Ataxia, ophthalmoplegia, and impairment of consciousness in a 19-month-old American boy.

A 19-month-old, white, Pennsylvanian boy, with an unremarkable medical history, presented to our hospital with a 3-week history of nonbloody, nonbilious emesis up to 5 times a day and nonbloody diarrhea. Ten days before admission, his gait became progressively unsteady, until he finally refused to walk. A day before admission, he found it difficult to move his eyes. The patient was hypoactive. History, physical and neurologic examination, blood and cerebrospinal (CSF) fluid studies, and neuroimaging studies ruled out the most frequent causes of acute ataxia. The etiology of bilateral, complete ophthalmoplegia was also taken into consideration. Magnetic resonance imaging (MRI) findings of bilateral thalami and mammillary bodies provided diagnostic clues. Additional history and specific tests established the final diagnosis and treatment plan. The patient improved to a normal neurologic state. This case provides important practical information about an unusual malnutrition cause of acute ataxia, particularly in young children of developing countries.

Cerebellar gliomatosis in a toddler: case report of a challenging condition and review of the literature.

Gliomatosis confined to the cerebellum is most unusual. We report such a case in a 20-month-old male who presented with unsteadiness. Magnetic resonance imaging revealed a diffuse area of abnormal signal intensity within both cerebellar hemispheres, which did not enhance after contrast administration. The patient underwent a biopsy, which revealed a diffuse glioma infiltrating the cerebellum. Overall, the tumor cells had oligodendroglioma-like features and exhibited only focal vimentin immunoreactivity. They were negative for glial fibrillary acidic protein, synaptophysin, ßIII-tubulin, and neurofilament protein. Immunofluorescence, performed on primary biopsy explants maintained in cell culture without exposure to growth factors or differentiation-promoting agents, revealed widespread nestin immunoreactivity and immunolabeling of occasional cells with antibodies to platelet-derived growth factor-α and O1/O4, markers of oligodendrocyte precursor-cells and immature oligodendrocytes, respectively. Fluorescent in situ hybridization performed on explants, touch preparations, and paraffin sections failed to reveal loss of heterozygosity for either 1p36 or 19q13. The patient was treated with temozolomide and remains stable, albeit with residual quiescent tumor, more than 3 years after surgery. This report calls attention to an unusual presentation of gliomatosis confined to the cerebellum of a toddler and addresses salient aspects of clinical and radiological differential diagnosis, as well as therapeutic challenges encountered.

Imaging tumors of the pediatric central nervous system.

Primary tumors of the central nervous system (CNS) are the second most common neoplasms in children and the leading cause of death in this patient population. The primary objective of this article is to describe the most common pediatric brain tumors and to offer an overview of their respective imaging features, primarily on magnetic resonance imaging. Precise anatomic characterization is essential for developing an appropriate differential diagnosis. Once equipped with this critical information, physicians should be better able to make firm diagnoses, leading to improved disease management and patient outcomes in the setting of CNS tumors of childhood.

Acute VI nerve palsy in a 4 year-old girl with Chiari I malformation and pontomedullary extension of syringomyelia: case report and review of the literature.

We report the case of a previously healthy 4 year-old African American female who presented to the emergency department with acute onset of unilateral abducens nerve palsy and torticollis. Within 12 h of presentation, the patient's symptoms progressed to include ipsilateral facial nerve palsy and gait ataxia. On exam, the patient demonstrated right cranial nerve VI and VII palsies, ataxic gait with left lateropulsion, spasticity of bilateral lower extremities with clonus, and the presence of bilateral Babinski sign. MRI of the brain and spinal cord revealed severe Chiari I malformation with associated extensive holochord syringomyelia and syringobulbia. The patient underwent successful surgical decompression 72 h after initial presentation. We review the literature on Chiari malformations and syringomyelia, including epidemiology, presentation and neurological manifestations, and treatment recommendations. As our patient had a very acute presentation, we additionally review the previously reported cases of acute and atypical presentation of patients with Chiari I malformation and syringomyelia. The aim of this report is to make practitioners aware of the acuteness with which children with Chiari malformation type I with syringomyelia and syringobulbia can present.

The galactocele of male infants: an intriguing entity. Study and reflection about a case, with review of the literature.

In this report, the authors investigate and discuss a galactocele that developed in the breast of a 5-month-old male. Based on the histological and immunohistochemical findings, they suggest that the rare and intriguing process that is exclusively observed in males in the absence of any detectable hormonal stimulation at time of investigation could represent a developmental anomaly possibly promoted by an obstructive phenomenon involving a defect of hollowing of some primary epidermal buds, the precursors of the mammary ducts.

An adolescent with a mediastinal mass, diagnosed with Graves disease and thymic hyperplasia.

Graves disease is an autoimmune disorder characterized by thyroid enlargement and hyperthyroidism. Thyrotropin receptor (TSHR) autoantibodies bind the TSHR on the membrane of thyroid follicular cells and stimulate cell proliferation and thyroid-hormone synthesis. TSHR has also been identified in extrathyroidal organs, including the human thymus. Thus far, radiologically detectable thymic enlargement has only been reported in adults with Graves disease. We present here the case of a child with Graves disease and significant thymic hyperplasia. L. K. was a 15-year-old girl evaluated for cough and dyspnea on exertion. A chest radiograph was obtained, and it revealed a widened superior mediastinum. A computed-tomography scan of her chest identified a mass in the anterior mediastinum without associated lymphadenopathy. Because of these radiologic findings and her weight loss, she was referred to the oncology service; a biopsy of the mediastinal mass was obtained and revealed thymic reactive hyperplasia. Because of persistent tachycardia, thyroid studies were obtained, and the diagnosis of Graves disease was established. The child's physical examination revealed a minimally enlarged thyroid gland and no exophthalmos. One month after medical treatment was initiated, a repeat computed-tomography scan of her chest identified significantly reduced thymic size. To our knowledge, this is the first pediatric patient reported with Graves disease and significant thymic enlargement. Considering the diagnosis of Graves disease for a child with an anterior mediastinal mass and without the typical physical findings of autoimmune hyperthyroidism (goiter, exophthalmos) may prevent unnecessary diagnostic studies and their associated financial and emotional costs.

Terminal ileal atresia, total colonic aganglionosis, and thrombophilia.

Inherited thrombophilia, a predisposition for a hypercoagulable state, has been associated with cases of intestinal atresia. In this communication, we report a case of terminal ileal atresia and total colonic aganglionosis (Hirschsprung's disease), a rarely documented association, in a neonate who seemed to have a hypercoagulable state. The case stresses the need for recognition of this sequence of events in order to achieve optimal management.

Absence of mutation in the follicle-stimulating hormone receptor gene in severe primary hypothyroidism associated with gonadal hyperstimulation.

BACKGROUND: Severe hypothyroidism can cause a distinct form of precocious puberty in children, characterized by delayed skeletal maturation, predominance of FSH-mediated effects over LH-mediated function, and reversal of sexual precocity upon thyroid hormone replacement. The etiology of this unusual form of precocious puberty in children remains poorly understood. Recently, three mutations of the FSH receptor gene have been identified in women with spontaneous ovarian hyperstimulation during pregnancy. All three mutated receptors displayed abnormally high sensitivity to hCG which caused gonadal stimulation. Two of these mutations displayed concomitant increase in sensitivity of the mutated receptor to TSH. In this report, we describe four children with primary hypothyroidism and gonadal hyperstimulation. The aim of this study was to determine whether these patients' gonadal hyperstimulation is due to a mutation in their FSH receptor gene. METHODS: DNA was extracted from all four patients with primary hypothyroidism and gonadal stimulation. The entire FSH receptor gene was sequenced and analyzed. RESULTS: Direct sequencing of these patients' FSH receptor gene did not demonstrate any mutation, proving that the cause of gonadal stimulation in these patients is not due to the increased sensitivity or constitutive activation of a mutated FSH receptor. CONCLUSIONS: The elevated TSH in these patients and prior demonstration of the in vitro ability of TSH to bind to the FSH receptor lead us to hypothesize that the gonadal stimulation in these patients is TSH-mediated. The fact that gonadal stimulation is not seen in all patients with severe hypothyroidism raises the question as to whether polymorphisms of the FSH receptor gene and/or possible changes in the TSH molecular structure may contribute to the TSH-mediated activation of the FSH receptor.

Glioneuronal phenotype in a diencephalic pilomyxoid astrocytoma.

We report the presence of divergent populations of cells in a hypothalamic/chiasmatic pilomyxoid astrocytoma of an 11-month-old male, exhibiting differential immunohistochemical localizations for glial fibrillary acidic protein (GFAP) and synaptophysin. The tumor cells were negative for Neu-N and neurofilament protein. Ultrastructurally, the tumor comprised 2 cell types, one with features attributable to a neuronal phenotype alongside cells exhibiting an overt astroglial phenotype. This composite organization was confirmed by confocal microscopy, which revealed 2 distinct, albeit tightly interwoven, populations of GFAP and synaptophysin-labeled tumor cells. Our results indicate that a subset of the so-called pilomyxoid astrocytomas of the hypothalamic/chiasmatic region may represent phenotypically mixed glioneuronal neoplasms distinct from the pilocytic astrocytomas.

Anterior encephalocele associated with subependymal nodular heterotopia, cortical dysplasia and epilepsy: case report and review of the literature.

The presence of subependymal nodular heterotopia and cortical dysgenesis has been infrequently reported in patients with encephalocele. The majority of these patients were found to have posterior encephaloceles. We report a case of a Hispanic female with a frontoethmoidal encephalocele who developed epilepsy at 15 years of age. Magnetic resonance imaging of the brain demonstrated left subependymal nodular heterotopia, partial agenesis of the corpus callosum and left fronto-temporal cortical dysplasia with polymicrogyria. This case illustrates the association of anterior encephalocele with subependymal nodular heterotopia, cortical dysplasia and epilepsy. It underscores the importance of screening for intracranial abnormalities in patients with anterior encephalocele.

Application of computer-assisted design in craniofacial reconstructive surgery using a commercial image guidance system. Technical note.

The technology of digital image guidance systems has transformed many aspects of neurosurgery, including intracranial tumor surgery, functional neurosurgery, and spinal surgery. Despite the central role of imaging studies in diagnosis and treatment planning, intraoperative image guidance has so far had very limited application to the surgical correction of craniofacial deformities, particularly those associated with craniosynostosis. The authors report an example of the marriage of computer-assisted design methods to a commercially available neurosurgical image-guidance system in the treatment of a case of anterior plagiocephaly due to unilateral coronal synostosis. They discuss the steps that must yet be taken to make this technology applicable to the management of craniosynostosis in infants.

Tacrolimus induced subacute cerebellar ataxia.

Tacrolimus is a macrolide immunosuppressant that is widely used in transplant surgery. Both mild and major neurologic side effects have been reported in patients receiving tacrolimus. Reversible posterior leukoencephalopathy syndrome is one of the major tacrolimus induced neurologic side effects. We report a case of a tacrolimus induced isolated lesion of the cerebellum with no supratentorial involvement, presenting as a subacute cerebellar ataxia, which was partially reversible upon discontinuing the tacrolimus.

Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis.

OBJECTIVES: To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing on (1) the relationship between clinical course and MRI findings and (2) the response to plasmapheresis in a subgroup of patients. METHODS: A retrospective record review was conducted of 13 children who were admitted as inpatients with the diagnosis of ADEM during the period 1998-2003. RESULTS: Diagnosis was established by clinical signs and symptoms, cerebrospinal fluid changes and multifocal involvement of deep gray and white matter based on MRI. Initial therapy was high-dose methylprednisolone and intravenous immunoglobulin in 12 patients. One child improved spontaneously. Six of 12 children did not improve with corticosteroid treatment. All 6 had an acute progressive course neurologically, and 5 of them also showed a delay in the onset of neuroimaging changes, eventually developing lesions in the deep gray matter and brainstem. This latter group received 5 sessions of plasmapheresis and recovered over the course of several months with varying degrees of residual neurologic deficits. CONCLUSIONS: Presentation of ADEM with delayed development of MRI lesions in deep gray matter and brainstem may herald a prolonged clinical course and lack of response to glucocorticoid therapy. Plasmapheresis might be an effective therapeutic intervention in these patients. The role of plasmapheresis versus corticosteroids and intravenous immunoglobulin as a primary treatment of ADEM needs to be investigated further.

Evaluation of platybasia with MR imaging.

BACKGROUND AND PURPOSE: Platybasia, or abnormal obtuseness of the basal angle, was first measured on plain skull images. At present, evaluation of the brain and skull more commonly involves CT and MR imaging. We evaluated a new MR imaging method of evaluating platybasia. METHODS: We retrospectively evaluated midline sagittal MR images in 200 adults and 50 children. The basal angle of the skull base was measured by using two methods: The standard MR imaging technique measured the angle formed by two lines-one joining the nasion and the center of the pituitary fossa connected by a line joining the anterior border of the foramen magnum and center of the pituitary fossa. The modified technique measured the angle formed by a line across the anterior cranial fossa and dorsum sellae connecting a line along the clivus. RESULTS: With the standard MR imaging technique, we obtained mean angles of 129 degrees +/- 6 degrees for adults and 127 degrees +/- 5 degrees for children, compared with 135.3 degrees (composite mean) in previous series. The modified technique produced values of 117 degrees +/- 6 degrees for adults and 114 degrees +/- 5 degrees for children, which were significantly lower that those of standard MR imaging and traditional radiography (P <.05). CONCLUSION: Both the standard and modified MR imaging techniques produced basal angles lower than those previously reported with standard radiography. The modified technique uses clearly featured landmarks that can be reproduced consistently on midline sagittal T1 images. This technique and its corresponding values can be used as the new standard for evaluating the basal angle.

Infantile leukoencephalopathy owing to mitochondrial enzyme dysfunction.

Mitochondrial disease is classically associated with deep gray-matter lesions. When white matter is involved, the lesions are typically subcortical and overshadowed by more significant disease in the gray matter. We report six infants in five families who developed neurodegenerative diseases characterized primarily by abnormalities in deep white-matter structures such as the periventricular region, internal capsule, and corpus callosum. Five patients had impairments of mitochondrial enzymes, including a pre-electron transport chain defect and defects in respiratory chain complexes I, III, and IV (cytochrome-c oxidase). One patient, the sibling of one of the others, was diagnosed clinically with complex III deficiency. These six patients, along with others in the literature, appear to represent a distinct syndrome of mitochondrial infantile leukoencephalopathy. Our observations suggest that infants with leukoencephalopathies, especially leukodystrophies, who do not have one of the more common causes of white-matter disease should be evaluated for mitochondrial dysfunction.

Magnetic resonance of metabolic and degenerative diseases in children.

Cerebral magnetic resonance imaging and spectroscopy form an integral part in the diagnosis and management of the vast spectrum of metabolic and degenerative disorders in children. These varied disorders have been classified in many different ways, according to anatomic location, head size, enzyme disorder, or cellular morphology and function. The clinical features and magnetic resonance imaging appearances of the most common disorders are discussed.