Journal of Child Neurology

Frequent migraine headaches can have a significant impact on disability, prompting the need for early recognition and treatment. The objective of this study is to compare the efficacy of topiramate and sodium valproate for the prevention of pediatric migraine, retrospectively. Mean monthly migraine frequency, intensity, and duration in the 28 patients treated with topiramate decreased from 15.3 ± 10.1 to 4.4 ± 5.5 episode, from 6.8 ± 1 to 3.2 ± 1, and from 10.2 ± 9.4 to 2.4 ± 3.1 hours, respectively. Headache disability improved with a reduction of Pediatric Migraine Disability Assessment score from 36 ± 29.5 to 4.6 ± 6.5 (P < .05). Similarly, mean monthly headache frequency, headache intensity, headache duration, and Pediatric Migraine Disability Assessment score in the 20 patients treated with sodium valproate decreased from 20.1 ± 10.2 to 6.6 ± 8.6, from 7.1 ± 1 to 3.4 ± 2.1, from 7 ± 12 to 1.4 ± 2.5 hours, and from 20.5 ± 16.1 to 5.5 ± 9.2, respectively (P < .05). In conclusion, valproate and topiramate seem to be able to manage successfully childhood migraine without substantial differences in efficacy.

Neurocutaneous melanosis is a rare noninherited embryonic neuroectodermal dysplasia, which is observed sporadically and never affects the entire integument. The hallmark of neurocutaneous melanosis in the neonatal period is the presence of a large bilateral hairy dark nevus with satellite nevi over the trunk and neck. The diagnosis should be considered in neonates with large pigmented nevi and in those with more than 3 hairy dark nevi regardless of their size. Neonates with neurocutaneous melanosis are at risk of developing neurological problems. The most common neurological complications are hydrocephalus, seizures, cranial nerve dysfunction, and signs of spinal cord and root involvement. The authors report 3 cases of histologically confirmed neurocutaneous melanosis and describe the course of neurological symptoms and clinical findings including cognitive tests and neuroimaging. The case reports are complemented by an up-to date review on this clinical entity.

A retrospective cohort design using medical and pharmacy claims from one state's Medicaid program compared incidence rates for neurological adverse events associated with antipsychotic use in 4140 youths prescribed antipsychotic medications and an untreated sample of 4500 youths, January 1998 to December 2005. The treated cohort evinced a higher prevalence of involuntary movements, sedation, and seizures. The odds of incident involuntary movements were significantly higher for those taking aripiprazole, risperidone, haloperidol, and multiple antipsychotics. The odds of incident seizures were greater for those taking risperidone, multiple antipsychotics, and serotonin-specific reuptake inhibitors. The odds of incident sedation were greater for those taking ziprasidone, risperidone, quetiapine, multiple antipsychotics, and serotonin-specific reuptake inhibitors. Exposure to risperidone, multiple antipsychotics, and serotonin-specific reuptake inhibitors consistently confers a higher risk of developing a range of neurological adverse events in young patients, especially those with preexisting central nervous system, mental retardation, or cardiovascular disorders.

The aim of this study is to establish the prevalence of fragile X syndrome among Estonian mentally retarded and also among the entire children's population born during the years 1984-2005. The study group consisted of 516 patients (448 boys and 68 girls) who were screened for full mutations in the FMR1 gene during the period 1997-2006. Fourteen boys (2.7%) were found with full mutations of the total mentally retarded individuals tested (3.1% of mentally retarded boys); the full mutation was not detected among girls. The live-birth prevalence of full mutation among boys was 1:13 947. The overall live-birth prevalence of fragile X syndrome was 1:27 115. It was found that the prevalence of fragile X syndrome among mentally retarded individuals in Estonia was the same as in previous studies, but the live-birth prevalence of fragile X syndrome among boys was significantly lower.

Contrary to belief, neonatal hypoglycemia is relatively common and can cause more severe neurological sequelae than is currently believed. Prevention of hypoglycemic brain damage by hindering prolonged and profound neonatal hypoglycemia might contribute to psychomotor development. At Erciyes University, between December 1996 and 2005, of the patients who applied to Paediatric Neurology Department, 60 cases with a history of neonatal hypoglycemia were included in the study. The magnetic resonance imaging (MRI) scans and clinical records of all patients were reviewed retrospectively. It was noted that the sequelae with glucose levels of 0 0 to 40 were more serious and intense. The same results were also observed in cranial MRI evaluation. In conclusion, intractable epilepsy, mental motor retardation, cerebral palsy, and visual disturbance were found to be the most common and severe conditions affecting sufferers of neonatal hypoglycemia. In the first 3 days of life, the close monitoring of patients at risk is critical, and hospitalization of severe cases should be considered.

Autoimmunity to brain could play an etiopathogenic role in a subgroup of autistic patients. The frequency of serum anti-myelin—associated glycoprotein antibodies, as an index for autoimmunity to brain, and their relation to family history of autoimmunity were investigated in 32 autistic and 32 healthy matched children. Autistic children had significantly higher serum anti-myelin—associated glycoprotein antibodies than healthy children (2100 [1995] and 1138 [87.5] Buhlmann titre unit, P < .001). Anti-myelin—associated glycoprotein positivity was elicited in 62.5% of autistic children. Family history of autoimmunity in autistic children (50%) was significantly higher than controls (9.4%). Anti-myelin—associated glycoprotein serum levels were significantly higher in autistic children with than those without such history (P < .05). In conclusion, autism could be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further studies are warranted to shed light on the etiopathogenic role of anti-myelin—associated glycoprotein antibodies and the role of immunotherapy in autism.

To analyze cranial growth and size of anterior fontanel during the first year of life, we undertook a cohort study with a sample of 33 infants assessed at birth and reexamined at 1, 2, 3, 4, 5, 6, 9, and 12 months. Examination included assessment of head circumference, anterior fontanel size, anteroposterior distance, biauricular distance, and cephalic index. All infants were neurologically normal. Mean size of the anterior fontanel at birth was 1.77 cm² and, in disagreement with literature data, fontanel size increased up to 2 months of age; fontanel was closed at 1 year for 27.3% of infants. Significant differences in cranial anthropometry were not found in relation to method of delivery (vaginal or cesarean section), gender and gestational age. Our results indicate the need to reevaluate anthropometric examination data and to establish patterns of normality, particularly for miscegenated populations that have not been widely investigated.

The outcome of obstetric brachial plexus palsy depends on the severity of the lesion of the nerve fibers. The aim of the prospective study is to evaluate if differences in force used in downward traction on the fetal head correlate to the number of nerve roots affected. At final neurological examination at 18 months of age, complete neurological recovery occurred in 80 of 98 children (82%). Downward traction of the fetal head was applied more often and with greater force in the group with persistent damage. There was a significant correlation between the force used to the number of nerve roots affected. The risk of persistent obstetric brachial plexus palsy at age 18 months depended on obstetric management and increased significantly with increasing force used in downward traction of the fetal head.

Hyperekplexia (MIM #149400) is a rare neurological disorder characterized by an exaggerated startle response, infantile hypertonia and hyperreflexia without spasticity, a hesitant gait that usually improves by 3 years of age, and nocturnal myoclonus. Familial hyperekplexia is usually autosomal dominant resulting from mutations in the inhibitory glycine receptor subunit alpha 1 (GLRA1) gene on chromosome 5q. We identified a 3-generation family with progressively severe phenotypes of hyperekplexia. All affected family members were found to be heterozygous for a novel arginine271proline mutation in GLRA1. Long-term follow-up of the affected members of the third generation, now aged 6 and 7 years, reveals enhanced startle responses and persistent hypertonia of the extremities without clonus or a catch, tight heel cords and abnormal toe-walking gait, and plantar flexor reflexes. The 7-year-old child recently reponded well to a benzodiazepine. Future studies are warranted to examine whether this new missense mutation is solely responsible for this atypical phenotype.

Primary spinal atypical teratoid/rhabdoid tumor is extremely rare. The authors present a case of atypical teratoid/rhabdoid tumor occurring in a 4-year-old girl. Magnetic resonance imaging The authors showed an intramedullary mass extending from the bulbomedullary junction to T1 with leptomeningeal dissemination. The patient died 2 weeks after diagnosis.

The clinical manifestations and histopathologic and neuroimaging findings in 4 Indian patients with a variant form of mucolipidosis IV are described. The presenting symptoms were psychomotor delay, spastic paraplegia, and mild mental retardation. One patient also had visual deterioration due to optic atrophy. None had corneal or retinal abnormalities. Magnetic resonance imaging in 3 patients showed a uniformly thin corpus callosum in all patients and white matter changes in 2 patients. Electron microscopic examination of skin biopsy specimens revealed storage bodies characteristic of mucolipidosis IV. These patients differ from previously described patients with this disorder in the absence of corneal abnormalities and in their presentation with spastic paraplegia during the second decade of life. Correct diagnosis is needed for genetic counseling, prognostication. and reduction of additional familial burden of this rare disease.

Myoclonic epilepsy associated with ragged red fibers (MERRF) syndrome is one of the major mitochondrial encephalomyopathies, with the involvement of various organs, which could be caused by mitochondrial A8344G DNA mutation. Monostotic fibrous dysplasia of bone, an asymptomatic developmental disorder, was reported to result from c-fos overexpression in osteogenic cells. Mitochondrial A8344G mutation has been shown to increase c-fos expression in a MERRF cybrid cell line. The authors describe a boy aged 10 years and 2 months with MERRF syndrome and A8344G mutation. Visual disturbance developed and deteriorated rapidly 5 months after the diagnosis of MERRF. A brain magnetic resonance imaging revealed optic nerve compression by sphenoid fibrous dysplasia, which was confirmed by histology. Fibrous dysplasia has never been mentioned in MERRF patients in the literature. This rare association may be because of underestimation, or it could be a coincidence. Care should be taken to explore the skeletal system in MERRF patients with focal symptoms.

It is difficult to precisely measure articular arc movement in newborns using a goniometer. This article proposes an objective method based on trigonometry for the evaluation of lower limb abduction. With the newborn aligned in the dorsal decubitus position, 2 points are marked at the level of the medial malleolus, one on the sagittal line and the other at the end of the abduction. Using the right-sided line between these 2 points and a line from the medial malleolus to the reference point at the anterior superior iliac spine or umbilical scar, an isosceles triangle is drawn, and half of the inferential abduction angle is obtained by calculating the sine. Twenty healthy full-term newborns comprise the study cohort. Intersubject and intrasubject variability among the abduction angle values (mean [SD], 37° [4]°) is low. This method is advantageous because the measurement is precise and because the sine can be used without approximation.

Pyridoxine-dependent seizures are a rare condition recognized when numerous seizures respond to pyridoxine treatment and recur on pyridoxine withdrawal. For decades the diagnosis was confirmed only with pyridoxine treatment withdrawal trial. Recently described biochemical and molecular pathology improved the diagnostic process for those cases in which seizures are caused by alpha amino adipic semialdehyde dehydrogenase deficiency. This article presents a girl with recurrent status epilepticus episodes resistant to phenobarbital and phenytoin and partly responding to midazolam. Eventually the seizures were completely controlled with pyridoxine; however, due to the severe condition of this child when seizing, no trial of withdrawal has been performed. The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated α-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. Due to the availability of reliable laboratory testing, confirmation of the diagnosis was made without the life-threatening trial of pyridoxine withdrawal.

Cerebral folate deficiency syndrome, a recently recognized cause of developmental delay, regression, and seizures, is associated with autoantibodies against folate receptors. A female child with developmental delay and a history of seizures who presented with seizures and unexplained coma is reported. Extensive testing to evaluate the patient's coma and subsequent developmental regression were unrevealing until the results of her cerebrospinal fluid neurotransmitter analysis returned. These showed low levels of methyltetrahydrofolate, the active metabolite of folate in the cerebrospinal fluid; subsequently, elevated titers of autoantibodies against folate receptors were found. Despite treatment with folinic acid, she developed intractable epilepsy and severe developmental delay.

The objective of this study was to compare the effectiveness of baclofen versus tizanidine as adjuvant treatment of botulinum toxin type A botulinum toxin type A in the management of children with spasticity. Thirty children with gastrocnemius spasticity were retrospectively reviewed at Gaziantep University Hospital, Gaziantep, Turkey. All patients were treated with localized botulinum toxin injections and baclofen or tizanidine for spasticity and were followed at 2- to 4-week intervals and evaluated for a total of 12 weeks; 17 children (57%) received baclofen and 13 (43%) received tizanidine. The mean score of Gross Motor Functional Measurement (76.63 ± 5.88 vs 68.17 ± 1.99; P < .001) and caregiver questionnaire scores (70.23 ± 4.76 vs 66.59 ± 3.53; P = .03) for the tizanidine group were significantly higher as compared with the baclofen group. This study suggests that combination of botulinum toxin type A with oral tizanidine is more effective with fewer side effects than combination of botulinum toxin type A and oral baclofen for spastic cerebral palsy.

Pituitary carcinoma, an uncommon tumor in adults, generally presents with craniospinal and systemic metastases. We report a case of pituitary carcinoma with multiple craniospinal metastases in a child. A 9-year-old girl, who had had a ventriculoperitoneal shunt operation 3 years ago, presented with complaints of progressive visual disturbance, headache, speech difficulty, and gait disturbance for the past 2 months. Neurological examination revealed papilledema, visual loss, and dysarthria. Cranial magnetic resonance imaging revealed a large contrast-enhanced tumor in the left frontal region together with multiple lesions in the sellar-parasellar region and posterior fossa. Multiple intraspinal contrast-enhanced metastatic lesions were also seen. Histopathological and immunohistochemical examination of the excised left frontal mass revealed pituitary carcinoma. Treatment with cyclic temozolomide was started after the operation, but the patient died after 2 months without response to medical therapy. This is the first pediatric case, to the authors' knowledge, of a pituitary carcinoma with widespread intracranial and intraspinal metastases.

We describe 3 patients with different degrees of cerebellar hypoplasia and continuous spike-waves during sleep: the more extensive the cerebellar hypoplasia, the more compromised the neuropsychological abilities and behavior. Cerebellar hypoplasia is a risk factor for epilepsy and/or neuropsychological and psychiatric disorders. Epilepsy is also strongly associated with familial antecedents for seizures, as previously reported. The cerebellum is implicated in controlling epileptic seizures and in regulating motor, cognitive, and emotional functions with a topographic organization. The association between cerebellar hypoplasia and continuous spike-waves during sleep has never been reported. We suggest that continuous spike-waves during sleep may further compromise neuropsychological and behavioral features that are associated with cerebellar hypoplasia.

We report 2 patients with obstetrical brachial plexus palsy, ipsilateral leg weakness, and contralateral motor cortical dysplasia. To our knowledge, this is the first description of such an association. In both cases, the diagnosis of obstetrical brachial plexus palsy was established clinically shortly after birth and later confirmed neurophysiologically. Motor cortex dysplasia was diagnosed by magnetic resonance imaging (MRI). The association of obstetrical brachial plexus palsy and contralateral motor cortex dysplasia, a condition known to produce congenital hemiparesis, raises the possibility that the cortical dysplasia was a predisposing factor for obstetrical brachial plexus palsy in these cases.

Gangliogliomas are usually benign slow-growing neoplasms, seen mainly in the first 3 decades of life and are prevalently located supratentorial, mostly in the temporal and frontal lobe. The authors present a rare case of a brainstem ganglioglioma in an 11-year-old boy who was referred to their hospital complaining of episodes of blurry vision, loss of memory, gait disturbances, and morning headache with vomiting, lasting for over a month. Computed tomography and magnetic resonance imaging scans revealed a mass on the dorsal surface of the brainstem, compressing the brainstem and producing secondary obstructive hydrocephalus. The patient was operated upon, and the histopathology revealed the presence of a ganglioglioma grade II (World Health Organization classification). On follow-up examination after 1 year, a minor gait imbalance was the only finding. A total resection should be always attempted, where possible in brainstem gangliogliomas. Close follow-up is mandatory, and re-resection or radiotherapy should be considered in case of tumor recurrence.

During almost 4 decades of clinical practice of pediatrics and pediatric neurology, the senior authors have rarely made a formal presentation on the topic of “febrile seizures.” In any large pediatric teaching hospital, questions regarding the diagnosis and management of febrile seizures are raised by medical students, pediatric residents, and adult and pediatric neurology residents. The acronym FIRST was developed as a teaching tool to present a simple and pragmatic clinical approach to children presenting with a single seizure or cluster of seizures in 1 day associated with a febrile illness before, during, or after the seizure event(s). FIRST refers to Febrile, Illness, Related, Seizure(s) and Template, with the latter representing an outline of the basic cause(s). The authors propose the use of the Table as a tool to help determine the underlying etiology of febrile seizures because this is the major factor affecting the choice of treatment.