Frameless stereotactic procedures in pediatric patients: safety and diagnostic efficacy

Purpose  

The aim of our retrospective study was to evaluate the feasibility, safety, and diagnostic yield of a frameless method for stereotactic neurosurgical procedures in pediatric patients.     

Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy

Purpose: To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. Methods: We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients’ epilepsy and the outcome of lacosamide treatment was gathered and analyzed. Results: Twenty-one patients (16 boys, 5 girls) were included, with a median age of 13.9 (range, 1.2–17.9) years. The mean number of concomitant antiepileptic drugs was 3.0 (range, 1–6) and the mean duration of follow-up was 10.1 (range, 6.1–13.0) months. The mean maintenance dose of lacosamide was 5.4 (range, 1.4–9.8) mg/kg/day. Fourteen patients (67%) were responders; four of these were seizure free at the last follow-up. Seven patients (33%) were nonresponders: two of these presented with <50% seizure reduction and five showed no change in seizure frequency. Two patients (10%) discontinued oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-related adverse events were observed in eight of the 21 patients (38%). Conclusions: Lacosamide represents a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and is well tolerated.     

Lacosamide in refractory mixed pediatric epilepsy: a prospective add-on study

Lacosamide is a new antiepileptic drug that is currently approved by the US Food and Drug Administration (FDA) for adults 17 years or older for partial-onset seizures. The authors reviewed 21 pediatric patients (<17 years) with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy. Five patients were excluded due to less than 3 months of meaningful follow-up. Maintenance dosages used ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50% reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%) patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome. Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8 (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure reduction. None of these very refractory patients remained seizure free.     

齐拉西酮与利培酮治疗精神分裂症患者的对照研究

目的:比较齐拉西酮与利培酮治疗精神分裂症患者的疗效与不良反应。方法:120例符合中国精神障碍分类与诊断标准第3版精神分裂症诊断标准的患者随机分为两组,每组60例,分别给予齐拉西酮与利培酮治疗8周,采用阳性与阴性症状量表(PANSS)评定疗效,治疗中出现的症状量表(TESS)评定不良反应,用世界卫生组织编制的生活质量量表(WHOQOL-100)评定生活质量。结果:治疗8周后,齐拉西酮组显效率73.3%,有效率90.0%,利培酮组显效率66.7%,总有效率86.7%,两组疗效比较差异无统计学意义(P>0.05);两组WHOQOL-100各领域评分较治疗前均明显改善(P>0.01);齐拉西酮组不良反应发生率16.7%,利培酮组为13.3%,两组差异无统计学意义(P>0.05)。结论:齐拉西酮与利培酮治疗精神分裂症患者的疗效相当,不良反应小,明显改善患者生活质量。     

Efficacy and safety of lamotrigine in pediatric patients

Accumulating data suggest that lamotrigine, which has been available for adult use in epilepsy for more than a decade in clinical practice, also confers effective, well-tolerated control of a range of childhood epilepsies. Lamotrigine is currently approved for the treatment of epilepsy by regulatory authorities in 93 countries, more than 70 of which have approved its use in pediatric patients on the basis of data from well-controlled clinical trials. The controlled clinical trials data have been supplemented over the years by clinical practice data, primarily from uncontrolled studies, confirming or demonstrating additional efficacy of lamotrigine for a range of seizure types. This article reviews the data from well-controlled clinical trials and studies conducted in clinical practice to present an updated perspective on the efficacy and safety of lamotrigine in pediatric patients.     

Lacosamide as add-on in brain tumor-related epilepsy: preliminary report on efficacy and tolerability

Lacosamide (LCM) is an antiepileptic drug (AED) that has demonstrated a good efficacy in controlling seizures as an add-on in adult epilepsy. To date, there have been no studies on LCM in patients with brain tumor-related epilepsy (BTRE). To evaluate efficacy and tolerability of LCM as an add-on in BTRE, we followed 14 patients suffering from BTRE who had already been treated with other AEDs and who had not experienced adequate seizure control. Eleven patients underwent chemotherapy while being treated with LCM. Mean duration of follow up was 5.4 months (min < 1 max 10 months). Mean seizure number in the last month prior to the introduction of LCM had been 15.4. At last follow-up, the mean seizure number was reduced to 1.9/month. Lacosamide mean dosage was of 332.1 mg/day (min 100 max 400 mg/day). Responder rate was 78.6%. One patient discontinued LCM because of side-effects. There were no other reported side-effects. Preliminary data on the use of LCM in add-on in patients with BTRE indicate that this drug may represent a valid alternative as an add-on in this particular patient population. However, larger samples are necessary in order to draw definitive conclusions.     

Ziprasidone: efficacy and safety in patients with bipolar disorder

Atypical antipsychotics have been increasingly shown to have efficacy in the treatment of various phases of bipolar disorder. Ziprasidone acts primarily through serotonergic and dopaminergic receptor antagonism, and exerts effects as an inhibitor of serotonin and norepinephrine reuptake. Ziprasidone exhibits dose proportional, linear changes in exposure and is hepatically metabolized primarily by aldehyde oxidase. In studies of patients with acute manic or mixed episodes, treatment with ziprasidone monotherapy or in combination with lithium, resulted in rapid symptom improvement and was generally well tolerated. Results from open-label extension studies of ziprasidone indicate continued improvement in manic symptoms. Preliminary data in pediatric patients with bipolar disorder also suggest it may be efficacious in this population. Ziprasidone is considered as a first-line treatment option in patients with bipolar manic or mixed episodes, with or without psychosis and displays a favorable side-effect profile.     

Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a 2-week randomized outpatient trial

BackgroundEsmirtazapine (Org 50081), a high-affinity antagonist at 5-HT_2A and H₁ receptors, was assessed for its hypnotic efficacy.MethodsIn this double-blind, randomized study, non-elderly patients with primary insomnia (but otherwise healthy) were treated with esmirtazapine (1.5, 3.0, or 4.5 mg) or placebo for two weeks. The primary end point was patient-reported total sleep time (TST); other patient–reported end points included sleep latency (SL), wake time after sleep onset (WASO), number of awakenings, sleep quality, and satisfaction with sleep duration. Measures to assess the potential adverse effects of treatment included morning alertness, daytime function/napping, and rebound insomnia during a single-blind placebo run-out week after treatment ended. Adverse events (AEs) were also assessed.ResultsOverall, 526 patients were randomized and 463 (88%) completed treatment. All esmirtazapine doses significantly improved TST, SL, sleep quality, and satisfaction with sleep duration versus placebo. Relative to placebo, TST was increased by 30–40 min and SL decreased by ~12 min for all doses. The highest dose (4.5 mg) also significantly reduced WASO and number of awakenings. Across doses, AEs occurred in 25.5–32.8% of patients, compared with 20.7% with placebo. The most common AE was somnolence (~10% for esmirtazapine and 2% for placebo). The incidence of AEs leading to discontinuation was low (≤7%), and there were no serious drug–related AEs. Finally, there was no evidence of a rebound insomnia after discontinuation of esmirtazapine.ConclusionsTwo weeks of treatment with esmirtazapine consistently and significantly improved patient-reported sleep parameters, and it was well tolerated in patients with primary insomnia.     

Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy

This paper comprises a series of experiments in rodent models of partial and generalized epilepsy which were designed to describe the anti-convulsant profile of the functionalized amino acid lacosamide. Lacosamide was effective against sound-induced seizures in the genetically susceptible Frings mouse, against maximal electroshock test (MES)-induced seizures in rats and mice, in the rat hippocampal kindling model of partial seizures, and in the 6Hz model of psychomotor seizures in mice. The activity in the MES test in both mice (4.5mg/kg i.p.) and rats (3.9 mg/kg p.o.) fell within the ranges previously reported for most clinically available anti-epileptic drugs. At both the median effective dose for MES protection, as well as the median toxic dose for rotorod impairment, lacosamide elevated the seizure threshold in the i.v. pentylenetetrazol seizure test, suggesting that it is unlikely to be pro-convulsant at high doses. Lacosamide was inactive against clonic seizures induced by subcutaneous administration of the chemoconvulsants pentylenetetrazol, bicuculline, and picrotoxin, but it did inhibit NMDA-induced seizures in mice and showed full efficacy in the homocysteine model of epilepsy. In summary, the overall anti-convulsant profile of lacosamide appeared to be unique, and the drug displayed a good margin of safety in those tests in which it was effective. These results suggest that lacosamide may have the potential to be clinically useful for at least the treatment of generalized tonic-clonic and partial-onset epilepsies, and support ongoing clinical trials in these indications.     

Longer-term follow-up of nusinersen efficacy and safety in adult patients with spinal muscular atrophy types 2 and 3

The effectiveness of nusinersen treatment in patients with spinal muscular atrophy (SMA) was established in clinical trials only for pediatric patients. Few cohort studies confirmed its benefit in adults up to 22 months of treatment. We report a longer-term observation of nusinersen treatment effects and safety in a large cohort of adult patients. Patients with SMA type 2 and 3 treated with nusinersen at Tel-Aviv Medical Center between March 2018 and September 2020 were prospectively recruited. Neurological impairment, motor, respiratory function, and side effects were recorded. We compared baseline measurements with those after 6, 14, and 26 months of treatment and calculated the annual rates of change. Overall, 37 patients were treated (21–64 years old). 16 completed 26 months, and 8 completed 30 months of treatment. The median score on the Medical Research Council strength scale increased from baseline to visits at 6 and 14 months (p ≤ 0.03), but not afterwards, with a median increase of 1.85 points per year. Revised Hammersmith Scale median score increased only from baseline to 6 months (p = 0.02), with a calculated annual rate of change of 0 points. No significant change was noticed in the respiratory function. The only side effect was post lumbar puncture headache. In conclusion, our study further supports the efficacy and safety of nusinersen treatment in adult patients with SMA2 and SMA3, with modest improvement in muscle strength, and stabilization of motor function over a relatively long period of observation.     

左乙拉西坦治疗成人癫痫的疗效及安全性分析

目的分析左乙拉西坦在成人癫痫患者中的疗效、耐受性及安全性。方法选取我院2013-02—2014-06收治的98例癫痫患者为研究对象,随机分为试验组(LEV治疗)和对照组(常规用药)各49例,疗程40d,观察疗效及不良反应。结果观察组有效率81.6%,对照组为61.2%,2组疗效比较差异有统计学意义(P0.05)。2组指标异常、厌食、嗜睡等不良反应差异无统计学意义(P0.05)。个别患者出现皮疹、白细胞下降症状并不是应用左乙拉西坦造成的。结论左乙拉西坦(LEV)作为一种新型药物,安全性较高,在癫痫治疗的初、中期患者耐受性好,单独使用其治疗效果也十分显著。     

Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial

ObjectiveEsmirtazapine (Org 50081), a medication that binds with high affinity to serotonin 5-HT_2A and histamine-1 receptors, was evaluated as a potential treatment for insomnia.MethodsAdults with primary insomnia were treated with esmirtazapine (3.0 or 4.5 mg) or placebo in this 6-week, double-blind, randomized, polysomnography (PSG) study. The end points included wake time after sleep onset (WASO) (primary), latency to persistent sleep, and total sleep time. Patient-reported parameters were also evaluated, including sleep quality and satisfaction with sleep duration. Residual daytime effects and rebound insomnia (sleep parameters during the single-blind placebo run-out week after treatment ended) were also assessed.ResultsOverall, 419 patients were randomized and 366 (87%) completed treatment. The median decrease in PSG WASO (double-blind average) was 20.5 min for placebo, and 52.0 min and 53.6 min for the 3.0- and 4.5-mg esmirtazapine groups, respectively (P < 0.0001 vs. placebo for both doses). Changes in the other PSG parameters and in all patient-reported parameters were also statistically significant with both doses versus placebo. Overall, 35–42% of esmirtazapine-treated patients had adverse events (AEs) versus 29% in the placebo group. AEs were mild or moderate in most esmirtazapine-treated patients. Furthermore, the incidence of AEs leading to discontinuation was low (<8%).ConclusionsSix weeks of treatment with esmirtazapine was associated with consistent improvements in objective and patient-reported parameters of sleep onset, maintenance, and duration. It was generally well tolerated, and residual daytime effects were minimal and no rebound insomnia was observed.     

Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy

Accumulating data suggest that the antiepilepsy drug lamotrigine, which has been available for adult use for more than a decade, also confers broad-spectrum, well-tolerated control of epilepsy in children. The current study--the open-label continuation phase of several short-term clinical trials--was conducted to assess the long-term tolerability and efficacy of lamotrigine as open-label adjunctive therapy or monotherapy in pediatric patients for a variety of seizure types and syndromes including partial seizures, absence seizures, and Lennox-Gastaut syndrome. Clinic visits occurred every 24 weeks throughout the treatment period. A total of 252 patients under 16 years of age were enrolled in the study. The numbers of patients exposed to at least 48 weeks, 96 weeks, and 144 weeks of treatment with lamotrigine were 185 (73.4%), 119 (47.2%), and 60 (23.8%), respectively, for an average duration of exposure of 96.7 weeks. The most common adverse events considered by the investigator to be drug related were dizziness (9.1%), somnolence (7.9%), nausea (6.3%), vomiting (5.2%), and headache (5.2%). The most common serious adverse events (regardless of suspected cause) included pneumonia (3.0%) and infection (1.9%). Investigators judged that the overall clinical status of three-fourths of the patients had improved at treatment weeks 48 and 96 relative to prelamotrigine clinical status. Lamotrigine administered as monotherapy or adjunctive therapy for an average of 2 years (96.7 weeks) was well tolerated and effective in pediatric patients with partial or generalized epilepsy. These results complement and extend the large body of data demonstrating the tolerability and efficacy of lamotrigine with short- and long-term use in adults.     

Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy.

Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its use is common in the elderly whose psychosis is a feature of neurological morbidity (Parkinson's disease, dementia, etc.), making it difficult to ascertain the safety, tolerability, and efficacy in psychiatric disorders in late life. The aim of the present review is to evaluate clozapine's effect in elderly psychiatric patients with no neurological comorbidity. A computerized literature search (MedLine 1966 to 1997) revealed 133 patients fulfilling said criteria. Fifteen patients had side effects and/or adverse events during treatment; nine of these were receiving a dosage greater than 100 mg clozapine daily. In 19 patients, treatment was discontinued, three due to noncompliance and 16 due to side effects. In seven patients, leukopenia/agranulocytosis was reported. The majority of side effects (27 of 34) and treatment discontinuations were within the first 90 days of treatment. Although efficacy is difficult to compare across studies because of differing methods of evaluation, the great majority of patients showed moderate to marked improvement of psychotic features. The reported effectiveness in patients able to continue treatment for extended periods is significant. Thus, clozapine at a relatively low mean dose (134 mg daily) seems to be safe, tolerated, and effective in elderly psychiatric patients. Agranulocytosis is more frequent than in younger adults and should be monitored carefully.     

Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study

Purpose

To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures.