Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of new-onset seizures and narcolepsy in a previously healthy 40-year-old man. He developed severe daytime somnolence and cataplexy over the course of a few months. Brain MRI was normal, and polysomnography with multiple sleep latency testing confirmed a diagnosis of narcolepsy. His HLA haplotype is DQB1*0602 and cerebrospinal fluid analysis showed no detectable hypocretin. Approximately 18 months later, he developed complex partial seizures. Further MRI showed a progressively enlarging lesion involving the left frontotemporal and insular areas. Pathology from a partial resection was consistent with Rasmussen's syndrome. Evaluation for tumor, infectious, and paraneoplastic etiologies was negative. There was no further progression of the residual lesion on serial MRI. Although the pathophysiologic bases of narcolepsy and Rasmussen's syndrome are unknown, they may have an autoimmune basis. This unique case of both disorders in a single patient suggests the possibility of a common underlying disease process.
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PMID:Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an adult. 1469 22

A 7-year-old Japanese female diagnosed as having acute disseminated encephalomyelitis presented seizures, visual symptoms, and hypersomnia with bilateral lesions in the white matter, basal ganglia, and hypothalamus. Her clinical findings and demonstrated lesions in neuroimages were similar to those of Von Economo's encephalitis lethargica. Her hypocretin, the hypothalamic neuropeptide controlling sleep-awake cycle, was significantly low in the cerebrospinal fluid (146 pg/mL) on admission. Successive measures resulted in the gradual recovery of cerebrospinal fluid hypocretin to the normal range (263 pg/mL) as her excessive daytime sleepiness was reduced. Decreased hypothalamic hypocretin neurotransmission may be involved in this symptomatic case of hypersomnia associated with acute disseminated encephalomyelitis.
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PMID:Hypersomnia and low cerebrospinal fluid hypocretin levels in acute disseminated encephalomyelitis. 1551 22

Deep brain stimulation (DBS) is a promising therapy for intractable epilepsy, yet the optimum target and underlying mechanism remain controversial. We used the rat pentylenetetrazol (PTZ) seizure model to evaluate the effectiveness of DBS to three targets: two known to be critical for arousal, the histaminergic tuberomammillary nucleus (TMN) and the orexin/hypocretinergic perifornical area (PFN), and the anterior thalamic nuclei (ATH) now in clinical trial. TMN stimulation provided the strong protection against the seizure, and PFN stimulation elicited a moderate effect yet accompanying abnormal behavior in 25% subjects, while ATH stimulation aggravated the seizure. Power density analysis showed EEG desynchronization after DBS on TMN and PFN, while DBS on ATH caused no effect with the same stimulation intensity. EEG desynchronization after TMN stimulation was inhibited in a dose-dependent manner by pyrilamine, a histamine H(1) receptor selective antagonist, while the effect of PFN stimulation was inhibited even at a low dose. In parallel, in vivo microdialysis revealed a prominent increase of histamine release in the frontal cortex after TMN stimulation, a moderate level with PFN and none with ATH. Furthermore, antiepileptic effect of DBS to TMN was also blocked by an H(1) receptor antagonist. This study clearly indicates that EEG desynchronization and the activation of the histaminergic system contributed to the antiepileptic effects caused by DBS to the posterior hypothalamus.
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PMID:Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert antiepileptic effect in rat pentylenetetrazol model. 1732 22

The effects of seizures on the hypocretin/orexin system have not yet been investigated in epileptic patients. The present study aimed to assay hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized tonic-clonic (GTC) seizures. Study groups consisted of 21 patients after GTC seizures and 19 controls. Diagnostic lumbar puncture was performed in control and epileptic patients within 48 h after the GTC seizures. Hypocretin-1 levels were measured in unextracted CSF samples, using a standardized commercial radioimmunoassay. There was a significant overall difference in median CSF hypocretin-1 concentrations between controls and patients with GTC patients (p < 0.001). The lowest concentrations were noted in a subgroup of patients with repetitive GTC seizures (RS) compared to those with a single GTC seizure (SS) (p > 0.05) or controls (p < 0.001). The current results suggest that the hypocretin-1 system deficiency contributes to the complex pathophysiology of repetitive GTC seizures and status epilepticus (SE) and could be associated with typical somnolence after seizure attacks.
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PMID:Decreased cerebrospinal fluid hypocretin-1 (orexin A) in patients after repetitive generalized tonic-clonic seizures. 1917 90

Orexins have been implicated with physiological function including sleep-wake cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and memory but their effects on excitability are controversial. We investigated the effects of intracortical injections of orexin A (100 pmol) and B (100 pmol) on the electrophysiological manifestation of epileptic seizures induced by cortical penicillin application in adult male rats. In comparison to saline, orexin A and B enhanced significantly the spike number, spike amplitude and spectral power values induced by cortical penicillin. Our findings indicates that orexins enhances the hyperexcitable and hypersyncronic cortical epileptic activity induced by focal application of penicillin-G.
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PMID:Orexins increase penicillin-induced epileptic activity. 2239 54

We report a 5-year-old boy with epilepsy and narcolepsy-cataplexy. He developed myoclonic seizures at the age of 4 years, which manifested as head shaking to the left. Approximately 6 months later, narcolepsy-cataplexy with excessive daytime sleepiness occurred. Although a short-time electroencephalography (EEG) and 24-hour ambulatory EEG monitoring found epileptiform discharges, no seizures were determined. Oxcarbazepine was used and led to increased attacks. Video EEG testing finally confirmed the diagnosis of epilepsy; therefore, valproate was given and seizures were controlled completely. Typical cataplexy triggered by laughing, together with the positive multiple sleep latency tests confirmed a diagnosis of narcolepsy-cataplexy. Human leukocyte antigens DQB1*0602 was positive, and the hypocretin level in cerebrospinal fluid was found to be decreased. Combination of valproate, methylphenidate, and clomipramine treatment improved the symptoms of both narcolepsy-cataplexy and seizure. The coexistence of both disorders in this single patient indicated that there might be a common mechanism between epilepsy and narcolepsy-cataplexy.
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PMID:Epilepsy and narcolepsy-cataplexy in a child. 2259 15

One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit without cost. However, intranasal delivery is emerging as a noninvasive option for delivering drugs to the CNS with minimal peripheral exposure. Additionally, this method facilitates the delivery of large and/or charged therapeutics, which fail to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth factors, hormones, neuropeptides and therapeutics including insulin, oxytocin, orexin, and even stem cells, intranasal delivery is emerging as an efficient method of administration, and represents a promising therapeutic strategy for the treatment of diseases with CNS involvement, such as obesity, Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, anxiety, autism spectrum disorders, seizures, drug addiction, eating disorders, and stroke.
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PMID:Intranasal treatment of central nervous system dysfunction in humans. 2313 22

Sleep deprivation has been shown to be an activator of seizures in clinical and animal studies. Orexin-A was speculated to be involved in the aggravation of seizures by sleep deprivation through the activation of its receptors: orexin-1 and orexin-2 receptor (OX1R and OX2R, respectively). Therefore, we aimed to investigate the effects of pre-treating sleep-deprived Wistar rats with the OX1R or OX2R antagonists, SB334867 (30 nM/kg) or TCS OX2 29 (30 nM/kg), respectively, followed by a convulsive dose of 50 mg/kg pentylenetetrazol administration (seizure induction), on seizure behavior, and hippocampal neurodegeneration and cellular proliferation. Our results revealed that treatment with SB334867 or TCS OX2 29 significantly prolonged the latency and reduced the duration of seizures, while also lowering the mortality rate in sleep-deprived rats exposed to pentylenetetrazol. In addition, SB334867 or TCS OX2 29 reduced the damage to hippocampal CA3 neurons and the number of bromodeoxyuridine-positive cells in the dentate gyrus (particularly in the hilus). Overall, the effect of TCS OX2 29 was greater than that of SB334867. Taken together, these data suggest that OX1R and OX2R antagonists may alleviate the damage of pentylenetetrazol-induced seizures that are exacerbated by sleep deprivation, and furthermore could be associated with a reduction of neuronal damage in the hippocampus and the inhibition of cellular proliferation in the dentate gyrus.
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PMID:Pentylenetetrazol-induced seizures are exacerbated by sleep deprivation through orexin receptor-mediated hippocampal cell proliferation. 2385 14

Epilepsy is characterized by the occurrence of repetitive seizures and can greatly affect a patient's cognition, particularly in terms of learning and memory. Orexin-A is an excitatory neuropeptide produced by the lateral hypothalamus that has been shown to be involved in learning and memory. A reduction in the levels of orexin-A after seizures may underlie the learning and memory impairments induced by epilepsy. Thus, we used pentylenetetrazol (PTZ)-kindled rats to investigate the effects of orexin-A on learning and memory and the involvement of neurogenesis in the dentate gyrus in OX1R-mediated ERK1/2 activation. A Morris water maze test revealed reduced escape latencies, prolonged times in the target quadrant and an increased number of platform crossings in PTZ-kindled rats exposed to orexin-A. These ameliorating effects of orexin-A on spatial learning and memory were attenuated by the intracerebroventricular injection of the OX1R antagonist SB334867 or the ERK1/2 inhibitor U0126. Further studies using bromodeoxyuridine (BrdU) revealed that orexin-A increased the number of BrdU-positive cells, doublecortin (DCX)/BrdU levels and the number of NeuN/BrdU double-positive nuclei in the dentate gyrus of PTZ-kindled rats. However, these effects were inhibited by treatment with SB334867 or U0126. Taken together, these data suggest that orexin-A attenuated the impairment of spatial learning and memory in PTZ-kindled rats and that this attenuation involved neurogenesis in the dentate gyrus via OX1R-mediated ERK1/2 activation.
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PMID:Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis. 2432 Nov 99

Des-acyl ghrelin, widely accepted to work independently of the ghrelin receptor, is increasingly being implicated in a number of biological functions. The involvement of des-acyl ghrelin in epilepsy has only been recently reported. In this study, apart from unravelling the effect of des-acyl ghrelin on seizure thresholds and seizure severity in two models of pilocarpine-induced seizures, we mainly attempted to unravel its anticonvulsant mechanism of action. Since it was found that des-acyl ghrelin administration affected food intake via the orexin pathway, we first determined whether this pathway was responsible for des-acyl ghrelin's seizure-attenuating properties using the dual orexin receptor antagonist almorexant. We noted that, while des-acyl ghrelin showed dose-dependent anticonvulsant effects against focal pilocarpine-evoked seizures in rats, almorexant did not affect seizure severity and did not reverse des-acyl ghrelin's anticonvulsant effect. Subsequently, to investigate whether the ghrelin receptor was implicated in des-acyl ghrelin's anticonvulsant properties, we tested this peptide in ghrelin receptor deficient mice and wild type mice, all infused with pilocarpine intravenously. Unexpectedly, we found that des-acyl ghrelin significantly elevated seizure thresholds in C57Bl/6 and wild type mice but not in ghrelin receptor knock-out mice. Taken together, our results indicate the involvement of the ghrelin receptor in the anticonvulsant effects of des-acyl ghrelin on pilocarpine-induced seizures. We also show for the first time that dual antagonism of hippocampal orexin receptors does not affect seizure severity.
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PMID:Des-acyl ghrelin attenuates pilocarpine-induced limbic seizures via the ghrelin receptor and not the orexin pathway. 2600 75


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