Limitations to plasticity of language network reorganization in localization related epilepsy.

Neural networks for processing language often are reorganized in patients with epilepsy. However, the extent and location of within and between hemisphere re-organization are not established. We studied 45 patients, all with a left hemisphere seizure focus (mean age 22.8, seizure onset 13.3), and 19 normal controls (mean age 24.8) with an fMRI word definition language paradigm to assess the location of language processing regions. Individual patient SPM maps were compared to the normal group in a voxel-wise comparison; a voxel was considered to be significant if its z-value exceeded mid R:2mid R:. Subsequently, we used principal component analysis with hierarchical clustering of variance patterns from individual difference maps to identify four patient sub-groups. One did not differ from normal controls; one had increased left temporal activation on the margin of regions activated in controls; two others had recruitment in right inferior frontal gyrus, middle frontal gyrus and temporal cortex. Right hemisphere activation in these two groups occurred in homologues of left hemisphere regions that sustained task activation. Our study used novel data driven methods to find evidence for constraints on inter-hemispheric reorganization of language in recruitment of right homologues, and, in a subpopulation of patients, evidence for intra-hemispheric reorganization of language limited to the margins of typical left temporal regional activation. These methods may be applied to investigate both normal and pathological variance in other developmental disorders and cognitive domains.

Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group.

PURPOSE: The Children's Cancer Group conducted a phase I trial of temozolomide stratified by prior craniospinal irradiation (CSI). PATIENTS AND METHODS: Children and adolescents with recurrent or progressive cancer were enrolled. Temozolomide was administered orally daily for 5 days, with subsequent courses administered every 21 to 28 days after full hematologic recovery. Dose levels tested included 100, 150, 180, 215, 245, and 260 mg/m2 daily. RESULTS: Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the first three dose levels (100, 150, and 180 mg/m2 daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m2 daily had grade 3 hematologic toxicity. Three of eight patients (38%) treated at 245 to 260 mg/m2 daily had dose-limiting toxicity (DLT), which included both neutropenia and thrombocytopenia. Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematologic DLT occurred in one of six patients (17%) at 100 mg/m2 daily and in two of four patients (50%) at 215 mg/m2 daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the patients. After two courses of temozolomide, 10 patients had stable disease (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 months of follow-up. CONCLUSION: The maximum-tolerated dose (MTD) of temozolomide for children and adolescents without prior CSI is 215 mg/m2 daily and for those with prior CSI is 180 mg/m2 daily for 5 days, with subsequent courses that begin on day 28. Temozolomide is well tolerated and should undergo phase II testing in children and adolescents.

Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: A Children's Cancer Group Study.

PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% +/- 4% at 3 years and 79% +/- 7% at 5 years. Sites of relapse for the 14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.

'Complicated migraine-like episodes' in children following cranial irradiation and chemotherapy.

Neurologic sequelae may occur months to years after cranial irradiation. The site of primary damage is probably the vascular endothelium. Over a 2.8-year period, four children with brain tumors, a mean of 11 years of age at diagnosis (range, 6.5 to 15.5 years), had new onset of severe intermittent unilateral headaches associated with nausea, episodic visual loss, hemiparesis, aphasia, or hemisensory loss. The headaches lasted 2 to 24 hours. All patients had previously received whole-brain (2,400 to 3,600 cGy) and additional local boost (1,800 to 3,100 cGy) cranial irradiation, as well as cisplatin-, lomustine-, and vincristine-containing chemotherapy regimens. Symptoms began 1.2 to 2.8 years after the diagnosis, when all had stable disease and were off treatment. MRI studies were unchanged, and CSF cytology, EEGs, echocardiograms, and magnetic resonance angiograms were normal in all. Cerebral angiograms, performed in three children, were normal but led to severe headaches and neurologic deficits (hemiparesis in one and visual loss in two) that resolved after 24 to 48 hours. Response to antimigraine and antiplatelet medications was variable. We conclude that (1) "complicated migraine-like episodes" may occur in children after cranial irradiation and chemotherapy as a sequela of therapy; (2) these headaches may not be the harbinger of impending strokes, severe intracranial vasculitis, or tumor recurrence; and (3) while cerebral angiography may be useful in differential diagnosis, it may cause transient worsening of symptoms.

Stroke after zoster ophthalmicus in a 12-year-old girl with protein C deficiency.

A 12-year-old girl who had zoster ophthalmicus 10 months earlier presented with hemiparesis and corresponding basal ganglionic infarction related to middle cerebral artery branch thrombosis ipsilateral to the zoster. Hematologic evaluation disclosed protein C deficiency. This represents the first zoster-associated stroke reported in childhood associated with protein C deficiency, with extension of the latency period between zoster and infarction, previously reported to be 6 months.

Language dominance in partial epilepsy patients identified with an fMRI reading task.

BACKGROUND: fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. OBJECTIVE: To identify temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. METHODS: Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AI) were calculated ([L-R]/[L+R]) and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). RESULTS: The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. CONCLUSIONS: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.

Patient with craniosynostosis and marfanoid phenotype (Shprintzen-Goldberg syndrome) and cloverleaf skull.

Marfanoid phenotype with craniosynostosis (Shprintzen-Goldberg syndrome) is a rare disorder previously described in only 5 patients. We report on the sixth known patient with this condition. The findings which distinguish our patient from others reported previously are that she was ascertained prenatally as having a cloverleaf skull; this is the first female patient described with this condition. Postnatally, she presented with arachnodactyly, camptodactyly, and clover-leaf skull. Imaging studies of the brain documented microcephaly with malformed brain, hydrocephaly, and hypoplasia of the corpus callosum. She also had choanal atresia and stenosis, a clinical finding previously reported only once, in this disorder.

Acute identification of cranial burst fracture: comparison between CT and MR imaging findings.

BACKGROUND AND PURPOSE: Scalp swelling associated with cranial burst fracture, a widely diastatic skull fracture of infants associated with dural laceration and acute cerebral extrusion, may be confused with that of a simple subgaleal hematoma. Both conditions can also be associated with hemorrhagic shock. We sought to improve the early evaluation of infants believed to have sustained cranial burst fracture by including MR imaging, since this study clearly delineates the dural-cortical interface, the site of injury. METHODS: Seven infants aged 1 through 11 months who sustained cranial burst fractures, all initially imaged with skull radiography and CT, were studied or treated from 1992 through 1996. MR imaging was obtained after resuscitation and stabilization. RESULTS: Surgery or autopsy confirmed MR findings (dural laceration and extracalvarial cerebral tissue) in all seven infants. CONCLUSION: MR imaging allows early diagnosis of skull fracture associated with acute cerebral extrusion.

Imaging and clinical evaluation of isolated atresia of the oval window.

BACKGROUND AND PURPOSE: Congenital causes of hearing loss in children commonly are encountered, and imaging aids in diagnosis as well as presurgical evaluation. Atresia of the oval window not associated with atresia of the external auditory canal (EAC) is a rare cause of congenital hearing loss in children. We present the clinical and imaging findings in children with isolated oval-window atresia. METHODS: Atresia of the oval window was defined as the absence of the structure with the presence of a bony plate superimposed between the vestibule and middle ear. The bony plate is within the expected region of the oval window. Using a computerized database, nine patients with isolated oval-window atresia were found. All had been evaluated with high-resolution computed tomography (HRCT) and all had medical records available for review, including audiogram results. Imaging studies were interpreted by the consensus of two pediatric neuroradiologists. RESULTS: Atresia of the oval window was documented in all cases using HRCT criteria. The most common anomalies associated with oval-window atresia were inferomedial malposition of the facial nerve (n = 8), malformed incus (n = 6), and displaced stapes (n = 2). Four patients had symmetric bilateral involvement. Hearing tests were not specific, because conductive, sensorineural, and mixed patterns were found. CONCLUSION: Anomalies of the oval window should be sought in all patients with congenital hearing loss. Associated findings, such as facial nerve aberrancy and ossicular anomalies, are important in both diagnosis and surgical planning.

Pleomorphic xanthoastrocytoma, a distinctive astroglial tumor: neuroradiologic and pathologic features.

PURPOSE: To analyze and discuss CT and MR features of pleomorphic xanthoastrocytoma (PXA) and present salient histopathologic features of this distinctive astroglial tumor. METHOD: CT, MR, and histopathologic studies on seven patients with the histologic diagnosis of PXA were reviewed retrospectively. RESULTS: All patients were in their first 3 decades of life when first diagnosed and demonstrated peripherally situated supratentorial tumors of varying size involving the superficial cortex and leptomeninges. Five of six cases examined with CT showed areas of mixed attenuation with four demonstrating well-demarcated enhancement. MR demonstrated low or mixed signal intensity on T1-weighted and high or mixed signal intensity on T2-weighted sequences. All five who received gadopentetate dimeglumine showed well-defined enhancement. Three showed cyst formation. Typical histologic features included marked cellular pleomorphism with giant cells, bizarre nuclei, variable cytoplasmic lipidization and positive immunoreactivity for glial fibrillary acidic protein. Necrosis and endothelial-pericytic cell proliferation were absent. CONCLUSION: PXA has a highly suggestive neuroradiologic and distinctive histopathologic appearance.

Tumoral multiple sclerosis of the cerebellum in a child.

We present a case of cerebellar tumoral multiple sclerosis in an 11-year-old girl and emphasize these two features: (1) Tumoral multiple sclerosis can occur within the posterior fossa and should be strongly considered in the differential diagnosis of mass lesions of the posterior fossa when typical white matter lesions are seen on T2-weighted images. (2) Tumoral multiple sclerosis can demonstrate ring enhancement on MR.

Cerebrovascular complications of HIV in children.

Two uncommon but important cerebrovascular manifestations of human immunodeficiency virus (HIV) infection in children are arteritis with formation of fusiform aneurysms and arterial sclerosis with vascular occlusion. We studied the CT and MR imaging features of HIV in two girls and one boy (9 to 18 years old) and compared them with autopsy findings in two patients. One of the children had findings consistent with small areas of subacute infarction and the other two had fusiform dilatation of the major vessels of the circle of Willis. The ischemic lesions and arteriopathy were confirmed at autopsy. In one patient, an incidental B-cell lymphoma (not visible on the imaging studies) was diagnosed.

Relative incidence and alternative approaches for surgical drainage of different types of deep neck abscesses in children.

OBJECTIVES: To determine the relative frequency of retropharyngeal abscesses (RPAs) vs lateral pharyngeal abscesses (LPAs) and to analyze alternative approaches for surgical drainage. DESIGN: Retrospective chart review. SETTING: Tertiary care children's hospital. PATIENTS: Seventy pediatric patients who were evaluated, admitted, and treated for presumed deep neck abscesses (RPAs and LPAs) between January 1, 1986, and December 31, 1996. INTERVENTION: Intravenous antibiotic therapy and surgical drainage. MAIN OUTCOME MEASURE: Clinical resolution of the abscess. RESULTS: Fifty-eight patients were evaluated with computed tomographic scan. Thirteen of these patients did not have surgical intervention. Of 12 patients diagnosed as having an isolated RPA, all had intraoral surgical drainage and 9 had evidence of pus at surgery. Twenty-one patients had an isolated LPA. Sixteen of these underwent intraoral drainage and 5 underwent external drainage. Purulence was found at surgery in 14 and 2 patients, respectively. The remaining 12 patients had a combination of RPA and LPA. Eight patients underwent intraoral drainage, and 4 patients required both intraoral and external approaches. Purulence was found at surgery in 5 and 4 patients, respectively. Of the 12 patients who were not evaluated with computed tomographic scan, two thirds were treated prior to 1987. Six of these 12 patients underwent surgical drainage via an intraoral approach, and 4 of the 6 patients had pus. The remaining 6 improved without surgery. CONCLUSIONS: Most deep neck abscesses in children are located in the retropharyngeal or in the lateral pharyngeal space medial to the great vessels. Therefore, most can be managed successfully with intraoral rather than external drainage. External approaches are better reserved for those abscesses that are lateral to the great vessels or that involve multiple spaces. In this patient population, LPAs were more commonly seen than RPAs.

Enlarged vestibular aqueduct and sensorineural hearing loss in childhood.

OBJECTIVE: To determine if all children with enlarged vestibular aqueducts (EVAs) have development of uniform progressive sensorineural hearing loss (SNHL). To determine whether the size of the EVA correlates with severity, frequencies involved, and stability of SNHL. To determine if the audiologic pattern of SNHL correlates with likelihood of progression of SNHL. DESIGN: Retrospective study. SETTING: Children's National Medical Center, Washington, DC, a tertiary care center with a large otologic practice. PATIENTS: Fifteen children (26 ears) with EVA on computed tomographic scan. METHODS: History, physical examination, computed tomographic scans, and serial audiograms were reviewed. Factors analyzed included age at diagnosis, audiometric configuration (high tone, midtone, low tone, flat), degree of hearing loss at presentation, length of follow-up, and presence of associated inner ear anomalies. RESULTS: Nine ears had progressive SNHL, 16 ears had stable SNHL, and 1 ear had profound SNHL. The predominant audiologic configuration was flat. The audiogram configuration does not correlate with progression of SNHL. The size of the vestibular aqueduct does not correlate with the level, type, or progression of SNHL. CONCLUSION: Our study failed to uncover factors that might be predictive of progression of hearing loss. We conclude that until a better understanding of the natural history and pathophysiologic condition of EVAs is achieved, there is no surgical or other intervention that can be demonstrated as being efficacious.

Diagnostic imaging in neuro-oncology.

Recent advances in imaging techniques, biologic characterization, and histologic classification have contributed to improving management of children with brain tumors. The overall prognosis of children with brain tumors nevertheless lags behind that of other pediatric oncologic diseases. This article reviews recent developments in tumor imaging.

Infratentorial brain tumors of childhood.

One half of brain tumors in children originate in the posterior fossa. Although a wide variety of lesions occurs, four tumor types account for more than 95% of cases. Knowledge of their modes of presentation, CT and MR features, and pattern of spread can usually lead to a correct diagnosis.

Brainstem gliomas.

Brainstem gliomas, a relatively common form of childhood brain tumor, are highly resistant to therapy. With computed tomography and magnetic resonance imaging, these lesions can be diagnosed with a high degree of reliability. The indications for surgery are unclear. Focal lesions may be amenable to partial resections. Stereotactic approaches can be used for diffuse lesions, but it has not been shown that the information obtained changes the approach to treatment or outcome. Higher dose radiotherapy has been recently used but has not improved survival for most patients. Patients with brainstem gliomas must be stratified into risk groups, and new means of treatment are needed.

Neurodevelopmental and neuroimaging correlates in nonsyndromal microcephalic children.

This descriptive study examined the relationship between head size, developmental functioning, and neuroimaging findings in children with absolute microcephaly. Subjects, aged 1 to 48 months, were assigned to one of two groups based on occipitofrontal head circumference (OFC). Group A included subjects with an OFC of 2 to 2.99 standard deviations below the mean, and Group B included subjects with an OFC of 3 or more standard deviations below the mean. Brain scan findings for 62% of the subjects were abnormal. Findings included cerebral atrophy, cortical dysplasia, myelination delay, and white matter hypoplasia. Mean scores for developmental measures in Groups A and B were less than 70. Mean developmental scores in the normal imaging group were 70 or greater, whereas developmental scores in the abnormal imaging group were 52 or less. Forty-three percent of the subjects in Group A and 80% of those in Group B had abnormal findings from imaging studies (p = .0394). Subjects with one or more brain abnormalities determined on the basis of magnetic resonance images or computed tomographic scans had significantly lower scores in all developmental areas (p < .05). The authors concluded that abnormal brain images seem to be a better reflection of developmental performance than the degree of microcephaly. J Dev Behav Pediatr 21:12-18, 2000. Index terms: microcephaly, neuroimaging, neurodevelopment.

[Current technique of myelography]. / La technique actuelle de la myélographie.

Myelography performed with fine needle technique has become virtually innocuous and can be more liberally used in conjunction with CT to produce the CT-myelogram, a product of remarkable diagnostic precision. The authors contention is based on a series of 1,357 consecutive myelograms or CT-myelograms recently performed using exclusively 26-gauge spinal needles.

Brain perfusion in encephalopathic newborns after therapeutic hypothermia.

BACKGROUND AND PURPOSE: Cerebral perfusion patterns in neonates with HIE after therapeutic hypothermia have not been well described. The objectives of this study were to compare global and regional perfusion between infants with HIE and neonate controls and to relate measures of cerebral perfusion to brain injury on conventional MR imaging in neonates with HIE. MATERIALS AND METHODS: Term encephalopathic neonates meeting criteria for hypothermia between June 2011 and January 2012 were enrolled in this prospective observational study. MR imaging-ASL was performed in the second week of life. Comparisons were made with data from neonate controls who underwent the same imaging protocol. NIRS measures of cerebral oxygenation during and immediately after hypothermia were also evaluated in a subset of patients. Secondary analyses were performed to assess cerebral perfusion and oxygenation differences by pattern of injury on qualitative MR imaging interpretation. RESULTS: We enrolled 18 infants with HIE and 18 control infants. Mean global CBF and regional CBF in the basal ganglia, thalamus, and anterior white matter were higher in cases compared with controls. Infants with HIE with injury on MR imaging, however, had lower CBF (significant in the thalamus) compared with those with normal MR imaging. Decreased FTOE by NIRS further differentiated patients with HIE with injury on MR imaging. CONCLUSIONS: Disturbed cerebral perfusion is observed in the second week of life in some babies with HIE despite treatment with hypothermia. Infants with HIE with injury on MR imaging have lower regional CBF in the thalamus compared with those without injury, possibly representing pseudonormalization of CBF and low metabolic demand after progression to irreversible brain injury.