bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticosteroids in Duchenne Muscular Dystrophy: A Reappraisal
Authors: Wong Brenda L. Y. , Christopher Caroline
Published: March 2008

Duchenne muscular dystrophy is the most common and most severe form of childhood muscular dystrophies, resulting in early loss of ambulation between the ages of 7 and 13 years and death in the teens and twenties. Despite the phenomenal advances made in the understanding of the molecular genetics of the disease, no definitive cure has been found. Of all of the therapeutic drugs studied in Duchenne muscular dystrophy, only prednisone seems to have the potential for providing interim functional improvement for boys with Duchenne muscular dystrophy while they wait for a cure with gene or cell therapy. There is still no consensus regarding recommending corticosteroids as standard therapy for boys. This is an evidence-based review of all of the studies of corticosteroids (prednisone, deflazacort, and oxandrolone) in Duchenne muscular dystrophy. From this review, it is clear that until a definitive treatment for Duchenne muscular dystrophy is available, the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of function in such a common devastating disorder of young growing boys. (J Child Neurol 2002;17:183-190).
Assessment of Cardiac Function in Adolescents With Duchenne Muscular Dystrophy: Importance of Neurohormones
Authors: Ramaciotti Claudio , Scott William A. , Lemler Matthew S. , Haverland Cherie , Iannaccone Susan T.
Published: March 2008

Initial signs of cardiac dysfunction caused by Duchenne muscular dystrophy are usually detected during adolescence. However, decreased physical activity can allow better tolerance of decreased cardiac function. Mild myocardial dysfunction secondary to ischemic or idiopathic cardiomyopathy is accompanied by elevation of plasma levels of norepinephrine and atrial natriuretic factor. This is considered an adaptation to maintain adequate perfusion. We evaluated neurohormone levels in 17 adolescents (median age 14 years) with Duchenne muscular dystrophy and different degrees of ventricular dysfunction determined by echocardiography. All patients were asymptomatic. Electrocardiographic abnormalities were present in 14 of 17 (82%). Shortening fraction was below normal in 9 of 17 (53%). Norepinephrine plasma levels were elevated in 3, and all had normal atrial natriuretic factor levels. There was no association between fractional shortening and norepinephrine plasma level (P =.66). The majority of younger adolescents with Duchenne muscular dystrophy and abnormal ventricular function do not show signs of inadequate perfusion, as evidenced by normal measurements of neurohormones. (J Child Neurol 2002;17:191-194).
Epileptic Disorder as the First Neurologic Manifestation of Blue Rubber Bleb Nevus Syndrome
Authors: Eiris-Punal Jésus , Picon-Cotos Monica , Viso-Lorenzo Augusto , Castro-Gago Manuel
Published: March 2008

Blue rubber bleb nevus syndrome is an uncommon neurocutaneous disorder characterized by distinctive vascular malformations on the body surface. Vascular malformations of internal organs (typically the gastrointestinal tract) are also frequently present. However, malformations of the central nervous system have only rarely been described. We report a case of blue rubber bleb nevus syndrome in a 5-month-old boy with cutaneous manifestations characteristic of this process present from birth and multiple cerebral angiomas detected by magnetic resonance imaging. At age 1½ months, the patient showed myoclonic seizures and complex partial seizures that were refractory to various antiepileptic regimens. At age 5 months, electroencephalograms (EEGs) showed continuous generalized slow spike-waves, predominantly in the right temporal region; however, EEGs normalized after induction of coma with intravenous midazolam. At age 13 months, the patient suffered from occasional seizures and slightly retarded psychomotor development. Epilepsy is rare in this syndrome but as in other neurocutaneous syndromes (eg, Sturge-Weber syndrome) can compromise psychomotor development; thus, every effort should be made to control seizures. (J Child Neurol 2002;17:219-222).
Pyridoxine-Dependent Seizures Associated With Hypophosphatasia in a Newborn
Authors: Lahorgue Nunes Magda , Mugnol Fabiana , Bica Igor , Machado Fiori Renato
Published: March 2008

Pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. Pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. Pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome. (J Child Neurol 2002;17:222-224).
Valproate-Associated Stomatitis
Authors: Ryan Melody , Baumann Robert J. , Miller Craig S. , Baker Chris
Published: March 2008

The purpose of this article is to report a case of severe stomatitis in a patient with pediatric epilepsy taking divalproex sodium. The case was reviewed with detailed oral examinations. This 5-year-old child developed severe stomatitis 18 months after institution of divalproex sodium. Cessation of the medication was associated with resolution of the stomatitis. A review of the pertinent literature is also provided. Stomatitis is a rare but potentially serious adverse effect of divalproex sodium administration. (J Child Neurol 2002;17: 225-227).
Fluctuation of Computed Tomographic Findings in White Matter in Alexander's Disease
Authors: Shiihara Takashi , Kato Mitsuhiro , Honma Tomomi , Ohtaki Shinsuke , Sawaishi Yukio , Hayasaka Kiyoshi
Published: March 2008

A Japanese boy developed febrile seizures and gait disturbance at 2 years of age and dysarthria a year later. He had generalized tonic-clonic seizures once or twice a year from the age of 4 years. Brain computed tomography (CT) showed symmetric low-density areas in the white matter of the frontal lobes. However, abnormal CT findings fluctuated occasionally, with no apparent change in clinical manifestations. Clinical evaluation at 9 years of age revealed hyperreflexia, psychomotor retardation, megalencephaly, and slurred nasal speech. Magnetic resonance imaging showed white matter abnormalities, predominantly in the frontal lobes. He was a heterozygote of the Arg239Cys mutation of the glial fibrillary acidic protein gene and was diagnosed with Alexander's disease. Fluctuation of CT findings in white matter may reflect blood-brain barrier dysfunction in Alexander's disease. (J Child Neurol 2002;17: 227-230).
Recurrent Attacks of Fear and Visual Hallucinations in a Child
Authors: Huppertz Hans-Jürgen , Franck Peter , Korinthenberg Rudolf , Schulze-Bonhage Andreas
Published: March 2008

The case of a 7-year-old boy suffering from recurrent nocturnal and occasional daytime attacks with intense fear and complex visual hallucinations is presented. His state was otherwise normal, as were routine electroencephalographic (EEG) and magnetic resonance imaging (MRI) investigations in the past. Several differential diagnoses such as panic disorder, pavor nocturnus, and nightmares were considered but could not be definitely established or excluded. Since the attacks appeared after the divorce of his parents, an adjustment disorder was suspected, and the patient received psychotherapy for more than 2 years without an effect on the attacks. Only when long-term video-EEG recorded two typical attacks with left temporal ictal seizure patterns was focal epilepsy diagnosed and successfully treated with antiepileptic medication. A suspected origin of seizures in the amygdala was supported by a high-resolution MRI showing a cortical dysplasia extending from the left anteromedial temporal lobe to the amygdala. The case exemplifies difficulties in the differential diagnosis of panic-like attacks and underlines the value of long-term video-EEG, which may be necessary to establish the correct diagnosis and to prevent ineffective therapeutical approaches. (J Child Neurol 2002;17:230-233).
A 15-Year-Old Boy With Central Nervous System Vasculopathy Presenting With Dysarthria-Clumsy Hand Syndrome
Authors: Golomb Meredith R. , Weiss Shelly K. , Ibrahim Shahnaz H. , deVeber Gabrielle A.
Published: March 2008

Dysarthria-clumsy hand stroke syndrome has been described frequently in adults but not in children. We report a 15-year-old right-handed boy with sudden onset of dysarthria, dysphagia, right facial weakness, and mild right-hand clumsiness. Computed tomographic scan and magnetic resonance imaging demonstrated infarction in the genu and posterior limb of the left internal capsule. Magnetic resonance angiography and conventional angiography demonstrated stenosis of the supraclinoid portion of the left internal carotid artery and the origin of the left ophthalmic artery. Lacunar infarction in an older adult is not the only mechanism leading to dysarthria-clumsy hand syndrome. (J Child Neurol 2002;17: 241-243).
α[ 11C]Methyl-L-Tryptophan Positron Emission Tomography in Patients With Alternating Hemiplegia of Childhood
Authors: Pfund Zoltán , Chugani Diane C. , Muzik Otto , Juhász Csaba , Behen Michael E. , Lee Jennifer , Chakraborty Pulak , Mangner Thomas , Chugani Harry T.
Published: March 2008

Based on previous reports suggesting a role of the neurotransmitter serotonin in the pathomechanism of alternating hemiplegia of childhood and speculation that it may be a migraine variant, we measured brain serotonin synthesis in children with alternating hemiplegia of childhood. Clinical and neurodevelopmental data, as well as standard uptake values in 25 brain regions and whole-brain serotonin synthesis capacity (unidirectional uptake rate constant or K-complex), were assessed in six patients with alternating hemiplegia of childhood (three girls and three boys; mean age = 76/12 years) using α[ 11C]methyl-L-tryptophan positron emission tomography (PET). The PET studies were performed interictally in three patients, during the ictal state in two patients, and postictally in one patient. The PET data were compared to those obtained interictally from six age-matched patients with focal epilepsy (two girls and four boys; mean age = 78/12 years) and six non-age-matched apparently normal siblings of autistic children (two girls and four boys; mean age = 911/12 years). Patients with alternating hemiplegia of childhood studied in the ictal or postictal state showed increased serotonin synthesis capacity in the frontoparietal cortex, lateral and medial temporal structures, striatum, and thalamus when compared to controls, and subjects with alternating hemiplegia of childhood studied interictally. The involvement of these brain regions was consistent with the semiology of the hemiplegic attacks. In patients with interictal studies and in the controls, the PET scans revealed similar and bilaterally symmetric regional patterns of serotonin synthesis capacity. Increased whole-brain serotonin synthesis capacity (reported in migraine subjects without aura) was not found in the alternating hemiplegia of childhood group. There was no correlation between the neurodevelopmental scores and regional standard uptake values; however, patients with a larger estimated lifetime attack number showed greater delay in communication (P = .005) and daily living skills (P = .042). These studies suggest increased regional serotonergic activity associated with attacks in alternating hemiplegia of childhood. Furthermore, the attack number may have an effect on neurodevelopmental delay, thus supporting the notion that alternating hemiplegia of childhood may be a progressive disorder. (J Child Neurol 2002;17:253-260).
Insulin Resistance in Epileptic Girls Who Gain Weight After Therapy With Valproic Acid
Authors: Verrotti Alberto , Basciani Fania , De Simone Michele , Trotta Daniela , Morgese Guido , Chiarelli Francesco
Published: March 2008

Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 ± 25.3 versus 28.2 ± 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid. (J Child Neurol 2002;17:265-268).
Parameters for Predicting Favorable Responses to Botulinum Toxin in Children With Cerebral Palsy
Authors: Fattal-Valevski Aviva , Giladi Nir , Domanievitz Dafna , Zuk Luba , Masterman Ronit , Harel Shaul , Wientroub Shlomo , Hayek Shlomo
Published: March 2008

We sought markers for predicting a favorable outcome of botulinum toxin A injected to the lower-extremity muscles of 26 children with hemiplegic or diplegic cerebral palsy. Clinical assessment preceding and 1 month following injection included gross motor function measure, a modified Ashworth scale, and evaluation of range of motion of knee extension and ankle dorsiflexion. Response to treatment was classified based on a parent questionnaire. The 19 children (73%) considered by their parents as being good responders were compared to the 7 (27%) considered as being poor responders. In the good responders, the preinjection Ashworth scale (spasticity) was significantly higher (P < .05) and gross motor function measure scores (function) were lower (P < .05). Sixty-eight percent of the good responders were nonindependent walkers compared to 14% of the poor responders (P < .05). There were no differences in age, type of cerebral palsy, and dose of injection. An Ashworth scale indicating increased muscle tone, lower gross motor function measure scores, and nonindependent ambulatory status were predictive for a favorable response to botulinum toxin A injections and can guide patient selection and expectations of treatment outcome. (J Child Neurol 2002;17:272-277).
Ictal Electroencephalography in a Case of Benign Centrotemporal Epilepsy
Authors: Clemens Béla
Published: March 2008

The purpose of this research was to publish a complete ictal electroencephalographic (EEG) record of a child with benign centrotemporal epilepsy. The record includes a brief description of the patient's epilepsy syndrome, analysis of interictal and ictal EEG records, and a description of corresponding clinical ictal events. Ictal EEG activity appeared over the right rolandic cortex and spread to adjacent sites. Initial rhythmic activity was followed by bilateral series of sharply contoured slow waves. The electric field of the seizure discharge changed during the seizure. Tangentially oriented dipolar field was found in the middle part of the seizure. Evolution of clinical seizure phenomena roughly corresponded to propagation of the ictal discharge. In terms of topography and electromorphology, this ictal record was similar but not completely identical with those reported previously. Collection of further ictal records in benign rolandic or centrotemporal epilepsy of childhood and other epilepsy syndromes is necessary. (J Child Neurol 2002;17:297-300).
Combined Partial Deficiencies of Carnitine Palmitoyltransferase II and Mitochondrial Complex I Presenting as Increased Serum Creatine Kinase Level
Authors: Tsao Chang-Yong , Mendell Jerry R.
Published: March 2008

Increased serum creatine kinase level is a marker of neuromuscular disorders. When combined with exercise intolerance, muscle cramps, fatigue, myoglobinuria, or muscle weakness, metabolic myopathies of a variety of causes should be considered. We encountered an adolescent male with a persistently high serum creatine kinase level and chronic fatigue who was found to have combined partial defects of carnitine palmitoyltransferase II and mitochondrial complex I. Metabolic myopathy may present with chronic fatigue and a persistently high serum creatine kinase level but without muscle weakness and may be attributable to combined enzyme defects. (J Child Neurol 2002;17:304-306).
Unilateral Auditory Neuropathy: Case Study
Authors: Podwall Arthur , Podwall David , Gordon Toni G. , Lamendola Paula , Gold Arnold P.
Published: March 2008

This article reports on an 11-year-old boy who was diagnosed with unilateral auditory neuropathy. After failing his annual medical and school hearing screenings, he was referred for audiologic testing, which identified a profound sensorineural hearing loss in his left ear that has remained stable for the past 31/ 2 years. Subsequently, otoacoustic emissions revealed findings that were consistent with an auditory neuropathy. Neurologic evaluation was remarkable only for a left ear hearing loss. Radiologic studies were unremarkable. Auditory neuropathy is a condition in which patients, on audiologic evaluation, are found to have normal outer hair cell function and abnormal neural function at the level of the eighth nerve. These patients, on clinical testing, are found to have normal otoacoustic emissions, whereas auditory brainstem response audiometry reveals the absence of neural synchrony. Unlike space-occupying lesions, radiologic evaluation reveals normal results. This case is noteworthy because only a handful of the cases of auditory neuropathy reported to date have been unilateral. (J Child Neurol 2002;17:306-309).
Children With Irreversible Brain Damage Associated With Hypothyroidism and Multiple Intracranial Calcifications
Authors: Arii Junko , Tanabe Yuzo , Makino Michiko , Sato Hirokazu , Kohno Yoichi
Published: March 2008

Children who develop clinical hypothyroidism in early childhood have various degrees of irreversible brain damage, albeit less severe than cases detected by neonatal screening test for hypothyroidism in the first months of the life. We report three patients with hypothyroidism of childhood onset after a normal neonatal thyroid-stimulating hormone screening who showed deceleration in linear growth, spasticity in the lower limbs with deformity, mild intellectual impairment, and multiple calcifications in the basal ganglia and subcortical areas. The neurologic symptoms were not progressive but were irreversible in spite of thyroxine treatment. Motor disturbances commonly observed in postnatal-onset hypothyroidism are similar to those of cerebral palsy. Specific distribution of intracranial calcifications may result from metabolic derangement as a result of hypothyroidism, although the mechanism of calcification is not fully understood. We emphasize the need to re-evaluate thyroid function in diplegic patients with specific intracranial calcifications but normal neonatal thyroid-stimulating hormone screening. (J Child Neurol 2002;17:309-313).
Topical Review : Friedreich's Ataxia
Authors: Pilch Jacek , Jamroz Ewa , Marsza Elibieta
Published: March 2008

Friedreich's ataxia is one of the most frequent hereditary ataxias of childhood. The disease is inherited in an autosomal recessive mode. The current state of knowledge concerning genetics, pathophysiology, pathology, clinical course, differential diagnosis, genotype-phenotype correlation, and therapy is presented. (J Child Neurol 2002;17:315-319).
Congenital Muscular Dystrophy in Israeli Families
Authors: Rachmiel Marianna , Nevo Yoram , Lahat Eli , Kutai Miriam , Harel Shaul , Shahar Eli
Published: March 2008

Twelve patients from 11 Israeli families with congenital muscular dystrophy were evaluated between 1991 and 2001. There were six males and six females, of whom six were merosin negative and six were merosin positive. Serum creatine kinase levels were highly elevated in the merosin-negative group. Four of the children were cognitively normal but nonambulant. Two had unusual clinical findings of severe cognitive and motor developmental dysfunction. Four infants in the merosin-positive group who had normal serum creatine kinase levels had early-onset severe motor weakness and died within the first year of life owing to ventilatory insufficiency. The other two were ambulant and had normal cognitive development and elevated serum creatine kinase levels. Noteworthy, two of the six children with merosin-negative congenital muscular dystrophy had cognitive impairment, and four of the six children with merosin-positive congenital muscular dystrophy had a severe form of the disease with ventilatory insufficiency and death during infancy. (J Child Neurol 2002;17:333-336).
Practical Management of Combined Methylmalonicaciduria and Homocystinuria
Authors: Smith Debra L. , Bodamer Olaf A.
Published: March 2008

Combined methylmalonicaciduria and homocystinuria is a disorder of intracellular cobalamin metabolism that remains a challenge to the physician unfamiliar with the diagnosis. We have followed six patients with combined methylmalonicaciduria and homocystinuria (four males, two females, age 4.2-24 years) for a median of 6.5 years (range 4-9 years). Age at diagnosis was between 18 days and 14 months in early-onset cases (n = 4) and 15 and 19 years in late-onset cases. Predominant clinical features include microcephaly, hydrocephalus, seizures, and white-matter changes on magnetic resonance imaging in early-onset cases. The white-matter changes may be secondary to impaired methylation owing to a lack of readily available methyl groups. Spastic quadriparesis and diplegia are long-term sequelae in late-onset cases. Management consists of hydroxycobalamin intramuscular injections, oral folate, betaine, and camitine supplementation. Dietary protein restriction may be necessary when metabolic control remains difficult. The implementation of an emergency regimen should alleviate episodes of metabolic decompensation and reduce the rate of hospital admissions. ( J Child Neurol 2002;17:353-356).
Effects of Prenatal Exposure to Carbamazepine on Brainstem Auditory Evoked Potentials in Infants of Epileptic Mothers
Authors: Poblano Adrián , Belmont Aurora , Sosa Jesús , Ibarra Jorge , Rosas Yolanda , López Vivián , Garza Saúl
Published: March 2008

The purpose of this study was to determine if there are any correlations between carbamazepine serum levels of epileptic mothers during pregnancy and the brainstem auditory evoked potentials in their infants as an index of drug neurotoxicity in newborns exposed prenatally. We included 20 epileptic mothers with carbamazepine medication and their 20 otherwise healthy infants. The study was conducted from September 1, 1993, to December 15, 1999. Serum carbamazepine determinations were performed monthly by enzymatic immunoanalysis in the mothers, and the averages for each trimester during pregnancy were calculated. Brainstem auditory evoked potentials were performed at 10.2 ± 4.6 weeks of postnatal life. Pearson's correlations were calculated between carbamazepine serum levels during pregnancy and waves and interwave intervals of brainstem auditory evoked potentials. Both examinations were performed without knowledge of the results of the other investigations. No alterations in the infants' brainstem auditory evoked potentials were evident, and carbamazepine determinations were within therapeutic levels. Significant Pearson's correlations between latencies of waves III and V and third trimester of carbamazepine serum concentration levels and I-V interwave intervals to third-trimester minimum serum levels of carbamazepine were found. The findings suggest that the higher carbamazepine levels in mothers are related to increased latencies in waves III and V and I-V interwave intervals in infants subclinically, which could be an early index of fetal neurotoxicity. (J Child Neurol 2002;17:364-368).
Hemimegalencephaly: Part 1. Genetic, Clinical, and Imaging Aspects
Authors: Flores-Sarnat Laura
Published: March 2008

Hemimegalencephaly is a rare hamartomatous malformation of the brain, remarkable for its extreme asymmetry. It can be isolated or associated with several neurocutaneous syndromes; less frequently, it also involves the brain stem and cerebellum. Traditionally, hemimegalencephaly has been considered a primary neuroblast migratory disturbance. At present, genetic theories of pathogenesis and modem histopathology provide a basis for this complex malformation as a primary disturbance in cellular lineage, differentiation, and proliferation, interacting with a disturbance in gene expression of body symmetry, with earlier onset than radial neuroblast migration. From my personal experience with 10 patients with hemimegalencephaly and review of the literature, I have found the same clinical neurologic, neuroimaging, and neuropathologic features in isolated and syndromic hemimegalencephaly. Magnetic resonance imaging (MRI) reveals abnormal gyration, ventriculomegaly, colpocephaly, an "occipital sign" (displacement of the occipital lobe across the midline), and increased volume and T signal of white matter, in addition to the overall increased size of the involved hemisphere. Mild, moderate, and severe grades of severity can be recognized, providing a functional neurologic prognosis and therapeutic plan. Early diagnosis is crucial because despite neuroimaging and pathologic evidence, hemimegalencephaly sometimes still is unrecognized. Also, misdiagnosis of obstructive hydrocephalus or cerebral neoplasm can lead to unnecessary surgical procedures. Although hemispherectomy has a high morbidity, it is recommended early for patients with severe, intractable epilepsy. The mildest forms of hemimegalencephaly are infrequent and the least recognized. ( J Child Neurol 2002;17:373-384).
Normally Developed Infant With a Suppression Burst Pattern on Electroencephalography in the Neonatal Period
Authors: Yoshikawa Hideto
Published: March 2008

The background activity on neonatal electroencephalography (EEG) is a good prognostic indicator. An EEG suppression burst pattern usually indicates severe brain dysfunction and has been considered to be associated with a serious neurodevelopmental outcome. We report here a 2-year-old girl who developed generalized convulsions without any perinatal brain insult at 3 days of age. At that time, her EEG constantly showed a suppression burst pattern, and her prognosis was considered to be poor. However, her seizures were well controlled with the oral administration of carbamazepine, and the suppression burst pattern on EEG disappeared at 27 days of age. Unexpectedly, she developed normally for the following 2 years. Although children with normal development, despite the appearance of suppression burst, are extremely rare, and the reason why this patient showed a favorable outcome remains unknown, the clinical course of this patient proved that an EEG suppression burst pattern is not always associated with a poor prognosis. ( J Child Neurol 2002;17:387-389).
Primary Antiphospholipid Syndrome Presenting With a Branch Retinal Artery Occlusion in a 15-Year-Old Boy
Authors: Saxonhouse Matthew A. , Bhatti M. Tariq , Driebe William T. , Freeman Bridget E. , Maria Bernard L. , Camey Paul R.
Published: March 2008

Acute vascular events are rare in the pediatric population, but there is an association with the presence of antiphospholipid antibodies. When there is no other underlying medical disorder, this is referred to as primary antiphospholipid syndrome. We present a case of a 15-year-old boy who developed an acute superior branch retinal artery occlusion. Complete evaluation revealed significant elevations in antiphospholipid antibodies. To our knowledge, there are no cases in children of primary antiphospholipid syndrome presenting with this clinical manifestation. ( J Child Neurol 2002;17:392-394).
Adolescent Asystolic Syncope
Authors: Shore Paul M. , Painter Michael
Published: March 2008

When the etiology of syncope is considered, age is a major parameter. Breath-holding spells are thought of as an entity of early childhood, whereas neurogenic syncope is limited to older children and adults. Both entities, however, involve a similar derangement of the autonomic nervous system. We report an adolescent with a history of breath-holding spells presenting to our institution with neurogenic syncope. Her response to vagal stimulation is consistent with that seen by other investigators in both entities. We propose that pallid breath-holding spells and neurogenic syncope are the same entity. ( J Child Neurol 2002;17:395-397).
Central Nervous System Prophylaxis With High-Dose Methotrexate Does Not Give Rise to Significant Electroencephalographic Changes in Children With Acute Lymphoblastic Leukemia
Authors: Korinthenberg Rudolf , Schneider Annette , Niemeyer Charlotte
Published: March 2008

Acute, subacute, and chronic neurologic complications have been reported in children treated with high-dose methotrexate for various malignant diseases. It was the aim of this study to monitor central nervous system treatment with high-dose methotrexate in children with acute lymphoblastic leukemia by serial electroencephalographic (EEG) examinations. Electroencephalographic examinations with quantitative computed analysis were performed in 21 children before and on the third day after each of four high-dose methotrexate infusions with leucovorin rescue according to protocol M of trial ALL-BFM 90 of the German Society for Pædiatric Haematology and Oncology. Six patients with a medium risk of relapse also received L-asparaginase. In the cohort treated with methotrexate solely, no statistically significant changes of the quantitative EEG parameters could be demonstrated. Only two children with delayed serum methotrexate clearance showed reversible diffuse EEG slowing of a slight to moderate degree. In the group with additional L-asparaginase treatment, slight transient EEG slowing also occurred. Our findings indicate that in patients with a normal methotrexate clearance during central nervous system treatment with high-dose methotrexate according to trial BFM-ALL 90, usually no subacute or cumulative EEG changes have to be expected. If neurologic or psychiatric symptoms or EEG slowing occur, delayed methotrexate clearance must be suspected. ( J Child Neurol 2002;17:409-412).
Levetiracetam in Refractory Pediatric Epilepsy
Authors: Wheless James W. , Ng Yu-tze
Published: March 2008

Levetiracetam, one of the newer-generation antiepilepsy drugs, is not currently approved for use in children. Given its favorable efficacy, pharmacokinetic, and, particularly, safety profile in adults, we felt that it may be a useful antiepilepsy drug for children with refractory epilepsy. We treated 39 patients (mean age 8.6 years) with open-label levetiracetam for up to 9 months. Seizure frequency, drug dosages, adverse events, and neurologic examinations were documented at baseline and routine follow-up visits. Levetiracetam, as add-on therapy, was effective in reducing seizure frequency in a variety of seizure types but was most effective for partial-onset seizures. Fourteen patients were discontinued for lack of efficacy or adverse events. Ten patients reported improvements in cognition or behavior. Levetiracetam was generally effective and well tolerated in this open-label study. Its apparent positive effects on cognition in some patients are encouraging. Large, well-controlled studies are needed to fully define levetiracetam's potential in children with refractory epilepsy. (J Child Neurol 2002;17:413-415).
Functional Outcome Following Stroke in Children
Authors: Gordon Anne L. , Ganesan Vijeya , Towell Anthony , Kirkham Fenella J.
Published: March 2008

The aim of this study was to describe the functional consequences of childhood stroke in terms of activity limitation and to explore the relationship between extent of brain damage, impairment, and functional sequelae. A further aim was to describe the health of the parents of these children. Seventeen children and adolescents with cerebral infarction in the territory of the middle cerebral artery were enrolled in the study. A new activity limitation measure with a 4-point Likert scale (the Paediatric Stroke Activity Limitation Measure) was designed to examine the degree of difficulty experienced by the children in daily activities. The relationship between activity limitation scores, standardized health-related quality of life assessment (Child Health Questionnaire), extent of brain damage, and results of a comprehensive neurologic examination (Pediatric Stroke Outcome Measure) were investigated. Parent health was assessed using the Short-Form 36 General Health Survey. Activity limitation was evident in the domains of education, self-care, and motor skills. There was very good interobserver agreement using the new activity limitation scale between the occupational therapist and pediatric neurologist (Cohen's kappa = 0.88). In comparison with population norms, the subjects scored below average in both physical and psychologic health. There was a clear relationship between radiologically apparent extent of brain damage, degree of impairment, and functional outcome. Parental health also rated generally lower than expected. This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs. (J Child Neurol 2002;17:429-434).
Mitochondrial Dysfunction in Patients With Hypotonia, Epilepsy, Autism, and Developmental Delay: HEADD Syndrome
Authors: Filiano James J. , Goldenthal Michael J. , Harker Rhodes C. , Marin-Garcia José
Published: March 2008

A group of 12 children clinically presenting with hypotonia, intractable epilepsy, autism, and developmental delay, who did not fall into previously described categories of mitochondrial encephalomyopathy, were evaluated for mitochondrial respiratory enzyme activity levels, mitochondrial DNA, and mitochondrial structural abnormalities. Reduced levels in specific respiratory activities were found solely in enzymes with subunits encoded by mitochondrial DNA in seven of eight biopsied skeletal muscle specimens evaluated. Five cases exhibited increased levels of large-scale mitochondrial DNA deletions, whereas pathogenic point mutations previously described in association with mitochondrial encephalomyopathies were not found. Mitochondrial structural abnormalities were present in three of four patients examined. Our findings suggest that mitochondrial dysfunction, including extensive abnormalities in specific enzyme activities, mitochondrial structure, and mitochondrial DNA integrity, may be present in children with a clinical constellation including hypotonia, epileptic seizures, autism, and developmental delay. The acronym HEADD is presented here to facilitate pursuit of mitochondrial defects in patients with this clinical constellation after other causes have been excluded. (J Child Neurol 2002;17:435-439).
Friedreich's Ataxia Associated With Mitochondrial Myopathy: Clinicopathologic Report
Authors: Gallagher Catherine L. , Waclawik Andrew J. , Beinlich Brad R. , Harding Cary O. , Pauli Richard M. , Poirer Josée , Pandolfo Massimo , Shahriar Salamat M.
Published: March 2008

A 13-year-old boy with clinical and electrophysiologic findings of Friedreich's ataxia developed unusually prominent myopathy. Skeletal muscle biopsy showed mitochondrial proliferation and structural abnormalities. No mutation was found in skeletal muscle mitochondrial DNA to explain this finding. Molecular genetic and pathologic studies confirmed a diagnosis of Friedreich's ataxia in the proband and affected relatives. Although the Friedreich's ataxia phenotype results from decreased expression of a mitochondrially targeted protein, frataxin, mitochondrial myopathy has not been described as a feature of the disease. The association between the frataxin gene mutation and mitochondrial myopathy in this case suggests that severe or cumulative insults to mitochondrial function may produce myopathic changes in some cases of Friedreich's ataxia. The patient also responded clinically to carnitine supplementation, suggesting a potential palliative therapy for the disease. (J Child Neurol 2002;17:453-456).
Ectodermal Dysplasia and Brain Cystic Changes: Confirmation of a Novel Neurocutaneous Syndrome
Authors: DiFazio Marc P. , Levin Sondra , Depper Mark
Published: March 2008

Ectodermal dysplasia is a rare congenital disorder characterized by dry, brittle hair, dental malformations, and skin abnormalities. It is thought to be the result of embryonic ectodermal dysgenesis, affecting tissues and structures that are widely separated but with common developmental origins. Recently, this disorder has been associated with a unique neuroimaging appearance, consisting of widely dilated perivascular spaces. This association has been proposed as a novel neurocutaneous syndrome, identified in one report as "cerebrum polycystica vera." We report a similar patient with dilated perivascular spaces associated with dermatologic manifestations consistent with ectodermal dysplasia. This patient was otherwise normal, without neurocognitive deficit. Additional neuroimaging findings included widespread white-matter high signal intensity on T2-weighted magnetic resonance imaging, as well as normal findings on magnetic resonance spectroscopy. This case confirms the association of ectodermal dysplasia and brain cystic changes and appears to expand the phenotypic manifestations that may be seen in such patients. (J Child Neurol 2002;17:475-478).
Rippling Muscle Disease in Childhood
Authors: Schara Ulrike , Vorgerd Matthias , Popovic Nikola , Schoser Benedikt G.H. , Ricker Kenneth , Mortier Wilhelm
Published: March 2008

Rippling muscle disease is a rare autosomal dominant disorder first described in 1975. Recently, it could be classified as a caveolinopathy; in European families, mutations in the caveolin-3 gene were revealed as causing this disease. Although clinical symptoms were almost all described in adulthood, we are now reporting clinical data of seven children with rippling muscle disease owing to mutations in the caveolin-3 gene. Initial symptoms were frequent falls, inability to walk on heels, tiptoe walking with pain and a warm-up phenomenon, calf hypertrophy, and an elevated serum creatine kinase level. Percussion-/pressure-induced rapid contractions, painful muscle mounding, and rippling could be observed even in early childhood. The diagnosis can be confirmed by molecular genetic analysis. Muscle biopsy must be considered in patients without muscle weakness or mechanical hyperirritability to differentiate between rippling muscle disease and limb-girdle muscular dystrophy 1C. (J Child Neurol 2002;17:483-490).
Clinical Characteristics and Muscle Pathology in Myopathic Mitochondrial DNA Depletion
Authors: Nevo Yoram , Soffer Dov , Kutai Miriam , Zelnik Nathanel , Saada Anne , Jossiphov Joseph , Messer Glenda , Shaag Avraham , Shahar Eli , Harel Shaul , Elpeleg Orly
Published: March 2008

Four nonrelated children with myopathic mitochondrial DNA depletion are described. Two of them initially had normal motor development and two had mild motor delay. Motor arrest and regression started at age 6 to 21 months. All four had mitochondrial DNA:nuclear DNA ratios reduced to 16 to 22% of the control mean and mutations in their mitochondrial thymidine kinase 2. Muscle pathology was genotype related: homozygosity for a missense mutation at position 181 was associated with severe myopathic changes, including marked variation in muscle fiber size, myofiber necrosis, regeneration, and interstitial fibrosis, whereas homozygosity for a missense mutation at position 90 was associated with essentially normal muscle histology. No ragged red fibers were detected in any study child. Mitochondrial DNA depletion should be considered in children with myopathy, worsening hypotonia, motor regression, and death during infancy or early childhood. The severity of pathologic findings on muscle biopsy is variable and may correlate with specific mutations and thymidine kinase 2 protein residual activity. (J Child Neurol 2002;17:499-504).
Hypoplasia of the Corpus Callosum and Obsessive-Compulsive Symptoms
Authors: Farchione Tiffany R. , Lorch Elisa , Rosenberg David R.
Published: March 2008

Abnormalities in the corpus callosum, which connects the cerebral hemispheres, have been implicated in the pathogenesis of obsessive-compulsive disorder. This is a report of two cases of obsessive-compulsive disorder associated with hypoplasia of the corpus callosum. These data provide further support for corpus callosum-mediated dysfunction in obsessive-compulsive disorder. (J Child Neurol 2002;17:535-537).
Review Article : Clinical Features and Pathobiology of Neurofibromatosis 1
Authors: Korf Bruce R.
Published: March 2008

Neurofibromatosis 1 is a progressive multisystem disorder. The hallmark feature is the occurrence of nerve sheath tumors, neurofibromas. Other features include tumors such as optic gliomas and malignant peripheral nerve sheath tumors. There are also nontumor manifestations, such as skeletal dysplasia and learning disabilities. Since the NF1 gene was identified, much has been learned about the molecular genetics of the disorder; recently, this has led to insights about pathogenesis. Ultimately, it is hoped that this will be translated into specific means of treatment. This review describes the various clinical features of neurofibromatosis 1 and considers them in the context of the pathophysiology of the disorder. (J Child Neurol 2002; 17:573-577).
Review Article : Cognitive Deficits in Neurofibromatosis 1
Authors: North Kathryn , Hyman Shelley , Barton Belinda
Published: March 2008

Cognitive deficits and academic learning difficulties are the most common neurologic "complication" of neurofibromatosis 1 in childhood and can be responsible for significant lifetime morbidity. There is a slight increase in the frequency of mental retardation (Wechsler Full-Scale IQ < 70) in children with neurofibromatosis 1, but the mean Full-Scale IQ for the patient group is within 1 SD of the population mean. Academic difficulties are common, as are specific deficits in visuospatial ability, executive function, expressive and receptive language, and attentional skills. Behavioral and psychosocial problems have a major impact on quality of life, although there are few objective studies in this area. Current research is focusing on the pathogenesis of the disorder. Clinical studies have identified possible radiologic and pathologic markers for cognitive deficits in neurofibromatosis 1, which can now be explored in animal models. (J Child Neurol 2002;17:605-612).
Review Article : Intracranial Neoplasms in Children With Neurofibromatosis 1
Authors: Rosser Tena , Packer Roger J.
Published: March 2008

Neurofibromatosis 1 is associated with an increased risk for the development of benign and malignant tumors involving neural and non-neural tissues. Children as well as adults with neurofibromatosis 1 are affected. Central nervous system neoplasms represent a significant portion of these malignancies and appear primarily in children less than 10 years of age. Optic pathway gliomas and brainstem gliomas are the most common intracranial neoplasms found in neurofibromatosis 1, although there also is an increased incidence of other brain tumors in this population. The majority of these intracranial neoplasms are benign pilocytic astrocytomas, which may behave in a less aggressive manner than histologically identical tumors in non-neurofibromatosis 1 patients. Owing to the indolent nature of these tumors, conservative management with close follow-up is recommended. When intervention is required, conventional treatment with surgery, radiation, or chemotherapy has been used with variable results. The current challenge lies in understanding the pathogenesis of gliomas in neurofibromatosis 1, which may lead to the development of biologically directed therapies with less associated morbidity and mortality for neurofibromatosis 1 as well as non-neurofibromatosis 1 children. (J Child Neurol 2002;17:630-637).
Hemiconvulsion-Hemiplegia Syndrome and Elevated Interleukin-6: Case Report
Authors: Kimura Masahiko , Tasaka Masaru , Sejima Hitoshi , Takusa Yuichi , Ichiyama Takashi , Yamaguchi Seiji
Published: March 2008

We report a 2-year-old boy who developed hemiconvulsion-hemiplegia syndrome with left-sided hemiplegia after a seizure lasting 35 minutes. The interleukin-6 level in the cerebrospinal fluid 2 hours after seizure onset was elevated to levels seen in patients with encephalitis. At 1 year after onset of the seizure, the patient remained hemiplegic on the left side, and magnetic resonance imaging showed severe right hemispheric atrophy. Acute changes seen on imaging studies and electroencephalograms in this patient were consistent with seizure-induced brain damage. Elevation of cerebrospinal fluid interleukin-6 may be related to the severe neurologic sequelae of our patient despite the relatively short seizure duration. (J Child Neurol 2002;17:705-707).
Topical Review : Neuropsychiatric Problems in Tuberous Sclerosis Complex
Authors: Asato Miya R. , Hardan Antonio Y.
Published: March 2008

Tuberous sclerosis complex is an autosomal dominant disorder characterized by abnormal cellular differentiation and proliferation, as well as abnormal neuronal migration. It is a disease affecting multiple organ systems and typically has brain involvement, causing severe disabilities. This article reviews the literature of the commonly associated neuropsychiatric complications, including mental retardation, autism-like features, and other behavior problems, which are discussed in the context of the neuropathology and epilepsy observed in tuberous sclerosis complex. The potential pathogenesis of neuropsychiatric problems is explored, including links to the genetics, neuropathology, neurotrophins, and epilepsy factors associated with tuberous sclerosis complex. Treatment of neuropsychiatric symptoms, including autism-like features, attention deficits, and sleep disorders, is also discussed. (J Child Neurol 2004;19:241-249).