Calcium channel blockade with nimodipine reverses MRI evidence of cerebral oedema following acute hypoxia.

Acute cerebral hypoxia causes rapid calcium shifts leading to neuronal damage and death. Calcium channel antagonists improve outcomes in some clinical conditions, but mechanisms remain unclear. In 18 healthy participants we: (i) quantified with multiparametric MRI the effect of hypoxia on the thalamus, a region particularly sensitive to hypoxia, and on the whole brain in general; (ii) investigated how calcium channel antagonism with the drug nimodipine affects the brain response to hypoxia. Hypoxia resulted in a significant decrease in apparent diffusion coefficient (ADC), a measure particularly sensitive to cell swelling, in a widespread network of regions across the brain, and the thalamus in particular. In hypoxia, nimodipine significantly increased ADC in the same brain regions, normalizing ADC towards normoxia baseline. There was positive correlation between blood nimodipine levels and ADC change. In the thalamus, there was a significant decrease in the amplitude of low frequency fluctuations (ALFF) in resting state functional MRI and an apparent increase of grey matter volume in hypoxia, with the ALFF partially normalized towards normoxia baseline with nimodipine. This study provides further evidence that the brain response to acute hypoxia is mediated by calcium, and importantly that manipulation of intracellular calcium flux following hypoxia may reduce cerebral cytotoxic oedema.

Predictors for delayed encephalopathy following acute carbon monoxide poisoning.

BACKGROUND: In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether "delayed neuropsychiatric sequelae (DNS)" will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases. METHODS: This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc. RESULTS: Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions. CONCLUSION: In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks' follow-up to watch for the development of DNS is considered necessary.

Pseudohypoxic brain swelling after elective clipping of an unruptured anterior communicating artery aneurysm.

A case of pseudohypoxic brain swelling, a newly defined entity, is described. The patient experienced generalized seizures and did not awake initially after a seemingly uneventful elective craniotomy for clipping of an unruptured anterior communicating artery aneurysm. Neuroimaging findings demonstrated diffuse brain swelling, especially in the bilateral basal ganglia and thalami. The rarity of this postoperative complication is addressed and the pathogenesis discussed.

Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings.

Conventional MR, diffusion-weighted, and diffusion tensor imaging were performed in an 8-day-old girl with citrullinemia. She had severe hyperammonemia for several days. On conventional T2-weighted MR images, symmetric, confluent high signal intensity was found in the bilateral thalami, basal ganglia, cortex, and subcortical white matter. Diffusion-weighted imaging demonstrated decreased apparent diffusion coefficient in these areas, reflecting cytotoxic edema. Follow-up MR imaging at the age of 4 months revealed subcortical cysts, ulegyric changes, and atrophy, which were most prominent in the occipital lobes. Diffusion tensor imaging revealed decreased anisotropy throughout the brain, consistent with diffuse injury to the oligodendro-axonal unit. Diffusion-weighted and diffusion tensor imaging are valuable techniques for the detection of irreversible brain damage and for the characterization of hyperintense lesions on T2-weighted MR images in patients with the neonatal form of citrullinemia.

[Time course of toxic hypoxic encephalopathy during combined therapy including hyperbaric oxygenation]. / Dinamika toksikogipoksicheskoi éntsefalopatii pod vozdeistviem kompleksnogo lecheniia s primeneniem giperbaricheskoi oksigenatsii.

The mechanisms of action of hyperbaric oxygenation (HBO) in toxic hypoxic encephalopathy (THE) were studied using clinical psychopathological examinations, functional and laboratory tests in 268 patients with THE treated by a therapeutic complex including HBO and 75 patients with THE treated routinely (controls). The earliest possible addition of HBO to a complex of treatment of THE patients led to involution of signs of brain edema shown by computer tomography (CT) and improvement of its functional activity, while in patients exposed to HBO later the psychoorganic symptoms and CT signs of cerebral ischemia did not disappear. Detoxifying, neuroimmunomodulating, and neuroimmunostimulating effects of HBO in THE were demonstrated. Early HBO treatment decreased the dysfunction of various compartments of the brain characteristic of THE. The technology of HBO developed by the authors prevented the development of socially dysadapting psychoneurological disorders and reduced the mortality of THE patients.

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

FDG-PET analysis and findings in amnesia resulting from hypoxia.

The assumptions underlying neuroimaging, and problems in its analysis and interpretation, are commonly underestimated in neuropsychology. The ways in which fluoro-deoxy-glucose (FDG) positron emission tomography (PET) data can be analysed are discussed. PET findings from four patients who had suffered severe amnesia, following episodes of acute hypoxia, are presented. These patients had shown evidence of medial temporal (hippocampal and parahippocampal) atrophy on MRI brain scans. The PET data were analysed in several different ways. The converging findings were that the patients showed bilateral thalamic hypometabolism, and there was also evidence of retrosplenial hypometabolism bilaterally. Cognitively, these patients performed most like other patients with medial temporal lesions, but the results indicate that structural lesions can have distal metabolic effects on structures elsewhere. These findings are interpreted in the light of neuroanatomical observations concerning parallel projections between medial temporal lobe structures and the thalamus, some of which pass via the retrosplenium.

Cerebral oxygenation and the recoverable brain.

Oxygenation is the most critical function of blood flow and a sudden reduction in oxygen availability is an inevitable consequence of severe ischemia. The resulting cascade of events may result in the failure of membrane integrity of some cells and necrosis, but in the surrounding zone of tissue, less affected by hypoxia, cells survive to form the ischemic penumbra. The timing of these events is uncertain, but sufficient oxygen is available to these cells to maintain membrane ion pump mechanisms, but not enough for them to generate action potentials and therefore function as neurons. The existence of such areas has been suspected for some time based upon the nature of clinical recovery, but has now been demonstrated by SPECT imaging with a high plasma oxygen concentration under hyperbaric conditions as a tracer. A course of hyperbaric oxygen therapy frequently results in a permanent improvement in both flow and metabolism. These changes apparently represent a reversal of the changes that render neurones dormant and the activity of cells, previously undetectable by standard electrophysiological methods, can now be demonstrated. Three patients are presented in whom recoverable brain tissue has been identified using SPECT imaging and increased cerebral oxygenation under hyperbaric conditions. Improved perfusion from reoxygenation has correlated with clinical evidence of benefit especially with continued therapy.

[Hypoxic cerebral lesions. X-ray computed tomography and MRI aspects. Apropos of 20 cases. Selective vulnerability of the striatopallidum]. / Lésions cérébrales hypoxiques. Aspects TDM et IRM. A propos de 20 cas. Vulnérabilité sélective du striatopallidum.

Brain lesions following hypoxic-ischaemic injuries are known from autopsy studies, but their appearance in live patients has been only occasionally described, and only sporadic reports have been published on their CT and MRI images. Over a 2-year period (1991-93) we studied the clinical, MRI and CT features in 20 patients shortly after a severe hypoxia. Clinical examination showed motor extrapyramidal signs in 13 cases and coma in 7 cases. MR with inversion recovery (IR) and T2-weighted spin echo (SE) sequences was performed in 17 patients and CT in 15. Bilateral lesions were found in 11 cases, but in 13 of them CT was normal. Radiological lesions were always symmetrical and bilateral, located in the pallidum in 10 cases, the striatum in 4 cases and the thalamus in 2 cases. Additional white matter lesions were present in only 4 MRI examinations. No relationship was found between the mechanism of hypoxia and the severity of clinical signs. The course of the clinical signs was correlated with the presence of radiological lesions. In comatous patients there was a relation between parkinsonism and abnormalities of basal ganglia. None of the patients who had perinatal asphyxia had radiological lesions. The presence of pallidal or striatal confirmed the hypoxic origin of neurological symptoms, especially in patients with parkinsonism. MRI, particularly in IR sequences, makes it possible to detect small lesions in basal ganglia after hypoxic injuries.

Identification of hypometabolic areas in the brain using brain imaging and hyperbaric oxygen.

Current neurologic assessments consider idling neurons and ischemic penumbras to be metabolically lethargic and electrically nonfunctional or nonviable. Diagnosis, prognosis, and therapeutics of central nervous system dysfunctions require differentiation between viable and nonviable neurons. It is necessary to develop and document efficacious and safe techniques for reactivating idling neurons. The authors present a case study of a near drowning 12 years earlier. Areas of cortical hypometabolism were identified by using SPECT imaging in conjunction with hyperbaric oxygen therapy (HBOT). Delayed imaging after HBOT (1 hour, 1.5 atm abs) suggested viable but metabolically lethargic neurons. After HBOT (80 1-hour treatments, monoplace chamber, 1.5 atm abs), marked improvements in cognitive and motor functioning were demonstrated. The data support the hypothesis that idling neurons and ischemic penumbras, when given sufficient oxygen, are capable of reactivation. Thus, changes in tracer distribution after a single exposure to HBOT may be a good prognostic indicator of viable neurons. HBOT may be valuable not only in recovery from anoxic encephalopathy but also from other traumatic and nontraumatic dysfunctions of the central nervous system, including stroke. HBOT in conjunction with physical and rehabilitative therapy may help reactivated idling neurons to remain permanently active.

Ultrasonographic findings in thalamus and basal ganglia in term asphyxiated infants.

Three severely asphyxiated term neonates demonstrated bilateral hyperechogenicity in the thalamus and basal ganglia. During evolution, areas of attenuated echogenicity appeared in these structures at the same time as periventricular cysts were evident in 2 patients with coexistent periventricular leukomalacia. All 3 patients developed ventricular dilatation; in the 2 patients with periventricular leukomalacia, the ventricular border was irregular in the outer (dorsal) margin, and interhemispheric fissures were widened as a manifestation of cerebral atrophy. Furthermore, the thalamic inner (ventral) margins of the lateral ventricles were irregular in all 3 patients. This previously unrecognized finding points to a particular form of cerebral atrophy localized in the gangliothalamic region that contributes to the development of ventriculomegaly. The reported sonographic sequence implies profound damage in the thalamus and basal ganglia in asphyxiated infants which undoubtedly has contributed to the poor outcomes of our patients.

Reversal sign on CT: effect of anoxic/ischemic cerebral injury in children.

A retrospective study was performed to determine the clinical and pathologic features, etiology, and outcome of children with the reversal sign. The reversal sign, a striking CT finding, probably represents a diffuse, anoxic/ischemic cerebral injury. CT features of the reversal sign are diffusely decreased density of cerebral cortical gray and white matter with a decreased or lost gray/white matter interface, or reversal of the gray/white matter densities and relatively increased density of the thalami, brainstem, and cerebellum. Twenty children with the reversal sign were retrospectively analyzed. We divided the patients into three groups: (1) acute reversal, (2) intermediate group, and (3) chronic reversal. There were nine cases of trauma (seven of child abuse); nine hypoxia/anoxia incidents (birth asphyxia, drowning, status epilepticus); one bacterial meningitis; and one degenerative encephalitis. All acute- and intermediate-group patients had respiratory problems requiring ventilator support and intensive care. In five of seven patients who died, autopsy findings were consistent with anoxic/ischemic encephalopathy. Surviving patients have profound neurologic deficits with severe developmental delay. The CT reversal sign carries a poor prognosis and indicates irreversible brain damage.