Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes.

OBJECTIVE: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes. METHODS: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a neuropsychological test battery. RESULTS: Few cognitive differences were found between the athlete groups at the preseason or postseason assessments. However, a higher percentage of the contact sport athletes performed more poorly than predicted postseason on a measure of new learning (California Verbal Learning Test) compared to the noncontact athletes (24% vs 3.6%; p < 0.006). On 2 postseason cognitive measures (ImPACT Reaction Time and Trails 4/B), poorer performance was significantly associated with higher scores on several head impact exposure metrics. CONCLUSION: Repetitive head impacts over the course of a single season may negatively impact learning in some collegiate athletes. Further work is needed to assess whether such effects are short term or persistent.

Programmable CSF shunt valves: radiographic identification and interpretation.

The programmable CSF shunt valve has become an important tool in hydrocephalus treatment, particularly in the NPH population and in pediatric patients with complex hydrocephalus. The purpose of this study is to provide a single reference for the identification of programmable shunt valves and the interpretation of programmable shunt valve settings. Four major manufacturers of programmable shunts agreed to participate in this study. Each provided radiographic images and legends for their appropriate interpretation. Issues of MR imaging compatibility for each valve are also discussed.

Dystrophic neuritic processes in epileptic cortex.

Cortical dysplasia is a frequent finding in cortical resections from children with refractory epilepsy. Diagnostic criteria and a classification scheme for cortical dysplasia has been proposed, though the relationship between specific cortical dysplasia features and their causal relationship with epilepsy is poorly understood. We reviewed 28 surgical resections from children and identified a common and easily recognized feature of cortical dysplasia: maloriented, misshapen and occasionally coarse neurofilament stained process forming a dystrophic neuritic background. The dystrophic neuritic background was associated with other features of cortical dysplasia in all 28 patients with cortical dysplasia, 26 with refractory epilepsy and 2 patients with other neurologic diagnoses. In seven children with refractory epilepsy due to other pathologic diagnosis such as vascular or glial lesions, the dystrophic neuritic background was only found in one patient with a ganglioglioma and other features suggestive of an associated cortical dysplasia. Our data indicate that a dystrophic neuritic background is a common and relatively specific neuropathologic finding in cortical dysplasia.

Role of MAP kinase pathways in primitive neuroectodermal tumors.

Mitogen-activated protein kinase and Phosphatidylinositol-3 kinase/Akt-mediated signaling pathways play a major role in controlling cell proliferation, differentiation and cell death. Phosphorylation and dephosphorylation of their specific Thr/Tyr residues is critical in determining their activity. We determined the expression pattern and activity of MAP kinases and Akt in Primitive Neuroectodermal Tumors (PNETs). The kinase activity of extracellular signal-regulated kinase (ERK) was higher in both primary tumors and cell lines, as evident from the increased phosphorylation of ERK1 and ERK2. We did not observe the activation of C-jun N-terminal kinase (JNK) or p38 MAPK The expression of Raf-1, a kinase acting upstream of ERK, was significantly increased in primary tumors compared to normal brain. The PI-3 kinase-activated phosphorylation of Akt was also higher in primary tumors. These results suggest that activation of the Raf-1/ERK module of the MAP kinase pathway play an important role in PNETs.

Metachronous Epstein-Barr virus-related smooth muscle tumors in a child after heart transplantation: case report and review of the literature.

Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV) infection in patients who have had transplants. The authors report 2 metachronous EBV-containing smooth muscle tumors in a child who had a heart transplant, and review the literature on posttransplant soft tissue tumors.

Evaluation and management of children younger than two years old with apparently minor head trauma: proposed guidelines.

OBJECTIVE: In children <2 years old, minor head trauma (HT) is a common injury that can result in skull fracture and intracranial injury (ICI). These injuries can be difficult to detect in this age group; therefore, many authors recommend a low threshold for radiographic imaging. Currently, no clear guidelines exist regarding the evaluation and management of head-injured infants. We sought to develop guidelines for management based on data and expert opinion that would enable clinicians to identify children with complications of HT and reduce unnecessary imaging procedures. METHODS. EVIDENCE: References addressing pediatric HT were generated from a computerized database (Medline). The articles were reviewed and evidence tables were compiled. EXPERT PANEL: The multidisciplinary panel was comprised of nine experts in pediatric HT. CONSENSUS PROCESS: A modified Delphi technique was used to develop the guidelines. Before the one meeting, panel members reviewed the evidence and formulated answers to specific clinical questions regarding HT in young children. At the meeting, guidelines were formulated based on data and expert consensus. RESULTS: A management strategy was developed that categorizes children into 4 subgroups, based on risk of ICI. Children in the high-risk group should undergo a computed tomography (CT) scan. Those in the intermediate risk group with symptoms of possible ICI should either undergo CT scan or observation. Those in the intermediate risk group with some risk for skull fracture or ICI should undergo CT and/or skull radiographs or observation. Those in the low-risk group require no radiographic imaging. CONCLUSIONS: We have developed a guideline for the evaluation of children <2 years old with minor HT. The effect of these guidelines on clinical outcomes and resource utilization should be evaluated.

Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia is characterized by disorganized cortical lamination, dysplastic and heterotopic neurons, and an association with epilepsy. The contribution that dysplastic and heterotopic neurons make to epileptogenesis in focal cortical dysplasia is unknown and the phenotype of these cells may be distinct. The authors hypothesized that the expression of genes encoding glutamatergic (glutamate [GluR] and N-methyl-D-aspartate NMDA receptors [NR]) and gamma-aminobutyric acid A receptor (GABA(A)R) subunits is distinct in dysplastic and heterotopic neurons and that changes in receptor gene expression could be defined in a cell-specific pattern. METHODS: Single immunohistochemically labeled dysplastic and heterotopic neurons were microdissected from human focal cortical dysplasia specimens obtained during epilepsy surgery. Pyramidal neurons were microdissected from postmortem control cortex and from temporal cortex without dysplasia resected during temporal lobectomy. Poly (A) messenger RNA (mRNA) from single neurons was amplified, radiolabeled, and used to probe complementary DNA (cDNA) arrays containing GluR(1-6), NR(1A,1B), NR(2A-D), and GABA(A)Ralpha(1-6), and -Rbeta(1-3) subunit cDNAS: The relative hybridization intensities of each mRNA-cDNA hybrid were quantified by phosphorimaging. RESULTS: GluR, NR, and GABA(A)R subunit mRNA expression did not differ between control neurons and nondysplastic epilepsy specimens. Expression of GluR(4), NR(2B), and NR(2C) subunit mRNA was increased, and NR(2A) and GABA(A)Rbeta(1) subunit mRNA was decreased in dysplastic compared with pyramidal and heterotopic neurons. In contrast, GABA(A)Ralpha(1), -Ralpha(2), and -Rbeta(2) as well as GluR(1) mRNA levels were reduced in both dysplastic and heterotopic neurons. CONCLUSIONS: Differential expression of GluR, NR, and GABA(A)R mRNA in dysplastic and heterotopic neurons demonstrates cell specific gene transcription changes in focal cortical dysplasia. These results suggest that dysplastic and heterotopic neurons may be pharmacologically distinct and make differential contributions epileptogenesis in focal cortical dysplasia.

Age-related differences in acute physiologic response to focal traumatic brain injury in piglets.

INTRODUCTION: The goal of the present study was to determine whether age-related differences in the acute physiologic response to scaled cortical impact injury contribute to differences in vulnerability to traumatic brain injury (TBI). METHODS: Heart rate (HR), mean arterial pressure (MAP), brain temperature (BrT) and cerebral blood flow (CBF) were measured in 22 piglets (7 of age 5 days, 8 of age 1 month, 7 of age 4 months) at baseline and for 3 h following scaled cortical impact injury. RESULTS: There were no age-dependent variations from baseline in HR, MAP or BrT following injury. CBF increased in the 5-day-old animals following injury while CBF in the 1- and 4-month-old animals decreased following injury (p = 0.0049). CONCLUSION: CBF was shown to have a significant age-dependent response to TBI with the youngest animals exhibiting increased CBF following injury.

Maturation-dependent response of the piglet brain to scaled cortical impact.

OBJECT: The goal of this study was to investigate the relationship between maturational stage and the brain's response to mechanical trauma in a gyrencephalic model of focal brain injury. Age-dependent differences in injury response might explain certain unique clinical syndromes seen in infants and young children and would determine whether specific therapies might be particularly effective or even counterproductive at different ages. METHODS: To deliver proportionally identical injury inputs to animals of different ages, the authors have developed a piglet model of focal contusion injury by using specific volumes of rapid cortical displacement that are precisely scaled to changes in size and dimensions of the growing brain. Using this model, the histological response to a scaled focal cortical impact was compared at 7 days after injury in piglets that were 5 days, 1 month, and 4 months of age at the time of trauma. Despite comparable injury inputs and stable physiological parameters, the percentage of hemisphere injured differed significantly among ages, with the youngest animals sustaining the smallest lesions (0.8%, 8.4%, and 21.5%, for 5-day-, 1-month-, and 4-month-old animals, respectively, p = 0.0018). CONCLUSIONS: These results demonstrate that, for this particular focal injury type and severity, vulnerability to mechanical trauma increases progressively during maturation. Because of its developmental and morphological similarity to the human brain, the piglet brain provides distinct advantages in modeling age-specific responses to mechanical trauma. Differences in pathways leading to cell death or repair may be relevant to designing therapies appropriate for patients of different ages.

CHOP Infant Coma Scale ("Infant Face Scale"): a novel coma scale for children less than two years of age.

The Glasgow Coma Scale (GCS) is the most frequently used tool worldwide for assessing the severity of neurologic injury after brain trauma, although applying this scale to infants and younger children can be problematic. The CHOP Infant Coma Scale, or Infant Face Scale (IFS), is a novel scale for children under 2 years of age which differs from other pediatric coma scales in the following ways: (1) it relies on objective behavioral observations; (2) it assesses cortical as well as brainstem function; (3) it parallels the GCS in scoring but is based on infant-appropriate behaviors; and (4) it can be applied to intubated patients. We report the results of a prospective study designed to compare interrater reliability between the IFS and GCS in children less than 2 years of age. Seventy-five hospitalized children less than 2 years of age were assessed simultaneously by a pair of observers, representing a spectrum of health care professionals, who scored the children using both the IFS and GCS. Interrater reliability for each pair of observers for each scale was assessed using the kappa statistic. A second series of 10 infants in the intensive care unit with specific diagnoses of acute traumatic or hypoxic/ischemic brain injury were similarly assessed. In the 75 hospitalized infants with a variety of diagnoses, interrater reliability for the GCS was in the "almost perfect," "slight," and "fair" range for the eye-opening, motor, and verbal subtests, respectively. In contrast, the IFS showed interrater reliability in the "almost perfect," "substantial," and "almost perfect" ranges for the three subtests. When applied to infants in an intensive care unit with acute traumatic brain injury or hypoxia/ischemia, the GCS interrater reliability scores were in the "fair" range, while the IFS scores were in the "almost perfect" range. The IFS demonstrates improved interrater reliability in direct comparison to the GCS, particularly in the "verbal/face" component where most pediatric coma scales are deficient. The IFS may prove to be a simple and practical bedside index of brain injury severity in children less than two years of age.

Tonsillar pain mimicking glossopharyngeal neuralgia as a complication of vagus nerve stimulation: case report.

An adolescent girl presented with severe, lancinating tonsillar pain exacerbated by swallowing 6 weeks after initiation of left vagus nerve stimulation for intractable epilepsy. Her symptoms mimicked those seen in glossopharyngeal neuralgia and were relieved by temporary cessation of stimulation. Gradual reinstitution of therapy with alteration in stimulus parameters resulted in improved seizure control as well as cessation of pain symptoms. Direct stimulation of the vagus nerve may result in vagoglossopharyngeal neuralgia, which, in this case, was amenable to stimulus modification.

Extrarenal nephroblastic proliferation in spinal dysraphism. A report of 4 cases.

Four cases of extrarenal nephrogenic proliferation in the sacrococcygeal region with spinal dysraphism are presented. In two of the cases, features of Wilm's or incipient Wilm's tumor were present. The previous literature on sacrococcygeal nephrogenic tissue is reviewed, and the impact of these findings on the histogenesis of extrarenal sacrococcygeal Wilm's tumor is discussed.

Language-related cognitive declines after left temporal lobectomy in children.

Presented is a case series demonstrating that clinically significant language-related cognitive declines not detected by intelligence quotient (IQ) testing occur after left temporal lobectomy in school-aged children. In this series, comprehensive preoperative and postoperative neuropsychologic evaluations were completed in eight school-aged patients who underwent temporal lobectomy (five left, three right) for temporal lobe epilepsy. Mean age at surgery was 13 years, 11 months +/- 2 years, 1 month. Testing included measurement of IQ, verbal learning, naming, visual memory, sight word recognition, reading comprehension, and calculation. All five left temporal lobectomy patients demonstrated significant language-related cognitive declines on postoperative neuropsychologic testing, including deficits in verbal IQ (one patient), verbal learning (four patients), naming (one patient), and reading comprehension (one patient). These deficits were clinically evident in four of the five left temporal lobectomy patients, leading to declines in educational performance. IQ testing alone did not reliably identify these deficits. No significant declines were found after surgery in three right temporal lobectomy patients. Average or high preoperative functioning may have predisposed patients to postoperative deficits in this series, whereas magnetic resonance imaging or pathologic abnormalities did not protect against postoperative deficits. Outcome studies of temporal lobectomy in childhood should use comprehensive neuropsychologic testing to identify cognitive deficits.

Retinal hemorrhages caused by accidental household trauma.

Traumatic retinal hemorrhages in young children are considered pathognomonic of child abuse. We identified 3 children with unilateral retinal hemorrhages caused by accidental household trauma. The hemorrhages were ipsilateral to intracranial hemorrhage and isolated to the posterior retinal pole.

Treatment of villous hypertrophy of the choroid plexus by endoscopic contact coagulation.

Villous hypertrophy of the choroid plexus (VHCP) is a condition characterized by overproduction of cerebrospinal fluid by bilaterally symmetric and enlarged, yet histologically normal, choroid plexi. Medical and surgical therapy have been met with variable success. Traditional shunting procedures often result in failure to correct the underlying problem as well as failure to absorb the large volume of fluid produced. Craniotomy for open surgical resection of the choroid is associated with considerable morbidity. The authors describe a technique of endoscopic contact coagulation as an effective and safe treatment of VHCP. A 14-month-old hydrocephalic girl with VHCP who failed ventriculoperitoneal shunting as the sole treatment of her hydrocephalus presented with increasing ascites. She was successfully treated with ventriculoperitoneal shunting and endoscopic Bugby wire-directed monopolar contact coagulation of the hyperplastic choroid plexus. Postoperatively her head circumference and cognitive development is normal for her age, and her ascites has resolved. Endoscopic contact coagulation of the hyperplastic choroid plexus is a minimally invasive surgical method which treats the cause of the CSF production while avoiding the operative complications of open choroid plexus resection.

Imaging studies in a unique familial dysmyelinating disorder.

We report the imaging findings in five patients with a unique dysmyelinating disorder. MR studies of these infants showed obstructive hydrocephalus caused by mass effect produced by an enlarged cerebellum. The white matter of an enlarged cerebrum and cerebellum showed delayed myelination. Proton spectroscopy showed normal N-acetylaspartate (NAA) levels. While the dysmyelinating disorder was clearly differentiated from Canavan disease by an absence of elevated NAA and differing histopathologic findings and autosomal-dominant inheritance pattern, there were similarities to this disease in the presentation and, to some extent, in the initial imaging findings.

Visual impairment associated with mutism after posterior fossa surgery in children.

OBJECTIVE: To report four children with visual impairment associated with mutism after posterior fossa surgery. Mutism after posterior fossa surgery is a well-described phenomena, but to our knowledge, visual impairment has not been reported in association with it. METHODS: Record review of four children (age range, 3-7 yr) who underwent posterior fossa surgery (via suboccipital craniotomies) for removal of a medulloblastoma (three patients) or ependymoma (one patient). Each presented with headache, ataxia, or nausea and vomiting, but none had preoperative visual complaints other than diplopia. Postoperatively, all patients were mute, and because of apparent visual loss, neuro-ophthalmic consultation was requested. Postoperative scans and examinations were also reviewed. RESULTS: Each child was awake but appeared withdrawn without verbal output. No child blinked to threat or fixed or followed. In each case, pupillary reactivity was normal, and funduscopic examinations revealed only papilledema. One child reached for money. Within weeks or months postoperatively, the mutism spontaneously resolved, and visual behavior in general improved, roughly in parallel. During the follow-up period, papilledema resolved and the disc color was normal in each case. Magnetic resonance images obtained postoperatively revealed nothing remarkable, except surgical defects, without lesions in the retrogeniculate pathway. CONCLUSION: Impaired visual behavior, mimicking cortical visual loss, may be associated with mutism after posterior fossa surgery in children. The prognosis for recovery is excellent and parallels the return of normal speech. The mechanism is unclear.

Lateral meningocele syndrome: three new patients and review of the literature.

One female and two male patients with multiple lateral meningoceles are presented. They do not have neurofibromatosis or Marfan syndrome and share findings with the two previously described patients with multiple lateral meningoceles. The original report by Lehman et al. [1977: J Pediatr 90:49-54] was titled "familial osteosclerosis," because osteosclerosis was present in the proposita and her mother; the patient described by Philip et al. [1995: Clin Dysmorphol 4:347-351] also had increased bone density of the skull base and the sutures. Thickened calvaria were present in one of our patients; two had a prominent metopic suture. Other shared findings include multiple lateral meningoceles, Wormian bones, malar hypoplasia, downslanted palpebral fissures, a high narrow palate, and cryptorchidism in males. In addition, our patients showed ligamentous laxity, keloid formation, hypotonia, and developmental delay. A short umbilical cord was noted in two patients. One had a hypoplastic posterior arch of the atlas and an enlarged sella, as reported by Lehman et al. [1977]. Our patients appear to have the same syndrome as previously reported. We suggest it be called "lateral meningocele syndrome," because of this unique finding.