Ependymoma Presenting as a -Rim-Enhancing Lesion in the Brainstem.

INTRODUCTION: The posterior fossa is the most common intracranial location for pediatric ependymoma. While ependymoma usually arises from the ventricular lining of the fourth ventricle as a solid mass, it rarely originates from the brainstem. Grade II ependymomas also infrequently appear as a cavitary ring-enhancing lesion. CASE PRESENTATION: We describe a case of a 6-year-old boy with an ependymoma arising within the medulla with imaging features of a thick-walled rim-enhancing cavitary lesion. A stereotactic biopsy was obtained which confirmed a grade II ependymoma. The patient received focal proton beam radiation therapy and is doing well with no concerns for disease progression at 28 months after diagnosis. CONCLUSION: Posterior fossa ependymomas typically arise from ependymal cells within the fourth ventricle or foramina of Luschka. They rarely invade or arise within the brainstem parenchyma. Our case had atypical imaging findings in addition to the atypical tumor location. The lesion was described as a thick-walled rim-enhancing focal cystic necrotic lesion centered within the medulla with surrounding nonenhancing expansile infiltrative changes. Ring-enhancing lesions can be seen in patients with anaplastic ependymoma, but is not commonly reported in grade II ependymomas. In summary, this report highlights a unique case of a posterior fossa ependymoma in a pediatric patient arising in an atypical brainstem location as well as having unique imaging features.

Survival and Neurologic Recovery After Prompt Diagnosis and Aggressive Management of Severe Idiopathic Hyperammonemic Encephalopathy in a Patient with Acute Myeloid Leukemia.

A case of a 19-year-old female with low-risk acute myeloid leukemia is presented who was diagnosed with idiopathic hyperammonemic encephalopathy following the development of abrupt neurologic decline, respiratory alkalosis, and elevated plasma ammonia levels of unknown etiology. Delayed symptom recognition of this exceedingly rare condition contributes to the often fatal outcomes of idiopathic hyperammonemic encephalopathy. As illustrated by this case, prompt diagnosis and utilization of a variety of ammonia-modulating treatment modalities can result in remarkable clinical recovery. This case provides guidance to clinicians in counseling families about the possibility of neurologic recovery in similar clinical scenarios.

From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.

PARN encodes poly(A)-specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal-Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN-associated IPF have not been described. We report a family with a rare missense, p.Y91C, and a novel insertion, p.(I274*), PARN variant. We found PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted. Detailed analysis of the consequences of these variants revealed that, while PARN protein was lowest in the severely affected biallelic child who had the shortest telomeres, it was also reduced in his mother with the p.(I274*) variant but telomeres at the 50th percentile. Increased adenylation of telomerase RNA, human telomerase RNA, and certain small nucleolar RNAs, and impaired ribosomal RNA maturation were observed in cells derived from the severely affected biallelic carrier, but not in the other, less affected biallelic carrier, who had less severely shortened telomeres, nor in the monoallelic carriers who were unaffected and had telomeres ranging from the 1st to the 50th percentiles. We identified hsa-miR-202-5p as a potential negative regulator of PARN. We propose one or more genetic modifiers influence the impact of PARN variants on its targets and this underlies incomplete penetrance of PARN-associated disease.

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle.

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care.

Lymphocytic hypophysitis associated with pediatric multiple sclerosis.

BACKGROUND: Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland and infundibulum most often observed in the setting of autoimmune disease with a variety of clinical and endocrine presentations. The association between lymphocytic hypophysitis and multiple sclerosis has not been reported. PATIENT AND RESULTS: We describe an adolescent boy with polyfocal neurological signs including optic neuritis as well as hypopituitarism and diabetes insipidus related to lymphocytic hypophysitis. His imaging met 2010 McDonald criteria for multiple sclerosis. This diagnosis was further supported by cerebrospinal fluid analysis and a negative evaluation for an alternate diagnosis. Imaging features of lymphocytic hypophysitis include an absent posterior pituitary bright spot with an enlarged cystic pituitary gland, stalk thickening, and improvement with corticosteroid therapy. CONCLUSIONS: Lymphocytic hypophysitis and multiple sclerosis share a common autoimmune pathogenesis, perhaps explaining the co-occurrence of the diseases. The presentation of endocrinologic disturbances such as diabetes insipidus with typical features of a multiple sclerosis attack should prompt further investigation of possible comorbid inflammatory disease involving the hypothalamic-pituitary axis.

Estimation of normal computed tomography measurements for the upper cervical spine in the pediatric age group.

OBJECT: Upper cervical spine injuries in the pediatric age group have been recognized as extremely unstable from ligamentous disruption and as potentially lethal. Few measurement norms have been published for the pediatric upper cervical spine to help diagnose this pathological state. Instead, adult measurement techniques and results are usually applied inappropriately to children. The authors propose using high-resolution reconstructed CT scans to define a range of normal for a collection of selected upper cervical spine measurements in the pediatric age group. METHODS: Sagittal and coronal reformatted images were obtained from thin axial CT scans obtained in 42 children (< 18 years) in a 2-month period. There were 25 boys and 17 girls. The mean age was 100.9 months (range 1-214 months). Six CT scans were obtained for nontrauma indications, and 36 were obtained as part of a trauma protocol and later cleared for cervical spine injury. Six straightforward and direct linear distances-basion-dental interval (BDI); atlantodental interval (ADI); posterior atlantodental interval (PADI); right and left lateral mass interval (LMI); right and left craniocervical interval (CCI); and prevertebral soft-tissue thickness at C-2-that minimized logistical and technical distortions were measured and recorded. Statistical analysis including interobserver agreement, age stratification, and sex differences was performed for each of the 6 measurements. RESULTS: The mean ADI was 2.25 ± 0.24 mm (± SD), the mean PADI was 18.3 ± 0.07 mm, the mean BDI was 7.28 ± 0.10 mm, and the mean prevertebral soft tissue width at C-2 was 4.45 ± 0.43 mm. The overall mean CCI was 2.38 ± 0.44 mm, and the overall mean LMI was 2.91 ± 0.49 mm. Linear regression analysis demonstrated statistically significant age effects for PADI (increased 0.02 mm/month), BDI (decreased 0.02 mm/month), and CCI (decreased 0.01 mm/month). Similarly significant effects were found for sex; females demonstrated on average a smaller CCI by 0.26 mm and a smaller PADI by 2.12 mm. Moderate to high interrater reliability was demonstrated across all parameters. CONCLUSIONS: Age-dependent and age-independent normal CT measurements of the upper cervical spine will help to differentiate physiological and pathological states in children. The BDI appears to change significantly with age but not sex; on the other hand, the LMI and ADI appear to be age-independent measures. This preliminary study suggests acceptable levels of interrater reliability, and further expanded study will aim to validate these measurements to produce a profile of normal upper cervical spine measurements in children.

Pathologic fractures in children with acute Staphylococcus aureus osteomyelitis.

BACKGROUND: Osteomyelitis is a common pediatric musculoskeletal infection. This infection can weaken the normal bone structure, resulting in the risk of a pathologic fracture. The purpose of this study was to evaluate the risk factors for pathologic fracture in children with Staphylococcus aureus osteomyelitis. METHODS: Seventeen children who were treated for a pathologic long-bone fracture secondary to Staphylococcus aureus osteomyelitis between January 2001 and January 2009 at a tertiary-care pediatric hospital were identified. These patients were compared with a control group consisting of forty-nine children with Staphylococcus aureus osteomyelitis without a fracture who were matched for age, sex, and methicillin susceptibility. A retrospective review of the clinical records, magnetic resonance imaging (MRI) studies, and microbiologic findings was performed. RESULTS: Patients who developed a fracture presented with osteomyelitis at a mean age of 8.8 years (range, two to seventeen years). Fifteen of the seventeen patients had methicillin-resistant Staphylococcus aureus (MRSA) isolates, and two had methicillin-susceptible Staphylococcus aureus (MSSA). The mean time from disease onset to fracture was 72.1 days (range, twenty to 150 days). The duration of hospitalization, number of surgical procedures, duration of antibiotic treatment, and total number of complications differed significantly between the two groups. MRI studies at the time of admission demonstrated a significantly greater prevalence of subperiosteal abscess and greater circumferential size of such an abscess in the patients with a fracture. A sharp zone of abnormally diminished enhancement of the marrow was also more common in these patients. The USA300-0114 pulsotype was more commonly associated with an elevated likelihood of fracture. CONCLUSIONS: Staphylococcus aureus osteomyelitis is a serious infection that may predispose children to pathologic fractures. Protected weight-bearing and activity restriction are recommended in children with Staphylococcus aureus osteomyelitis who have the risk factors demonstrated in this study.

Hereditary neuropathy with liability to pressure palsies: case report and discussion.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an uncommon diagnosis that should be considered in patients with multiple compressive neuropathies. We present the case of a woman who presented with bilateral hand numbness and weakness. Electrodiagnostic testing revealed bilateral carpal tunnel syndrome, bilateral ulnar neuropathy at the elbow, left peroneal neuropathy at the fibular head, and a primarily demyelinating generalized sensorimotor neuropathy. Subsequent genetic testing identified a deletion at chromosome 17p11.2 to confirm the diagnosis of HNPP. Treatment of this largely self-limiting disease is controversial, and this patient suffered minimal disability with treatment including splinting and surgical releases.

Möbius syndrome.

We describe a case of Möbius syndrome in a 3-month-old infant. Striking imaging findings of pontine hypoplasia in the region of the 6th and the 7th nerve complexes were noted. In addition, absence of the middle cerebellar peduncles was noted, a finding that, to our knowledge, has never been reported before in the literature. Clinical presentations, other radiologic findings, and a possible pathogenesis are discussed.

A rare case of lymphangiomatosis of the craniocervical spine in conjunction with a Chiari I malformation.

Lymphangiomatosis of the bone is rare. The axial as well as appendicular skeleton may be affected. Neurosurgical consultation may be called for several reasons: (1) lesions involving the calvarium and/or spine; (2) nondiagnostic biopsies from more accessible and less morbid locations, and (3) persistent CSF leak and/or recurrent meningitis. Thus, it is important for the neurosurgeon to be familiar with this disease entity and consider it in the differential diagnoses of multifocal lytic lesions of the axial skeleton. We present a case report of a 4-year-old girl with lymphangiomatosis of the skull base and upper cervical spine with concurrent Chiari I malformation and briefly review the literature.

Castleman's disease in a child presenting with a partly mineralized solitary meningeal mass.

We report a case of solitary intracranial childhood Castleman's disease (CD) presenting with a sudden onset of partial seizures due to a meningeal and cortical mass lesion. The patient was a previously healthy 8-year-old girl who developed a new onset of simple partial seizures with motor signs. On physical examination, she was neurologically intact. Other findings included low-grade fever, mild microcytic anemia and lymphopenia. Magnetic resonance imaging (MRI) of the brain revealed a left posterior parietal, partly mineralized, contrast-enhancing meningeal mass with cortical invasion and adjacent white matter edema. A complete surgical resection of the dural-based component and a subtotal resection of the adherent, invasive cortical lesion were performed. Pathohistology and flow cytometry of the dural-based lesion disclosed a hyaline-vascular type of CD with striking proliferation of polyclonal B lymphocytes, scattered plasma cells and extensive multifocal cortical mineralization. At the 6-month follow-up, the patient was seizure free on antiepileptics and had returned to normal daily activities. MRI showed no residual lesion, and a workup for systemic disease was negative.

Cervicothoracic extradural arachnoid cyst: possible association with obstetric brachial plexus palsy.

The association of cervicothoracic extradural arachnoid cysts and obstetric brachial plexus palsy has not previously been reported. We report two patients with this association. The first patient is a 9-month-old boy with left obstetric brachial plexus palsy that developed bilateral leg weakness at 6 months of age owing to compression of the spinal cord by a C6 to T8 left cervicothoracic extradural arachnoid cyst. The second patient is a 3-year-old girl with bilateral brachial plexus palsy and spastic paraparesis who had magnetic resonance imaging at 3 days of age that showed intraspinal cord injury and a cervicothoracic extradural arachnoid cyst compressing the spinal cord. We believe that the association of cervicothoracic epidural arachnoid cysts and obstetric brachial plexus palsy in these patients was causal and recommend that the possibility of a cervicothoracic epidural arachnoid cyst be considered in patients with brachial plexus palsy and evidence of spinal cord injury.