Thomas Pittman

Stroke Associated with Marijuana Abuse

We present the case of a 15-year-old with a cerebellar infarct that involved multiple arterial territories. It was temporally related to, and probably caused by, heavy marijuana use. While the mechanism of marijuana-associated stroke is unclear, the drug is known to cause hypotension and to impair peripheral vasomotor reflexes. We suspect that the child had diminished cerebral autoregulatory capacity and developed the stroke during a period of hypotension.

Significance of a Subdural Hematoma in a Child with External Hydrocephalus

Most physicians take the presence of a subdural hema-toma in a child without a history of trauma as presump-tive evidence of abuse. This assumption rests on our understanding of the pathophysiology of subdural hemorrhage ; subdural hematomas are caused by tearing intra-cranial bridging veins and it requires substantial force to rupture the veins and cause bleeding. The force required is thought to be more than can be generated in a short fall or by typical household accidents. Moreover, subdural hematomas most frequently occur in conjunction with other injuries, such as retinal hemorrhages and long bone fractures, which are indicative of severe trauma. There are some conditions, however, that are recognized to pre-dispose a child to develop a subdural hematoma after even minor injury: among them are coagulopathies, glu-taric aciduria, large arachnoid cysts and osteogenesis im-perfecta [1–5]. There have been suggestions that the presence of external hydrocephalus (i.e. familial macrocepha-ly, benign subdural effusions of infancy) also puts a child at risk [6–8]. Both theoretical and clinical evidence supports this position. Theoretical evidence comes from Papasian and Frim [9], who have created a mathematical model specifically to examine the forces required to cause a subdural hema-toma in a child with external hydrocephalus. They used two concentric hollow spheres to represent the brain and skull. Bridging veins were modeled to run orthogonally between the two spheres. Using currently accepted information about venous length and tensile strength, the authors calculated the strain on the veins caused by various forces and then defined the likelihood that the veins would fail in a given situation. They found that the same force caused veins to stretch proportionately more in children with extra axial collections than in those without. They calculated that the forces associated with low impact injuries were sufficient to cause venous rupture in children with external hydrocephalus. This finding held true for simulations with a variety of vessel lengths and diameters. Other groups have come to similar conclusions [10]. As a practical issue, it does appear that a disproportionate number of children with external hydrocephalus develop subdural hemorrhages. Several groups have commented on the relationship. Laubscher et al. [11] described 22 children with megalencephaly and enlarged subarachnoid spaces. Three of the 22 had subdural hema-tomas: all apparently did well and none had recognized trauma. Similar results were reported by Mori et al. [12], Azais and Echenne [13] and, later, by Piatt [14]. The clinical association …

Latex Allergy in Children with Spina bifida

We studied the prevalence of latex-specific IgE among the children in our myelomeningocele clinic and several groups of controls using skin tests, a commercially available ELISA and an in-house RAST. Thirty-nine of 83 (47%) children with myelomeningocele had antibodies directed against latex as did 6 of 40 (15.7%) chronically ill controls, 4 of 105 (3.8%) medical controls and 2 of 75 (2.7%) well controls. Within each study group the likelihood of a positive skin test increased with the number of operations the subject had undergone. Children with myelomeningocele were much more likely to have antibodies to latex than were chronically ill controls with similar surgical histories. A retrospective chart review of 18 years and a total of 646 operations disclosed only one episode of intraoperative anaphylaxis which appeared to be related to latex within our study group.

Growing skull fractures: strategies for repair and reconstruction.

Most skull fractures in growing children heal rapidly and without significant contour irregularity. Skull fractures in infants associated with dural injuries, however, may progressively enlarge as a result of bone erosion by leptomeningeal herniation at the dural tear sites and are known as “growing skull fractures.” Over a 6-year period, seven growing skull fractures occurred in a population of 592 consecutive pediatric head injuries at Cardinal Glennon Childrens Hospital (prevalence, 1.2%). Prompt recognition of growing skull fractures, repair by regional craniectomy and pericranial dural inlay graft, and immediate contour reconstruction with rigidly fixed cranial bone graft ensure reliable aesthetic and functional restoration of the growing neurocranium.

Autophagy and oxidative stress in gliomas with IDH1 mutations

IDH1 mutations in gliomas associate with longer survival. Prooxidant and antiproliferative effects of IDH1 mutations and its d-2-hydroxyglutarate (2-HG) product have been described in vitro, but inconsistently observed. It is also unclear whether overexpression of mutant IDH1 in wild-type cells accurately phenocopies the effects of endogenous IDH1-mutations on tumor apoptosis and autophagy. Herein we investigated the effects of 2-HG and mutant IDH1 overexpression on proliferation, apoptosis, oxidative stress, and autophagy in IDH1 wild-type glioma cells, and compared those results with patient-derived tumors. 2-HG reduced viability and proliferation of U87MG and LN18 cells, triggered apoptosis in LN18 cells, and autophagy in U87MG cells. In vitro studies and flank xenografts of U87MG cells overexpressing R132H IDH1 exhibited increased oxidative stress, including increases of both manganese superoxide dismutase (MnSOD) and p62. Patient-derived IDH1-mutant tumors showed no significant differences in apoptosis or autophagy, but showed p62 accumulation and actually trended toward reduced MnSOD expression. These data indicate that mutant IDH1 and 2-HG can induce oxidative stress, autophagy, and apoptosis, but these effects vary greatly according to cell type.

Persistent Coxsackie B encephalitis: Report of a case and review of the literature

Although the diagnosis is rarely confirmed, enteroviruses are a common cause of meningitis. Coxsackie B is responsible for more than half of the cases of aseptic meningitis in infants less than 3 months old, but is less common as a cause of neurological disease in older persons. In addition to aseptic meningitis, Coxsackie B has been reported to cause a wide range of other neurological disorders, albeit rarely. The authors report a young adult with persistent Coxsackie B encephalitis that was heralded by focal seizures and evolved to intractable coma with multifocal myoclonus. The diagnosis was established by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) on tissue obtained at brain biopsy. Cerebrospinal fluid (CSF) viral cultures and PCR were negative for enteroviruses. This case highlights unusual features of a persistent infection that could easily have been mistaken for a neurodegenerative or other noninfectious process. It also emphasizes the importance of performing brain biopsy on individuals with neurological disease of obscure nature.

Linezolid for the Treatment of a Heteroresistant Staphylococcus aureus Shunt Infection

The emergence of multidrug-resistant bacteria as the cause of ventriculoperitoneal shunt infections is a disconcerting phenomenon that often requires the use of alternative antimicrobials due to resistance against commonly used agents. The following is a case report describing the successful treatment of a ventriculoperitoneal shunt infection caused by a heteroresistant strain of Staphylococcus aureus with linezolid. Linezolid may have utility in treating pediatric CNS infections due to its tolerability, excellent blood-brain barrier penetration, and activity against multiple resistant Gram-positive organisms such as S. aureus, vancomycin-resistant Enterococcus faecium and Streptococcus pneumoniae.

Long-term treatment with temozolomide in malignant glioma.

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.

Interhemispheric lipoma connected to subcutaneous lipoma via lipomatous stalk

Lipomas are rare intracranial lesions and are generally thought to be asymptomatic. The vast majority of intracranial lipomas are viewed as incidental findings on imaging studies and treated conservatively. Intracranial lipomas are frequently accompanied by additional intracranial congenital malformations, but only rarely has an association with subcutaneous lipomas been described. We report an infant with a subgaleal lipoma in the region of the anterior fontanelle connected to a large interhemispheric (pericallosal) lipoma via a tiny lipomatous stalk. Because of this association, infants who present with a subcutaneous lipoma of the scalp might be considered for MR imaging to evaluate for an intracranial component.

Neural Network Classification of Pediatric Posterior Fossa Tumors Using Clinical and Imaging Data

A neural network was developed that utilizes both clinical and imaging (CT and MRI) data to predict posterior fossa tumor (PFT) type. Data from 33 children with PFTs were used to develop and test the system. When all desired information was available, the network was able to correctly classify 85.7% of the tumors. In cases with incomplete data, it was able to correctly classify 72.7% of the tumors. In both instances, the diagnoses made by the network were more likely to be correct than those made by the neuroradiologists.