levetiracetam and Multiple-Sclerosis

Tremor is a relatively common symptom in Multiple Sclerosis (MS). It can negatively affect several aspects of the patients' life and is one of the most disabling symptoms in MS. Pharmacological treatment of MS-related tremor was studied for several years, though treatment is still challenging. This study will review all studies on the pharmacological treatment of tremor in MS and update the treatment recommendations.. Any relevant English-language clinical trial that investigated the pharmacological treatment of MS-related tremor in adults was eligible in this study. We searched Medline (PubMed), Scopus, EMBASE, and Web of Science. Bias assessment was performed by the CASP (Critical Appraisal Skills Programme) checklist. All methods followed PRISMA guidelines.. The initial search resulted in 3024 articles; 26 articles were included as eligible studies, 13 articles had a low risk of bias, and remained for full manuscript review. The results of studies on 5-HT3 receptor antagonists as a single dose treatment were inconsistent. Botulinum toxin A had significant effects on MS-related tremor, but adverse effects and injection procedures limited its application. The application of cannabis-based medicine to treat MS-related tremor could not be recommended due to inconclusive therapeutic effects and several side effects. Levetiracetam had inconsistent results, and other anti-epileptic drugs were not studied precisely. Isoniazid has minor therapeutic effects and possible adverse effects in the treatment of MS-related tremor.. Further well-designed comparative clinical trials with a large sample size can improve clinical management of tremor in patients with MS.

Topics: Adult; Botulinum Toxins, Type A; Humans; Levetiracetam; Multiple Sclerosis; Tremor

The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients.. In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration.. Forty-eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0-T1) in group 1.. Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs.

Topics: Adult; Anticonvulsants; Cross-Over Studies; Double-Blind Method; Humans; Levetiracetam; Middle Aged; Multiple Sclerosis; Piracetam; Treatment Outcome; Upper Extremity

Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well as pain intensity of more than 4 on a 0 to 10-point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Eighty-nine patients were screened for participation and 30 patients entered the study. Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.

Topics: Adult; Analgesics; Anticonvulsants; Chronic Pain; Cross-Over Studies; Female; Humans; Hyperalgesia; Levetiracetam; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Pain Threshold; Patient Satisfaction; Piracetam; Placebos; Treatment Failure

Central neuropathic pain (CNP) is a prevalent and distressing symptom in patients with multiple sclerosis (MS). The anticonvulsant levetiracetam (LEV) has been shown to be efficacious in some types of CNP, but its efficacy in MS-related CNP has not been confirmed.. To investigate the tolerability and potential effects of LEV against CNP in MS subjects, we performed a single-center, prospective, randomized, single-blind, placebo-controlled study in twenty patients with MS and CNP. Outcomes before and during the 3-month study were assessed using validated measures of pain, depression, disability and quality of life.. The medication was well tolerated and analysis revealed a significant difference between the LEV and placebo arm in all study outcomes related to pain (mean pain intensity score, mean pain difference, percentage of patients with a clinically significant pain reduction). Furthermore, the individual quality of life rating improved in treated patients, showing a significant correlation with pain reduction.. These findings suggest that further studies with larger samples of patients be carried out in order to confirm the efficacy of LEV in MS-related CNP population.

Topics: Adult; Analgesics; Anticonvulsants; Depression; Disability Evaluation; Female; Humans; Levetiracetam; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Pain Measurement; Pilot Projects; Piracetam; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

The aim of this study was to evaluate the activity measured by kinematic analysis, tolerability and efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients affected by cerebellar symptoms, in a randomized single-blind, placebo-controlled cross-over study.. Eight MS subjects with cerebellar signs (five female and three male; mean EDSS: 4.77; mean disease duration 9.2) performed a reaching task on a digitizing tablet and their trajectories went through a kinematic analysis. The subjects were assessed at baseline, after 21 days of treatment, after wash-out period (day 35) and after 21 days of treatment (day 56). LEV was used at the maximum dosage of 1500 mg daily. The primary outcome was the modification on smoothness (JERK) whilst aiming error (AAI) and centripetal acceleration (CA) were considered as secondary outcomes.. Two subjects were excluded from the final analysis. Primary outcome (i.e. JERK) was significantly affected by the administration of LEV overtime (nine arms in active treatment versus three arms in placebo decreased the mean values of their JERK). Regarding secondary outcomes CA was significantly affected by the administration of LEV. No statistical significant results were found comparing clinical scales during the four assessments.. The results indicate that LEV was able to modify kinematic parameter so the medication was active but no improvement in clinical scales was observed. LEV needs to be tested in a larger group of subjects designed to verify treatment efficacy using higher dosage of the medication.

Topics: Biomechanical Phenomena; Cerebellum; Female; Humans; Levetiracetam; Male; Multiple Sclerosis; Nootropic Agents; Pilot Projects; Piracetam; Tremor

Secondary paroxysmal dyskinesias (SPDs) are short, episodic, and recurrent movement disorders, classically related to multiple sclerosis (MS). Carbamazepine is effective, but with risk of adverse reactions. We identified 7 patients with SPD among 457 MS patients (1.53%). SPD occurred in face ( n = 1), leg ( n = 2), or arm +leg ( n = 4) several times during the day. Magnetic resonance imaging (MRI) showed new or enhancing lesions in thalamus ( n = 1), mesencephalic tegmentum ( n = 1), and cerebellar peduncles ( n = 5). Patients were treated with clonazepam and then acetazolamide ( n = 1), acetazolamide ( n = 5), or levetiracetam ( n = 1) with response within hours (acetazolamide) to days (levetiracetam). No recurrences or adverse events were reported after a median follow-up of 33 months.

Topics: Acetazolamide; Adult; Anticonvulsants; Cerebellum; Clonazepam; Dyskinesias; Dystonia; Female; Follow-Up Studies; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Piracetam; Tegmentum Mesencephali; Thalamus; Treatment Outcome

Levetiracetam (LEV) is an established anticonvulsant with numerous mechanisms of action. Apart from its anti-epileptic effects, recent experimental studies suggest anti-inflammatory properties via modulation of interleukin (IL)-1β and transforming-growth-factor (TGF)-β1. However, its anti-inflammatory properties have not yet been examined in an autoimmune inflammatory disease of the central nervous system (CNS). We investigated LEV anti-inflammatory properties in experimental autoimmune encephalomyelitis, an established mouse model of multiple sclerosis. FACS analyses, ELISA, histology and rt-PCR experiments were done to explore potential anti-inflammatory effects. In line with prior studies, we demonstrate that LEV modulates both the relative gene expression and secretion of IL-1β and TGF-1β. However, these changes were not sufficient to alter the disease course or histological parameters. Additionally, LEV showed no effects on the absolute number of different immune cell subsets. In summary, LEV showed only minor anti-inflammatory effects not sufficient to ameliorate disease course in an autoimmune inflammatory disease of CNS.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Disease Models, Animal; Disease Progression; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Expression Regulation; Immunomodulation; Interleukin-1beta; Levetiracetam; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Neuroglia; Peptide Fragments; Piracetam; Transforming Growth Factor beta1

The incidence of seizures is generally accepted to be greater in patients with multiple sclerosis (MS) than in the general population, and rarely, MS can initially present as seizure. To present a case report of seizure as the initial symptom of MS, to quantify the occurrence of seizures among MS patients, and to classify patients according to when seizures occur relative to onset of MS. The medical history of patients presenting with MS and seizure in our clinic was examined. In addition, 25 scientific papers were reviewed and the number and characteristics of patients with MS and seizure recorded. Data from the literature review and from our own clinical series were combined and examined. Of the MS patients, 1.95% experienced seizures at any time during life. Patients experiencing seizures before MS diagnosis were classified into three categories: (a) 25 (7.3% of patients with MS and seizures) with seizure as the initial presentation of MS; (b) 27 (7.9%) with seizures appearing with other signs and symptoms of MS; and (c) 68 (20%) with seizures occurring years or an unknown period of time before MS onset. Seizure occurring as a symptom of MS relapse was found in 29 patients. The prevalence of seizures among MS patients was higher than that in the general population, indicating a relationship between seizures and MS. Seizures occurred before MS diagnosis in a small percentage of patients.

Topics: Adult; Anticonvulsants; Brain; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Multiple Sclerosis; Piracetam; Seizures; Vitamin B 12; Vitamin B 6; Vitamins

Disabling tremor is frequent in multiple sclerosis (MS) and its treatment remains challenging. We conducted an open-label trial to evaluate the effect of levetiracetam (LEV) to treat cerebellar tremor in MS patients.. Fourteen MS patients, aged 27 to 57 years, with cerebellar tremor. Tremor duration ranged from 3 to 14 years. The tremor clinical rating scale, the spiral drawings scale, and ataxia clinical scale were used to assess the severity of tremor. Data about the tremor-induced disability were obtained by using the specific Activities of Daily Living Questionnaire (ADL). LEV was orally administered at a starting dose of 500 mg twice daily for one week followed by increments of 500 mg twice daily each week up to the target dose of 50 mg/Kg/day. Patients were evaluated at baseline and two weeks after the end of titration phase. The Wilcoxon matched-pairs test was used for statistical analysis.. Eleven patients completed the trial. LEV administration was associated with subjective and objective improvement of the tremor, with significant lowering of all tremor measurements' sum of scores as well as of ADL mean score between the baseline and follow-up. No correlation was found between the degree of improvement of the tremor and the disease duration or progression. LEV was well tolerated by subjects who completed the study.. LEV could be useful for the management of cerebellar tremor in MS and the good tolerability makes it easy to test. LEV long-term efficacy should be confirmed in extended studies.

Topics: Activities of Daily Living; Adult; Anticonvulsants; Cerebellar Neoplasms; Disability Evaluation; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Multiple Sclerosis; Pilot Projects; Piracetam; Severity of Illness Index; Statistics, Nonparametric

Spasticity is a common and debilitating symptom of multiple sclerosis (MS). Current treatments are effective, but may be difficult to tolerate for many patients.. To determine if levetiracetam, a second-generation antiepileptic drug, may be useful for the treatment of spasticity in MS.. A retrospective medical record review of patients attending the Multiple Sclerosis Program at the University of Texas, Southwestern Medical Center at Dallas was performed. A series of 12 patients who had been treated with levetiracetam for spasticity was identified. Most of the patients were female (10/11), and the mean age was 41.0 years. The main outcome measure was a change in Penn spasm score or modified Ashworth score. Both scores are measured on a scale of 0 to 4.. The Penn Spasm score (a measure of phasic spasticity) was decreased for all patients following treatment with levetiracetam. The mean +/- SD Penn Spasm score was 2.7 +/- 0.65 at baseline and decreased to 0.9 +/- 0.29 at follow-up. There was no change in modified Ashworth scores (a measure of tonic spasticity). Five patients reported adverse events; 1 patient discontinued treatment owing to an adverse event (edema). Three patients incidentally reported improvements in neuropathic pain.. Levetiracetam was effective for reducing phasic spasticity but not tonic spasticity in this 12-patient case series. The drug was well tolerated and therefore shows promise as a treatment for phasic spasticity. Large, well-controlled trials are needed to confirm these findings.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Piracetam; Retrospective Studies; Severity of Illness Index