Pub Date : 2023-12-25eCollection Date: 2023-01-01DOI: 10.1177/17562864231214846
Dongmei Wang, Meirong Li, Yue Pan, Zhenzhou Lin, Zhong Ji, Xiaomei Zhang, Miaoqin Tan, Suyue Pan, Yongming Wu, Shengnan Wang
Background: Generalized convulsive status epilepticus (GCSE) is one of the most challenging life-threatening neurological emergencies. If GCSE becomes super-refractory, it is associated with significant mortality. Although aggressive management of prolonged status epilepticus was conducted, the mortality has not decreased since the late 1990s.
Objectives: The present study aimed to explore the risk factors for progression to super-refractory in patients with generalized convulsive status epilepticus (GCSE). Moreover, we illustrated the risk factors for mortality in GCSE patients.
Design: An observational retrospective cohort study.
Methods: We conducted a retrospective study of patients with GCSE admitted to our neurocritical unit, in Guangzhou, China, from October 2010 to February 2021. The data of sociodemographic information, etiology, laboratory results, treatment, and prognosis were collected and analyzed.
Results: A total of 106 patients were enrolled; 51 (48%) of them developed super-refractory status epilepticus (SRSE). Multivariate logistic regression analysis demonstrated that patients with autoimmune encephalitis (p = 0.015) and intracranial infection (p = 0.019) are likely to progress to SRSE. The in-hospital mortality was 11.8% and 9.1% for patients in the SRSE and non-SRSE groups, respectively (p = 0.652). Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratios (NLR) at admission were independently associated with in-hospital mortality. Up to 31.4% of SRSE patients and 29.1% of non-SRSE patients died within 6 months after discharge (p = 0.798). Multivariate logistic regression analysis showed that plasma exchange (PE) was a protective factor for 6-month mortality. A high NLR at discharge was a risk factor for 6-month mortality.
Conclusion: In the current study, about 48% of GCSE patients progressed to SRSE. Regarding etiology, autoimmune encephalitis or intracranial infection was prone to SRSE. No significant differences were observed in the in-hospital and 6-month mortality between SRSE and non-SRSE groups. Multivariate logistic regression analysis showed that NLR at admission and discharge was an independent predictor of in-hospital and 6-month mortality, respectively. Moreover, PE significantly reduced the 6-month mortality.
{"title":"Risk factors for super-refractory and mortality in generalized convulsive status epilepticus: a 10-year retrospective cohort study.","authors":"Dongmei Wang, Meirong Li, Yue Pan, Zhenzhou Lin, Zhong Ji, Xiaomei Zhang, Miaoqin Tan, Suyue Pan, Yongming Wu, Shengnan Wang","doi":"10.1177/17562864231214846","DOIUrl":"10.1177/17562864231214846","url":null,"abstract":"<p><strong>Background: </strong>Generalized convulsive status epilepticus (GCSE) is one of the most challenging life-threatening neurological emergencies. If GCSE becomes super-refractory, it is associated with significant mortality. Although aggressive management of prolonged status epilepticus was conducted, the mortality has not decreased since the late 1990s.</p><p><strong>Objectives: </strong>The present study aimed to explore the risk factors for progression to super-refractory in patients with generalized convulsive status epilepticus (GCSE). Moreover, we illustrated the risk factors for mortality in GCSE patients.</p><p><strong>Design: </strong>An observational retrospective cohort study.</p><p><strong>Methods: </strong>We conducted a retrospective study of patients with GCSE admitted to our neurocritical unit, in Guangzhou, China, from October 2010 to February 2021. The data of sociodemographic information, etiology, laboratory results, treatment, and prognosis were collected and analyzed.</p><p><strong>Results: </strong>A total of 106 patients were enrolled; 51 (48%) of them developed super-refractory status epilepticus (SRSE). Multivariate logistic regression analysis demonstrated that patients with autoimmune encephalitis (<i>p</i> = 0.015) and intracranial infection (<i>p</i> = 0.019) are likely to progress to SRSE. The in-hospital mortality was 11.8% and 9.1% for patients in the SRSE and non-SRSE groups, respectively (<i>p</i> = 0.652). Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratios (NLR) at admission were independently associated with in-hospital mortality. Up to 31.4% of SRSE patients and 29.1% of non-SRSE patients died within 6 months after discharge (<i>p</i> = 0.798). Multivariate logistic regression analysis showed that plasma exchange (PE) was a protective factor for 6-month mortality. A high NLR at discharge was a risk factor for 6-month mortality.</p><p><strong>Conclusion: </strong>In the current study, about 48% of GCSE patients progressed to SRSE. Regarding etiology, autoimmune encephalitis or intracranial infection was prone to SRSE. No significant differences were observed in the in-hospital and 6-month mortality between SRSE and non-SRSE groups. Multivariate logistic regression analysis showed that NLR at admission and discharge was an independent predictor of in-hospital and 6-month mortality, respectively. Moreover, PE significantly reduced the 6-month mortality.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Neurosarcoidosis is a rare manifestation of sarcoidosis with heterogeneous presentations. Patient management is challenging due to the current lack of knowledge about the long-term disease course.
Objective: To identify specific disease courses of neurosarcoidosis according to the clinical and paraclinical presentations at onset.
Methods: We conducted an observational multicenter cohort study by retrospectively collecting data from the medical records of 84 patients diagnosed with definite, probable, or possible neurosarcoidosis in three tertiary referral centers in France (Nancy, Strasbourg, and Bordeaux). We collected demographic characteristics, clinical and paraclinical data at the beginning of patient management, and during follow-up under the different treatment lines. Two expert neurologists determined disease course profiles.
Results: The mean follow-up was 6.6 years. Almost every patient (96.4%) received steroids at some point of their follow-up. Tumor Necrosis Factor-alpha blockers were given in 10.7% as first-line treatment and in 33.3% during follow-up. Every patient presented with a relapsing disease, often monophasic (75%) and sometimes polyphasic with the recurrence of identical manifestations (11.9%). Patients developing new neurological symptoms during follow-up were a minority (13.1%). No patients exhibited a progressive course. Patients with isolated cranial nerves injury or aseptic meningitis always exhibited a monophasic course, and 62.5-75% of them had a full recovery after first-line treatments. This proportion was 15.6% in other forms of the disease. Those with peripheral presentations were more likely to present a polyphasic course than patients with other forms of neurosarcoidosis. Spinal cord presentations were monophasic, but resulted in sequelae and exhibited poor response to first-line treatments despite frequent use of TNF-alpha blockers.
Conclusion: Identification of these disease course profiles, based on the initial clinical and paraclinical presentation, could guide the clinician to select the optimal therapeutic approach and follow-up modalities for their patients with neurosarcoidosis.
{"title":"Defining the course of neurosarcoidosis according to presentation at onset and disease modifying treatment: a cohort study of 84 patients.","authors":"Inès Bekkour, Edouard Courtin, Cécile Dulau-Metras, Pierre Duffau, Laurent Kremer, Guillaume Mathey","doi":"10.1177/17562864231205954","DOIUrl":"https://doi.org/10.1177/17562864231205954","url":null,"abstract":"<p><strong>Background: </strong>Neurosarcoidosis is a rare manifestation of sarcoidosis with heterogeneous presentations. Patient management is challenging due to the current lack of knowledge about the long-term disease course.</p><p><strong>Objective: </strong>To identify specific disease courses of neurosarcoidosis according to the clinical and paraclinical presentations at onset.</p><p><strong>Methods: </strong>We conducted an observational multicenter cohort study by retrospectively collecting data from the medical records of 84 patients diagnosed with definite, probable, or possible neurosarcoidosis in three tertiary referral centers in France (Nancy, Strasbourg, and Bordeaux). We collected demographic characteristics, clinical and paraclinical data at the beginning of patient management, and during follow-up under the different treatment lines. Two expert neurologists determined disease course profiles.</p><p><strong>Results: </strong>The mean follow-up was 6.6 years. Almost every patient (96.4%) received steroids at some point of their follow-up. Tumor Necrosis Factor-alpha blockers were given in 10.7% as first-line treatment and in 33.3% during follow-up. Every patient presented with a relapsing disease, often monophasic (75%) and sometimes polyphasic with the recurrence of identical manifestations (11.9%). Patients developing new neurological symptoms during follow-up were a minority (13.1%). No patients exhibited a progressive course. Patients with isolated cranial nerves injury or aseptic meningitis always exhibited a monophasic course, and 62.5-75% of them had a full recovery after first-line treatments. This proportion was 15.6% in other forms of the disease. Those with peripheral presentations were more likely to present a polyphasic course than patients with other forms of neurosarcoidosis. Spinal cord presentations were monophasic, but resulted in sequelae and exhibited poor response to first-line treatments despite frequent use of TNF-alpha blockers.</p><p><strong>Conclusion: </strong>Identification of these disease course profiles, based on the initial clinical and paraclinical presentation, could guide the clinician to select the optimal therapeutic approach and follow-up modalities for their patients with neurosarcoidosis.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15eCollection Date: 2023-01-01DOI: 10.1177/17562864231216637
Jeremy Molad, Hen Hallevi, Estelle Seyman, Einor Ben-Assayag, Tali Jonas-Kimchi, Udi Sadeh, Ofer Rotschild, Naaem Simaan, Anat Horev, Jose Cohen, Ronen R Leker, Asaf Honig
Background: The role of intravenous thrombolysis (IVT) as bridging treatment prior to endovascular thrombectomy (EVT) is under debate and better patient selection is needed.
Objectives: As the efficacy and safety of IVT diminish with time, we aimed to examine the impact of bridging treatment within different time frames from symptom onset.
Design: A retrospective registry study.
Methods: Data were extracted from ongoing prospective EVT registries in two large tertiary centers. The current study included IVT-eligible patients with onset to door (OTD) < 4 h. We examined the efficacy and safety of bridging treatment through a comparison of the IVT + EVT group with the direct-EVT group by different time frames.
Results: In all, 408 patients (age 71.1 ± 14.6, 50.6% males) were included, among them 195 received IVT + EVT and 213 underwent direct EVT. Both groups had similar characteristics. In the IVT + EVT group only, longer OTD was associated with lower rates of favorable outcome (p = 0.021) and higher rates of hemorrhagic transformation (HT; p = 0.001). In patients with OTD ⩽ 2 h, IVT + EVT compared to direct EVT had higher rates of TICI 2b-3 (86.2% versus 80.7%, p = 0.038). In patients with OTD > 2 h, IVT + EVT had lower rates of favorable outcome (33.3% versus 56.9%, p = 0.021), worse discharge National Institutes of Health Stroke Scale [7 (2-13) versus 3 (1-8), p = 0.024], and higher rates of HT (34.0% versus 8.5%, p < 0.001).
Discussion: In this study, we found OTD times to have a significant effect on the impact of IVT bridging treatment. Our study shows that among patients with OTD < 2 h bridging treatment may be associated with higher rates of successful recanalization. By contrast, in patients with OTD > 2 h, bridging treatment was associated with worse outcomes. Further time-sensitive randomized trials are needed.
{"title":"The pivotal role of timing of intravenous thrombolysis bridging treatment prior to endovascular thrombectomy.","authors":"Jeremy Molad, Hen Hallevi, Estelle Seyman, Einor Ben-Assayag, Tali Jonas-Kimchi, Udi Sadeh, Ofer Rotschild, Naaem Simaan, Anat Horev, Jose Cohen, Ronen R Leker, Asaf Honig","doi":"10.1177/17562864231216637","DOIUrl":"https://doi.org/10.1177/17562864231216637","url":null,"abstract":"<p><strong>Background: </strong>The role of intravenous thrombolysis (IVT) as bridging treatment prior to endovascular thrombectomy (EVT) is under debate and better patient selection is needed.</p><p><strong>Objectives: </strong>As the efficacy and safety of IVT diminish with time, we aimed to examine the impact of bridging treatment within different time frames from symptom onset.</p><p><strong>Design: </strong>A retrospective registry study.</p><p><strong>Methods: </strong>Data were extracted from ongoing prospective EVT registries in two large tertiary centers. The current study included IVT-eligible patients with onset to door (OTD) < 4 h. We examined the efficacy and safety of bridging treatment through a comparison of the IVT + EVT group with the direct-EVT group by different time frames.</p><p><strong>Results: </strong>In all, 408 patients (age 71.1 ± 14.6, 50.6% males) were included, among them 195 received IVT + EVT and 213 underwent direct EVT. Both groups had similar characteristics. In the IVT + EVT group only, longer OTD was associated with lower rates of favorable outcome (<i>p</i> = 0.021) and higher rates of hemorrhagic transformation (HT; <i>p</i> = 0.001). In patients with OTD ⩽ 2 h, IVT + EVT compared to direct EVT had higher rates of TICI 2b-3 (86.2% <i>versus</i> 80.7%, <i>p</i> = 0.038). In patients with OTD > 2 h, IVT + EVT had lower rates of favorable outcome (33.3% <i>versus</i> 56.9%, <i>p</i> = 0.021), worse discharge National Institutes of Health Stroke Scale [7 (2-13) <i>versus</i> 3 (1-8), <i>p</i> = 0.024], and higher rates of HT (34.0% <i>versus</i> 8.5%, <i>p</i> < 0.001).</p><p><strong>Discussion: </strong>In this study, we found OTD times to have a significant effect on the impact of IVT bridging treatment. Our study shows that among patients with OTD < 2 h bridging treatment may be associated with higher rates of successful recanalization. By contrast, in patients with OTD > 2 h, bridging treatment was associated with worse outcomes. Further time-sensitive randomized trials are needed.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Thrombotic microangiopathy (TMA) is a rare side effect of interferon-beta (IFN-β) therapy. The clinical characteristics of IFN-β-induced TMA are unknown.
Objectives: To explore the clinical characteristics of IFN-β-induced TMA and provide reference for the prevention of TMA.
Design: Articles on IFN-β-induced TMA were collected by searching the literature in relevant Chinese and English databases from inception to 31 July 2023.
Methods: Data in the articles were extracted and analyzed retrospectively.
Results: Forty-seven patients, with a median age of 41 years (range 22, 66), were included in the analysis. The median time to the diagnosis of IFN-β-induced TMA was 8 years (range 0.1-30) after administration. The main clinical symptoms were neurological symptoms (51.1%), hypertension (78.7%), dyspnea (19.1%), edema (19.1%), asthenia/fatigue (19.1%), and digestive symptoms (17.0%). Most patients presented with hemolytic anemia (76.6%), thrombocytopenia (63.8%), and acute kidney injury (70.2%). All patients stopped IFN-β and received plasma exchange therapy (53.2%), systemic steroids (46.8%), antihypertensive therapy (46.8%), eculizumab (12.8%), and rituximab (12.8%). Kidney damage was not completely reversible; 40.4% of patients achieved renal function and hematology remission, 27.7% developed chronic kidney disease, 25.5% developed end-stage renal disease, and 2.1% died.
Conclusion: IFN-β-induced TMA is a rare but serious complication that can be life-threatening. It may occur after many years of IFN-β therapy, and patients taking IFN-β should be monitored for symptoms such as headache and hypertension.
{"title":"Clinical characteristics, treatments, and outcomes of interferon-beta-induced thrombotic microangiopathy: a literature-based retrospective analysis.","authors":"Chunjiang Wang, Weijin Fang, Wei Sun, Shaoli Zhao, Liping Peng","doi":"10.1177/17562864231216634","DOIUrl":"https://doi.org/10.1177/17562864231216634","url":null,"abstract":"<p><strong>Background: </strong>Thrombotic microangiopathy (TMA) is a rare side effect of interferon-beta (IFN-β) therapy. The clinical characteristics of IFN-β-induced TMA are unknown.</p><p><strong>Objectives: </strong>To explore the clinical characteristics of IFN-β-induced TMA and provide reference for the prevention of TMA.</p><p><strong>Design: </strong>Articles on IFN-β-induced TMA were collected by searching the literature in relevant Chinese and English databases from inception to 31 July 2023.</p><p><strong>Methods: </strong>Data in the articles were extracted and analyzed retrospectively.</p><p><strong>Results: </strong>Forty-seven patients, with a median age of 41 years (range 22, 66), were included in the analysis. The median time to the diagnosis of IFN-β-induced TMA was 8 years (range 0.1-30) after administration. The main clinical symptoms were neurological symptoms (51.1%), hypertension (78.7%), dyspnea (19.1%), edema (19.1%), asthenia/fatigue (19.1%), and digestive symptoms (17.0%). Most patients presented with hemolytic anemia (76.6%), thrombocytopenia (63.8%), and acute kidney injury (70.2%). All patients stopped IFN-β and received plasma exchange therapy (53.2%), systemic steroids (46.8%), antihypertensive therapy (46.8%), eculizumab (12.8%), and rituximab (12.8%). Kidney damage was not completely reversible; 40.4% of patients achieved renal function and hematology remission, 27.7% developed chronic kidney disease, 25.5% developed end-stage renal disease, and 2.1% died.</p><p><strong>Conclusion: </strong>IFN-β-induced TMA is a rare but serious complication that can be life-threatening. It may occur after many years of IFN-β therapy, and patients taking IFN-β should be monitored for symptoms such as headache and hypertension.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15eCollection Date: 2023-01-01DOI: 10.1177/17562864231214041
Juliane Klehmet, Yvonne Begus-Nahrmann, Kirsi Taipale, Gabriele Niemczyk, Karin Rehberg-Weber
Background: Based on data from two large cohort studies, a label update became applicable for the class of interferon beta therapies in 9/2019, allowing interferons during pregnancy and breastfeeding.
Objective: To assess pregnancy outcomes of women with multiple sclerosis (MS) exposed to peginterferon beta-1a or intramuscular interferon beta-1a therapy (IFN).
Methods: PRIMA was conducted from April to October 2021 in Germany. Retrospective pregnancy data were retrieved from adult female patients diagnosed with relapsing-remitting MS or clinically isolated syndrome, exposed to IFN before or during pregnancy and registered in the patient support programme (PSP) of the marketing authorization holder's MS Service Centre. The primary endpoint was the outcome of pregnancy. Prospective postpartum data were collected from mothers reporting live births.
Results: In total, 426 women reporting 542 pregnancies between December 2001 and July 2020 (14 pregnancies after the label update) were enrolled. Among patients with confirmed exposure during pregnancy (N = 362), 306 pregnancies (84.5%) resulted in live births (77.6% without defects, 1.9% with defects and 4.4% preterm). Spontaneous abortion, elective termination and stillbirth were reported in 10.9%, 2.8% and 0.2% of the cases, respectively. Higher rates of spontaneous abortions were reported in women with continuous IFN use. A total of 162 women completed the questionnaire for 192 live births within the prospective study part. Mothers restarted IFN therapy or switched to another disease-modifying therapy postpartum in 51.0% and 14.1% of cases, respectively. 158/192 infants (82.3%) were breastfed [34/158 (21.5%)] during IFN therapy. Postpartum relapse activity was low (mothers of 87.3% of breastfed infants remained relapse-free during lactation).
Conclusion: Overall, the prevalence of spontaneous abortions and congenital anomalies of females exposed to IFN exposure before or during pregnancy was within the range reported for the general population. Most mothers paused IFN during pregnancy and breastfeeding. Relapse activity during pregnancy and lactation was observed to be low. These real-world data from a PSP corroborate European and Scandinavian registry data.
{"title":"Pregnancy outcomes in female multiple sclerosis patients exposed to intramuscular interferon beta-1a or peginterferon beta-1a reported in a German Patient Support Programme - results from the non-interventional post-authorization safety study PRIMA.","authors":"Juliane Klehmet, Yvonne Begus-Nahrmann, Kirsi Taipale, Gabriele Niemczyk, Karin Rehberg-Weber","doi":"10.1177/17562864231214041","DOIUrl":"https://doi.org/10.1177/17562864231214041","url":null,"abstract":"<p><strong>Background: </strong>Based on data from two large cohort studies, a label update became applicable for the class of interferon beta therapies in 9/2019, allowing interferons during pregnancy and breastfeeding.</p><p><strong>Objective: </strong>To assess pregnancy outcomes of women with multiple sclerosis (MS) exposed to peginterferon beta-1a or intramuscular interferon beta-1a therapy (IFN).</p><p><strong>Design: </strong>Non-interventional post-authorization safety study.</p><p><strong>Methods: </strong>PRIMA was conducted from April to October 2021 in Germany. Retrospective pregnancy data were retrieved from adult female patients diagnosed with relapsing-remitting MS or clinically isolated syndrome, exposed to IFN before or during pregnancy and registered in the patient support programme (PSP) of the marketing authorization holder's MS Service Centre. The primary endpoint was the outcome of pregnancy. Prospective postpartum data were collected from mothers reporting live births.</p><p><strong>Results: </strong>In total, 426 women reporting 542 pregnancies between December 2001 and July 2020 (14 pregnancies after the label update) were enrolled. Among patients with confirmed exposure during pregnancy (<i>N</i> = 362), 306 pregnancies (84.5%) resulted in live births (77.6% without defects, 1.9% with defects and 4.4% preterm). Spontaneous abortion, elective termination and stillbirth were reported in 10.9%, 2.8% and 0.2% of the cases, respectively. Higher rates of spontaneous abortions were reported in women with continuous IFN use. A total of 162 women completed the questionnaire for 192 live births within the prospective study part. Mothers restarted IFN therapy or switched to another disease-modifying therapy postpartum in 51.0% and 14.1% of cases, respectively. 158/192 infants (82.3%) were breastfed [34/158 (21.5%)] during IFN therapy. Postpartum relapse activity was low (mothers of 87.3% of breastfed infants remained relapse-free during lactation).</p><p><strong>Conclusion: </strong>Overall, the prevalence of spontaneous abortions and congenital anomalies of females exposed to IFN exposure before or during pregnancy was within the range reported for the general population. Most mothers paused IFN during pregnancy and breastfeeding. Relapse activity during pregnancy and lactation was observed to be low. These real-world data from a PSP corroborate European and Scandinavian registry data.</p><p><strong>Trial registration: </strong>NCT04655222, EUPAS38347.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-09eCollection Date: 2023-01-01DOI: 10.1177/17562864231211077
Valerie E Teschner, Ann-Katrin Fleck, Carolin Walter, Anna-Sophie Schwarze, Melanie Eschborn, Timo Wirth, Olga V Steinberg, Andreas Schulte-Mecklenbeck, I-Na Lu, Marisol Herrera-Rivero, Claudia Janoschka, Jan D Lünemann, Nicholas Schwab, Gerd Meyer Zu Hörste, Julian Varghese, Catharina C Gross, Refik Pul, Christoph Kleinschnitz, Simone Mader, Edgar Meinl, Monika Stoll, Heinz Wiendl, Luisa Klotz
Background: Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect.
Objectives: Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response.
Design: We performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years.
Methods: We performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4+ T cells, CD8+ T cells, and CD19+ B cells as well as single-cell RNA sequencing of peripheral blood mononuclear cells in a total of 23 MS patients before and at different time points up to 24 months after cladribine treatment. Data were correlated with clinical and cranial magnetic resonance imaging (MRI) disease activity.
Results: Flow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity.
Conclusion: We describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.
背景:克拉利宾是一种高效的免疫疗法,在两年内分两个短期疗程使用,可降低复发性多发性硬化症(MS)患者的复发率和疾病进展。尽管治疗时间较短,但即使在淋巴细胞计数恢复后,克拉利宾仍能对疾病活动产生长期影响,这表明克拉利宾具有尚未确定的长期免疫调节作用:我们的目的是更深入地了解克拉利宾的详细作用,以及患者的治疗反应:设计:我们进行了一项开放标签、探索性、前瞻性、单臂研究,研究了接受克拉利宾治疗两年以上的多发性硬化症患者淋巴细胞亚群的详细发展情况:我们通过流式细胞术、CD4+ T细胞、CD8+ T细胞和CD19+ B细胞的大量RNA测序以及外周血单核细胞的单细胞RNA测序,深入分析了克拉利宾对外周血淋巴细胞的影响。数据与临床和头颅磁共振成像(MRI)疾病活动相关:结果:流式细胞术显示,与其他 B 细胞亚群相比,记忆 B 细胞在克拉利宾治疗后主要持续减少,而 T 细胞亚群则以更均匀的模式略有减少。全血 B 细胞的整体转录谱显示促炎症基因和 T 细胞激活基因的表达减少,而单细胞转录组学显示,每个 B 细胞集群内的基因表达并没有随着时间的推移而改变。与有临床或脑磁共振成像疾病活动的患者相比,病情稳定的患者所选择的记忆B细胞集群减少得更厉害:我们描述了克拉利宾对记忆 B 细胞区系的明显而持续的影响,由此导致的 B 细胞亚群组成的变化引起了 B 细胞转录谱的显著改变,从而降低了促炎和激活 T 细胞的能力。克拉利宾对特定记忆 B 细胞群的抑制程度可预测治疗反应。
{"title":"Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response.","authors":"Valerie E Teschner, Ann-Katrin Fleck, Carolin Walter, Anna-Sophie Schwarze, Melanie Eschborn, Timo Wirth, Olga V Steinberg, Andreas Schulte-Mecklenbeck, I-Na Lu, Marisol Herrera-Rivero, Claudia Janoschka, Jan D Lünemann, Nicholas Schwab, Gerd Meyer Zu Hörste, Julian Varghese, Catharina C Gross, Refik Pul, Christoph Kleinschnitz, Simone Mader, Edgar Meinl, Monika Stoll, Heinz Wiendl, Luisa Klotz","doi":"10.1177/17562864231211077","DOIUrl":"https://doi.org/10.1177/17562864231211077","url":null,"abstract":"<p><strong>Background: </strong>Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect.</p><p><strong>Objectives: </strong>Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response.</p><p><strong>Design: </strong>We performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years.</p><p><strong>Methods: </strong>We performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and CD19<sup>+</sup> B cells as well as single-cell RNA sequencing of peripheral blood mononuclear cells in a total of 23 MS patients before and at different time points up to 24 months after cladribine treatment. Data were correlated with clinical and cranial magnetic resonance imaging (MRI) disease activity.</p><p><strong>Results: </strong>Flow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity.</p><p><strong>Conclusion: </strong>We describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-22eCollection Date: 2023-01-01DOI: 10.1177/17562864231213243
Todd D Rozen, Zlatko Devcic, Andrew R Lewis, Sukhwinder J S Sandhu, Young Erben, Beau B Toskich
The authors have published on a unique subset of patients whose headaches worsened in the Trendelenburg position and who on time-resolved MR angiography demonstrated left renal vein compression (nutcracker physiology) with retrograde left second lumbar vein (L2LV) flow and regional spinal epidural venous plexus (EVP) congestion. We hypothesized that the spinal EVP congestion subsequently causes a secondary congestion of the cerebral venous system, which then leads to an elevation of CSF pressure above that individuals CSF pressure set point. This results in a daily headache from onset. Thus, eliminating the spinal EVP could conceivably improve or eliminate the manifested headache syndrome. We now present a case series of four patients with long-term follow-up utilizing lumbar vein coil embolization as a new therapeutic approach. In each patient, the MR angiography findings were verified by catheter-based venography. Treatment consisted of endovascular embolization of the second lumbar vein. Four patients have had coil embolization of which three are 1 year or longer from their procedure while one is 10 months posttreatment. All patients were women. Duration of daily headache prior to embolization ranged from 4 to 8 years. Post-embolization: Three patients are either headache free or 90-95% improved with substantial pain free time. There were no procedure-related complications. Our results suggest that embolization of L2LV in a specific patient population with nutcracker physiology may substantially improve head pain issues. This is a minimally invasive outpatient technique with no apparent side effects.
{"title":"A secondary daily persistent headache from onset with underlying nutcracker physiology and spinal epidural venous congestion: case series with lumbar vein embolization as a therapeutic approach.","authors":"Todd D Rozen, Zlatko Devcic, Andrew R Lewis, Sukhwinder J S Sandhu, Young Erben, Beau B Toskich","doi":"10.1177/17562864231213243","DOIUrl":"https://doi.org/10.1177/17562864231213243","url":null,"abstract":"<p><p>The authors have published on a unique subset of patients whose headaches worsened in the Trendelenburg position and who on time-resolved MR angiography demonstrated left renal vein compression (nutcracker physiology) with retrograde left second lumbar vein (L2LV) flow and regional spinal epidural venous plexus (EVP) congestion. We hypothesized that the spinal EVP congestion subsequently causes a secondary congestion of the cerebral venous system, which then leads to an elevation of CSF pressure above that individuals CSF pressure set point. This results in a daily headache from onset. Thus, eliminating the spinal EVP could conceivably improve or eliminate the manifested headache syndrome. We now present a case series of four patients with long-term follow-up utilizing lumbar vein coil embolization as a new therapeutic approach. In each patient, the MR angiography findings were verified by catheter-based venography. Treatment consisted of endovascular embolization of the second lumbar vein. Four patients have had coil embolization of which three are 1 year or longer from their procedure while one is 10 months posttreatment. All patients were women. Duration of daily headache prior to embolization ranged from 4 to 8 years. Post-embolization: Three patients are either headache free or 90-95% improved with substantial pain free time. There were no procedure-related complications. Our results suggest that embolization of L2LV in a specific patient population with nutcracker physiology may substantially improve head pain issues. This is a minimally invasive outpatient technique with no apparent side effects.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-18eCollection Date: 2023-01-01DOI: 10.1177/17562864231212254
Jiajie Mo, Wenyu Dong, Lin Sang, Zhong Zheng, Qiang Guo, Xiuming Zhou, Wenjing Zhou, Haixiang Wang, Xianghong Meng, Yi Yao, Fengpeng Wang, Wenhan Hu, Kai Zhang, Xiaoqiu Shao
Background: Posterior cortex epilepsy (PCE) primarily comprises seizures originating from the occipital, parietal, and/or posterior edge of the temporal lobe. Electroclinical dissociation and subtle imaging representation render the diagnosis of PCE challenging. Improved methods for accurately identifying patients with PCE are necessary.
Objectives: To develop a novel voxel-based image postprocessing method for better visual identification of the neuroimaging abnormalities associated with PCE.
Design: Multicenter, retrospective study.
Methods: Clinical and imaging features of 165 patients with PCE were retrospectively reviewed and collected from five epilepsy centers. A total of 37 patients (32.4% female, 20.2 ± 8.9 years old) with magnetic resonance imaging (MRI)-negative PCE were finally included for analysis. Image postprocessing features were calculated over a neighborhood for each voxel in the multimodality data. The postprocessed maps comprised structural deformation, hyperintense signal, and hypometabolism. Five raters from three different centers were blinded to the clinical diagnosis and determined the neuroimaging abnormalities in the postprocessed maps.
Results: The average accuracy of correct identification was 55.7% (range from 43.2 to 62.2%) and correct lateralization was 74.1% (range from 64.9 to 81.1%). The Cronbach's alpha was 0.766 for the correct identification and 0.683 for the correct lateralization with similar results of the interclass correlation coefficient, thus indicating reliable agreement between the raters.
Conclusion: The image postprocessing method developed in this study can potentially improve the visual detection of MRI-negative PCE. The technique could lead to an increase in the number of patients with PCE who could benefit from the surgery.
{"title":"Multimodal imaging-based diagnostic approach for MRI-negative posterior cortex epilepsy.","authors":"Jiajie Mo, Wenyu Dong, Lin Sang, Zhong Zheng, Qiang Guo, Xiuming Zhou, Wenjing Zhou, Haixiang Wang, Xianghong Meng, Yi Yao, Fengpeng Wang, Wenhan Hu, Kai Zhang, Xiaoqiu Shao","doi":"10.1177/17562864231212254","DOIUrl":"https://doi.org/10.1177/17562864231212254","url":null,"abstract":"<p><strong>Background: </strong>Posterior cortex epilepsy (PCE) primarily comprises seizures originating from the occipital, parietal, and/or posterior edge of the temporal lobe. Electroclinical dissociation and subtle imaging representation render the diagnosis of PCE challenging. Improved methods for accurately identifying patients with PCE are necessary.</p><p><strong>Objectives: </strong>To develop a novel voxel-based image postprocessing method for better visual identification of the neuroimaging abnormalities associated with PCE.</p><p><strong>Design: </strong>Multicenter, retrospective study.</p><p><strong>Methods: </strong>Clinical and imaging features of 165 patients with PCE were retrospectively reviewed and collected from five epilepsy centers. A total of 37 patients (32.4% female, 20.2 ± 8.9 years old) with magnetic resonance imaging (MRI)-negative PCE were finally included for analysis. Image postprocessing features were calculated over a neighborhood for each voxel in the multimodality data. The postprocessed maps comprised structural deformation, hyperintense signal, and hypometabolism. Five raters from three different centers were blinded to the clinical diagnosis and determined the neuroimaging abnormalities in the postprocessed maps.</p><p><strong>Results: </strong>The average accuracy of correct identification was 55.7% (range from 43.2 to 62.2%) and correct lateralization was 74.1% (range from 64.9 to 81.1%). The Cronbach's alpha was 0.766 for the correct identification and 0.683 for the correct lateralization with similar results of the interclass correlation coefficient, thus indicating reliable agreement between the raters.</p><p><strong>Conclusion: </strong>The image postprocessing method developed in this study can potentially improve the visual detection of MRI-negative PCE. The technique could lead to an increase in the number of patients with PCE who could benefit from the surgery.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-16eCollection Date: 2023-01-01DOI: 10.1177/17562864231207272
Laura Schnetzer, Jürgen Steinbacher, Gerhard Bauer, Alexander Baden Kunz, Jürgen Bergmann, Martin Kronbichler, Eugen Trinka, Mark McCoy
The locked-in syndrome (LiS) is defined as the loss of most voluntary muscle movements with preserved cognitive abilities due to a ventral pontine lesion. However, some patients may also have severe impairment of consciousness [locked-in plus syndrome (LiPS)]. Here we aimed to explore structural differences between LiS and LiPS patients of vascular aetiology, focusing on lesion patterns and locations to better delineate the clinical spectrum of LiS and LiPS. In this retrospective case series study, we report nine patients (two women), ages 29-74 years (median 50) with LiS and LiPS who were diagnosed between 2007 and 2021. Clinical parameters, MRI findings including the lesioned structures, and a shape feature calculation are presented for every patient. The lesioned structures were determined by a senior neuroradiologist. Two of nine patients had fully retained consciousness (LiS) and seven showed various degrees of impaired consciousness (LiPS). Lesions of LiS patients are round and confined to the pons, whereas lesions of LiPS patients are more elongated and reach neighbouring areas such as the mesencephalon, thalamus or ascending reticular activating system. Lesions involving the mesencephalon and the thalamus are strong indicators of LiPS, whereas for lesions restricted to the pons, the dorsal extension and the associated damage to the ascending reticular activating system are crucial to differentiate LiS from LiPS. Recognizing LiPS using clinical and radiological findings is important as these patients may need different therapies and care and, most importantly, should not be mistaken as unresponsive wakefulness syndrome.
{"title":"The vascular locked-in and locked-in-plus syndrome: A retrospective case series.","authors":"Laura Schnetzer, Jürgen Steinbacher, Gerhard Bauer, Alexander Baden Kunz, Jürgen Bergmann, Martin Kronbichler, Eugen Trinka, Mark McCoy","doi":"10.1177/17562864231207272","DOIUrl":"https://doi.org/10.1177/17562864231207272","url":null,"abstract":"<p><p>The locked-in syndrome (LiS) is defined as the loss of most voluntary muscle movements with preserved cognitive abilities due to a ventral pontine lesion. However, some patients may also have severe impairment of consciousness [locked-in plus syndrome (LiPS)]. Here we aimed to explore structural differences between LiS and LiPS patients of vascular aetiology, focusing on lesion patterns and locations to better delineate the clinical spectrum of LiS and LiPS. In this retrospective case series study, we report nine patients (two women), ages 29-74 years (median 50) with LiS and LiPS who were diagnosed between 2007 and 2021. Clinical parameters, MRI findings including the lesioned structures, and a shape feature calculation are presented for every patient. The lesioned structures were determined by a senior neuroradiologist. Two of nine patients had fully retained consciousness (LiS) and seven showed various degrees of impaired consciousness (LiPS). Lesions of LiS patients are round and confined to the pons, whereas lesions of LiPS patients are more elongated and reach neighbouring areas such as the mesencephalon, thalamus or ascending reticular activating system. Lesions involving the mesencephalon and the thalamus are strong indicators of LiPS, whereas for lesions restricted to the pons, the dorsal extension and the associated damage to the ascending reticular activating system are crucial to differentiate LiS from LiPS. Recognizing LiPS using clinical and radiological findings is important as these patients may need different therapies and care and, most importantly, should not be mistaken as unresponsive wakefulness syndrome.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-10eCollection Date: 2023-01-01DOI: 10.1177/17562864231200627
Kimberley Allen-Philbey, Stefania De Trane, Amy MacDougall, Ashok Adams, Lucia Bianchi, Thomas Campion, Gavin Giovannoni, Sharmilee Gnanapavan, David W Holden, Monica Marta, Joela Mathews, Benjamin P Turner, David Baker, Klaus Schmierer
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.
{"title":"Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis.","authors":"Kimberley Allen-Philbey, Stefania De Trane, Amy MacDougall, Ashok Adams, Lucia Bianchi, Thomas Campion, Gavin Giovannoni, Sharmilee Gnanapavan, David W Holden, Monica Marta, Joela Mathews, Benjamin P Turner, David Baker, Klaus Schmierer","doi":"10.1177/17562864231200627","DOIUrl":"10.1177/17562864231200627","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>Of <i>n</i> = 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.</p><p><strong>Conclusion: </strong>Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}