Characteristic Cochlear Hypoplasia in Patients with Walker-Warburg Syndrome: A Radiologic Study of the Inner Ear in α-Dystroglycan-Related Muscular Disorders.

BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan-related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α-dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia.

Diffusion-weighted imaging of the cerebellum in the fetus with Chiari II malformation.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging can be used to characterize brain maturation. MR imaging of the fetus is used in cases of suspected Chiari II malformation when further evaluation of the posterior fossa is required. We sought to investigate whether there were any quantitative ADC abnormalities of the cerebellum in fetuses with this malformation. MATERIALS AND METHODS: Measurements from ROIs acquired in each cerebellar hemisphere and the pons were obtained from calculated ADC maps performed on our Avanto 1.5T imaging system. Values in groups of patients with Chiari II malformations were compared with those from fetuses with structurally normal brains, allowing for the dependent variable of GA by using linear regression analysis. RESULTS: There were 8 fetuses with Chiari II malformations and 23 healthy fetuses, ranging from 20 to 31 GW. There was a significant linear decline in the cerebellar ADC values with advancing gestation in our healthy fetus group, as expected. The ADC values of the cerebellum of fetuses with Chiari II malformation were higher [1820 (±100) × 10⁻6 mm²/s] than ADC values in the healthy fetuses (1370 ± 70) × 10⁻6 mm²/s. This was statistically significant, even when allowing for the dependent variable of GA (P = .0126). There was no significant difference between the pons ADC values in these groups (P = .645). CONCLUSIONS: While abnormal white matter organization or early cerebellar degeneration could potentially contribute to our findings, the most plausible explanation pertains to abnormalities of CSF drainage in the posterior fossa, with increased extracellular water possibly accounting for this phenomenon.

Cyclosporine A neurotoxicity in a patient with idiopathic renal magnesium wasting.

We report a female child who had idiopathic renal magnesium wasting secondary to suspected Gitleman syndrome and cyclosporine A neurotoxicity after a heart transplant. The child had acute, progressive encephalopathy, intractable seizures, quadriparesis, and extensive, bilateral cortical involvement on neuroimaging. Two days after discontinuation of the cyclosporine, the child's condition improved dramatically, including an improved level of consciousness, and she became seizure free. By 6 weeks, she was fully ambulatory. Follow-up magnetic resonance imaging and electroencephalograms demonstrated significant improvement. This patient had drug-induced neurotoxicity, exacerbated by hypomagnesemia. Cyclosporine should be used cautiously in transplant patients with Gitelman syndrome or other acquired magnesium homeostasis disorders because of the possible increased risk of neurotoxicity. This report is the first case of a patient with both cyclosporine neurotoxicity and magnesium-wasting nephropathy.

Disorders of cortical formation: radiologic-pathologic correlation.

The advent of newer imaging techniques, such as high resolution MR imaging and surface reconstructions of 3-dimensional data sets, has led to a greater in-vivo understanding of cortical malformations of the brain. The disorders of cortical formation are illustrated with routine imaging, surface reconstruction, and pathologic specimens.

Schimke immunoosseous dysplasia complicated by moyamoya phenomenon.

Schimke immunoosseous dysplasia (SID) is an autosomal recessive spondyloepiphyseal dysplasia that was first described by Schimke et al. [1971: Lancet 2:1088-1089]. It is associated with premature arteriosclerosis and cerebral ischemia; however, the cerebral vascular abnormalities causing ischemia have not been described [Spranger et al., 1991: J Pediatr 119:64-72; Ehrich et al., 1995: Clin Nephrol 43:89-95]. Based on magnetic resonance angiography (MRA) and magnetic resonance venography (MRV), we now report on 2 girls with SID who have cerebral ischemia associated with moyamoya phenomenon. In addition, one patient also has an absent or occluded left transverse sinus and diffuse aortic narrowing. This is the first characterization of the cerebral vascular abnormality found in SID and raises the possibility that cerebral moyamoya may represent another major manifestation of the underlying genetic defect in SID.

MRI findings in macrocephaly-cutis marmorata telangiectatica congenita.

We describe a child with macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC), cherry red macules, megalencephaly with hemifacial and segmental overgrowth, macrosomia, and cutis marmorata telangiectasia congenita of the trunk, and visceral and subcutaneous cavernous hemangiomas. The megalencephaly is accompanied by MRI findings of CNS dysgenesis with protrusion of the cerebellar tonsils through the foramen magnum (Chiari I), lumbar syrinx, and hydrops of the optic nerves. The report of this additional patient further confirms the newly described macrocephaly-cutis marmorata telangiectatica congenita as a distinct clinical phenotype.

Central nervous system malformations in ethylmalonic encephalopathy.

Central nervous system malformations have been reported in a number of inherited enzyme defects. Ethylmalonic encephalopathy, an organic aciduria of unknown pathogenesis, has not been reported previously in association with brain or spinal cord malformations. We report on 2 sibs with confirmed ethylmalonic encephalopathy and malformations of the central nervous system; one with tethered cord, the other with cerebellar tonsillar ectopia (Chiari I malformation).

Immunoablation does not delay the neurologic progression of X-linked adrenoleukodystrophy.

We report the results of a near total myeloablation in preparation for bone marrow transplantation in a boy with minimal symptoms of X-linked adrenoleukodystrophy. Severe cerebral X-linked adrenoleukodystrophy developed in the patient after failure of bone marrow transplantation. This experience suggests that immunotherapy alone is not responsible for the improvement observed in some patients with X-ALD after BMT.

Recurrent seizures in metachromatic leukodystrophy.

The unusual presentation of juvenile onset metachromatic leukodystrophy (MLD) and frequent complex partial seizures in a patient led us to perform a retrospective study of 18 patients with MLD to identify the prevalence and type of recurrent seizures during the first 2 years of the disease. Five of 17 patients (29%) had developed recurrent seizures within 12 months of the onset of symptoms, and one patient was lost to follow-up. By 24 months after onset of symptoms, 5 patients were lost to follow-up, and 6 of the remaining 13 patients (46%) had developed recurrent seizures. In all, 7 patients, 4 with late infantile-onset and 3 with juvenile-onset disease, developed recurrent seizures. Four patients, including 3 with juvenile-onset disease had complex partial seizures. We conclude that recurrent seizures are common in MLD and may occur at any stage of the disease, particularly in patients with juvenile onset. Generalized seizures are more frequent in patients with late infantile-onset, whereas partial seizures are more common in those with juvenile-onset disease.

Long-term survival of an infant with 'anaplastic' astrocytoma.

Anaplastic astrocytomas are intermediate in differentiation between astrocytoma and glioblastoma multiforme. Survival with anaplastic astrocytoma is favorably affected by extensive anaplasia, maximal resection and presentation in early life. We report a 2-month-old infant who had a tumor of astrocytic lineage with anaplastic features of necrosis, nuclear atypia and mitotic activity. Following subtotal resection the child is alive but has a radiologically visible tumor.

Spinal subdural enhancement after suboccipital craniectomy.

PURPOSE: To characterize transient intraspinal subdural enhancement (potentially mimicking the subarachnoid spread of tumor) seen on MR images in some children after suboccipital craniectomy for posterior fossa tumor resection. METHODS: Radiologic and medical records of 10 consecutive children who had MR imaging for spinal staging after resection of posterior fossa tumor during a 9-month period were reviewed retrospectively. In addition, one case with similar findings of intraspinal enhancement on spinal staging MR images obtained at another institution was included in the review. RESULTS: Intraspinal enhancement thought to be subdural was seen in four of 10 patients undergoing spinal staging MR imaging 6 to 12 days after surgery. In these four patients, MR studies 50 to 18 days later, without intervening treatment, showed resolution of the abnormal enhancement. A fifth patient (from another institution) with similar intraspinal enhancement underwent CT myelography 4 days later, which showed no subarachnoid lesions. No metastases have developed in any of these five patients during the 2.5- to 3.5-year follow-up period. conclusions: From analysis of the MR appearance and on the basis of prior myelographic experience, we suggest an extraarachnoid, probably subdural, location of this enhancement. Awareness of this phenomenon will reduce the rate of false-positive diagnoses of metastatic disease. Preoperative spinal staging should be considered for patients undergoing suboccipital craniectomy.

Neuroradiology of pediatric posterior fossa medulloblastoma.

Medulloblastoma of the cerebellum is a common intracranial neoplasm in children and presents many faces in medical imaging. Characteristic or classic features, such as increased attenuation on unenhanced CT, midline location and well defined margins, are commonly present in childhood cases of posterior foassa medulloblastoma, although atypical imaging features are being noted more frequently with the increased dependence on MR as the diagnostic modality of choice. Carefully performed CT and MR both initially provide suitable geography and characteristics, but MR is superior in the detection of pre- or post-operative neoplastic spread elsewhere in the subarachnoid space. Accurate establishment of disease extent is essential in planning both surgical resection and adjuvant therapy.

Evolution of the neuroimaging changes in fucosidosis type II.

We report on clinical and neuroradiological findings in two patients with fucosidosis type II; a 7-year-old Jordanian boy and a 3 1/2-year-old Anglo-Canadian girl. This rare, autosomal recessive disorder is caused by deficiency of lysosomal alpha-fucosidase and is manifested clinically by progressive mental and motor deterioration, coarse facies, growth retardation, recurrent infections, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly and seizures. Cranial CT and magnetic resonance imaging showed density and signal abnormalities in the thalamus, globus pallidus and internal capsules bilaterally, as well as progressive CT density alterations in supratentorial white matter including the internal medullary laminae of the thalami and the internal capsules.

Neurologic manifestations of pediatric systemic lupus erythematosus.

Central nervous system involvement is a common but rarely reviewed feature of pediatric systemic lupus erythematosus (SLE). We retrospectively reviewed the charts of 91 patients with pediatric SLE and using a standardized data abstraction form documented 40 patients with central nervous system (CNS-SLE) involvement. The mean age of onset of SLE was 13.3 years. In 19 patients the CNS manifestation was a presenting symptom, in 12 patients CNS involvement was present within the first year of diagnosis, and in 9 patients it took up to 7 years for CNS disease to become evident. Nineteen children (48%) manifested neuropsychiatric SLE, which included depression, concentration or memory problems, and frank psychosis. Seizures were present in 8 patients (20%), 6 had cerebral ischemic events (15%), 1 had chorea (3%), 2 had papilledema (5%), and 2 patients had a peripheral neuropathy (5%). Nine patients (22%) had severe headache consistent with lupus headache. Seven children had more than one CNS manifestation. In the investigation of CNS-SLE, computed tomography and/or magnetic resonance imaging scans were helpful in patients with focal ischemic lesions and venous sinus thrombosis. Electroencephalography was abnormal only in 33% of patients with seizure disorders and rarely helpful in patients with diffuse neuropsychiatric symptoms. Single-photon emission computed tomography scans were abnormal in most patients with neuropsychiatric SLE, especially in those with frank psychosis. The lupus anticoagulant was present in the patient with chorea and was frequently present in patients with cerebral vascular events. Long-term outcome was good: only 1 child died of cerebral hemorrhagic infarction and 3 others had significant persistent CNS deficits. The majority of patients (90%) had excellent recovery from CNS-SLE.

Eye problems in children with multiple sclerosis.

In a retrospective review, the eye symptoms of 17 children (mean age: 13 1/2 years) who had definite multiple sclerosis (Poser's criteria) and 15 who had probable multiple sclerosis over the last 18 years were evaluated. Follow-up varied from 3 weeks to 6 years. Of 94% of children (16 of 17) with ophthalmologic symptoms, 47% (8 of 17) presented with an initial disturbance of vision. Twelve children had optic neuritis, 1 progressive uveitis, and 4 brainstem symptoms (i.e., VIth nerve palsy, 1 1/2 syndrome, internuclear ophthalmoplegia). Four children had cerebellar signs (nystagmus, saccadic pursuit). In 4 children, clinical localization was less specific. Recovery was generally good in most of the children; cerebellar problems were most persistent. Multimodal potentials were more helpful for investigation of optic neuritis and cerebellar lesions than for brainstem lesions. In the cohort of probable multiple sclerosis of 15 children, 11 had eye symptoms (5 with neuromyelitis optica, 4 optic neuritis, 1 internuclear ophthalmoplegia, and 1 cerebellar symptoms). Ophthalmologic symptoms are slightly more frequent in children with multiple sclerosis than in adults and should be specifically investigated to establish the diagnosis.

Neuroradiology of lysosomal disorders.

The role of neuroimaging in the lysosomal disorders has previously been limited to the initial evaluation and diagnosis of these disease processes and to the detection of treatable disease-related complications, such as hydrocephalus. Localization of changes to the gray or the white matter was useful in guiding the metabolic evaluation when clinical findings were indeterminate or unclear. Imaging features such as dilated VR spaces in MPS storage disease or focal calcifications in Krabbe's disease were occasionally pathognomonic for or highly suggestive of a specific disorder. Now that treatment options, including enzyme replacement therapy and bone marrow transplantation, are available for some of the neurometabolic disorders, staging before the initiation of therapy and evaluation throughout therapy are additional important roles. Even in those disease processes that are currently untreatable, imaging is useful in defining the radiographic appearance of the natural course of a given disorder, to aid in staging and treatment evaluation of future patients with that same disorder when treatment becomes available.

Radiology of the developing central nervous system.

Functional and anatomical imaging of the developing central nervous system continue to engender considerable interest. Structural anomalies have been further defined and catalogued, aiding in the diagnosis and genetic counseling of children with developmental delay. Anomalous development of the brain has recently been linked to certain neuropsychiatric disorders. The natural course of many of the metabolic brain disorders has now been chronicled with imaging studies, rendering standards on which to evaluate efficacy of treatment.

Aggressive surgical management of craniopharyngiomas in children.

The cases of 50 patients with craniopharyngioma operated on at The Hospital for Sick Children in Toronto between January, 1975, and December, 1989, are reviewed. All patients were under 18 years of age (mean 9.39 years). Headaches, endocrine deficiencies, and visual deficits were the most common symptoms on admission. Forty-five patients underwent what was considered by the surgeon to be total excision of their tumor, and five had subtotal excision. Tumors recurred in 17 patients (mean time of recurrence 32.6 months after surgery). One patient died in the postoperative period and three have been lost to follow-up study. Of the remaining 46 patients, 28 are leading a normal or nearly normal life, although all are receiving endocrine replacement and some have required help to overcome mild deficits in memory or visual acuity. Twelve patients are able to function reasonably well and attend school despite being hampered by intellectual or visual deficits or problems with weight control; four have a significant handicap, and two have died.

Arteriopathy and coarctation of the abdominal aorta in children with mucopolysaccharidosis: imaging findings.

Eight children with mucopolysaccharidosis I (MPS I), representing 33% of all children with MPS I seen at our institution during an 18-year period, developed hypertension. Five of these hypertensive children also exhibited symptoms of aortic coarctation. The radiographic evaluation of four of these children with MPS I (three with Hurler syndrome, MPS I H, and one with Scheie disease, MPS I S) and arteriopathy affecting the thoracic aorta, abdominal aorta, and visceral and renal arteries is presented. Hypertension developed in all four children before they were 4 years old; three had differences between upper- and lower-extremity blood pressures. Irregular narrowing of the abdominal aorta with either multiple minor asymmetric wall lesions (n = 2) or abrupt concentric narrowing (n = 2) was present in all children as shown by aortography (n = 3), sonography (n = 3), MR imaging (n = 2), and/or autopsy (n = 1). A variety of other vessels also were involved, including the ascending aorta (n = 1) and vertebral (n = 1), axillary (n = 1), intercostal (n = 2), lumbar (n = 2), mesenteric (n = 3), renal (n = 2), and iliac arteries (n = 3). Autopsy in one child demonstrated thickened heart valves, narrowing of the coronary arteries, and irregularity of the aorta due to deposition of mucopolysaccharide material within the intima. Our series demonstrates various facets of the arteriopathy of MPS I as shown by sonography, MR imaging, and angiography.