Alemtuzumab treatment in real clinical practice: Experience in a multicenter cohort.

BACKGROUND: Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed. METHODS: A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded. RESULTS: A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients. CONCLUSION: Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.

Creutzfeldt-Jakob disease and non-convulsive status epilepticus: a clinical and electroencephalographic follow-up study.

OBJECTIVE: To describe the clinical and electroencephalographic findings from a confused elderly woman with Creutzfeldt-Jakob disease (CJD) that initially were compatible with the diagnosis of non-convulsive status epilepticus (NCSE). METHODS AND RESULTS: A 75-year-old right-handed woman was admitted to our hospital because of confusion and alteration of mental status. The two first electroencephalograms (EEGs) showed continuous diffuse spikes, rhythmic sharp waves and sharp-and-slow wave complexes which were completely abolished after the administration of 10 mg of intravenous diazepam. Over the following days, the clinical state of the patient was unmodified despite aggressive antiepileptic therapy. A third EEG revealed pseudo-periodic negative or positive-negative slow waves localised in the right frontal region. Subsequently, two consecutive EEGs showed continuous periodic generalised bi-triphasic complexes at a rate of 1 Hz, compatible with the diagnosis of CJD. Finally, the patient died, and postmortem examination was diagnostic of the sporadic form of CJD. CONCLUSIONS: Clinical and electroencephalographic features in the early stages of CJD may resemble NCSE. The administration of intravenous benzodiazepines and its clinical and electroencephalographic correlation, response to the antiepileptic therapy, and monitoring with serial EEG recordings may be helpful considerations in the differential diagnosis.

[The efficacy of the valproic acid-ethosuximide combination in the continuous slow point wave syndrome during sleep]. / Eficacia de la asociación ácido valproico-etosuximida en el síndrome de punta-onda lenta continua durante el sueño.

Continuous spikes and waves during slow sleep (CSWS) is a syndrome with a serious prognosis due to the frequent association with neuropsychological dysfunction. It is mandatory to consider this syndrome if an epileptic child suffers from behavioral changes, dysarthria or learning difficulties. We report on two patients with CSWS syndrome with focal abnormalities on the nondominant hemisphere and a proportion of generalized spike-waves discharges in more than 85% of their NREM sleep on the EEG. Both had a good response to the treatment with sodium valproate and ethosuximide at high doses. Both suffered a relapse of their clinical and EEG semiology after withdrawal of their treatment. After restarting treatment they became clinically normal with a normal sleep EEG recording. We propose the association of sodium valproate and ethosuximide for CSWS; this treatment should be maintained until adolescence.