Brain glutamine by MRS in a patient with urea cycle disorder and coma

In patients who undergo metabolic decompensation from urea cycle disorders, cerebrospinal fluid glutamine level may be a better marker of cerebral dysfunction than blood ammonia or glutamine levels. However, obtaining cerebrospinal fluid by lumbar puncture carries risk in these acutely ill patients with cerebral edema. Using magnetic resonance single voxel spectroscopy as an alternative to cerebrospinal fluid analysis, elevated brain glutamine/glutamate complex levels were detected in a patient with carbamyl phosphate synthetase deficiency, who had been comatose for many days after normalization of blood ammonia and improvement in blood glutamine levels. Brain glutamine by single voxel spectroscopy decreased toward normal with neurologic recovery. We conclude that brain glutamine may be a better marker than serum ammonia for the management of urea cycle disorders, particularly in patients with prolonged mental status changes.     

Carbamyl phosphate synthetase 1 deficiency: a destructive encephalopathy

Carbamyl phosphate synthetase I is a urea cycle enzyme. Severe deficiency of carbamyl phosphate synthetase I presents in the neonatal period as hyperammonemic encephalopathy with altered consciousness and occasional seizures after feeding begins. Episodes of altered consciousness with or without seizures and focal neurologic deficits are seen later with patients of partial carbamyl phosphate synthetase I deficiency. Fatal cerebral edema with brain herniation may develop on occasion. Three patients presenting with carbamyl phosphate synthetase I deficiency are reported with neuroimaging and pathologic findings illustrating the destructive encephalopathy with acute cerebral edema, followed by diffuse cerebral atrophy and occasional cystic encephalomalacia. The deterioration in carbamyl phosphate synthetase I deficiency occurs during the hyperammonemic crises. This deficiency may be difficult to treat despite the current advances in treatment strategies, especially in neonatal-onset patients with low carbamyl phosphate synthetase I activity.     

Hyperammonemia-induced toxicity for the developing central nervous system

In pediatric patients, hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle deficiencies or organic acidemias. The brain is much more susceptible to the deleterious effects of ammonium during development than in adulthood. Hyperammonemia can provoke irreversible damages to the developing central nervous system that lead to cortical atrophy, ventricular enlargement and demyelination, responsible for cognitive impairment, seizures and cerebral palsy. Until recently, the mechanisms leading to these irreversible cerebral damages were poorly understood. Using experimental models allowing the analysis of the neurotoxic effects of ammonium on the developing brain, these last years have seen the emergence of new clues showing that ammonium exposure alters several amino acid pathways and neurotransmitter systems, as well as cerebral energy metabolism, nitric oxide synthesis, oxidative stress, mitochondrial permeability transition and signal transduction pathways. Those alterations may explain neuronal loss and impairment of axonal and dendritic growth observed in the different models of congenital hyperammonemia. Some neuroprotective strategies such as the potential use of NMDA receptor antagonists, nitric oxide inhibitors, creatine and acetyl-l-carnitine have been suggested to counteract these toxic effects. Unraveling the molecular mechanisms involved in the chain of events leading to neuronal dysfunction under hyperammonemia may be useful to develop new potential strategies for neuroprotection.     

Neurologic disorders associated with mitral valve prolapse

Mitral valve prolapse has been reported to be associated with a variety of neurologic disorders, including cerebral ischemia, transient global amnesia, migraine, autonomic dysfunction, and psychiatric disease. The evidence supporting these associations and possible pathogenetic mechanisms are discussed. Some neurologic disorders may be direct complications of mitral valve prolapse, while others may occur as part of an underlying genetic defect or common link.     

Evaluation of coma and brain death

Coma is a nonspecific sign of widespread central nervous system impairment resulting from various metabolic and structural etiologies. The rapid recognition of this neurologic emergency and results from the history, physical examination, and early investigative studies are key to the identification and treatment of its underlying cause. The prognosis for recovery depends greatly on the underlying etiology as well as on its optimal treatment, which seeks to preserve neurologic function and maximize the potential for recovery by reversing the primary cause of brain injury, if known, and preventing secondary brain injury from anoxia, ischemia, hypoglycemia, cerebral edema, seizures, infections, and electrolyte and temperature disturbances. Brain death must be diagnosed with similar care and precision, and families approached compassionately about the diagnosis and their decisions regarding organ donation.     

Cerebral Edema After Cardiopulmonary Resuscitation: A Therapeutic Target Following Cardiac Arrest?

We sought to review the role that cerebral edema plays in neurologic outcome following cardiac arrest, to understand whether cerebral edema might be an appropriate therapeutic target for neuroprotection in patients who survive cardiopulmonary resuscitation. Articles indexed in PubMed and written in English. Following cardiac arrest, cerebral edema is a cardinal feature of brain injury and is a powerful prognosticator of neurologic outcome. Like other conditions characterized by cerebral ischemia/reperfusion, neuroprotection after cardiac arrest has proven to be difficult to achieve. Neuroprotection after cardiac arrest generally has focused on protecting neurons, not the microvascular endothelium or blood–brain barrier. Limited preclinical data suggest that strategies to reduce cerebral edema may improve neurologic outcome. Ongoing research will be necessary to determine whether targeting cerebral edema will improve patient outcomes after cardiac arrest.     

Types of brain dysfunction in critical illness

Cerebral dysfunction and injury in the ICU presents as focal neurologic deficits, seizures, coma, and delirium. These syndromes may result from a primary brain insult, such as stroke or trauma, but commonly are a complication of a systemic insult, such as cardiac arrest, hypoxemia, sepsis, metabolic derangements, and pharmacologic exposures. Many survivors of critical illness have cognitive impairment, which is believed to underlie the poor long-term functional status and quality of life observed in many critical illness survivors. Although progress has been made in characterizing the epidemiology of cerebral dysfunction in the ICU, more research is needed to elucidate underlying mechanisms that might represent targets for therapeutic intervention.     

Cerebral edema and a transtentorial brain herniation syndrome associated with pandemic swine influenza A (H1N1) virus infection

Acute encephalitis, encephalopathy, and seizures are known rare neurologic sequelae of respiratory tract infection with seasonal influenza A and B virus, but the neurological complications of the pandemic 2009 swine influenza A (H1N1) virus, particularly in adults, are ill-defined. We document two young adults suffering from H1N1-associated acute respiratory distress syndrome and renal failure who developed cerebral edema. The patients acutely developed a transtentorial brain herniation syndrome including a unilateral third nerve palsy (dilated and unresponsive pupils), elevated intracranial pressure, coma, and radiological evidence of diffuse cerebral edema. In both patients, neurological deterioration occurred in the context of hyponatremia and a systemic inflammatory state. These patients illustrate that severe neurologic complications, including malignant cerebral edema, can occur in adults infected with H1N1 virus, and illustrate the need for close neurological monitoring of potential neurological morbidities in future pandemics.     

Effect of open heart surgery on intellectual performance

Abstract

The interrelationship between postoperative psychosis, neurologic symptoms, and changes in tests of cognitive performance have been studied in a series of 60 cardiac valvular patients who underwent open heart surgery. The effects of preoperative psychological, psychiatric, and cardiologic factors on postoperative cognitive changes were analyzed. The investigation period was from five months before up to five months after the operation. There was a general trend towards improvement in intellectual performances. The psychotic group, however, still showed a persisting impairment in some visual and psychomotor tests several months after the surgery. The group with neurologic symptoms showed impairment in one visual test. Of the preoperative variables, mitral valve disease, a high level of hypochondriasis and anxiety, and poor performance in some visual and psychomotor tests predicted postoperative intellectual impairment. The results suggest two types of cerebral complications of open heart surgery. Postoperative psychosis reflects diffuse brain dysfunction manifesting itself in psychological tests long after the clinical symptoms have resolved. The presence of neurologic symptoms refers to a focal or lateralized injury. Both the neurologic and neuropsychologic findings indicate that the right hemisphere may be more prone to dysfunction than the left hemisphere.     

Thrombotic thrombocytopenic purpura: brain CT and MRI findings in 12 patients

Clinical-neuroimaging analysis of 12 thrombotic thrombocytopenic purpura (TTP) patients revealed a variety of brain lesions. These included reversible cerebral edema lesions with MRI features of reversible posterior leukoencephalopathy syndrome (RPLS). Most of the RPLS patients had hypertension and renal dysfunction, suggesting RPLS due to hypertensive encephalopathy. Prompt treatment usually led to neurologic recovery and disappearance of edematous lesions. Those with infarcts or hematomas had a poorer outcome. TTP should be added to the expanding spectrum of RPLS and hypertensive encephalopathy.     

Is major depression a neurologic disorder with psychiatric symptoms?

In the last decade, multiple investigator groups have identified structural changes of various neuroanatomic structures in patients with idiopathic major depression and bipolar disorders. Using high-resolution MRI of the brain and functional neuroimaging studies (i.e., PET, SPECT), researchers have described decreases in the volume of hippocampal formation, amygdala, entorhinal cortex, various frontal lobe structures, and basal ganglia, in addition to abnormal cerebral blood flow and metabolic activity in these structures as well as in thalamic nuclei. Similar structural and functional changes have been identified in patients with depression associated with a variety of neurologic disorders (i.e., stroke, Parkinson's disease, epilepsy, Alzheimer's dementia). In addition, recent data have shown that depression is a risk factor for the development of several neurologic disorders, including epilepsy, stroke, and Parkinson's disease and bears a negative impact on the course and outcome of most neurologic disorders. This article reviews these data and provides evidence that major depressive and bipolar disorders may in fact be neurologic disorders with psychiatric symptoms.     

Spontaneous intracerebral hematomas in juvenile diabetic ketoacidosis

Ketoacidosis is one of the common complications of Type I insulin-dependent diabetes mellitus. Several neurologic (cerebral) deficiencies have been associated with diabetic ketoacidosis, including cerebral edema with increased intracranial pressure resulting in coma; partial and generalized seizures; and cerebrovascular occlusive disease resulting in motor and/or sensory dysfunction. Intracerebral hematomas have not been reported. A child is described who had insulin-dependent diabetes mellitus with hyperglycemic ketoacidosis who developed multiple spontaneous intracerebral hematomas. Possible mechanisms are discussed.     

Mechanisms of Global Cerebral Edema Formation in Aneurysmal Subarachnoid Hemorrhage

A growing body of clinical literature emphasizes the impact of cerebral edema in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Aneurysm rupture itself initiates global cerebral edema in up to two thirds of cases. Although cerebral edema is not a universal feature of aSAH, it portends a poor clinical course, with quantitative analysis revealing a direct correlation between cerebral edema and poor outcome, including mortality and cognitive deficits. Mechanistically, global cerebral edema has been linked to global ischemia at the time of aneurysm rupture, dysfunction of autoregulation, blood breakdown products, neuroinflammation, and hyponatremia/endocrine abnormalities. At a molecular level, several culprits have been identified, including aquaporin-4, matrix metalloproteinase-9, SUR1-TRPM4 cation channels, vascular endothelial growth factor, bradykinin, and others. Here, we review these cellular and molecular mechanisms of global cerebral edema formation in aSAH. Given the importance of edema to the outcome of patients with aSAH and its status as a highly modifiable pathological process, a better understanding of cerebral edema in aSAH promises to hasten the development of medical therapies to improve outcomes in this frequently devastating disease.     

热射病导致的脑梗死或脑出血的诊治分析

目的 探讨热射病导致的脑梗死或脑出血的影像学表现、治疗方法及其效果。方法 回顾性分析2012～2022年收治的20例热射病导致的脑出血或脑梗死的临床资料。结果 2例出现微出血病灶,部位为右额叶及左顶叶;18例出现缺血样改变,包括放射冠、基底节、额叶、颞叶、顶叶、枕叶、皮层下白质、胼胝体、海马,其中2例伴有明显脑水肿。出院时,11例恢复正常,未遗留明显肢体活动障碍、言语障碍及逻辑思维能力障碍;2例出现认知功能减退,主要存在语言表达能力障碍、遵嘱动作较差、小脑共济失调（轮替试验阳性、Romberg阳性）;3例深度昏迷,GCS评分3～4分;4例死亡。结论 热射病导致的脑梗死或脑出血,临床少见,多数病人保守治疗预后良好。建议早期进行康复治疗,以减少神经功能障碍。     

Progressive neurologic impairment from an arteriovenous malformation vascular steal

Approximately 15% of all cerebral arteriovenous malformations (AVMs) present with progressive neurologic deficits, the pathogenic mechanism of which has not been established. One suggestion is that AVMs by expanding over time compress normal surrounding cerebral parenchyma and thereby cause progressive neurologic impairment. Alternatively, a vascular steal results in progressive ischemia of normal cerebral tissue. Because the area occupied by the AVM and the area of observed blood flow reductions in all reported patients have overlapped, delineating the relative contribution of local compression from that of vascular steal has not been possible. We present a 7-month-old girl and a 7-year-old boy with AVMs restricted to the diencephalon who had progressive cognitive impairment and dystrophic cerebral hemispheral calcification (in the 7-month-old girl) indicating diffuse cerebral cortical involvement remote from the AVM. These patients provide evidence for vascular steal, and not local compression, as the primary mechanism underlying a progressive neurologic course associated with some AVMs.     

The blood-brain barrier: an overview: structure, regulation, and clinical implications

The blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most compounds from blood to brain. Three cellular elements of the brain microvasculature compose the BBB-endothelial cells, astrocyte end-feet, and pericytes (PCs). Tight junctions (TJs), present between the cerebral endothelial cells, form a diffusion barrier, which selectively excludes most blood-borne substances from entering the brain. Astrocytic end-feet tightly ensheath the vessel wall and appear to be critical for the induction and maintenance of the TJ barrier, but astrocytes are not believed to have a barrier function in the mammalian brain. Dysfunction of the BBB, for example, impairment of the TJ seal, complicates a number of neurologic diseases including stroke and neuroinflammatory disorders. We review here the recent developments in our understanding of the BBB and the role of the BBB dysfunction in CNS disease. We have focused on intraventricular hemorrhage (IVH) in premature infants, which may involve dysfunction of the TJ seal as well as immaturity of the BBB in the germinal matrix (GM). A paucity of TJs or PCs, coupled with incomplete coverage of blood vessels by astrocyte end-feet, may account for the fragility of blood vessels in the GM of premature infants. Finally, this review describes the pathogenesis of increased BBB permeability in hypoxia-ischemia and inflammatory mechanisms involving the BBB in septic encephalopathy, HIV-induced dementia, multiple sclerosis, and Alzheimer disease.     

脑出血患者血清基质金属蛋白酶水平与脑水肿和神经损害的关系

目的探讨脑出血患者血清基质金属蛋白酶(MMPs)水平与脑水肿和神经功能损害的关系。方法应用酶联免疫吸附法测定31例脑出血患者发病后1d、3d、7d和14d时血清MMP-9和MMP-2水平;发病当日及14d时头颅CT测定血肿及其周围脑水肿体积,同时进行卒中评分量表(NIHSS)评分。结果血清MMP-9、MMP-2水平发病后各时间点明显高于正常对照组(均P<0.05);发病7d及14d时MMP-9水平与血肿周围水肿体积呈正相关(r=0.748,P<0.001;r=0.436,P<0.05),与血肿体积及NIHSS评分无相关;各时间点MMP-2水平与血肿体积、血肿周围水肿体积及NIHSS评分无相关。结论脑出血后MMP-9过表达参与血肿周围水肿的形成。     

Parieto-occipital encephalomalacia in neonatal hyperammonemia with ornithine transcarbamylase deficiency: A case report

Urea cycle disorders are congenital metabolic disorders that often cause episodic hyperammonemia. Neuroimaging in episodic hyperammonemia demonstrates several patterns of brain injuries, including focal lesions in the lentiform nucleus, insula, cingulate gyrus, and perirolandic fissure, as well as diffuse cerebral edema. In cases with neonatal onset of hyperammonemia, similar lesions have also been reported. We herein report a boy with severe neonatal hyperammonemia caused by ornithine transcarbamylase deficiency. He presented with parieto-occipital encephalomalacia, which resembles severe neonatal hypoglycemia on magnetic resonance imaging. This radiological finding may indicate parieto-occipital vulnerability not only to hypoglycemia but also to hyperammonemia.     

Comparison of the effects of hypertonic glycerol and urea on brain edema, energy metabolism and blood flow following cerebral microembolism in the rat. Deleterious effect of glycerol treatment

Cerebral microembolism was performed in rats by injecting radioactive calibrated 50 mu microspheres into the left internal carotid artery. The use of radioactive microspheres as embolic agents enabled the number of microspheres to be determined in each cerebral hemisphere. Edema was assessed 24 h after embolization by measuring brain water, sodium, and potassium content. Equiosmolal doses (40 mmol/kg) of glycerol or urea were injected i.p. at various times before sacrifice. Both treatments caused similar changes in water and electrolyte content, brain dehydration being maximal 30 min after urea and 2 h after glycerol injection. Cerebral energy metabolism and regional blood flow were evaluated at the times of maximal brain dehydration. Urea treatment resulted in an improvement of the cerebral circulation whereas glycerol treatment led to a deterioration of cerebral blood flow which cannot be explained by failure to reduce edema and the consequent microcirculatory impairment. Urea treatment had no marked effect on cerebral energy metabolism whereas glycerol injection resulted in an important increase in brain lactate level which may be relevant to the impairment of cerebral reperfusion. These results point out that administration of a metabolized solute like glycerol may exert deleterious effects on the ischemic brain.     

Long-term neurological and functional outcome in Nipah virus infection

OBJECTIVE: Nipah virus (NiV) is an emerging zoonosis. Central nervous system disease frequently results in high case-fatality. Long-term neurological assessments of survivors are limited. We assessed long-term neurologic and functional outcomes of 22 patients surviving NiV illness in Bangladesh. METHODS: During August 2005 and May 2006, we administered a questionnaire on persistent symptoms and functional difficulties to 22 previously identified NiV infection survivors. We performed neurologic evaluations and brain magnetic resonance imaging (MRI). RESULTS: Twelve (55%) subjects were male; median age was 14.5 years (range 6-50). Seventeen (77%) survived encephalitis, and 5 survived febrile illness. All but 1 subject had disabling fatigue, with a median duration of 5 months (range, 8 days-8 months). Seven encephalitis patients (32% overall), but none with febrile illness had persistent neurologic dysfunction, including static encephalopathy (n = 4), ocular motor palsies (2), cervical dystonia (2), focal weakness (2), and facial paralysis (1). Four cases had delayed-onset neurologic abnormalities months after acute illness. Behavioral abnormalities were reported by caregivers of over 50% of subjects under age 16. MRI abnormalities were present in 15, and included multifocal hyperintensities, cerebral atrophy, and confluent cortical and subcortical signal changes. INTERPRETATION: Although delayed progression to neurologic illness following Nipah fever was not observed, persistent fatigue and functional impairment was frequent. Neurologic sequelae were frequent following Nipah encephalitis. Neurologic dysfunction may persist for years after acute infection, and new neurologic dysfunction may develop after acute illness. Survivors of NiV infection may experience substantial long-term neurologic and functional morbidity.