Convulsive Episodes Research Articles

Effects of pain stimulation on bispectral index, heart rate and blood pressure at different minimal alveolar concentration values of sevoflurane

The aim of the present study was to examine the level of unconsciousness measured with bispectral index (BIS) at different minimal alveolar concentration (MAC) levels of sevoflurane, and to study the hemodynamic and BIS reactions during noxious stimulation with transcutaneous electrical nerve stimulation (TENS) and an ice water pain test (IWP). This study was approved by the Ethics Committee and was performed on 10 healthy, young volunteers (six males and four females), ASA physical status I. Anesthesia was induced and maintained with sevoflurane in an oxygen/air mixture. The volunteers were spontaneously breathing, but if necessary, ventilation was mechanically supported. TENS and IWP were performed at 1.0, 1.5 and 2.0 MAC of sevoflurane. At 1.0 MAC, there was a significant increase in BIS during pain stimulation both with IWP (P<0.03) and with TENS (P<0.005), but at 1.5 MAC there were no changes. A marked variation in BIS was seen at 2.0 MAC, with periods of burst suppression and periods of high BIS values despite clinical signs of deep anesthesia. These marked variations in BIS were seen before, during and after pain stimulation. One volunteer (# 8) had a short episode of convulsions at 2.0 MAC. BIS, heart rate and blood pressure increased during pain stimulation at 1.0 MAC but not at 1.5 MAC of sevoflurane. There was a remarkable variation in BIS at 2.0 MAC of sevoflurane, with BIS values indicating wakefulness despite clinical signs of deep anesthesia. This BIS variation is probably caused by epileptogenic activity due to sevoflurane.

Multifocal pneumocyte hyperplasia in tuberous sclerosis

A 29-year-old woman, a known case of tuberous sclerosis, presented to our hospital with a 1-day history of multiple episodes of convulsions. This was associated with vague chest and abdominal...

Hemodialysis: A therapeutic option for severe attacks of acute intermittent porphyria in developing countries

Acute intermittent prophyria (AIP) is an autosomal dominant disease that results from a defect in the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the most common of hepatic porphyrias and can tax the therapeutic capabilities of the physician to the limit. Motor weakness is a major feature of an acute attack, and flaccid paralysis of all extremities can occur rapidly, within a matter of days. The acute attacks may be life threatening. Hematin (Heme Arginate) should be given early during an acute attack to prevent neurologic sequel. Hemodialysis and hemoperfusion have been tried in the treatment of acute attacks of AIP with success. As hematin is not available in India, a severe acute attack of AIP in a patient was managed with hemodialysis successfully. Later, hematin was imported and provided to the patient. An 18-year-old girl was admitted to our hospital with recurrent abdominal pain and 2 episodes of convulsions. She had undergone an appendectomy earlier at another hospital for abdominal pain. On evaluation, she had hyponatremia, episodic abnormal behavior, generalized muscle pain, hypertension, and sinus tachycardia. In view of the above clinical picture, a clinical diagnosis of acute intermittent porphyria was made. Her 24-hr urinary porphobilinogen was 90.8 mg/day (<2 mg-normal) and alpha amino levalunic acid was 108.8 mg/day (1-7 mg-normal), consistent with the diagnosis. Her hyponatremia was corrected. Arrangements were made to import hematin and she was managed with dextrose infusion. Meanwhile, she developed flaccid quardriparesis with urinary incontinence and bulbar palsy. Her brain MRI was normal. Her nerve conduction study was suggestive of motor radiculoneuropathy. Specific treatment for severe porphyric crisis was planned. She failed to improve with dextrose infusion alone. As hematin was not readily available in the country, other therapeutic options were considered. As few case reports of AIP being successfully treated with hemodialysis were available, the option of dialytic support was explained to the family. After procuring informed consent, she was subjected to hemodialysis for 4 hr in the first day, increasing to 6 hr a day for the next 6 days. Her abdominal pain and myalgia subsided on the third day of dialysis. Her lower limb muscle power improved and she became ambulant by the fourth day. Urinary retention improved within 4 days. Hematin was imported by then from the United States. Later, 2 doses of hematin (4 mg/kg-160 mg in 20% albumin) were given via a central vein. She was maintained on physiotherapy. Repeat nerve conduction study revealed recovery. She has been provided with a list of drugs that have to be avoided. Currently, she is on outpatient follow-up with occasional abdominal pain, which subsides with intravenous dextrose therapy.

Diphenyl Diselenide-Induced Seizures in Rat Pups: Possible Interaction with Glutamatergic System

The aims of the present study were to investigate the possible involvement of glutamatergic system in seizures induced by diphenyl diselenide in rat pups (postnatal day, 12-14) and to evaluate the role of oxidative stress in seizures induced by diphenyl diselenide/glutamate. Glutamate (4 g/kg of body weight) administered in association with diphenyl diselenide (500 mg/kg of body weight) increased the latency for the appearance of the first seizure episode, reduced lipid peroxidation levels and catalase, Na+,K+-ATPase and delta-ALA-D activities. At the lowest dose (5 mg/kg of body weight), diphenyl diselenide reduced the appearance of seizure episodes induced by glutamate but did not alter the latency for the onset of the first episode. Glutamate uptake was inhibited in glutamate, diphenyl diselenide (the highest dose) and in the association of diphenyl diselenide (both doses) and glutamate groups. Pre-treatment with a N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (5S,10R-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), significantly prolonged the latency for the onset for the first convulsive episode. A non-NMDA receptor antagonist, DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect seizures induced by diphenyl diselenide. The results of the present study demonstrated that: (a) when diphenyl diselenide and glutamate were administered concomitantly in pups, glutamate was the main responsible for the neurotoxic effects; (b) oxidative stress was not involved in glutamate-induced seizures; (c) NMDA glutamatergic receptors, were at least in part, involved in diphenyl diselenide- induced seizures; and (d) diphenyl diselenide, at the lowest dose, protected seizures induced by glutamate.

Association of HAX1 Deficiency with Neurological Disorder

Severe congenital neutropenia (SCN) is a rare, heterogeneous, primary immunodeficiency disorder characterized by early onset of severe bacterial infections. We here describe a case of SCN associating neutropenia and neurodevelopmental delay. The girl was well until the age of 9 months, when she suffered from an episode of convulsion. Subsequently, she developed several episodes of superficial abscesses, oral ulcers and otitis media. Further work-up revealed severe congenital neutropenia caused by a homozygous mutation (R86X) in the antiapoptotic molecule HAX1. She also suffered from psychomotor retardation and recurrent seizures. This case illustrates that HAX1 deficiency may be associated with a neurological phenotype.

Hyperventilation-stage electroencephalography in lateral temporal lobe epilepsy.

To observe spike activity in electroencephalograms (EEGs), patients with symptomatic partial epilepsy are rarely monitored during the hyperventilation stages. A 38-year-old woman suffered from a ruptured arteriovenous malformation in the left temporal lobe. One and a half years later, the patient experienced her first generalized convulsion. EEG showed small spikes in the posterior of the left temporal lobe, which was observed during the hyperventilation and posthyperventilation stages. Because the location of the spikes correlated with the site of the lesion as observed from radiographic findings, she was diagnosed with lateral temporal lobe epilepsy. Drug treatment resulted in no further convulsive episodes and the patient has since returned to work. EEG recordings during hyperventilation should be regarded as an effective technique in analyzing epilepsy because of its ease and cost-effectiveness compared with other methods such as single-photon emission computed tomography.

Ammonia poisoning causes muscular but not liver damage in cattle

Twelve steers were intraruminally administered a high dose (0.5g/kg BW) of urea to study the damage effect of ammonia poisoning on liver and/or muscles. Blood samples were collected to determine ammonia and activities of gammaGT, AST and CK. Eleven steers were successfully poisoned and treated properly, but one succumbed. Poisoned cattle showed high concentration of ammonia, and higher activities of AST and CK. The higher the ammonia, the greater were the activities of AST (r=0.59) and CK (r=0.61). The correlation between AST and CK was high and significant (r=0.80), but not between AST and gammaGT (r=0.19). The activities of AST and CK were higher after the beginning of the convulsive episodes due to ammonia poisoning. Those results showed that occurred muscle damage instead of liver damage since CK is a typical enzyme from skeletal muscle; AST is found either in skeletal muscle and hepatocytes, while gammaGT is present in hepatic cells.

Orofacial injuries associated with prehospital management of febrile convulsion in Nigerian children

The aim of this prospective study was to determine in a population of pediatric patients with febrile convulsions the prevalence and pattern of orofacial and dental injuries caused by traditional remedies used in a suburban Nigerian community. Over the study period of 28 months, 75 cases of febrile convulsion presented to the Children's Emergency unit of our hospital. Of these, 27 children (36%) sustained orofacial injuries caused by forceful insertion of a spoon into the mouth (96.3%) or a bite (3.7%) during convulsive episodes. The ages of the patients ranged from 12 to 84 months with a mean 39.8 +/- 18.3 months. There were 15 males and 11 females with a male to female ratio of 1.4:1. The orofacial and dental injuries sustained from prehospital treatment at home were lacerations and bruising of soft tissues including lips, tongue, mucosa and commissures and tooth subluxation, displacement or avulsion. Other injuries sustained outside the mouth include second-degree burns to the feet, a chin laceration and facial bruises resulting from a fall. Many oral injuries were overlooked by pediatricians. Prompt recognition and appropriate management of febrile convulsion would be of great benefit to the pediatric patients.

Malformación arteriovenosa cerebelosa

Se presenta el caso de una paciente de sexo femenino de 20 meses de edad que consultó al servicio de urgencias pediátricas por cuadro de pérdida súbita y progresiva de la fuerza del hemicuerpo izquierdo, asociada con episodio convulsivo, pérdida del conocimiento de cerca de 15 segundos, astenia, adinamia, irritabilidad y somnolencia. Niega trauma craneoencefálico. La presentación de este caso y su estudio posterior obliga a la revisión de las causas más frecuentes de cuadros convulsivos en niños, síndromes hemipléjicos y hemiparéticos, con el fin de enfocar un buen diagnóstico y diseñar un plan de manejo adecuado enfocado hacia las malformaciones vasculares cerebrales o cerebelosas. Abreviaturas: AICA, arteria cerebelosa anterior e inferior; PICA, arteria cerebelosa posterior e inferior.

Successful management of primary hypomagnesaemia with high‐dose oral magnesium citrate: A case report

We report a 40-d-old female infant who presented to our clinic with afebrile generalized convulsive episodes due to severe hypomagnesaemia with secondary hypocalcaemia. Laboratory investigations revealed mild hypoparathyroidism, which was to return normal following magnesium (Mg) treatment, and normal fractional renal excretion of Mg (0.8%). After the diagnosis of primary hypomagnesaemia was established, the patient was discharged with oral Mg subcarbonate and intramuscular Mg sulphate. On regular follow-up until the age of 4 y, the child was asymptomatic. Mean serum calcium levels remained normal, while mean serum Mg levels remained subnormal. During this 4-y period, oral Mg dose was gradually increased while the doses and frequency of administration of parenteral Mg were decreased. Additionally, oral Mg subcarbonate was switched to Mg citrate because of its side effects. Finally, parenteral Mg was discontinued as the dosage of oral Mg supplementation reached a level of 90 mg/kg/d elemental Mg citrate, without any gastrointestinal side effects. Some screening tests were performed to evaluate the complications of chronic hypomagnesaemia. Bone age, bone densitometry, ECG and renal sonography were all normal. Our patient is now 5 y old and symptom free. Treatment with high doses of oral Mg was successful in keeping our patient symptom free and normocalcaemic, but cannot fully normalize serum Mg concentrations. Thus, during the regular follow-up of patients with primary hypomagnesaemia, the main target must be to increase oral Mg supplementation to a dosage which can maintain normocalcaemia rather than normomagnesaemia.

Methylene blue prevents methylmalonate-induced seizures and oxidative damage in rat striatum

Methylene blue (MB) is a thiazine dye with cationic and lipophilic properties that acts as an electron transfer mediator in the mitochondria. Due to this metabolic improving activity and free radicals scavenging effects, MB has been used in the treatment of methemoglobinemia and ifosfamide-induced encephalopathy. Considering that methylmalonic acidemia consists of a group of inherited metabolic disorders biochemically characterized by impaired mitochondrial oxidative metabolism and reactive species production, we decided to investigate whether MB, protects against the behavioral and neurochemical alterations elicited by the intrastriatal injection of methylmalonate (MMA). In the present study we showed that intrastriatal injection of MB (0.015–1.5 nmol/0.5 μl) protected against seizures (evidenced by electrographic recording), protein carbonylation and Na +,K +-ATPase inhibition ex vivo induced by MMA (4.5 μmol/1.5 μl). Furthermore, we investigated whether convulsions elicited by intrastriatal MMA administration are accompanied by striatal protein carbonyl content increase and changes in Na +,K +-ATPase activity in rat striatum. The effect of MB (0.015–1.5 nmol/0.5 μl) and MMA (4.5 μmol/0.5 μl) on striatal NO x (NO 2 plus NO 3) content was also evaluated. Statistical analysis revealed that the MMA-induced NO x content increase was attenuated by intrastriatal injection of MB and the duration of convulsive episodes correlated with Na +,K +-ATPase inhibition, but not with MMA-induced total protein carbonylation. In view of that MB decreases MMA-induced neurotoxicity assessed by behavioral and neurochemical parameters, the authors suggest that MB may be of value to attenuate neurological deficits of methylmalonic acidemic patients.

A randomized prospective open labeled study of oral amoxicillin-clavulanate with intravenous ceftriaxone and amikacin in low risk febrile neutropenia

18551 Background: Empiric oral antibiotic administration is a treatment option in low risk febrile neutropenia. Methods: Low risk febrile neutropenia patients (expected neutropenic duration &lt;7 days with no comorbid features) between 15 and 75 years of age were randomized to receive either oral amoxicillin-clavulanate 625 mg twice daily and levofloxacin 500 mg once daily or intravenous (i.v.) ceftriaxone 2 g and amikacin 15 mg/kg once daily. Most patients were treated on out patient basis. The primary end point was response to therapy- defervescence of fever within 72 hours with improvement in any clinical manifestation of infection and no recurrence of fever for 48 hours without use of antipyretics. Use of growth factors was not permitted except in treatment failure. The study was cleared by the institute ethics committee. Results: Sixty four episodes in 53 patients were evaluable, 33 in the i.v. group and 31 in the oral antibiotics group. The underlying diagnosis was bone and soft tissue sarcomas in 32 episodes, hematological cancers in 22 and other solid cancers in 10. The groups were equally matched for age (median 25 years in the i.v. arm and 19 years in the oral arm), gender, type of cancer, baseline absolute neutrophil count (median 200/μL in both arms) and duration of neutropenia (5 days and 4 days in the i.v. and oral groups respectively). A focus of infection was identified clinically in 15% of episodes and microbiologically in 11% of episodes; 57% of which were gram positive organisms and the rest gram negative. Seventy two percent (95% confidence interval 58% to 88%) in the i.v. arm and 77% (95% confidence interval 63% to 92%) in the oral arm responded to therapy. The only serious toxicity was one episode of convulsions in the i.v. group. All treatment failures received second line i.v. antibiotics. There was no mortality in either group. Comparing the two groups for equivalence (assuming a 25% difference between the two arms as unequal) the two groups were found to be equivalent with a power of 59% (p = 0.03). Conclusion: Oral antibiotics have comparable efficacy as intravenous antibiotics in the management of low risk febrile neutropenia. No significant financial relationships to disclose.

Cerebral malaria owing toPlasmodium vivax: case report

Cerebral malaria is a diffuse encephalopathy associated with seizures and status epilepticus which can occur in up to one-third of children with severe malaria, particularly that caused by Plasmodium falciparum. We report a unique case of P. vivax infection complicated by status epilepticus. A 4-year-old boy was admitted to the emergency outpatient clinic with intractable seizures for the previous hour. During resuscitation, two episodes of left-focal tonic convulsions occurred and he received phenytoin. Because of a history of P. vivax infection in the family 3 months previously, a blood slide for malaria was undertaken. Thin blood smears demonstrated P. vivax. He was treated with chloroquine and primaquine. An initial EEG was normal but after 3 months of follow-up a second EEG showed generalised epileptic activity. Rarely, cerebral malaria is a presenting complication or occurs during the course of P. vivax infection. In endemic areas such as Turkey, the possibility of cerebral malaria should be considered.

Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome: Clinical and Molecular Analysis of a Case

Blepharophimosis-ptosis-epicanthus inversus syndrome (OMIM #U10100) is a rare autosomal-dominant disorder in which an eyelid malformation is associated (type I) or not (type H) with premature ovarian failure in the affected female. It is invariably characterized by 4 major features: (1) bilaterally shortened horizontal palpebral fissure (blepharophimosis); (2) severe impairment of the superior palpebral levator (ptosis); (3) a vertical skin fold arising from the lower eyelid, which inserts medially in the upper lid (epicanthus inversus) and (4) an increased inner can-thal distance with a normal outer canthal distance (telecanthus). The mutations causing this disorder are found in the FOXL2 gene, a forkhead transcription factor, located in 3q23. Although many patients with blepharophimosis-ptosis-epicanthus inversus syndrome have an affected parent, a conspicuous number of sporadic cases also have been reported. We describe here a sporadic case with a mutation in the FOXL2 gene that was well characterized both clinically and molecularly.

Use of Lidocaine Injection During Endoscopic Resection for Early Gastric Cancer

Introduction: Endoscopic resection (ER) is becoming a standard treatment for early gastric cancer (EGC) and nowadays is being performed in an increasing number of patients. Although the complications of the method like bleeding, perforation and significant pain are rare, their prevalence will accordingly increase in the future. A decrease of post ER pain would lead to its wider acceptance. Recent evidence suggests that instillation of local anesthetic both into the peritoneum and the skin incision may be beneficial in minimally invasive surgery such as laparoscopic cholecystectomy. There is no report on lidocaine use during ER, for post-ER analgesia. Aim&Methods: We attempted to reduce the percentage of patients experiencing significant pain by means of local anesthesia injection. We evaluated the action of lidocaine when injected into submucosa during ER. We randomized 17 patients (12 males, age range 51∼80) who underwent ER for early gastric cancer from September to November in 2005, in 2 groups; 8 patients received 0.5% lidocaine with epinephrine while 9 received saline with epinephrine as placebo. All procedures were carried out under standard sedation (midazolam, pentazocine). The patients, operator, and assistant were blinded on the nature of the injected agent. During the procedure we monitored ECG, heart rate, oxygen saturation, and blood pressure. The patients reported the level of pain felt on days 0, 1 and 2 after the procedure and on the same time blinded doctors examined them physically focusing on the existence of epigastric discomfort and tenderness. The level of white blood cell and C-reactive protein was also recorded. Results: No abnormality on ECG, heart rate, oxygen saturation, and blood pressure was seen in any patient of either group. Only one patient out of the eight of the lidocaine group presented abdominal findings contrasting to three patients out of nine in the saline group on day 0. The mean dosage of midazolam necessitated in the lidocaine group (8.5 mg/person) was lower from the one in the placebo group (11.6 mg/person). The dosage of pentazocine was similar. Mean dosage of lidocaine was 195 mg. No episode of lidocaine intoxication, convulsion or arrhythmia was seen. In particular, when the resected tumors were located in the antrum, 40% of the patients belonging to the saline group had abdominal findings at day 0 as compared to none of the lidocaine group. Conclusion: Lidocaine injection into submucosal layer during ER seems to be safe and to reduce pain in the immediate post ER period. Its efficacy should be further investigated.

GM1 ganglioside prevents seizures, Na+,K+-ATPase activity inhibition and oxidative stress induced by glutaric acid and pentylenetetrazole

Monosialoganglioside (GM1) is a glycosphingolipid that protects against some neurological conditions, such as seizures and ischemia. Glutaric acidemia type I (GA-I) is an inherited disease characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). In this study, we show that GA inhibits Na+,K+-ATPase activity and increases oxidative damage markers (total protein carbonylation and thiobarbituric acid-reactive substances-TBARS) production in striatal homogenates from rats in vitro and ex vivo. It is also shown that GM1 (50 mg/kg, i.p., twice) protects against GA-induced (4 micromol/striatum) seizures, protein carbonylation, TBARS increase, and inhibition of Na+,K+-ATPase activity ex vivo. Convulsive episodes induced by GA strongly correlated with Na+,K+-ATPase activity inhibition in the injected striatum but not with oxidative stress marker measures. Muscimol (46 pmol/striatum), but not MK-801 (3 nmol/striatum) and DNQX (8 nmol/striatum) prevented GA-induced convulsions, increase of TBARS and protein carbonylation and inhibition of Na+,K+-ATPase activity. The protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na+,K+-ATPase activity maintenance ex vivo. In addition, GM1 (50-200 microM) protected against Na+,K+-ATPase inhibition induced by GA (6 mM) but not against oxidative damage in vitro. GM1 also decreased pentylenetetrazole (PTZ)-induced (1.8 micromol/striatum) seizures, Na+,K+-ATPase inhibition, and increase of TBARS and protein carbonyl in the striatum. These data suggest that Na+,K+-ATPase and GABA(A) receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1.

Intravenous lidocaine for status epilepticus during childhood

The clinical efficacy of lidocaine for convulsive status epilepticus in 53 convulsive episodes was examined in 37 children (17 males, 20 females). Mean age of patients receiving lidocaine was 3 years 7 months (SD 3y 5mo). Lidocaine administration achieved control of status epilepticus in 19 of 53 convulsive episodes (35.8%). Seizures ceased within 5 minutes of lidocaine administration in all 19 patients who were responsive to the drug. Regarding aetiology of status epilepticus and types of seizures, there was no statistical difference in effectiveness. Mild decrease of oxygen saturation, monitored by pulse oximetry, was observed in one patient, which improved by oxygenation using a mask. Lidocaine is a useful anticonvulsive agent; however, the response rate to lidocaine appears to be quite low, as less than half of the seizures were effectively controlled by lidocaine. Favourable properties of the drug include prompt responses, less alteration of consciousness, and fewer adverse effects, including less respiratory depression.

The histories of withdrawal convulsions and delirium tremens in 1648 alcohol dependent subjects.

A small proportion of alcohol-dependent men and women experience delirium tremens (DTs) and/or convulsions during alcohol withdrawal. While some characteristics of individuals most likely to show these severe sequelae of the abstinence syndrome have been described, it is not clear whether these risk factors operate independently in their association with severe withdrawal. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview was used to evaluate 1648 alcohol dependent men and women (including 540 women). The background characteristics and drinking histories of the 160 men and 51 women (12.8% of the subjects) who reported ever having had at least one episode of DTs and/or convulsions during withdrawal were compared with the characteristics of the remaining alcohol dependent individuals. Compared to other alcohol-dependent subjects, those with histories of severe withdrawal reported a greater maximum number of drinks in any 24-hour period (40.9 +/- 25.71 versus 24.9 +/- 17.72), more withdrawal episodes (28.2 +/- 33.74 versus 15.9 +/- 26.84), more non-medicinal use of sedative-hypnotics (56.4% versus 32.9%) and a greater number of medical problems. Hierarchical logistic regression analysis revealed that the most powerful differences between those with histories of more and less severe withdrawals related to the maximum number of drinks per day and the total number of withdrawal episodes. The remaining variables still added significantly to the relationship to more severe withdrawal. The etiology of DTs and convulsions is complex and involves the interaction of diverse characteristics representing relatively unique domains. It is hoped that these data will help clinicians identify individuals most likely to have experienced severe withdrawal syndromes and will aid researchers attempting to understand more about the etiology of these problems.

Decreased Subunit Stability as a Novel Mechanism for Potassium Current Impairment by a KCNQ2 C Terminus Mutation Causing Benign Familial Neonatal Convulsions

KCNQ2 and KCNQ3 K+ channel subunits underlie the muscarinic-regulated K+ current (I(KM)), a widespread regulator of neuronal excitability. Mutations in KCNQ2- or KCNQ3-encoding genes cause benign familiar neonatal convulsions (BFNCs), a rare autosomal-dominant idiopathic epilepsy of the newborn. In the present study, we have investigated, by means of electrophysiological, biochemical, and immunocytochemical techniques in transiently transfected cells, the consequences prompted by a BFNC-causing 1-bp deletion (2043deltaT) in the KCNQ2 gene; this frameshift mutation caused the substitution of the last 163 amino acids of the KCNQ2 C terminus and the extension of the subunit by additional 56 residues. The 2043deltaT mutation abolished voltage-gated K+ currents produced upon homomeric expression of KCNQ2 subunits, dramatically reduced the steady-state cellular levels of KCNQ2 subunits, and prevented their delivery to the plasma membrane. Metabolic labeling experiments revealed that mutant KCNQ2 subunits underwent faster degradation; 10-h treatment with the proteasomal inhibitor MG132 (20 microm) at least partially reversed such enhanced degradation. Co-expression with KCNQ3 subunits reduced the degradation rate of mutant KCNQ2 subunits and led to their expression on the plasma membrane. Finally, co-expression of KCNQ2 2043deltaT together with KCNQ3 subunits generated functional voltage-gated K+ currents having pharmacological and biophysical properties of heteromeric channels. Collectively, the present results suggest that mutation-induced reduced stability of KCNQ2 subunits may cause epilepsy in neonates.

Convulsive episodes in patients with group A xeroderma pigmentosum

To clarify the incidence of convulsive episodes in patients with group A xeroderma pigmentosum (XPA). By investigating the history of convulsive episodes of our 33 XPA patients through either their medical charts or direct interviews with their caretakers. Five patients had several episodes of afebrile convulsion at ages older than 12. With the exception of one patient who began to show convulsive episodes at 13, no other XPA patients exhibited febrile seizures. As far as our 33 XPA patients were concerned, 15% exhibited epilepsy, and 3% experienced febrile seizures. Japanese XPA patients showed a lower incidence of febrile seizures, while exhibiting a higher incidence of epilepsy. It is assumed that the brain of young patients with XPA is difficult to develop convulsions.