phosphocreatine and Atrophy

We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS).. Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations.. In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores.. DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.

Topics: Adult; Aspartic Acid; Atrophy; Creatine; Diffusion Magnetic Resonance Imaging; Energy Metabolism; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multiple Sclerosis; Phosphocreatine; Thalamus; White Matter

Magnetic resonance (MR) spectroscopy can be used to determine the side of seizure onset in patients with temporal lobe epilepsy. Some patients with abnormal MR spectroscopy findings also have contralateral abnormalities, which in some cases have been reported to normalize after temporal lobe resection. With the aim of better understanding the mechanisms underlying abnormal MR spectroscopy findings, the current study was performed to define patient features that would predict this postoperative normalization.. Fifteen patients with temporal lobe epilepsy were subjected to preoperative and postoperative 1H-MR spectroscopy investigations, and the preoperative and postoperative metabolite levels in the contralateral hippocampus and contralateral lateral temporal lobe (CLTL) were determined.. In the CLTL, postoperative normalization was more pronounced for patients showing extensive preoperative ipsilateral and contralateral abnormalities on MR spectroscopy. A second factor that influenced the degree to which the metabolite levels changed postoperatively was the focus lateralization. Surgery tended to have a more pronounced effect on the contralateral metabolite levels in patients with a right temporal focus, whereas in patients with left temporal foci, postoperative metabolite levels were virtually unchanged. In the contralateral hippocampal region, neither preoperative abnormalities nor focus side was related to postoperative normalization.. We have thus identified 2 different factors (widespread preoperative MR spectroscopy abnormalities and right-sided focus) that predict postoperative normalization of contralateral MR spectroscopy abnormalities. We suggest that both factors indicate a more generalized epileptic disease (ie, that the patients in whom the MR spectroscopy abnormalities normalize are recovering from a more severe impairment).

Topics: Adult; Aspartic Acid; Atrophy; Choline; Creatine; Dominance, Cerebral; Electroencephalography; Energy Metabolism; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Postoperative Complications; Prognosis; Reference Values; Sclerosis; Temporal Lobe

The objective of this study was to assess which features of temporal lobe proton magnetic resonance spectroscopic imaging (1H-MRSI) are associated with satisfactory surgical outcome in patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy. We studied 21 patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy defined by magnetic resonance imaging volumetric measurements who underwent surgical treatment. 1H-MRSI was used to determine the relative resonance intensity ratio of the neuronal marker N-acetylaspartate to creatine + phosphocreatine (NAA/Cr) for mid and posterior temporal lobe regions of the left and right hemisphere, as well as an asymmetry index. Values lower than 2 SDs below the normal mean were considered abnormal. We used Engel's classification to assess surgical outcome with respect to seizure control. Eleven patients (52%) were in class I-II and 10 (48%) were in class III-IV. All 21 were operated on the side of maximal electroencephalographic (EEG) lateralization. Concordant lateralization of decreases in NAA/Cr to the side of surgery and normal NAA/Cr values in the contralateral posterior-temporal region were significantly associated with good surgical outcome: 11 (69%) of 16 patients with 1H-MRSI abnormalities concordant with EEG lateralization and none of the 5 patients with nonconcordant 1H-MRSI had a good outcome (class I-II); 10 (77%) of 13 patients with normal NAA/Cr contralateral to the EEG lateralization versus 1 (12.5%) of 8 of those with NAA/Cr reduction contralateral to EEG lateralization were in class I-II. Regression correlation analysis showed significant linear correlation between the midtemporal NAA/Cr relative asymmetry ratio and surgical outcome; the greater the asymmetry, the better the outcome. We conclude that discriminant 1H-MRSI features associated with favorable surgical outcome in patients with temporal lobe epilepsy and bilateral hippocampal atrophy were (1) concordant 1H-MRSI lateralization, (2) a greater side-to-side asymmetry of NAA/Cr, and (3) an absence of contralateral posterior NAA/Cr reduction.

Topics: Adolescent; Adult; Aspartic Acid; Atrophy; Brain; Creatine; Dominance, Cerebral; Electroencephalography; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Phosphocreatine; Prognosis; Treatment Outcome

To evaluate by magnetic resonance spectroscopy the age-related cerebral alterations present in myotonic dystrophy (MD) and to compare these results with those obtained by magnetic resonance imaging.. Twenty-one patients (aged 16-63 years) with MD were compared with 16 age-matched healthy control subjects.. In magnetic resonance spectroscopy, the mean (+/- SD) ratio of N-acetylaspartate to creatine and phosphocreatine in the patients with MD (1.09 +/- 0.32) was significantly lower than that in the control subjects (1.93 +/- 0.43) (P<.001). The mean ratio of N-acetylaspartate to choline-containing compounds in the patients with MD (1.70 +/- 0.44) was also significantly lower than that in the control subjects (2.75 +/- 0.53) (P<.001). These changes could be observed already in the younger patients. In magnetic resonance imaging, the mean brain area was significantly decreased and the mean ventricular space was significantly increased in patients with MD compared with the control subjects. Although we have confirmed brain atrophy in patients with MD in previous reports, a regression analysis indicated that the brain shrinks progressively with age in patients with this disorder and in control subjects, resulting in overlapping values for younger subjects.. Magnetic resonance spectroscopy indicates that the cerebral abnormalities in patients with MD may be present at an early stage, when the results of magnetic resonance imaging studies are still equivocal.

Topics: Adolescent; Adult; Aspartic Acid; Atrophy; Case-Control Studies; Cerebral Cortex; Creatine; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myotonic Dystrophy; Phosphocreatine

The authors studied 23 patients with cerebellar degeneration including multiple systemic atrophy (MSA) and cerebellar cortical atrophy (CCA) by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS allowed noninvasive measurement of the signal intensities derived from N-acetylaspartate (NAA), creatine + phosphocreatine (CRE), and choline-containing compounds (CHO). There was significant reduction of the NAA/CRE level in the frontal cortex, putamen, cerebellar hemisphere and cerebellar vermis of patients with MSA, and in the frontal cortex, cerebellar hemisphere and cerebellar vermis of patients with CCA as compared with those of normal controls. There was significant reduction of the NAA/CRE level also in the putamen of patients with MSA as compared with that of patients with CCA. These results indicated the presence of a degenerative process and/or functional impairment in the frontal cortex and putamen of patients with MSA and in the frontal cortex of patients with CCA, in addition to a degenerative process in the cerebellum. There was a significant correlation between the NAA/CRE level and the severity of clinical signs. 1H-MRS is valuable in providing information regarding the pathophysiology and the progress of cerebellar degenerative diseases.

Topics: Adult; Aged; Aspartic Acid; Atrophy; Cerebellar Diseases; Cerebellum; Choline; Creatine; Disease Progression; Female; Frontal Lobe; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multiple System Atrophy; Neurodegenerative Diseases; Phosphocreatine; Protons; Putamen

Proton magnetic resonance spectroscopy (1H-MRS), localized to the lentiform nucleus, was carried out in 12 patients with idiopathic Parkinson's disease (IPD), seven patients with multiple-system atrophy (MSA), seven patients with progressive supranuclear palsy (PSP), and 10 healthy age-matched controls. The study assessed the level of N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), and choline (Cho) in the putamen and globus pallidus of these patients. NAA/Cho and NAA/Cr ratios were significantly reduced in MSA and PSP patients. No significant difference was found between IPD patients and controls. These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of MSA and PSP patients. 1H-MRS is a noninvasive technique that can provide useful information regarding striatal neuronal loss in basal ganglia of patients with atypical parkinsonian disorders and represents a potential tool for diagnosing these disorders.

Topics: Aged; Antiparkinson Agents; Aspartic Acid; Atrophy; Cerebral Cortex; Choline; Corpus Striatum; Creatinine; Female; Globus Pallidus; Humans; Levodopa; Magnetic Resonance Spectroscopy; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary; Phosphocreatine; Protons; Putamen; Supranuclear Palsy, Progressive

To determine whether cerebral atrophy in systemic lupus erythematosus is associated with decreased levels of the neuronal marker N-acetyl-aspartic acid.. Two groups of patients with systemic lupus erythematosus were studied, those with significant atrophy (n = 11) and those without significant atrophy (n = 10), using proton MR spectroscopy on a 1.5-T imaging unit. The solvent-suppressed, short-echo, volume-localized proton spectroscopy technique showed typical brain metabolites, including N-acetylaspartate, creatine/phosphocreatine, and choline-containing compounds.. The N-acetylaspartate-to-creatine/phosphocreatine ratio was smaller in those patients with significant cerebral atrophy (1.68 +/- 0.27) than in those patients with minimal or no atrophy (2.17 +/- .30). The degree of atrophy was negatively correlated with the N-acetylaspartate-to-creatine/phosphocreatine ratio. The choline-to-creatine/phosphocreatine ratio was not significantly altered in systemic lupus erythematosus patients with atrophy.. These data suggest that cerebral atrophy in systemic lupus erythematosus is associated with neuronal dropout (or damage), which results in decreased N-acetylaspartate ratios. A change in choline ratios is not implicated in the biochemical changes associated with cerebral atrophy. Proton MR spectroscopy may be useful in correlating brain metabolites with cerebral structural changes in patients with autoimmune diseases.

Topics: Adolescent; Adult; Aspartic Acid; Atrophy; Brain; Choline; Creatine; Energy Metabolism; Female; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine

Localized proton nuclear magnetic resonance spectroscopy (MRS), obtained with stimulated echo and spin echo sequences, MR imaging (MRI) and MR angiography (MRA) were used to study the brain in 13 children and adolescents with sickle cell disease. Regions of interest (ROI) studied by MRS included regions appearing normal on MRI as well as regions showing complications of sickle cell disease, including focal deep white matter areas of high signal intensity (deep white matter ischemia, DWMI) seen on long TR images, focal atrophic brain areas, and infarcts. The findings in these studies are summarized as follows: Normal-appearing regions on MRI have normal MRS. In ROI including small areas of DWMI, lactate elevation was not detected, but the levels of N-acetyl-aspartate (NAA) appeared slightly elevated. In areas of DWMI 1-2 cm in size, reduced blood flow could be seen on MRA and lactate elevation could be detected with MRS. When blood flow to a DWMI region was normal, NAA was reduced and there was little lactate elevation, as cell death had already occurred. ROI consisting of atrophic tissue had reduced NAA levels but total creatine levels were not changed. Sometimes lipids, presumably from broken cell membrane, could be detected. In regions of past massive stroke, all metabolites were absent except for small amounts of lactate or lipids.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Aspartic Acid; Atrophy; Brain; Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Child; Choline; Creatine; Female; Frontal Lobe; Humans; Hydrogen; Lactates; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine

To test whether compromised high-energy phosphate metabolism is implicated in the neurologic impairment of acquired immunodeficiency syndrome dementia complex (ADC), brain phosphate metabolite concentrations and ratios were measured noninvasively in 12 patients with mild to moderate ADC and 29 healthy volunteers by use of localized phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) magnetic resonance (MR) imaging. In patients, brain phosphocreatine (PCr) and nucleoside triphosphate (NTP) concentrations in sections through the centrum semiovale that were seen with NMR spectroscopy were reduced significantly from normal values of 4.92 mmol/kg wet weight +/- .13 (standard error of the mean) and 2.79 mmol/kg +/- .11, respectively, to 3.33 mmol/kg +/- .26 and 1.99 mmol/kg +/- .13 (P less than .0001). The ratios of metabolites detectable with P-31 NMR spectroscopy did not differ significantly from those of control subjects. The magnitude of the PCr and NTP deficits in ADC was not explicable by focal abnormalities or cerebral atrophy quantified in images of the same regions. These results are consistent with the hypothesis of a generalized virus-associated toxic process affecting brain cell function in ADC. Noninvasive measurement of metabolite concentrations with NMR spectroscopy provides new functional information that may help quantify disease progression and response to therapy.

Topics: Adult; AIDS Dementia Complex; Atrophy; Brain; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Nucleotides; Organophosphates; Phosphates; Phosphocreatine

On day 12 of incubation 0.4% and 4.0% aqueous emulsions of Wofatox 50 EC (50% methylparathion) were injected into the air space of the chicken egg. The eggs were opened on the day 19 of incubation and samples were obtained from both cervical and femoral muscles. Atrophy was found only in the cervical muscles by light microscopic evaluation. It is known that the inhibition of acetylcholine esterase causes a permanent inflow and accumulation of Ca2+ especially in the cervical muscle due to the increased mass and energy utilization in the last period before hatching. Changes in the activity of creatine kinase were expressed in a decreased creatine and creatine-phosphate content.

Topics: Abnormalities, Drug-Induced; Animals; Atrophy; Calcium; Chick Embryo; Cholinesterase Inhibitors; Creatine; Creatine Kinase; Magnesium; Methyl Parathion; Muscles; Parathion; Phosphocreatine

Attempts have been made to evaluate the role of intracellular creatine in conditions leading to increased or decreased amounts of contractile protein in rat skeletal muscles. Resting concentrations of intracellular creatine ([Cr]i) and creatine phosphate ([CrP]i) were compared in gastrocnemius and soleus muscles with those immediately after a 20-s tetanic stimulation. The hydrolysis of creatine phosphate was the same after heavily and lightly loaded contractions, suggesting that hypertrophy of isometric exercise is not mediated by creatine. With atrophy after denervation or interruption of sciatic axoplasmic flow [Cr]i also remained unchanged, though [CrP]i and the rate of Cr uptake fell after denervation. The major change in adult red and white muscle bulk with unaltered [Cr]i suggests that the Cr sensitivity found by others in developing muscle in vitro has been supplemented or replaced by other control mechanisms.

Topics: Animals; Atrophy; Biological Transport, Active; Creatine; Hypertrophy; Male; Muscle Contraction; Muscle Denervation; Muscles; Organ Size; Phosphocreatine; Rats

Topics: Aging; Aortic Coarctation; Atrophy; Cardiomegaly; Cell Count; Cell Membrane; Cell Physiological Phenomena; Hemodynamics; Hypertrophy; Membrane Potentials; Muscles; Myocardium; Organ Size; Phosphocreatine; Protein Biosynthesis