Epilepsy in Wolf-Hirschhorn syndrome (4p-)

PURPOSE: We investigated the evolution of epilepsy, seizure types, and effective drugs in Wolf-Hirschhorn syndrome, which is a malformation syndrome often with refractory seizures and status epilepticus. METHODS: We reviewed 11 cases of Wolf-Hirschhorn syndrome (age range, 2-25 years; SD, 7.2 years) and who were treated in Osaka University or Osaka Medical Center of Research Institute for Maternal and Child Health. RESULTS: In all patients, febrile or afebrile convulsions had developed. Epileptic seizures included alternative hemiconvulsions, generalized tonic-clonic seizures, focal clonic seizures, tonic seizures, and epileptic spasms. Seizures were often induced by a high fever or a hot bath. Status epilepticus occurred in all patients, including one patient who died at the first status epilepticus. In some cases, intratracheal intubation was needed because of respiratory insufficiency. The effective antiepileptic drugs for long-term use were sodium bromide (four of four), followed by clorazepate (CLP; one of two), and nitrazepam (NZP; two of four). Sodium bromide was particularly effective for preventing status epilepticus. The mean age of last status epilepticus in patients receiving sodium bromide (1 year 8 months) was significantly younger than that in those not treated with sodium bromide (3 year 4 months). CONCLUSIONS: We identified that, in most patients of Wolf-Hirschhorn syndrome, the frequency of both seizures and status epilepticus decreased gradually after age 5 years. However, during infancy, status epilepticus sometimes resulted in permanent disability or even death. We propose that sodium bromide should be used as the initial treatment for the prevention of the development of status epilepticus associated with Wolf-Hirschhorn syndrome.     

FOLLOW-UP STUDY OF 482 CASES WITH CONVULSIVE DISORDERS IN THE FIRST YEAR OF LIFE

A total of 482 patients who had had one or more seizures in the first year of life were followed for at least five years (most for more than 10 years). The patients were divided into four groups: febrile convulsions, infantile spasms, status epilepticus and 'other'. Of those with febrile convulsions, 62 per cent developed normally, compared with 14 per cent in the group with infantile spasms, 15 per cent with status epilepticus, and 24 per cent in the 'other' group. Findings on recurrent seizures, epilepsy and mental retardation and/or neurological abnormalities are also reported. Epilepsy developed equally frequently among those with partial and with generalised seizures, but the former more frequently became mentally retarded. The effects of severity of seizures and other factors are discussed. In general, this research confirmed the grave prognosis after seizures during the first year of life, and not only for West syndrome and status epilepticus. The outcome was more favourable when the seizures were cryptogenic or febrile, isolated, with onset in the second six months, generalised, and when the EEG was normal between seizures.     

Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone

Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs had a mean of 18.3 generalized convulsions over a mean period of 103.8 min. Electrographic patterns seen during status epilepticus are described and are very similar to those seen during human status epilepticus. Phenytoin, phenobarbital, diazepam and lorazepam were all effective in arresting the generalized seizures when given i.p. after the second such seizure. Efficacy was serum drug concentration dependent. Concentrations effective in arrest of generalized seizures in this model are similar to those reported to be effective in the treatment of human status epilepticus. Diazepam ED50s for control of generalized tonic-clonic seizures and for arrest of all seizure activity were determined.     

Epileptogenic properties of cocaine in humans.

Ninety-eight of 945 patients admitted to Hennepin County Medical Center with acute medical complications of cocaine intoxication presented with seizures within 90 min of cocaine ingestion. Cocaine-related seizures were most frequently single, generalized convulsions, and these individuals all had normal cranial CT and EEG. Of the 945 patients, 18.4% of the women presented with seizures, compared with only 6.2% of the men. All subjects who presented with new onset focal seizures following cocaine ingestion had acute cocaine-related cerebral strokes or hemorrhages. Individuals with a history of cocaine-unrelated seizures, had their typical convulsions precipitated with "recreational" doses of cocaine. All four subjects with status epilepticus had ingested massive doses of cocaine, were resistant to medical treatment, and had significant morbidity and mortality. We were able to characterize four subgroups of subjects at risk for cocaine-related convulsions. First, individuals who had ingested massive doses of cocaine (2-8 gms) in whom cocaine induced seizures by its direct, dose-related convulsant effects. Second, individuals with a history of epilepsy had their typical seizures precipitated by lowering the seizure threshold. Third, females are at greater risk for cocaine-related compared to males. Fourth, years of chronic, habitual cocaine abuse may result in "chemical" kindling of epilepsy.     

Maturational changes in postictal refractoriness and seizure susceptibility in developing rats

The ability of the central nervous system to suppress recurrent seizures as a function of age was determined in rats. Eight electrical stimulations were delivered to the amygdala at 2-minute intervals in adult and suckling rats that were previously kindled from the left amygdala. During this 16-minute period, prolonged and severe convulsions were repeatedly elicited in the 16-day-old rat pups, whereas convulsions were not always elicited in adul rats. The results suggest that immature rats are more prone to develop status epilepticus than adult rats. Subsequently, the rat pus and implanted but not stimulated littermates were allowed to grow. At maturity, all the surviving animals were kindled from the contralateral (right) amygdala. The previously kindled rats developed seizures significantly faster than did their littermates. However, their respective abilities to suppress recurrent seizures did not differ at 150 and 210 days of age, being similar to the seizure suppression abilities of naive controls and significantly greater than those evidenced in infancy. We conclude that the propensity to develop single seizures in adulthood is directly related to infant seizure history, whereas the ability to suppress multiple seizures is a dynamic process that is modified by age, being minimal early in life and enhanced with maturation independently of history of infantile convulsions.     

High incidence of status epilepticus and ongoing seizures on arrival to the hospital due to high prevalence of febrile seizures in Izumo,Japan: A questionnaire-based study

ObjectivesTo determine the incidence of prolonged febrile seizures and status epilepticus in the first three years of life.MethodsA questionnaire was sent to 1560 families between April 2016 and March 2017 before their child attended a routine health check at three years of age in Izumo, Shimane prefecture, Japan. The questionnaire included an overview of febrile seizures, including the age at which febrile seizures occurred, the duration, and how the condition was managed.ResultsWe received 1089 (69.8%) responses and these showed that 134 (12.3%) children had a history of febrile seizures. Fourteen children with febrile seizures (10.4%) had prolonged seizures lasting 10–30 min and six children (4.5%) had status epilepticus. Ongoing febrile seizures that did not terminate on arrival to the hospital were observed in 11 children (8.2%) with febrile seizures. The incidence rates of status epilepticus, prolonged febrile seizures including status epilepticus and ongoing febrile seizures were 184, 612 and 337 per 100,000 children aged 36 months or less, respectively.ConclusionsThere was a greater incidence of status epilepticus than previously thought, possibly due to the high prevalence of febrile seizures in Japan. Eight percent of children with febrile seizures were seizing on arrival to the hospital. These ongoing seizures requiring emergency interventions were almost twice more than status epilepticus. Thus, it is necessary to develop an early intervention for the termination of prolonged febrile seizures.     

Long-term observations of two siblings with Lafora disease treated with zonisamide

We have reported long-term clinical follow-up for two siblings with Lafora disease, a brother and sister, one of whom autopsied. Both siblings had repeated attacks of severe myoclonus, tonic and tonic-clonic convulsions, and intractable status epilepticus. The addition of orally administered zonisamide brought about striking effective seizure control for about 12-14 years in both patients, relieving not only myoclonus and generalized tonic-clonic seizures but also intractable status epilepticus.     

Infantile status epilepticus and future seizure susceptibility in the rat

The long-term effects of infantile seizures on the development of seizures in adulthood were studied in rats. Infantile seizures of varying severity were induced with intraperitoneal injections of kainic acid in 15-day-old rats. In adulthood the seizure susceptibility of the rats was determined by kindling the left amygdala and by measuring their ability to resist recurrent seizures. The results suggest that infantile status epilepticus is associated with a very high mortality; however in the surviving rats, infantile seizures even as severe as status epilepticus do not cause neuronal brain damage and do not predispose to the development of convulsions later in life.     

Status Epilepticus Caused by Nefopam

Nefopam, a centrally acting analgesic, has been used to control postoperative pain. Reported adverse effects are anticholinergic, cardiovascular or neuropsychiatric. Neurologic adverse reactions to nefopam are confusion, hallucinations, delirium and convulsions. There are several reports about fatal convulsive seizures, presumably related to nefopam. A 71-year-old man was admitted for surgery for a lumbar spinal stenosis. He was administered intravenous analgesics : ketorolac, tramadol, orphenadrine citrate and nefopam HCl. His back pain was so severe that he hardly slept for several days; he even needed morphine and pethidine. At 4 days of administration of intravenous analgesics, the patient suddenly started generalized tonic-clonic seizures for 15 seconds, and subsequently, status epilepticus; these were not responsive to phenytoin and midazolam. After 3 days of barbiturate coma therapy the seizures were controlled. Convulsive seizures related to nefopam appear as focal, generalized, myoclonic types, or status epilepticus, and are not dose-related manifestations. In our case, the possibility of convulsions caused by other drugs or the misuse of drugs was considered. However, we first identified the introduced drugs and excluded the possibility of an accidental misuse of other drugs. Physicians should be aware of the possible occurrence of unpredictable and serious convulsions when using nefopam.     

热性惊厥持续状态复发的危险因素分析

目的探讨儿童热性惊厥持续状态(FSE)复发的危险因素。方法收集138例FSE患儿的临床资料,并于出院后进行2个月至8.3年的随访。根据随访结果,将患儿分为热性惊厥复发组、癫痫进展组及无惊厥复发组,分析FSE复发的相关因素。结果根据随访结果,热性惊厥复发30例(21.7%)(热性惊厥复发组),8例(5.8%)进展为癫痫(癫痫进展组),100例(72.5%)无复发(无惊厥复发组)。与无惊厥复发组比较,热性惊厥复发组低热时出现惊厥、既往有热性惊厥病史、阳性惊厥家族史及异常EEG的比率显著升高(P<0.05~0.01)。多因素Logistic回归分析显示,低热时出现惊厥、既往有热性惊厥病史及阳性惊厥家族史为FSE热性惊厥复发的独立危险因素(P<0.05~0.01)。FSE进展为癫痫的危险因素为低热时出现惊厥、既往有热性惊厥病史、异常EEG及异常头颅MRI(P<0.05~0.01)。结论低热时出现惊厥、既往有热性惊厥病史及阳性惊厥家族史为FSE热性惊厥复发的独立危险因素。低热时出现惊厥、既往有热性惊厥病史、异常EEG及异常头颅MRI为FSE进展为癫痫的危险因素。对于有危险因素的FSE患儿,应早期合理选择预防用药,改善预后。