Teriflunomide treatment outcomes in multiple sclerosis: A Portuguese real-life experience.

Teriflunomide is an oral disease-modifying therapy for relapsing-remitting multiple sclerosis patients. A decline in physical and cognitive functions, which negatively impacts their quality of life (QoL), is observed in relapsing-remitting multiple sclerosis patients. The aim of this study was to characterise adult Portuguese relapsing-remitting multiple sclerosis patients treated with teriflunomide in routine clinical practice concerning their quality of life, comorbidities, treatment effectiveness, satisfaction, compliance and safety. TeriLIVE-QoL was a multicentre, non-interventional, prospective cohort study that collected demographic and clinical characteristics, patient-reported outcomes and adverse events from patients treated with teriflunomide of 14 mg over 2 years. Notably, around 18 months of this period occurred during the COVID-19 pandemic. Of the 99 participants, 25% were treatment-naïve. Annualised relapse rate and the score for the Hospital Anxiety and Depression Scale decreased after 1 (p = 0.01) and 2 years of treatment (p < 0.001), respectively. Convenience (p = 0.001), effectiveness (p = 0.002) and global satisfaction scores (p < 0.001) presented high values (up to 95.6) and continued to improve along the study. Treatment persistence was 77%, and compliance reached 82% 2 years after initiation. Three patients experienced serious adverse events. TeriLIVE-QoL provides real-world evidence of clinical effectiveness, high treatment satisfaction, consistent safety and improved psychiatric outcomes, associated with elevated treatment persistence and compliance in patients treated with teriflunomide.iance reached 82% 2 years after initiation. Three patients experienced serious adverse events.

Consensus for the Early Identification of Secondary Progressive Multiple Sclerosis in Portugal: a Delphi Panel.

INTRODUCTION: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. MATERIAL AND METHODS: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. RESULTS: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. CONCLUSION: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.

Oral Cladribine in Patients who Change From First-Line Disease Modifying Treatments for Multiple Sclerosis: Protocol of a Prospective Effectiveness and Safety Study (CLAD CROSS).

Background: Recently, the number of available disease modifying therapies for multiple sclerosis (MS) has increased. However, a proportion of patients treated with these agents continue to experience relapses and disease progression. Cladribine tablets, approved in 2017 for highly active relapsing MS, comprise a sparsely administered oral treatment which exerts its therapeutic effect through a reduction and subsequent repletion of the lymphocyte population. Purpose/Study Sample: Here we describe the design of CLAD CROSS, a prospective, non-interventional, multicenter, Phase IV study in patients with a confirmed diagnosis of RRMS who switch from first-line disease modifying drugs (DMDs) to treatment with cladribine tablets in routine clinical practice. 242 adult patients will be recruited in 61 sites (6 countries) over 30 months and will be followed up for 2 years following prescription of cladribine tablets per the decision of the treating physicians. Research Design: The primary endpoint is the change in annualized relapse rate (ARR) between the 12-month pre-baseline period and over the 12-month period before end of study. Secondary endpoints are the percentage of patients with 6-month disability progression or improvement at the end of the study, measured by the Expanded Disability Status Scale, Timed 25 Foot Walk and 9-Hole Peg Test scales and quality of life, treatment satisfaction, and healthcare resource utilization, measured through the MSIS-29, TSQM 1.4, and EQ-5D-3L scales, respectively. MRI lesions will be compared in the exploratory setting between the 12-month pre-baseline period, baseline, and at years 1 and 2. Adverse events will be monitored throughout the study. Interim analyses are pre-planned when 30% and 60% of patients will complete the 12-month follow-up visit. Conclusions: CLAD CROSS will provide efficacy data on cladribine tablets, used as a follow-up treatment to first-line DMDs in the real-world setting, will further establish its safety profile and will collect information to support pharmacoeconomic studies.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Seguridad y efectividad del rtPA en el ictus isquémico agudo en pacientes con cáncer activo: estudio de casos y controles / Safety and outcome of rtPA in acute ischemic stroke in patients with active cancer: case-control study

Introducción. Los pacientes con cáncer tienen un mayor riesgo de ictus debido a los efectos malignos directos e indirectos. La trombólisis intravenosa con activador tisular del plasminógeno recombinante (rtPA) constituye un tratamiento médico estándar para el ictus isquémico agudo. Objetivo. Revisar el uso de rtPA en el ictus isquémico agudo en pacientes con cáncer activo. Sujetos y métodos. Estudio retrospectivo observacional de casos y controles para evaluar pacientes con ictus isquémico agudo y cáncer admitidos en la unidad de ictus entre enero de 2010 y junio de 2015. Resultados. Se identificaron siete casos (86% varones; mediana de edad: 76 años) y también se incluyeron 20 controles pareados por edad y clasificación del Oxfordshire Community Stroke Project. Un 29% de casos experimentó complicaciones directas del procedimiento frente a un 30% en el grupo control. Un 14% sufrió transformación hemorrágica (frente a un 20%). Un paciente (caso) sufrió una hemorragia sistémica grave, y otro (control), una hemorragia intracerebral grave. A los tres meses, un 43% era independiente (frente a un 25% de los controles) y un 29% había fallecido (frente a un 30%). Un subtipo etiológico indeterminado (clasificación TOAST) era más frecuente en pacientes con cáncer (71% frente a 20%). Conclusión. Complicaciones hemorrágicas graves, potenciadas por el rtPA, pueden incrementar el riesgo de morbilidad y mortalidad. Sin embargo, pacientes seleccionados con cáncer que padecen un ictus isquémico agudo pueden beneficiarse del tratamiento con rtPA. Un cáncer activo no debería considerarse una contraindicación de uso de rtPA, aunque debe evaluarse el riesgo de complicaciones y la esperanza de vida para tomar la decisión (AU)

Introduction. Cancer patients have increased stroke risk from direct and indirect malignancy effects. Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is standard medical treatment for acute ischemic stroke (AIS). Aim. To review rtPA use in AIS patients with active cancer. Subjects and methods. Retrospective observational case-control study evaluating patients with AIS and cancer admitted to our stroke unit between January/2010 and June/2015. Results. Seven cases were identified (86% male; median age: 76), and 20 controls were included matched for age and Oxfordshire Community Stroke Project classification. 29% experienced direct procedure complications vs 30% within the control group, 14% suffered haemorrhagic transformation (vs 20%), one patient experienced serious systemic haemorrhage (case) and one patient experienced serious intracerebral haemorrhage (control). After three months’ follow-up, 43% were independent compared with 25% controls, and 29% had died (vs 30%). Undetermined aetiology subtype (TOAST classification) was more frequent in cancer patients when compared to controls (71% vs 20%). Conclusion. Severe haemorrhagic complications, potentiated by rtPA, carry increased risk of morbidity and mortality. Nevertheless, selected cancer patients with AIS may benefit from rtPA treatment. Active cancer should not be considered an absolute contraindication to rtPA use. Risk of complications and life expectancy should be assessed when making this decision (AU)

Comparison between the results of the Symptom Checklist-90 in two different populations with temporal lobe epilepsy.

We performed a prospective psychopathological analysis of two distinct populations with temporal lobe epilepsy (TLE), medically treated patients (n=18) and patients surgically treated for mesial temporal sclerosis (n=19), and compared the psychopathology in the surgical population pre- and postoperatively. The Symptom Checklist-90 (SCL-90) was administered to both groups, with the surgical patients being tested before and 6 months after surgery. A multivariant comparison of the SCL-90 subscales was made between medically treated patients and patients before and after surgical treatment. Surgically treated patients had less psychopathology after surgery than before. The comparison of surgically treated patients with medically treated patients showed statistically significant differences in most subscales. Except for the subscale of Hostility, no statistically significant differences were found between medically treated patients and the surgical population before lobectomy.

Vertebrobasilar transcranial color-coded duplex ultrasonography: improvement with echo enhancement.

BACKGROUND AND PURPOSE: The diagnostic yield of vertebrobasilar transcranial color-coded duplex ultrasonography (US) is often hampered by insufficient acoustic penetration, anatomic variations, and vessel tortousity. The purpose of this study was to evaluate the effect of echo enhancement on vertebrobasilar transcranial color-coded duplex US. METHODS: In 23 consecutive patients (mean age, 61.0 +/- 11.1 years) with vertebrobasilar stroke, the vertebrobasilar system (P1 segment of the posterior cerebral artery [PCA], basilar head, V4 segment of the vertebral artery, and basilar artery) was examined with transcranial color-coded duplex US before and after injection of an echo-enhancer. The acoustic window was graded according to visibility of parenchymal structures, and vessel imaging was graded according to the appearance of the color mode signal. Maximum depth of the basilar color signal was recorded. All patients with an abnormal or inconclusive US finding underwent either digital subtraction angiography or MR angiography. RESULTS: In the P1 PCA, V4 vertebral artery, basilar artery, and basilar head, image quality was insufficient in 65%, 82%, 83%, and 38%, respectively, before echo enhancement, and in 15%, 30%, 35%, and 9%, respectively, after echo enhancement. In all graded vessels, the improved image quality with echo enhancement was statistically significant. Compared with the reference examinations in the 15 cases of occlusion or stenosis, definite diagnosis was possible in 60% (nine cases) with nonenhanced transcranial color-coded duplex US and in 93% of (14 cases) after echo enhancement. CONCLUSION: Echo enhancement resulted in improved image quality of the vertebrobasilar system and markedly increased diagnostic confidence.

A sudden arterial blood pressure decrease is compensated by an increase in intracranial blood volume.

BACKGROUND: A sudden decrease in arterial blood pressure (ABP) will cause the intracranial blood volume (IBV) to rise, despite the fact that arterial cerebral blood flow decreases. The aim of this study was to test the hypothesis that the increase in IBV is caused by a relative decrease of intracranial venous outflow. METHODS AND RESULTS: In 10 healthy volunteers we studied cerebral autoregulation (CA) by causing an ABP drop with bilaterally deflating leg cuffs. Blood flow velocities (BFV) in the middle cerebral artery and the straight sinus were monitored continuously with transcranial Doppler ultrasound, and the ABP with a non-invasive photoplethysmographic method. After transforming all variables in relative changes, the arterio-venous BFV difference was calculated. Allowing for diameter changes of the intracranial vessels of up to 10 %, and assuming a resting averaged cerebral blood flow of 55 to 60 ml per 100 g brain tissue per minute, an IBV increase of 9 to 10 ml could be calculated. CONCLUSIONS: In intact CA, a steep decrease of ABP results in an increase of intracranial blood volume. The transformation of our IBV data by means of the human intracranial pressure-volume relationship results in an excellent agreement with previously reported ICP increases of 10 mmHg. The increase in intracranial blood volume might be of clinical relevance in orthostatic dysregulation by increasing the ischemic tolerance of the brain before cerebral autoregulation becomes effective.

Assessment of intracranial collateral flow by transcranial color-coded duplex sonography using a temporal and frontal axial insonation plane.

BACKGROUND AND PURPOSE: The insonation of the posterior communicating artery (PcomA) is often hampered by the unfavorable insonation angle when the temporal acoustic bone window (TBW) is used. This problem may be ameliorated by a lateral frontal bone window (LFBW). This study evaluated the TBW and LFBW for the assessment of collateral intracranial flow conditions and aimed at defining diagnostic transcranial color-coded duplex sonography (TCCS) criteria that do not need compression maneuvers. METHODS: The A1 segment of the anterior cerebral artery (ACA), the PcomA, and the P1 segment of the posterior cerebral artery (PCA) were insonated by TCCS in 40 controls and 20 patients (16 internal carotid artery [ICA] occlusions or high grade stenoses, 3 middle cerebral artery stenoses or occlusions, 1 PCA stenosis). RESULTS: Detection rates for the A1 ACA and P1 PCA were higher for the TBW (94%, 98%) compared to the LFBW (86%, 81%) in controls. The PcomA was identified more frequently through the LFBW (86%) compared to the TBW (80%). Through the LFBW angle, corrected flow velocity (FV) measurements were possible for the PcomA with an average correction of 6.5 degrees. In controls, in > 80% of identified PcomAs, flow was directed towards the ICA. Side to side differences were below 7% for peak systolic FVs. In the patients with ICA disease, a flow reversal in the ipsilateral A1 ACA and a FV difference of > 30% seemed feasible for diagnosis of anterior communicating artery crossflow. Criteria for PcomA crossflow were side differences of FVs in the PcomA of > or = 30% and in the P1 PCA of > or = 20%. CONCLUSIONS: The LFBW proved useful as a complementary insonation plane to assess intracranial crossflow conditions, especially via the PcomA. We were able to define TCCS criteria for functional relevant collateralization without the need of compression maneuvers.