Reduction in temporal N-acetylaspartate and creatine (or choline) ratio in temporal lobe epilepsy: does this 1H-magnetic resonance spectroscopy finding mean poor seizure control?

Mendes-Ribeiro, J.A.; Soares, Rodolfo Daniel de Almeida; Simões-Ribeiro, Fernanda; Guimarães, Monick Lindenmeyer

doi:10.1136/jnnp.65.4.518

Cited by 25 publications

(19 citation statements)

References 12 publications

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“…Alternatively, several groups have reported decreased NAA levels estimated by proton magnetic resonance spectroscopy in epileptic patients correlating with increased seizure frequency (Vainio et al, 1994;Vermathen et al, 1997;Mendes-Ribeiro et al, 1998), which appears inconsistent with our results. However, this apparent discrepancy might be explained by the different location of NAA between human epileptic patients and NAA-injected rats.…”

Section: Discussioncontrasting

confidence: 57%

Accumulation of N‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System

Kitada

Akimitsu

Shigematsu

et al. 2000

Journal of Neurochemistry

103

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Abstract:The tremor rat is a mutant that exhibits absence-like seizure and spongiform degeneration in the CNS. By positional cloning, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. Accordingly, no aspartoacylase expression was detected in any of the tissues examined, and abnormal accumulation of N-acetyl-L-aspartate (NAA) was shown in the mutant brain, in correlation with the severity of the vacuole formation. Therefore, the tremor rat may be regarded as a suitable animal model of human Canavan disease, characterized by spongy leukodystrophy that is caused by aspartoacylase deficiency. Interestingly, direct injection of NAA into normal rat cerebroventricle induced 4-to 10-Hz polyspikes or spikewave-like complexes in cortical and hippocampal EEG, concomitantly with behavior characterized by sudden immobility and staring. These results suggested that accumulated NAA in the CNS would induce neuroexcitation and neurodegeneration directly or indirectly. Key Words: Tremor rats-Epilepsy-Neurodegeneration-Positional cloning-Aspartoacylase -N-Acetyl-L-aspartate. J. Neurochem. 74, 2512Neurochem. 74, -2519Neurochem. 74, (2000.Epilepsy is a diverse neurological abnormality that is characterized by recurrent seizures, affecting 1-2% of the population worldwide (McNamara, 1999). Epileptic seizures comprise alterations in sensory and motor systems and in consciousness. They result from the disordered, synchronous, and rhythmic firing of certain populations of neurons in the CNS. Current therapies are not satisfactory, as they do not provide symptomatic relief in some subsets of affected individuals and are sometimes accompanied by toxic effects. Elucidation of the cellular and molecular mechanisms underlying epileptogenesis, therefore, should lead to the development of new fundamental therapies and prevention methods, or even a cure. Seizure disorders or epilepsy syndromes are presently classified into Ͼ40 distinct types (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). Although most epilepsies are considered to be multifactorial diseases, some specific types are considered single-gene disorders (Steinlein et al., 1995;Pennacchio et al., 1996;Biervert et al., 1998;Charlier et al., 1998;Fox et al., 1998;Singh et al., 1998;Wallace et al., 1998;McNamara, 1999).The tremor rat is a single-gene mutant found in the Kyoto:Wistar colony that exhibits absence-like seizure characterized by sudden immobility and staring, simultaneously with the appearance of 5-to 7-Hz spike-wave complexes in cortical and hippocampal EEG (Yamada et al., 1985;Serikawa et al., 1987;Hanaya et al., 1995). Homozygous rats (tm/tm) for the causative genetic locus tremor (tm) exhibit absence-like seizure after the age of 14 weeks, whereas heterozygotes (tm/ϩ) exhibit the same seizure less frequently after 26 weeks (Higashiguchi et al., 1991). In older age groups, wild running and jumping episodes are sometimes observed in tm/tm rats. However, spongiform degene...

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Section: Discussioncontrasting

confidence: 57%

Accumulation of N‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System

Kitada

Akimitsu

Shigematsu

et al. 2000

Journal of Neurochemistry

103

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“…This does not imply that patients with abnormal NAA/Cr ratios could not achieve seizure control. Mendes-Ribeiro et al (53) reported single voxel temporal lobe 'H-MRS findings in 10 seizure-free TLE patients treated with AEDs. Eight patients had normal NAA/Cr values; however, two patients had significant NAA/Cr reduction despite a long period of seizure freedom (3 years) using AEDs.…”

Section: Discussionmentioning

confidence: 99%

Proton Magnetic Resonance Spectroscopic Imaging Studies in Patients with Newly Diagnosed Partial Epilepsy

Dubeau

Andermann

et al. 2000

Epilepsia

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Summary:Purpose: To assess whether the N-acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr.Patients and Methods: Proton magnetic resonance spectroscopic imaging ('H-MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow-up ' H-MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging.Results: Initial 'H-MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow-up 'H-MRSI were seizure-free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 'H-MRSI examination and follow-up 'H-MRSIs showed no significant difference (Z = 135, p = 0.893, 2-tailed) for five seizure-free patients.Conclusions: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure-free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAAlCr improvement and observed variable response warrants further investigation. Key Words: MRS-Epilepsy-Newly diagnosed epilepsyNeuronal recovery. In brain proton magnetic resonance spectroscopy ('H-MRS), the most intense signal is visible at 2.02 ppm and corresponds to N-acetyl groups, mainly N-acetyl aspartate (NAA) (1). NAA is synthesized in brain mitochondria from acetyl-coenzyme A and aspartate by the enzyme L-aspartate N-acetyltransferase (2-4), and is confined to neurons and neuronal processes of the mature brain (5,6). The NAA signal in the mature brain derives only from the neuronal pool, areas of decreased NAA signal intensity are interpreted as neuronal loss and dysfunction. The assumption of neuronal loss is supported by both experimental (7-12) and clinical observations (13,14). The assumption of neuronal dysfunction is supported by in vivo (15-17) and in vitro (12,18,19) (17) performed proton magnetic resonance spectroscopic imaging ( 'H-MRSI) in 16 patients with symptomatic carotid artery stenosis before and after endarterectomy. They found that metabolic changes seen preoperatively (LNAA, Tiactate) normalized 4 days after endarterectomy. Matthews et al. (18) showed that neurons under stress conditions in vitro express less NAA, and this reverses with optimization of the culture media, reflecting the survival of a population of viable neurons. Bates et al. (19) showed that inhibition of mitochondrial oxygen consumption and ATP synthesis also inhibited NAA production, suggesting that impaired neuronal mitochondria function, if ...

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“…Recently, MR spectroscopy has been used in the evaluation of mesial temporal sclerosis (22). The use of single-voxel proton spectroscopy adds about 10 or 15 minutes to the total examination time and shows decreased N-acetylaspartateto-creatine ratios in the hippocampus on the affected side.…”

Section: Complex Partial Seizuresmentioning

confidence: 99%

MR Imaging Evaluation of Seizures

Bradley

Shey²

2000

Radiology

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It is imperative for a radiologist to determine the type of seizure a patient has prior to magnetic resonance (MR) imaging to optimally provide the clinician with the information he or she requires. Specifically, complex partial seizures require evaluation of the frontal lobes and the hippocampus (for mesial temporal sclerosis). These are best evaluated with fluid-attenuated inversion recovery (FLAIR) imaging; the use of intravenously administered contrast material is not required. Other types of chronic seizures are best evaluated with nonenhanced FLAIR or T2-weighted imaging for low-grade tumors, vascular malformations, gliosis after infarction, inflammation, or trauma. The presence of new-onset seizures in an adult or the worsening of chronic seizures warrants T2-weighted or FLAIR imaging and gadolinium-enhanced T1-weighted imaging (to look for primary or metastatic tumors, infections, or inflammatory lesions). If available, echo-planar diffusion imaging should be used also (to look for acute infarcts).

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Reduction in temporal N-acetylaspartate and creatine (or choline) ratio in temporal lobe epilepsy: does this 1H-magnetic resonance spectroscopy finding mean poor seizure control?

Cited by 25 publications

References 12 publications

Accumulation of N‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System

Accumulation of N‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System

Proton Magnetic Resonance Spectroscopic Imaging Studies in Patients with Newly Diagnosed Partial Epilepsy

MR Imaging Evaluation of Seizures

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