Liana Beni-Adani

Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions.

Memory and neurobehavioral dysfunctions are among the sequelae of traumatic brain injury (TBI). The Neurological Severity Score (NSS) includes 10 tasks and was previously designed to assess the functional status of mice after TBI. The object recognition task (ORT) measures specific episodic memory and is expressed by the percent time spent by an animal at a novel, unfamiliar object (Discrimination Index [DI]). It is an ideal tool for evaluating cognitive function after TBI. The present study sought to validate the use of the NSS and ORT in severe and mild focal TBI in mice, and to confirm that the spontaneous recovery and the radiological abnormalities, shown by T2-weighted magnetic resonance imaging (MRI), are dependent upon injury severity. Mice were subjected to severe and mild closed head injury (NSS at 1 h 7.52 +/- 0.34 and 4.62 +/- 0.14, respectively). NSS was evaluated for 25 days and showed a decrease by 3.86 +/- 0.26 and 2.54 +/- 0.35 units in the severely and mildly injured mice, respectively. ORT revealed DI in severely injured group of 51.7 +/- 6.15%, (vs approximately 75-80% in uninjured animal) on day 3 and 66.2 +/- 6.81% on day 21. In contrast, the mildly injured mice did not show cognitive impairment throughout the same period. The damage seen by MRI at 24 h after injury, strongly correlated with NSS(1h) (R = 0.87, p < 0.001). We conclude that NSS is a reliable tool for evaluation of neurological damage in head-injured mice, NSS(1h) predicts the motor dysfunction, cognitive damage, and brain-damage characteristics as depicted by T2-weighted MRI. The combined assessment of neurobehavioral and cognitive function along with MRI is most useful in evaluating recovery from injury, especially when testing effectiveness of novel treatments or genetic manipulations.

The occurrence of obstructive vs absorptive hydrocephalus in newborns and infants: relevance to treatment choices

Background and objectiveThe classification of hydrocephalus in newborns and in infants is different from the classification in adulthood. This difference exists due to disparity in the source pathologies that produce the hydrocephalus, and the practical distinctions in prognosis and treatment choices. The objective of this paper is to present the spectrum of obstructive-communicating hydrocephalus, which is more complex in the pediatric group, and to propose the relevance of this particular classification to treatment options.Materials and methodsThe authors categorized infants with active hydrocephalus at time of presentation into the following four groups along the spectrum of communicating vs obstructive HCP. Group 1: patients with a purely absorptive (communicating) HCP. In these patients, tetraventricular dilatation is usually observed with occasional extraaxial fluid accumulation. An extracranial CSF diversion (shunt) is the treatment of choice. Group 2: patients with an obstructive component together with a persistent absorptive component. In these patients, a technically successful endoscopic procedure will not prevent progression of clinical symptoms of HCP. An extracranial CSF diversion (shunt) should be the treatment of choice even though some of these patients are currently treated by endoscopy. Group 3: patients with an obstructive component together with a temporary absorptive component. In these patients, a technically successful ETV should be followed by temporary CSF drainage [via LP, continuous spinal drainage (CLD), or ventriculostomy] with or without supplemental medical treatment (i.e., Diamox) for several days. Such temporary drainage may decrease failure rate in this subgroup. Group 4: patients with a purely obstructive HCP. In these patients, an endoscopic procedure (ETV) is the treatment of choice. According to this spectrum classification, the authors classify different entities with representative cases and discuss relevancy to treatment options and prognosis.ResultsThe data suggest that obstructive hydrocephalus in the very young population may be rather a combination of obstructive and absorptive problem. The outcome of the patient depends mainly not only on the basic pathology causing the hydrocephalus but also on the treatment that is chosen and its complications. While bleeding and infection represent the major causes for communicating hydrocephalus, patients with complex pathologies of congenital type and intra- or interventricular obstructions may reflect obstructive hydrocephalus. Treatment of these patients may be successful by shuntless procedures if the absorptive problem is not the major component. In transient absorptive hydrocephalus, temporary measures were effective in many cases leading to successful procedures of ETV and/or posterior-fossa decompression in selected cases.ConclusionsShuntless procedures are the dream of a pediatric neurosurgeon provided it solves the problem and does not imply unacceptable risk. However, the benefit has to be evaluated years after the procedure is performed, as only prospective multicenter studies will truly show which procedure may have the best overall results in the developing child. Until such studies are available, understanding the basic pathology or the combination of pathologies leading to hydrocephalus in a given child may open the window of opportunities for other than shunt surgery in many hydrocephalic children with major obstructive component.

A single administration of the peptide NAP induces long-term protective changes against the consequences of head injury

The femtomolar-acting eight-amino-acid peptide (NAP), derived from activity-dependent neuroprotective protein (ADNP), provides long-term protection against the deleterious effects of closed head injury (CHI) in mice. Fifteen minutes after injury, mice were divided into two groups, control and NAP-treated and a single subcutaneous injection of NAP or vehicle was administered. A third group served as sham-treated (not subjected to head trauma). Each mouse was assessed for its clinical function, using neurological severity score, at various time intervals following CHI, up to 30–45 d. Total cerebral cortex RNA was prepared from the site of injury of CHI mice, and from parallel regions in peptide-treated and sham brains. RNA was then reversed transcribed to yield radioactive cDNA preparations that were hybridized to Atlas array membranes containing 1200 cDNAs spots. Comparison of sham-treated individual mice showed differential expression levels of at least 15 mRNA species. Furthermore, results indicated that one of the genes that did not change among individuals but specifically increased after CHI and decreased after NAP treatment was the cell surface glycoprotein Mac-1 (CD11B antigen). Thus, Mac-1 is suggested as a marker for the long-term outcome of head injury and as a potential target for NAP protective actions.

Timing of external ventricular drainage and neurodevelopmental outcome in preterm infants with posthemorrhagic hydrocephalus.

OBJECTIVE To delineate the impact of early (≤ 25 days of life) versus late (> 25 days) external ventricular drainage (EVD) on the neurodevelopmental outcome of preterm infants with posthemorrhagic hydrocephalus (PHH) following intraventricular hemorrhage (IVH). METHODS We retrospectively categorized 32 premature infants with PHH into two groups according to whether they underwent early (n = 10) or late (n = 22) EVD. We administered the Battelle Developmental Inventory II and a neuromotor examination (median age, 73 months, range: 29-100). RESULTS In adjusted comparisons, early EVD was associated with better scores than late EVD in adaptive (79 ± 22.6 vs. 58.8 ± 8.1, P = .01), personal social (90.7 ± 26 vs. 67.3 ± 15.9, P = .02), communication (95.4 ± 27.5 vs. 69.6 ± 20.5, P = .04) and cognitive (78.9 ± 24.4 vs. 60.7 ± 11.5, P = .055) functions. Three (30%) early EVD infants had severe (<2.5 standard deviation) cognitive disability compared to 18 (82%) late EVD infants (P = .03). The incidences of cerebral palsy and neurosurgical complications were equal for the two groups. Subgroup analyses suggested that early EVD was beneficial in infants with original grade III IVH (n = 15, P < 0.05), but that it had no beneficial effects in infants with prior parenchymal injury (n = 17, P = NS). CONCLUSION In this small retrospective series, early EVD is associated with lower rates of cognitive, communication and social disabilities than later EVD in infants with PHH without prior parenchymal injury. A randomized prospective trial is warranted.

International survey on the management of skin stigmata and suspected tethered cord

ObjectivesWe designed a survey to investigate current international management trends of neonates with lumbar midline skin stigmata suspicious of tethered cord, among pediatric neurosurgeons, focusing on the lower risk stigmata, simple dimples, deviated gluteal folds, and discolorations. Our findings will enable physicians to assess their current diagnosis routine and aid in clarifying management controversies.Study designA questionnaire on the proposed diagnostic evaluation of seven case reports, each accompanied by relevant imaging, was distributed by e-mail to members of the International Society for Pediatric Neurosurgery, the European Society for Pediatric Neurosurgery, and via the PEDS server list between March and August 2008.ResultsSixty-two questionnaires, completed by experienced professionals with a rather uniform distribution of experience levels, were analyzed. Forty-eight percent do not recommend any imaging of simple dimples, 30% recommend US screening and 22% recommend MR. Seventy-nine percent recommend imaging of deviated gluteal fold with 30% recommending MR. Ninety-two percent recommend imaging infants with hemangiomas with 74% recommending MR. MR for sinus tracts is recommended by 90% if sacral and by 98% if lumber. Eighty-four percent recommend MR for filar cyst.ConclusionsOur survey demonstrates that management of low-risk skin stigmata, simple dimple, deviated gluteal fold, and discolorations lacks consensus. In addition, a significant sector of the professional community proposes a work-up of simple dimples, sacral tracts, and filar cysts that contradicts established recommendations. A simple classification system is needed to attain a better approach, enabling correct diagnosis of tethered cord without exposing neonates to unnecessary examinations.

Malignant transformation in pediatric spinal intramedullary tumors: case-based update

BackgroundIn children, intramedullary spinal cord neoplasms are rare. These are typically low-grade neuroepithelial tumors, most commonly astrocytomas, ependymomas, and gangliogliomas. Malignant transformation, while common in recurrent adult low-grade gliomas, is an unusual event in pediatric low-grade neoplasms, specifically in intramedullary spinal cord tumors.Illustrative casesWe report two cases of malignant transformation in low-grade neuroepithelial tumors of the pediatric intramedullary spinal cord. Two children with intramedullary tumors, one with a WHO grade I ganglioglioma and one with a low-grade astrocytoma, were treated surgically, diagnosed histologically, and followed through the course of their disease. Both patients’ tumors transformed to higher grades without prior irradiation or chemotherapy, and without a genetic predisposition to tumorigenesis.DiscussionMalignant transformation can occur in low-grade intramedullary neoplasms in children. This is a novel documented event for pediatric intramedullary spinal cord tumors and a rare event for all pediatric low-grade neuroepithelial tumors without induction by irradiation. A survey of the relevant literature reveals an underwhelming number of studies focusing on malignant transformation in children’s CNS tumors relative to adults. Further investigation into molecular mechanisms of pediatric low-grade neoplasms may reveal more aggressive tumor sub-variants predisposed to malignant degeneration.