The effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampus

PurposeLevetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine. Because of little preclinical or clinical data concerning the outcomes of LEV in SE-induced neuronal death and vasogenic edema, we investigated the effect of LEV on SE-induced injury in comparison to diazepam (DZP), and valproate (VPA).MethodsTwo hours after pilocarpine-induced SE, rats were given one of the following drugs; (1) DZP, (2) LEV, (3) VPA, (4) DZP + LEV, (5) DZP + VPA, and (6) DZP + oxiracetam. Three–four days after SE, neuronal damage and vasogenic edema were evaluated by Fluoro-Jade B (FJB) staining and serum-protein extravasation, respectively.ResultsLEV (≥50 mg/kg) was effective to protect neuronal damage from SE in comparison to DZP and VPA. LEV as an add-on drug with DZP could not alleviate neuronal damage as compared to LEV alone. VPA (≥100 mg/kg) was effective to protect neuronal damage from SE, as compared to DZP. VPA as an add-on drug with DZP reduced neuronal damage, as compared to DZP alone.ConclusionThese findings suggest that LEV may negatively interact with DZP, and be more effective to prevent SE-induced neuronal death as a first line drug than as a second line therapy after BDZ treatment.     

Vestibular neuritis: Vertigo and the high-acceleration vestibulo-ocular reflex

Abstract   Patients after vestibular neuritis (VN) often report persistent dizziness and disequilibrium. We correlated persistent symptoms with sustained impairment of the high-acceleration horizontal vestibulo-ocular reflex as determined by quantitative searchcoil head-impulse testing (qHIT). In 47 patients, qHIT was recorded 0–60 months and symptoms assessed with the Yardley Vertigo Symptom Scale short form ≥ 18 months after VN onset. No correlation between the magnitude of high-acceleration vestibular impairment and the severity of vertigo symptoms was observed. The lack of a symptom-qHIT correlation suggests that defective compensation at a more rostral level in the central nervous system may be responsible for protracted symptoms in VN patients.     

Left ventricular long-axis function in myasthenia gravis

Abstract   Myasthenia gravis (MG) primarily affects skeletal muscles, but influence on cardiac function has been suggested. The aim of this study was to assess left ventricular long-axis function in MG patients compared to healthy controls, and to examine whether any MG-related heart involvement was influenced by the acetylcholine-esterase inhibitor pyridostigmine. We found that early diastolic atrioventricular-plane velocity and tissue Doppler peak systolic strain was lower in MG patients than in controls before pyridostigmine. The differences disappeared following administration of pyridostigmine. Also, tissue velocities at systole and early diastole tended to be lower in patients before pyridostigmine. In multivariate analyses adjusting for between-group differences in blood pressure, MG was no longer associated with lower longaxis function. Conventional echocardiographic measures of left ventricular diastolic and systolic function did not differ between groups. In conclusion, this study, using modern tissue Doppler imaging as well as conventional echocardiography, could not demonstrate definite MG-related cardiac involvement in a group of MG patients without known cardiac disease, but indicates that pyridostigmine-responsive MG-related alterations in cardiac muscle function exist in MG patients.     

Long-term levetiracetam treatment of epilepsy patients: Clinical audit

PurposeThe long-term efficacy and tolerability of levetiracetam (LEV) was analysed in 218 epilepsy patients. One hundred and ninety-nine patients were treated for at least 6 months. We evaluated LEV efficacy for all types of seizures together, and for simple partial, complex partial and secondary generalized seizures individually.ResultsA significant decrease in the number of seizures occurred after 6 months of treatment (p < 0.001). Mean seizure frequency (irrespective of type) before LEV was 19.2 a month. The mean monthly frequency at 6, 12, 24 and 36 months dropped to 12.7, 10.5, 9.7 and 7.1 seizures a month, respectively. The mean percentage reduction in seizures at these times was 45.7, 52.1, 59.1 and 64.2% and the number of responding patients was 51.3, 54.2, 59.8 and 62.2%. The number of patients completely seizure free was 18.6, 16.7, 15.2 and 16.2%. We found similar results in the last three categories for partial simple, complex and secondary generalized seizures individually. Side effects in 18.3% of patients caused treatment discontinuation in 6.4%. The most frequent were somnolence, moodiness and dizziness. The retention rate at 6, 12, 24 and 36 months was 0.848, 0.72, 0.62 and 0.5, respectively.ConclusionsLEV is effective and well tolerated for long-term treatment of epilepsy.     

Measurement of levetiracetam drug levels to assist with seizure control and monitoring of drug interactions with other anti-epileptic medications (AEMs)

PurposeLevetiracetam (LEV) therapeutic range (20–40 mg/L) and potential drug interactions were assessed in people with epilepsy (PWE).MethodFifty-two PWE had LEV and concomitant medications [carbamazepine (CBZ); valproate (VPA); lamotrigine (LTG)] blood levels measured and compared to seizure activity. Lacosamide (LCM) levels were unavailable. Adopted therapeutic ranges were: 20–40 mg/L – LEV; 25–50 μmol/L – total CBZ; 6–13 μmol/L – free CBZ; 300–750 μmol/L – total VPA; 30–75 μmol/L – free VPA; and 40–60 μmol/L – LTG. Seizure-freedom was assessed and patients followed for almost two years.Results23 of 52 PWE (44%) used LEV monotherapy and 16/23 (70%) had ‘therapeutic’ LEV with 13/16 (81%) seizure-free. 29 of 52 (56%) used polytherapy and 16/29 (55%) had ‘therapeutic’ LEV with 7/16 (44%) seizure-free. 11 of 29 (38%) used CBZ: 4/11 (36%) had therapeutic mean LEV levels and 7/11 (64%) were seizure-free. Fourteen (48%) used VPA: 9/14 (64%) had therapeutic mean LEV levels and 8/14 (57%) were seizure-free. 13 of 29 (45%) used LTG: 8/13 (62%) had therapeutic mean LEV levels and 5/13 (38%) were seizure-free. LEV did not alter CBZ, but CBZ affected LEV. LEV elevated VPA free levels but not VPA total levels. Dosage/concentration was lowered with polytherapy.ConclusionLEV range (20–40 mg/L) assisted epilepsy management and anti-epileptic medication interactions were suggested with polytherapy thus possibly explaining the impaired efficacy of LEV with polytherapy.     

Clinical value of therapeutic drug monitoring for levetiracetam in pediatric patients with epilepsy

PurposeTo identify pediatric patients who require therapeutic drug monitoring (TDM) of levetiracetam (LEV).MethodsWe retrospectively investigated 2413 routine therapeutic drug monitoring data on serum LEV concentration from 1398 pediatric patients (age, 0–15 years). Samples were grouped by age (infants, < 1 year; preschool children, 1–5 years; primary school children, 6–11 years; and adolescents, 12–15 years), and the LEV concentration-to-dose (CD) ratio was calculated.ResultsThe mean CD ratio was highest in adolescents (analysis of variance, p < 0.001); 22.5 % and 15.7 % higher in adolescents than in preschool children and school children, respectively (Scheffé test, p < 0.001); and higher in infants than in preschool children. Preschool children had the lowest ratio and tended to show an increase in the ratio from age 2 to 5 years. Use of enzyme-inducing antiseizure medication reduced the CD ratio by 6.1 % in infants, 12.2 % in preschool children, 5.9 % in primary school children, and 9.4 % in adolescents. The mean CD ratio was 2.7 %, 26.9 %, and 39.3 % higher in preschool children, primary school children, and adolescents with defined chronic kidney disease (CKD) than in the respective age group of patients without CKD. The therapeutic concentration range for a long-term LEV therapy was 11 to 32 μg/mL.ConclusionsLEV pharmacokinetics are significantly different between infant and preschool children, so TDM of LEV is clinically useful in these patients. In pediatric patients at higher risk for CKD, glomerular filtration rate and LEV levels should be carefully monitored.     

Factors that influence adherence with disease-modifying therapy in MS

Abstract Background   The complexity and cost of injection treatment can represent a formidable challenge for patients affected by a chronic illness, particularly those whose treatment is primarily preventative and only modestly effective on the more conspicuous symptomatic aspects of the disease process. The aim of this investigation was to identify which factors most influenced nonadherent behavior with the available diseasemodifying injection therapies for multiple sclerosis (MS). Methods   A multicenter, observational (threewave) study using surveys was developed and administered to patients with MS through the World Wide Web. Healthcare providers at 17 neurology clinics recruited patients for the study. Results   A total of 798 patients responded to the baseline wave of the study (708 responded to all three waves). The nonadherence rates for all patients (missing one or more injections) across these waves remained relatively stable at 39 %, 37 %, and 36 %, respectively. The most common reason participants listed for missing injections was that they simply forgot to administer the medication (58 %). Other factors including injection-site reactions, quality of life, patients’ perceptions on the injectable medications, hope, depression, and support were also assessed in relation to adherence. Conclusions   This study characterizes factors that are associated with failure to fully adhere with disease modifying injection therapy for MS and underscores the principles associated with optimizing adherence and its implications for effective treatment of the disease process in MS.     

Levetiracetam efficacy in children with epilepsy with electrical status epilepticus in sleep

PurposeEpilepsy with electrical status epilepticus in sleep (ESES) is a devastating disease, and we sought to evaluate the efficacy of levetiracetam (LEV) for the treatment of patients with this epileptic encephalopathy in China.MethodsClinical data from all patients with ESES who received LEV therapy at our pediatric neurology outpatient clinic between 2007 and 2014 (n = 71) were retrospectively analyzed. The LEV dosage was 30–50 mg/kg/day. Electroencephalography recordings and neuropsychological evaluations were performed repeatedly for 3–75 months after the start of LEV therapy.ResultsThirty-five (70%) of 50 patients who had seizures at the start of LEV therapy had a > 50% reduction in seizure frequency. Positive response on EEG was found during the first 3–4 months of LEV therapy in 32 (45%) of 71 patients, with normalization of EEG in 5 patients. Relapse occurred in 8 (25%) of the initial electrical responders. Hence, 47 patients (66%) still suffered from ESES and only 13 patients regained their baseline level of function at the last follow-up. The response to LEV was significantly associated with ESES duration, age at onset of ESES, and etiology of epilepsy. Although fatigue and anorexia were the primary adverse events, LEV was well-tolerated by all patients.ConclusionsLevetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.     

Valproate but not levetiracetam slows the EEG alpha peak frequency – A pharmaco-EEG study

ObjectiveStudies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF).MethodsWe retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients’ APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level.ResultsThe APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = −0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = −0.17 ± 0.18 across patients, p = 0.4072).ConclusionsOur results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment.SignificanceOur study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.     

Self-reported aggressiveness during treatment with levetiracetam correlates with depression

PurposeThe purpose of this study was to identify clinical correlates of self-reported aggressiveness (SRA) in patients with epilepsy treated with levetiracetam (LEV) with special reference to the role of depression.MethodsA consecutive sample of adult outpatients with epilepsy was assessed with the Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event Profile (AEP), and the Emotional Thermometer.ResultsFrom a total sample of 163 consecutive patients treated with LEV, SRA at any level (from rarely a problem to always) was associated with a 7-fold increased risk of being depressed (95% CI: 3.0–17.5; p < 0.001). Self-reported aggressiveness was reported as “always” a problem by 9.8% of the patients. In these patients, apart from depression, SRA was associated with high AEP total scores (55.1 vs. 39.3; p < 0.001) and polytherapy (43.8% vs. 19.8%; p = 0.034). Anxiety scores were not elevated (4.9 vs. 3.6; p = 0.183).ConclusionsSelf-reported aggressiveness during treatment with LEV is not an isolated symptom but is associated with depressed mood. Anxiety-mediated mechanisms do not seem to be involved.     

Serum free hemoglobin as a novel potential biomarker for acute ischemic stroke

Abstract Objective   Currently, no practical biomarker is available for the diagnosis of acute ischemic stroke. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has being applied extensively to analyze large biomolecules such as proteins. The technique is likely to be of remarkable value as indicators of systemic processes such as atherosclerosis and stroke. The aim of this study is to identify potential protein biomarkers for ischemic stroke diagnosis utilizing MALDITOF MS. Methods   Serum samples obtained from acute ischemic stroke patients (n = 47) and controls (n = 34) were analyzed by MALDI-TOF MS. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS), subtype by the Trial of Org 10172 in Acute Stroke Treatment (TOAST), functional outcome by the modified Rankin Scale (mRS) and infarct volume by the diffusion-weighted images. Risk factors and routine laboratory data of the stroke patients were registered prospectively. Results   The peaks of hemoglobin (Hb) α-chain and β-chain were differentially expressed between stroke patients and controls (p < 0.0001). Hb ions were detected in the samples collected from 33 (70.2 %) stroke patients and 5 (14.7 %) controls. The sensitivity is 70.2 % and the specificity is 85.3 %. Among stroke patients, there is no significant correlation (p > 0.05) between Hb peaks and the NIHSS, TOAST, mRS, stroke risk factors, infarct volume, infarct location and laboratory data. Conclusions   Serum free Hb may serve as a novel potential biomarker for the diagnosis of acute ischemic stroke. The clinical value of this potential biomarker may be clarified by further studies quantifying serum free Hb levels. Both authors have equally contributed to the work and are corresponding authors.     

Loss of the initial efficacy of levetiracetam in patients with refractory epilepsy

PurposeThe efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures.MethodsWe enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period.ResultsA total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P = 0.054). Based on Kaplan–Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months.ConclusionThis study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.     

Levetiracetam in the treatment of neonatal seizures: A pilot study

PurposeAt present, neonatal seizures are usually treated with Phenobarbital (PB) despite the limited efficacy and the potential risk this treatment holds for the developing brain. We report here a prospective pilot feasibility study on the use of Levetiracetam as monotherapy in the treatment of neonatal seizures.MethodsSix newborns (body weight > 2000 g, gestational age > 30 weeks) presenting with neonatal seizures were enrolled. Patients whose seizures were caused by electrolyte disturbances or hypoglycemia, or whose seizures did respond to pyridoxine were excluded. Patients previously treated with other antiepileptic drugs (AEDs), with the exception of single PB doses before and during titration, were excluded. LEV was administered orally, increasing the dose by 10 mg/(kg day) over 3 days. Endpoint was the need of any additional AEDs (or PB) after day 3, or 3 months of LEV treatment. A decision regarding further treatment was made on an individual basis and follow-up was documented up to 8 months of age.ResultsNo severe adverse effects were observed. Mild sedation was reported in one infant. All six patients treated with oral LEV became seizure free within 6 days. Five patients remained seizure free after 3 months with ongoing LEV monotherapy. One infant developed pharmacoresistent epilepsy. Seizures relapsed later in the clinical course of two more patients, one of whom was no longer under LEV therapy.DiscussionResults from our small patient group indicate that LEV may be an alternative therapeutic option in neonatal seizures.     

Levetiracetam for levodopa-induced dyskinesia in Parkinson’s disease: a randomized, double-blind, placebo-controlled trial

The aim of this study was to assess the efficacy, safety and tolerability of the antiepileptic compound levetiracetam (LEV) for the treatment of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). We thus performed a randomized, double-blind, placebo-controlled, parallel-group pilot study in PD patients with moderate-to-severe LID on stable dopaminergic therapy. Placebo or LEV was administered twice daily (titrated from 250 to 2,000 mg/day) as add-on therapy. Subjects underwent evaluation of the unified-PD-rating scale (UPDRS) and the modified abnormal involuntary movement scale (AIMS). The primary outcome variable was the change of the AIMS score between baseline and end-of-treatment visit. Secondary variables included total UPDRS score and response to levodopa challenge. Of 32 randomized patients (mean age 65.2 years, 62.5% women), 17 received LEV and 15 placebo. After 11 weeks of treatment, mean changes of the modified AIMS from baseline were −1.5 (−26%) for LEV (p = 0.332) and +0.9 (+13%) for placebo (p = 0.588) without significant differences between groups. Mean changes of the UPDRS item 32/33 sum score from baseline showed significant improvement of dyskinesia in the LEV group [−1.0 (−20%); p = 0.012], but not in the placebo group [−0.4 (−8%); p = 0.306]. Treatment had no effects on UPDRS motor score or levodopa response. Frequency and quality of adverse events were similar in both treatment groups. Together, LEV showed only mild antidyskinetic effects without worsening of Parkinsonian symptoms or compromising levodopa efficacy. LEV was well tolerated in doses up to 2,000 mg/day. Further large controlled studies are warranted to evaluate the impact of LEV on LID in PD patients.     

Hyperhomocysteinemia and schizophrenia: case control study

Objectives

Homocysteine (Hcys) is a sulphur-containing amino acid that has been widely investigated for its putative role in neuropsychiatric disorders. Elevated plasma homocysteine levels have been associated with schizophrenia. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. The aim of the study was to determine plasma Hcys, folate and vitamin B12, and the frequency and severity of hyperhomocysteinemia in patients with schizophrenia, and to investigate the association between Hcys and clinical features and its relationship with folate and vitamin B12 levels.

Methods

This was a case-control study carried out on 61 (54 males and seven females, mean age = 33.3 ± 9.2) inpatients with chronic schizophrenia according to DSM-IV criteria and 46 (25 males and 21 females, mean age = 45.9 ± 14.2) healthy controls. Most of patients (90.2%) were treated by first generation antipsychotics with a mean daily dosage of 401.6 mg chlorpromazine equivalents. Total homocysteine serum levels were determined quantitatively by fluorescence-polarization immunoassay (FPIA) with an AxSYM analyzer™ (Abbott). Quantitative vitamin B12 and folate serum levels were measured with an Elecsys 2010 analyzer™ (Roche Diagnostics). Differences between patients and controls were examined using a two-way Ancova with gender and diagnosis as independent variables, adjusting for age.

Results

Patients with schizophrenia showed higher plasma Hycs and lower plasma folate than controls (mean = 16.1 μmol/L in patients versus 10.9 μmol/L in controls; P = 0.028 for Hycs and 4.2 μg/L in patients versus 8.2 μg/L in controls; P < 0.001 for folate). Patients and controls did not differ in vitamin B12 levels. Both male and female patients had increased plasma Hcys compared to controls. Hyperhomocysteinemia (Hcys levels > 15 μmol/L) was present in 34.4% of the patients versus 15.2% in controls. The prevalence of moderate hyperhomocysteinemia (Hcys levels: 15–29 μmo/L) was 26.2% and that of intermediate hyperhomocysteinemia (Hcys levels: 30–100 μmol/L) was 8.2%. In patients with schizophrenia, plasma Hcys was not correlated with age (r = 0.07; P = 0.56), duration of illness (r = –0.04; P = 0.78) and did not differ with gender and clinical sub-types. Moreover, plasma Hcys was higher in patients without family history of psychiatric disorders (19.2 μmol/L) versus 12.7 μmol/L in patients with family history of psychiatric disorders (P = 0.032). Concerning therapeutic features, plasma Hcys did not differ with type of antipsychotic and was not related to daily dosage of antipsychotics. A negative correlation was found between plasma Hcys and vitamin B12 levels (r = –0.26; P = 0.04).

Conclusion

These results confirm an increase of Hcys levels in schizophrenic patients and suggest that it is associated with absence of family history of psychiatric disorders and with low vitamin B12 levels. Hyperhomocyteinemia could be related to the pathophysiology of aspects of this illness. Homocysteine should be considered as a factor to consider in monitoring and management of patients with schizophrenia.     

Course of matrix metalloproteinase-9 isoforms after the administration of uric acid in patients with acute stroke

Abstract   Oxidative stress as well as expression and activity of matrix metalloproteinase 9 (MMP-9) are rapidly enhanced after cerebral ischemia. The magnitude of these effects is related to stroke outcome. In human stroke, the extent of oxidative stress correlates well with increased MMP-9 expression. The aim of this study was to evaluate whether treatment with the antioxidant molecule uric acid (UA) decreased the levels of MMP-9 in stroke patients treated with rtPA. The patients were part of a pilot, double-blind, randomized, vehiclecontrolled study of patients with acute stroke treated with rtPA (< 3 h) and randomized to receive an intravenous infusion of UA (n = 16) or vehicle (n = 8). Total matrix metalloproteinase (tMMP)-9 and active (aMMP-9) levels were measured in serum at baseline (< 3 h), at the end of study treatment infusion (< 5.5 h), and at 48 hours. Total MMP-9 and aMMP-9 increased very early after stroke onset in patients allocated vehicle after rtPA therapy. Lower increments of aMMP-9 were associated with better outcome at 3 months. UA treatment was associated with reduced levels of aMMP-9 at T1 (p < 0.02) in multivariate models adjusted for age, NIHSS score, and baseline aMMP-9 levels. The decline of aMMP-9 attained after UA administration supports further clinical assessment of UA therapy in patients with acute stroke.     

Telemedicine in acute stroke

Abstract Background   Telemedicine is increasingly being used in acute stroke care. Some of the first studies and network projects are already applying remote audiovisual communication for patient evaluation. Formerly the telephone was the method of choice to contact experts for case discussion. We compared remote video-examination and telephone consultation in acute stroke care. Methods   Two district hospitals were linked to stroke centers in Northern Bavaria. Patients with symptoms suggestive of an acute stroke were included. Remote video examination (RVE) was provided by live audiovisual communication and access to brain images; telephone consultation (TC) was done via standard telephone using a structured interview. There was a weekly rotation of the two methods. Demographic data and other data concerning process and quality of care as well as outcome 10 days after stroke were recorded and compared between the two groups. Results   Within the study period 151 consultations were made in acute stroke patients (mean age 66.8 years). 77 patients were seen by RVE and 74 by TC. Total examination times were 49.8 min for RVE and 27.2 min for TC (p < 0.01). Patients were more frequently transferred to the stroke center after TC consultation (9.1 % vs. 14.9 %, p < 0.05) and had a higher mortality 10 days after stroke (6.8 % vs. 1.3 %, p < 0.05). Diagnosis made by TC had to be corrected more frequently (17.6 % vs. 7.1 %; p < 0.05). Conclusions   Creating a network improves stroke care by establishing cooperation between hospitals. Telephone consultation could be a simple method of telemedicine to support cooperation as it is easy and widely available. However, outcome parameters like mortality indicate that remote video examination is superior to TC. Therefore, full-scale audiovisual communication is recommended for remote consultation in acute stroke care.     

Quality of life,mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group

ObjectiveBrain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated.Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n = 19) treated with Levetiracetam as an add-on.MethodsWe recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3 months and at 6 months.This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28–70) with uncontrolled partial-onset seizures treated with LEV as add-on.The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency.ResultsTwelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400 mg/die (mean final dose 300 mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy.In the historical control group treated with LEV (mean final dose 2000 mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs.In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures ≥ 50%, 2 stable and 1 patient with number of seizures increased.Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P = 0.005). The Responder Rate was 86.4%.Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p = 0.31).In our patients treated with LCM we didn't observe significant difference at 3 and 6 months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6 months of follow-up (KPS p = 0.003; BI p = 0.007).No clinical side effects were observed.ConclusionComparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV.In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.     

Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds

Abstract Background   Retrospective studies suggested that cerebral microbleeds (MB) on magnetic resonance images (MRI) increase risk of intracerebral haemorrhage (ICH). Objective   To compare the benefit of anti-thrombotic agents in stroke prevention (absolute risk reduction 2.49 –6 %) versus risk of ICH in ischaemic stroke patients with MB. Materials and methods   We prospectively studied patients admitted consecutively for acute ischaemic stroke between 1999 and 2004. MB on MRI were documented. Primary end points were subsequent ICH, recurrent cerebral infarct (CI) and mortality. Results   A total of 908 patients were recruited. MB were identified in 252 (27.8 %) patients. Mean follow-up period was 26.6 ± 15.4 months. Risk of subsequent ICH increased significantly with quantity of MB: 0.6 % (no MB), 1.9 % (1 MB), 4.6 % (2–4 MB) and 7.6 % (≥ 5 MB) (p < 0.001). There was also a significant increase in mortality from ICH: 0.6 %, 0.9 %, 1.5 % and 3.8 % respectively (p = 0.054). Rate of recurrent CI was 9.6 %, 5.6 %, 21.5 % and 15.2 % respectively (p = 0.226). Mortality from CI and myocardial infarction did not increased with quantity of MB. Survival analyses showed that age, presence of MB, mixed cortical-subcortical distribution of MB were independent predictors of subsequent ICH. Conclusion   Risk and mortality of ICH increased with quantity of MB. As tendency to recurrent CI exceed that of ICH, anti-thrombotic agents are still warranted. However, in patients with ≥ 5 MB, the high risk and mortality of ICH seem to outweigh the modest benefit of antithrombotic agents. Extra precautions should be taken to minimize risk of ICH. Further studies in patients on Coumadin and assessment of functional outcome are warranted to support these preliminary findings.     

Effects of levetiracetam on seizure frequency and neuropsychological impairments in children with refractory epilepsy with secondary bilateral synchrony

PurposeIn epilepsy with continuous spikes and waves during slow sleep (CSWS), which is a representative epileptic syndrome of secondary bilateral synchrony (SBS), the urgent suppression of this electroencephalographic (EEG) abnormality may be necessary to prevent the progression of neuropsychological impairments. The purpose of this study was to determine the efficacy of levetiracetam (LEV) on SBS, seizure frequency, and neuropsychological impairments in children with refractory epilepsy.MethodsEleven (seven male and four female) patients with refractory epilepsy with SBS on EEG, aged between 4.7 years and 11.3 years, were included in this study. After a 3-month baseline period, the patients were given LEV at an initial dose of 10 mg/kg/day for the first week, followed at increments of 5 mg/kg/day every week, up to 20 mg/kg/day. The LEV dose was then adjusted up to a maximum of 60 mg/kg/day, according to the clinician's judgment. EEG recordings and clinical evaluations were performed every 3 months, focusing on SBS. The occurrence of SBS was then scored, and the relationship between the score and the response to LEV treatment was evaluated. In comparison with the baseline SBS frequency, the EEG response to LEV treatment was classified, and responders were identified as having a ≥50% reduction in SBS frequency. In addition, in comparison with the baseline seizure frequency, response to LEV treatment was classified. Responders were identified as patients with complete cessation (100% seizure control) and a response of ≥50% reduction in seizures. Furthermore, neuropsychological impairments such as hyperactivity, impulsiveness, and inattention were evaluated before and after LEV treatment.ResultsEight patients (72.7%) were considered responders. In addition, all eight patients were also considered responders for clinical seizures. Furthermore, 7 of 8 (87.5%) patients with response showed decreased hyperactivity and impulsivity after LEV administration.ConclusionsThe present data clearly indicate the usefulness of LEV in reducing both SBS on EEG and seizure frequency. LEV represents an important addition to the treatments available for refractory childhood epilepsies with SBS on EEG.