Lissencephaly: fetal pattern of glucose metabolism on positron emission tomography?

BACKGROUND: In classical lissencephaly, the cerebral cortex is four-layered, containing neurons that have failed to complete their migration between 12 and 16 weeks of gestation. METHODS: The authors studied the functional activity of lissencephalic cortex using 2-deoxy-2[(18)F]fluoro-D-glucose PET (FDG PET) in eight patients (six girls and two boys, mean age 7.5 years) with isolated lissencephaly sequence. RESULTS: The PET scans revealed a remarkably similar and bilaterally symmetric pattern of glucose metabolism in all eight patients. The cerebral cortex of lissencephaly showed two layers that could be differentiated based on metabolic activity. The inner layer, which probably corresponds to the inner cellular layer of lissencephalic cortex, showed 8 to 63% higher glucose utilization rate than the outer layer, which probably represents a composite of the molecular, outer cellular, and cell-sparse layers. Patients with a higher metabolic ratio between the cortical layers (inner/outer) showed greater delay in communication (p = 0.007) and socialization (p = 0.03). CONCLUSIONS: These findings are consistent with [(14)C]-2-deoxyglucose autoradiography studies in fetal sheep that have shown that before the development of significant numbers of axons, dendrites, and synapses, glucose metabolism appears to be highest in regions with the highest density of cell bodies, compared to the more mature state when glucose metabolism is highest in areas of greatest dendritic arborization. FDG PET studies of classical lissencephaly provide a different perspective in the analysis of brain gyral anomalies than those with traditional neuroanatomic imaging techniques.

Three malformation complexes related to neural crest development.

We present an individual with three distinct malformation complexes, DiGeorge syndrome, CHARGE association and Dandy-Walker malformation. An extensive literature review has shown that DiGeorge syndrome and CHARGE association rarely occur simultaneously. The presence of both these malformation complexes with Dandy-Walker malformation has not been previously reported. These three malformation complexes may all be related by neural crest maldevelopment.

Diffuse infiltrating astrocytoma of the cervicomedullary region: clinicopathologic entity.

Recent imaging and neurosurgical techniques have led to an improvement in the surgical management of children with brainstem tumors (BSTs). Many children with tumors previously considered 'inoperable' can now benefit from surgery. Increased experience has brought about new theories concerning the growth pattern, natural history, classification and optimal management of these tumors. Cervicomedullary (CM) tumors commonly have an indolent presentation reflecting either medullary or cervical spinal cord dysfunction and tend to arise in the upper cervical cord growing into the medulla in a posterior exophytic fashion. Intrinsic BSTs often present acutely with cranial nerve dysfunction and generally arise in the pons with a diffuse infiltrating growth pattern. A 21-month-old patient had developed feeding difficulty and reactive airway disease at approximately 8 months of age. MRI showed a diffuse, nonenhancing tumor in the CM region. Following radical resection, and an unremarkable perioperative course, he aspirated, developed pulmonary insufficiency and expired. Postmortem examination revealed a low-grade diffuse fibrillary astrocytoma extending from C6 to the medulla. The medullary portion arose in a paramedian location and infiltrated dorsally into the fourth ventricle, the obex, the leptomeninges, and the adjacent cerebellum. This case demonstrates the growth pattern of a distinct subset of CM tumors that behave in a manner similar to intrinsic diffuse BST. Future identification of these subsets by a careful analysis of the clinical presentation and MRI images will enable better operative planning and optimal management.

Neonatal diagnosis of Schwartz-Jampel syndrome with dramatic response to carbamazepine.

We report a female infant, born at 30 weeks of gestation, who exhibited generalized myotonia, facial dysmorphism, blepharophimosis, and short stature at birth. These clinical findings, along with abnormal electromyogram and muscle biopsy, are consistent with Schwartz-Jampel syndrome. Our patient, diagnosed at 4 weeks of life, lacks the major skeletal anomalies, such as pectus carinatum, congenital hip dysplasia, and bowing of the long bones usually associated with this syndrome. Treatment with carbamazepine, initiated at age 7 months (corrected age of 5 months) has produced marked and continued resolution of myotonia, lessened malformation of her bell-shaped chest, and developmental progress. We suggest that the relaxation of myotonia due to early diagnosis and treatment may prevent development of the classic skeletal dysplasia of Schwartz-Jampel syndrome.

Delayed myelination in infants and young children: radiographic and clinical correlates.

Magnetic resonance imaging (MRI) is the best method for assessing myelination in infants and young children. Although delayed myelination is a common neuroradiologic diagnosis, there are few or no data regarding the reliability of this diagnosis or radiographic and clinical findings in cohorts of such patients. We evaluated the cranial MRI scans of 109 patients from age 0 to 36 months, without knowledge of any patient's age or previous clinical or radiologic diagnosis. For each cranial MRI, seven neuroradiologic landmarks were evaluated and established criteria used to assess the state of myelination. We found that in 12 of 109 patients, delayed myelination was misdiagnosed, whereas the diagnosis of delayed myelination was missed in four other patients. Lack of familiarity with the myelination milestones of infancy was the most common reason for a misdiagnosis of delayed myelination. Failure to recognize delayed myelination was due to a failure to appreciate the forceps minor as a landmark. Overall, the diagnosis of delayed myelination was inaccurately applied or missed in 15% of the patients in this series. Of the 14 patients identified as having delayed myelination, 10 had other central nervous system structural abnormalities seen on MRI, most commonly cortical atrophy. Developmental delay was the most common clinical correlate of delayed myelination and was documented in 12 of the 14 patients. To increase the reliability of neuroradiologic assessments in young children, we propose that central nervous system myelin maturation be evaluated and expressed as a myelination age equivalent, analogous to the assessment of pediatric bone age using conventional radiographs.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic hamartoma and the Pallister-Hall syndrome.

The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic 'hamartoblastoma' syndrome in 1980. Cardinal manifestations of the syndrome consist of a hypothalamic hamartoma and extracranial abnormalities, initially thought to be fatal in the perinatal period. The original pathologic description of these hypothalamic lesions were from infants who died in the perinatal period and revealed small cells of variable density which resembled primitive undifferentiated germinal cells and appeared to invade the hypothalamic nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been removed from older infants and children with this syndrome and reveal a more mature histologic appearance typical of a hypothalamic hamartoma. We present 2 new cases of PHS who underwent surgery and demonstrate the maturational nature of the hypothalamic lesion and the phenotypic variability of the syndrome.

Focal tectal tumors: management and prognosis.

A 7-year review at our institution identified 12 children with midbrain tectal tumors. All presented with signs of increased intracranial pressure, had hydrocephalus on initial imaging, and were treated with ventriculoperitoneal (VP) shunts. Three had clinical and radiographic progression of disease. Two were treated with radiation and chemotherapy, with progression of disease in one. The third received radiation alone. All patients are alive, with a median follow-up of over 4 years. Median progression-free survival is at least 24 months and median total survival is beyond 50 months. The tectal glioma syndrome is a relatively benign variant of the brainstem glioma. The majority of patients may be managed with a VP shunt alone.

Neonatal seizures.

Seizures are a frequent symptom seen in intensive care nurseries and may be the only sign of a central nervous system disorder in the neonate. The clinical manifestations of neonatal seizures are widely variable and may be indicative of alternate pathophysiology. The advent of portable video electroencephalographic monitoring has improved the ability to correlate clinical behaviors with electrocortical activity and may facilitate diagnosis. The ability to accurately recognize seizures and determine their cause is crucial to providing treatment.