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Ammonia is a ubiquitous waste product of protein metabolism that can accumulate in numerous metabolic disorders, causing neurological dysfunction ranging from cognitive impairment to tremor, ataxia, seizures, coma and death [...]

We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia). By analysis of linkage we localize the putative causative gene to a 2.5-Mb segment of chromosome 1q23.2-23.3. Direct DNA sequencing of KCNJ10, which encodes an inwardly rectifying [K.sup.+] channel, identifies previously unidentified missense or nonsense mutations on both alleles in all affected subjects. These mutations alter highly conserved amino acids and are absent among control chromosomes. Many of these mutations have been shown to cause loss of function in related [K.sup.+] channels. These findings demonstrate that loss-of-function mutations in KCNJ10 cause this syndrome, which we name SESAME. KCNJ10 is expressed in gila in the brain and spinal cord, where it is believed to take up [K.sup.+] released by neuronal repolarization, in cochlea, where it is involved in the generation of endolymph, and on the basolateral membrane in the distal nephron. We propose that KCNJ10 is required in the kidney for normal salt reabsorption in the distal convoluted tubule because of the need for [K.sup.+] recycling across the basolateral membrane to enable normal activity of the [Na.sup.+]-[K.sup.+]-ATPase; loss of this function accounts for the observed electrolyte defects. Mice deficient for KCNJ10 show a related phenotype with seizures, ataxia, and hearing loss, further supporting KCNJ10's role in this syndrome. These findings define a unique human syndrome, and establish the essential role of basolateral [K.sup.+] channels in renal electrolyte homeostasis. Gitelman syndrome | hypokalemia | hypomagnesemia | inwardly rectifying [K.sup.+] channel | renal salt wasting

Most human seizures occur early in life, consistent with established excitability-promoting features of the developing brain. Surprisingly, the majority of developmental seizures are not spontaneous but are provoked by injurious or stressful stimuli. What mechanisms mediate 'triggering' of seizures and limit such reactive seizures to early postnatal life? Recent evidence implicates the excitatory neuropeptide, corticotropin-releasing hormone (CRH). Stress activates expression of the CRH gene in several limbic regions, and CRH-expressing neurons are strategically localized in the immature rat hippocampus, in which this neuropeptide increases the excitability of pyramidal cells in vitro. Indeed, in vivo, activation of CRH receptors - maximally expressed in hippocampus and amygdala during the developmental period which is characterized by peak susceptibility to 'provoked' convulsions - induces severe, age-dependent seizures. Thus, converging data indicate that activation of expression of CRH constitutes an important mechanism for generating developmentally regulated, triggered seizures, with considerable clinical relevance.

The development of moyamoya syndrome may be associated with congenital heart disease, and should be considered when evaluating these patients for complications such as strokes or seizures. This syndrome is characterized by a proliferation of blood vessels in certain areas of the brain in response to a narrowing of vital arteries. Five patients with congenital heart disease who developed moyamoya syndrome were identified. These patients presented with stroke in three cases and seizures in two cases. Early diagnosis and surgical correction may reduce damage from this abnormality., Objective. To describe the association between moyamoya syndrome and congenital heart disease and to discuss its clinical implications. Study Design. Retrospective analysis of a case series from two institutions. Results. Five patients with moyamoya syndrome and structural congenital heart disease were identified. Coarctation of the aorta was present in 3 patients, in association with a ventricular septal defect (1 patient), aortic and mitral valve stenoses (1 patient), and tetralogy of Fallot (1 patient). Tetralogy of Fallot and a large paramembranous ventricular septal defect were found in the other 2 patients. Four patients underwent surgical repair of their congenital heart disease during the first year of life and 1 patient had balloon dilation of aortic coarctation at 5 years of age. In all patients, moyamoya syndrome was diagnosed after surgical intervention for congenital heart disease--at 6 months of age in 1 patient, at 2 years of age in 3 patients, and at 6 years in 1 patient. Strokes were the most common presenting sign (3 patients) followed by seizures (2 patients). By the age of 33 months, 4 of 5 patients had undergone cerebral revascularization surgery to halt the clinical progression of moyamoya syndrome. Conclusions. Moyamoya syndrome should be considered in the differential diagnosis of seizures and stroke in patients with structural congenital heart disease. Prompt diagnosis and surgical management of the occlusive cerebral angiopathy should lead to improved neurological outcome in these patients. Pediatrics 1998;101:5760; congenital heart disease, moyamoya syndrome, neurosurgery, seizure, stroke., Moyamoya is a chronic cerebrovascular disease of unknown etiology characterized by progressive stenosis and occlusion of the arteries comprising the circle of Willis and its branches, especially the internal carotid [...]

A 30-year-old bartender with a mass in the left temporal lobe of the brain was admitted to the hospital after a seizure and an earlier motorcycle accident. The man had been sexually active without protection while visiting Brazil in the previous year. After ruling out tumor and the complication of a sexually transmitted disease, a brain biopsy was analyzed. Further diagnostic tests revealed granulomatous encephalitis and a Schistosoma mansoni infection in the brain. After taking praziquantel and corticosteroids, the patient recovered without further seizures but continued with phenytoin therapy.

A child with seizures nonresponsive to medication was diagnosed as having focal cortical dysplasia. Focal cortical dysplasia is abnormal brain cell development, and improvements in imaging technology are finding that it may be the underlying cause of intractable seizures in more children than previously suspected. Epileptic episodes began at age four, and by the time the child was eight, seizures were frequent and uncontrollable with medication. Seizures were focused in the temporal lobe of the brain, which was removed. This cured the seizures. Microscopic analysis of tissue samples from the temporal lobe revealed oversized, abnormally arranged nerve cells, confirming the diagnosis.

A number of children may develop seizures due to isoniazid (INH) neurotoxicity or poisoning. INH is an effective drug in the treatment and prevention of tuberculosis but also causes massive seizures. Seven children with acute INH neurotoxicity were treated. All patients had been taking INH prescriptions to prevent tuberculosis. One 5-day-old infant boy had received high doses of preventive INH due to a prescription error. Therapy with pyridoxine or vitamin B resolved his seizures and tremors. The remaining 6 adolescents had taken large amounts of INH either accidentally or intentionally to end their lives. In addition to seizures, patients may experience nausea, vomiting, dizziness, and low blood pressure. Delays in starting pyridoxine therapy due to unavailability may result in late treatment. A recent rise in tuberculosis infection may be related to the increase of INH poisoning among children., Objectives. To describe the presentation and treatment of acute isoniazid (INH) neurotoxicity appearing at an inner-city municipal hospital. Design. Case series. Participants. Seven patients (eight patient visits) with an age range of 5 days to 14.9 years. Results. At our institution, no children appeared with acute INH neurotoxicity in the period 1985 through 1990, whereas seven patients were treated from 1991 through 1993. This paralleled the rise in the number of children with tuberculous infection and disease seen at our institution, from an average 96 per year to 213 per year during these two time periods. AR seven patients were receiving INH daily for tuberculosis (TB) prophylaxis. Accidental ingestion (five episodes) and suicidal attempts (three episodes) accounted for these visits. The total amount ingested range from 14.3 to 99.3 mg/kg (mean, 54 mg/kg). All but one patient presented with afebrile seizures. One patient presented twice with seizures. Acute INH neurotoxicity was not suspected on the first admission; however, when readmitted 4 weeks later with another seizure, the diagnosis of acute INH neurotoxicity was made. Intervention. Intravenous pyridoxine was used in five episodes. Because it was not a stocked item in our pediatric emergency cart (as well as at another hospital, necessitating a transfer of a patient with refractory seizures to our hospital), the average delay was 5.8 hours (range, 1.3 to 13 hours) before it was given. Two patients with refractory seizures failed to respond to anticonvulsants, and their seizures were controlled only after parenteral pyridoxine. Conclusions. We have seen an increased incidence of acute INH neurotoxicity because of the resurgence of TB in New York City. Others as well may see a similar rise based on local trends in TB infection and disease. Acute INH toxicity should be suspected in children presenting with seizures with or without fever. In patients with a known access to INH, seizures should be considered to be caused by INH toxicity unless proved otherwise. Parenteral pyridoxine, the specific antidote for INH-induced refractory seizures, should be readily available in every emergency department in the areas similarly experiencing increasing trends of TB. Pediatrics 1995,95:700-704; acute isoniazid neurotoxicity., The incidence of tuberculosis (TB) in Brooklyn, NY, increased from 30.7 new cases per 100 000 population in 1985 to 51.8 new cases per 100 000 population in 1992. In [...]

Video game-related seizures (VGRS) may occur in persons who are susceptible to epileptic seizures triggered by visual excitations, and may be treated by simple avoidance of video games. Some epileptic seizures may be stimulated by repetitive light flashes or line patterns. Researchers evaluated 10 patients complaining of VGRS (Group I) and reviewed reported cases of 25 other patients with VGRS (Group II). The average age of Group I patients was 12.4 years, and of Group II patients, 13.6 years. The number of patients who had experienced seizures prior to their VGRS was six in Group I and two in Group II. The types of seizures included absence seizures, confusional episodes, simple partial seizures and generalized tonic-clonic seizures. Of 15 patients who abstained from further video game playing, 11 had no more seizures. Patients who do not want to abstain or who continue to have seizures should be treated with anticonvulsant drugs., Objective. To further describe the features, postulated pathophysiology, treatment, and outcome of seizures occurring while playing or watching video games (video game-related seizures (VGRS)). Design. We evaluated retrospectively 10 patients with VGRS seen by us and reviewed 25 reported cases. Results. The 35 patients ranged in age from 1 to 36 years (mean: 13.2); and 26 subjects (74%) were male. Eight individuals (29%) had prior infrequent nonfebrile seizures, 4 (11%) had febrile convulsions, and 2 (6%) had a family history of epilepsy. VGRS consisted of generalized tonic-clonic seizures in 22 of 35 individuals (63%); absences in 2 (6%); simple partial seizures in 6 (19%); complex partial seizures in 4 (11%); and other manifestations in 4. Neurologic examination and computed tomographic and magnetic resonance imaging scans were normal. Electroencephalograms demonstrated generalized or focal, interictal or ictal epileptic patterns in 11 of 21 patients (52%) and photoparoxysmal responses in 17 of 32 (53%). Eleven of 15 individuals (73%) treated with video game (VG) abstinence alone, 3 of 6 who received anticonvulsants but played VGs, and 7 of 12 treated with combined VG abstinence and anticonvulsants had no further seizures. Conclusions. We postulate that a special convulsive susceptibility of selected neurons in striate, peristriate, infratemporal, and posterior parietal cortices to particular visual stimuli plays a major role in VGRS. VG abstinence is the treatment of choice of VGRS. Anticonvulsant medication is suggested only for those individuals who continue to play VGs or suffer from seizures triggered by other, unavoidable visual stimuli, or from unprovoked attacks. Pediatrics 1994;93:551-556; stimulus-sensitive epilepsy, reflex epilepsy, video games, video game-related seizures, photoparoxysmal response.

Children exposed to cocaine may have seizures or other forms of neurologic impairment. Young children may be exposed to cocaine by accidental ingestion or by passive intoxication if they are present in a closed room where cocaine is smoked. Older children may actually try the drug themselves. Physicians at one emergency department examined 41 children between the ages of two months and 18 years who were determined by urinalysis to have been exposed to cocaine. In 14 patients, neurologic effects of cocaine could not be ascertained because of trauma, such as gunshot wounds, crash injuries or head injuries. Nineteen patients had signs of neurologic impairment. Seizures were the most common manifestation of cocaine exposure, followed by dulled senses, delirium, dizziness, drooling and lethargy. In an urban setting, a urine screen for cocaine exposure is recommended when evaluating children having seizures for the first time., Objective. To describe the neurologic manifestations of cocaine exposure in children and adolescents as the neurologic effects of cocaine have been described in adults and neonates. Methods. During 1-year period, 41 children between the ages of 2 months and 18 years who had been exposed to cocaine, were examined in the emergency department at the Children's National Medical Center. Cocaine exposure was documented on urine samples; all were confirmed by urine gas chromatographic/mass spectrometric analysis. Results. Nineteen (46%) of 41 had neurologic abnormalities, including seizures (7), obtundation (6), delirium (4), dizziness (1), drooling (1), and ataxia (1). In 14 others, the neurologic effects of cocaine were difficult to determine because of other concomitant medical conditions, including head injuries and severe abdominal or chest trauma. Two major age-related patterns were seen: (a) in each child 8 years of age, manifestations are similar to those in adults; 6) trauma and motor vehicle accidents were seen in the adolescent age group exposed to cocaine; and 7) urine toxicological study in cocaine exposure is recommended in all first-time seizures as well as first-time febrile seizures. Pediatrics 1994;93:557-560; cocaine exposure, passive intoxication, neurologic impairment, seizure, obtundation, delirium, dizziness, drooling, ataxia, trauma.

Biologically active pertussis toxin may not be the cause of severe reactions in children vaccinated with the diphtheria-tetanus-pertussis (DTP) vaccine. Pertussis toxin is the part the vaccine that protects against the development of whooping cough. Among 60 children who had a severe reaction within 48 hours of receiving the DTP vaccine, 32 had seizures only, two had a fever of 40.5 deg C or more, four cried for three hours or more, six had seizures and a fever of 40.5 deg C or more, and two had seizures and cried for at least three hours. Ninety percent of the children who developed seizures had a fever of 38 deg C or more. Many had a personal or family history of seizures. Episodes of persistent crying were usually caused by a painful reaction at the injection site. Blood samples from children who had a severe reaction did not contain biologically active pertussis toxin.

Objective.--To describe 10 infants with benign neonatal sleep myoclonus. Design.--Patient series, representing the experience of one pediatric neurologist. Setting.--Referral-based Pediatric Neurology Service at a Children's Hospital. Patients.--Sequential sample of 10 neonates referred for assessment of seizures and found to have benign neonatal sleep myoclonus. Neonates who did not have the events of concern during electroencephalography or in whom electroencephalography was not done were excluded even if the clinical features suggested the entity. Results.--Our patients met the criteria for the diagnosis. The myoclonus often increased with gentle restraint. The amplitude and duration of events mimicked convulsive status epilepticus and serial seizures in four neonates. In two of them the myoclonus worsened in spite of anticonvulsant therapy, decreasing substantially when such treatment was stopped. Conclusion.--Benign neonatal sleep myoclonus, an entity characterized by (1) neonatal onset, (2) myoclonic jerks only during sleep, (3) abrupt and consistent cessation with arousal, (4) absence of concomitant electrographic changes suggestive of seizures, and (5) good outcome must be included in the differential diagnosis of neonatal seizures. (AJDC. 1992;146:1236-1241)

Theophylline is used in the treatment of asthma; it works by relaxing the airways which become constricted. Theophylline is a member of the class of drugs called xanthines, which includes the common substance caffeine. Like caffeine, theophylline is a stimulant of the central nervous system. It has long been appreciated that in larger doses theophylline may cause seizures. However, it is less well appreciated that seizures resulting from theophylline are not limited to patients receiving excessive doses. Twelve patients are described in whom theophylline-induced seizures occurred despite the fact the amount of theophylline was at or close to what are usually considered acceptable amounts. It has been presumed that amounts of theophylline between 10 and 20 milligrams per liter of blood are safe. However, one of the 12 patients in the present report had blood levels of 14 milligrams per liter, while the others' levels were not much greater, ranging from 20 to 35 milligrams per liter. The patients in this series were all seriously affected by the seizures, which persisted for prolonged periods. Eight of the patients died. No attempt was made to identify unaffected patients taking theophylline, so no comparison can be done to reveal which factors might prove to have a high risk for theophylline toxicity. However, the characteristics of the 12 patients suggest that theophylline might well be used conservatively in older patients, patients with pre-existing brain injury or disease, and patients with especially severe pulmonary disease. There is also some indication that a low level of albumin in the blood plasma might also be a risk factor for theophylline toxicity. (Consumer Summary produced by Reliance Medical Information, Inc.)

Abuse of cocaine can lead to serious medical consequences, including neurologic complications such as stroke, brain hemorrhage, seizures, and convulsions; some cases are fatal. In this article, 11 adults who developed seizures due to cocaine abuse are described, and the literature on this issue is presented. The 11 patients were all treated at one medical center during 1987; they sought medical attention after experiencing a seizure. Four of the patients had a previous history of epilepsy, but the seizures in question had been stimulated by use of cocaine. Ten of the 11 patients survived their seizures; all of these had smoked 'crack' cocaine. The one individual who died had ingested massive amounts of the drug, a method of administration that has been most often linked to death. The seizures came on within 24 hours of cocaine use in all patients, and all had abused cocaine for a long period of time, suggesting that neurological changes that develop over time may lead to the seizures. Previous studies of different types of fatal and non-fatal seizures resulting from cocaine abuse are reviewed. (Consumer Summary produced by Reliance Medical Information, Inc.), INTRODUCTION Cocaine abuse has been associated with systemic complications and in addition has produced a variety of pediatric and adult acute neurologic and psychiatric complications. Neurologic sequelae of cocaine abuse [...]

A 16-year-old boy from Bombay, India had suffered repeated seizures and was admitted to the hospital. A computed tomographic (CT) scan showed swelling and a mass in the left frontal region of the brain. The three most common conditions which could cause lesions in the brain of a child from India are tumor, tuberculoma (a tumor-like mass in the brain caused by Mycobacterium tuberculosis, which causes tuberculosis), and cysticercosis (caused by tape worms). The clinical features did not indicate diagnosis of a cerebral glioma, a type of tumor which occurs in children and causes seizures. It was thought that the mass was a tuberculoma as tuberculosis is endemic in Bombay and the clinical features were compatible with the diagnosis of tuberculoma without manifestations outside the brain. The patient had been vaccinated against tuberculosis in childhood, but vaccination is not an assurance that the disease will not develop later in life. However, the patient was given drugs for the treatment of tuberculosis and still had the seizures. Cysticercosis was still a possible diagnosis. Abscesses caused by infectious agents such as bacteria, fungi and protozoa, or parasites were also considered. A brain biopsy was performed and examination of the tissue revealed that the patient had cysticercosis, which was manifested as a granulomatous abscess in the brain. (Consumer Summary produced by Reliance Medical Information, Inc.)

There is no doubt that long-term alcohol abuse increases the risk of seizures during withdrawal. However, it is not clear if increasing length of alcohol abuse increases the risk of seizures. In fact, at least one study has suggested that the risk of seizures is increased by repeated cycles of abuse and detoxification, rather than by the length of abuse. To examine this possibility, 256 men and 45 women voluntarily admitted to a detoxification program were interviewed and subjected to a battery of neurological tests. Although none of the patients experienced a seizure during the course of the study, 64 had a history of seizures. Roughly 12 percent of alcoholics may be expected to develop seizures during withdrawal; the absence of seizures in the study population is probably due to the use of chlordiazepoxide and thiamine during detoxification. Forty-two patients had significantly abnormal electroencephalograms during the detoxification program, and these abnormalities were present in some individuals without a history of seizures. Analysis of the data demonstrated that the history of seizures did not correlate with the duration of alcohol abuse or the lifetime consumption of alcohol. There was, however, a significant correlation between the number of inpatient detoxifications and seizures; this correlation remained even when provocative drug use was taken into account in the analysis. The drug chlordiazepoxide seems to be effective in the management of seizures related to alcohol withdrawal, even though it is a generally unreliable drug for the management of seizures that are due to other causes. (Consumer Summary produced by Reliance Medical Information, Inc.)

In the first medical reports of seizures as a result of cocaine toxicity, the seizures preceded death in massively overdosed patients. But information from emergency rooms around the nation has now made it clear that convulsions are a relatively common side effect of recreational cocaine use. It is difficult to estimate the frequency of seizures, however, since emergency room patients represent only a small fraction of all cocaine users. Nevertheless, examination of these patients indicates that the likelihood of convulsions seems to be dependent upon not only the size of the cocaine dose, but also how the dose was taken. Intravenous and 'crack' cocaine appear to be most likely to cause seizures. Furthermore, there has been some suggestion that the seizures are related to the acute toxic effects and not to lasting brain abnormalities in these patients. The relationship of these factors to cocaine-induced seizures was explored by reviewing the cases of 474 patients who were seen because of problems relating to cocaine toxicity. Of these patients, 71 had medical histories of seizures which were unrelated to cocaine use. Of the remaining 403 patients, seizures beginning within 90 minutes of cocaine use were the primary symptom in 32, or 7.9 percent. Seizures were slightly more common among patients with a history of seizures; 12 of 71, or 16.9 percent, of these patients were affected by seizures. Among the subjects with no previous history of seizures, the majority (84.4 percent) used intravenous cocaine or crack. However, among the patients with a history of seizures, convulsions may be common even after nasal cocaine use; 58.3 percent of the seizures in this group were induced by nasal cocaine. Seizures resulting from cocaine use were proportionately more common in women than men and were also proportionately more common among blacks than whites. As a subgroup, black women had the highest rate of seizures, which affected 23.7 percent of the black, female cocaine-abusing patients in the study. (Consumer Summary produced by Reliance Medical Information, Inc.)

A 15-month old baby in New York City was accidentally poisoned by a product created to kill rodents. It had been brought from China illegally. It contained a chemical called tetramethylene-disulfotetramine (TETS), which causes seizures.