Nontraumatic brain hemorrhage in children: etiology and presentation.

The clinical and radiographic findings of 68 children and adolescents with nontraumatic intraparenchymal brain hemorrhage were analyzed retrospectively. There were 43 boys and 25 girls, and the average age was 7.1 years (range, 3 months to 18 years). The most common presenting symptom was a combination of headache or vomiting (40 cases, or 58.8%). Hemiparesis was the major presenting sign in 11 (16.2%) of the children, seizures occurred in 25 (36.8%) patients, and 6 (8.8%) children were irritable. Only 2 (2.9%) children were comatose at presentation. One or more risk factors for hemorrhage were found in 61 (89.7%) of 68 children. A third (23 cases, or 33.8%) had an arteriovenous malformation or fistula; altogether 29 (42.6%) children had some type of congenital vascular anomaly. Hematologic or coagulation disorders were present in 22 (32.4%) patients, and 9 (13.2%) patients had brain tumors. Hemorrhage could not be attributed to systemic hypertension in any child. The likelihood of establishing the cause of bleeding was greater when evaluation included cerebral angiography (97.3% versus 80.4% without angiography). Half (34 cases, or 50.0%) of the patients regained normal neurologic function. Six (8.8%) patients died, either directly or partly as a consequence of the hemorrhage. The remaining patients had various neurologic sequelae, including 17 (25.0%) with hemiparesis, 5 (7.4%) with aphasia, 7 (10.3%) with epileptic seizures, and 3 (4.4%) with hydrocephalus. More detailed follow-up studies are needed to obtain more information about the frequency of cognitive sequelae.

Stroke in children: recognition, treatment, and future directions.

Childhood stoke is increasingly recognized, but studies remain largely descriptive. Important differences from adult stroke include the following: (1) frequently delayed or missed diagnosis, (2) heterogenous and overlapping risk factors, and (3) developmental differences in the cerebrovascular, neurologic, and coagulation systems. These aspects limit the extrapolation of the results of adult stroke research and present challenges in caring for children with stroke. The incidence of childhood ischemic stroke exceeds 3.3 in 100,000 children per year, more than double the estimates from past decades. The increased incidence reflects, in part, increased survival in previously fatal conditions predisposing to stroke, including congenital heart disease, sickle cell anemia, and leukemia. Risk factors for stroke are recognized in more than 75% of children. Common risk factors include congenital heart disease and sickle cell disease. Progressive arteriopathies, including vasculitis and moyamoya syndrome, are rare in children with stroke; however, transient arteriopathies including post-varicella angiopathy are increasingly recognized. Prothrombotic abnormalities are frequently present but of unclear significance. Adverse outcomes after childhood stroke, including death in 10%, recurrence in 20%, and neurologic deficits in two thirds of survivors could be reduced with available stroke treatments. Aggressive prehospital emergency care and transfer could improve access to hyperacute stroke therapies including tPA. Currently, the diagnosis is delayed by more than 24 hours from onset in most children. As in adults, tPA will likely produce unacceptable rates of intracerebral hemmorrhage unless given within 3 hours of stroke symptom onset. The appropriate choices for in hospital treatment and secondary preventative strategies, including aspirin and anticoagulants, are controversial. Empiric recommendations are published; however, age-appropriate clinical trials are urgently needed. The large multinational networks of investigators necessary for designing and conducting these future trials are now being formed.

Discontinuation of antiepileptic drug treatment after two seizure-free years in children with cerebral palsy.

OBJECTIVE: The risk of seizure relapse after antiepileptic drug (AED) discontinuation in children has been reported to vary between 6% and 40%. It has been suggested that neurologic deficit and mental retardation are poor prognostic factors for seizure relapse after AED discontinuation. Because epileptic children with cerebral palsy (CP) have neurologic deficits, and many have mental retardation, it is important to know their risk for seizure relapse. METHODS: AED treatment was discontinued in 65 children with CP and histories of epilepsy after 2 seizure-free years. All of the patients were followed until they had seizure relapses or for at least 2 years without seizures after AEDs were stopped. Multiple factors were analyzed for possible association with seizure relapse. RESULTS: Twenty-seven patients (41.5%) had seizure relapses. Patients with spastic hemiparesis had the highest relapse rate (61.5%), and those with spastic diplegia had the lowest rate (14.3%). No other factor correlated significantly with the risk of seizure relapse. CONCLUSIONS: Discontinuation of AEDs in children with CP can, and should, be practiced when possible after patients have been seizure-free for at least 2 years. AED discontinuation in patients with spastic hemiparesis is significantly more likely to lead to seizure relapse than in patients with other CP types, but no other factor is yet known to increase the chance of relapse.

Reading-induced absence seizures.

Reading epilepsy usually presents with jaw myoclonus and generalized tonic-clonic seizures. We report a 12-year-old girl with absence seizures induced by reading, which were diagnosed by video EEG. An absence seizure with generalized 3-Hz spike-and-wave discharge occurred within 30 seconds of each reading session. Treatment with valproate caused complete seizure control, with therapy successfully discontinued after 2 years.

Fryns syndrome: neurologic findings in a survivor.

Fryns syndrome, a multiple congenital anomaly syndrome associated with diaphragmatic defects, craniofacial dysmorphism, distal digital hypoplasia, and neurologic abnormalities, was first described in 1979. This autosomal recessive disorder is usually associated with stillbirth or death immediately after birth. Detailed neurologic findings in the third survivor beyond the neonatal period are reported, and neurologic abnormalities in other cases are reviewed. Initially, hypotonia, areflexia, and weakness were seen. Myoclonus developed immediately after birth and was well controlled with high-dose valproate. Electroencephalography revealed slowing and irregular paroxysmal discharges with spikes and sharp waves that disappeared with time and treatment. Magnetic resonance imaging demonstrated partial agenesis of the corpus callosum, a Dandy-Walker malformation, and progressive cerebral and brainstem atrophy. This syndrome should be considered in patients with unusual facial features and digital abnormalities associated with frequent early myoclonus.

Hemisomatic spasms in children.

We report two children with hemisomatic spasms caused by neoplastic lesions in the region of the ipsilateral cerebellopontine angle. In this condition, seizure misdiagnoses are frequent and EEGs are normal, even ictally. MRI should be performed early to prevent delay of appropriate treatment.

Thrombocytopenia secondary to high valproate levels in children with epilepsy.

We reviewed the frequency of valproate-induced thrombocytopenia in children with epilepsy in our institution. Sixty-four (21%) of 306 children taking valproate developed thrombocytopenia. Thirty-two of these 64 patients had at least one platelet count lower than 100 x 10(3)/mm3. Eight patients developed signs of bleeding. Low platelet levels were typically noted in patients with serum valproate levels of over 140 micrograms/mL, and reduction of the medication dose usually resulted in a prompt increase in the number of platelets. Only one patient developed thrombocytopenia unrelated to high serum drug levels, and her platelet count did not improve until the drug was discontinued. Neither the age of the patient nor the use of additional antiepileptic medication correlated with the platelet count. However, duration of valproate use was related. These data suggest that, although valproate may cause thrombocytopenia via more than one mechanism, by far the most common factor is the presence of high valproate levels. Thus, the medication can be safely lowered in most patients with thrombocytopenia rather than discontinued altogether. Platelet counts should probably be monitored more carefully in patients known to have higher drug levels.

Etiology of stroke in children.

Cerebrovascular disorders are more common than once suspected, and our ability to diagnose stroke in children has improved with the development of newer imaging techniques in recent years. Children have a wide array of risk factors that promote cerebral infarction or hemorrhage, and a likely cause can eventually be pinpointed in about two thirds of patients if a thorough diagnostic evaluation is performed. Ideally, a systematic evaluation should confirm the presence of a cerebrovascular lesion and also identify the cause, concentrating initially on the more common or treatable risk factors. Recognition of the cause of a child's stroke is important, because the likelihood of recurrence depends largely on the etiology and whether treatment is available.

Reassessment of the clinical significance of periodic lateralized epileptiform discharges in pediatric patients.

A review of clinical data from 18 pediatric patients with periodic lateralized epileptiform discharges and bilateral independent periodic lateralized epileptiform discharges (PLEDs and BIPLEDs) showed 2 with chronic neurologic illness, 6 with a history of prior seizures, 14 with depressed sensorium at the time of EEG, 5 deaths, and 8 of 13 survivors with neurologic deficits. These findings are similar to the combined data from reports involving adult patients only. Separating pediatric patients with PLEDs from those with BIPLEDs shows some influence from patients with BIPLEDs. Overall, our data do not suggest significant clinical differences for PLEDs between children and adults.

Therapeutic bioequivalency study of brand name versus generic carbamazepine.

We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency.

Transient magnetic resonance imaging abnormalities during partial status epilepticus.

Magnetic resonance imaging is an important tool in the evaluation of patients with seizures. Frequently, abnormalities are found that lead to further, invasive testing. The first child with transient abnormal findings on magnetic resonance imaging during a time of frequent partial seizures is presented. This lesion disappeared with seizure control. The imaging literature is reviewed concerning transient findings on any imaging modality during frequent seizures. Caution in recommending invasive procedures is suggested when abnormalities are found on magnetic resonance imaging during frequent seizures.

Management of seizures.

Seizure patients represent a population that is frequently seen in medical practice. Critical care physicians will encounter chronically epileptic patients as well as patients with isolated seizures that develop in the course of treatment of surgical and other medical disorders. In such circumstances, knowledge of seizure type and common antiepileptic medications facilitates appropriate medical management. More emergently, SE may constitute a life-threatening indication for admission to an intensive care unit. Rapid treatment of SE is necessary to prevent multiple medical complications leading to morbidity and mortality.

Juvenile myoclonic epilepsy: long-term response to therapy.

Data from 50 patients with juvenile myoclonic epilepsy (JME) were analyzed retrospectively to assess the response to drug therapy--long-term seizure control, relapse rates, and confounding factors in seizure recurrence. Valproate is the only available antiepileptic drug that has been shown to be effective in controlling the generalized seizure components of JME--myoclonic, tonic--clonic, and absence seizures--without significant side effects. Data were collected using the EpiMonitor software and represented case follow-up from 2 months to 9 years. Forty-three patients (86%) were seizure free for at least 1 year; 25 patients (50%) relapsed at some point during follow-up. Relapses were precipitated most frequently by fatigue, noncompliance, stress, sleep deprivation, and alcohol consumption. With accurate diagnosis and appropriate therapy, seizures in JME can be adequately controlled, although JME is a chronic disorder that may require lifelong therapy. To minimize relapse, patient management must also focus on patient lifestyle to eliminate or control lifestyle-associated precipitants of seizure relapse.

Magnetic resonance imaging in pediatric neurologic disorders.

We present our initial experience with magnetic resonance imaging (MRI) in 301 pediatric patients with a variety of neurologic disorders. MRI does not require ionizing radiation and can be done easily and safely in children. It is equal or superior to computed cranial tomographic (CT) scans in demonstrating most types of pediatric neurologic disorders. MRI is often superior to CT scans in demonstrating intracranial tumors, although both studies are usually abnormal in highly malignant tumors. No clear advantage was shown with either MRI or CT scans for fluid-filled intracranial lesions. Lesions of the brain stem and upper cervical region, such as Chiari malformation, are well delineated by MRI. Increased signal from the paranasal sinuses was frequently evident by MRI, but, in most instances, there was no clinical indication of sinus disease. Large arteries can be visualized as an area of diminished signal, and intracranial hemorrhage, dural sinus thrombosis, and cerebral infarction were demonstrated. The increased anatomic detail pictured by MRI allows the diagnosis of congenital defects, such as agenesis of the corpus callosum or septum pellucidum, that are not always apparent with CT scans. Although our experience with spinal cord lesions was not extensive, fluid-filled lesions within the cord can be reliably demonstrated.

Magnetic resonance imaging and complex partial seizures.

Magnetic resonance imaging (MRI) is a new imaging modality with potential usefulness in the evaluation of patients with seizure disorders. We studied 100 consecutive patients with complex partial seizures comparing computerized cranial tomography (CCT) with MRI. Our study revealed 36 patients with CCT abnormalities. Of these, 30 (83%) had focal abnormalities. MRI demonstrated 45 patients with abnormalities, 34 (76%) were focal. Intracranial calcifications were not visualized by MRI, but were easily demonstrated by CCT. MRI was more sensitive in visualizing cerebral atrophy, abnormal cerebral vasculature, and lesions in the posterior fossa and suprasellar region. Most importantly, several patients who had normal CCTs had abnormal MRIs consistent with neoplastic lesions. As MRI becomes more available, this imaging modality along with EEG, should be the studies of choice in evaluating patients with partial epilepsy.

Regional cerebral blood flow characteristics of the Sturge-Weber syndrome.

Four patients with the Sturge-Weber syndrome were studied using the non-invasive Xenon-133 inhalation technique. All four patients had decreased regional cerebral blood flow in the area of their lesion, and in two patients who were subsequently tested with 5% carbon dioxide inhalation, impaired vasomotor reactivity was documented. Diminished regional cerebral blood flow is consistent with previously described nuclide flow studies which demonstrated a delay in the initial perfusion blush in the region of the abnormal vasculature. The focal decrease in blood flow was greatest in the most severely affected patient, but was also prominent in the two younger patients, both of whom have excellent neurologic function. These studies suggest that localized decrease in blood flow and vasomotor dysfunction in Sturge-Weber syndrome can precede the occurrence of severe neurologic impairment and extensive cerebral atrophy and possibly be a major contributing factor in progressive dysfunction. A secondary observation was that the blood flow in the unaffected hemisphere was significantly greater in two children compared to the two adults and was similar to the age-related differences reported for normal children and adults.

Chronic seizure disorders: contribution of MR imaging when CT is normal.

One hundred consecutive patients with complex partial seizures were studied by magnetic resonance (MR) imaging and computed tomography (CT). Thirty-four patients had seizures of more than 5 years' duration, yet neurologic examinations and previous pre- and postinfusion CT scans had been normal. MR imaging demonstrated surgical lesions of potentially therapeutic significance in four of these 34 patients. Two patients underwent surgery with removal of a thrombosed arteriovenous malformation and a glioma. Although CT has been found to detect structural abnormalities, its yield of therapeutically significant abnormalities has been low.

Wilson's disease: evoked potentials and computed tomography.

Multi-modality evoked potentials and computed cranial tomography (CT) were performed in ten patients with Wilson's disease to determine if any of these studies would correlate reliably with neurologic status. While all four patients with CT abnormality had neurologic signs, two additional patients with neurologic findings had normal scans. Evoked responses were normal in nine patients. The remaining patient displayed abnormal visual, brainstem, and somatosensory evoked potentials, and follow-up studies after clinical deterioration revealed worsening of the brainstem and visual evoked potentials. This patient died unexpectedly from a subdural hematoma, and postmortem examination confirmed the radiographic findings of cortical atrophy of the cerebrum and cerebellum and bilateral cystic degeneration of the basal ganglia. However, localized demyelination in the visual, auditory, and sensory pathways was not present. We conclude that the clinical neurologic status of patients with Wilson's disease cannot be reliably predicted by either CT or multi-modality evoked potentials.