Journal of Child Neurology

This review article presents a summary of the current state-of-the-art of functional brain imaging, with a primary focus on childhood neuropsychiatric disorders. Coverage is emphasized for developments that appear to be of current or potential future importance for the child neurologist and related pediatric specialist, and also from the perspective of the developmental neuroscientist. Emphasis is placed on the modalities of single photon emission computed tomography (SPECT), positron emission tomography (PET), and both "conventional" and "functional" magnetic resonance imaging, (MRI) including reference to the major new radiopharmaceutical and magnetic resonance-based imaging agents and techniques. The fundamental physicochemical processes underlying such studies are outlined, with citation of sources of more detailed information for the interested reader. A variety of imaging studies are reviewed for selected groups of childhood neuropsychiatric disorders, designed to illustrate the achievements and future promise of these imaging modalities. Areas of concentration are suggested for future imaging research in the field of childhood behavioral disorders, where these methods seem critical to improved understanding of pathogenetic mechansisms, as well as development of more effective treatment strategies. (J Child Neurol 1999; 14:207-221).

Metachromatic leukodystrophy refers to a group of genetic neurologic diseases caused by deficiencies of the enzyme arylsulfatase A and the resulting accumulation of sulfatides in white matter. Bone marrow transplantation has been advocated as a treatment in an attempt to correct the enzyme deficiency. Such a transplant was performed in 1991 in a 16-year-old girl with a form of late juvenile metachromatic leukodystrophy caused by a homozygous P426L mutation in the arylsulfatase A gene. Engraftment was prompt and resulted in constant enzymatic normalization of circulating lymphocytes. The elevated urinary excretion of sulfatides remained unaffected. Clinical findings up until transplantation consisted of gait disturbances, impairment of cognitive functioning, and deterioration in school performance over several years. During a 6-year follow-up period, the patient's condition was subject to major fluctuations but, on the whole, findings showed slow neurologic and neurophysiologic deterioration. The clinical course observed after bone marrow transplantation probably more or less reflects the natural course expected in this form of late-onset metachromatic leukodystrophy. (J Child Neurol 1999; 14:222-228).

In this pilot study we investigated the hypothesis that intrinsic and extrinsic brainstem lesions situated within the pontomedullary region would effect the integrity of respiratory sinus arrhythmia. The study sample consisted of three patients with anatomic brainstem abnormalities associated with isolated Chiari I malformation, Chiari II malformation with syringobulbia, and achondroplasia with cervicomedullary compression. They were compared to an age- and sex-matched control group of nine patients. Each subject's electrocardiogram was recorded in a quiet room and digitized by a personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heartrate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. Analysis revealed a significant reduction in respiratory sinus arrhythmia (P < .05), defined as the summated area under the curve, with a mean for controls of 35.42 ± 28.13 SD and for subjects of 17.20 ± 11.50 SD. There was a gradient of abnormality noted, with the mildest deviation in respiratory sinus arrhythmia for the patient with isolated Chiari I malformation and maximum deviation seen in the patient with extrinsic cervicomedullary compression. (J Child Neurol 1999; 14:229-232).

Fibromuscular dysplasia of the carotid artery is uncommon, but not rare. Although the true incidence and prevalence of the disease are not known, reported figures in adults range between 0.6% by angiography and 1.1% at autopsy. Most case reports of stroke caused by carotid fibromuscular dysplasia describe findings in adult subjects, although there are a few reports of the disease in children. In the present case, we describe a 16-year-old boy with fibromuscular dysplasia confined to one internal carotid artery and its branches, and in whom the disease declared itself by stroke. This case serves as a basis for considering diagnostic methods, treatment options, and future research in pediatric patients with cerebrovascular disease caused by fibromuscular dysplasia. (J Child Neurol 1999;14:233-238).

Subclinical or nonconvulsive status epilepticus may cause severe postmorbid neurologic dysfunction. It is, therefore, critical to rapidly identify and treat these cases. The recent availability of injectable valproic acid (Depacon) provides an additional method for treatment of status epilepticus, although studies concerning its effectiveness are not widely available in the literature. We report four cases (three pediatric, one adult) of patients who presented to us in status epilepticus. All had previously failed more than one other common method of treatment for this condition. Treatment with injectable valproic acid resulted in the elimination of all clinical indications of status epilepticus as well as a return to the baseline EEG condition in all four cases. Seizure types included focal, multifocal, and generalized spike and wave forms, suggesting potential benefit from injectable valproic acid treatment in a wide range of status epilepticus patients. We present these cases for review. (J Child Neurol 1999; 14:239-242).

In unselected adult patients with brain damage, the Judgment of Line Orientation Test and the Facial Recognition Test are considered valid instruments for detecting right cerebral hemisphere lesions. It is unknown, however, whether this applies to children as well. Performance levels on the Judgment of Line Orientation Test and the Facial Recognition Test of 18 children with acquired left cerebral lesions and 14 children with acquired right cerebral lesions were reviewed. Subjects were unselected for age, sex, or etiology. Age-related norms were obtained in 81 normal controls, aged 7 to 14 years. Judgment of Line Orientation Test and Facial Recognition Test performance levels did not predict the presence of cerebral pathology per se in our unselected groups with demonstrated unilateral cerebral lesions, nor did they contribute to the prediction of the side of the lesion within the two groups with cerebral lesions. These results cast serious doubt on an important aspect of the clinical utility of both tests in children, namely their discriminative validity in the assessment of etiologically unselected populations with brain damage. (J Child Neurol 1999;14:243-248).

Acute necrotizing encephalopathy is a novel disease entity, proposed by Mizuguchi et al in 1995, that shows a characteristic selective and symmetric involvement of the thalamus, brain stem, and cerebellum. It usually leaves sequelae. The etiology of acute necrotizing encephalopathy is unknown. We describe here six patients aged 6 months to 5 years (four boys and two girls). Four cases were typical, and the patients' cranial computed tomographic scans and magnetic resonance imaging showed irreversible symmetric involvement of the thalamus, brain stem, and cerebellum. Three of the patients died, and one was left with severe sequelae. In the other two patients, who had selective reversible thalamic involvement, the disease was mild; one also showed transient unilateral thalamic involvement. These patients recovered completely. We consider the illness in these two patients to fit the criteria of the mild form of acute necrotizing encephalopa thy. We believe that acute necrotizing encephalopathy has some clinical diversity, as is seen in other neurologic disorders, and that a mild form could exist. (J Child Neurol 1999;14:249-255).

The past 3 decades have witnessed impressive progress in our understanding of inherited neurometabolic diseases, promoted by the rapid development and application of molecular genetic strategies. Such progress has required the juxtaposition of clinical evaluations and basic science techniques. The central role of careful and complete assessment of affected children cannot be overemphasized and in no way has been diminished by technologic advances. Indeed, enhanced clinical and laboratory evaluations have led to important conceptual advances. Molecular genetics has elucidated those disorders with known metabolic defects through functional cloning and explained the variability of disease expression based on specific mutational events. Alternatively, positional cloning has identified molecular defects for those disorders with clear phenotypic patterns, but lacking a defined metabolic abnormality. Regarding heterogeneous expression, disorders with clearly different phenotypes can arise from different mutations within the same gene. The multiple variants of β-hexosaminidase deficiency (Tay-Sachs disease) are, arguably, the best examples. Conversely, disorders with similar phenotypes are explainable by quite different mutational events. In addition, the identification of specific diseases exhibiting both biochemical abnormalities and disturbed organogenesis has blurred conventional dogma regarding separation of genetic disorders into strict metabolic and structural categories. Disorders of peroxisomal function and the neuronal ceroid lipofuscinoses are prototypes for the points noted above and raise important issues regarding our approaches to children with these disorders. These issues include a high index of suspicion for an inherited neurometabolic disease and an open mind to possible interrelations with other known and seemingly dissimilar conditions. (J Child Neurol 1999;14:256-262).

Human amniotic epithelial cells express makers of glial and neural stem cells. These cells also synthesize and release acetylcholine and catecholamines. This study of amniotic fluid demonstrated that acetylcholine and catecholamines can be readily identified in the fluid. Norepinephrine was the major catecholamine present, although dopamine and DOPAC could also be detected. The physiologic role of these amniotic fluid neurotransmitters in fetal-placental interactions and nervous system development is currently under investigation. (J ChiLd NeuroL 1999;14:265-266).

We report a 10-year-old girl with Marin-Amat syndrome, a rare facial synkinesis sometimes referred to as the inverted Marcus Gunn phenomenon. Symptoms were apparent 6 months following unilateral peripheral facial nerve palsy Her facial synkinesis failed to improve, despite improvement in her facial palsy consistent with an aberrant regeneration of the facial nerve. The clinical features of the reported cases of Marin-Amat syndrome are briefly reviewed. To our knowledge, this is the first documented report of Marin-Amat syndrome in a child. ( J Child Neurol 1999; 14:266-267).

A 10-year-old boy with congenital human immunodeficiency virus (HIV) infection developed recurrent episodes of left hemiparesis at age 7 years. The progression of his disease was followed by computed tomography, magnetic resonance imaging, magnetic resonance angiography, and cerebral angiography. The series of images showed progressive stenosis of both carotid arteries at the suprasellar origin with involvement of his anterior and middle cerebral arteries, while prominent collateral vessels developed from his external carotid supply through ophthalmic and middle meningeal arteries. The pattern of cerebrovascular disease is consistent with moyamoya syndrome. We suggest that further studies on the pathophysiology of cerebrovascular disease in patients with HIV could be helpful in understanding the cause of moyamoya disease as well. Also, with the various advances in treatment of HIV, neurovascular complications could be seen more frequently as the long-term survival in these patients improves. (J Child Neurol 1999; 14:268-270).