Brain death

Current law in the United States authorizes physicians to diagnose brain death by applying generally accepted neurologic criteria for determining loss of function of the entire brain. This article offers a medical-legal perspective on problems that may arise with respect to the determination of brain death. These include the possibility of diagnostic error, conceptual disagreements that may constrain the use of neurologic criteria to diagnose death, and the conflation of brain death and loss of consciousness. This article also addresses legal aspects of the debate over whether to expand the definition of brain death to include permanent unconsciousness. Although existing laws draw a clear distinction between brain death and the persistent vegetative state, many courts have authorized removal of life support from individuals whose unconsciousness is believed to be permanent on proof that removal accords with preferences expressed before sentience was lost.     

唑吡坦对脑损伤植物状态患者促醒疗效的观察

目的 观察非常规促醒药物唑吡坦对脑损伤昏迷植物状态患者的促醒作用,分析该作用是否存在干预时间相关性. 方法 采用单光子发射型计算机体层摄影技术观察7例服用唑吡坦的持续性植物状态患者服药0.5 h前后及1周后99Tcm-双半光乙酯(ECD)脑灌注显像.做可视化分析;应用脑状态监测仪(CSM)进行检测,对比用药前后脑状态指数、肌电指数、爆发抑制指数的变化;观察患者临床指标变化,包括语言功能、肢体运动功能、肌张力、睡眠质量等的变化. 结果 (1)患者服药后脑状态指数、肌电指数均高于服药前爆发抑制指数低于用药前,差异均有统计学意义(P<0.05).(2)服药后7例患者脑损害区血流较服药前明显增加.(3)7例患者中3例成功促醒,表现为服药后0.5 h能与家人及医生进行简单的交流,用药后第2天便能做简单的数学运算,下肢可遵嘱做屈曲运动.其中1例原有的肢体震颤及扭转痉挛明显缓解:余4例肌张力及睡眠质量改善. 结论 唑吡坦能恢复部分脑损害持续性植物状态患者的脑功能,脑功能的改善与服药时间长短无关,脑功能的改善是"一步到位"而非"逐步改善".     

Xenon computed tomography measuring cerebral blood flow in the determination of brain death in children

Local cerebral blood flow was measured using stable xenon computed tomography in 21 children, 10 of whom were clinically brain dead and had electrocerebral silence as determined by electroencephalography. Radioisotopic brain scanning in 9 patients showed no visible cerebral activity in all patients and minimal residual sagittal sinus activity in 4. In this population, mean cerebral blood flow as measured by xenon computed tomography was 1.3 +/- 1.6 ml/min/100 gm. Respiratory support was discontinued in 8 patients, and 2 patients had cardiac arrest. Eleven profoundly comatose children who did not meet all clinical criteria for brain death and who had markedly suppressed but not isoelectric electroencephalograms had an average cerebral blood flow of 33.5 +/- 16.3 ml/min/100 gm. There was no difference in cerebral blood flow in those children who survived (30.4 +/- 16.3 ml/min/100 gm; n = 7) compared with those who died acutely (38.3 +/- 14.3 ml/min/100 gm; n = 4). Two patients who survived had average total flows of only 11.8 and 12.1 ml/min/100 gm. Our findings suggest that in infants and children older than 1 month, (1) cerebral blood flow below approximately 10 ml/min/100 gm is consistent with clinical brain death, (2) cerebral blood flow of less than 5 ml/min/100 gm is consistent with no flow as demonstrated by radionuclide techniques, and (3) flow of more than 10 to 15 ml/min/100 gm is associated with the potential for survival.     

Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats

In infants, a common consequence of systemic perinatal insults is disruption of neonatal brain development. Such insults can cause cerebral palsy, cognitive delay, epilepsy and other chronic neurologic deficits in children. The mechanisms underlying disruption of brain development after perinatal insults are poorly defined. To mimic human systemic insults, a transient prenatal hypoxic-ischemic insult model was developed in rodents. Ischemic animals showed reproducible histological lesions including oligodendrocyte loss, gliosis, and axonal disruption. Ischemic animals displayed persistent postnatal loss of oligodendrocyte lineage cells and cortical neurons, decreased cell proliferation, increased cell death, elevated pro-inflammatory cytokine levels, and impaired motor skills as young adults. Progressive ischemic intervals produced a graded pattern of injury. This systemic rodent prenatal hypoxic-ischemic insult accurately models human perinatal brain injury in several important criteria, including functional association of altered brain development with motor delay, and consequently provides novel insights into the pathogenesis of human perinatal brain insults.     

Technetium-99m-HmPAO brain SPECT in infantile Gaucher's disease

The authors report serial technetium-99m hexamethylpropylene-amine-oxime brain single photon emission computed tomography (SPECT) findings in two infants with Gaucher's disease type 2. Detailed neurologic and laboratory examinations, including bone marrow biopsies and enzymatic assays, were described. Serial brain magnetic resonance imaging studies in one patient illustrated the progressive cerebral atrophy in the frontal and temporal lobes. The SPECT in both cases demonstrated positive findings of initial scattered hypoperfusion, with extending to hypoperfusion of the entire cerebrum after 4 months of clinical deterioration. These changes in the SPECT findings may reflect progressive degeneration of the cerebrum in Gaucher's disease type 2. Brain SPECT may provide useful information on cerebral flow and metabolic distribution corresponding to the neurologic deficits of neuronopathic Gaucher's disease.     

Neurologic complications in long-standing nephropathic cystinosis

The central nervous system has been considered to be uninvolved in nephropathic cystinosis. Survival into adulthood, following renal dialysis and transplantation, has brought attention to the sequelae of long-standing cystinosis. We examined 14 patients with cystinosis, 12 of whom had undergone renal transplantation. Two patients had neurologic symptoms. One patient had progressive bradykinesia, dementia, and spasticity with computed tomographic scan evidence of cerebral atrophy and multifocal mineralization in bilateral internal capsules and periventricular white matter. One patient had behavioral and, to a lesser extent, cognitive disturbance and computed tomographic scan evidence of marked, progressive cerebral atrophy. Although the remaining patients had normal results of neurologic examinations, 11 had roentgenographic evidence of generalized cerebral atrophy; 2 of these had abnormal electroencephalograms, 1 had borderline-deficient intellectual function, and 2 had computed tomographic scan evidence of multifocal, intracerebral mineralization. The patients with nervous system abnormalities were not distinguished by patterns of medication use, demographic or laboratory features, or the relative severity of cystinosis. Although the neurologic involvement in these patients suggests that cystinosis may eventually involve the central nervous system, the differential diagnosis must include other complications from renal failure, dialysis, and immunosuppression.     

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.     

Results of N-methyl-d-aspartate antagonists in perinatal cerebral asphyxia therapy

Perinatal cerebral asphyxia, which results in significant neurologic and cognitive disabilities in infants and children, remains a major health problem. Potential neurologic sequelae include cerebral palsy, mental retardation, and epilepsy. Over the next few years, neuroprotective agents that prevent asphyxial neuronal injury and death are likely to be developed. These agents may also be effective in prophylaxis and treatment of chronic neurologic disorders, including epilepsy and neurodegenerative disorders, such as Huntington disease.     

Results of N-methyl-D-aspartate antagonists in perinatal cerebral asphyxia therapy

Perinatal cerebral asphyxia, which results in significant neurologic and cognitive disabilities in infants and children, remains a major health problem. Potential neurologic sequelae include cerebral palsy, mental retardation, and epilepsy. Over the next few years, neuroprotective agents that prevent asphyxial neuronal injury and death are likely to be developed. These agents may also be effective in prophylaxis and treatment of chronic neurologic disorders, including epilepsy and neurodegenerative disorders, such as Huntington disease.     

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.     

Multimodality comparison of neuroimaging in pediatric traumatic brain injury

Traumatic brain injury is a common cause of death and disability in children; early neuroimaging has assumed an increasingly important role in evaluating the extent and severity of injury. Several imaging methods were assessed in a study of 40 children with traumatic brain injury: computed tomography (CT), T(2)-weighted magnetic resonance imaging (MRI), fluid-attenuated inversion recovery (FLAIR) MRI, and susceptibility-weighted imaging (SWI) MRI to determine which were most valuable in predicting 6-12 month outcomes as classified by the Pediatric Cerebral Performance Category Scale score. Patients were subdivided into three groups: (1) normal, (2) mild disability, and (3) moderate/severe disability/persistent vegetative state. T(2), FLAIR, and SWI showed no significant difference in lesion volume between normal and mild outcome groups, but did indicate significant differences between normal and poor and between mild and poor outcome groups. Computed tomography revealed no significant differences in lesion volume between any groups. The findings suggest that T(2), FLAIR, and SWI MRI sequences provide a more accurate assessment of injury severity and detection of outcome-influencing lesions than does CT in pediatric traumatic brain injury patients. Although CT was inconsistent at lesion detection/outcome prediction, it remains an essential part of the acute traumatic brain injury work-up to assess the need for neurosurgic intervention.     

Neonatal asphyxia: vulnerability of basal ganglia, thalamus, and brainstem

Two infants who suffered acute intrapartum asphyxia resulting in severe neonatal encephalopathy are described. Although computed tomography revealed no abnormalities, magnetic resonance imaging documented unequivocal lesions in the thalamus, basal ganglia, parasagittal cortex, brainstem tectum, and midline cerebellum in one patient and in the basal ganglia and parasagittal cortex in the other. Thus, magnetic resonance imaging was more sensitive than computed tomography in detecting acute brain damage after neonatal asphyxia and may become an important tool in improving our understanding of the relationship between adverse perinatal events, neonatal encephalopathy, and neurologic morbidity.     

Xenon-enhanced computed tomography in brain death

The absence of cerebral blood flow is a valuable adjunct confirming clinical criteria of brain death. However, current methods to confirm absent cerebral blood flow have problems that limit their clinical use. We reviewed cerebral blood flow data obtained with xenon-enhanced computed tomography in nine patients who were being evaluated for brain death. In eight patients who met clinical criteria for brain death, mean cerebral blood flow was 1.6 +/- 2.0 mL X 100 g X min. This value was within the range of error inherent in the method, and therefore represented absent flow. In a patient with persistent respiratory efforts, flow values compatible with absent flow were obtained in the supratentorial compartment, while mean flows as high as 24 mL X 100 g X min were measured in selected regions of interest in the infratentorial compartment, correlating with the clinical evidence of residual function of the brain stem. Xenon-enhanced computed tomography may be a useful test to confirm the absence of cerebral blood flow in patients being evaluated for brain death.     

Detecting residual cognitive function in persistent vegetative state

Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H(2)(15)O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.     

Detecting Residual Cognitive Function in Persistent Vegetative State

Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H 2 15 O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.     

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.     

Disorders of consciousness: the basis for ethical assessment

During the past few years there is an ethical debate about neurological disease entities that are characterised by a) prolongation of life owing to medical treatment, b) limited chances of cure, and c) impaired to unbearable life quality: akinetic mutism, vegetative state ("Wachkoma", apallic syndrome), and locked-in syndrome. These are compared to typical coma and brain death. According to Gerstenbrand (1967) [34] the vegetative state is differentiated into the transitional state following typical coma, the variations of typical and incomplete vegetative state, the remission state and the "Durchgangssyndrom" (characterized by preserved wakefulness with affective lability, disorientation, and amnesia). With regard to pathogenesis we differentiate posttraumatic and posthypoxic origin and variable lesions in cerebral cortex, thalamus or mesencephalic reticular formation. Uncertainty of prognosis is stressed. In respect of brain death we compare a) neocortical death, b) brain stem death, and c) whole brain death, and discuss problems of difficult delimitation and uncertainty of diagnosis. These syndromes are compared to anencephaly and hydranencephaly. Regarding the locked-in syndrome, typical, incomplete and complete (total) forms are distinguished. The differential diagnosis between the complete locked-in syndrome and brain stem death seems problematic. Difficulties in decisions limiting therapeutic effort stem from a) essentially intuitive judgement about observations, b) variability of syndromes and courses, c) uncertainty of prognosis, and d) differences in understanding and valuation throughout society. Emphasis is on a trustful and open colloquy among the persons concerned.     

Epilepsy in children with attention deficit disorder: cognitive, behavioral, and neuroanatomic indices

Our study examined the hypothesis that if epilepsy adversely influences the cognitive and behavioral performance of children, then children with both attention deficit-hyperactivity disorder and epilepsy (ADHD-Sz) should exhibit more severe cognitive and behavioral difficulties and be more likely to demonstrate abnormalities on cranial computed tomography than ADHD children without epilepsy. We compared ADHD-Sz and ADHD patients using a variety of psychologic, behavioral, and educational measures, as well as cranial computed tomography. ADHD-Sz children scored significantly below the ADHD group on the Wechsler Intelligence Scale for Children-Revised (performance and full scale scores). In both ADHD-Sz and ADHD groups, the prevalence of learning disabilities (LD) and a variety of behavioral features were similar. Neither seizure disorder nor ADHD was associated with an increased incidence of structural abnormalities or asymmetries of the brain. These findings support the belief that epilepsy adversely affects IQ but does not appear to affect the prevalence of LD or behavioral abnormalities in ADHD children. They further support the accumulating body of data demonstrating normal brain anatomy in ADHD by computed tomography.     

Cerebral venous thrombosis in neonates and children.

Twenty-five patients (10 neonates, 15 children) with cerebral venous thromboses diagnosed by magnetic resonance imaging or computed tomography over a 10-year period were reviewed retrospectively. Two groups were analyzed separately because of their differing modes of presentation and outcome. Eighty percent of neonates presented with seizures and the outcomes were unfavorable in more than 50%. Thrombosis usually was associated with an acute systemic illness, such as shock or dehydration. In comparison, headache was the most common mode of presentation in the older children (excluding infants) and their outcomes generally were favorable. Thrombosis in this group usually occurred in the setting of a hypercoagulable state or an infectious process. In both groups, global or focal neurologic findings on initial examination unrelated to increased intracranial pressure correlated with the presence of an infarction on computed tomography or magnetic resonance imaging. Infants and children with infarction due to a deep venous thrombosis often had persistent neurologic disability at subsequent examination. No sequelae were observed in those children and neonates only with thrombosis or with superficial venous infarction. Treatment for both groups was conservative. No patient was anticoagulated specifically for the thrombosis. The good outcomes in most patients suggest that acute anticoagulation may not be indicated.     

Progress in periventricular leukomalacia

Periventricular leukomalacia (PVL) is the predominant form of brain injury and the leading known cause of cerebral palsy and cognitive deficits in premature infants. The number of low-birth-weight infants who survive to demonstrate these neurologic deficts is increasing. Magnetic resonance imaging-based neuroimaging techniques provide greater diagnostic sensitivity for PVL than does head ultrasonography and often document the involvement of telencephalic gray matter and long tracts in addition to periventricular white matter. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Premyelinating oligodendroglia are highly vulnerable to death caused by glutamate, free radicals, and proinflammatory cytokines. Studies in animal models of PVL suggest that pharmacologic interventions that target these toxic molecules will be useful in diminishing the severity of PVL.