Intracranial fibromuscular dysplasia in a six-year-old child: a rare cause of childhood stroke.

Intracranial fibromuscular dysplasia is a nonatheromatous angiopathy that most commonly affects adult women and is rarely recognized in children. Symptoms include stroke and headache, although the vasculopathy may be asymptomatic. Diagnosis is based on angiographic appearance, commonly described as a "string of beads." The etiology of intracranial fibromuscular dysplasia is not known, although possible causes include genetic predisposition, trauma, and underlying connective tissue disease. Treatment of intracranial fibromuscular dysplasia is largely supportive once symptoms become manifest. We report a 6-year-old girl who presented to our center for further evaluation of a large left middle cerebral artery distribution infarction. The patient was previously healthy, without known risk factors for stroke. Initial symptoms consisted of a dense global aphasia and a right hemiparesis. On arrival, the patient's aphasia had improved but she continued to have significant deficits in both receptive and expressive language as well as residual right hemiparesis. Magnetic resonance imaging and conventional angiographic studies demonstrated characteristic beading of the distal portion of the left internal carotid artery, as well as the proximal middle cerebral artery. Laboratory evaluation, echocardiogram, and renal ultrasound were normal. The renal vasculature did not demonstrate evidence of intracranial fibromuscular dysplasia. In conclusion, intracranial fibromuscular dysplasia should be considered in the differential diagnosis of childhood stroke. When recognized, other sites of vascular involvement should be sought, and consideration of underlying disorders is important, as connective tissue disorders have been associated with a propensity to develop this vascular abnormality. Careful follow-up is warranted, due to possible progression of disease.

Utility of early single photon emission computed tomography (SPECT) in neonatal gelastic epilepsy associated with hypothalamic hamartoma.

Gelastic epilepsy, or laughing seizures, is a rare seizure manifestation often associated with hypothalamic hamartoma. This seizure type is well described in older children and adults, but has only rarely been reported in neonates, oftentimes recognized in retrospect when the children are older. We report a child diagnosed at 3 months of age with a large hypothalamic mass after evaluation for spells occurring since birth. The spells were characterized by bursts of hyperpnea, followed by repeated "cooing" respirations, giggling, and smiling. These spells were recognized soon after birth in the delivery room, and occurred at 15-20 minute intervals. They did not interrupt feeding and occurred during sleep. On referral to our center, the patient was noted to be thriving, with normal medical and neurologic examinations except for his spells. The laboratory evaluation was normal, as were endocrine and ophthalmologic evaluations. Neuroimaging was performed, with magnetic resonance imaging demonstrating a large 2.8-cm isodense, nonenhancing hypothalamic mass. Electroencephalogram was abnormal, demonstrating bi-frontal sharp and spike-wave discharges. Video-EEG did not demonstrate ictal discharges associated with the patient's spells. Single photon emission computed tomography (SPECT) demonstrated dramatic ictal uptake in the area of the tumor, with normalization during the interictal phase. Partial excision of hamartomatous tissue has minimally improved the spells. In conclusion, this patient manifested an unusual, early presentation of a rare seizure type. SPECT scanning confirmed the intrinsic epileptogenesis of the hamartoma, further justifying a surgical approach to such patients. Early surgical intervention is probably indicated in an attempt to minimize or prevent the cognitive and behavioral sequelae commonly seen with this seizure type.

Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin.

An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc.

Digital chest radiography: effect of temporal subtraction images on detection accuracy.

PURPOSE: To improve early detection of disease in chest radiographs, the authors developed a digital processing technique that geometrically warps and subtracts a previous radiograph from a current radiograph to produce a temporal subtraction image. An observer test was performed to evaluate the effects of the temporal subtraction image technique on detection of interval change. MATERIALS AND METHODS: Fifty pairs of chest radiographs, including a baseline examination and a subsequent radiograph, were selected (25 cases in which potentially important new abnormalities had developed, and 25 in which there was no interval change). The baseline examination was chosen from multiple prior radiographs to minimize initial misregistration. By means of receiver operating characteristic (ROC) analysis, the ability of 11 observers to detect pathologic change when viewing the paired digitized baseline and subsequent radiographs was compared with their ability when viewing the same paired radiographs together with temporal subtraction images. Positive cases demonstrated focal new abnormalities that were greater than 1 cm in diameter. RESULTS: The mean area (Az) under the ROC curves increased from 0.89 without to 0.98 with the temporal subtraction images. When the paired digitized previous and current chest radiographs were viewed in conjunction with the temporal subtraction images, a significant improvement in detection of new abnormalities was achieved (P = .00004), whereas the mean interpretation time was reduced by 19.3% (from 52 to 42 seconds, including the time to record the score and to move to the next case) (P = .0019). CONCLUSION: The temporal subtraction technique can significantly improve sensitivity and specificity for detection of interval change in chest radiographs.

Early diagnosis of spinal cord arteriovenous malformation in a 7-year-old child.

Spinal cord arteriovenous malformations (AVMs) are relatively uncommon in the pediatric age group. Early diagnosis is rarely made and the resulting complications arising from the AVM may have devastating long-lasting neurologic sequelae. Early diagnosis requires a high degree of clinical suspicion. We report the case of spinal cord AVM in a child who presented with two episodes of "neck stiffness" without headache in whom the prompt diagnosis and treatment prevented neurologic sequelae.

Glutamate receptors in the substantia nigra of Parkinson's disease brains.

Glutamic acid and its analogs are excitotoxins that might contribute to the pathogenesis of Parkinson's disease (PD). We measured four subtypes of glutamate binding sites autoradiographically in 20-microns sections from control and PD midbrains. N-Methyl-D-aspartate (NMDA) binding sites (eight control, eight PD) were very low in control (20 +/- 7 [SEM] fmol/mg protein) and were reduced in the PD pars compacta (2.6 +/- 1.1 fmol/mg protein; p less than 0.02). NMDA binding was also reduced in the red nucleus but not in periaqueductal gray (PAG). We measured alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), metabotropic, and non-NMDA, nonkainate, non-quisqualate (NNKQ) sites in 10 PD and 12 control midbrains. AMPA binding sites were reduced from 175 +/- 20 to 99 +/- 16 (p less than 0.05) fmol/mg protein in PD pars compacta, NNKQ sites from 86 +/- 10 to 50 +/- 12 (p less than 0.05) fmol/mg protein in total nigra, and metabotropic sites (15 +/- 5 fmol/mg protein) were unchanged. AMPA, metabotropic, and NNKQ binding were unchanged in red nucleus and PAG. The very low number of NMDA binding sites suggests that factors other than excitotoxicity mediated via NMDA receptors on nigral cell bodies play roles in the pathogenesis of PD. There may be a generalized loss of NMDA receptors in PD brains. AMPA and NNKQ binding sites appear to be located on dopamine neurons, although the role of NNKQ sites in normal nervous system function and human disease is unknown.