had common support from MS nurses (@315 PLwMS/FTE MS nurse), MS coordinators, neuroradiology, neuropharmacist and administration.ResultsEstimates for 1-FTE-MSologist/year/service model were: Core: new-PCL=81 (range=46–115); existing- PCL=798 (range=672–923). Aspirational: new-PCL=21 (range=28–69); existing-PCL=481 (range=401–561). Alternative/DGH: new-PCL=89 (range=51–126); existing-PCL=874 (range=733–1015).ConclusionsThese MS PCL/FTE-MSologist estimates enable future NHS manpower planning to optimally staff specialist MS services. It is notable that few (if any) UK MS services have the support considered pre- requisite. Much of the direct clinical care work undertaken is “unseen” and not formally job-planned. These results have significant implications formal time and motion studies may be required to improve estimates’ accuracy.Support.Karen Bateman was supported by Novartis. Disclosures: See poster g.giovannoni@qmul.ac.uk

IntroductionCladribine tablets (Mavenclad®) are licensed for treating people with relapsing multiple sclerosis (pwRMS). We treated people with relapsing (pwRMS) and progressive MS (pwPMS) using sub- cutaneously administered cladribine (SCAC) since 2014. Here, we present up to five year follow-up on safety and efficacy.MethodsSCAC 10mg was given on 3–4 days during week 1. 0–3 doses were administered at week 5, according to week 4 lymphocyte count. A second cycle of SCAC was administered 11 months later. Follow-up included clinical outcome evaluation and pharmacovigilance. The proportion of pwMS with no evidence of (i) disease activity (NEDA) and (ii) progression or active disease (NEPAD) was calculated.Results211 pwMS received SCAC. 154/211 completed two treatment cycles. At baseline age was 44 (17–72) years, EDSS 1–8.5. Tolerability was good. One myocardial infarction and one breast cancer occurred. Two severely disabled pwMS died (one of influenza, one of encephalitis). Lymphopenia grade 3 was detected in <3%. At 2 years, 71% (CI 54%, 85%) of pwRMS had NEDA; 38% (CI 23%, 54%) of pwPMS had NEPAD.ConclusionsSCAC was well tolerated. Frequency of significant lymphopenia was low. Efficacy in pwRMS corresponds with trial data. NEPAD rates in pwPMS were similar to licensed DMT.k.allen-philbey@nhs.net

Background: In multiple sclerosis (MS) neurofilament light chain (NfL) is a marker of neuronal damage secondary to inflammation and neurodegeneration. NfL levels drop after commencement of disease-modifying treatment, especially the highly active ones. However, the factors that influence this drop are unknown. Objective: To examine the patient and treatment-related factors that influence CSF NfL before and after starting treatment. Methods: Eligible patients across two centres with two CSF NfL measurements, clinical and MRI data were included as part of an observational cohort study. Results: Data were available in 61 patients, of which 40 were untreated at the first CSF sampling (T1) and treated at the second (T2; mean T1-T2: 19 months). CSF NfL reduction correlated with age (beta = 1.24 95%CI (1.07,1.43); R-2 = 0.17; p = 0.005), Expanded Disability Status Scale (EDSS) (beta = 1.12 95%CI(1.00,1.25); R-2 = 0.21; p = 0.05) and the type of MS (beta = 0.63 95%CI(0.43, 0.92); R-2 = 0.12; p = 0.018; reference=relapsing MS). The treatment effect on a baseline NfL of 702 pg/mL was 451 pg/ml 95%CI(374,509) in a 30-year-old versus 228 pg/ml 95%CI(63,350) in a 60-year-old. There was no association in CSF NfL reduction with BMI, disease duration or sex. In cladribine- and alemtuzumab-treated patients, the CSF NfL T2/T1 ratio did not correlate with lymphocyte depletion rate at 23 weeks. Conclusions: In this observational study, we found that factors reflecting early disease stage, including a younger age, lower disability and relapsing MS were associated with treatment response in CSF NfL. Other factors were not found to be related, including lymphopaenia in highly-active treatments.

The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys [median (IQR) 5.03 (3.71, 6.34)], MSWS-12 [median (IQR) 5.28 (3.62, 6.94)] and HADS-Depression [median (IQR) 0.71 (0.47, 0.96)] scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores [median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively] while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis.

BackgroundSome people with multiple sclerosis (pwMS) are at increased risk of severe Coronavirus disease 19 (COVID-19) and should be rapidly vaccinated. However, vaccine supplies are limited, and there are concerns about side-effects, particularly with the ChAdOx1nCoV-19 (AstraZeneca) vaccine.ObjectivesTo report our first experience of pwMS receiving the AstraZeneca vaccine.MethodsService evaluation. pwMS using the MS service at Barts Health NHS Trust were sent questionnaires to report symptoms following vaccination.ResultsThirty-three responses were returned, 29/33 pwMS received a first dose of AstraZeneca vaccine, the remaining four received a first dose of BioNTech/Pfizer vaccine.All but two patients (94%) reported any symptoms including a sore arm (70%), flu-like symptoms (64%), fever (21%), fatigue (27%), and headache (21%). In more than 2/3 patients, symptoms lasted up to 48 hours, and with the exception of two pwMS reporting symptom duration of 10 and 12 days, respectively, symptoms in the remainder resolved within seven days. No severe adverse effects occurred.ConclusionspwMS report transient symptoms following AstraZeneca vaccination, characteristics of which were similar to those reported in the non-MS population. Symptoms may be more pronounced in pwMS due to the temperature-dependent delay in impulse propagation (Uhthoff's phenomenon) due to demyelination.

Introduction: The COVID-19 pandemic caused major disruption to health services across the Globe, including the UK. Quick adaptations were required to switch from face-to-face to remote consultations and to further develop remote monitoring (RM) of people with multiple sclerosis (pwMS) in the community. Objective: To evaluate the views of pwMS under the care of our team who participated in RM. Methods: RM included completion of the nine-hole peg test, Timed 25-foot walk, ABILHAND questionnaire and WebEDSS at home. Electronic health records were queried for pwMS who participated in RM from May 2020-July 2020. Questionnaires (N=72) were sent via post or email asking about their experience of RM. Data were analysed using descriptive statistics. This service evaluation project was registered with the clinical effectiveness unit at Barts Health NHS Trust (Registration:11945). Results: 23 pwMS (mean age 49 years (SD11.7);18 women, 5 men;relapsing MS: 17;progressive MS: 6;EDSS 0-8) responded to the survey. The majority viewed RM as a way for healthcare professionals to provide pwMS with the necessary support (83%) and to manage MS symptoms (70%);65% were keen to know more about how RM scores can be used to help them manage their MS symptoms. Overall, 60% of respondents felt confident completing assessments at home;52% said they will continue with RM after the pandemic. Conclusions: RM enabled monitoring of pwMS during the pandemic. Results suggest pwMS understood and generally agreed with the intentions of RM. There is also evident potential to facilitate patient activation and self-management. The apparent reluctance to continue RM in half of our sample after the pandemic warrants further exploration. Whilst bias may play a role due to limited returns, further reasons may include lack of digital confidence and associated risk of health inequalities.

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak ® ) in multiple sclerosis (MS) patients. Methods: Litak ® was offered to MS-patients irrespective of disease course. Litak ® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak ® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.