Wendy G. Mitchell

Very-high-dose phenobarbital for refractory status epilepticus in children

Status epilepticus refractory to initial anticonvulsant therapy is a serious condition with a high morbidity and mortality. We present 50 cases with refractory status epilepticus (RSE) treated with very-high-dose phenobarbital (VHDPB) without reference to a predetermined maximum level or dose. Maximum serum levels ranged from 70 to 344 μg/ml (median, 114 μg/ml). VHDPB controlled seizures in all cases where no limits were imposed upon maximum dose (47/50). We found no maximum dose beyond which further doses are likely to be ineffective. Forty patients were intubated prior to VHDPB, but recovered respiratory drive and could be removed from the ventilator despite very high serum levels. This is explained by acute drug tolerance. Hypotension was unusual, related to the highest levels, and easily controlled. VHDPB has many relative advantages over other therapies presently used for RSE.

Academic Underachievement in Children with Epilepsy

Academic achievement was studied in 78 children with epilepsy, ages 5 to 13 years, to determine how seizures, treatment of seizures, and sociocultural factors influence academic achievement. Cognitive abilities were assessed with either the McCarthy Scales of Childrens Abilities or the Wechsler Intelligence Scale for Children-Revised. Achievement was measured with the Peabody Individual Achievement Tests. Achievement scores were corrected for cognitive ability (IQ), and underachievement was defined as achievement score 1/2 standard deviation or more below IQ. Information regarding seizure history (severity, duration) and treatment with anticonvulsant drugs was obtained. In addition, the family was extensively interviewed regarding the childs environment, behavior, and demographic background. The Home Observation for Measurement of the Environment (HOME) scale was completed on a home visit. Underachievement was frequent, ranging from 16% (Reading Recognition) to 50% (General Knowledge), but there was no relationship between severity or duration of seizure disorder or total exposure to anticonvulsant medications and achievement. Major determinants of achievement included subscales of the HOME scale, age (older children more likely to be underachieving), and parental education. An equal proportion of newly diagnosed and/or untreated subjects were underachieving compared to those with longstanding epilepsy and anticonvulsant drug treatment. (J Child Neurol 1991;6:65-72).

Status Epilepticus and Acute Repetitive Seizures in Children, Adolescents, and Young Adults: Etiology, Outcome, and Treatment

Summary: Status epilepticus (SE) is one of the most common neurologic emergencies in children, adolescents, and young adults. SE may be due to acute neurologic conditions such as meningitis, encephalitis, or stroke, complicated febrile seizures, intractable epilepsy, degenerative diseases, intoxication, or may be the first manifestation of epilepsy. Initial treatment of convulsive SE is usually with an intravenous benzodiazepine (BZD) [lorazepam (LZP) or diazepam (DZP)], phenobarbital (PB), or phe‐nytoin (PHT). LZP is less likely to cause respiratory depression than DZP and is therefore preferred. Sequelae and risk for recurrence of SE are primarily related to the underlying cause. Refractory SE (RSE) is most often symptomatic of an acute neurologic condition or neuro‐degenerative disease. Treatment for RSE is difficult, usually requiring intensive support of vital functions. Reported treatments for RSE include very high dose PB, continuous infusions of pentobarbital or BZDs (DZP, mi‐dazolam), lidocaine, inhalation anesthesia, and propofol. Outcome is related to underlying cause. Nonconvulsive SE may present as confusion or may mimic psychiatric illness. Response to BZDs is usually rapid but may not be sustained. Rapid initiation of oral or rectal valproate may be useful. Epilepsia partialis continua (EPC) is almost always due to an acute or chronic destructive lesion. Surgical treatment may be the only effective modality in some children with EPC. Acute treatment of breakthrough seizures and clusters of seizures at home with rectal BZDs (usually DZP, 0.2–0.5 mg/kg) may prevent progression to SE in some children and adolescents and reduce the need for visits to emergency facilities.

Treating repetitive seizures with a rectal diazepam formulation A randomized study

Objective: To evaluate the effectiveness and safety of a single-dose treatment for acute repetitive seizure (ARS) episodes (e.g., clusters) administered in a nonmedical setting by caregivers. Background: Patients with epilepsy may experience ARS episodes despite optimal anticonvulsant treatment. Such episodes require rapid treatment as medical emergencies. Typically, the patient is treated in an emergency medical setting with IV medication by trained medical personnel. Methods: The authors undertook a multicenter, randomized, parallel, double-blind study of a single administration of Diastat (diazepam rectal gel) for treating episodes of ARS. ARS episodes and treatment criteria were defined for each patient at the start of the study. Caregivers were taught to determine ARS episode onset, administer a predetermined dose of study medication, monitor outcome, count respirations, and record seizures and adverse events. Results: A total of 29 centers enrolled 158 patients, of whom 114 patients had a treated ARS episode (Diastat, n = 56; placebo, n = 58). Diastat treatment reduced median seizure frequency (p = 0.029). More Diastat patients were seizure free post-treatment (Diastat, 55%; placebo, 34%; p = 0.031). Kaplan-Meier analysis of the time to the next seizure favored Diastat treatment (p < 0.007). The most common adverse event was somnolence. Conclusion: Administration of a single rectal dose of Diastat was significantly more effective than placebo in reducing the number of seizures following an episode of ARS. Caregivers could administer treatment safely and effectively in a nonmedical setting.

Lorazepam in childhood status epilepticus and serial seizures: Effectiveness and tachyphylaxis

We report our experience with 300 consecutive parenteral doses of lorazepam (LOR) for status epilepticus (SE) or serial seizures in 77 children and young adults. The median dose for SE in children less than 12 years old was 0.10 mg/kg. LOR stopped the SE in 79% and diminished the intensity of SE in an additional 4%. Prior acute or chronic anticonvulsant use (excepting chronic benzodiazepines) did not alter effectiveness or increase side effects. Duration of freedom from seizures following acute therapy was independent of LOR dosage. In patients requiring sequential doses, LOR becomes progressively less effective. Side effects were few and, when present, always associated with a single or first dose in a series. LOR is a safe and effective acute anticonvulsant agent for in-hospital control of SE in the pediatric age group. Tachyphylaxis of anticonvulsant action occurs when serial doses are used.

Stroke as a late sequela of cranial irradiation for childhood brain tumors.

Cerebrovascular disease involving large and medium-size vessels is thought to be an uncommon sequela of treatment of childhood brain tumors. We reviewed 11 children who developed cerebrovascular disease manifested by strokes or transient ischemic attacks 6 months to 4 years after treatment of brain tumors, while their tumors were in remission. All had received radiation therapy, and seven had received chemotherapy. One child died of acute bilateral cerebral infarctions due to carotid occlusion on one side and marked stenosis on the other 2 years after receiving radiation therapy for an incompletely resected craniopharyngioma. Pathologically, there was marked subendothelial fibrosis of the vessels of the circle of Willis, with inflammatory changes surrounding some of the vessels. In addition to the widely recognized small-vessel damage caused by radiation and chemotherapy in children (mineralizing microangiopathy), damage to medium and large intracranial vessels may result in late sequelae, manifested by stroke or transient ischemic attacks. (J Child Neurol 1991;6:128-133).

Clobazam in the treatment of Lennox-Gastaut syndrome

Purpose:  This randomized, double‐blind, dose‐ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox‐Gastaut syndrome (LGS).

Brain-adrenal axis hormones are altered in the CSF of infants with massive infantile spasms

Massive infantile spasms (MIS), a seizure disorder unique to infants, is considered an age-dependent response of the immature brain to various insults and stressors. The seizures improve with ACTH and glucocorticoids, both major components of the brain-adrenal axis. We hypothesized that CNS levels of these hormones are abnormal in infants with MIS and studied CSF from 14 infants with MIS and 13 age-matched controls by analysis for corticotropin-releasing hormone (CRH), ACTH, cortisol, and interleukin-1-beta. ACTH levels in CSF of patients were significantly lower than those of controls, but differences in cortisol levels between patients and controls were not statistically significant. CRH levels in both groups were similar and fluctuated diurnally. These results indicate an alteration of specific CNS components of the brain-adrenal axis in MIS.

Opsoclonus-Ataxia Due to Childhood Neural Crest Tumors: A Chronic Neurologic Syndrome

Five children with subacute or acute onset of cerebellar ataxia and opsoclonus are described. Two had cerebrospinal fluid pleocytosis at the onset of ataxia and were initially thought to have acute parainfectious cerebellar ataxia of childhood. All were found to have tumors of neural crest origin (two neuroblastomas, three ganglioneuroblastomas). Tumors were small and only found by computed tomographic techniques. Urinary catecholamine metabolites were elevated in only two of the patients. Four of the five failed to improve neurologically with resection of the tumor. All four have had a steroid-sensitive chronic ataxic syndrome that worsens with acute nonspecific illnesses and has resulted in long-term deficits, particularly in speech and gross motor function. This is a metabolic encephalopathy associated with permanent residual neurologic deficits but without visible lesions on neuroimaging studies. We stress the frequency of cerebrospinal fluid pleocytosis in patients with tumor-associated opsoclonus and the clinical difficulty in separating tumor-associated cases from those due to other 1990;5:153-158).

Clinical utility of video-EEG monitoring

This study investigated the efficiency of simultaneous video-electroencephalography (EEG) monitoring in documenting paroxysmal events, the value in clinical diagnosis, and the effect on treatment. In this retrospective review, 230 children underwent this procedure between January, 1990 and December, 1992. The data demonstrated that video-EEG monitoring can be used as a daytime procedure with a high success rate (80%) in detecting and differentiating the nature of recurrent paroxysmal behaviors that have occurred on a daily basis. Video-EEG monitoring has a high diagnostic rate in differentiating seizure versus nonseizure events (70%), in classifying seizure types (88%), and in evaluating the candidacy for epilepsy surgery (64%). Video-EEG diagnosis resulted in an alteration of clinical management in 45% of patients. Continuous video-EEG monitoring is an efficient and valuable procedure in the diagnosis and management of paroxysmal disorders in children.