Diffusion-weighted imaging in moyamoya disease.

Moyamoya disease is characterized by progressive intracranial vascular stenoses of the circle of Willis, resulting in successive ischemic events. We report serial diffusion-weighted imaging studies in a case of moyamoya disease. A 4-year-old right-handed patient presented with multiple infarcts in the right and left hemispheres. Each new infarct was unambiguously recognized as bright on diffusion-weighted imaging. Previous infarcts, readily detected on other magnetic resonance imaging sequences, were not bright on diffusion-weighted imaging. The patient subsequently underwent bilateral synangiosis. In this case, the diffusion-weighted images were helpful in assessing the extent of infarcts, determining the age of the lesion, and correlation with new clinical findings. We emphasize the usefulness of diffusion-weighted imaging for following the clinical course of children with moyamoya disease, in whom new focal deficits are highly suspicious of new infarcts.

Moyamoya and Down syndrome. Clinical and radiological features.

BACKGROUND AND PURPOSE: Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the supraclinoid internal carotid artery, with the secondary development of enlarged basal collateral vessels. It may occur as a primary disease or as a syndrome in association with a variety of conditions, and its pathogenesis remains unexplained. There are relatively few reports describing the occurrence of moyamoya in Down syndrome. The aim of this study is to describe the clinical and radiological features of moyamoya syndrome associated with Down syndrome (MM-DS) and to explore theories of moyamoya pathogenesis in these patients. METHODS: Seven children with MM-DS underwent brain imaging, transfemoral angiography, and serial neurological exams. Neurological deficits, poststroke recovery, radiographic infarct characteristics, and angiographic abnormalities were reviewed. RESULTS: The clinical and radiological features of primary moyamoya disease overlap with those of MM-DS. Hemiplegia and aphasia were the most common presentations. Motor recovery was excellent in five of seven cases. Cerebral infarcts were superficial or deep and can occur in a watershed distribution. Angiography demonstrated involvement of the internal carotid artery and its branches bilaterally in all seven cases and the posterior cerebral arteries in four cases. CONCLUSIONS: The clinical and radiological features of MM-DS overlap with primary moyamoya disease. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. Although the neuronal substrate is abnormal in Down syndrome patients, recovery from hemiplegic stroke in patients with MM-DS is comparable to recovery in patients with primary moyamoya.

Vertebral artery dissection: issues in diagnosis and management.

Vertebral artery dissection is an uncommon cause of stroke in children. Accuracy of diagnosis by magnetic resonance angiography (MRA) instead of invasive transfemoral angiography (TFA) has been controversial. The need for anticoagulation and duration of such therapy is also arguable. We report 2 boys with vertebral artery dissection: one, aged 7 years, presented with hemiparesis and seizures and the other, aged 4 years, presented with ataxia. Each boy's initial MRA was not interpreted as delineating occlusive lesions to explain the posterior circulation infarcts visualized on computed tomography and magnetic resonance imaging scans. However, subsequent MRAs were suspicious for vertebral artery dissection, which was confirmed by TFA. Both children were treated with anticoagulation therapy. The first patient continued to manifest evidence of new infarcts despite treatment (initially with aspirin alone, followed by anticoagulation with heparin and warfarin), and is now maintained on a combination of high dose warfarin and aspirin. The second patient is now maintained on aspirin alone after initial anticoagulation for 6 months with heparin followed by warfarin. A high index of suspicion for vertebral artery dissection may allow diagnosis on the basis of MRA alone. Previous reports have indicated good outcomes of vertebral artery dissection in children and adults irrespective of anticoagulation treatment. Our experience suggests that anticoagulation may be beneficial in preventing further strokes caused by the dissection.

Cognitive disorders in children.

Cognitive disorders affect thinking and perceptual processes and the acquisition of knowledge and new information. They have an enormous societal impact because special educational resources are required, and independent living often cannot be achieved. Learning problems may lead to behavioral disorders in the home and community. The pathogenesis of most mild and moderate cognitive disorders is poorly understood. Severe cognitive impairment is usually accompanied by somatic abnormalities, and an etiology can be identified in many cases. Specific treatments are available for disorders such as cogenital hypothyroidism, some metabolic acidurias, and congenital toxoplasmosis. Other disorders affecting cognition such as fetal alcohol syndrome, maternal cocaine and heroin exposure, HIV encephalopathy, and prematurity require aggressive prevention and education to reduce their occurrence. The recent advances in molecular genetics offer a faster and better method of diagnosing fragile X syndrome, now recognized as the most common inheritable cause of mental retardation. In the future, DNA analysis may elucidate the basis of many other cognitive disorders.

Mitochondrial disorder associated with newborn cardiopulmonary arrest.

A female infant who died 2.5 d after birth with hypoglycemia, lactic acidosis, and sudden multisystem failure was studied. Biochemical studies showed complex III and IV deficiency in liver, kidney, and muscle, with muscle most severely affected. Southern blot analysis of the patient's mitochondrial DNA did not reveal any deletions. Denaturing gradient gel analysis, which detects single base changes by differences in melting behavior, showed an extra band that was not seen in mitochondrial DNA from the mother, the mother's identical twin sister, or an unrelated normal subject. This extra band indicated heteroplasmy for a restriction fragment containing the apocytochrome b and transfer RNA(thr) genes. Sequencing revealed an A to G mutation at nucleotide 15923, the last base of the anticodon loop of the transfer RNA(thr) gene. The mutation lengthens the anticodon stem by added pairing and reduces the anticodon loop size from 7 to 5 nucleotides, potentially compromising transfer RNA(thr) function in translation and/or in processing the polycistronic RNA transcript. The patient's mother previously had a male infant who also died at 1.5 d postnatal, and both the mother and her twin have had multiple miscarriages. Amniocentesis for a genetic screen was performed on the mother's twin sister during a recent pregnancy; some of the cultured cells were made available for this study. The mutation was not found in the amniocytes or in umbilical cord blood obtained at birth; the baby was normal at birth and remains healthy. It is concluded that the mutation at nucleotide 15923 was most likely the cause of the fatal disease in the index case.(ABSTRACT TRUNCATED AT 250 WORDS)

Desmoplastic cerebral astrocytomas of infancy: a histopathologic, immunohistochemical, ultrastructural, and molecular genetic study.

The desmoplastic cerebral astrocytoma of infancy (DCAI) is a rare tumor that presents as a large hemispheric mass in infants. Despite an ominous histologic picture that may resemble a sarcoma, the tumor is astrocytic and has a good prognosis. We present two cases of DCAI, with histopathologic, immunohistochemical, ultrastructural, and molecular genetic data, and draw the following conclusions: (1) the diagnosis of DCAI requires a high index of suspicion and immunohistochemical or ultrastructural proof of astrocytic differentiation; (2) the data argue against nosologically equating these tumors with the desmoplastic infantile ganglioglioma, pleomorphic xanthoastrocytoma, or gliofibroma; (3) the components of the extensive tumor basal lamina may be elaborated by the tumor cells themselves and may contribute in an autocrine fashion to the slow growth of these lesions; and (4) if the lack of allelic loss on chromosomes 17p (including the p53 tumor suppressor gene locus) and 10 seen in our cases is found in other cases of DCAI, this may further distinguish the DCAI from other astrocytomas.

The late appearance of hypopigmented maculae in tuberous sclerosis.

Tuberous sclerosis (TS) is a dominantly inherited disorder characterized by seizures, developmental delay, and specific skin lesions. Hypopigmented maculae that occur in 80% of patients with TS have become important for the clinical diagnosis of TS in young children. These lesions are claimed to be present from birth, in contrast with other dermatologic manifestations of TS that usually appear much later. We studied seven children in whom hypopigmented maculae appeared months to years after repeated negative skin examinations. Our findings emphasized that the absence of hypopigmented maculae in young children does not preclude their later appearance nor rule out the diagnosis of TS. The need for repeated skin examinations in infants and children with suspected TS or with seizures and/or mental retardation of unknown cause is apparent.

Acute Kingella kingae endocarditis with recurrent cerebral emboli in a child with mitral prolapse.

An 11-year-old girl had sudden onset of right hemiplegia and dysphasia with fever. Blood cultures grew Kingella kingae. Echocardiography showed a prolapsed mitral valve vegetation, which became larger during a prolonged course of antibiotics. After seven weeks of therapy, when surgery was being planned, the child deteriorated abruptly. A repeat echocardiogram showed that the vegetation had disappeared. Conservative medical management is usually inadequate in treating vegetations associated with bacterial endocarditis; surgery is advised.

Neonatal herpes simplex meningoencephalitis associated with fetal monitor scalp electrodes.

Two full-term unrelated infants developed herpetic lesions at the site of scalp fetal monitor electrodes several days after uncomplicated labor and vaginal delivery. The mothers had been asymptomatic during pregnancy. In addition to the scalp vesicles, one infant had unilateral herpetic conjunctivitis; the other infant had vesicles on the face without ocular involvement. Both babies had cerebrospinal fluid (CSF) pleocytosis and elevated protein. Herpes virus was cultured from the vesicles and CSF. Computed tomography showed low density areas in the frontotemporal regions. On follow-up, seizures persisted and neurologic development was impaired. These patients illustrate the potential risk of infection when internal fetal monitoring is used in low risk pregnancies.

Complex partial status epilepticus in young children.

Complex partial status epilepticus (CPSE) has rarely been described in children. We have recently studied four girls, aged 1 to 4 years, who presented with CPSE. Their seizures were characterized by decreased level of consciousness, lack of response to familiar persons, diminished response to pain, starting, slow visual tracking, eye deviation, picking at nearby objects, and lip smacking. Three patients developed focal clonic activity during their seizures and one progressed to a generalized motor seizure after 4 hours of CPSE. Two patients had ictal electroencephalograms demonstrating temporooccipital polyspikes and slow waves.

A case of adult microcephaly.

A microcephalic woman who walked, spoke a few words, and was capable of some self-care, died at age 20. The brain weighed 260 g--the equivalent of that of an infant of eight months' gestation. The remarkable neuropathological features in our case included very small cerebral hemispheres, normal cerebral cortex, myelinated white matter, and large neuronal heterotopias situated along the ventricular walls and deep in the white matter adjacent to the intact nuclei of the basal ganglia, amygdala, and thalamus. The brainstem and cerebellum were relatively less reduced in size and showed normal structure and no heterotopias. In rats, microcephaly can be induced experimentally by giving carcinogens during sensitive periods of embryogenesis. Here, the microcephaly appears to result from necrosis of the neuroblasts lining the ventricles, and from a concomitant reduction in DNA synthesis. The pathogenesis of the microcephaly in our patient and others remains undefined. Our study shows that a great discrepancy may exist between brain size and level of function.

Computed tomography in Hallervorden-Spatz disease.

Computed tomography (CT) in a 34-year-old woman with Hallervorden-Spatz disease (established on the basis of clinicopathologic findings in a sister, and a typical clinical course) showed severe diffuse cerebral atrophy and ventricular enlargement. Ratios between the intercaudate distance and the width of the frontal horns (FH:CC) or the outer tables of the skull (CC:OTcc) exceeded those found in patients with Huntington disease. CT may be helpful diagnostically in progressive cerebral disorders of late childhood or adolescence.

Neurological outcome in cold water drowning.

It is widely believed that the child who drowns and is in cardiopulmonary arrest on arrival at the emergency room will probably suffer severe neurological sequelae despite resuscitation. In cases of cold water drowning, however, hypothermia (less than 32 degrees C) may confer substantial protection to the CNS if the basic hypoxic state can be readily reversed.

Ophthalmoplegia and Ondine's curse.

Ocular abnormalities and psychomotor difficulties were prominent in two unrelated children; in addition, the older child had respiratory irregularity during sleep. The pathologic findings included lesions of the optic nerve in the case with available material and established the diagnosis of Leigh's subacute necrotizing encephalopathy. This disorder is thought to result from inhibition of a thiamine-dependent enzymatic process and may be modified by greatly increased thiamine intake. Suspicion of the diagnosis in a child with ophthalmoplegia or other ocular abnormalities may lead to earlier recognition and more successful treatment of the disease.

Left-right asymmetries of the temporal speech areas of the human fetus.

Left-right asymmetries of the transverse temporal (Heschl) gyri and the temporal plane become recognizable by 31 weeks' gestation. The transverse temporal gyri are larger in number and extent on the right side in 54% of 207 serially sectioned fetal brains ranging in gestational age from 10 to 44 weeks, and the temporal plane is larger on the left side in those brains. There are two transverse temporal gyri on the left and a single right transverse temporal gyrus on the right in 18% of the brains. No asymmetry of number of transverse temporal gyri or extent of the temporal plane is apparent in 28%. These findings, which confirm those in adult brains, suggest that anatomical asymmetries for left hemispheral speech and language dominance may be established during the last trimester of fetal life.

Melanotic neuroectodermal tumor of infancy: its histological similarities to fetal pineal gland.

Striking similarities between the pineals of 107 fetuses and infants and a pigmented neuroectodermal tumor occurring in the right orbital and right frontal regions in a 6-month-old Puerto Rican boy were found. Both the human fetal pineal and melanotic neuroectodermal tumors of infancy are characterized by pigmented (melanin) epithelial cells, small undifferentiated cells, and a fibrovascular stroma. Our findings suggest the fetal pineal may be a normally occurring precursor of the melanotic neuroectodermal tumor of infancy, or that melanin production may be a normal capability of differentiating neuroepithelial cells.