唑吡坦对失眠症患者睡眠影响的多导睡眠图研究

目的 应用多导睡眠图(PSG)探讨唑吡坦对失眠症患者睡眠脑电活动的影响.方法 对27例符合国际疾病分类标准第10版(ICD-10)非器质性失眠症诊断标准的患者连续进行3晚PSG描记,其中第3晚睡前予10 mg唑吡坦,观察用药后PSG的变化.正常对照组33名,作1夜适应和1夜基础PSG监测.结果 与基线睡眠比较,患者服用唑吡坦后睡眠效率提高[(91%±4%)vs(87%±8%),P＜0.05],觉醒时间减少[(24±6)min vs(39±16)min,P＜0.01],S1减少[(18%±6%)vs(30%±18%),P＜0.01],S2增加[(60%±5%)vs(44%±18%),P＜0.01],睡眠潜伏期缩短[(36±18)min vs(22±11)min,P＜0.01].结论 唑吡坦对失眠症患者夜间多导睡眠图脑电有影响.     

唑吡坦治疗慢性意识障碍的研究进展

唑吡坦是非苯二氮卓类的咪唑吡啶类药物,是选择性GABA（A）受体激动剂,常用于治疗失眠。临床发现唑吡坦对部分慢性意识障碍患者有显著"促醒"作用,但扩大样本的研究在群体水平上未发现唑吡坦的显著疗效,提示其治疗效果与个体敏感程度有关。     

唑吡坦按需治疗失眠症的临床研究

目的　探讨唑吡坦非每夜给药 (按需治疗 )对慢性失眠症的疗效及不良反应。方法　比较唑吡坦非每夜给药 (按需治疗 )和唑吡坦每夜给药 (持续治疗 )的疗效和不良反应。对慢性失眠者 40例进行对照研究。结果　持续治疗和按需治疗疗效相近 ,治疗过程中无反跳现象及撤药反应。结论　唑吡坦按需治疗方法有效可行 ,对不需每夜服药 ,又害怕对药物产生依赖的患者提供了一个较好的长期治疗方案。     

唑吡坦按需治疗失眠症的临床研究

目的 探讨唑吡坦非每夜给药(按需治疗)对慢性失眠症的疗效及不良反应。方法 比较唑吡坦非每夜给药(按需治疗)和唑吡坦每夜给药(持续治疗)的疗效和不良反应。对慢性失眠者40例进行对照研究。结果 持续治疗和按需治疗疗效相近，治疗过程中无反跳现象及撤药反应。结论 唑吡坦按需治疗方法有效可行，对不需每夜服药，又害怕对药物产生依赖的患者提供了一个较好的长期治疗方案。     

θ爆发刺激治疗卒中相关失眠的疗效分析

目的 观察连续性θ爆发刺激(cTBS)治疗卒中相关失眠的疗效。方法 纳入亚急性期脑梗死患者60例，采用匹兹堡睡眠质量指数(PSQI)进行测评，以PSQI量表总分>7分作为判断睡眠障碍的标准。随机分为药物治疗组、联合治疗组，各30例。药物治疗组给予唑吡坦10 mg口服、联合治疗组给予唑吡坦5 mg口服+cTBS模式刺激右侧背外侧前额叶和顶枕区域，分别比较两组患者抗失眠药物停药时间和2周停药率、PSQI减分率、NIHSS评分、HAMD和HAMA评分的变化，以观察cTBS治疗卒中相关失眠的临床疗效。结果 联合治疗组平均停药时间短于药物治疗组，2周停药率均高于药物治疗组(P<0.05);两组患者NIHSS评分、HAMD及HAMA评分随治疗时间呈现好转趋势，同一随访时间组间比较无明显差异。由于两组患者HAMD、HAMA评分交互P有统计学意义，说明随着时间的变化，两组间的HAMD、HAMA评分会出现差异。结论 cTBS对于卒中相关失眠的治疗具有明显作用，且一定程度上改善了患者的焦虑抑郁状态。     

曲唑酮片联合唑吡坦治疗失眠对SDRS PSQI评分及PSG指标的影响

目的 分析曲唑酮片联合唑吡坦治疗失眠对睡眠障碍评定量表(SDRS)、匹兹堡睡眠质量指数(PSQI)及多导睡眠图(PSG)的影响.方法 纳入120例于2018-05—2021-10于郑州大学第二附属医院接受治疗的失眠患者,A组40例施予曲唑酮片治疗,B组40例施予唑吡坦治疗,C组40例施予曲唑酮片联合唑吡坦治疗,对比3组SDRS、PSQI评分及PSG各指标.结果 治疗后7 d、14 d、28 d,C组SDRS评分分别为(14.04±5.57)分、(10.15±4.32)分、(7.82±3.62)分,均较A组(18.73±6.41、12.15±5.53、11.37±4.55)、B组(18.32±5.92、12.42±4.37、11.23±4.65)低,差异均有统计学意义(P<0.05);C组PSQI评分分别为(12.29±1.29)分、(12.35±1.04)分、(7.14±0.63)分,均较A组(15.83±1.34、14.32±1.27、12.29±1.29)、B组(15.84±1.43、14.45±1.15、12.35±1.04)低,差异均有统计学意义(P<0.05);C组中PSG睡眠效率、睡眠总时间、醒觉时间、入睡时间(82.53±6.74、389.24±33.34、80.27±32.63、29.24±4.77)各项指标优于A组(74.18±6.83、333.61±34.69、120.53±33.48、36.08±4.17)、B组(73.84±7.03、334.63±35.75、120.63±34.15、35.93±3.84),差异均有统计学意义(P<0.05).结论 失眠患者给予曲唑酮片联合唑吡坦治疗效果显著,有助于改善患者的SDRS、PSQI评分及PSG指标.     

脑电生物反馈治疗失眠症的疗效观察

目的：观察脑电生物反馈对失眠症的治疗效果。方法：将70例失眠症患者随机分为研究组和对照组各35例，研究组进行脑电生物反馈治疗，对照组进行药物治疗，治疗前后进行匹茨堡睡眠质量指数量表（PSQI）评定，比较两组疗效。结果：治疗后，研究组PSQI总分及睡眠潜伏期、睡眠持续性、习惯性、使用睡眠药物、睡眠紊乱、白天功能紊乱等因子分均较治疗前显著降低；与对照组比较，研究组治疗后睡眠潜伏期，睡眠持续性，白天功能紊乱等因子分降低更明显。结论：脑电生物反馈治疗可以明显改善失眠症患者症状，疗效优于传统药物治疗。     

急性脑梗死偏瘫肢体出现肌张力的时间对功能恢复的影响

目的 探讨急性脑梗死患者偏瘫肢体肌张力出现的早晚对临床疗效、运动功能、日常生活能力的影响.方法 按脑梗死后10d出现或不出现肌张力,将所选急性脑梗死患者分为A组和B组,对2组患者治疗前及治疗后1个月的神经功能缺损程度积分,运动功能评分(FMA)、修订的巴氏指数(MBI)进行比较.结果 A、B组治疗1个月后神经功能缺损程度积分、 FMA、 MBI均有显著性差异.结论 急性脑梗死患者偏瘫肢体肌张力出现越早,其临床疗效越好,运动功能恢复越好,日常生活能力越强.     

头针配合平衡针刺法治疗脑卒中后肌张力增高的临床疗效

目的 探讨头针配合平衡针刺法治疗脑卒中后肌张力增高的疗效。方法 选取2013年10月-2016年10月本院神经内科收治的脑卒中后肌张力增高患者66例,采用简单随机化方法将患者分为观察组31例与对照组35例; 观察组采用头针配合平衡针刺法,对照组采用传统脑卒中恢复期针刺方法; 比较2组患者治疗前后肌张力、肢体运动功能及生活自理能力。结果 治疗前2组患者肌张力评分比较无显著性差异(P>0.05); 治疗结束后观察组肌张力评分显著优于对照组(P<0.05); 疗程结束后2组患者肢体运动功能及生活自理能力均能显著改善观察组治疗前后比较有极显著性差异(P<0.01),对照组治疗前后比较有显著性差异(P<0.05); 2组观察组Fugl-Meyer及Barther Index评分优于对照组(P<0.05)。结论 头针配合平衡针刺法能够有效降低脑卒中后增高的肌张力,改善患者日常生活自理能力,促进肢体运动功能恢复。     

认知行为自助疗法和唑吡坦治疗慢性失眠的对照研究

目的 比较电话指导下的认知行为自助疗法(CBTI-SH)和酒石酸唑吡坦对慢性失眠的疗效. 方法 选择自2011年7月至2012年10月中山大学附属三院精神心理科门诊慢性失眠患者60例,按奇偶数法分为研究组和对照组各30例.对照组给予睡眠卫生教育+剂量递减的酒石酸唑吡坦治疗:药物起始剂量为10 mg/d,每周递减1/4剂量,疗程4周;研究组给予睡眠卫生教育+CBTI-SH治疗:疗程4周,内容包括认知重建、睡眠限制、刺激控制、放松训练,将CBTI-SH的内容制成文字材料,由患者自助实施,第1、3周末分别给予15 min的电话指导.在基线时及第2、4、6周末应用匹茨堡睡眠质量指数量表(PSQI)、Epworth嗜睡量表(ESS)对睡眠情况进行评价;要求患者每天记录睡眠日志,评价指标包括入睡潜伏期、入睡后觉醒时间、睡眠时间、卧床时间、睡眠效率;要求患者进行依从性评价,即过去1周内有多少天按照要求执行了CBTI-SH或睡眠卫生教育的6种主要成分. 结果 重复测量的方差分析显示,研究组和对照组PSQI量表、ESS量表评分及入睡潜伏期、睡眠效率、睡眠时间、卧床时间、入睡后觉醒时间在治疗前后不同时间之间的差异均有统计学意义(P＜0.05),且研究组的改善明显优于对照组,效应量分别为1.93、0.04、1.00、0.98、0.11、0.57、0.43.研究组对“不在床上做其他事”和“不在床上担忧”的依从性高于对照组,而对“限制卧床时间”、“不能睡则离开床”的依从性低于对照组,差异均有统计学意义(P＜0.05). 结论 和应用剂量递减的酒石酸唑吡坦治疗策略相比,CBTI-SH治疗慢性失眠及伴随的日间思睡的疗效更优,但部分依从性有待提高.     

Induced arousal following zolpidem treatment in a vegetative state after brain injury in 7 cases Analysis using visual single photon emission computerized tomography and digitized cerebral state monitor

BACKGROUND: Several studies have reported the use of zolpidem for induced arousal after permanent vegetative states. However, changes in brain function and EMG after zolpidem treatment requires further investigation. OBJECTIVE: To investigate the effect of zolpidem, an unconventional drug, on inducing arousal in patients in a permanent vegetative state after brain injury using visual single photon emission computerized tomography and digitized cerebral state monitor. DESIGN: A self-controlled observation. SETTING: Shenzhen People's Hospital.PARTICIPANTS: Seven patients in a permanent vegetative state were selected from the Department of Neurosurgery, Shenzhen People's Hospital from March 2005 to May 2007. The group included 5 males and 2 females, 24–55 years of age, with a mean age of 38.5 years. All seven patients had been in a permanent vegetative statement for at least six months. The patient group included three comatose patients, who had sustained injuries to the cerebral cortex, basal ganglia, or thalamus in motor vehicle accidents, and four patients, who had suffered primary/secondary brain stem injury. Informed consents were obtained from the patients’ relatives. METHODS: The patients brains were imaged by 99Tcm ECD single photon emission computerized tomography prior to treatment with zolpidem [Sanofi Winthrop Industrie, France, code number approved by the State Food & Drug Administration (SFDA) J20040033, specification 10 mg per tablet. At 8:00 p.m., 10 mg zolpidem was dissolved with distilled water and administered through a nasogastric tube at 1 hour before and after treatment and 1 week following treatment, respectively. Visual analysis of cerebral perfusion changes in the injured brain regions before and after treatment was performed. Simultaneously, three monitoring parameters were obtained though a cerebral state monitor, which included cerebral state index, electromyographic index, and burst suppression index. MAIN OUTCOME MEASURES: Comparison of the three brain function indices, cerebral perfusion in the areas of brain injury, and clinical indices before and after treatment. RESULTS: All seven patients were included in the final analysis. ① Following treatment, the parameters of cerebral state index and electromyographic index were significantly higher than before treatment (P < 0.05). The burst suppression index was significantly lower than before treatment (P < 0.05). ② Cerebral perfusion in areas of brain injury improved significantly in all subjects compared to before treatment. CONCLUSION: The findings of visual single photon emission computerized tomography and digitized cerebral state monitor reveal that Zolpidem appears to be an effective treatment for restoring brain function to certain patients in a permanent vegetative state.     

Impetuous suicidality with zolpidem use: a case report and minireview

Zolpidem is a clinically effective hypnotic medication for treating chronic insomnia. In the last decade, there has been increasing documentation of altered consciousness and behavioral changes following zolpidem administration. This report presents a case of a probable zolpidem induced suicide attempt and highlights similar studies of suicidal thoughts and behaviors of other patients that have taken the drug. We examine zolpidem and other treatments for insomnia, including the FDA approved hypnotics and frequently prescribed off-label medications, in terms of prescribing practices and adverse effects, especially altered consciousness and risk of suicide. Parallels are identified between the untoward activating side effects of zolpidem and its off-label use for patients in persistent vegetative states. We hypothesize that similar to the proposed mechanism in which the wakefulness promoted by zolpidem in vegetative patients is mediated by disruption of GABAergic tone in neurodormant brain regions, there may occur in patients with parasomnias interference of GABA activity in brain regions that maintain a high level of inhibitory regulation. Dosing recommendations are offered together with the FDA Safety Announcement addressing dose reductions for women due to possible carry-over effects the morning after ingesting zolpidem.     

The role of evoked potentials in anoxic-ischemic coma and severe brain trauma.

The early recognition of comatose patients with a hopeless prognosis-regardless of how aggressively they are managed-is of utmost importance. Median somatosensory evoked potentials supplement and enhance neurologic examination findings in anoxic-ischemic coma and severe brain trauma, and are useful as an early guide to outcome. The key finding is that bilateral absence of cortical evoked potentials, generated by thalamocortical tracts, reliably predicts unfavorable outcome in comatose patients after cardiac arrest, and correlates strongly with death or persistent vegetative state in severe brain trauma. The author studied 50 comatose patients with preserved brainstem function after cardiac arrest. All 23 patients with bilateral absence of cortical evoked potentials died without awakening. Neuropathologic study in seven patients disclosed widespread ischemic changes or frank cortical laminar necrosis. The remaining 27 patients with normal or delayed central conduction times had an uncertain prognosis because some died without awakening or entered a persistent vegetative state. The majority of patients with normal central conduction times had a good outcome, whereas a delay in central conduction times increased the likelihood of neurologic deficit or death. This report includes a systematic review of the literature concerning adults in anoxic-ischemic coma and severe brain trauma, in which somatosensory evoked potentials were used as an early guide to predict clinical outcome. Greater use of somatosensory evoked potentials in anoxic-ischemic coma and severe brain trauma would identify those patients unlikely to recover and would avoid costly medical care that is to no avail.     

GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke – A case report

ObjectiveThe paradoxical effects of the hypnotic imidazopyridine zolpidem, widely reported in persistent vegetative state, have been replicated recently in brain-injured and cognitively impaired patients. However, the neuronal mechanisms underlying these benefits are yet to be demonstrated. We implemented contemporary neuroimaging methods to investigate sensorimotor and cognitive improvements, observed in stroke patient JP following zolpidem administration.MethodsWe used Magnetic-Resonance-Imaging (MRI) and Magnetic-Resonance-Spectroscopy (MRS) to anatomically and chemically characterize stroke damage. Single-photon-emission-computed-tomography (SPECT) and magnetoencephalography (MEG) were used to identify changes in cerebrovascular perfusion and neuronal network activity in response to sub-sedative doses of zolpidem, zopiclone and placebo. Cognitive improvements were measured using the WAIS-III and auditory-verbal tasks.ResultsMRI and MRS revealed a lesion with complete loss of neuronal viability in the left temporal–parietal region; whilst SPECT indicated improved perfusion in the affected hemisphere following zolpidem. MEG demonstrated high-amplitude theta (4–10 Hz) and beta (15–30 Hz) oscillations within the peri-infarct region, which reduced in power coincident with zolpidem uptake and improvements in cognitive and motor function.ConclusionsIn JP, functional deficits and pathological oscillations appear coincidentally reduced following administration of low-dose zolpidem.SignificanceGABA(A) alpha-1 sensitive desynchronisation of pathological oscillations may represent a biomarker and potential therapeutic target in brain injury.     

脑挫裂伤患者亚急性期脑疝临床分析

目的探讨脑挫裂伤患者亚急性期突发脑疝的发病原因、临床特点及治疗方法。方法回顾性分析我科1995年1月～2007年9月间收治的27例脑挫裂伤患者在亚急性期突发脑疝的临床资料。结果脑挫裂伤后一周左右继发脑水肿加重、迟发性脑内血肿脑挫裂伤患者亚急性期突发脑疝的常见时间及原因。本组有16例在病情恶化后接受手术治疗,术后死亡2例,持续植物状态2例,重残2例,中残1例,恢复良好9例。保守治疗11例,死亡1例,恢复良好10例。结论外伤后一周左右是大多数脑挫裂伤患者亚急性期发生脑疝的高峰期,及时保守治疗和手术治疗是治疗的有效方法。     

Differences in cerebral blood flow and glucose utilization in vegetative versus locked-in patients

Positron emission tomographic studies of regional cerebral metabolic rate for glucose (rCMRGlc) and cerebral blood flow were performed in 7 vegetative and 3 locked-in patients to determine objectively the level of brain function underlying these clinical states. Cortical gray rCMRGlc in the vegetative patients was 2.73 +/- 0.13 (mean +/- SEM) mg/100 gm/min, less than half the normal value of 6.82 +/- 0.23 (p less than 0.001). Cerebral blood flow exhibited similar but more variable reductions. By contrast, cortical rCMRGlc in the locked-in patients was 5.08 +/- 0.69, a 25% reduction (p less than 0.02) from normal. The massive reduction in vegetative rCMRGlc involved not only the cerebral cortex but also the basal nuclei and cerebellum. Such metabolic hypoactivity has precedent only in deep anesthesia and supports clinical evidence that cerebral cognitive function is lost in the vegetative state, leaving a body that can no longer think or experience pain.     

A case of primary brain-stem injury recovered from persistent vegetative state after L-dopa administration]

A 51-year-old male was transferred to our hospital just after traffic accident. On admission, the patient was comatose (Glasgow Coma Scale of 6) and showed a left hemiparesis with a left oculomotor nerve palsy. Computed tomography demonstrated a traumatic subarachnoid hemorrhage without mass lesion. Magnetic resonance imaging showed high intensity lesions on the left dorsolateral midbrain and the right cerebral peduncle. The distribution of lesions implied diffuse axonal injury involving dopaminergic systems such as the substantia nigra and the ventral tegmental area. After several months of conservative management, the patient showed no recovery and was diagnosed as persistent vegetable state. The administration of L-dopa was then started and the patient showed remarkable neurological improvement. Therefore the patient's neurological status was thought to be modified with primary brain stem injury and accompanying traumatic Parkinson's syndrome. It is important to understand "pseudo" persistent vegetative state in the management of patients showing prolonged consciousness disturbance. L-dopa should be considered as the drugs of pharmacological intervention for the patients of masked parkinsonism behind "pseudo" persistent vegetative state whose dopaminergic systems might have been damaged.     

Evoked potentials for the prediction of vegetative state in the acute stage of coma

For comatose patients in intensive care units, it is important to anticipate their functional outcome as soon and as reliably as possible. Among clinical variables the Glasgow Coma Score (GCS) and the patient's pupil reactivity are the strongest predictive variables. Evoked potentials help to assess objectively brain function. Over the past 20 years, numerous studies have assessed their prognostic utility in terms of awakening from coma. Fewer studies, however, have focused upon the utility of evoked potentials in predicting progression to the vegetative state. In this area evoked potentials appear to have a highly predictive value. In anoxic coma the abolition of somatosensory evoked potentials (SEPs) is related to a poor outcome, defined as death or survival in a vegetative state, with a 100% specificity. Following traumatic brain injury, the predictive value for unfavourable outcome is 98.5% when there are no focal injuries likely to abolish SEP cortical components. In contrast, the presence of event-related evoked potentials, and particularly mismatched negativity (MMN), is a strong predictor of awakening and precludes comatose patients from moving to a permanent vegetative state (PVS).     

Neocortical death in infants: Behavioral, neurologic, and electroencephalographic characteristics

Neocortical death is a form of the persistent vegetative state characterized by the maintenance of sleep/wakeful cycles and spontaneous respirations and the lack of cognitive function. It is difficult to diagnose in neonates and young infants because their cognitive skills are limited by inexperience and by immaturity of the central nervous system. Because neocortical death has not been described previously for this age group, we report the neurologic, behavioral, electroencephalographic, and computed tomographic characteristics of three infants who survived in the persistent vegetative state following severe brain injury. Each infant appeared to exhibit some complex behaviors, including interaction with the environment and the examiners, although the electroencephalograms documented no electrical activity of cerebral origin. Computed tomography revealed extensive destruction of the cerebral hemispheres. Infants and newborns with a history suggesting brain injury and with the neurologic and behavioral characteristics described here should be evaluated with serial electroencephalograms and computed tomography to diagnose the syndrome of neocortical death.     

Clinical features of cases whose cerebral blood flow was preserved only in the basal ganglia region

In the series of our studies of positron emission tomography (PET), we had some cases whose cerebral blood flow was reduced in the cerebrum, cerebellum and brain stem, and was preserved only in the basal ganglia region. We studied their clinical features and electrophysiological findings of these cases. These 5 cases included neuronal ceroid lipofuscinosis, Krabbe disease, Tay-Sachs disease, progressive myoclonus epilepsy and subacute sclerosing panencephalitis. Clinically they showed symptoms associated with diffuse cerebral and brain stem involvements. Electrophysiological studies also revealed the involvements of cerebrum and brain stem. These 5 cases were classified to persistent vegetative state clinically. Vegetative state was considered to be heterogeneous concerning about cerebral metabolism. There may be one group presenting a peculiar cerebral metabolic condition described here in vegetative states. And this condition may be specific to some neurodegenerative or metabolic disorders that involve cerebellum and brain stem as well as cerebrum.