The clinical characteristics of cataplectic attack in narcolepsy type 1

ObjectiveCataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1).MethodsWe experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features.ResultsWe observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score.ConclusionFour-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.     

流式细胞仪检测成年人脑脊液T淋巴细胞亚群百分比参考范围

目的初步建立脑脊液T淋巴细胞亚群正常参考范围。方法使用四色流式细胞仪检测49例无神经系统疾病人群脑脊液和血液的T淋巴细胞亚群(CD3+CD4+、CD3+CD8+、CD3+CD69+)百分比水平。结果 (1)正常脑脊液T淋巴细胞亚群构成以T辅助细胞(CD3+CD4+T细胞)为主。T辅助细胞平均占脑脊液T淋巴细胞总数的68.27%,参考范围为54.77%～81.77%。T抑制细胞(CD3+CD8+T细胞)平均占脑脊液T淋巴细胞总数的31.73%,参考范围为18.23%～45.23%。活化T细胞(CD3+CD69+T细胞)平均占脑脊液T淋巴细胞总数的2.76%,参考范围为0.29%～26.29%。脑脊液CD4/CD8比值平均为2.21,参考范围为1.16～4.21。脑脊液的T辅助细胞百分比、活化T细胞百分比和CD4/CD8比值高于血液,T抑制细胞百分比低于血液(P<0.05)。(2)脑脊液与血液各T淋巴细胞亚群在各年龄组间无统计学差异。(3)脑脊液和血液各T淋巴细胞亚群在男女之间亦无统计学差异。结论本文初步建立了脑脊液T淋巴细胞亚群百分比的参考范围;正常脑脊液T淋巴细胞中以T辅助细胞为主,且其亚群分布特点与血液T淋巴细胞亚群不同。     

Elevated glial fibrillary acidic protein levels in the cerebrospinal fluid of patients with narcolepsy

Glial fibrillary acidic protein (GFAP) is an established indicator of astrogliosis. Therefore, variable cerebrospinal fluid (CSF) concentrations of this protein might reflect disease-specific pathologic profiles. In patients with narcolepsy, a loss of hypocretin-1 (hcrt-1) neurons in the brain and low concentrations of hcrt-1 in CSF have been reported. We performed a commercially available enzyme-linked immunosorbent assay to investigate if GFAP also is altered in the CSF of these patients. Here we detected significantly higher CSF levels of GFAP in patients with low hcrt-1 levels, of which the majority had a diagnosis of narcolepsy and cataplexy (NC); however, this finding was not observed in patients with hcrt-1 levels that were within reference range. In conclusion, GFAP may be useful as an additional disease biomarker in patients with narcolepsy, and this hypothesis should be investigated in larger studies.     

Using actigraphy to assess sleep and wake rhythms of narcolepsy type 1 patients: a comparison with primary insomniacs and healthy controls

Objective/backgroundIt has been shown that actigraphy may have a discriminant function (DS) for the diagnosis of narcolepsy type 1 patients (NT1), based on a combination of nighttime and daytime parameters. Here, we aimed to test those findings using another actigraph model with a different clinical sample as control (ie, primary insomniacs, PI), carrying out a secondary analysis of previously collected data.Patients/methodsThe study sample consisted of 13 NT1 (nine females; mean age 39.38 ± 11.48), 13 PI (nine females; mean age 38.69 ± 10.72) and 13 Healthy Controls (HC) (nine females; mean age 38 ± 10.77). Participants wore the Actiwatch AW64 (Cambridge Neurotechnology Ltd, Cambridge, UK) around the non-dominant wrist for seven consecutive days.ResultsSignificant differences between groups were observed with a higher number of episodes of wakefulness (wake bouts, WB) in PI than HC, a higher fragmentation index (FI) in NT1 than HC and PI, a higher duration of the longest nap (LNAP) in NT1 than HC and PI and higher DS in PI and NT1 than HC. A new DS (NDS), with LNAP and FI as independent variables, was proposed; which was higher in NT1 than HC and PI.ConclusionsThe present study confirms that actigraphy discriminates NT1 from HC. However, considering PI, a new discriminant function NDS which takes into account LNAP and FI is better for this actigraph model.     

T-cell subsets in the cerebrospinal fluid and blood of patients with multiple sclerosis

The absolute numbers and ratios of helper/inducer (T4) and cytotoxic/suppressor (T8) T-cells were determined in cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS) and various other neurologic diseases (OND). In patients with MS, the T4:T8 ratio was higher in both blood and CSF, and the increase was significantly greater in CSF than in blood. These findings were due to an increased proportion of T4-lymphocytes in the CSF and to a decreased proportion of T8-cells in blood. These results indicate the need for additional studies of CSF lymphocytes in patients with MS.     

Conventional autoantibodies against brain antigens are not routinely detectable in serum and CSF of narcolepsy type 1 and 2 patients

Narcolepsy with cataplexy (NT1) is a chronic hypothalamic disorder with a presumed immune-mediated etiology leading to a loss of hypocretin neurons. Previous studies reported conflicting results in terms of presence of auto-antibodies involved in narcolepsy pathophysiology. A total of 86 patients with primary/idiopathic narcolepsy (74 NT1, 12 NT2) and 23 control patients with excessive daytime sleepiness due to other causes were tested for the presence of a wide range of anti-neuronal antibodies in both serum and cerebrospinal fluid (CSF). Anti-neuronal antibodies were rarely found in patients with narcolepsy (n = 2) and in controls (n = 1). Our results are in line with previous reports. We can therefore support the current evidence, that conventional anti-neuronal antibodies are not routinely detected during the workup of NT1 and other CDH patients.     

High prevalence of ADHD symptoms in unmedicated youths with post-H1N1 narcolepsy type 1

ObjectivesTo characterize attention deficit-hyperactivity disorder (ADHD) symptoms in unmedicated post-H1N1 narcolepsy type 1 (NT1) youths, and explore associations between ADHD symptoms and the narcolepsy phenotype.MethodsA total of 50 consecutively enrolled post-H1N1 NT1 youths (7–20 years, 62% females, 98% HLA-DQB1106:02-positive, 98% CSF hypocretin-1 deficient, 88% vaccinated) were assessed after two weeks off medication for ADHD (ADHD diagnosis pre/post-narcolepsy, parent-rated ADHD symptoms) and narcolepsy-phenotyped (semi-structured interview, Stanford Sleep Questionnaire, Epworth Sleepiness Scale, polysomnography (PSG), Multiple Sleep Latency Test (MSLT)).ResultsIn sum, 26 (52%) and 15 (30%) of participants had ADHD symptoms above and below the clinical significant cut-off, respectively, while 9 (18%) had no ADHD symptoms. High values were found for ADHD total score (mean (SD), 17.9 (9.5)) and ADHD subscores (inattentive score, 11.0 (6.3); hyperactive/impulsivity score, 6.9 (4.7)). These were significantly higher than previously reported in a mainly medicated narcolepsy cohort (p < 0.0001). Age, gender and disease duration did not influence scores. Two participants (4%) had ADHD diagnosis prior to narcolepsy onset. ADHD symptoms were correlated with parent-rated, but not with patient rated ESS scores, objective sleepiness (mean sleep latency), sleep fragmentation (sleep stage shift index, awakening index), or CSF hypocretin-1 level.ConclusionComorbid ADHD symptoms were more prevalent in unmedicated post-H1N1 NT1 youths than previously reported in mainly medicated pediatric narcolepsy cohorts. The high prevalence was not due to pre-existing ADHD and generally not correlated with core narcolepsy sleep/wake phenotype characteristics, indicating that the ADHD symptoms were not a direct consequence of disturbed sleep or daytime sleepiness.     

Flow cytometric analysis of lymphocytes in cerebrospinal fluid in patients with tick-borne encephalitis

Introduction – Cerebrospinal fluid (CSF) lymphocyte subsets were examined by flow cytometry in 33 patients with tick-borne encephalitis (TBE) in order to determine their values. Patients and methods – Lymphocytes were isolated from CSF and lymphocyte subsets were determined: lymphocytes T (CD3+), lymphocytes B (CD19+), NK cells (CD3-CD56+), helper T cells (CD3+CD4+) and cytotoxic T cells (CD3+CD8+). The expression of IL-2 receptors (CD25+) and transferrin receptors (CD71+) on T cells and HLA-DR molecules on T cell subsets was examined. Furthermore, possible relationships among different TBE patient population variables (gender, age, severity of disease, duration of meningitis) were considered. Results – The analyses of the CSF lymphocyte population subsets are presented. Lymphocytes T (CD3+) were significantly higher in the CSF than in the peripheral blood as was the case with the T cells that expressed transferrin receptors (CD71). Lymphocytes B (CD19+) and NK cells (CD3-CD56+) prevailed in the peripheral blood. In the early course of the disease, a higher expression of HLA-DR molecules on T lymphocytes was observed, while later a higher expression of IL-2 receptors (CD25+) was observed. Discussion – Significant differences in lymphocyte subsets between the CSF and the peripheral blood were found. Significant time-dependent changes of CSF lymphocyte subsets during course of infection were observed. The results of the present study give us deeper insight into CNS cellular immunopathogenic mechanisms in patients with TBE.     

Semantic priming effect during REM-sleep inertia in patients with narcolepsy

Patients with narcolepsy-cataplexy (NC) present excessive daytime sleepiness (EDS), cataplexy and an altered architecture of nocturnal sleep, with frequent episodes of REM-sleep at sleep onset (SOREM-sleep). This altered organization of nocturnal sleep may be accompanied by some differences in the functioning of the cognitive processes involved in the access, organization and consolidation of information during sleep. This study attempts to ascertain whether the activation of semantic memory during REM-sleep, as measured using a technique of semantic priming (namely, the facilitation of the activation of strongly-related rather than weakly-related and, overall, unrelated pairs of prime-target words) is different in NC patients compared to normal subjects. A lexical decision task (LDT) was carried out twice in wakefulness (at 10a.m. and after a 24h interval) and twice in the period of sleep inertia following awakening from SOREM and 4th-cycle REM-sleep on 12 NC patients and from 1st- and 4th-cycle REM-sleep on 12 matched controls. Reaction time (RT) to target words, taken as a measure of the semantic priming effect, proved to be longer (a) in NC patients than in control subjects; (b) in the period of REM-sleep inertia than in wakefulness; (c) in the first rather than the second session; and (d) for unrelated compared to weakly-related and, overall, strongly-related prime-target pairs. RT in post-REM-sleep sessions was less impaired, compared to waking sessions, and less dependent on the associative strength of prime-target pairs in NC patients than in normal subjects. Finally, RT of NC patients, although longer than that of normal subjects in waking sessions, significantly improved in the second session, as a consequence of either the amount of exercise or the consolidation advantage provided by REM-sleep for the procedural components of the task. The whole picture suggests a greater effectiveness of the activation of semantic memory during (SO)REM-sleep in NC patients rather than in normal subjects, and overall for the organization of new and unexpected relationships (such as those between unrelated pairs) between items of information.     

Decreased concentration of klotho and increased concentration of FGF23 in the cerebrospinal fluid of patients with narcolepsy

Objectiveto explore the status of concentration of klotho and fibroblast growth factor 23 (FGF23) in cerebrospinal fluid (CSF) of patients with narcolepsy.Patients/methods59 patients with narcolepsy and 17 control individuals were enrolled. We used radioimmunoassay, human klotho enzyme-linked immunosorbent assay (ELISA), human intact FGF23 ELISA and spectrophotometry to measure hypocretin-1, klotho, FGF-23 and phosphorus, respectively. T-Student Test was used to compare klotho and phosphate concentrations, Mann–Whitney U Test were used to compare FGF-23 levels between groups. ANOVA Test was used to compare klotho and phosphate CSF concentrations among narcolepsy patients with CSF hypocretin-1 <110 pg/ml (HCRT-) and narcolepsy patients with CSF hypocretin-1 >110 pg/ml (HCRT+) versus control subjects.ResultsKlotho and phosphorus CSF levels were lower in narcoleptic patients than in control (908.18 ± 405.51 versus 1265.78 ± 523.26 pg/ml; p = 0.004 and 1.34 ± 0.25 versus 1.58 ± 0.23 mg/dl; p = 0.001, respectively). We found higher FGF-23 levels in narcoleptic patients (5.51 versus 4.00 pg/mL; p = 0.001). Klotho and phosphorus CSF levels were lower in both HCRT- and HCRT+ than controls. Moreover, there were higher FGF-23 levels in both HCRT-/HCRT+ groups versus controls. However, we did not find differences comparing HCRT- and HCRT+ groups, analyzing CSF klotho, FGF-23 or phosphorus levels.ConclusionsPatients with narcolepsy have decreased CSF concentration of klotho and increased CSF levels of FGF-23. These findings may play a role in understanding the pathogenesis of narcolepsy.     

Immunoglobulin gene rearrangement analysis in cerebrospinal fluid of patients with lymphoproliferative processes

OBJECTIVE: To determine the sensitivity and specificity of clonal immunoglobulin heavy chain gene rearrangement (IGHR) analysis in the distinction of benign and malignant lymphoproliferative diseases. METHODS: A retrospective analysis was conducted of patients in whom a malignant lymphoproliferative process was suspected. Cells of CSF samples were collected by centrifugation, resuspended in 100 microl of the supernatant and boiled. A 10 microl aliquot of this lysate served as template for semi-nested polymerase chain reaction using variable and joining region consensus primers. PCR products were analyzed by polyacrylamide gel electrophoresis. Cytopathological diagnosis and flow cytometry results were recorded. Sensitivity and specificity of IGHR analysis, cytopathology and flow cytometry were calculated. RESULTS: Eleven patients (12 specimens) had involvement of leptomeninges at the time of lumbar puncture. Another 25 cases (27 specimens) had normal CSF findings or were diagnosed with benign lymphoproliferative conditions. Sensitivity of CSF cytopathology, flow cytometry and IGHR analysis were 0.27 [95% confidence interval 0.06, 0.61], 0.1 [0.003, 0.45] and 0.58 [0.28, 0.85]. Specificity was 1 [0.86, 1], 0.95 [0.77, 1.0] and 0.85 [0.66, 0.96]. INTERPRETATION: IGHR analysis appears to be a useful addition to morphological and flow cytometry analysis of cerebrospinal fluid in the evaluation of CNS lymphoproliferative processes.     

A role for natural killer cells in the immunopathogenesis of multiple sclerosis

Seventeen relapsing–remitting (R/R) multiple sclerosis (MS) patients and age/sex matched controls were studied every 6 weeks for 2 years. Disease activity, determined both clinically and by serial MRI, was correlated with natural killer (NK) cell functional activity (FA) and phenotype. Mean NK cell FA is significantly lower in MS patients, compared to controls (P<0.001), while variability around the means is significantly greater (P<0.01). The spectrum of mean NK cell FA, observed in the patient cohort, along with cyclical nature of the FA and phenotype over time, observed in both patients and controls, may begin to explain the discrepant results reported in previous studies. In R/R MS, there is a significant correlation between reductions (valleys) in NK cell FA and the development of active lesions on MRI, new (P<0.001) or enlarging (P=0.05). More importantly, a significant number of active lesions, new (P=0.01) and enlarging (P=0.02), are preceded by a reduction in NK cell FA. The correlation between the onset of clinical attacks and valleys of NK cell FA is also significant (P=0.002). When taken together, the results suggest that reductions (valleys) in NK cell FA represent periods of susceptibility for the development of active lesions on MRI and clinical attacks. A significant positive correlation is also identified between mean NK cell FA for each R/R MS patient and total number of active MRI lesions developed by that patient over the 2 years (P=0.001). The results would suggest that R/R MS patients with a higher mean NK cell FA are at greater risk for the development of active lesions. These results support the proposal that NK cells may play a role in the immunopathogenesis of R/R MS.     

Interferon production and natural killer (NK) activity in leukocyte cultures from multiple sclerosis patients

Peripheral blood leukocyte (PBL) cultures from only 37% of MS patients produced detectable HuIFN-gamma in response to ConA as opposed to 85% of the cultures derived from normal blood donors. However, the yields in patient-derived cultures that were responsive, were not lower than those in cultures from controls. Production of HuIFN-alpha after stimulation with Sendai virus was not aberrant in cells taken from MS patients. The difference in HuIFN-gamma response rate between MS and normal donor-derived cells was more pronounced when DR2+ carriers were compared amongst each other than when DR2-k carriers were compared. Among the MS patients, the failure of PBLs to produce HuIFN-gamma in response to ConA was not correlated with age, sex, disease duration and type of disease. However, positive correlations were found with current disability indices and past disease progression rates. Unstimulated NK-activities of MS patient-derived PBLs were not different from those of normal donor-derived cells. the degree of augmentation of the activity by stimulation with ConA and interferon-alpha was also normal. Within the MS patients group, but not in the control group, there was a trend for DR2+ carriers to have lower spontaneous and stimulated NK-activities than DR2- individuals.     

Natural killer (Nk) Cell activity and nk cell subsets in workers with a tendency of burnout

The involvement of cellular immunity in the burnout syndrome remains to be elucidated. We assessed three components of burnout of the Maslach Burnout Inventory: emotional exhaustion; depersonalization (DP); and personal accomplishment, as well as natural killer cell activity (NKCA) and NK cell subsets in 42 male workers. Workers with a higher DP score showed a lower NKCA and a lower proportionality of CD57⁺CD16⁺ to total lymphocytes. There were no differences in any of the health behaviors (e.g., smoking, alcohol, or obesity) between workers showing higher burnout and those showing lower burnout. A stepwise multiple regressions analysis demonstrated that NKCA was closely correlated with DP, independent of other variables, including a stress index. These results suggest that the relationship between reduced cellular immunity and DP is not due to traditional work stress or health behavioral problems. Further studies on DP as a psychosomatic disorder as well as an occupational health problem should be performed in the future.     

Reliability and validity of the Chinese version of Narcolepsy Severity Scale in adult patients with narcolepsy type 1

ObjectiveTo evaluate reliability and validity of the Chinese version of Narcolepsy Severity Scale (NSS) in adult patients with narcolepsy type 1 (NT1).MethodsOne hundred and fifty-one adult patients (≥18 years) with NT1 were recruited. All filled out the 15-item Chinese version of NSS. Item analysis included critical ratio and correlation analysis. The validity of NSS was assessed by exploratory factor analysis, discriminant validity and convergent validity. Reliability of NSS was assessed by Cronbach's α coefficient, spilt-half reliability and test-retest reliability.ResultsCritical value of all 15 items ranged from 3.01 to 13.36. Each item was significantly correlated with the total score by a correlation coefficient (r) ranging from 0.219 to 0.700. Three common domains were extracted and 15 items explained 54.86% of the total variance. There was a shift in domains compared to the English version likely due to cultural differences. Cronbach's α coefficient for the total scale of 15 items was 0.821 and for three factors was 0.726, 0.748 and 0.760 respectively. The NSS had good correlation with Epworth sleepiness scale scores, Insomnia severity index scores and moderate correlation with mean the sleep latency of polysomnographic recording, and European Quality of Life-5 Dimensions Questionnaire. The Chinese version of NSS showed good spilt-half reliability and test-retest reliability.ConclusionThe Chinese version of NSS shows satisfactory psychometric properties with good validity and reliability. It is applicable to evaluate the severity and consequences of symptoms in Chinese adult patients with NT1.     

Plasma and cerebrospinal fluid substance P in post-stroke patients with depression

Aims: To investigate the correlation between the incidence of post‐stroke depression (PSD) and the levels of substance P (SP) in the plasma and cerebrospinal fluid (CSF). Methods: Ninety‐one stroke patients were divided into PSD (n = 46) and post‐stroke (without depression) groups (n = 45). PSD must have occurred 2–4 weeks after the onset of the stroke and was determined by the Hamilton Rating Scale for Depression (HAMD). In addition, the subjects were divided into anterior (n = 67) and posterior circulation stroke groups (n = 24) based on the location of the focus as determined by computed tomography. All recruited patients were graded by the National Institutes of Health Stroke Scale (NIHSS). Results: The results included the following findings: (i) the level of plasma SP in the PSD group (58.47 ± 14.39) was higher than that of the PS group (36.98 ± 9.49; P = 0.000), while the level of CSF SP in the PSD group (72.13 ± 13.06) was higher than that of the post‐stroke group (37.30 ± 12.57; P = 0.03); (ii) the level of plasma SP was positively correlated with the HAMD and NIHSS score; (iii) the level of plasma SP (38.45 ± 12.23), the HAMD score (9.08 ± 8.72), and the NIHSS score (3.25 ± 1.90) of the anterior stroke group (51.21 ± 16.27, 17.46 ± 15.96, and 6.91 ± 3.30, respectively) were higher than those of the posterior stroke group (38.45 ± 12.23, 9.08 ± 8.7, and 3.25 ± 1.90, respectively; P = 0.017, P = 0.001, and P = 0.000, respectively). Conclusions: SP in the plasma and CSF of patients exhibited a close correlation with neural damage and the incidence of PSD. This study also suggested that anterior hemispheric strokes may play a significant role in development of PSD.     

Lung involvement in Niemann-Pick disease type C1: improvement with bronchoalveolar lavage

Abstract Progressive lung infiltration is a major cause of death in Niemann–Pick disease type A and B (NPA, NPB) and in the recently defined type C2. In type C1 (NPC1), the main manifestations are neurological. We report a patient with a classic, neurological, late infantile form of NPC1 disease, carrying the mutation P474L and the variant I642M in the NPC1 gene, who suffered recurrent respiratory manifestations. Bronchoalveolar lavage of a lung segment due to deteriorating respiratory condition revealed many foamy macrophages and was followed by an improvement in symptoms. Pneumopathy may therefore be considered a feature of NPC1 disease for which a partial bronchoalveolar lavage could be a useful treatment.     

Abnormal subpopulations of monocytes in the cerebrospinal fluid of patients with Parkinson's disease

We performed immune cell profiling by multiparameter flow cytometry in cerebrospinal fluid (CSF) and peripheral blood (PB) of Parkinson's Disease (PD) patients (n = 9) and healthy controls (n = 8). Classical and non-classical monocytes were increased in the CSF of PD patients.     

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

Fingolimod is an approved oral treatment for relapsing–remitting multiple sclerosis (RRMS) that modulates agonistically the sphingosin-1-phosphate receptor (S1PR), inhibiting thereby the egress of lymphocytes from the lymph nodes. In this interventional prospective clinical phase IV trial, we longitudinally investigated the impact of fingolimod on frequencies of NK cell subpopulations by flow cytometry in 17 RRMS patients at baseline and 1, 3, 6, and 12 months after treatment initiation. Clinical outcome was assessed by the Expanded Disability Status Scale (EDSS) and annualized relapse rates (ARR). Over the study period, median EDSS remained stable from month 3 to month 12, and ARR decreased compared to ARR in the 24 months prior treatment. Treatment was paralleled by an increased frequency of circulating NK cells, due primarily to an increase in CD56^dimCD94^low mature NK cells, while the CD56^bright fraction and CD127⁺ innate lymphoid cells (ILCs) decreased over time. An unsupervised clustering algorithm further revealed that a particular fraction of NK cells defined by the expression of CD56^dimCD16⁺⁺KIR^+/−NKG2A⁻CD94⁻CCR7^+/−CX₃CR1^+/−NKG2C⁻NKG2D⁺NKp46⁻DNAM1⁺⁺CD127⁺ increased during treatment. This specific phenotype might reflect a status of aged, fully differentiated, and less functional NK cells. Our study confirms that fingolimod treatment affects both NK cells and ILC. In addition, our study suggests that treatment leads to the enrichment of a specific NK cell subset characterized by an aged phenotype. This might limit the anti-microbial and anti-tumour NK cell activity in fingolimod-treated patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01078-7.