经椎弓根钉板内固定治疗上颈椎疾患的个性化设计及临床应用

背景：上颈椎疾患从后路行椎弓根固定在国内个别大型医院虽已相继开展,但该手术仍为颈椎外科高难度手术。为了将手术风险降至最低,作者设计了一套个体化手术方案,并结合自行研制的椎弓根定位导向器行术中精确定位置钉,经检索相关数据库在国内未见报道。 目的：提高内固定置钉的一次成功率及植入体的生物力学效应,利用辅助检查资料为寰枢椎椎弓根螺钉的置钉制定简单、实用的个性化方案。 方法：选择2002-01/2006-09解放军第二五一医院骨科患者31例。术中采用自制的寰枢椎定位导向器,根据寰枢椎椎弓根X射线-CT个体化测量的结果,确定进钉点、入钉的角度,选择直径及长度合适的椎弓根螺钉置入。寰椎椎弓根进钉点：左侧(19.93± 1.32) mm,右侧(19.16±1.30) mm,寰椎椎弓根向内侧进钉角度：左侧(23.72±2.09)°,右侧(23.35±1.91)°,寰椎向头侧进钉角度(9.00±1.20)°。枢椎椎弓根进钉点：左侧(13.14±0.82) mm,右侧(13.85±0.79) mm。 枢椎椎弓根向内侧进钉角度：左侧(24.52±1.26)°,右侧(20.42±1.42)°,枢椎向头侧进钉角度(25.00±3.00)°。 结果与结论：①31例患者置入124枚椎弓根螺钉,1次置钉成功122枚螺钉,正确率为98.39%,有2枚因内倾角偏差不够,穿破椎弓根的外侧骨皮质而改为2次定位。②2例术后出现枕大神经痛,经对症治疗1个月后痊愈,2例螺钉穿破寰椎左侧椎弓根外侧壁,未发现脊髓、椎动脉损伤。③所有患者X射线平片显示寰椎完全复位,枢椎齿状突骨折处对位良好。CT片示螺钉与椎动脉的脊髓位置关系良好。④平均随访10.5个月,均获得骨性融合,未发现钉板断裂材料反应。无炎症、排异等宿主反应。⑤按JOA评分标准,优16例,良12例,可2例,差1例,优良率90%。提示从生物力学角度实施植入体置入,可提高寰枢椎椎弓根螺钉的置入成功率。     

寰枢椎定位导向内固定置钉点、角度、直径及长度的个性化设计

目的：为提高内固定置钉的一次成功率，利用辅助检查资料为寰枢椎椎弓根螺钉的置钉制定简单、实用的个性化方案。 方法：选择2002-01/2006-09解放军第二五一医院骨科患者31例。术中采用自制的寰枢椎定位导向器，根据寰枢椎椎弓根X射线-CT个体化测量的结果，确定进钉点、入钉的角度，选择直径及长度合适的椎弓根螺钉置入。寰椎椎弓根进钉点：左侧（19.93±1.32）mm，右侧（19.16±1.30）mm，寰椎椎弓根向内侧进钉角度：左侧（23.72±2.09）°，右侧（23.35±1.91）°，寰椎向头侧进钉角度（9.00±1.20）°。枢椎椎弓根进钉点：左侧（13.14±0.82）mm，右侧（13.85±0.79）mm。 枢椎椎弓根向内侧进钉角度：左侧（24.52±1.26）°右侧（20.42±1.42）°，枢椎向头侧进钉角度（25.00±3.00）°。 结果：①对31例患者置入124枚椎弓根螺钉，1次置钉成功122枚螺钉，正确率为98.39%，有2枚因内倾角偏差不够，穿破椎弓根的外侧骨皮质而改为2次定位。②2例术后出现枕大神经痛，经对症治疗1个月后痊愈，2例螺钉穿破寰椎左侧椎弓根外侧壁，未发现脊髓、椎动脉损伤。③所有患者X射线片显示寰椎完全复位，枢椎齿状突骨折处对位良好。CT片示螺钉与椎动脉的脊髓位置关系良好。④平均随访10.5个月，均获得骨性融合，未发现钉板断裂材料反应。⑤按JOA评分标准，优16例，良12例，可2例，差1例，优良率90.32%。 结论：X射线-CT个性化设计方案可提高寰枢椎椎弓根螺钉的置入成功率。     

寰枢侧方关节撑开结合关节重塑技术治疗颅底凹陷合并寰枢椎脱位的临床疗效

目的观察寰枢侧方关节间撑开结合关节重塑技术治疗颅底凹陷合并寰枢椎脱位的临床效果。方法回顾性分析2019年10月至2021年9月首都医科大学三博脑科医院脊髓脊柱中心诊治的12例颅底凹陷合并寰枢椎脱位患者的临床资料。所有患者均合并寰枕融合, 斜坡枢椎角度均减小。术中均行关节间撑开松解侧方关节, 再进行关节重塑, 调整关节面的倾斜角度;然后置入融合器, 使寰椎向上及向后方旋转移动, 并进行固定。所有患者采用日本骨科协会(JOA)评分评估临床症状的改善情况;测量手术前后寰齿间距、齿状突超过钱氏线的距离、斜坡枢椎角度及延髓脊髓角度的变化, 评估寰枢椎复位及齿状突成角移位的矫正情况。结果所有患者均成功重塑关节面并置入螺钉, 均行枕骨-枢椎内固定。手术时长为(191.7±46.9)min, 术中出血量为(182.5±69.3)ml, 无一例患者发生椎动脉及硬脊膜损伤。术后1周内, 颈椎CT显示12例患者的寰枢椎脱位均获得复位, 其中齿状突超过钱氏线的距离由术前的(10.0±3.5)mm减少至术后的(4.2±2.3)mm, 寰齿间距由术前的(6.7±2.1)mm减少至术后的(1.4±0.8)mm;颈椎...     

自发性寰枢关节脱位后路复位内固定术中枢椎椎弓根螺钉置入不能时的备选方法

目的探讨自发性寰枢关节脱位后路内固定过程中枢椎椎弓根螺钉置入不能时,其他备选螺钉内固定技术的安全性及有效性。方法对贵州省人民医院神经外科未采用枢椎椎弓根螺钉内固定治疗的11例自发性寰枢关节脱位患者的临床资料进行回顾性分析。在枢椎椎弓根螺钉置入不能时,采用枢椎椎板螺钉、峡部螺钉、枢椎下关节突螺钉及延长固定节段至C3侧块螺钉来增加稳定性的方法。手术前后分别行CT及MRI检查,评价脊髓受压程度、脱位复位情况、螺钉位置、骨融合情况;通过比较术前、术后日本骨科协会(JOA)评分来评价疗效。结果 11例患者均为枢椎椎弓根置钉不能,改用备选方法置钉,全部行枕颈钉棒内固定。共置入枢椎椎板锣钉14枚,枢椎峡部螺钉5枚,枢椎下关节突螺钉1枚,延长固定节段至C3侧块螺钉4枚。术中均未发生椎动脉和脊髓神经根损伤。11例患者的寰枢关节脱位均得到不同程度的复位,随访中无患者出现螺钉松动、滑脱、断钉及复位丢失等情况,JOA评分为显著增加。结论对自发性寰枢关节脱位后路内固定过程中枢椎椎弓根螺钉置入不能时,可根据情况,个性化选用枢椎椎板螺钉、峡部螺钉、枢椎下关节突螺钉及延长固定节段至C3侧块螺钉的方法来固定,是可行且有效的。     

不同类型椎动脉V3段颅底凹陷合并寰枢椎脱位的内固定策略

目的研究颅底凹陷合并寰枢椎脱位患者椎动脉V3段的危险变异类型和发生率, 探讨不同类型椎动脉V3段患者的内固定策略。方法回顾性分析2017年1月至2019年1月首都医科大学宣武医院神经外科采用内固定融合手术重建颅颈交界区稳定性的56例颅底凹陷合并寰枢椎脱位患者的临床和影像学资料。对于不合并椎动脉解剖变异的患者, 采取寰椎侧块螺钉联合枢椎椎弓根螺钉行内固定治疗;对于椎动脉骨外段变异患者, 术中尽可能采取枕骨螺钉替代寰椎侧块螺钉;对于高跨椎动脉(骨内段变异)患者, 采用枢椎椎板螺钉或者峡部螺钉代替椎弓根螺钉。所有患者术后均常规行颈椎X线平片和头颈部CT检查评估内固定器械的位置以及是否发生后循环缺血梗死。结果 56例患者中, 不合并椎动脉变异患者18例(32.1%);椎动脉骨外段变异20例(35.7%), 包括永存第一节间椎动脉16例, 椎动脉开窗和硬膜外起源小脑后下动脉各2例;高跨椎动脉28例(50.0%)。其中, 骨外段变异合并高跨椎动脉变异10例(17.9%)。56例患者在置入枢椎螺钉时均未出现椎动脉损伤情况。1例椎动脉开窗患者术中显露寰椎侧块和寰枢椎关节时, 开窗椎动脉下干损伤大出血,...     

前外侧入路治疗颈椎病的应用解剖学研究

目的通过对颈椎C3～C7各项指标的测量,为前外侧入路治疗颈椎病提供解剖学依据。方法测量35例C3～C7干燥标本的横突孔、钩椎关节、椎体和椎管的相关数据。结果①椎体前缘至横突孔前缘距离C3～C6逐渐减小,C3为(8.28±1.70)mm,C6为(7.17±1.15)mm。②横突孔横径一般左侧大于右侧,横突孔横径平均为(5.94±0.48)mm,在C5最小,为(5.35±0.81)mm。③横突孔间距离C3～C7逐渐增加,C3为(23.12±0.93)mm,C7为(31.64±2.28)mm。④钩椎关节间距离C3～C7逐渐增加,C3为(19.09±1.54)mm,C7为(25.02±2.97)mm。⑤钩椎关节至椎间孔内侧缘的距离C7最大,为(4.76±1.49)mm;C5最小,为(3.79±0.73)mm。⑥C3～C7椎体前后径平均值为(15.78±1.64)mm。⑦椎管直径相差不大,平均为13～14mm。结论颈椎前外侧入路是治疗颈椎病的理想术式,研究和熟悉手术入路相关解剖结构对指导手术十分必要。     

颅颈交界区螺钉-钛棒(板)内固定技术的临床应用

目的 探讨螺钉-钛棒(板)内固定技术治疗颅颈交界区不稳定的临床经验.方法 27例颅颈交界区不稳定患者(先天性寰枢关节脱位21例、颅底凹陷症经口齿状突切除致寰枢关节脱位1例、外伤致寰枢关节脱位1例、经口斜坡脊索瘤切除致寰枢关节脱位3例和椎管内神经纤维瘤病致寰枕关节破坏1例),手术前日本整形外科协会(JOA)评分1～13分,平均(7.45±1.62)分,施行枕骨钉或寰椎侧块-枢椎椎弓根螺钉内固定术,并通过螺钉间撑开技术使寰枢关节复位.根据手术后JOA评分和影像学改善程度,评价手术疗效.结果 27例患者中除1例手术后临床症状无明显变化,余26例均明显改善.手术后2周CT检查椎体间融合良好,仅2例(2枚)枢椎椎弓根螺钉穿破骨皮质,但未造成血管损伤或神经压迫,其余螺钉位置良好.随访3～36个月,平均10.50个月.手术后3个月,患者JOA评分1～13分,平均(13.26±1.02)分,与手术前比较,差异具有统计学意义(t=24.210,P=0.001);平均改善率为(60±12)%.结论 枕骨钉或寰椎侧块.枢椎椎弓根螺钉内固定术治疗颅颈交界区不稳定安全有效.     

Ⅰ期术中复位经后路枕颈融合术治疗原发性颅底凹陷合并寰枢椎脱位

目的探讨原发性颅底凹陷合并寰枢椎脱位的临床特点、外科手术治疗方式及临床效果。方法回顾分析2008年1月-2011年12月住院治疗且经影像学检查明确诊断的89例原发性颅底凹陷合并寰枢椎脱位患者的临床资料,男性28例,女性61例;年龄10~69岁,平均45.42岁。经后正中入路Ⅰ期施行复位器辅助寰枢关节复位,以两块AO钢板连接枕骨与第2,3颈椎侧块螺钉内固定,取自体髂骨行枕颈植骨融合,并随访观察手术效果。结果共随访6~48个月,大多数患者临床症状明显改善,日本骨科协会评分由术前的8.80±1.36增至术后的15.35±1.47,手术前后比较差异有统计学意义(t=17.225,P=0.001);手术改善率达82.93%。手术前后影像学测量平均值比较,寰齿间距(9.22mm∶3.72mm)和齿状突顶点至Chamberlain线垂直距离(10.41mm∶3.23mm)减小,而延髓颈髓角(130°∶150°)和脊髓可用空间(11.13mm∶15.54mm)增加,4项指标均不同程度改善。结论术中Ⅰ期复位辅助植骨融合内固定术治疗原发性颅底凹陷合并寰枢椎脱位操作步骤简单,安全性高,疗效确切,但远期手术疗效尚有待长期随访观察。     

定量解剖学观察髋臼前柱骨折螺钉内固定置入的力学特征

背景：近年来切开复位内固定成为骨盆骨折和髋臼骨折的一种重要治疗手段,但是在内固定过程中有时会发生螺钉穿入关节内、损伤盆腔内重要血管或神经等严重并发症。 目的：测量髋臼前柱骨折拉力螺钉内固定技术中螺钉的最佳进钉点、角度和长度。 设计、时间及地点：测量性实验,于2008-06/10在山东大学医学院解剖学教研室完成。 材料：取成年男性半骨盆标本20个,制作髋臼前柱系列断面。 方法：在单螺钉技术中,测量进钉点O与坐骨大切迹顶点Q之间的水平距离OP和垂直距离PQ的长度,测量螺钉长度。在双螺钉技术中,分别测量内侧螺钉的进钉点O1和外侧螺钉的进钉点O2与坐骨大切迹顶点Q之间的水平距离O1P1、O2P2和垂直距离P1Q、P2Q的长度,分别测量内侧螺钉和外侧螺钉的长度。测量螺钉矢状面的角度α和冠状面的角度β,将测量数据输入到SPSS 10.0软件进行统计学分析。 主要观察指标：髋臼前柱拉力螺钉技术中螺钉的进钉点、角度和长度。 结果：单螺钉技术：OP和PQ的长度分别为(23.5±2.2) mm和(16.8±1.6) mm,螺钉长度为(84.9±4.7) mm。双螺钉技术：O1P1和P1Q的长度分别为(26.3±2.3) mm和(13.6±1.4) mm,内侧螺钉的长度为(69.8±4.1) mm;O2P2长度(20.7±2.1) mm,P2Q长度(20.1±1.8) mm,外侧螺钉的长度(61.2±3.7) mm。α角为(123.4±4.1)°,β角为(62.2±5.8)°。 结论：单螺钉技术螺钉的进钉点位于坐骨大切迹顶点处垂直于后柱内侧缘向外17 mm,再平行于后柱内侧缘向上24 mm,长度约85 mm。双螺钉技术内侧螺钉的进钉点位于坐骨大切迹顶点处垂直于后柱内侧缘向外14 mm,再平行于后柱内侧缘向上26 mm,螺钉长度70 mm。外侧螺钉的进钉点位于坐骨大切迹顶点处垂直于后柱内侧缘向外20 mm,再平行于后柱内侧缘向上21 mm,螺钉长度61 mm。拉力螺钉与后柱内侧缘平行线所成的角度为123°左右,与后柱内侧缘平行线的垂线所成的角度为62°左右。螺钉位置一定要通过多角度、多方位的透视证实。     

I期术中复位经后路枕颈融合术治疗原发性颅底凹陷合并寰枢椎脱位

目的探讨原发性颅底凹陷合并寰枢椎脱位的临床特点、外科手术治疗方式及临床效果。方法回顾分析2008年1月-2011年12月住院治疗且经影像学检查明确诊断的89例原发性颅底凹陷合并寰枢椎脱位患者的临床资料,男性28例,女性61例;年龄10～69岁,平均45．42岁。经后正中人路I期施行复位器辅助寰枢关节复位,以两块AO钢板连接枕骨与第2,3颈椎侧块螺钉内固定,取自体髂骨行枕颈植骨融合,并随访观察手术效果。结果共随访6～48个月,大多数患者临床症状明显改善,日本骨科协会评分由术前的8．80±1．36增至术后的15．35±1．47,手术前后比较差异有统计学意义（t=17．225,P=0．001）;手术改善率达82．93％。手术前后影像学测量平均值比较,寰齿间距（9．22mm：3．72mm）和齿状突顶点至Chamberlain线垂直距离（10．41mm：3．23mm）减小,而延髓颈髓角（130°：1500）和脊髓可用空间（11．13mm：15．54mm）增加,4项指标均不同程度改善。结论术中I期复位辅助植骨融合内固定术治疗原发性颅底凹陷合并寰枢椎脱位操作步骤简单,安全性高,疗效确切,但远期手术疗效尚有待长期随访观察。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.