Pediatric Wegener's granulomatosis complicated by central nervous system vasculitis.

An unusual case of central nervous system vasculitis in pediatric Wegener's granulomatosis, a rare disorder that infrequently presents during childhood, is reported. A 13-year-old girl with Wegener's granulomatosis, whose initial presentation resembled Henoch-Schonlein purpura, developed recurring seizures. MRI of the brain demonstrated multiple areas of increased signal in the occipital, parietal, and frontal lobes, consistent with central nervous system vasculitis. Although both peripheral and cranial neuropathies have been reported in patients with Wegener's granulomatosis, cerebral vasculitis is unusual, particularly in childhood. This case emphasizes the need to consider Wegener's granulomatosis in the differential diagnosis of both unexplained seizures and central nervous system vasculitis in children with systemic illness.

Sturge-Weber syndrome with no leptomeningeal enhancement on MRI.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by a facial nevus flammeus associated with seizures, developmental delay, and, often, with hemiparesis and hemianopia. On MRI, the most characteristic finding has been reported to be leptomeningeal enhancement, believed to represent leakage of contrast medium through the anomalous pial vessels that characterize the disease. We present a case of SWS with no evidence of leptomeningeal enhancement. This case illustrates that leptomeningeal enhancement need not be present in SWS, and the absence of this characteristic finding does not preclude the diagnosis.

Deep gray matter involvement in children with acute disseminated encephalomyelitis.

PURPOSE: To review the frequency, distribution, and extent of deep gray matter disease in children with acute disseminated encephalomyelitis. METHODS: The MR examinations of 10 patients, who were discharged with the clinical diagnosis of acute disseminated encephalomyelitis between 1986 and 1992, were retrospectively reviewed. Locations of abnormal signal in the cerebral and cerebellar cortices, white matter, and deep gray matter nuclei were recorded. Precontrast and postcontrast images were compared, when available, to assess degree of enhancement (if any). RESULTS: Six patients had foci of prolonged T2 relaxation in the deep gray matter, ranging in size from less than 1 cm to 4 cm. The caudate heads were involved in 4 patients, caudate body in 3, globus pallidus in 3, putamina in 3, and thalami in 4. In 1 patient, the thalami were involved nearly symmetrically, with mild mass effect. Asymmetric subcortical white matter involvement was present as well. Prolonged T2 relaxation was present within the cerebral cortex in 4 patients and was associated with subcortical white matter abnormality in 3 and more central white matter disease in 1. Nine of 10 patients demonstrated foci of T2 prolongation in white matter, most commonly involving the subcortical region, corona radiata, and centrum semiovale. Three patients also had periventricular foci. Of the 3 patients receiving gadolinium, one showed no enhancement. Two of the patients showed enhancement of some but not all lesions. One patient, who had normal brain MR findings and symptoms of myelopathy, underwent spine MR which demonstrated focal linear areas of T2 prolongation in the spinal cord at levels C-1 to C-2 and T-6. CONCLUSION: Involvement of deep gray matter was common in our small series. The finding of T2 prolongation in these structures does not preclude the diagnosis of acute disseminated encephalomyelitis in the proper clinical setting. Because thalamic involvement is reported to be rare in multiple sclerosis, it may prove useful in distinguishing between acute disseminated encephalomyelitis and the initial presentation of multiple sclerosis.

Optimized diagnostic strategy for neuroblastoma in opsoclonus-myoclonus.

Infantile myoclonic encephalopathy (opsoclonus-myoclonus or IME) is a rare clinical syndrome associated with occult neuroblastoma in 20%-50% of all cases. IME is the initial presentation of neuroblastoma in 1%-3% of children. Imaging approaches including chest radiography and abdominal computed tomography (CT) have been proposed to detect neuroblastoma in IME. Metaiodobenzylguanidine (MIBG) is highly effective in the detection of neuroblastoma. These scans can identify both soft-tissue and skeletal lesions anywhere in the body. Our purpose was to attempt to determine the best screening method for detection of occult neuroblastoma in patients with IME. Records of all neuroblastoma patients from 1983 to May 1991 were reviewed. Four cases of IME with neuroblastoma were identified in which imaging studies included an MIBG scan. All four patients had positive MIBG scans (100%) while only two had masses on initial CT (50%). In the three patients initially evaluated by traditional methods, the mean time to diagnosis and the mean number of advanced radiologic studies were 7.5 mo and 7.3 studies respectively. The patient screened with MIBG had only cranial and abdominal CT prior to surgery. Although based on a limited number of patients, results suggest that MIBG may prove to be a useful screening procedure in patients with IME. Traditional imaging modalities can then be directed to evaluate sites of disease identified by MIBG scans.

Mitochondrial disorders: analysis of their clinical and imaging characteristics.

PURPOSE: Investigation of the clinical, imaging, and in vivo MR spectroscopy (MRS) characteristics of disorders of mitochondrial function. METHODS: Clinical, imaging (five CT and 20 MR examinations), and MRS (six studies in five patients) findings in 19 patients with mitochondrial disorders were retrospectively reviewed. Results were critically analyzed and, when applicable, compared with results in the literature. RESULTS: Patients included four with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), two with myoclonus, epilepsy, and ragged red fibers (MERRF), two with Kearns-Sayre syndrome, seven with Leigh syndrome, one with progressive cerebral poliodystrophy (Alpers syndrome), and three with trichopoliodystrophy (Menkes disease). MELAS, MERRF, and Kearns-Sayre tended to occur in older children and adults, whereas Leigh syndrome, Alpers syndrome, and Menkes disease occurred in infants and young children. All diseases involved gray matter early in their course, manifest primarily as T2 prolongation, with the deep cerebral nuclei being involved more often than the cerebral cortex. When T2 prolongation was seen in the white matter (MELAS, MERRF, Kearns-Sayre, Leigh), the peripheral and retrotrigonal white matter showed early involvement. Patients with Menkes disease showed rapidly progressive atrophy accompanied by large subdural hematomas. Proton MRS showed an elevated lactate level in involved regions of the brain; the lactate peak disappeared in old areas of T2 prolongation. CONCLUSIONS: Mitochondrial disorders have a wide range of both clinical and imaging findings. Although no one set of findings is diagnostic of these disorders, the combination of deep gray matter involvement and peripheral white matter involvement in young adults or children should suggest the diagnosis, especially when associated with an elevated lactate level on proton MRS.

Optic neuritis in children with poor recovery of vision.

We reviewed the records of 10 children with optic neuritis in whom recovery of vision was poor or incomplete. Our cases were otherwise similar to those described in previous studies in that they were always bilateral, often accompanied by a viral prodrome (seven of 10), and usually associated with disc oedema (seven of 10). Seven of twenty eyes had a final visual acuity of 6/60 or worse and only one patient regained 6/6 vision in either eye. In three patients the best vision in either eye was 6/60 or worse. Recovery of vision was often slow, taking up to six years. Five of 10 patients have developed multiple sclerosis (MS), and one child had acute disseminated encephalomyelitis (ADEM) with optic neuritis. Optic neuritis in children does not always carry a good prognosis for recovery of vision; however, the failure of vision recovery in a short period of time does not necessarily indicate a poor outcome. Some children with optic neuritis develop MS, which can develop even when optic neuritis follows a viral illness.

Current concepts of neurocutaneous disorders.

The neurocutaneous diseases are a loosely bound group of clinical entities that were initially considered to have dysplastic and/or neoplastic changes of the nervous system and skin, though other organ systems are frequently involved. During the last several decades a variety of additional diseases have been included in this disease category despite their not having any known cutaneous abnormality. The major neurocutaneous syndromes are considered in this review.

Brother/sister pairs affected with early-onset, progressive muscular dystrophy: molecular studies reveal etiologic heterogeneity.

An autosomal recessive (AR) form of muscular dystrophy that clinically resembles Duchenne/Becker types exists, but its frequency is unknown. We have studied three unrelated affected brother/sister pairs and their families for deletions and polymorphisms with the entire dystrophin cDNA and other DNA probes from the Xp21 region to test for involvement of the DMD locus. In family 1 a large intragenic deletion was found in the affected male. The affected sister was heterozygous for this deletion, but the mother was not, implying germinal mosaicism. In family 2, no deletion was detected in the affected male. RFLP analysis revealed that the affected male and an unaffected sister shared a complete Xp21 haplotype while the affected sister had inherited a recombinant Xp21 region resulting from a crossover between pERT 87-15 and J-Bir. Only the 5' region of the dystrophin gene was shared with the affected boy. X-inactivation studies using a polymorphism in the 5'-flanking region of the HPRT gene, in conjunction with methylation-sensitive enzymes, revealed random X inactivation in the affected girl's leukocytes. In a muscle biopsy from the affected male, the dystrophin protein was present in normal amount and size. Family 3 was informative for four RFLPs detected with dystrophin cDNA probes which span the entire gene. The affected male was found to share the complete dystrophin RFLP haplotype with his unaffected brother, while his affected sister had inherited the other maternal haplotype. It is concluded that the clinical presentation of early-onset, progressive muscular dystrophy in a male and in his karyotypically normal sister can be caused by mutations at different loci. While in family 1 a deletion in the dystrophin gene is responsible, this gene does not appear to be involved in families 2 and 3.

Use of botulinum toxin to treat blepharospasm in a 16-year-old with a dystonic syndrome.

A 16-year-old boy with generalized dystonia had continuous, severe blepharospasm and facial grimacing. Local intradermal injections of botulinum A toxin greatly reduced the spasms and improved function. No side effects were observed. Local botulinum A toxin injections may be useful in the treatment of eyelid and facial spasms in patients with generalized dystonias.

Ambulatory EEG recordings in epileptic and nonepileptic children.

We examined the cassette-recorded 24-hour ambulatory EEG findings in children who had either clinically definite seizures or episodic behavioral disturbances not regarded as epileptic on clinical grounds. Among 40 epileptic patients, 22 had one or more attacks during the 24-hour recording session. In 15 of these patients all clinical attacks had appropriate ictal electrographic accompaniments; in another 6 some (but not all) attacks did so. Among 55 children with nonepileptic spells clinically, the 24-hour recording was uninterpretable for technical reasons in one, and in 30 it provided no relevant information because there were no recorded clinical or electrographic attacks. In the remaining 24 patients, one or more clinical attacks were captured, and in no instance was there any accompanying electrographic change. Our findings indicate that the absence of ictal EEG changes during attacks cannot be used in isolation to make a diagnosis of pseudoseizures, but support such a diagnosis made on clinical grounds. The more important role of the ambulatory EEG is to exclude a diagnosis of nonepileptic attacks by demonstrating electrographic seizure activity accompanying typical clinical attacks. Whether the technique will have a useful role in the evaluation of patients when the nature of an episodic disturbance of cerebral function is unclear clinically remains to be established, but will require long-term follow-up to validate any conclusions reached by the electrophysiologic technique.

Orbital optic glioma in neurofibromatosis. Magnetic resonance diagnosis of perineural arachnoidal gliomatosis.

In a patient with neurofibromatosis and orbital optic glioma, T2-weighted axial magnetic resonance images showed a fusiform area of high signal intensity with a central linear core of lower signal intensity. Computed tomographic images did not show a corresponding variation in tumor density. Histopathologic examination of the tumor revealed dense, circumferential, perineural glial proliferation. This "arachnoidal gliomatosis" is a feature of orbital optic gliomas in neurofibromatosis and, in our magnetic resonance scans, accurately corresponded with the region of high signal intensity within the tumor.

Neurology residency training programs in the United States.

A survey of 127 neurology residency training programs (124 approved by the Accreditation Council for Graduate Medical Education; 3 by the American Osteopathic Association) in the United States indicated that 80% were sponsored by medical schools. Of the 2,700 MD neurology faculty in 1982, 3/5 were full-time. As of 1982, there were 1,300 neurology trainees, including 334 fourth-year postgraduates (PG4s); 21% were women, and 3% held DO degrees. From 1960 through 1983, about 5,000 PG4s were produced, and for 1984 through 1990 the program directors estimated that this number will be about 3,000; our own projection, however, was only 2,400.

Outcome of brain abscess treatment in children: reduced morbidity with neuroimaging.

Records were reviewed of 17 patients, ages 4 months to 18 years, who had been diagnosed as having brain abscesses between 1975-1984. Serial computed tomography was used to guide treatment; consequently, 8 patients were managed medically and 9 received surgical intervention. All medically treated patients were free of neurologic residua upon subsequent examination. Positive identification of organisms from systemic cultures and close computed tomographic monitoring prevented the need for surgical intervention in these patients. The surgically treated patients were sicker at presentation, and of the 9 patients requiring surgical intervention, 4 had neurologic sequelae and 1 patient died. Brain abscess aspiration or excision revealed organisms in 7 of the 9 surgically treated patients. The reduction in morbidity and mortality was due in part to early recognition and monitoring of abscess size with contrast-enhanced computed tomography and avoidance of surgical excision of the abscess.

MR imaging of intracranial tuberous sclerosis.

The role of MR in evaluating tuberous sclerosis is reviewed in 15 patients. These studies were compared with CT scans, which were available in 14 patients. Four characteristic findings were noted on the MR images obtained. Subependymal nodules projecting into the lateral ventricles were seen in 12 of 15 patients on T1-weighted images. This was the most specific finding. Distortion of the normal cortical architecture was seen in 10 of 11 patients in whom T1-weighted images were obtained using a 256 X 256 matrix. These foci corresponded to multiple cortical areas of increased signal on T2-weighted images. Dilated ventricles were seen in five patients. In one patient, a known astrocytoma showed increased signal on the T2-weighted images, allowing differentiation from a benign subependymal nodule. MR depicted the cortical hamartomas more completely than did CT. The MR scans were abnormal in all cases, and a diagnosis could be confidently made in all 11 cases scanned using a 256 X 256 matrix. Our preliminary experience suggests that MR will at least equal and probably exceed CT, both for sensitivity and specificity, given the use of a 256 X 256 matrix.

Giant axonal neuropathy. A neuropathological study.

Giant axonal neuropathy (GAN) is a disease characterized by a slowly progressive neuropathy and signs of central involvement, manifested by visual impairment, corticospinal tract dysfunction, ataxia, and dementia. Pathological hallmarks of the disease include axonal swellings packed with neurofilaments in both peripheral and central nervous systems, and accumulations of intermediate filaments in Schwann cells, fibroblasts, melanocytes, endothelial, and Langerhans cells. Rosenthal fibers, sometimes appearing in masses and mimicking Alexander's disease, emerge as a conspicuous characteristic in longstanding GAN.

Neurologists in the United States--past, present, and future.

Neurologists in the United States were enumerated for each year from 1935 to 1984 on two bases: board certification (including Child Neurology and Psychiatry and Neurology) and completion of PG4 neurology residency training. The annual incidence of new neurologists was calculated at less than 200 until 1970; then it rose steadily to 380 in 1980, and plateaued thereafter at 385. The estimated number of neurologists present at one time (prevalence) was 1,500 in 1950, 2,400 in 1970, 4,600 in 1980, 8,100 in 1990, and 11,000 in 2000. These numbers for total neurologists will plateau at 12,200 by about 2010, at which time the number of certified neurologists will also plateau at 9,900. Both numbers are notably less than our prior estimate of needs: 16,500 neurologists by 1990, 19,100 in 2010.

Dural sinus thrombosis: study using intermediate field strength MR imaging.

The magnetic resonance (MR) images of six patients with thrombosis of a dural sinus were reviewed. The diagnosis had been verified by computed tomographic scans in three patients and arteriograms in two; in the sixth patient, only MR imaging was used to confirm the clinical syndrome. In all patients, high-intensity signal was seen from the thrombus within the affected dural sinus on all echoes. This persistent signal intensity allowed intravascular clot to be distinguished from normal causes of increased signal such as flow-related enhancement (entry phenomenon) and even-echo rephasing. MR imaging demonstrated the cause of the thrombosis in three patients: two were secondary to adjacent tumors, and one was secondary to unsuspected mastoiditis. Complications such as infarction were also demonstrated. Using MR imaging, one can easily and safely diagnose thrombosis of a dural sinus. MR should be the imaging method of choice in patients suspected of having thrombosis of a dural sinus.

Magnetic resonance imaging in subacute necrotizing encephalomyelopathy (Leigh's disease).

Magnetic resonance imaging (MRI) offers a sensitive alternative to computed tomography (CT) for lesion localization. Patients with subacute necrotizing encephalomyelopathy (SNE) may be diagnosed by finding focal lesions on CT that correspond to sites of anatomical involvement. We report serial CT and MRI scanning findings in a patient with clinical, radiographic, and laboratory evidence of SNE. MRI was more sensitive in detecting lesions involving the basal ganglia, brainstem, and cortex. We believe MRI is a valuable and sensitive means to establish an antemortem diagnosis of SNE.

On national needs for neurologists in the United States.

Estimates of the number of neurologists needed in the United States have been widely divergent. For direct patient care needs alone in a US population of 243.5 million, the Joint Commission on Neurology (ANA-AAN) estimate was 14,000 neurologist, the Delphi Panel median (Battelle/GMENAC) 11,200, and the Advisory Panel (Battelle/GMENAC) 6,200; our review suggests a need for 12,600. Total needs for clinical neurologists including faculty were 8,400 (Advisory Panel), 14,500 (Delphi Panel), and 16,500 (ours) for respective rates of 3.44, 5.96, and 6.76 neurologists per 100,000 population.