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.

Effect of alcohol and smoking on pancreatic lithogenesis in the course of chronic pancreatitis.

The aim of the study was to establish whether correlations were discernible between calcification, smoking, and other variables--including alcohol intake--in chronic pancreatitis. A total of 637 patients with chronic pancreatitis diagnosed over the period of 1973-1989 were reviewed. Only patients who had had one or more instrumental tests (ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, plain film of the abdomen) every 3 years were included in the study. Onset of calcification was taken as the end point of the follow-up. No statistically significant correlation was found between alcohol intake and calcification. As regards smoking habits, patients were divided into two groups: nonsmokers and medium-to-heavy smokers (> or = 10 cigarettes/day). Of 637 patients, only 570 fulfilled our criteria. Three hundred seventy-six patients (66%) developed calcifications, whereas 64 (10%) already presented calcifications at the time of diagnosis. Smoking correlated with formation of calcifications (p < 0.004). The mean time to onset of calcification in smokers was 8 years as against 12 years in nonsmokers. The relative risk of calcification in smokers versus nonsmokers was 1.21 (95% confidence limits: 1.10-1.32). By the end of follow-up (17 years), 277 smokers (69%) with chronic pancreatitis had developed calcifications compared with only 93 nonsmokers (55%). The results show that, in this sample of chronic pancreatitis sufferers, smokers present a significantly increased risk of developing calcifications.

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.

Valproate-associated pancreatitis.

To assess the clinical characteristics of valproate (VPA)-associated pancreatitis, information from three sources was gathered: (a) a survey among 507 physicians with a special interest in treatment of epilepsy, (b) a review of the authors' patient population, and (c) a review of the literature. Of 366 physicians answering the survey, 53 (14.5%) reported a case of pancreatitis. Thirty-nine cases were available for review (24 from the medical literature, 12 from the survey, and 3 from the authors). Pancreatitis appeared to be more frequent in young persons (mean age 16.4 years) but may occur at any age. The highest risk appears to exist during the first months of treatment: 43.8% of the cases developed during the first 3 months, and 68.8% developed during the first year. Seventy-six percent of patients were receiving polytherapy, and 41% had some form of associated chronic encephalopathy. In most patients, the reaction was rapidly reversible when VPA was discontinued. It was severe in 6 patients, with 3 deaths reported. Rechallenge with VPA was attempted in 9 patients, with a high incidence of relapses. Asymptomatic elevation of serum amylase in patients receiving VPA was reported by 40 (10.9%) of the physicians surveyed. Awareness of the problem and early discontinuation of VPA may be effective in preventing serious reactions.

Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988.

To determine trends in the incidence of pancreatic cancer and associated survival, we conducted a population-based study in Olmsted County, Minnesota. From 1940 through 1988, 219 residents of Olmsted County (120 men and 99 women) were diagnosed as having exocrine pancreatic cancer. All patients were Caucasians, and 92% had a histologically confirmed diagnosis. The mean annual adjusted incidence of pancreatic cancer per 100,000 population was 8.5 overall (11.3 for men and 6.6 for women). During the course of the study, the incidence rates increased in women (P < 0.05) and in both genders combined (P = 0.06) but not in men (P = 0.4). The male:female ratio decreased from approximately 2:1 for 1940 through 1949 to 1.5:1 for 1980 through 1988. The incidence was significantly associated with increasing age (P < 0.001) and male gender (P < 0.001) but not calendar period (P = 0.19). The overall median duration of survival was 2.8 months. The 1-year survival rate was only 14%, and no patient lived for more than 55 months after pancreatic cancer was diagnosed. Men and women had similar survival rates. The increased incidence of pancreatic cancer among women may be due in part to the increasing life span of women and the increasing occurrence of pancreatic cancer in the aged.

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.

Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests.

Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

Measuring gastric PGE2 release in healthy and alcoholic subjects after ethanol stimulation.

The aim of this work was to study the effect of 20% and 40% ethanol, administered acutely, on gastric PGE2 release in normal subjects and alcoholics. Ethanol 20% did not modify the release of PGE2 into the gastric juice, whereas 40% ethanol increased PGE2 release only in healthy subjects. The basal PGE2 levels were higher in alcoholic patients.

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.

Pancreatic calcifications in patients with chronic pancreatitis. A sign of long-lasting or severe disease?

Pancreatic calcifications are particularly frequent in patients with severe pancreatic insufficiency and long-lasting chronic pancreatitis. To clarify whether calcifications point to a more severe form of the disease, irrespective of its duration, we have retrospectively analyzed patients with chronic pancreatitis submitted to the secretin-cerulein test in our center over a six-year period. Out of 120 patients, calcifications were found in 55. Higher alcohol intake and longer duration of the disease were found in patients with calcifications, compared with patients without calcifications (p less than 0.001). In both groups, lipase and chymotrypsin were more severely impaired than bicarbonate; a greater reduction of pancreatic exocrine function was found in patients with calcifications, compared to those without (p less than 0.001, Mann-Whitney U-test). When the patients were classified according to the duration of the disease or the severity of exocrine function impairment, higher percentages of patients with calcifications were found in the classes with more advanced disease. A log-linear analysis showed that the prevalence of calcifications was associated with pancreatic function impairment, even within the same class of duration of the disease. It is likely that calcifications mark more severe forms of chronic pancreatitis, even in the early phases of the disease.

Retroperitoneal and peritoneal drainage and lavage in the treatment of severe necrotizing pancreatitis.

In severe necrotizing pancreatitis, the retroperitoneum is the main site both of autodigestion and of the production of toxins. With the aim of removing necrotic tissues and active enzymes from the retroperitoneum, we developed a surgical approach based on a wide exposure of the pancreas and on the insertion of multiple drainages with postoperative irrigations with hypertonic solutions and antiproteases. We treated 191 patients, and our results correlated with the timing of the operation. The operative mortality rate ranges from 8.1 in patients undergoing our procedure within 48 hours from the onset of the disease to 28.4 per cent when the operation was delayed for more than 96 hours. Our technique is detailed and the indications as to the timing of surgical treatment in instances of pancreatitis are discussed.

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.