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Herpes encephalitis in neonates or young infants entails significant risk of mortality or morbidity. Prompt and aggressive treatment may lessen the chronic toll of herpes encephalitis. Unfortunately, an apparent uneventful recovery from herpes encephalitis may disguise evolving cerebral devastation. The discordance between evolving cerebral injury revealed by imaging and a patient's clinical improvement is illustrated by two patients, treated a decade apart., (Copyright 2010 Elsevier Inc. All rights reserved.)

Two consanguineous siblings presented with developmental regression and emerging spasticity. Cranial magnetic resonance imaging in both showed diffuse leukoencephalopathy. Further investigation established the siblings as having complex 1 deficiency consequent to a novel homozygous mutation in NDUFV1, a nuclear-encoded subunit of complex 1. Diffuse leukoencephalopathy may be a presentation of complex 1 deficiency.

Acquired obstructive hydrocephalus has developed rarely in patients with globoid cell leukodystrophy. This report describes a 21-month-old female with this concurrence.

Mortality in pediatric epilepsy is the subject of this review. Epilepsy in both adults and children increases the risk of premature death. Conditions that are comorbid with epilepsy may carry an increased mortality risk. Patients with neurologic compromise may be at risk for aspiration and critical respiratory disease. Epilepsy per se enhances the risks of accidents, particularly drowning. Epilepsy may result in unwitnessed or, less frequently, witnessed sudden death. Witnessed sudden death frequently involves an observed seizure. Cardiac and respiratory mechanisms for epileptic sudden death have been proposed. Reducing the number of seizures should reduce the risk for sudden death. Awareness of the increased risk for premature death associated with epilepsy may enhance patients' and parents' cooperation with therapy.

A patient with neonatal macrocephaly due to bilateral chronic subdural hematoma is presented. There was no history of intrauterine trauma or coagulopathy. Such patients are apparently rare. The pathogenesis of intrauterine chronic subdural hematoma in such patients is unclear.

Carnitine transporter defect is characterized by severely reduced transport of carnitine into skeletal muscle, fibroblasts, and renal tubules. All children with dilated cardiomyopathy or hypoglycemia and coma should be evaluated for this transporter defect because it is readily amenable to therapy that results in prolonged prevention of cardiac failure. This article details the cases of 3 children who have carnitine transporter defect, 2 of whom had severe dilated cardiomyopathy. Plasma and skeletal muscle carnitine levels were extremely low and both children were treated with oral L-carnitine, resulting in resolution of severe cardiomyopathy and prevention of recurrence or cardiac enlargement for more than 5 years. The third child had hypoglycemia and coma as presenting findings of the transporter defect and had mild left ventricular hypertrophy but no cardiac failure. The prognosis for long-term survival in pediatric dilated cardiomyopathy is poor. Children with carnitine transporter defect can have a different outcome if their underlying condition is detected early and treated medically.

During an evaluation for complicated migraine, a 14-year-old adolescent female was found to have a left frontoparietal cortical infarction on magnetic resonance imaging study. A transthoracic echocardiogram was normal, but a transesophageal echocardiogram, with contrast study, showed occasional right to left shunting through a patent foramen ovale. The role of cardiac anomalies in the pathogenesis of migraine-associated stroke is discussed.

An 11-year-old girl presented with a syndrome of inappropriate antidiuretic hormone secretion, which was transitory and, initially, of obscure origin. Subsequently, the patient's hypothalamic disorder emerged as a component of a steroid-responsive relapsing encephalomyelitis with cerebral pathology restricted to the basal ganglia and brainstem. Where such a disorder fits in the spectrum from acute disseminating encephalomeylitis to multiple sclerosis is discussed.

Two patients with congenital lactic acidemia of unknown etiology developed striking and extensive cranial computed tomography abnormalities of acute or subacute onset. In addition to Leigh syndrome and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), other lactic acidemia disorders may produce evolving cerebral radiographic abnormalities. An aggressive effort should be made in such patients to obtain a specific diagnosis through biochemical and molecular genetic studies.

Two particularly common, and frequently frightening, forms of syncope and anoxic seizure in early childhood are pallid and cyanotic breath-holding spells. Pallid breath-holding spells result from exuberant vagally-mediated cardiac inhibition. Cyanotic breath-holding spells are of more complex pathogenesis, involving an interplay among hyperventilation, Valsalva maneuver, expiratory apnea, and intrinsic pulmonary mechanisms. The history is the mainstay of diagnosis; videotape documentation may be possible. Performance of an electrocardiogram to evaluate for prolonged QT syndrome should be strongly considered. In patients with pallid breath-holding spells, a characteristic sequence of changes may be documented on an electroencephalogram with ocular compression, if this study is performed. Spontaneous resolution of breath-holding spell, without sequelae, is anticipated. Reassurance is the mainstay of therapy. Occasionally, pharmacologic intervention may be of benefit.

A 4-year-old boy became paraplegic during the course of hepatitis A infection. There were significant magnetic resonance imaging changes in the cervical spinal cord and brainstem. The patient's cervical myelopathy resolved entirely after 10 weeks.

Autopsy reports in I-cell disease patients describe no salient abnormality of central nervous system morphology. Magnetic resonance imaging of the cranium in a patient with I-cell disease showed ventriculomegaly with frontal lobe atrophy and bifrontal leukomalacia. Central nervous system morphological abnormalities may occur in a subset of patients with I-cell disease.

Mitochondrial oxidation of a variety of substrates produces the bulk of energy requirements for most cell types. Impairment of oxidative metabolism may result in a broad spectrum of clinical signs and symptoms. A disorder of oxidative metabolism should be suspected when an unexplained association of signs and symptoms occurs, particularly when it is progressive, involving organs with no common embryologic origin. Encephalopathy and myopathy are a particularly suspect combination. Numerous specific disorders affect oxidative metabolism. Lactate elevation frequently occurs and additional laboratory abnormalities often assist in focusing investigation. Diagnostic specificity may require, in addition to the blood and urine studies, tissue sampling, cerebral imaging, in vivo studies of tissue energetics, or molecular genetic analysis.

Magnetic resonance imaging of the spine in 45 patients with myelomeningocele revealed hydrosyringomyelia in 24 and diastematomyelia in two. No patient at initial imaging manifested symptoms referable to hydrosyringomyelia; both patients with diastematomyelia had flaccid lower extremities. One patient developed an upper extremity monoparesis which resolved with syringo-peritoneal shunt placement; no other patient manifested symptoms or required surgery. Ventriculoperitoneal shunt malfunction produced reversible distention of the syrinx in another patient who remained asymptomatic.

A defect in intracellular uptake of carnitine has been identified in patients with severe carnitine deficiency. To define the clinical manifestations of this disorder, the presenting features of 15 affected infants and children were examined. Progressive cardiomyopathy, with or without chronic muscle weakness, was the most common presentation (median age of onset, 3 years). Other patients presented with episodes of fasting hypoglycemia during the first 2 years of life before cardiomyopathy had become apparent. A defect in carnitine uptake was demonstrable in fibroblasts and leukocytes from patients. The defect also appears to be expressed in muscle and kidney. Concentrations of plasma carnitine and rates of carnitine uptake in parents were intermediate between affected patients and normal control subjects, consistent with recessive inheritance. Early recognition and treatment with high doses of oral carnitine may be life-saving in this disorder of fatty acid oxidation.

Muscle biopsy was used to attempt determination of carrier status in mothers and maternal relatives of patients with severe neonatal centronuclear (myotubular) myopathy, an X-linked recessive disorder. We report findings from muscle biopsies of 3 mothers, one an obligate carrier. All biopsies showed abnormalities of nonspecific character. Whether such abnormalities assist in defining carrier status is uncertain. A more specific tissue marker for this disorder is required before muscle biopsy will facilitate carrier identification.

Plasmapheresis is used for treating the complications of liver failure. We performed plasmapheresis on 6 children with hepatic encephalopathy resulting from acute hepatic failure and prospectively assessed its effects on neurologic and electrophysiologic (electroencephalography and evoked potentials) function. Clinical improvement was observed in 3 of 6 patients; changes in the serum ammonia value or the results of initial electrophysiologic tests did not predict the patient response. Two patients underwent transplantation after neurologic improvement was produced by plasmapheresis; however, despite plasmapheresis, 4 patients progressed to brain death. Our data demonstrate that plasmapheresis may transiently improve the encephalopathy of acute hepatic failure but is not curative alone. Therefore, plasmapheresis may be a useful adjunct in the treatment of liver failure, potentially improving the pretransplantation status of the patient.

Carnitine deficiency syndromes manifest as metabolic encephalopathy, lipid storage myopathy, or cardiomyopathy. Impairment of long-chain fatty acid metabolism and failure of energy production affect tissues reliant on oxidative metabolism. The accumulation of toxic fatty acyl derivatives impedes gluconeogenesis and urea cycle function which, in turn, causes hypoketotic hypoglycemia, transaminase elevations, and hyperammonemia. Oxidation of accumulated fatty acids through an alternative pathway, omega-oxidation, produces dicarboxylic aciduria. Carnitine must be transported into skeletal muscle. Myopathic carnitine deficiency occurs when this transport mechanism is defective. Most systemic carnitine deficiencies are secondary to other disorders that promote excretion of carnitine as acylcarnitine; however, primary systemic carnitine deficiency, likely due to impaired renal conservation of carnitine, also occurs.

Electroretinography (ERG) may provide laboratory support for the diagnosis of childhood myotonic dystrophy. The sensitivity of ERG may exceed that of electromyography for early detection of the disease. The electroretinographic abnormalities are not specific for myotonic dystrophy.

Though osseous abnormalities are associated with tuberous sclerosis, involvement of the skull base and orbit has not been reported. We describe a patient with superior displacement of the orbit and proptosis that were due to sphenoid hyperplasia and sclerosis characteristic of fibrous dysplasia. A pelvic osteosclerotic lesion suggested polyostotic involvement. The bony abnormalities implied neither concurrent neurofibromatosis nor McCune-Albright syndrome in this patient with tuberous sclerosis.

The concurrence of gelastic (laughing) seizures and precocious puberty has been reported in 18 patients, including 2 described here. At least 10 patients had hypothalamic hamartomas. Improvements in cerebral imaging permit noninvasive diagnosis. Surgical intervention in seven of these patients was of little diagnostic or therapeutic benefit.

Movement disorders developed in five children, ages 6 to 21 months, during the course of bacterial meningitis caused by Hemophilus influenzae (one), Streptococcus pneumoniae (one), Neisseria meningitidis (one), or Mycobacterium tuberculosis (two). Athetosis, choreoathetosis, and hemiballismus occurred, ranging in duration from hours to months. Cranial computed tomography, performed in four cases, showed no lesion of the basal ganglia. The movements were of such abrupt onset and severity that in four cases they were initially misinterpreted as seizures, and anticonvulsant therapy was contemplated. It is important to recognize the potential development of movement disorders during the acute phase of bacterial meningitis to preclude the inappropriate administration of anticonvulsant medication.

We report a unique presentation of X-linked recessive dystrophy as neonatal rhabdomyolysis. There was induration of the proximal musculature in an otherwise well neonate and striking CK elevation, without myoglobinuria. Muscle biopsy at age 1 year showed dystrophic alterations, and X chromosome analysis showed a deletion within or adjacent to the Duchenne/Becker locus.

Cardiac rhabdomyoma occurs frequently in patients with tuberous sclerosis (TS). Although there have been case reports of detection of cardiac rhabdomyoma by 2-dimensional echocardiography, no study has examined the frequency of cardiac rhabdomyoma detected by cardiac ultrasound in patients with TS. Echocardiography was performed in 16 consecutive patients with TS. Physical examination revealed normal cardiac findings in each. Discrete areas of increased acoustic density were found in 8 of the 16 patients (50%). The maximum diameters ranged from 3 to 20 mm. Multiple areas were found in 3 of 8. The left ventricle was involved in 5 of the 8. Six masses were intracavitary and 8 were intramyocardial. No atrial masses were seen. Left ventricular size and function were normal. Although other tumors cannot be excluded, the diagnosis of cardiac rhabdomyoma is almost certain in these young patients with TS. The male predominance and the high incidence of intracavitary and left ventricular masses are similar to those in reported autopsy series, also supporting the diagnosis of cardiac rhabdomyoma. The prognosis and potential for growth of these masses are not known, but can be determined by longitudinal follow-up. Cardiac ultrasound should be considered for all patients with TS regardless of physical findings.

This article reviews the neurologic manifestations of hyperammonemic disorders. A variety of inborn errors of metabolism, as well as transient neonatal or acquired hepatic dysfunctions, are identified as causes of hyperammonemia. The pathogenesis of hyperammonemia in these disorders is outlined. Catastrophic hyperammonemia and hyperammonemic coma are described; algorithms to establish specific diagnosis are suggested. Symptoms of less severe ammonia intoxication, which also occur in more common diseases, are described. The need to consider hyperammonemia as a potential etiology for these symptoms is emphasized. Finally, the neurotoxicity of ammonia is discussed.

Two patients are reported with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes in whom CT documented massive focal brain swelling with midline shift concurrent with exacerbations of their conditions. Brain swelling producing mass effect should be recognized as a feature of MELAS.