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- Acute Onset of Adult Alexander Disease and the Concept of GFAP Toxicity.Publication . Godinho, Filipe; Guerreiro, Carolina; Parente Freixo, João; Oliveira, Jorge; Lourenço Rosa, José
- Amyotrophic Lateral Sclerosis with SOD1 Mutation Presenting with Progressive Cerebellar Ataxia.Publication . Sequeira, Marta; Godinho, Filipe; Lourenço, JoãoAmyotrophic lateral sclerosis is a fatal neurodegenerative disorder that affects upper and lower motor neurons. SOD1 mutations are the second most commonly found in familial and sporadic cases. We describe a patient with a homozygous pathogenic mutation in SOD1 gene that presented with a progressive cerebellar ataxia and ultimately developed a complex phenotype of cerebellar ataxia and motor neuron disease. The linkage between the cerebellum and ALS is shortly discussed.
- Blood Neutrophils, Oligoclonal Bands and Bridging Corticosteroids As Predictive Factors for MOGAD Course: Insights From a Multicentric Portuguese Cohort.Publication . Neves, Ana Lídia; Cabral, Andrea; Serrão, Catarina; Oliveira, Daniela Santos; Alves, Janice; Alves, José Miguel; Soares, Mafalda; Santos, Ernestina; Seabra, Mafalda; Felgueiras, Helena; Ferreira, João; Brandão, Eva; Guerreiro, Rui; Nunes, Carla Cecília; Ladeira, Filipa; Vale, José; Sá, Maria José; Jorge, AndréBackground: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a heterogeneous entity with either a monophasic or relapsing course. Well-established predictors of relapsing disease are lacking. Objective: Identifying predictors of relapsing MOGAD, particularly at disease onset. Methods: A multicentre observational retrospective study was conducted to characterise a cohort of Portuguese adult MOGAD patients. Patients were identified from participating centre databases. Clinical and demographic data were collected from medical records. Bivariate analysis was conducted to compare patients with relapsing and monophasic MOGAD. Significant variables were included in a stepwise multiple regression analysis to identify independent predictors of relapse. Results: Eighty-seven MOGAD patients from 8 public hospitals were included. Relapsing MOGAD was found in 35.6% (n = 31). Mean diagnostic delay was 3.2 (±6.2) years and time to relapse was 4.4 (±6.4) years. Multiple logistic regression showed that higher neutrophil count (p < 0.01), presence of oligoclonal bands (p = 0.025) and no bridging corticosteroids (p = 0.038) at first attack were predictive of relapsing MOGAD. Conclusion: Neutrophil count and oligoclonal bands at first attack may facilitate early decision-making regarding maintenance immunotherapy. Bridging corticosteroids may also influence the course of MOGAD. Further studies with prospective design are warranted.
- Cerebral Edema in Patients with severe Hemispheric Syndrome: Incidence, Risk Factors, and Outcomes-Data from SITS-ISTR.Publication . Escudero-Martínez, Irene; Thorén, Magnus; Ringleb, Peter; Paiva Nunes, Ana; Cappellari, Manuel; Rand, Viiu-Marika; Sobolewski, Piotr; Egido, Jose; Toni, Danilo; Chen, Shih-Yin; Tsao, Nicole; Ahmed, NiazBackground and purpose: Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia. Methods: Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003-2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0-2) and death at 90 days. Results: Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02). Conclusions: In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.
- Cerebral Venous Sinus Thrombosis in Traumatic Brain Injury: a Systematic Review of its Complications, Effect on Mortality, Diagnostic and Therapeutic Management, and Follow-Up.Publication . Netteland, Dag Ferner; Sandset, Else Charlotte; Mejlænder-Evjensvold, Magnus; Aarhus, Mads; Jeppesen, Elisabeth; Aguiar de Sousa, Diana; Helseth, Eirik; Brommeland, Tor; FrontiersObjective: Cerebral venous sinus thrombosis (CVST) is increasingly being recognized in the setting of traumatic brain injury (TBI), but its effect on TBI patients and its management remains uncertain. Here, we systematically review the currently available evidence on the complications, effect on mortality and the diagnostic and therapeutic management and follow-up of CVST in the setting of TBI. Methods: Key clinical questions were posed and used to define the scope of the review within the following topics of complications; effect on mortality; diagnostics; therapeutics; recanalization and follow-up of CVST in TBI. We searched relevant databases using a structured search strategy. We screened identified records according to eligibility criteria and for information regarding the posed key clinical questions within the defined topics of the review. Results: From 679 identified records, 21 studies met the eligibility criteria and were included, all of which were observational in nature. Data was deemed insufficiently homogenous to perform meta-analysis and was narratively synthesized. Reported rates of venous infarctions ranged between 7 and 38%. One large registry study reported increased in-hospital mortality in CVSP and TBI compared to a control group with TBI alone in adjusted analyses. Another two studies found midline CVST to be associated with increased risk of mortality in adjusted analyses. Direct data to inform the optimum diagnostic and therapeutic management of the condition was limited, but some data on the safety, and effect of anticoagulation treatment of CVST in TBI was identified. Systematic data on recanalization rates to guide follow-up was also limited, and reported complete recanalization rates ranged between 41 and 86%. In the context of the identified data, we discuss the diagnostic and therapeutic management and follow-up of the condition. Conclusion: Currently, the available evidence is insufficient for evidence-based treatment of CVST in the setting of TBI. However, there are clear indications in the presently available literature that CVST in TBI is associated with complications and increased mortality, and this indicates that management options for the condition must be considered. Further studies are needed to confirm the effects of CVST on TBI patients and to provide evidence to support management decisions.
- Characteristics and Outcomes of Cerebral Venous Thrombosis Associated With COVID-19.Publication . Scutelnic, Adrian; van de Munckhof, Anita; Miraclin, Angel T; Aaron, Sanjith; Hameed, Sajid; Wasay, Mohammad; Grosu, Oxana; Krzywicka, Katarzyna; Sánchez van Kammen, Mayte; Lindgren, Erik; Moreira, Tiago; Acampora, Roberto; Negro, Alberto; Karapanayiotides, Theodoros; Yaghi, Shadi; Revert, Anna; Cuadrado Godia, Elisa; Garcia-Madrona, Sebastian; La Spina, Paolino; Grillo, Francesco; Giammello, Fabrizio; Nguyen, Thanh N; Abdalkader, Mohamad; Buture, Alina; Sofia Cotelli, Maria; Raposo, Nicolas; Tsivgoulis, Georgios; Candelaresi, Paolo; Ciacciarelli, Antonio; Mbroh, Joshua; Batenkova, Tatiana; Scoppettuolo, Pasquale; Zedde, Marialuisa; Pascarella, Rosario; Antonenko, Kateryna; Kristoffersen, Espen S; Kremer Hovinga, Johanna A; Jood, Katarina; Aguiar de Sousa, Diana; Poli, Sven; Tatlisumak, Turgut; Putaala, Jukka; Coutinho, Jonathan M; Ferro, José M; Arnold, Marcel; Heldner, Mirjam RIntroduction: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT. Patients and methods: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex. Results: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]). Conclusion: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.
- Early Prediction of Delayed Ischemia and Functional Outcome in Acute Subarachnoid Hemorrhage: Role of Diffusion Tensor Imaging.Publication . Fragata, Isabel; Alves, Marta; Papoila, Ana Luísa; Nunes, Ana Paiva; Ferreira, Patrícia; Canto-Moreira, Nuno; Canhão, PatríciaBackground and purpose: Diffusion tensor imaging (DTI) parameters are markers of cerebral lesion in some diseases. In patients with acute subarachnoid hemorrhage (SAH), we investigated whether DTI parameters measured at <72 hours might be associated with delayed cerebral ischemia (DCI) and with poor functional outcome at 3 months (modified Rankin Scale score ≥3). Methods: DTI was performed in a prospective cohort of 60 patients with nontraumatic SAH at <72 hours. Association of fractional anisotropy and apparent diffusion coefficient values at <72 hours with the occurrence of DCI and outcome at 3 months was evaluated with logistic regression models, adjusting for known predictors of prognosis. Results: At <72 hours after SAH, fractional anisotropy values at the cerebellum were associated with DCI occurrence (78% less odds of DCI for each 0.1 increase in fractional anisotropy; P=0.019). Early apparent diffusion coefficient values were not associated with DCI. After adjusting for confounding variables, an increase of 10 U in apparent diffusion coefficient at the frontal centrum semiovale corresponded to 15% increased odds of poor outcome (P=0.061). Conclusions: DTI parameters at <72 hours post-SAH are independently associated with the occurrence of DCI and functional outcome. These preliminary results suggest the role of DTI parameters as surrogate markers of prognosis in nontraumatic SAH.
- Editorial: Cerebral Venous Thrombosis.Publication . Heldner, Mirjam R; Aguiar de Sousa, Diana; Field, Thalia S; Coutinho, Jonathan M; Zuurbier, Susanna M
- Efficacy and Safety of IncobotulinumtoxinA in Older Patients with Upper Limb Spasticity: a Pooled Analysis.Publication . Munin, Michael C; Camões-Barbosa, Alexandre; Cordero-García, Carlos; Baricich, Alessio; Carda, Stefano; Althaus, Michael; Comes, Georg; Vacchelli, Matteo; Wissel, Jörg: The aim of this study was to compare the efficacy and safety of a single cycle of incobotulinumtoxinA versus placebo in pooled data from older patients (aged ≥65 years) with upper limb spasticity (ULS). : This study was a post hoc analysis of pooled data from seven prospective, multicenter, phase II or III trials of incobotulinumtoxinA in adult patients aged ≥65 years from across the world with post-stroke ULS or upper and lower limb spasticity, including a subgroup with moderate-to-severe ULS. Changes from baseline in ULS severity were evaluated using the (modified) Ashworth Scale across different spasticity patterns at 4 and 12 weeks after incobotulinumtoxinA injection. : In 267 older patients with ULS, including a subgroup of 207 with moderate-to-severe ULS, all ULS patterns statistically analyzed (elbow flexion, thumb-in-palm, clenched fist, wrist flexion, and pronated forearm) were improved more by incobotulinumtoxinA than placebo at week 4 ( < 0.05). For most of these patterns, the difference remained significant at week 12 ( < 0.05). IncobotulinumtoxinA was generally well tolerated. : This study, which analyzed data from the largest cohort of older patients in the literature, provides information regarding the use of incobotulinumtoxinA in ULS, the efficacy and favorable safety profile of incobotulinumtoxinA for the treatment of ULS in older patients, particularly in those with moderate-to-severe spasticity, was confirmed.
- Evaluation of the Efficacy of the SARS-CoV-2 Vaccine Additional and Booster Doses in Immunocompromised Patients With Multiple Sclerosis: the COVACiMS Study.Publication . Ladeira, Filipa; Nobrega, Claudia; Cerqueira, JoãoStudies evaluating COVID-19 primary vaccination with two vaccines reported a blunt response in Multiple Sclerosis (MS) patients under anti-CD20 and sphingosine-1-phosphate (S1P) modulators. An extended primary vaccination (EPV) was recommended in immunosuppressed MS patients. Data on the effectiveness of the EPV and subsequent booster dose are limited. A prospective cohort study (n = 270) was conducted to evaluate the humoral and cellular immunogenicity of the EPV scheme in immunocompromised MS patients (i.e., treated with anti-CD20, S1P modulators, natalizumab, teriflunomide, or dimethyl fumarate) vs. regular primary vaccination in non-treated patients - primary course (PC) cohort. The effect of a subsequent booster dose was also assessed - first booster (FB) cohort . The seroconversion rates were 55% and 56% in anti-CD20 and 75% and 67% in S1P modulators group in PC and FB cohort, respectively, and 100% in the remaining groups. A positive SARS-CoV-2 Spike T-spot was observed in 22% of patients under S1P modulators in PC cohort and 67% in FB cohort; the remaining groups had 75% or more. Similar rates of breakthrough infection were observed in both groups vs. controls. Compared to non-treated MS patients, immunosuppressed patients under anti-CD20 and S1P modulators drugs receiving EPV scheme or booster dose still present lower protection rates to SARS-CoV-2.
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