phosphocreatine and Brain-Damage--Chronic

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Brain; Brain Chemistry; Brain Damage, Chronic; Brain Edema; Carbon Dioxide; Cats; Cerebrovascular Circulation; Cerebrovascular Disorders; Electroencephalography; Heart Arrest; Humans; Hypotension; Hypoxia; Hypoxia, Brain; Indicator Dilution Techniques; Ischemia; Lactates; Mathematics; Oxygen; Phosphocreatine; Prognosis; Vasomotor System

Pyridoxine-dependent seizures are an extremely rare genetic disorder. Early diagnosis and treatment are important for the prevention of permanent brain damage. Elevated levels of glutamate and decreased levels of gamma-aminobutyric acid (GABA) in the frontal and parietal cortices are among the characteristic features of this disorder. These metabolic abnormalities eventually lead to seizures and neuronal loss. In this case report, we present magnetic resonance spectroscopy findings of a 9-year-old girl with pyridoxine-dependent seizures with mental retardation. The N-acetylaspartate-to-creatine ratio was found to be decreased in the frontal and parieto-occipital cortices, which could indicate neuronal loss. Magnetic resonance spectroscopy could be a useful tool in the neuroimaging evaluation for assessment of parenchymal changes despite a normal-appearing brain magnetic resonance image in patients with pyridoxine-dependent seizures.

Topics: Aspartic Acid; Brain Damage, Chronic; Child; Choline; Consanguinity; Creatine; Diagnosis, Differential; Epilepsy, Generalized; Female; Follow-Up Studies; Frontal Lobe; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Inositol; Intellectual Disability; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Occipital Lobe; Parietal Lobe; Phosphocreatine; Pyridoxine; Reference Values; Vitamin B 6 Deficiency

The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (31P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14 Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized 31P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized 31P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were calculated from the chemical shift difference between the inorganic phosphate (P) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%Pi), phosphocreatine (%PCr) and betaNTP signals, relative to the total 31P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to betaNTP were also measured. There were no differences between patients and volunteers in intracellular pH in 31P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy (West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change in the inorganic phosphate, phosphocreatine or betaNTP resonances in spectra acquired from the whole head. However, in spectra localized to the basal ganglia, there was a significant increase in mean P/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %Pi and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %betaNTP. When the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean P/NTP and %Pi (p=0.03; p=0.01), compared to the reference population. Our results suggest that there are detectable bioenergetic abnormalities in patients with minimal hepatic encephalopathy or stable, overt chronic hepatic encephalopathy, but any associated intracellular pH change is probably a secondary, rather than a primary phenomenon.

Topics: Adult; Aged; Brain; Brain Damage, Chronic; Female; Humans; Hydrogen-Ion Concentration; Liver Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Phosphates; Phosphocreatine; Phosphorus Isotopes

The aim of the study was to test the hypotheses that elevated cerebral lactate, detected by proton spectroscopy performed within 18 hours of suspected birth asphyxia, is associated with adverse outcome, and that increased lactate can be used to predict adverse outcome. Thirty-one term infants suspected of having had birth asphyxia and seven control infants underwent proton magnetic resonance spectroscopy, using three-dimensional chemical shift imaging, within 18 hours of birth. Adverse outcome was defined as death or neurodevelopmental impairment at 1 year of age or more. Nine infants had an adverse outcome. The other 22 and all of the control infants remained normal. Median (range) lactate/creatine plus phosphocreatine (lactate/creatine) ratios in the abnormal, the normal, and the control group were 1.14 (0.17 to 3.81), 0.33 (0 to 1.51), and 0.05 (0 to 0.6) respectively (P=0.003). Lactate/creatine >1.0 predicted neurodevelopmental impairment at 1 year of age with sensitivity of 66% and specificity of 95%, positive and negative predictive values of 86% and 88%, and a likelihood ratio of 13.2. Elevated cerebral lactate/creatine within 18 hours of birth asphyxia predicts adverse outcome.

Topics: Asphyxia Neonatorum; Brain; Brain Damage, Chronic; Creatine; Female; Humans; Image Processing, Computer-Assisted; Infant; Infant, Newborn; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Pregnancy; Sensitivity and Specificity

Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1) (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(-1). In seven of the animals, a "secondary" failure of energy metabolism then evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1) at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADCglobal correlated linearly with the concentration ratio [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear relationship was demonstrated between ADCglobal and the concentration ratio [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Blood-Brain Barrier; Body Water; Brain; Brain Damage, Chronic; Brain Edema; Diffusion; Humans; Hypoxia, Brain; Image Processing, Computer-Assisted; Infant, Newborn; Magnetic Resonance Spectroscopy; Phantoms, Imaging; Phosphates; Phosphocreatine; Swine

A 2.9 degrees C reduction in the intraischemic rectal temperature of neonatal piglets is associated with less brain damage compared with animals with normothermic rectal temperatures. This investigation studied one potential mechanism for this observation: better maintenance of energy stores and less brain acidosis secondary to reduced metabolic activity associated with modest hypothermia.. 31P MR spectroscopy was used to study piglets before, during, and after 15 minutes of partial brain ischemia with intraischemic rectal temperatures of either 38.3 +/- 0.4 degrees C (n = 10, normothermic) or 35.4 +/- 0.5 degrees C (n = 10, hypothermic). Animals were followed up for up to 72 hours after ischemia and were evaluated clinically and by brain histology.. Values for pHi remained 0.15 to 0.20 pH units greater in modestly hypothermic than in normothermic piglets during ischemia and the initial 30 minutes after ischemia (P = .049, group effect). Phosphocreatine, beta-ATP, and inorganic phosphorus were similar between groups. The relationship between the intraischemic energy state and subsequent clinical evidence of brain damage (irrespective of group assignment) revealed lower pHi over the last 7 minutes of ischemia for abnormal compared with normal piglets (5.98 +/- 0.22 versus 6.39 +/- 0.24, respectively; P = .002). In contrast, intraischemic beta-ATP (41 +/- 19% versus 57 +/- 21% of control) and inorganic phosphorus (273 +/- 31% versus 224 +/- 92% of control) for abnormal and normal piglets, respectively, did not differ between groups.. Intraischemic modest hypothermia attenuates the severity of brain acidosis during and 30 minutes after ischemia compared with normothermic animals and supports the concept that attenuated brain acidosis is a potential mechanism by which hypothermia may reduce ischemic brain damage.

Topics: Acidosis; Adenosine Triphosphate; Animals; Animals, Newborn; Body Temperature; Brain; Brain Damage, Chronic; Brain Diseases; Brain Ischemia; Energy Metabolism; Follow-Up Studies; Hydrogen-Ion Concentration; Hypothermia, Induced; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phosphorus Isotopes; Swine; Time Factors

Proton magnetic resonance spectra include signals from N-acetylaspartate, creatine + phosphocreatine, and choline-containing compounds. Abnormalities in these signals can be used in the assessment of patients with intractable epilepsy. In particular, they provide a means of identifying metabolic abnormalities within the temporal lobes, detecting bilateral and diffuse pathology, and aiding lateralization of the seizure focus. The pathology demonstrated on MRS can also be related to cognitive dysfunction.

Topics: Adult; Aspartic Acid; Brain Damage, Chronic; Brain Mapping; Child; Choline; Creatine; Dominance, Cerebral; Energy Metabolism; Epilepsy; Epilepsy, Temporal Lobe; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Neuropsychological Tests; Phosphocreatine; Temporal Lobe

Persistent alterations in cellular energy homeostasis may contribute to the brain damage that evolves from perinatal cerebral hypoxia-ischemia. Accordingly, the presence and extent of perturbations in high-energy phosphate reserves were analyzed during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation and hypoxia with 8% oxygen at 37 degrees C for 3 h, an insult that produces damage (selective neuronal necrosis or infarction) of the cerebral hemisphere ipsilateral to the common carotid artery ligation in 92% of animals. Rat pups were quick frozen in liquid nitrogen during hypoxia-ischemia and at 10, 30, and 60 min and 4 and 24 h of recovery for enzymatic, fluorometric analysis of phosphocreatine (PCr), creatine, ATP, ADP, and AMP. During hypoxia-ischemia, PCr, ATP, and total adenine nucleotides were decreased by 87, 72, and 50% of control, respectively. During recovery, PCr, ATP, and total adenine nucleotides exhibited a rapid (within 10 min) although incomplete and heterogeneous recovery that persisted for at least 24 h. Mean values for PCr remained between 55 and 85% of control, whereas ATP values remained between 57 and 67% of control. Individual ATP values were inversely related to tissue water content at 10 min of recovery, indicating a close correlation between failure of energy restoration and the extent of cerebral edema as a reflection of brain damage. Thus high-energy phosphate reserves display lingering alterations during recovery from hypoxia-ischemia. The interanimal variability in energy restoration presumably reflects the spectrum of brain damage seen in this model of perinatal cerebral hypoxia-ischemia.

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Body Water; Brain Damage, Chronic; Energy Metabolism; Functional Laterality; Ischemic Attack, Transient; Kinetics; Phosphocreatine; Rats; Rats, Inbred Strains; Reperfusion; Time Factors

Studies of cerebral oxidative metabolism were carried out by phosphorous magnetic resonance spectroscopy during the first week of life in 52 infants with clinical and/or biochemical evidence of birth asphyxia. 15 infants died and the 37 survivors were assessed by a wide range of neurodevelopmental tests at one year of age. The minimum recorded values for cerebral phosphocreatine/inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed a significant relation between the extent of derangement of oxidative metabolism and the severity of adverse outcomes, including death, neurodevelopmental impairment and reduced head growth.

Topics: Adenosine Triphosphate; Asphyxia Neonatorum; Birth Weight; Brain; Brain Damage, Chronic; Energy Metabolism; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Magnetic Resonance Imaging; Male; Neurologic Examination; Phosphates; Phosphocreatine

Post-ischemic reperfusion impairment, ("no-reflow phenomenon"), was studied in rats subjected to 8-30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and 31P-high energy phosphates (ATP/PCr) was observed. Brain intravascular perfusion defects were examined by injecting carbon black intravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy and intraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats given intraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in "pale tissue areas" suggestive of impaired perfusion (no-reflow). All rats given carbon black intravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of "pale tissue areas". In addition, post-ischemic cerebral reperfusion following 8-30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised. These findings indicate that the "no-reflow phenomenon" is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.

Topics: Adenosine Triphosphate; Animals; Artifacts; Brain; Brain Damage, Chronic; Brain Ischemia; Cerebral Arteries; Cerebral Cortex; Cerebrovascular Circulation; Male; Phosphocreatine; Postmortem Changes; Rats; Rats, Inbred Strains; Reperfusion Injury

The question of a possible brain damage during open heart surgery using extracorporeal circulation is still a problem, especially in infants with circulatory arrest under deep hypothermia. During the last years Magnetic Resonance Spectroscopy was developed, and with this method we have now a possibility to study brain energy metabolism non-invasively and continuously. Our aim was to develop an animal model (rabbit) for studying brain energy metabolism by 31-P Magnetic Resonance Spectroscopy during extracorporeal circulation. In a first step we have shown that the influence of hypothermia on energy metabolism in the brain can be measured in the intact animal by MR-Spectroscopy. In a second step a non-magnetic heart-lung machine for rabbits was constructed and is described here. We get a completely normal brain spectrum in the beginning and after two hours of extracorporeal circulation. The spectrum is also normal on extracorporeal circulation at 35 degrees C and during cooling down to 18 degrees C. With this animal model it will be possible to study different variables of extracorporeal circulation such as duration of circulatory arrest under deep hypothermia or changes of the priming including pharmacological changes.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Damage, Chronic; Energy Metabolism; Extracorporeal Circulation; Magnetic Resonance Spectroscopy; Phosphocreatine; Rabbits

Topics: Adenosine Triphosphate; Birth Injuries; Brain; Brain Damage, Chronic; Female; Fetal Hypoxia; Gangliosides; Histocytochemistry; Humans; Infant, Newborn; Lipid Metabolism; Lysosomes; Mitochondria; Oxygen Consumption; Phosphocreatine; Pregnancy; Time Factors

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain; Brain Damage, Chronic; Cerebrosides; Cholesterol; DNA; Gangliosides; Glucose; Glycogen; Humans; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Lipid Metabolism; Nerve Tissue Proteins; Organ Size; Phosphocreatine; Phospholipids; Rats; Sulfoglycosphingolipids