Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. Notably, we show that the sensitivity to PTZ epileptogenesis is decreased in MMP-9 knockout mice but is increased in a novel line of transgenic rats overexpressing MMP-9. Immunoelectron microscopy reveals that MMP-9 associates with hippocampal dendritic spines bearing asymmetrical (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9 deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis after mossy fiber sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE.
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PMID:Important role of matrix metalloproteinase 9 in epileptogenesis. 1833 22

The association of brain malformations and symptomatic epilepsy in the setting of neurofibromatosis type 1 (NF1) is rarely reported. When it occurs, patients can present clinically with infantile spasms, focal seizures, generalized tonic clonic seizures or atypical absences. We report on a 10-year-old (molecularly proven) NF1 girl manifesting a complex epileptic syndrome resembling the Foix-Chavany-Marie spectrum (also known as opercular syndrome) associated with bilateral (opercular and paracentral lobular) polymicrogyria (PMG). Anecdotal cases of unilateral PMG in the setting of NF1 have been described in association with other-than-opercular epileptic syndromes. The typical clinical opercular syndrome consisting in mild mental retardation, epilepsy and pseudobulbar palsy is usually associated to bilateral perisylvian PMG (BPP) CONCLUSION: To the best of our knowledge, the complex epileptic syndrome hereby reported has not been previously recorded in the setting of NF1. In addition, the present girl manifested all the clinical features of an opercular syndrome but had an asymmetrical PMG (not a BPP).
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PMID:Complex epileptic (Foix-Chavany-Marie like) syndrome in a child with neurofibromatosis type 1 (NF1) and bilateral (opercular and paracentral) polymicrogyria. 1914 Nov 42

Myoclonic jerks and myoclonic status (MS) are sometimes difficult to distinguish clinically from movement disorders such as hand stereotypies, tremor, and dystonia in Rett syndrome. We describe a rare and complete video-polygraphic study of a girl with Rett syndrome (MECP2 mutation) and MS misdiagnosed as movement disorders and disclosed after video-polygraphic recordings. Corresponding to closely recurring activity of diffuse spike and polyspikes-wave-type paroxysms, rhythmic and, especially, arrhythmic myoclonias, usually asymmetrical and asynchronous, involving mainly right muscle deltoid and rarely followed by an inhibitory phenomenon, appeared. The MS improved and, most importantly, disappeared after the use of levetiracetam, with an evident antimyoclonic efficacy and a marked improvement of daily life for the patient and her caregivers. The difficulty in differentiating some typical nonepileptic behavioral features and movement disorders of patients with Rett syndrome from seizures was overcome using prolonged video-polygraphic recordings in our case.
Epilepsy Behav 2009 Jun
PMID:Myoclonic status misdiagnosed as movement disorders in Rett syndrome: a video-polygraphic study. 1960 60

Na(+),K(+)-ATPase contributes to the asymmetrical distribution of sodium and potassium ions across the plasma membrane and to maintenance of the membrane potential in many types of cells. Alterations in this protein may play a significant role in many human neurological disorders, including epilepsy. We studied expression of the alpha3 isoform of Na(+),K(+)-ATPase in the freeze lesion (FL) microgyrus model of developmental epileptogenesis to test the hypothesis that it is downregulated following neonatal cortical injury. FL and sham-operated rat brains were examined at postnatal day (P)7, P10, P14, P21-28 and P50-60 after placement of a transcranial freeze lesion at P0 or P1. Immunohistochemistry and in situ hybridization were used to assess the expression of the alpha3 isoform of Na(+),K(+)-ATPase (termed alpha3, or alpha3 subunit below) in neuropil and the perisomatic areas of pyramidal cells and parvalbumin-containing interneurons. There was a significant decrease (P<0.05) in alpha3 subunit immunoreactivity (IR) in the neuropil of FL cortical layer V of the P14 and P21-28 groups that extended up to 360 mum from the border of the microgyrus, an area that typically exhibits evoked epileptiform activity. Alpha-3 was decreased in the perisomatic area of pyramidal but not parvalbumin-containing cells in P21-28 FL animals. A reduction in alpha3 mRNA was observed in the neuropil of FL cortical layer V up to 1610 mum from the microgyral edge. The developmental time course for expression of the alpha3 subunit between P7 and P60 was examined in naive rat cortices and results showed that there was a significant increase in alpha3 IR between P7 and P10. The significant decreases in Na(+),K(+)-ATPase in the paramicrogyral cortex may contribute to epileptogenesis.
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PMID:Temporal and topographic alterations in expression of the alpha3 isoform of Na+, K(+)-ATPase in the rat freeze lesion model of microgyria and epileptogenesis. 1936 29

A female infant suffered from epilepsy since the neonatal period, which evolved into West syndrome at the age of 2 months. Spasms in series and hypsarrhythmia disappeared after treatment with high-dose phenobarbital; however, single spasms persisted with right-sided predominance, and polyspike activity in the left parieto-temporal areas preceded or coincided with these spasms. Magnetic resonance imaging revealed a small calcification in the right occipital area, and positron emission tomography showed hypometabolism over the right hemisphere. Widespread epileptic discharges gradually increased on electroencephalography (EEG) during sleep thereafter. The patient presented with daytime unresponsiveness at 1 year and 6 months, when diffuse, irregular spike and wave activity characterized the waking EEG. Spasms or brief tonic seizures with right-sided predominance were provoked by auditory stimuli during this period, particularly by her mother's voice, with ictal EEG of right posterior predominant fast activity and subsequent desynchronization. The administration of clobazam resulted in the marked improvement of EEG findings and transient disappearance of spasms. Presumably, certain patients with asymmetrical epileptic spasms may be regarded as a unique type of localization-related epilepsy, and can show an unusual course of evolution in comparison to other cases of epilepsy that evolve after West syndrome.
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PMID:Non-convulsive status epilepticus and audiogenic seizures complicating a patient with asymmetrical epileptic spasms. 1973 86

The fine tuning of proliferation and neurogenesis, neuronal migration and differentiation and connectivity underlies the proper development of the cerebral cortex. Mutations in genes involved in these processes are responsible for neurodevelopmental disorders, such as cortical dysgeneses, which are usually associated with severe mental retardation and epilepsy. Over the past few years, the importance of cytoskeleton components in cellular processes crucial for cortical development has emerged from a body of functional data. This was reinforced by the association of mutations in the LIS1 and DCX genes, which both encode proteins involved in microtubule (MT) homeostasis, with cerebral cortex developmental disorders. The recent discovery of patients with lissencephaly and bilateral asymmetrical polymicrogyria (PMG) carrying mutations in the alpha- and beta-tubulin-encoding genes TUBA1A and TUBB2B further supports this view, and also raises interesting questions about the specific roles played by certain tubulin isotypes during the development of the cortex.
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PMID:Tubulin-related cortical dysgeneses: microtubule dysfunction underlying neuronal migration defects. 1986 38

Studies investigating the pathophysiology of epileptic photosensitivity indicate variable involvement of particular brain regions. Our aim was to identify metabolic differences between photosensitive idiopathic generalized epilepsy (IGE) patients and nonphotosensitive IGE patients and normal healthy subjects by using Magnetic Resonance Spectroscopy (MRS). Fourteen patients diagnosed with photosensitive IGE were investigated. The control groups consisted of 14 age- and sex-matched healthy volunteers and 14 IGE patients without photosensitivity. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr) were performed in the frontal and occipital cortex and the thalamus bilaterally using a stimulated echo acquisition mode (STEAM) technique with a voxel size of 20 x 20 x 20 mm. The values of the patients with IGE were compared with those of the normal controls and within subgroups according to the clinical variables by appropriate statistical tests. Photosensitive IGE patients showed significantly decreased concentrations of NAA in the right frontal lobe and left thalamus, decreased NAA/Cr ratio in left thalamus and significantly increased concentrations of Cho/Cr ratio in the right frontal lobe and NAA/Cr in the left occipital lobe when compared to normal controls. Furthermore, left occipital NAA concentration increased and left thalamus NAA/Cr ratios were decreased from the IGE patients without photosensitivity but without reaching statistical significance. Our results support previous MR studies suggesting an asymmetrical neuronal dysfunction in favor of the dominant occipital cortex and thalamus in photosensitive IGE patients.
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PMID:Magnetic resonance spectroscopy findings in photosensitive idiopathic generalized epilepsy. 2030 15

We report acute encephalopathy in two cases with severe congenital hydrocephalus. Case 1 was a 23-month-old girl, born at of 36weeks gestation and delivered by cesarean section due to congenital hydrocephalus. Magnetic resonance imaging (MRI) showed prominent ventricular dilation associated with hydrocephalus, Dandy-Walker variant and cortical malformation. The blood test for toxoplasmosis, syphilis, varicella-zoster, rubella, cytomegalovirus, and herpes simplex virus (TORCH) complex and various metabolic tests of blood and urine specimens yielded unremarkable results. She was admitted to our hospital for respiratory failure with fever and her clinical course deteriorated, progressing to hemiconvulsion hemiplegia epilepsy syndrome. Case 2 was a 17-month-old boy, born by spontaneous vertex delivery at 39weeks. Severe, asymmetrical ventricular dilation associated with hydrocephalus, cerebellar and brainstem hypoplasia, and punctuate calcifications of the thalamus, third and fourth ventricles, around the aqueduct, were observed on computed tomography (CT). The blood test for TORCH complex and various metabolic tests of blood and urine specimens yielded unremarkable results. He was admitted to our hospital for status epilepticus with fever and his clinical course progressed to hemorrhagic shock and encephalopathy syndrome. In patients with brain disorders, diagnosis and treatment are likely to be delayed and prognosis may thereby be worsened. When status epileptics or prolonged coma manifests even in patients with severe brain disorders, we must consider encephalopathy in the differential diagnosis.
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PMID:Acute encephalopathy in two cases with severe congenital hydrocephalus. 2109 88

We report a paradoxical effect of valproate sodium (VPA) observed in a 3-year-old girl with cryptogenic localization-related epilepsy. On admission she experienced two types of seizures that were confirmed by ictal EEGs : complex partial seizures (CPSs) originating from the left hemisphere and combined seizures that began with repetitive myoclonic seizures immediately followed by a CPS. These myoclonic seizures did not possess asymmetrical features, but the ictal EEGs showed left-side dominant multiple spike-waves. The patent's interictal EEGs on admission showed left posterior temporal- parietal spikes during wakefulness and frequent diffuse spike-waves during sleep. In the process of introduction and increase in the dosage of VPA, an aggravation of epileptic discharges, especially a dramatic increase in diffuse spike-waves during sleep, was observed. In the same period of time, myoclonic seizures not followed by CPS newly appeared, and there was an increase in the frequency of CPSs and combined seizures. Marked improvement of epileptic discharges, namely the disappearance of diffuse discharges, and complete suppression of all types of seizures were achieved by the introduction of carbamazepine (CBZ) along with the withdrawal of VPA. During the clinical course, the patient did not display any signs or symptoms of VPA encephalitis, overdose of VPA or metabolic aberration. The paradoxical effect of CBZ in localization-related epilepsy is well-known, yet in this case, VPA displayed a similar paradoxical effect. Additionally, CBZ was efficacious in the suppression of secondary bilateral synchrony on EEG and also successfully controlled CPSs, combined seizures and myoclonic seizures.
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PMID:[Aggravation of epilepsy by valproate sodium in a child with cryptogenic localization-related epilepsy]. 2140 Sep 33

The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40-65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease pathology. In summary, there is evidence of accelerated brain ageing in severe chronic epilepsy although progression to high Braak stages was infrequent. Traumatic brain injury, but not seizures, was associated with tau protein accumulation in this series. It is likely that Alzheimer's disease pathology is not the sole explanation for cognitive decline associated with epilepsy.
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PMID:Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study. 2190 28


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