Knobloch syndrome involving midline scalp defect of the frontal region.

We report on a 4-year-old boy with Knobloch syndrome. He has vitreoretinal degeneration, high myopia, cataract, telecanthus, hypertelorism, and a high-arched palate. He also has a defect of the anterior midline scalp with involvement of the frontal bone as documented by a computed tomography (CT) scan. The brain was normal on CT scan and magnetic resonance imaging. We present a review of the 23 published cases with this syndrome. Our patient illustrates the importance of investigating for underlying ocular and central nervous system pathology whenever midline scalp defects are present.

Acute-phase neurologic complications of Haemophilus influenzae type b meningitis: association with developmental problems at school age.

The purposes of this study were to describe the incidence of acute-phase neurologic complications in a sample of 126 children with Haemophilus influenzae type b meningitis, and to determine if these complications were associated with higher rates of learning and behavior problems at school age. Risks were assessed by comparing rates of adverse psychoeducational outcomes in the 53 children in the sample with complications to corresponding outcome rates in the 67 children who were free of neurologic complications and who did not have abnormal electroencephalograms (EEGs) or computed tomographic (CT) scans. Comparisons were made by means of logistic regression analysis. Twenty-nine children (23% of the sample) had seizures, 16 (13%) were comatose or obtunded, 15 (12%) had sensorineural hearing loss, 8 (6%) had hemiparesis, and 7 (6%) had cranial nerve deficits other than hearing loss. Relative to children without complications, those with complications had higher rates of grade repetition and substandard performance on neuropsychological and achievement testing. Adverse outcomes, however, consisted primarily of more subtle cognitive and learning problems; only two of the children in the sample obtained prorated IQ scores below 70. Sequelae were associated with persistent neurologic deficits and bilateral hearing loss, as well as with transient symptoms including seizures, coma, and hemiparesis. While study findings argue against adverse consequences for the vast majority of children treated for this disease, the results clarify learning and behavior outcomes and indicate which children are at greatest risk.

Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.

Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).

Multifactorial inheritance of non-syndromic macrocephaly.

OBJECTIVE: To reevaluate previous claims that non-syndromic macrocephaly is usually inherited as an autosomal dominant trait. DESIGN: Head size was measured in the parents and sibs of children with non-syndromic macrocephaly. OUTCOME MEASURES: If autosomal dominant inheritance is involved, the frequency distribution should be bimodal. RESULTS: Head circumference of parents and sibs of the macrocephalic probands had a mean significantly greater than the population norm, and a unimodal distribution. Probands with psychomotor impairment had bigger heads, and more had a history of birth difficulty, than did unimpaired probands. CONCLUSIONS: The usual genetic basis for non-syndromic macrocephaly is multifactorial with a polygenic genetic basis, rather than autosomal dominant. Risk of recurrence appears to be much lower than if it would be on the assumption of autosomal dominant inheritance. Macrocephaly in a parent or sib of an unborn child may present a risk for birth injury to that child. A larger series of patients will be necessary to resolve this question.

"Pseudo-BECRS": intracranial focal lesions suggestive of a primary partial epilepsy syndrome.

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical entity that is the most common primary partial epilepsy syndrome of childhood. Typically presenting between the ages of 3 and 13 years, it is characterized by a well-recognized seizure pattern arising in a normal child with EEG findings restricted to rolandic/centrotemporal regions. Seizure control is usually easily achieved and prognosis is believed to be uniformly good. Some authors have suggested that individuals fitting the electroclinical parameters of this entity need not undergo neuroimaging due to the benign evolution of this disorder. Five patients presenting over a 13-year period with peribuccal seizures, normal neurologic examinations, and EEG data initially suggestive of BECRS found to have focal lesions on neuroimaging are summarized. Independent bilateral centrotemporal epileptiform abnormalities were seen in 3 patients. Imaging studies (CT, MRI, or both) documented a mass lesion in all in variable locations. Histologic examination documented a low-grade astrocytoma in 3 patients and a cavernous angioma in another. The fifth patient refused treatment or biopsy. Careful retrospective review of the clinical features of these patients reveals variable atypical features in each. Therefore, despite an electroclinical phenotype initially suggestive of the BECRS presentation, the presence of atypical clinical features raises the possibility of an underlying structural lesion and thus a negative neuroimaging study may in some patients be essential to the definitive accurate diagnosis of BECRS.

Lesionectomy of MRI detected lesions in children with epilepsy.

The results of complete excision of cerebral lesions detected by MRI in 18 children presenting with epilepsy were analyzed. There were 14 boys and 4 girls with a mean age of 9.2 years. The average age of onset of seizures was 6.8 years. The mean time from onset of seizures to surgery was 2.3 years. Often, CT scans suggested that the lesions were indolent. MRI was better in differentiating neoplastic from developmental lesions. Angiography was non-contributory in this series. Interictal EEGs showed epileptiform activity correlating with imaging studies in 54% of children. The lesion was completely surgically excised in all patients. This was confirmed by intra-operative ultrasound and postoperative imaging. Electrocorticography was performed prior to and after the resection, but residual spiking did not lead to further resection. The average postoperative follow-up was 5.7 years. Five patients had low grade astrocytomas, 4 had gangliogliomas, 1 a mixed astrocytoma-oligodendroglioma, 3 had cortical dysplasia, 2 infantile desmoplastic gangliogliomas, 2 hamartomata, and 1 cavernous angioma. Sixteen patients have been seizure-free since surgery. Only 2 have partial seizures. Thus, all patients benefited from the resection, with respect to seizure control. In those with temporal lobe lesions, improvement in IQ was seen postoperatively. Early consideration of surgery in patients with epilepsy and lesions demonstrated by MRI is suggested.

Encephaloduroarteriosynangiosis (EDAS) for the treatment of childhood moyamoya disease.

Moyamoya disease is defined by the angiographic demonstration of stenosis or occlusion of the vessels of the anterior circulation at the base of the brain and the concomitant development of collateral blood supply. Untreated, the disease is often clinically progressive, resulting in significant neurologic sequelae. Encephaloduroarteriosynangiosis (EDAS), which involves the transposition of a segment of a scalp artery onto the surface of the brain, is a surgical treatment aimed at improving collateral blood flow. Six children underwent 8 EDAS procedures and were followed from 6 months to 9 years after surgery. No patient experienced further deterioration in neurologic status. Postoperative angiography demonstrated cerebral revascularization from the donor scalp artery on 3 of the 6 EDASs that were studied. The 2 patients who did not revascularize after EDAS demonstrated angiographic regression of their disease. The data suggest that EDAS is a safe procedure for the treatment of childhood moyamoya disease. Given the potential severity of the sequelae, early operative intervention is recommended in all children with this disease.

Newborn apnea caused by a neurofibroma at the craniocervical junction.

The authors report, for the first time, the finding by magnetic resonance imaging of a neurofibroma at the craniocervical junction with upper cervical cord and lower brainstem compression causing complete apnea from birth. Subsequent subtotal resection of the neurofibroma resulted in the successful extubation of a previously ventilator-dependent patient. After a two month period of breathing spontaneously, the newborn developed an upper respiratory tract infection and was reintubated. The patient, unable to be weaned off of the respirator, was extubated and expired shortly thereafter, at the age of five months. The authors suggest that in newborns with unexplained apnea, MRI of the cranio-cervical junction is indicated. Certain patients may be discovered who have less compromised cervico-medullary function and are afflicted by less aggressive forms of neurofibromatosis type 1. These patients may benefit permanently from a surgical decompression.

Transient oculosympathetic paresis (group II Raeder paratrigeminal neuralgia) of childhood: migraine variant.

Although a recognized migrainous phenomenon in adults, transient oculosympathetic paresis in childhood has been rarely observed. Six pediatric patients are reported with transient oculosympathetic paresis occurring within the context of characteristic vascular headaches. The clinical profiles of the patients suggest transient dysfunction of third-order ocular sympathetic pathways and represent most likely a benign, self-limited variant of pediatric migrainous neuralgia.

King syndrome: a genetically heterogenous phenotype due to congenital myopathies.

We report on a patient with myopathy, kyphoscoliosis, joint contractures, and a facial appearance consistent with King syndrome. Unlike other reported cases, our patient had hyperextensible joints, normal stature, and pectus excavatum. The cardiac ventricles, aorta, and pulmonary artery were dilated. Malignant hyperthermia did not occur under anaesthesia although there was a transient increase in CK levels. Muscle bulk and tone were significantly decreased but collagen and elastin fibres were normal. The variable clinical presentation of King syndrome suggests that the manifestations are caused by different congenital myopathies and in all cases there is probably an increased risk of malignant hyperthermia.

Syndrome of mental retardation and distal arthrogryposis in sibs.

Two sisters presented with a syndrome of characteristic facial anomalies and distal arthrogryposis. The older sister is now 4 years old and is severely mentally retarded. Her sister died of respiratory failure due to hypoplastic lungs shortly after birth. The occurrence of this potentially lethal syndrome in 2 sisters with unaffected parents suggests autosomal recessive inheritance.

The sequelae of Haemophilus influenzae meningitis in school-age children.

BACKGROUND: Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS: Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the children's hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS: Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute-phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS: We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b.

Headaches in Children: Is it Always Migraine?

Headache can occur in children. There are several causes, but the most common cause of recurrent severe headaches is migraine. There are several types of migraine, some of which are associated with neurologic deficits (so-called complicated migraine). Investigations, such as electroencephalography and computed tomography, might be necessary to exclude other disorders, but are unnecessary in most cases.

Neonatal dural sinus thrombosis.

Dural sinus thrombosis in the newborn period has been infrequently documented and its clinical presentation remains obscure. Seventeen patients, all of whom were born at term with dural sinus thrombosis diagnosed in the neonatal period, were retrospectively identified and reviewed. Diagnosis was determined by unenhanced computed tomography which demonstrated a dense sagittal sinus with concomitant small ventricles. Two patients had ancillary studies (i.e., cerebral angiography and nuclear flow scan) which confirmed the diagnosis. Only 4 patients had evidence of perinatal asphyxia. Three patients were identified as having associated conditions known to predispose them to dural sinus thrombosis. None of the patients tested had an identifiable hypercoagulable state. Neonatal seizures were the initial presentation in 15 patients. Seizure onset predominantly occurred during the first week of life. Subsequent examinations were available in all 17 patients and ranged up to 6 years. Only 3 patients had seizures beyond the neonatal period. In 11 of 12 infants with no history of perinatal asphyxia, neurodevelopmental outcomes were normal. Two of 4 infants with perinatal asphyxia had neurologic sequelae. Dural sinus thrombosis represents an important and under-recognized cause of neonatal seizures in term infants. In the absence of perinatal asphyxia, normal neuro-developmental outcome is likely and the risk of seizure recurrence is low.

Encephalitis among Cree children in northern Quebec.

We report a neurological disease among Cree Indian children in a northern Quebec village. The disease manifests as severe mental retardation, cerebral atrophy with white matter changes and calcifications, and systemic immunological abnormalities. Eleven cases are known in five families. The familial incidence of cases and the high degree of parental consanguinity suggest a genetic contribution. We propose that this entity may be caused by an unusual viral infection in a genetically vulnerable host.

Leukoencephalopathy among native Indian infants in northern Quebec and Manitoba.

We report 14 cases of a severe familial leukoencephalopathy among native North American Indian infants in northern Quebec and Manitoba. Affected infants have hypotonia and mild motor delay, followed by seizures, hypotonia or spasticity, eye deviation, and abnormal posture during a febrile illness around 6 months of age. Death follows a rigid, vegetative state that manifests days to months after disease onset and is marked in some cases by prominent autonomic disturbances, blindness, and cessation of head growth. Symmetrical hemispheric white matter lucencies and diffuse hypomyelination of the cerebral hemispheres and brainstem are the radiological and pathological hallmarks. This disease differs from the known diseases of cerebral myelin. An autosomal recessive pattern of inheritance awaits statistical confirmation. The proposed cause is a delay in development or abnormal turnover of central nervous system myelin.

Subacute necrotizing encephalomyelopathy (Leigh disease): CT study.

Leigh disease, or subacute necrotizing encephalomyelopathy (SNE), is a familial, degenerative disorder characterized by lesions of the gray and white matter in the brain and spinal cord. Low attenuation in the putamina on computed tomography (CT) scans is considered to be characteristic of the disease. The authors used CT to study five patients, in three of whom the disease was confirmed histologically. In one of the patients with documented SNE, there was extensive gray matter lucency with normal basal ganglia. CT scans obtained in a second patient showed diffuse, diseased white matter with focal cortical extension and bilateral caudate involvement. In the other three cases, CT scans revealed the usual changes that occur in the basal ganglia. The appearance of SNE on CT scans thus reflects the variable and widespread distribution of the disease. The absence of radiologically detectable abnormalities in the basal ganglia should not deter one from the diagnosis of Leigh disease given in the appropriate clinical context.

X-linked hydrocephalus.

Two French-Canadian families with seven cases of hydrocephalus in two generations are presented. The pattern of inheritance is consistent with an X-linked recessive transmission. The clinical and pathologic characteristics of this entity are reviewed. The anomaly of adducted thumbs was present in one patient and its cause is considered. The hypothesis of primary hydrocephalus and secondary compression of the aqueduct as the mechanism for aqueductal stenosis is discussed.

Aphasia and handedness in relation to hemispheric side, age at injury and severity of cerebral lesion during childhood.

The effects of the variables of hemispheric side of lesion, age at injury and severity of cerebral damage on language performance and hand dominance were investigated in groups of hemiparetic children. Severity of cerebral damage was defined by the degree of structural abnormality shown on computed tomography (CT) scans. Tests of auditory verbal comprehension and object naming were used as indicators of productive and receptive language skills. The responses to a series of questions on a handedness inventory provided a rated measure of hand dominance. The results indicated that language deficits characterize the performance of all patient groups with left cerebral injuries. Impairments are more profound, however, in the case of left hemisphere injuries acquired after the age of 5 years. In addition, prenatal and early postnatal left cerebral lesions consistently result in strong sinistrality. It is concluded that the crucial variable underlying the demonstration of language deficits and left hand dominance is not severity of lesion but age at injury and hemispheric side of lesion.