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.     

Clinicopathological studies of the vegetative state--distinction between the vegetative state and brain death]

10 cases showing vegetative state and 2 cases of brain death due to severe brain damage were observed and the differences of clinicopathological findings between both states were discussed. The cases of vegetative state can be divided into three groups, first is widespread lesion in the cerebral cortex, second is in the cerebral white matter and third is in the brain stem. While, the diffuse whole brain damage including the vegetative center of the central nervous system causes brain death. We should like to emphasize that the most important structure to maintain the human life is the vital center in the brain stem, and that a human being, in whom only those function can be preserved, is possible to be alive as vegetative state. Prognostic value of the EEG indicating quality of survival noted in early stage after severe brain damage has not so important as the flat EEG revealed in brain death.     

PET in coma and in vegetative state

Advances in resuscitation and critical care management have resulted in the survival of many patients despite severe brain damage. These patients may remain in coma or in vegetative state. The probability of recovery of conscious function is dependent on the extent of structural brain damage, which is difficult to assess by clinical, laboratory or functional tests. Positron emission tomography (PET) of 18F‐fluordeoxyglucose (FDG) can be used to investigate metabolic and functional impairment of the brain. In acute vegetative state (AVS, duration < 1 month), overall glucose utilization was significantly reduced in comparison with age‐matched controls. In a few cases with locked‐in syndrome, cortical metabolism was in the normal range. 11C‐Flumazenil (FMZ) measures the density of benzodiazepine receptors (BZRs) and thereby furnishes an estimate of neuronal integrity. PET with this tracer demonstrated a considerable reduction in BZRs in cortical areas, but indicated that the cerebellum was spared from neuronal loss. The comparison of FDG‐ and FMZ‐PET findings in AVS demonstrates that alterations of cerebral glucose consumption do not represent mere functional inactivation, but also irreversible structural damage. In some cases with minimally conscious state, auditory stimuli with emotional valence induced more brain activation (investigated by H215O‐PET) than meaningless noise; such studies can be used to detect residual cortical function. To improve prognostication of chances for recovery, a combination of functional activation studies and assessment of the extent of neuronal damage might be the optimal procedure and should be tested in larger cohorts of patients with comatose states of different severity.     

Brain function in the vegetative state

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.     

Brain glucose metabolism in postanoxic syndrome. Positron emission tomographic study

Thirteen positron emission tomographic studies of cerebral glucose utilization were carried out in 12 patients with postanoxic syndrome due to cardiac arrest. Seven subjects were in a persistent vegetative state. The 5 other subjects were normally conscious, but disclosed focal neurological signs. When compared with normal values, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative subjects, and to a lesser degree (+/- 25%) in conscious patients. The most consistent regional alterations were found in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories, followed by the frontomesial junction (5 cases), the striatum (3 cases with dystonia), thalamus (2 cases), and visual cortex (2 cases with cortical blindness). These data suggest that brain anoxia can result in global brain hypometabolism, which appears related to the vigilance state, as well as in regional alterations preferentially located in arterial border zones.     

严重头外伤后植物状态4例尸检报告

目的:探讨严重头外伤病人植物状态的原因。方法:对4例植物状态死者尸检观察。结果:4例尸检均可见脑及脑干弥漫性水肿,全部病例皮质及半数病例丘脑及豆状核有大灶性梗塞、出血,以及弥漫性轴索损害。结论:脑及脑干弥漫性水肿,广泛性缺血性损害及弥漫性轴索损害是严重头外伤后植物状态的形态学基础,致皮质间及皮质与丘脑间联系中断。     

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.     

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.     

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.     

Contralateral cerebellar hypometabolism following cerebral insult: a positron emission tomographic study

Positron emission tomographic studies of 16 patients with cerebral ischemia and brain tumor showed asymmetries in cerebellar metabolism not encountered in 14 normal control subjects. An asymmetry was present in 62.5% of cases. The lower metabolic rate occurred in the cerebellar hemisphere contralateral to the cerebral lesion (p less than 0.001; sign test). In all cases computed tomography showed the supratentorial lesion to be unilateral and the posterior fossa contents to be unaffected. The presence of depressed cerebellar metabolism was highly associated with involvement of the contralateral parietal lobe (p less than 0.02; phi coefficient). The presence of a cerebellar abnormality was not related to the presence of any particular sign. Serial studies showed normalization of cerebellar metabolism over time. It is likely that this effect is a result of interruption of the functional interconnections between the cerebrum and the cerebellum.     

Neonatal encephalopathy with neuronal vacuolar degeneration

A 6-month-old female with no family history of neurologic disease was born with dysmorphic features and hypotonia the cause of which could not be determined despite extensive laboratory evaluation for a primary metabolic disorder. Neuroimaging studies disclosed progressive cerebral atrophy and ventricular dilatation. Post-mortem examination of the brain revealed micrencephaly and severe neuronal cytoplasmic vacuolation notably in the thalamus and inferior olivary nuclei. The neurons of the cortex, cerebellum, and brain stem were also vacuolated, but to a lesser extent. The white matter was predominantly intact. While superficially reminsicent to the cases of spongy glio-neuronal dystrophy of Jellinger and Seitelberger [(1970) Acta Neuropathol (Berl) 16: 125–40], the severity of the neuronal vacuolation without neuronal loss and absence of seizures in this patient suggests that this condition represents a distinct pathologic entity.     

双侧大脑半球相继出血及血肿扩大合并脑干梗死的混合性卒中2例分析

目的探讨双侧大脑半球相继出血及血肿扩大合并脑干梗死的混合性卒中的可能发病机制、病因及诊治对策。方法对2例双侧大脑半球相继出血及血肿扩大合并脑干梗死的混合性卒中患者起病形式、临床表现、影像学特征以及疾病演变经过、诊治过程进行分析。结果 2例患者的起病形式、临床表现,以及影像学特征、疾病演变过程都极为相似而其脑血管病的危险因素有所不同。结论大脑半球相继出血及血肿扩大合并脑干梗死的病因、发病机制复杂,患者可能都存在相同对称的脑血管结构异常物质基础以及促发因素、脑血流动力学因素、血管活性物质的变化因素等,而脑血管病的危险因素有所不同,在诊断对策上要积极寻找原因,治疗上要慎重而周全,以免误诊误治。     

CEREBRAL BLOOD FLOW AND METABOLISM IN COMPLETE APALLIC SYNDROMES, IN STATES OF SEVERE DEMENTIA, AND IN AKINETIC MUTISM

In complete apallic syndromes with (almost total) loss of the telencephalic grey matter, the supratentorial blood flow and oxygen uptake were found to be only about 20 per cent of the normal. Such cases show no signs of higher functions and they have an isoelectric EEG. Due to the retention of brain stem structures they may, however, show clear-cut signs of arousability with lively brain stem reflexes and primitive motor reactions. In a permanently comatose case—also without higher functions—due to a selective reticular brain stem infarction, but with retained telencephalic morphology on the whole, extremely low values (about 20 per cent of normal) for the supratentorial oxygen uptake and blood flow were also demonstrated. Other states with a severe reduction, but not a complete loss of higher functions, due to posttraumatic stupor and advanced Alzheimer's disease showed higher cerebral blood flow and metabolic values than those related above. Such cases also showed a retention of an often pathological EEG. Two patients with akinetic mutism showed relatively high flow values and by and large a normal relative weight of the cortical grey matter, as well as a normal EEG. Both cases showed slight but definite signs of remaining higher functions. It is concluded that measurements of the supratentorial cerebral oxygen uptake and blood flow may be used to quantitate the functional state of the brain in patients with a loss of, or with a severe reduction of higher functions (signs of conscious awareness, voluntary motor activity, speech, and memory). It is emphasized that a complete loss of such functions may be caused by a total loss of the cortical grey matter (the complete apallic state), or by a selective lesion of the reticular system of the brain stem.     

The Marinesco-Sj?gren syndrome examined by computed tomography, magnetic resonance, and 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography

The Marinesco-Sj?gren syndrome is an autosomal recessive degenerative disorder characterized by congenital cataracts, cerebellar ataxia, spasticity, mental deficiency, and skeletal abnormalities. We studied two adult siblings with Marinesco-Sj?gren syndrome using anatomic and metabolic brain imaging techniques to characterize the pattern and nature of abnormalities in the brain. Computed tomographic and magnetic resonance imaging showed diffuse brain atrophy of mild to moderate degree, involving primarily the white matter of the cerebrum, cerebellum, brain stem, and cervical spinal cord. The pattern of atrophy resembled that seen in diffuse leukoencephalopathies. Measurements of local cerebral glucose metabolic rates with positron emission tomography revealed no statistically significant differences from normal control subjects in most regions, but metabolic rate was decreased in the thalamus in one patient. The findings support a diffuse white matter disorder in Marinesco-Sj?gren syndrome.     

Brain Levels of neuropeptide Y in experimental pneumococcal meningitis

Neuropeptide Y (NPY), which is found in high concentrations in several regions of the brain including nuclei of the brain stem and in nerve fibers surrounding cerebral vessels, has been proposed to play a role in regulating cerebral blood flow (CBF) and systemic vegetative functions. Since CBF is altered during meningitis, we examined whether NPY concentrations changed in various regions of the rabbit brain in response to experimental pneumococcal meningitis. Changes were most pronounced in the medulla, where NPY concentration increased threefold after 48 h of infection. Concomitantly, there was an increase in NPY immunoreactive fibers surrounding small vessels in the dorsolateral medulla, especially in the nucleus tractus solitarius. These results suggest that NPY may play a role in inducing some of the hemodynamic changes seen during pneumococcal meningitis.     

Consciousness in congenitally decorticate children: developmental vegetative state as self-fulfilling prophecy

According to traditional neurophysiological theory, consciousness requires neocortical functioning, and children born without cerebral hemispheres necessarily remain indefinitely in a developmental vegetative state. Four children between 5 and 17 years old are reported with congenital brain malformations involving total or near-total absence of cerebral cortex but who, nevertheless, possessed discriminative awareness: for example, distinguishing familiar from unfamiliar people and environments, social interaction, functional vision, orienting, musical preferences, appropriate affective responses, and associative learning. These abilities may reflect 'vertical' plasticity of brainstem and diencephalic structures. The relative rarity of manifest consciousness in congenitally decorticate children could be due largely to an inherent tendency of the label 'developmental vegetative state' to become a self-fulfilling prophecy.     

Pathological and etiological studies on cerebral infarction in the vertebrobasilar arterial system

25 cases of cerebral infarcts in vertebrobasilar arterial system are reported. Those were divided into 4 groups: 1. Embolism (10), the causes were NBTE, pulmonary infarct, rheumatic or congenital heart disease, coronary artery disease, respectively, and 2 unknown. 2. Thrombosis (5), the causes were arteriosclerosis, vascular malformations in the basal part of cerebrum. 3. Inflammatory infarcts (3), those were verified from tuberculosis, syphilis and aspergillosis respectively. 4. Lacunar infarcts (7), the causes were considered from hypertension. Pathologically, it was noticed that the location of embolism often situated at the terminal of basilar artery, and that if the embolism was completely obliterated, often a hemorrhagic infarction would follow. But the thrombosis in basilar artery, even the lumen was completely obliterated, any infarct would not follow, if the related collateral circulation was satisfactory. Clinically, the embolism in basilar artery often showed sudden onset, and that the symptoms of brain stem would aggravate quickly, but the thrombosis in basilar artery, if the collateral circulation was satisfactory, and symptom of brain stem might not follow.     

In vivo imaging of structural,metabolic and functional brain changes in glaucoma

Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.     

CT appearance of children in a persistent vegetative state

A morphometric CT study was performed on 17 children who were in a persistent vegetative state. Four cases with compromised brain stem function (group 1) showed a significantly smaller lateral pontine ratio (LPR, width of pons/greatest internal diameter between temporal bone) than the remaining 13 cases with preserved brain stem function (group 2) and controls. LPR was considered a useful indicator of brain stem atrophy and to correlate well with brain stem function.