Magnetic Resonance Imaging and Spectroscopy Findings After Focal Status Epilepticus

Summary: The etiology of cerebral abnormalities after focal status epilepticus (SE) is unknown. Possible causes include hypoxia and the excessive release of excitatory amino acids. Magnetic resonance imaging (MRI) of a 21–year-old patient with "cryptogenic" continuous motor seizures showed swelling and signal hyperintensity of the contralateral panetotemporal cortex, the thalamus, and the ipsilateral cerebellum on T₂-weighted images. These regions are connected by glutamatergic pathways. Proton magnetic resonance spectroscopy (MRS) of the cortical lesion yielded a signal peak at the resonance frequency of 2.29 ppm, suggesting a focal increase of glutamate or its degradation product glutamine. At 3–month follow-up, structural alterations had disappeared, but the N-acetylaspartatelcholine ratio was still reduced in the previously abnormal area. These findings are the first to demonstrate the contribution of MRS to pathophysiologic studies of focal SE in humans and, in combination with the pattern of imaging abnormalities, support a major role of glutamate for seizure-related brain damage.     

Use of 31P magnetic resonance spectroscopy to characterize evolving brain damage after perinatal asphyxia

We investigated postasphyxial brain damage with 31P magnetic resonance spectroscopy (MRS) and correlated it with neurologic assessment and standard laboratory evaluation during the first 10 months of life in 1 infant, baby G. We compared these observations to 31P MRS data from 7 healthy term newborns, 1 normal infant examined serially over the first 8.5 months of life, and 5 other term infants following perinatal asphyxia. MRS noninvasively provides biochemical correlates of the evolution of brain damage following perinatal asphyxia and suggests that pH derived from the inorganic phosphate peak may serve as a marker for brain injury.     

Energetic basis of brain activity: implications for neuroimaging

The complex activities of the brain need not distract us from the certainty that it uses energy and performs work very efficiently. The human brain, which claims approximately 2% of our body mass, is responsible for approximately 20% of our body oxygen consumption. In vivo magnetic resonance spectroscopy (MRS) follows the metabolic pathways of energy production (as glucose oxidation) and work (as monitored by the cycling of glutamate and GABA neurotransmitters). In the resting awake state, approximately 80% of energy used by the brain supports events associated with neuronal firing and cycling of GABA and glutamate neurotransmitters. Small differences in neuronal activity between stimulation and control conditions can be measured and localized using functional magnetic resonance imaging (fMRI). MRS and fMRI experiments show that the majority of cerebral activity, which is often disregarded in imaging experiments, is ongoing even when the brain appears to be doing nothing.     

Proton magnetic resonance spectroscopy of the brain in dementia

Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progresson or effects of drug therapy.     

Metabolic kinetics in the brains in infants with IUGR, respiratory distress syndrome, seizures and asphyxia]

31-P magnetic resonance spectroscopy (MRS) allows noninvasive measurements of cerebral phosphorus compounds: ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME) and phosphodiesters (PDE). In this paper we reported our MRS data from the brains of infants with intrauterine growth retardation, respiratory distress syndrome, neonatal seizures or neonatal asphyxia, and discussed the possibilities to prevent brain damage due to these perinatal troubles.     

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.     

Magnetic resonance findings in two episodes of repeated cerebral fat embolisms in a patient with autologous fat injection into the face

We report magnetic resonance image (MRI) and magnetic resonance spectroscopy (MRS) findings in a patient of cerebral fat embolism (CFE) occurred in a 26-year-old woman after an autologous fat injection into the face. After initial neurologic symptom onset, MRI and MRS data were obtained two times to investigate repeated CFE. We obtained the MRS data in the two different time intervals and two different echo times to compare the lesions with normal brain parenchyma. The results of MRS data showed that a decrease in N-acetyl-aspartate, an increase in lactate and a very high early peak of free lipids between 0.9 and 1.4 ppm were obtained at the acute infarcted lesion as compared with normal brain parenchyma. In addition, these findings were more clearly detected on short echo time spectrum rather than long spectrum. A close relationship between the clinical manifestations and MRI and MRS findings of the brain can helpful to distinguish CFE with other conditions and to evaluate the cause materials of infarctions rather than conventional MRI or diffusion-weighted imaging.     

Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis

Decreases in brain N-acetylasparatate are associated with neuronal loss or dysfunction. We report a longitudinal study in which changes in the N-acetylaspartate to creatine resonance intensity ratio measured by brain proton magnetic resonance spectroscopy were used to follow the progression of brain pathology in 7 patients with multiple sclerosis over an 18-month period. Four of the patients had a history of recurrent relapses and 3 had a secondary progressive course. All had clinical and magnetic resonance imaging evidence of persistent neurological abnormalaties. At 6-month intervals proton magnetic resonance spectra were obtained and the N-acetylaspartate–creatine ratio was determined for each patient. The volumes of hyperintense signal from lesions on conventional magnetic resonance images and the Kurtzke Expanded Disability Status Scale scores were determined concurrently. At the onset of the study, the N-acetylaspartate–creatine ratio was significantly (p < 0.05) lower in the central brain volumes from the patients than in 13 normal control subjects. At 12 and 18 months of follow-up, the ratio had decreased further in all patients (p < 0.05), consistent with progressive accumulation of neuronal damage. In contrast to magnetic resonance spectra data, changes in lesion volume on magnetic resonance images or disability status did not reach significance over this period. Subgroup analysis showed that changes (increases or decreases) in the N-acetylaspartate–creatine ratio between consecutive 6-month examinations correlated significantly (r = –0.74, p < 0.005) with changes in lesion volume on magnetic resonance images in patients with a history of relapses. This pilot study suggests that proton magnetic resonance spectroscopy may be useful in evaluating the progression of cerebral damage in multiple sclerosis using a novel quantitative index based on neuronal damage or dysfunction.     

Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders.

The use of magnetism in medicine has a long and colorful history since its legendary discovery in the Western world by the shepherd Magnes. More recent use of magnetism has centered on nuclear magnetic resonance. Magnetic resonance spectroscopy (MRS) provides chemical information on tissue metabolites. Both hydrogen 1 (1H) and phosphorus 31 resonances have been used to study brain tissue, but the magnetic resonance sensitivity for protons is far greater than it is for phosphorus. One of the most important contributions of 1H-MRS to clinical neurology is its ability to quantify neuronal loss and to demonstrate reversible neuronal damage. 1H-magnetic resonance spectroscopy has been found to be a useful research tool in elucidating the pathophysiology underlying certain diseases. This review focuses on the use of proton MRS to study various neurologic diseases, including epilepsy, multiple sclerosis, brain tumors, human immunodeficiency virus 1-associated neurologic disorders, as well as cerebrovascular, neurodegenerative, and metabolic diseases. It highlights the contributions of 1H-MRS to the diagnosis and the monitoring of these neurologic diseases that make it a useful adjunct in patient management.     

Interferon therapy-responsive brain metabolic abnormalities in a case of adult-onset subacute sclerosing panencephalitis evaluated by 1H MRS analysis

We describe a 22-year-old woman with an adult-onset, slowly progressive form of subacute sclerosing panencephalitis (SSPE), who was repeatedly evaluated by brain magnetic resonance spectroscopy (MRS). The brain lesion spectrum showed a decrease in N-acetylaspartate (NAA) resonance, an increase in inositol (Ins) resonance, and an unaltered choline signal. These findings suggest neuronal loss and reactive gliosis without inflammation, consistent with brain biopsy findings showing astrocytic proliferation unaccompanied by lymphocytic infiltrates. The unusually protracted clinical course might be attributable to an absence of inflammatory infiltrates in the brain. Intraventricular interferon injection plus oral inosine pranobex treatment produced a substantial improvement in the MRS findings, suggesting the validity of monitoring MRS in SSPE.     

What might be the impact on neurology of the analysis of brain metabolism by in vivo magnetic resonance spectroscopy?

In vivo nuclear magnetic resonance spectroscopy (MRS) of the human brain is a recently developed technique which allows to assay noninvasively in vivo key molecules of brain metabolism. After a review of the origin of the signals detected by phosphorus and proton MRS of human brain, the impact of MRS on clinical neurology is examined. MRS of the brain does not purport to be a metabolic biopsy, but unique applications for brain MRS are (1) quantitating the oxidative state of the brain and defining neuronal death, (2) assessing and mapping neuron damage, (3) evaluating membrane alterations, and (4) characterizing encephalopathies. In the near future brain MRS will be performed routinely after conventional MRI, as a valuable metabolic (and functional) complement to the anatomical evaluation of cerebral pathologies, particularly the toxic, metabolic and infectious encephalopathies.     

Developmental consequences of childhood frontal lobe damage.

A 33-year-old woman underwent neurologic and neuropsychological studies 26 years after she sustained damage to the frontal lobe. The findings of the neurologic examination were normal, and magnetic resonance imaging revealed a lesion in left prefrontal cortex and deep white matter. Cerebral blood flow studies showed an abnormal pattern in both left and right frontal regions. The patient exhibited striking neuropsychological defects in higher cognition, most notably in self-regulation of emotion and affect and in social behavior. Analysis of her behavioral development failed to yield a pattern of abrupt onset of defect immediately after the lesion occurred. On the contrary, there was a delayed onset of defects, followed by a period of seeming progression, and finally an arrest of development in adolescence. We suggest that this peculiar pattern is the natural consequence of the varied changes that occurred in brain development and social cognition during the patient's formative years. While certain long-term neuropsychological deficits in our case are similar to those following frontal damage in adults, the delayed onset and progression of deficits are different.     

Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury

OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (MRS), a newer radiographic technology, would be useful in the evaluation of the thalamus of patients in vegetative states resulting from traumatic brain injury. METHODS: 14 victims of severe traumatic brain injury who were in the vegetative state and whose magnetic resonance images of the thalamus were normal underwent bilateral thalamic proton (MRS) studies. The N-acetyl aspartate to creatine (NAA:Cr) and choline to creatine (Cho:Cr) ratios were obtained for each patient. The proton thalamic MRS findings of patients who were in a persistent vegetative state (n = 8) and in patients who had regained awareness after being in the vegetative state (n = 6) were compared with proton thalamic MRS findings in five healthy volunteers. RESULTS: While conventional magnetic resonance imaging suggested that each patient had a normal thalamus, proton MRS indicated that the thalamus of each patient in the series was damaged. The NAA:Cr ratio was significantly lower in the thalami of both the patients who remained in a persistent vegetative state for the duration of the study and in those who regained awareness after being in the vegetative state (p < 0.001). In addition, NAA:Cr ratios were lower in the group of patients who remained in a persistent vegetative state than in the group of patients who regained awareness after being in the vegetative state (p < 0.001). CONCLUSIONS: Results suggest that the NAA:Cr ratio within the thalamus is significant and that thalamic MRS may be helpful when attempting to determine the degree of severity of neuronal and axonal injury in patients in the vegetative state.     

MRS Findings in Cerebral Coenurosis due to Taenia Multiceps

Cerebral coenurosis due to Taenia multiceps is a rare infection with no case reports from India. A 55‐year‐old male patient had presented with progressive symptoms of hemiparesis of 1‐year duration. Magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) of the lesion was performed that showed a septated cystic lesion in left parieto‐occipital lobe. Multivoxel MRS through the lesion was performed using repetition time of 1500 ms and time to echo of 144 ms at 3T MRI. MRS showed mildly elevated choline (Cho), depressed creatine (Cr), and N‐acetyl aspartate (NAA), a large peak of lactate, pyruvate, and acetate peaks. To best of our knowledge, there has been no reported case of in vivo proton MRS finding ever reported. We present MRS findings in this operatively proven case of T. multiceps cyst of the brain.     

Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain

Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging.     

Pure representational neglect after right thalamic lesion

Recent reports highlight the utility of in vivo magnetic resonance spectroscopy (MRS) techniques to recognize creatine deficiency syndromes affecting the central nervous system (CNS). Reported cases demonstrate partial reversibility of neurologic symptoms upon restoration of CNS creatine levels with the administration of oral creatine. We describe a patient with a brain creatine deficiency syndrome detected by proton MRS that differs from published reports. Metabolic screening revealed elevated creatine in the serum and urine, with normal levels of guanidino acetic acid. Unlike the case with other reported creatine deficiency syndromes, treatment with oral creatine monohydrate demonstrated no observable increase in brain creatine with proton MRS and no improvement in clinical symptoms. In this study, we report a novel brain creatine deficiency syndrome most likely representing a creatine transporter defect.     

In Vivo 1H Magnetic Resonance Spectroscopic Measurement of Brain Glycine Levels in Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of glycine metabolism. Defective glycine cleavage causes elevated concentrations of glycine in plasma, urine, and cerebrospinal fluid. A longitudinal study using magnetic resonance imaging (MRI) and single-voxel 1H magnetic resonance spectroscopy (MRS) was performed on an infant with the typical clinical picture of NKH. He was examined twice during the course of treatment with sodium benzoate and dextromethorphan. At the age of 10 months, MRI showed normal brain structure, while MRS detected a prominent glycine peak in the brain. Repeat MRS at the age of 13 months showed a small increase in glycine peak and a prominent glutamate/glutamine peak not previously detected. The MRS measurements were consistent with the slight increase in blood glycine level and the elevation in glutamine level, indicating that 1HMRS can be a valuable tool in the diagnosis and monitoring of treatment effects in patients with NKH.     

Expression of citrulline-nitric oxide cycle in lipopolysaccharide and cytokine-stimulated rat astroglioma C6 cells

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine (Arg) and other guanidino compounds (GC). Convulsions, lethargy and psychomotor delay are predominant clinical features of this disease. Considering that some GC are epileptogenic and cause a decrease in membrane fluidity and that Na+,K(+)-ATPase, a membrane-bound enzyme, is essential for cellular excitability and is decreased in experimental and human epilepsy, in the present study we determined the in vitro effects of Arg, N-acetylarginine (NAA), argininic acid (AA) and homoarginine (HA) on the activity of Na+,K(+)-ATPase in the synaptic plasma membrane from cerebral cortex of young rats in the hope to identify a possible mechanism for the brain damage in hyperargininemia. The results showed that all GC tested, except Arg, significantly inhibited Na+,K(+)-ATPase activity at concentrations similar to those observed in plasma and CSF of patients with hyperargininemia. In addition, competition between NAA, AA and HA for the binding to the enzyme was observed, suggesting a common binding site for the GC. It is therefore possible that the inhibitory effect of GC on Na+,K(+)-ATPase may be related to the brain dysfunction observed in hyperargininemia.     

Proton magnetic resonance spectroscopy to study the metabolic changes in the brain of a patient with Leigh syndrome.

Localized proton magnetic resonance spectroscopy (MRS) was performed to study the metabolic changes in the brain of a patient with Leigh syndrome, who had a T-->G point mutation at nt 8993 of mitochondrial DNA. In this patient, sodium dichloroacetate therapy normalized the lactate and pyruvate levels in both blood and cerebrospinal fluid (CSF). However, his psychomotor retardation did not improve and magnetic resonance imaging showed progressive cerebral atrophy. In the patient's spectra, elevation of brain lactate was observed throughout the brain with regional variations, predominantly in the basal ganglia and brainstem with an abnormal MRI appearance. Although the lactate/creatine ratio observed on proton-MRS was related to the CSF lactate level, the ratio did not completely parallel the CSF lactate level, i.e. brain lactate was detected even when the CSF lactate level had become normalized. Furthermore, proton-MRS revealed a decrease in the N-acetylaspartate/creatine ratio and an increase in the choline/creatine ratio, representing neuronal loss and breakdown of membrane phospholipids. The clinical and MRI findings were well related to the changes in spectroscopically determined brain metabolites. These results indicate that the brain metabolites observed on proton-MRS are useful indicators of a response to therapy and prognosis in Leigh syndrome.     

MRS Metabolic Markers of Seizures and Seizure-Induced Neuronal Damage

Summary: Purpose: Proton magnetic resonance spectroscopy (MRS) was used to identify specific in situ metabolic markers for seizures and seizure-induced neuronal damage. Kainic acid (KA)-induced seizures lead to histopathologic changes in rat brain. The protective effect of cycloheximide treatment against neuronal damage caused by KA-induced seizures was studied, using in situ proton MRS imaging technique.
Methods: Rats were pretreated with placebo or cycloheximide 1 h before KA injection. Rat brains (n = 25) were scanned at the level of the hippocampus before, during, and 24 h after seizures. Spectra were recorded and the relative ratios of N-acetylaspartate (NAA), choline (cho), and lactate (Lac) to creatine (Cr) were calculated and compared between groups.
Results: A significant increase in Lac ratios was observed in KA-treated rats during and 24 h after seizure onset and this increase was prevented by cycloheximide pretreatment. NAA ratios were significantly higher during the ictal phase following KA treatment and this effect was not affected by cycloheximide pretreatment. Nissl staining confirmed previously reported prevention of KA-induced neuronal loss in CA1 and CA areas of the hippocampus by cycloheximide pretreatment.
Conclusions: Our results suggest that in situ Lac increase is a marker of seizure-induced neuronal damage, whereas N-acetylaspartate (NAA) changes during and after status epilepticus may be a reflection of neuronal activity and damage, respectively.