Alberto Alain Gabbai

The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison

BACKGROUND Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke. METHODS 1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805. FINDINGS In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015). INTERPRETATION Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.

Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy

OBJECTIVE To investigate the efficacy and safety of once-daily eslicarbazepine acetate (ESL) when used as add-on treatment in adults with > or = 4 partial-onset seizures per 4-week despite treatment with 1 to 3 antiepileptic drugs (AEDs). METHODS This double-blind, parallel-group, multicenter study consisted of an 8-week observational baseline period, after which patients were randomized to placebo (n=100) or once-daily ESL 400 mg (n=96), 800 mg (n=101), or 1200 mg (n=98). Patients then entered a 14-week double-blind treatment phase. All patients started on their full maintenance dose except for those in the ESL 1200 mg group who received once-daily ESL 800 mg for 2 weeks before reaching their full maintenance dose. RESULTS Seizure frequency per 4-week (primary endpoint) over the 14-week double-blind treatment period was significantly lower than placebo in the ESL 800 mg and 1200 mg (p<0.001) groups. Responder rate (> or = 50% reduction in seizure frequency) was 13.0% (placebo), 16.7% (400 mg), 40.0% (800 mg, p<0.001), and 37.1% (1200 mg, p<0.001). Median relative reduction in seizure frequency was 0.8% (placebo), 18.7% (400 mg), 32.6% (800 mg, p<0.001), and 32.8% (1200 mg). Discontinuation rates due to adverse events (AEs) were 3.0% (placebo), 12.5% (400 mg), 18.8% (800 mg), and 26.5% (1200 mg). The most common (>5%) AEs in any group were dizziness, somnolence, headache, nausea, diplopia, abnormal coordination, vomiting, blurred vision, and fatigue. The majority of AEs were of mild or moderate severity. CONCLUSIONS Treatment with once-daily eslicarbazepine acetate 800 mg and 1200 mg was more effective than placebo and generally well tolerated in patients with partial-onset seizures refractory to treatment with 1 to 3 concomitant AEDs.

The prevalence of multiple sclerosis in the city of São Paulo, Brazil, 1997.

July 1, 1997 was stipulated as the day for estimating the prevalence of multiple sclerosis within the city of São Paulo. The patients were identified via various sources, including associated universities and magnetic resonance services of the city of São Paulo. The area covered by the study has a population of 9,380,000, mainly white and of European origin, with a large number of immigrants from Spain and Portugal. The patients were classified in accordance with the criteria of Poser et al. (1983), and only those with defined multiple sclerosis were registered. The study gave a prevalence of 15.0/105 inhabitants, or three times the value obtained in a similar study in 1990. This increase reveals the larger number of cases encompassed by the study, and is attributed to the use of more detailed recording methods, improvements in diagnosis, and better conditions for treatment.

Efficacy and safety of eslicarbazepine acetate as add‐on treatment in patients with focal‐onset seizures: Integrated analysis of pooled data from double‐blind phase III clinical studies

Purpose: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial‐onset seizures.

Neuromyelitis optica in Brazil: a study on clinical and prognostic factors

Objectives To describe the clinical characteristics of patients with relapsing neuromyelitis optica (NMO) from a tertiary care center in Brazil and compare the groups with normal and abnormal brain magnetic resonance imaging (MRI). Methods Retrospective review of 41 patients followed at the Neuroimmunology Clinic of the Federal University of São Paulo, Brazil, from 1994 to 2007. Results All patients had relapsing-remitting optic-spinal disease, long extending spinal cord lesions, and brain MRI not meeting Barkhof criteria for multiple sclerosis (MS), thus fulfilling the 1999 and 2006 Wingerchuck criteria for NMO. Mean follow-up time was 52 months; mean age of onset was 32.6 years. The mean relapse rate (RR) and progression index (PI) were 1.0 and 0.9, respectively. Twenty-four patients had brain lesions not compatible with MS on MRI, and there were no statistical differences on PI and RR between patients who had brain lesions and patients who did not. Incomplete recovery, but not the type of first relapse, correlated with a worse prognosis. Seventeen patients were tested for NMO-IgG (anti-aquaporin-4 antibody) with 41% positivity. Conclusions In this series, we did not find a statistical difference of disease progression between patients with and without brain lesions, suggesting that the presence of brain abnormalities is not a marker of disease severity.

Creutzfeldt–Jakob disease and inclusion body myositis: Abundant disease‐associated prion protein in muscle

Pathologicalprion protein (PrPSc) is the hallmark of prion diseases affecting primarily the central nervous system. Using immunohistochemistry, paraffin‐embedded tissue blot, and Western blot, we demonstrated abundant PrPSc in the muscle of a patient with sporadic Creutzfeldt–Jakob disease and inclusion body myositis. Extraneural PrPC‐PrPSc conversion in Creutzfeldt–Jakob disease appears to become prominent when PrPC is abundantly available as substrate, as in inclusion body myositis muscle.

Long-term safety and efficacy of eslicarbazepine acetate as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy: Results of a 1-year open-label extension study

OBJECTIVE To evaluate the long-term safety, tolerability and efficacy of once-daily eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial-onset seizures. METHODS One-year open-label extension (OLE) study with ESL in patients who completed a randomised, double-blind placebo-controlled trial (study BIA-2093-302; Epilepsy Res. 89 (2010) 278-285). Starting dose was 800 mg once-daily, for 4 weeks; thereafter, dose could be individualised within the 400-1,200 mg range. Doses of concomitant antiepileptic drugs were to be kept stable. RESULTS Overall, 325 patients were enrolled (intent-to-treat population); 223 (68.6%) patients completed 1-year of treatment. ESL median dose was 800 mg once-daily. Compared to the baseline period of the double-blind study completed prior to this OLE study, median seizure frequency decreased by 32% in weeks 1-4, and between 37% and 39% thereafter. The responder rate (seizure reduction ≥ 50%) was 37% during weeks 1-4 and thereafter ranged between 38% and 42% per 12-week interval. Proportion of seizure-free patients per 12-week interval ranged between 5% and 11%. Improvements from baseline in several Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and Montgomery Asberg Depression Rating Scale (MADRS) scores were observed. Adverse events (AEs) were reported by 83% of patients. AEs occurring in ≥ 10% of patients were dizziness, headache and somnolence. AEs were usually of mild to moderate intensity. CONCLUSION In this study, ESL demonstrated a sustained therapeutic effect and was well tolerated during 1-year add-on treatment of adults with partial-onset seizures. Additionally, significant improvements in quality of life domains and depressive symptoms were observed under long-term treatment with once-daily ESL.

Cerebellar Cognitive Affective Syndrome in Machado Joseph Disease: Core Clinical Features

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey–Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color–Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color–Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Dengue: muscle biopsy findings in 15 patients

Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the brazilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

McArdle's disease in two generations: Autosomal recessive transmission with manifesting heterozygote

A 17-year-old boy had exercise-induced cramps and myoglobinuria. The mother had myalgia and weakness after exercise but the father was asymptomatic. Muscle biopsy was normal in the father but showed glycogen storage and absent or markedly decreased histochemical stain for phosphorylase in mother and son. Autosomal dominant McArdles disease was considered likely, but biochemical studies showed that muscle phosphorylase activity was 0.6% of normal in the son, 20% in the mother, and 45% in the father, with corresponding decreases of cross-reacting material by immunotitration. These data suggest autosomal recessive transmission. One of the parents was clinically silent and the other was a manifesting heterozygote.