Pub Date : 2025-01-22DOI: 10.1136/jnnp-2024-335325
Valerian L Altersberger, Johannes Kaesmacher, Leonid Churilov, Vignan Yogendrakumar, Jan Gralla, Daniel Strbian, David J Seiffge, Peter J Mitchell, Timothy J Kleinig, Bruce Cv Campbell, Urs Fischer
Background: Whether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear.
Methods: This is a causal inference study of observational data from the trials SWIFT DIRECT and EXTEND-IA TNK Parts 1 and 2 applying target trial emulation. We compared patients receiving thrombectomy alone to patients receiving tenecteplase 0.25 mg/kg or 0.40 mg/kg before thrombectomy. The primary outcome was functional independence (modified Rankin Scale (mRS) of 0-2) at 90 days. Secondary outcomes included improvement over the full ordinal mRS scale, freedom of disability (mRS 0-1), mortality and occurrence of symptomatic intracranial haemorrhage. The average causal treatment effect was estimated via inverse probability of treatment weighting and G-Computation. We calculated standardised risk differences (SRDs) and adjusted (common) ORs (a(c)ORs).
Results: Of 377 patients included in the target trial, 187 received thrombectomy alone and 190 tenecteplase before thrombectomy. Tenecteplase before thrombectomy did not increase the probability of patients achieving functional independence (SRD 0.04 (95% CI -0.06 to 0.13)) but resulted in a significant improvement in the mRS overall (acOR 1.56 (95% CI 1.07 to 2.23)) and in a higher probability of freedom from disability (SRD 0.10 (95% CI 0.01 to 0.20)). The probability for improvement of functional outcomes was further increased in patients treated within 140 min after onset (ordinal mRS acOR 1.63 (95% CI 1.04 to 2.56)). No significant differences in safety outcomes were observed between the two groups.
Conclusion: Tenecteplase before thrombectomy compared with thrombectomy alone did not increase the probability of functional independence but resulted in significant improvement over the full mRS scale. This improvement was most evident in patients treated early.
{"title":"Bridging thrombolysis with tenecteplase versus endovascular thrombectomy alone for large-vessel anterior circulation stroke: a target trial emulation analysis.","authors":"Valerian L Altersberger, Johannes Kaesmacher, Leonid Churilov, Vignan Yogendrakumar, Jan Gralla, Daniel Strbian, David J Seiffge, Peter J Mitchell, Timothy J Kleinig, Bruce Cv Campbell, Urs Fischer","doi":"10.1136/jnnp-2024-335325","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335325","url":null,"abstract":"<p><strong>Background: </strong>Whether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear.</p><p><strong>Methods: </strong>This is a causal inference study of observational data from the trials SWIFT DIRECT and EXTEND-IA TNK Parts 1 and 2 applying target trial emulation. We compared patients receiving thrombectomy alone to patients receiving tenecteplase 0.25 mg/kg or 0.40 mg/kg before thrombectomy. The primary outcome was functional independence (modified Rankin Scale (mRS) of 0-2) at 90 days. Secondary outcomes included improvement over the full ordinal mRS scale, freedom of disability (mRS 0-1), mortality and occurrence of symptomatic intracranial haemorrhage. The average causal treatment effect was estimated via inverse probability of treatment weighting and G-Computation. We calculated standardised risk differences (SRDs) and adjusted (common) ORs (a(c)ORs).</p><p><strong>Results: </strong>Of 377 patients included in the target trial, 187 received thrombectomy alone and 190 tenecteplase before thrombectomy. Tenecteplase before thrombectomy did not increase the probability of patients achieving functional independence (SRD 0.04 (95% CI -0.06 to 0.13)) but resulted in a significant improvement in the mRS overall (acOR 1.56 (95% CI 1.07 to 2.23)) and in a higher probability of freedom from disability (SRD 0.10 (95% CI 0.01 to 0.20)). The probability for improvement of functional outcomes was further increased in patients treated within 140 min after onset (ordinal mRS acOR 1.63 (95% CI 1.04 to 2.56)). No significant differences in safety outcomes were observed between the two groups.</p><p><strong>Conclusion: </strong>Tenecteplase before thrombectomy compared with thrombectomy alone did not increase the probability of functional independence but resulted in significant improvement over the full mRS scale. This improvement was most evident in patients treated early.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-19DOI: 10.1136/jnnp-2024-334957
Smathorn Thakolwiboon, Michael Gilligan, Emma Orozco, Jeffrey W Britton, Divyanshu Dubey, Eoin P Flanagan, A Sebastian Lopez-Chiriboga, Kelsey Smith, Cristina Valencia-Sanchez, Nicholas L Zalewski, Anastasia Zekeridou, Sean J Pittock, Andrew McKeon
Background: Data regarding long-term recovery from autoimmune encephalitis (AE) remain limited.
Methods: This retrospective observational study investigated outcomes in 182 patients who met the 2016 criteria for definite AE. Recovery data were available in 172 patients. Follow-up data at ≥24 months post-attack were available for 119. Recovery trajectory, residual symptoms, outcome predictors and causes of post-AE death were assessed.
Results: Of 172 patients, 138 (80%) achieved good recovery (modified Rankin Scale (mRS) ≤2) with a median recovery time of 4 months (95% CI: 2 to 6 months). Recovery varied by associated neural antibody, with the best recovery observed in leucine-rich glioma-inactivated 1 (97% good recovery, median recovery time 0 (0 to 2) months). Paraneoplastic AE (p=0.007), severe attacks (eg, mRS ≥4 at attack, p=0.007) and cerebrospinal fluid pleocytosis (p=0.005) were associated with a lower likelihood of good recovery, while seizure presentation (p=0.026) was associated with better recovery. Despite good recovery, several residual symptoms persisted ≥24 months post-AE, including cognitive deficits (53%), seizures (26%), depression (23%), sleep disorders (25%), brainstem/cerebellar symptoms (13%), other movement disorders (14%) and autonomic symptoms (12%). Predictors of long-term sequelae included disabling cognitive deficit at onset and delayed immunotherapy for post AE-dementia, and medial temporal atrophy as well as escalation to cyclophosphamide therapy for both drug-resistant epilepsy and chronic depression. Of 182 patients, 20 (11%) died; the most common cause of death was progression of AE (6/20 (30%)).
Conclusion: While the majority of patients achieved functional independence after AE, several residual symptoms persisted. Several clinical and paraclinical features were associated with long-term sequelae.
{"title":"Autoimmune encephalitis: recovery, residual symptoms and predictors of long-term sequelae.","authors":"Smathorn Thakolwiboon, Michael Gilligan, Emma Orozco, Jeffrey W Britton, Divyanshu Dubey, Eoin P Flanagan, A Sebastian Lopez-Chiriboga, Kelsey Smith, Cristina Valencia-Sanchez, Nicholas L Zalewski, Anastasia Zekeridou, Sean J Pittock, Andrew McKeon","doi":"10.1136/jnnp-2024-334957","DOIUrl":"https://doi.org/10.1136/jnnp-2024-334957","url":null,"abstract":"<p><strong>Background: </strong>Data regarding long-term recovery from autoimmune encephalitis (AE) remain limited.</p><p><strong>Methods: </strong>This retrospective observational study investigated outcomes in 182 patients who met the 2016 criteria for definite AE. Recovery data were available in 172 patients. Follow-up data at ≥24 months post-attack were available for 119. Recovery trajectory, residual symptoms, outcome predictors and causes of post-AE death were assessed.</p><p><strong>Results: </strong>Of 172 patients, 138 (80%) achieved good recovery (modified Rankin Scale (mRS) ≤2) with a median recovery time of 4 months (95% CI: 2 to 6 months). Recovery varied by associated neural antibody, with the best recovery observed in leucine-rich glioma-inactivated 1 (97% good recovery, median recovery time 0 (0 to 2) months). Paraneoplastic AE (p=0.007), severe attacks (eg, mRS ≥4 at attack, p=0.007) and cerebrospinal fluid pleocytosis (p=0.005) were associated with a lower likelihood of good recovery, while seizure presentation (p=0.026) was associated with better recovery. Despite good recovery, several residual symptoms persisted ≥24 months post-AE, including cognitive deficits (53%), seizures (26%), depression (23%), sleep disorders (25%), brainstem/cerebellar symptoms (13%), other movement disorders (14%) and autonomic symptoms (12%). Predictors of long-term sequelae included disabling cognitive deficit at onset and delayed immunotherapy for post AE-dementia, and medial temporal atrophy as well as escalation to cyclophosphamide therapy for both drug-resistant epilepsy and chronic depression. Of 182 patients, 20 (11%) died; the most common cause of death was progression of AE (6/20 (30%)).</p><p><strong>Conclusion: </strong>While the majority of patients achieved functional independence after AE, several residual symptoms persisted. Several clinical and paraclinical features were associated with long-term sequelae.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-333947
Victor Hvingelby, Fareha Khalil, Flavia Massey, Alexander Hoyningen, San San Xu, Joseph Candelario-McKeown, Harith Akram, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Marie T Krüger
Background: Since their introduction in 2015, directional leads have practically replaced conventional leads for deep brain stimulation (DBS) in Parkinson's disease (PD). Yet, the benefits of directional DBS (dDBS) over omnidirectional DBS (oDBS) remain unclear. This meta-analysis and systematic review compares the literature on dDBS and oDBS for PD.
Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Database searches included Pubmed, Cochrane (CENTRAL) and EmBase, using relevant keywords such as 'directional', 'segmented', 'brain stimulation' and 'neuromodulation'. The screening was based on the title and abstract.
Results: 23 papers reporting on 1273 participants (1542 leads) were included. The therapeutic window was 0.70 mA wider when using dDBS (95% CI 0.13 to 1.26 mA, p=0.02), with a lower therapeutic current (0.41 mA, 95% CI 0.27 to 0.54 mA, p=0.01) and a higher side-effect threshold (0.56 mA, 95% CI 0.38 to 0.73 mA, p<0.01). However, there was no relevant difference in mean Unified Parkinson's Disease Rating Scale III change after dDBS (45.8%, 95% CI 30.7% to 60.9%) compared with oDBS (39.0%, 95% CI 36.9% to 41.2%, p=0.39), in the medication-OFF state. Median follow-up time for dDBS and oDBS studies was 6 months and 3 months, respectively (range 3-12 for both). The use of directionality often improves dyskinesia, dysarthria, dysesthesia and pyramidal side effects. Directionality was used in 55% of directional leads at 3-6 months, remaining stable over time (56% at a mean of 14.1 months).
Conclusions: These findings suggest that stimulation parameters favour dDBS. However, these do not appear to have a significant impact on motor scores, and the availability of long-term data is limited. dDBS is widely accepted, but clinical data justifying its increased complexity and cost are currently sparse.
{"title":"Directional deep brain stimulation electrodes in Parkinson's disease: meta-analysis and systematic review of the literature.","authors":"Victor Hvingelby, Fareha Khalil, Flavia Massey, Alexander Hoyningen, San San Xu, Joseph Candelario-McKeown, Harith Akram, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Marie T Krüger","doi":"10.1136/jnnp-2024-333947","DOIUrl":"10.1136/jnnp-2024-333947","url":null,"abstract":"<p><strong>Background: </strong>Since their introduction in 2015, directional leads have practically replaced conventional leads for deep brain stimulation (DBS) in Parkinson's disease (PD). Yet, the benefits of directional DBS (dDBS) over omnidirectional DBS (oDBS) remain unclear. This meta-analysis and systematic review compares the literature on dDBS and oDBS for PD.</p><p><strong>Methods: </strong>Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Database searches included Pubmed, Cochrane (CENTRAL) and EmBase, using relevant keywords such as 'directional', 'segmented', 'brain stimulation' and 'neuromodulation'. The screening was based on the title and abstract.</p><p><strong>Results: </strong>23 papers reporting on 1273 participants (1542 leads) were included. The therapeutic window was 0.70 mA wider when using dDBS (95% CI 0.13 to 1.26 mA, p=0.02), with a lower therapeutic current (0.41 mA, 95% CI 0.27 to 0.54 mA, p=0.01) and a higher side-effect threshold (0.56 mA, 95% CI 0.38 to 0.73 mA, p<0.01). However, there was no relevant difference in mean Unified Parkinson's Disease Rating Scale III change after dDBS (45.8%, 95% CI 30.7% to 60.9%) compared with oDBS (39.0%, 95% CI 36.9% to 41.2%, p=0.39), in the medication-OFF state. Median follow-up time for dDBS and oDBS studies was 6 months and 3 months, respectively (range 3-12 for both). The use of directionality often improves dyskinesia, dysarthria, dysesthesia and pyramidal side effects. Directionality was used in 55% of directional leads at 3-6 months, remaining stable over time (56% at a mean of 14.1 months).</p><p><strong>Conclusions: </strong>These findings suggest that stimulation parameters favour dDBS. However, these do not appear to have a significant impact on motor scores, and the availability of long-term data is limited. dDBS is widely accepted, but clinical data justifying its increased complexity and cost are currently sparse.</p><p><strong>Prospero registration number: </strong>CRD42023438056.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"188-198"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions.
Methods: We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in LRP12, GIPC1 and RILPL1 genes was conducted using PCR and long-read sequencing technologies.
Results: We identified CGG repeat expansions in LRP12 from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with LRP12-oculopharyngodistal myopathy (p<0.0001). Additionally, GIPC1 and RILPL1 repeat expansions were absent in our IPN cases.
Conclusion: We initially elucidate LRP12 repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.
{"title":"Linking LRP12 CGG repeat expansion to inherited peripheral neuropathy.","authors":"Takahiro Hobara, Masahiro Ando, Yujiro Higuchi, Jun-Hui Yuan, Akiko Yoshimura, Fumikazu Kojima, Yutaka Noguchi, Jun Takei, Yu Hiramatsu, Satoshi Nozuma, Tomonori Nakamura, Tadashi Adachi, Keiko Toyooka, Toru Yamashita, Yusuke Sakiyama, Akihiro Hashiguchi, Eiji Matsuura, Yuji Okamoto, Hiroshi Takashima","doi":"10.1136/jnnp-2024-333403","DOIUrl":"10.1136/jnnp-2024-333403","url":null,"abstract":"<p><strong>Background: </strong>The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions.</p><p><strong>Methods: </strong>We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in <i>LRP12</i>, <i>GIPC1</i> and <i>RILPL1</i> genes was conducted using PCR and long-read sequencing technologies.</p><p><strong>Results: </strong>We identified CGG repeat expansions in <i>LRP12</i> from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with <i>LRP12</i>-oculopharyngodistal myopathy (p<0.0001). Additionally, <i>GIPC1</i> and <i>RILPL1</i> repeat expansions were absent in our IPN cases.</p><p><strong>Conclusion: </strong>We initially elucidate <i>LRP12</i> repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"140-149"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-333759
Nicolas Martinez-Majander, Shakar Kutal, Pauli Ylikotila, Nilufer Yesilot, Lauri Tulkki, Marialuisa Zedde, Tomi Sarkanen, Ulla Junttola, Annika Nordanstig, Annette Fromm, Kristina Ryliskiene, Radim Licenik, Phillip Ferdinand, Dalius Jatuzis, Liisa Kõrv, Janika Kõrv, Alessandro Pezzini, Suvi Tuohinen, Juha Sinisalo, Mika Lehto, Eva Gerdts, Essi Ryödi, Jaana Autere, Marja Hedman, Ana Catarina Fonseca, Ulrike Waje-Andreassen, Bettina von Sarnowski, Petra Redfors, Tiina Sairanen, Turgut Tatlisumak, Risto O Roine, Juha Huhtakangas, Heikki Numminen, Pekka Jäkälä, Jukka Putaala
Background: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age.
Methods: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS.
Results: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women.
Conclusions: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.
{"title":"Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.","authors":"Nicolas Martinez-Majander, Shakar Kutal, Pauli Ylikotila, Nilufer Yesilot, Lauri Tulkki, Marialuisa Zedde, Tomi Sarkanen, Ulla Junttola, Annika Nordanstig, Annette Fromm, Kristina Ryliskiene, Radim Licenik, Phillip Ferdinand, Dalius Jatuzis, Liisa Kõrv, Janika Kõrv, Alessandro Pezzini, Suvi Tuohinen, Juha Sinisalo, Mika Lehto, Eva Gerdts, Essi Ryödi, Jaana Autere, Marja Hedman, Ana Catarina Fonseca, Ulrike Waje-Andreassen, Bettina von Sarnowski, Petra Redfors, Tiina Sairanen, Turgut Tatlisumak, Risto O Roine, Juha Huhtakangas, Heikki Numminen, Pekka Jäkälä, Jukka Putaala","doi":"10.1136/jnnp-2024-333759","DOIUrl":"10.1136/jnnp-2024-333759","url":null,"abstract":"<p><strong>Background: </strong>The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age.</p><p><strong>Methods: </strong>Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS.</p><p><strong>Results: </strong>Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women.</p><p><strong>Conclusions: </strong>Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"114-121"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-333690
Chris Kato, Satoru Morimoto, Shinichi Takahashi, Shinichi Namba, Qingbo S Wang, Yukinori Okada, Hideyuki Okano
{"title":"Spinal cord motor neuron phenotypes and polygenic risk scores in sporadic amyotrophic lateral sclerosis: deciphering the disease pathology and therapeutic potential of ropinirole hydrochloride.","authors":"Chris Kato, Satoru Morimoto, Shinichi Takahashi, Shinichi Namba, Qingbo S Wang, Yukinori Okada, Hideyuki Okano","doi":"10.1136/jnnp-2024-333690","DOIUrl":"10.1136/jnnp-2024-333690","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"199-201"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-334514
Yun-Hee Jeon, Judy Simpson, Judith Fethney, Luisa Krein, Mirim Shin, Lee-Fay Low, Robert T Woods, Loren Mowszowski, Sarah Hilmer, Sharon L Naismith, Lindy Clemson, Henry Brodaty, Vasi Naganathan, Amanda Miller Amberber, Danelle Kenny, Laura Gitlin, Sarah Szanton
Background: We investigated the effectiveness of an Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence, health and well-being of people with dementia, family carer outcomes and costs.
Method: A multicentre pragmatic parallel-arm randomised controlled trial compared I-HARP to usual care in community-dwelling people with mild to moderate dementia and their family carers in Sydney, Australia (2018-2022). I-HARP is a 4-month, home-based, dementia rehabilitation model delivered by an interdisciplinary team. Assessments were conducted at baseline (time-1), 4-month (time-2) and 12-month (time-3) follow-up. The primary outcome measure was the client's functional independence using the Disability Assessment for Dementia (DAD) scale at time-2, based on intention-to-treat analyses.
Result: Of 130 recruited client-carer dyads, 116 dyads (58/group) completed the trial. The I-HARP group were not significantly better in most outcome measures than usual care at both time-2 and time-3; with the only statistically significant difference being a reduction in home environment hazards at time-2. Post hoc subgroup analysis of 66 clients with mild dementia found significantly better functional independence in the intervention group compared with those in usual care: difference 8.99 on DAD (95% CI 1.21, 16.79) at time-2 and difference 12.16 (95% CI 1.93, 22.38) at time-3. Economic evaluation suggests potentially lower resource use in I-HARP compared with usual care, but the cost-effectiveness is uncertain.
Conclusion: Primary outcomes were not met for a population of people with dementia, with severity ranging from mild to moderate and severe. The I-HARP model appeared to benefit functional independence of participants with mild dementia, with potential cost savings.
Trial registration number: ACTRN12618000600246.
背景:我们调查了跨学科家庭康复计划(I-HARP)在改善痴呆患者的功能独立性、健康和福祉、家庭护理结果和成本方面的有效性。方法:一项多中心实用平行组随机对照试验比较了I-HARP与澳大利亚悉尼社区居住的轻度至中度痴呆患者及其家庭护理人员的常规护理(2018-2022)。I-HARP是一个跨学科团队提供的为期4个月、以家庭为基础的痴呆症康复模式。在基线(时间-1)、4个月(时间-2)和12个月(时间-3)随访时进行评估。主要结局指标是基于意向治疗分析,使用时间-2时痴呆残疾评估(DAD)量表评估患者的功能独立性。结果:在招募的130对客户-护理者中,116对(58/组)完成了试验。在时间-2和时间-3时,I-HARP组在大多数结局指标上都没有明显优于常规护理;唯一有统计学意义的区别是家庭环境危害在时间2上的减少。对66名轻度痴呆患者进行的事后亚组分析发现,干预组的功能独立性明显优于常规护理组:在第2次时,DAD差异为8.99 (95% CI 1.21, 16.79);在第3次时,差异为12.16 (95% CI 1.93, 22.38)。经济评价表明,与常规护理相比,I-HARP的资源使用可能更低,但成本效益尚不确定。结论:痴呆患者的主要结局未达到,其严重程度从轻度到中度到重度不等。I-HARP模型似乎有利于轻度痴呆参与者的功能独立性,具有潜在的成本节约。试验注册号:ACTRN12618000600246。
{"title":"Effectiveness of the Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence of people living with dementia: a multicentre, pragmatic, randomised, open-label, controlled trial.","authors":"Yun-Hee Jeon, Judy Simpson, Judith Fethney, Luisa Krein, Mirim Shin, Lee-Fay Low, Robert T Woods, Loren Mowszowski, Sarah Hilmer, Sharon L Naismith, Lindy Clemson, Henry Brodaty, Vasi Naganathan, Amanda Miller Amberber, Danelle Kenny, Laura Gitlin, Sarah Szanton","doi":"10.1136/jnnp-2024-334514","DOIUrl":"https://doi.org/10.1136/jnnp-2024-334514","url":null,"abstract":"<p><strong>Background: </strong>We investigated the effectiveness of an Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence, health and well-being of people with dementia, family carer outcomes and costs.</p><p><strong>Method: </strong>A multicentre pragmatic parallel-arm randomised controlled trial compared I-HARP to usual care in community-dwelling people with mild to moderate dementia and their family carers in Sydney, Australia (2018-2022). I-HARP is a 4-month, home-based, dementia rehabilitation model delivered by an interdisciplinary team. Assessments were conducted at baseline (time-1), 4-month (time-2) and 12-month (time-3) follow-up. The primary outcome measure was the client's functional independence using the Disability Assessment for Dementia (DAD) scale at time-2, based on intention-to-treat analyses.</p><p><strong>Result: </strong>Of 130 recruited client-carer dyads, 116 dyads (58/group) completed the trial. The I-HARP group were not significantly better in most outcome measures than usual care at both time-2 and time-3; with the only statistically significant difference being a reduction in home environment hazards at time-2. Post hoc subgroup analysis of 66 clients with mild dementia found significantly better functional independence in the intervention group compared with those in usual care: difference 8.99 on DAD (95% CI 1.21, 16.79) at time-2 and difference 12.16 (95% CI 1.93, 22.38) at time-3. Economic evaluation suggests potentially lower resource use in I-HARP compared with usual care, but the cost-effectiveness is uncertain.</p><p><strong>Conclusion: </strong>Primary outcomes were not met for a population of people with dementia, with severity ranging from mild to moderate and severe. The I-HARP model appeared to benefit functional independence of participants with mild dementia, with potential cost savings.</p><p><strong>Trial registration number: </strong>ACTRN12618000600246.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-333834
Oriol Dols-Icardo, Álvaro Carbayo, Ivonne Jericó, Olga Blasco-Martínez, Esther Álvarez-Sánchez, Maria Angeles López Pérez, Sara Bernal, Benjamín Rodríguez-Santiago, Ivon Cusco, Janina Turon-Sans, Manuel Cabezas-Torres, Marta Caballero-Ávila, Ana Vesperinas, Laura Llansó, Inmaculada Pagola-Lorz, Laura Torné, Natalia Valle-Tamayo, Laia Muñoz, Sara Rubio-Guerra, Ignacio Illán-Gala, Elena Cortés-Vicente, Ellen Gelpi, Ricard Rojas-García
Background and objective: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.
Methods: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region.
Results: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes.
Conclusions: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.
背景和目的:5%到10%的肌萎缩侧索硬化症(ALS)病例有家族病史,其中30%的病例在对已知的ALS相关基因进行全面研究后,无法确定潜在的遗传原因。鉴于西班牙一个小地区的 ALS 发病率明显增加,这项工作的目的是在基因检测呈阴性的 ALS 病例中找出与 ALS 相关的新基因:与现有的人口统计学和流行病学数据相比,我们发现在西班牙的一个小地区,偶发性尤其是家族性 ALS 病例的发病率都有所上升。我们对这一独特地区的 12 例 ALS 患者(其中 5 例为家族性)进行了全基因组测序。我们扩大了研究范围,纳入了受影响的家庭成员和来自周边地区的其他病例:结果:我们在来自 7 个非亲缘家庭的 10 位 ALS 患者中发现了环 AMP 调节磷蛋白 21(ARPP21)基因中的一个共同错义突变(c.1586C>T; p.Pro529Leu),该基因编码一种 RNA 结合蛋白。其他导致 ALS 的基因没有发现突变:结论:尽管之前的研究否定了 ARPP21 在 ALS 中的因果作用,但我们的研究结果有力地证明 ARPP21 是 ALS 的新型致病基因。
{"title":"Identification of a pathogenic mutation in <i>ARPP21</i> in patients with amyotrophic lateral sclerosis.","authors":"Oriol Dols-Icardo, Álvaro Carbayo, Ivonne Jericó, Olga Blasco-Martínez, Esther Álvarez-Sánchez, Maria Angeles López Pérez, Sara Bernal, Benjamín Rodríguez-Santiago, Ivon Cusco, Janina Turon-Sans, Manuel Cabezas-Torres, Marta Caballero-Ávila, Ana Vesperinas, Laura Llansó, Inmaculada Pagola-Lorz, Laura Torné, Natalia Valle-Tamayo, Laia Muñoz, Sara Rubio-Guerra, Ignacio Illán-Gala, Elena Cortés-Vicente, Ellen Gelpi, Ricard Rojas-García","doi":"10.1136/jnnp-2024-333834","DOIUrl":"10.1136/jnnp-2024-333834","url":null,"abstract":"<p><strong>Background and objective: </strong>Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.</p><p><strong>Methods: </strong>We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region.</p><p><strong>Results: </strong>We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (<i>ARPP21)</i> gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes.</p><p><strong>Conclusions: </strong>While previous studies have dismissed a causal role of <i>ARPP21</i> in ALS, our results strongly support <i>ARPP21</i> as a novel ALS-causing gene.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"132-139"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-334062
Antonino Giordano, Ferdinando Clarelli, Béatrice Pignolet, Elisabetta Mascia, Melissa Sorosina, Kaalindi Misra, Laura Ferrè, Florence Bucciarelli, Ali Manouchehrinia, Lucia Moiola, Vittorio Martinelli, Maria A Rocca, Roland Liblau, Massimo Filippi, Federica Esposito
Background: Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity.
Methods: 230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality.
Results: Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041).
Conclusions: VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.
背景:维生素 D(VitD)会影响多发性硬化症(MS)的发病风险,但其对疾病活动性的影响还存在争议。我们评估了维生素 D 是否与疾病缓解治疗(DMT)开始两年后的无疾病活动证据-3(NEDA-3)状态有关,以及这种关联是因果关系还是混杂因素的结果。此外,我们还探讨了较高维生素D水平的遗传易感性是否会影响疾病活动的风险。方法:230名未经治疗的复发性缓解型多发性硬化症患者接受了血清25-OH-维生素D测定,并检测了经季节性调整的维生素D与疾病活动之间的关联。通过对约 40 万人进行的全基因组关联研究中的多基因风险评分建模,我们研究了高 VitD 遗传易感性对 1408 名独立多发性硬化症患者 NEDA-3 状态的影响。结果显示,基线VitD较低的多发性硬化症患者的NEDA-3状态较好,而基线VitD较高的多发性硬化症患者的NEDA-3状态较差:结果:基线 VitD 较低与 2 年后 NEDA-3 的概率降低有关(p=0.019)。结论:DMT开始前的VitD水平与NEDA-3的概率相关:DMT开始前的VitD水平会影响多发性硬化症的疾病活动风险。VitD水平较高的遗传易感性会降低疾病活动的风险,并与多发性硬化症的延迟发病有关。我们的研究提示今后应开展有关补充维生素 D 和生活方式干预的前瞻性研究,以阻碍多发性硬化症的疾病活动。
{"title":"Vitamin D affects the risk of disease activity in multiple sclerosis.","authors":"Antonino Giordano, Ferdinando Clarelli, Béatrice Pignolet, Elisabetta Mascia, Melissa Sorosina, Kaalindi Misra, Laura Ferrè, Florence Bucciarelli, Ali Manouchehrinia, Lucia Moiola, Vittorio Martinelli, Maria A Rocca, Roland Liblau, Massimo Filippi, Federica Esposito","doi":"10.1136/jnnp-2024-334062","DOIUrl":"10.1136/jnnp-2024-334062","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity.</p><p><strong>Methods: </strong>230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality.</p><p><strong>Results: </strong>Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041).</p><p><strong>Conclusions: </strong>VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"170-176"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1136/jnnp-2024-334319
Ken Uchino
{"title":"Ischaemic stroke in the young-is it time to consider alcohol reduction for stroke prevention?","authors":"Ken Uchino","doi":"10.1136/jnnp-2024-334319","DOIUrl":"10.1136/jnnp-2024-334319","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"104"},"PeriodicalIF":8.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}