Hypophosphatemia as a possible biomarker for epileptic seizures at the emergency department.

INTRODUCTION: Hypophosphatemia seems to be temporally associated with seizures, despite not being considered a trigger. We aimed to evaluate hypophosphatemia as a biomarker for seizures. METHODS: Retrospective study, including all consecutive patients admitted at our central hospital's emergency department from 01/01-31/03/2021, screened as "altered consciousness/syncope" or "seizures", with available phosphate levels. RESULTS: 277 patients included, mostly male (61.7%), mean age 64.3 years. Final diagnosis was "seizure" in 34.7% and "other diagnosis" in 65.3%. Patients with seizures were younger (p<0.001), had more frequent epilepsy (p<0.001) and alcoholism (p=0.01). Patients with other diagnosis had more often renal failure (p<0.001) and statin (p=0.02) or diuretic (p=0.003) therapy. Time to blood collection (from the event and from admission) was similar between groups. Patients with seizures had lower mean phosphate levels and more frequent hypophosphatemia (<2.4mg/dL) (p<0.001). Mean CK levels were similar in both groups (p=0.25). HyperCK (>200U/L) was more frequent in the seizure group (p=0.04). Odds ratio (OR) of hypophosphatemia for seizures was 4.330 (CI 95% 2.170-8.640, p<0.001), persisting after correction for confounders. OR of hyperCK was 1.890 (CI 95% 1.060-3.371, p=0.03), losing significance when adjusted. Sensitivity was low for both. Hypophosphatemia was more specific (91.2% vs 79.9%). CONCLUSIONS: Our findings support hypophosphatemia as a seizure biomarker. More studies are needed.

Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal.

OBJECTIVES: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up. METHODS: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021. RESULTS: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects. CONCLUSION: Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.

HBV and VZV seroprotection loss in MS patients under DMT.

BACKGROUND: Strategies recommended to decrease the risk of infection associated with the use of multiple sclerosis disease-modifying treatments include screening and immunization against common viral infections such as varicella-zoster (VZV) and hepatitis B (HBV). However, the data concerning the durability of those vaccine responses and the need for re-test is scarce. OBJECTIVES: We aimed to evaluate HBV and VZV seroprotection loss in MS patients under DMT. METHODS: We conducted a cohort study including patients with basal seroprotective titers against HBV/VZV viruses and a subsequent serology performed at least 3 months apart. We evaluated predictors of seroprotection loss through a binary regression. RESULTS: HBV seroprotection loss occurred in one-fifth of patients in a median interval of 21.3 months. Anti-CD20 treatment (OR 8.559 95%CI 3.467- 21.130, p < 000.1), age at last serology higher or equal to 55 years (OR 7.506, 95% CI 2.473-22.786, p < 0.001) and basal HBsAb titer (OR 0.992, 95%CI 0.987 -0.996, p=0.001) increase the risk of seroprotection loss. VZV seroprotection loss occurred rarely in a median interval of 21.3 months. We could not identify any factor associated with an increased risk of VZV seroprotection loss. CONCLUSIONS: Anti-CD20 drugs are associated with a loss of seroprotection against HBV in a short-interval follow-up.

Obstructive Sleep Apnea and Other Vascular Risk factors' Impact on Non-Motor Symptoms in Parkinson's Disease.

Background: Previous studies revealed an association between vascular comorbidities and obstructive sleep apnea (OSA) and the severity of motor and cognitive symptoms in Parkinson's disease (PD). However, there is a lack of studies assessing the entire spectrum of non-motor symptoms (NMS). Objective: To investigate the relationship between vascular comorbidities and NMS in PD patients. Methods: Patients were assessed at baseline and 4 years later with the Non-Motor Symptom Assessment Scale, Parkinson's Psychosis Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Apathy scale. After tetrachoric correlation matrix, we conducted linear regression models (adjusted for age, gender, disease duration, and UPDRS-III) to investigate the relationship between vascular comorbidities and NMS. Results: In 73 PD patients, (mean disease duration 7.1 [5.3]), 57% had hypertension, 44% body mass index >25, 44% elevated cholesterol, 15% diabetes mellitus, 15% OSA, 14% cigarette-smoking history, 8% prior stroke, and 8% coronary disease. Cognition, psychotic symptoms, apathy, urinary function, and miscellaneous domains significantly worsened at the 4-year follow-up. OSA was significantly associated with higher severity of hallucinations/illusions at baseline and with a more severe deterioration of attention/memory, psychotic symptoms, and apathetic mood at the 4-year follow-up. At baseline, but not at follow-up, hypertension was negatively associated with miscellaneous domain scores and coronary disease with autonomic function scores (gastrointestinal tract and urinary function domains). Conclusion: Among PD-associated comorbidities, OSA was the main factor of decline. In addition to cognitive impairment, OSA might also potentially worsen psychotic symptoms and apathy. Treatment of OSA could be a strategy to improve these important NMS.

Outcomes in Guillain-Barré Syndrome following a second therapeutic cycle - A single-centre retrospective observational study.

INTRODUCTION: The treatment of Guillain-Barré Syndrome (GBS) with intravenous immunoglobulin (IVIg) or plasma exchange (PE) reduces time to clinical recovery. Although sometimes used in clinical practice, the benefit of a second treatment cycle is of unproven benefit. AIMS: Our aim was to compare GBS prognosis in patients treated with one or two cycles of IVIg or PE. METHODS: We selected patients with electrophysiological studies compatible with acute inflammatory demyelinating polyneuropathy or acute motor-sensory axonal neuropathy, from January 2018 to December 2020 in our hospital. Our primary outcome was any improvement in the Guillain-Barré Syndrome Disability Score (GBS-DS) at a mean of twelve weeks. We compared patients treated with one or two treatment cycles with a binary regression. RESULTS: We included twenty-six patients, 65.4% with the classical presentation and 30.8% were treated with two cycles. Patients treated with two cycles presented a higher basal GBS-DS (median 4; IQR 1-5) compared with the group of patients treated with one cycle (median 3; IQR 1-5), p = 0.01. The remaining basal characteristics were similar between groups. The two-cycle treatment regimen did not associate with an improvement in GBS-DS (OR 0.28, 95% CI 0.03-2.35, p = 0.24). Likewise there was no benefit in the need for intensive care unit (OR 2.0, 95% CI 0.37-10.92, p = 0.42) or mechanical invasive ventilation (OR 10.2, 95% CI 0.86-120.96, p = 0.66). DISCUSSION: Our analysis reinforces the recent literature data regarding the absence of benefit of two treatment cycles in patients with GBS.

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Progression in Parkinson's Disease: Variation in Motor and Non-motor Symptoms Severity and Predictors of Decline in Cognition, Motor Function, Disability, and Health-Related Quality of Life as Assessed by Two Different Methods.

BACKGROUND: Parkinson's disease (PD) is multi-symptom disease with variable progression. OBJECTIVES: We performed a longitudinal study to address the evolution of motor symptoms (MS) and non-motor symptoms (NMS), predictors of motor-, cognitive-, disability-, and health-related quality of life (HRQL) status and the relative usefullness of a battery of separate NMS scales (BSS) versus the Non-Motor Symptom Scale (NMSS). METHODS: Seventy-two patients were assessed at baseline and 4 years later with the NMSS and BSS. We assessed the following outcomes: cognition (Montreal Cognitive Assessment scale [MoCA]), disability (Unified Parkinson's Disease Rating Scale Part II [UPDRS II], Schwab and England [S&E]), motor dysfunction (Unified Parkinson's Disease Rating Scale Part III [UPDRS III], Hoehn and Yahr [HY]), and HRQL (EuroQol [EQ] EQ-vertical visual analogue scale [VAS] and EQ-Index). Statistical analysis included a comparison between scales scores at both time points and multivariate regression analysis to calculate the impact of each baseline symptom in outcomes. NMSS and BSS were introduced in separate models. RESULTS: NMSS Domain 4: perception/hallucinations, Parkinson's Psychosis Questionnaire, Apathy Scale, NMSS Domain 7: urinary, S&E, UPDRS II, HY, and MoCA scores worsened significantly. Dementia increased to a 4-year prevalence of 39.8%. In the multivariate model using BSS, cognitive state variation was significantly predicted by baseline HY, EQ-Index, and S&E. Using the NMSS, MoCA change was significantly associated with NMSS Domain 4: perceptions/hallucination score, cognitive status with UPDRS III score, HRQL with NMSS Domain 4: perception/hallucinations score, and S&E. CONCLUSION: Our study suggests that NMS progress heterogeneously, BSS approach being more sensitive to change than NMSS. The multivariate analysis has shown that S&E and NMSS Domain 4: perception/hallucinations scores are the stronger predictors of HRQL and cognitive dysfunction variation, favoring NMSS over the BSS approach.

Seroconversion rate following HBV vaccination in clinical practice: The role of age and DMT treatment.

HBV screening and immunization is recommended in all MS patients and is mandatory before the start of some DMT. However, studies evaluating the immune response to HBV vaccine in MS patients are scarce. We aimed to evaluate the seroprotection rate following HBV immunization in MS patients and to assess if older age and DMT-treatment influenced seroprotection. We conducted a cohort study between 2016 and 2020 and compared the immune response to HBV vaccine in MS patients under different DMTs and in patients 50 years old or younger and older than 50. We found that patients under non-injectable DMT presented lower rates of seroprotection comparing to patients under injectable DMT's or without treatment. In patients older than 50, although the seroprotection rate was similar to the remaining patients, the antibody anti-HBV surface antigen titers following HBV immunization were lower and patients were more likely to require a 4th dose of the vaccine to achieve seroprotection. Our findings highlight to need to consider HBV immunization in MS patients early in the disease course, in order to ensure a proper immune response to the vaccine.

Polysomnographic predictors of sleep, motor and cognitive dysfunction progression in Parkinson's disease: a longitudinal study.

OBJECTIVE: To assess the predictive value of polysomnographic (PSG) data in the prospective assessment of cognitive, motor, daytime and nighttime sleep dysfunction in Parkinson's Disease (PD) patients. METHODS: PD patients were assessed at baseline with video-PSG and with cognitive (MoCA), Sleep (SCOPA-Sleep Nighttime and Daytime scores) and Motor (UPDRSIII) function scales at both baseline and four years later. Linear regression analysis was used to assess the relation between PSG variables at baseline and change in symptoms scores. RESULTS: We included a total of 25 patients, 12 with rapid eye movement (REM) sleep behavior disorder (RBD) (in 8 PSG was inconclusive, due to lack of REM sleep). MoCA scores decreased significantly at follow-up, while SCOPA-Sleep Daytime and SCOPA-Sleep Nighttime and UPDRSIII did not vary. Lower N3 percentage at baseline was significantly associated with MoCA decrease. Higher Periodic Limb Movements in Sleep index (PLMS) and the presence of RBD were significantly associated with SCOPA daytime score increase. Higher global severity of RBD, tonic RSWA and total number of motor events during REM sleep were associated with SCOPA Nighttime score increase. CONCLUSIONS: The present work suggests that PSG data could be useful for predicting PD cognitive and sleep dysfunction progression. Reduced SWS could predict deterioration of cognitive function, while baseline PLMS could be useful to predict worsening of daytime sleep dysfunction. Severity of RBD could be used for estimating nighttime sleep symptoms progression.

Do dreams tell the future? Dream content as a predictor of cognitive deterioration in Parkinson's disease.

Cross-sectional studies suggest a correlation between alterations in dream content reports and executive dysfunction tests in Parkinson's disease (PD), but this has not been assessed in longitudinal studies. Our objective was to assess the predictive value of dream content for progression of cognitive dysfunction in PD. We prospectively addressed all consecutive, non-demented patients with PD attending an outpatient clinic during a 1-year period. Dream reports were collected at baseline by means of a dream diary and analysed according to the Hall and Van de Castle system. Patients were assessed at baseline for rapid eye movement sleep behaviour disorder, motor stage, mood disorder and psychosis. The Montreal Cognitive Assessment (MoCA) was applied at baseline and 4 years later. Linear regression analysis was used to the test the relation between each dream index (predictors), demographic and other motor and non-motor variables (covariates), and change in MoCA scores (dependent variable). In all, 58 patients were assessed at both time points and 23 reported at least one dream (range 1-27, total 148). Aggression, physical activities, and negatively toned content predominated in dream reports. The MoCA scores decreased significantly from baseline to follow-up. In the multivariate model, negative emotion index was the strongest predictor of cognitive decline. We found a significant positive association between negative emotions in dreams at baseline and subsequent reduction in MoCA scores. These findings suggest that some dream content in patients with PD could be considered a predictor of cognitive decline, independent of other factors known to influence either dream content or cognitive deterioration.

Nivolumab-induced seronegative encephalitis.

Immune checkpoint inhibitors (ICIs) have emerged as a new therapeutic tool for numerous types of cancer. Neurological complications have been reported in 1% of patients who have undergone checkpoint inhibition therapy. ICIs-induced encephalitides occur in 0.1-0.2% of patients within weeks after ICIs initiation; are usually seronegative and have nonspecific changes on imaging, CSF and electroencephalogram (EEG) studies. Early recognition and prompt treatment are important to prevent significant morbidity and mortality. We present a case of nivolumab-induced encephalitis with very subtle clinical symptoms and full recovery following ICIs suspension and steroids.

Motor and non-motor function predictors of mortality in Parkinson's disease.

Doubts persist regarding the influence of Parkinson's disease (PD) on mortality. Our objective was to assess mortality rates in a prospectively followed cohort of PD patients and the impact of motor and non-motor symptoms in survival. 130 consecutive PD patients were followed during a 4-year period or until death. Baseline assessment included motor function (UPDRSIII, Hoehn and Yahr-HY), incapacity (Schwab and England-S&E, UPDRS II), Health-Related quality of life (EuroQol), non-motor symptoms (Non-Motor Symptom Scale-NMSS, MoCA, REM sleep behavior disorder symptoms questionnaire) and comorbidity burden (Charlson Comorbidity Index-CCI). These were used as predictor variables. Standardized mortality rates (SMR) were calculated, comparing with the general population. The association between mortality and predictors was tested with univariate and multivariate Cox proportional hazard regression models. Overall and gender-related SMRs were similar to the general population. SMR for pneumonia was five times higher than in the general population. Age, disease duration, CCI, EuroQol, dementia, MoCA, S&E, NMSS Hallucinations, HY, and PIGD motor phenotype were significantly associated with mortality. Adjusting for age, gender and disease duration, S&E remained significantly associated with mortality. In multivariate logistic regression analysis, death was significantly associated with disease duration, CCI and NMSS-mood/cognition scores. PD was not associated with an excess of mortality, but conferred a higher probability of dying from pneumonia. Comorbidity was a major determinant, but disease duration, baseline incapacity, cognition, psychosis, mood complaints and HRQL also contributed significantly to mortality.

Acute-onset chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 antibodies and bilateral facial nerve enhancement.

A 26-year-old female presented with acute onset distal paraparesis, upper limb tremor and bilateral facial palsy. Neurophysiology revealed a sensorimotor demyelinating polyneuropathy and lumbar puncture revealed an albuminocytologic dissociation. Neuroaxis MRI revealed bilateral facial nerve and cauda equina enhancement. Initially diagnosed as Guillain-Barré Syndrome, poor response to intravenous immunoglobulin, persistent deterioration, anti-neurofascin-155 antibodies and clinical response to steroid therapy led to diagnosis of acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP). CIDP patients with anti-neurofascin-155 antibodies are younger, with distal predominant weakness, tremor, and poor response to intravenous immunoglobulin. Up to 16% can present acutely, however bilateral facial weakness is rare.

A multicenter, non-interventional study to evaluate the disease activity in Multiple Sclerosis after withdrawal of Natalizumab in Portugal.

OBJECTIVES: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. PATIENTS AND METHODS: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. RESULTS: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ±â€¯8.3 years at diagnosis, and a mean age of 37.2 ±â€¯10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ±â€¯1.2, 0.2 ±â€¯0.5 and 0.6 ±â€¯1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. CONCLUSION: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.

Underuse of Prophylactic Treatment Among Portuguese Patients with Primary Headache: A Retrospective Observational Study.

AIMS: To evaluate prescription of prophylactic treatment before and after consultation in a neurology headache clinic and to determine predictors for prophylactic treatment and clinical improvement. METHODS: Clinical records of consecutive patients assessed in a neurologic headache clinic in Portugal and diagnosed with acute or chronic migraine and/or tension-type headache were assessed. Prescription of prophylaxis before and after the first visit to the clinic were compared. Logistic regression was used to evaluate predictors of the need for therapeutic intervention and clinical improvement. RESULTS: Among 409 patients (86.8% women; mean age 41.6 years), 315 (77%) had indication for prophylaxis, and 70 (22%) of these patients were already on prophylactic treatment. Among the 265 patients with information for follow-up, prophylactic treatment was added in 178 (67.2%), and there was a significant change in the number of treated patients between the first and second visits. Ongoing treatment was switched or the dose increased in 21 patients. Multivariate logistic regression revealed that women (odds ratio [OR] = 2.09, 95% confidence interval [CI] 1.1 to 3.97] and patients with medication overuse headache (MOH) (OR = 6.97, 95% CI 1.60 to 30.39) were more likely to need therapeutic intervention, whereas patients referred from the emergency room were less likely to need it (OR = 0.44, 95% CI 0.22 to 0.89). Of the 265 patients, 185 (69.8%) had improved at a follow-up. Having prophylactic treatment at the time of the second visit was associated with improvement (OR = 2.39, 95% CI 1.23 to 4.63; P = .01). CONCLUSION: Women and medication overuse headache patients were more likely to need therapeutic intervention. However, only a minority of patients with treatment indication were treated before their first visit to the headache clinic. Prophylaxis prescription was associated with clinical improvement at follow-up.

Effect of patients' expectations on clinical response to fampridine treatment.

INTRODUCTION: Patient expectation of treatment outcome is one of the primary mechanisms underlying the placebo effect. In multiple sclerosis trials with symptomatic treatments, a robust placebo effect is observed, which might be related to patient expectations. The aim of this study was to evaluate whether patient expectations regarding fampridine treatment influence the clinical response after 4 weeks and 6 months of treatment. MATERIALS AND METHODS: We designed and carried out a prospective study from June 2015 to August 2017. Before treatment, patients completed a questionnaire including a scale evaluating their expectations regarding the treatment. The effect of baseline positive expectancy on the response status after 4 weeks and 6 months of treatment was analyzed through univariable and, when applicable, multivariable analysis. RESULTS: A total of 47 consecutive patients were included in the study. At week 4, 37 (78.7%) patients were classified as responders; a one-point increase in the positive expectancy questionnaire was significantly associated with a fourfold increase in the likelihood of being a responder [OR = 4.020 (95% CI 1.082-14.933); p = 0.038]. At 6 months, 43 patients completed follow-up. The number of responders decreased to 28; at this point, positive expectancy at baseline was no longer associated with response status. CONCLUSION: Baseline positive expectancy regarding fampridine was determinant of the clinical response after 4 weeks of treatment. However, in the long term, fampridine efficacy was not dependent on expectations prior to treatment.

The Influence of Menopause in Multiple Sclerosis Course: A Longitudinal Cohort Study.

BACKGROUND: Hormonal variations are known to influence the course of multiple sclerosis (MS). OBJECTIVES: We aimed to evaluate the impact of menopause in MS course, including disease activity and disability progression. METHODS: We conducted a retrospective longitudinal cohort study including all women, older than 44, post-menopausal, with a diagnosis of MS at least 1 year before menopause. We evaluated the impact of menopause in MS course comparing clinical and radiologic outcomes within 5 years before and after menopause. We repeated the analysis in subgroups of patients without disease-modifying treatment (DMT) change or co-morbidities diagnosed during the observation period, considering that those factors might also impact MS outcomes. RESULTS: Thirty-seven women, with a mean age at the time of menopause of 49.8 (±4.06) years were included in the analysis. Within 5 years following menopause, we observed a decrease in the annualized relapse rate (0.37 ± 0.35 pre-menopause vs. 0.08 ± 0.18 post-menopause, p < 0.001) compared with the same period before menopause, while the EDSS progression rate remained stable (0.13 ± 0.24 EDSS point/year pre-menopausal vs. 0.13 ± 0.18 post-menopause, p = 0.935). EDSS progression events frequency was similar before and after the menopause (37.8 vs. 48.6%, respectively, p = 0.424). These observations persisted in patients' subgroups without DMT switch or co-morbidities. CONCLUSIONS: Following menopause, we observed a reduction in the relapse rate, but the disability progression continued at a similar rate, compared to the pre-menopausal period. These observations persisted in the subgroup of patients without changes in DMT or co-morbidities diagnosed during the observation period.

Prediabetes Is Associated with Unfavorable Outcome in Young Adult Patients with Ischemic Stroke.

BACKGROUND: Prediabetes has been associated with unfavorable short-term outcome in patients with ischemic stroke (IS). However, its effect in the subset of young adult patients has not been fully assessed. Our aim was to study the association between prediabetes and 3-month outcome in young adult patients with IS. METHODS: This is a retrospective analysis of consecutive patients aged 18-55 years with a clinical diagnosis of acute IS between January 2010 and December 2016. According to their glucose profile, patients were divided in 3 groups: normal glucose metabolism, prediabetes, and diabetes. The outcome at 3 months was assessed by the modified Rankin Scale (mRS) and dichotomized as good (mRS score ≤2) and poor (mRS score >2) outcomes. RESULTS: A total of 247 patients were included, the median age was 49 years (interquartile range 42-53), and 144 (58.3%) were men. Prediabetes was diagnosed in 79 patients (32.0%) and diabetes was diagnosed in 45 patients (18.2%). Prediabetic (adjusted odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.1, P = .031) and diabetic (adjusted OR 2.8, 95% CI 1.3-6.1, P = .020) patients had a worse prognosis at 3 months. A statistical significant shift in the distribution of the mRS score at 3 months was found in prediabetic (adjusted OR 2.5, 95% CI .3-1.5, P = .002) and diabetic (adjusted OR 3.74, 95% CI .5-2.2, P = .002) patients. CONCLUSION: In young adults with IS, prediabetes and diabetes increase the risk of unfavorable outcome at 3 months.

Cerebral amyloid angiopathy - The modified Boston criteria in clinical practice.

BACKGROUND: Early identification of patients with cerebral amyloid angiopathy (CAA) is relevant considering the increased risk for cerebral hemorrhage. A new set of diagnostic criteria for CAA was recently proposed, which include the presence of superficial siderosis. We aimed to assess the impact of applying these criteria regarding use of antithrombotic therapy. METHODS: Review of consecutive patients admitted to a Neurology Department from 2014 to 2016, with acute parenchymal or subarachnoid hemorrhage and/or atypical transient focal neurological episodes. Patients with a possible or probable CAA according to the original and modified Boston criteria were included. Information was collected regarding presentation, imaging findings and concomitant therapy. RESULTS: Among a total of 1436 admitted patients, 52 with acute hemorrhagic lesions or atypical TFNE were screened: 22 met criteria for CAA; 4 were deemed too young; 21 had other causes for hemorrhagic parenchymal lesions; and 5 had uncertain diagnosis. Using the modified Boston criteria, 8 patients fulfilled criteria for probable CAA and 14 for possible CAA. When we applied the original Boston criteria to the same patients, only 7 fulfilled criteria for probable CAA and 8 for possible CAA. Among the additional patients identified with the modified Boston criteria, 4 were using antithrombotic therapy. CONCLUSIONS: The use of the modified Boston criteria allowed for the identification of 7 additional patients, more than half of which were taking antithrombotic therapy. Systematic use of these criteria could have an important impact in clinical practice. Raising awareness on the different presentations of CAA among clinicians is of the utmost importance.