Constitutional LZTR1 mutation presenting with a unilateral vestibular schwannoma in a teenager.

Schwannomatosis is a rare neurofibromatosis clinically diagnosed by age-dependent criteria, with bilateral vestibular schwannoma and/or a constitutional NF2 mutation representing exclusion criteria. Following SMARCB1 germline mutations, constitutional mutations in LZTR1 were discovered. We report on the molecular investigation in a patient presenting at 14 years with a unilateral vestibular schwannoma, ultimately causing blindness and unilateral hearing loss, in the absence of other schwannomas or a positive family history. In DNA derived from frozen tumor tissue, a comprehensive NF2, SMARCB1 and LZTR1 analysis showed an NF2 truncating mutation c.1006_1021delins16; an LZTR1 mutation c.791+1G>A; and a partial 22q deletion including NF2, SMARCB1 and LZTR1. Sequence analysis on peripheral blood derived DNA showed the LZTR1 mutation to be constitutional, but the NF2 mutation and partial 22q deletion were not found, indicating them to be somatic events. RNA-based targeted analysis confirmed missplicing of LZTR1 intron 8, predicted to result in a premature stop codon. This LZTR1 mutation was paternally inherited. While isolated vestibular schwannoma or NF2 may be considered in a young individual with a unilateral vestibular schwannoma, this report suggests that LZTR1 -related schwannomatosis be added to this differential diagnosis.

Murres, capelin and ocean climate: inter-annual associations across a decadal shift.

To ensure energy demands for reproduction are met, it is essential that marine birds breed during periods of peak food availability. We examined associations of the breeding chronology of common murres (Uria aalge) with the timing of the inshore arrival of their primary prey, capelin (Mallotus villosus) from 1980 to 2006 across a period of pervasive change in the Northwest Atlantic ecosystem. We also assessed the influence of ocean temperature and the North Atlantic Oscillation (NAO; an index of winter climate and oceanography) on these interactions. We found a lagged linear relationship between variations in murre breeding chronology and the timing of capelin arrival in the previous year. On a decadal level, we found a non-linear threshold relationship between ocean temperature and the timing of capelin arrival and murre breeding. Centennially anomalous cold water temperatures in 1991 generated a marked shift in the timing of capelin spawning inshore and murre breeding, delaying both by more than 2 weeks. By the mid-1990s, ocean temperatures returned to pre-perturbation levels, whereas the temporal breeding responses of capelin and murres were delayed for a decade or more. Oceanographic conditions (temperature, NAO) were poor predictors of the timing of capelin arrival inshore in the current year compared to the previous one. Our findings suggest that knowledge of the timing of capelin availability in the previous year provides a robust cue for the long-lived murres, allowing them to achieve temporal overlap between breeding and peak capelin availability.

Population genetic structure in Atlantic and Pacific Ocean common murres (Uria aalge): natural replicate tests of post-Pleistocene evolution.

Understanding the factors that influence population differentiation in temperate taxa can be difficult because the signatures of both historic and contemporary demographics are often reflected in population genetic patterns. Fortunately, analyses based on coalescent theory can help untangle the relative influence of these historic and contemporary factors. Common murres (Uria aalge) are vagile seabirds that breed in the boreal and low arctic waters of the Northern Hemisphere. Previous analyses revealed that Atlantic and Pacific populations are genetically distinct; however, less is known about population genetic structure within ocean basins. We employed the mitochondrial control region, four microsatellite loci and four intron loci to investigate population genetic structure throughout the range of common murres. As in previous studies, we found that Atlantic and Pacific populations diverged during the Pleistocene and do not currently exchange migrants. Therefore, Atlantic and Pacific murre populations can be used as natural replicates to test mechanisms of population differentiation. While we found little population genetic structure within the Pacific, we detected significant east-west structuring among Atlantic colonies. The degree that population genetic structure reflected contemporary population demographics also differed between ocean basins. Specifically, while the low levels of population differentiation in the Pacific are at least partially due to high levels of contemporary gene flow, the east-west structuring of populations within the Atlantic appears to be the result of historic fragmentation of populations rather than restricted contemporary gene flow. The contrasting results in the Atlantic and Pacific Oceans highlight the necessity of carefully considering multilocus nonequilibrium population genetic approaches when reconstructing the demographic history of temperate Northern Hemisphere taxa.

Cervical spinal cord neurapraxia in the setting of Klippel-Feil anomaly: a diagnostic and therapeutic challenge.

STUDY DESIGN: Case report. SETTING: Temple University Children's Medical Center in USA. OBJECTIVES: To report a patient whose recurrent and transient episodes of quadriplegia mimicked cervical cord neurapraxia. Cervical spine neuroimaging revealed congenital intersegmental fusion of C5 through C7 (consistent with Klippel-Feil anomaly), corresponding abnormal spinal cord signals on T2-weighted images and enhancing focal lesion opposite the C4 vertebral body. A posterior cervical decompression at C4-C5 and lateral mass fixation was performed, and the episodic quadriplegia has not recurred. CONCLUSION: Understanding of the biomechanics of Klippel-Feil anomaly may facilitate prompt referral for surgical management and avoidance of permanent disability.

Use of tracer tests to evaluate the impact of enhanced-solubilization flushing on in-situ biodegradation.

Tracer tests were conducted to evaluate the effect of a complexing sugar flush (CSF) on in-situ biodegradation potential at a site contaminated by jet fuel, solvents, and other organic compounds. Technical-grade hydroxypropyl-beta-cyclodextrin was used during the CSF study, which was conducted in a hydraulically isolated cell emplaced in a surficial aquifer. In-situ biodegradation potential was assessed with the use of tracer tests, which were conducted prior to and immediately following the CSF study. Ethanol, hexanol, and benzoate were used as the biodegradable tracers, while bromide was used as a nonreactive tracer. The results indicate that the biodegradation of benzoate was similar for both tracer tests. Conversely, the biodegradation of ethanol (23% increase) and hexanol (41% increase) was greater for the post-CSF tracer test. In addition, analysis of core samples collected from within the test cell indicates that the population density of aerobic jet-fuel degraders increased in the vicinity of the injection wells during the CSF. These results indicate that the cyclodextrin flush did not deleteriously affect the indigenous microbial community. This study illustrates that tracer tests can be used to evaluate the impact of remediation activities on in-situ biodegradation potential.

Benefits and costs of increased levels of corticosterone in seabird chicks.

Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages.

Receiver-operating characteristic curves.

OBJECT: Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are frequently monitored in severely head injured patients. To establish which one (ICP or CPP) is more predictive of outcome and to examine whether there are significant threshold levels in the determination of outcome, receiver-operating characteristic (ROC) curves were used to analyze data in a large series of head-injured patients. METHODS: Data were obtained from a total of 291 severely head injured patients (207 adults and 84 children). Outcome was categorized as either independent (good recovery or moderate disability) or poor (severely disabled, vegetative, or dead) by using the Glasgow Outcome Scale; patients were also grouped according to the Marshall computerized tomography scan classification. CONCLUSIONS: The maximum value of a 2-minute rolling average of ICP readings (defined as ICPmax) and the minimum value of the CPP readings (CPPmin) were then used to calculate the sensitivity and specificity of the ROC curves over a range of values. Using ROC curves, a threshold value for CPPmin of 55 mm Hg and for ICPmax of 35 mm Hg appear to be the best predictors in adults. For children the levels appear to be 43 to 45 mm Hg for CPPmin and 35 mm Hg for ICPmax. Higher levels of CPPmin seem important in adults with mass lesions. These CPP thresholds (45 mm Hg for children and 55 mm Hg for adults) are lower than previously predicted and may be clinically important, especially in children, in whom a lower blood pressure level is normal. Also, CPP management at higher levels may be more important in adults with mass lesions. A larger observational series would improve the accuracy of these predictions.

Monozygotic twins discordant for external hydrocephalus.

External hydrocephalus (EH) is a transient, developmental condition in infancy characterized by macrocephaly and prominence of the subarachnoid spaces. The cause is unknown, but many patients have a family history consistent with autosomal dominant inheritance. This report describes a pair of monozygotic twins, only one of whom--the recipient of a twin-twin transfusion--has EH. Whatever the genotype of the twins, their discordant phenotypes suggest that the disproportionate calvarial growth that characterizes EH is set in motion--or not--during a limited, critical temporal window in fetal development.

Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks.

Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone.

Relationship of cerebral perfusion pressure and survival in pediatric brain-injured patients.

BACKGROUND: Adult brain injury studies recommend maintaining cerebral perfusion pressure (CPP) above 70 mm Hg. We evaluated CPP and outcome in brain-injured children. METHODS: We retrospectively reviewed the hospital courses of children at two Level I trauma centers who required insertion of intracranial pressure (ICP) monitors for management of traumatic brain injury. ICP, CPP, and mean arterial pressure were evaluated hourly, and means were calculated for the first 48 hours after injury. RESULTS: Of 188 brain-injured children, 118 had ICP monitors placed within 24 hours of injury. They suffered severe brain injury, with average admitting Glasgow Coma Scale scores of 6 +/- 3. Overall mortality rate was 28%. No patient with mean CPP less than 40 mm Hg survived. Among patients with mean CPP in deciles of 40 to 49, 50 to 59, 60 to 69, or 70 mm Hg, no significant difference in Glasgow Outcome Scale distribution existed. CONCLUSION: Low mean CPP was lethal. In children with survivable brain injury (mean CPP > 40 mm Hg), CPP did not stratify patients for risk of adverse outcome.

Mechanisms of population differentiation in marbled murrelets: historical versus contemporary processes.

Mechanisms of population differentiation in highly vagile species such as seabirds are poorly understood. Previous studies of marbled murrelets (Brachyramphus marmoratus; Charadriiformes: Alcidae) found significant population genetic structure, but could not determine whether this structure is due to historical vicariance (e.g., due to Pleistocene glaciers), isolation by distance, drift or selection in peripheral populations, or nesting habitat selection. To discriminate among these possibilities, we analyzed sequence variation in nine nuclear introns from 120 marbled murrelets sampled from British Columbia to the western Aleutian Islands. Mismatch distributions indicated that murrelets underwent at least one population expansion during the Pleistocene and probably are not in genetic equilibrium. Maximum-likelihood analysis of allele frequencies suggested that murrelets from "mainland" sites (from the Alaskan Peninsula east) are genetically different from those in the Aleutians and that these two lineages diverged prior to the last glaciation. Analyses of molecular variance, as well as estimates of gene flow derived using coalescent theory, indicate that population genetic structure is best explained by peripheral isolation of murrelets in the Aleutian Islands, rather than by selection associated with different nesting habitats. No isolation-by-distance effects could be detected. Our results are consistent with a rapid expansion of murrelets from a single refugium during the early-mid Pleistocene, subsequent isolation and divergence in two or more refugia during the final Pleistocene glacial advance, and secondary contact following retreat of the ice sheets. Population genetic structure now appears to be maintained by distance effects combined with small populations and a highly fragmented habitat in the Aleutian Islands.

Long-term follow-up data from the Shunt Design Trial.

BACKGROUND: A previously reported multicenter randomized trial assessed whether 2 new shunt valve designs would reduce shunt failure rates compared to differential pressure valves. The study did not show a significant difference in the time to first shunt failure. Patients entered the trial between October 1, 1993, and October 31, 1995. The primary results were based on the patients' status as of October 31, 1996 (a minimum follow-up of 1 year). This report describes the late complications based on the patients' most recent follow-up. METHODS: Three hundred and forty-four hydrocephalic children at 12 North American and European centers were randomized to 1 of 3 valves: a standard differential pressure valve; a Delta valve (PS Medical-Medtronic) or a Sigma valve (NMT Cordis). Patients were followed until their first shunt failure. Shunt failure was defined as shunt surgery for obstruction, overdrainage, loculation or infection. If the shunt did not fail, follow-up was continued until August 31, 1999. RESULTS: One hundred and seventy-seven patients had shunt failure. Shunt obstruction occurred in 131, overdrainage in 13, loculated ventricles in 2 and infection in 29. The overall shunt survival was 62% at 1 year, 52% at 2 years, 46% at 3 years, 41% at 4 years. The survival curves for the 3 valves were similar to those from the original trial and did not show a survival advantage for any particular valve. CONCLUSIONS: Prolonged follow-up to date does not alter the primary conclusions of the trial: there does not appear to be one valve that is clearly the best for the initial treatment of pediatric hydrocephalus.

A hazard of combining the infratentorial supracerebellar and the cerebellomedullary fissure approaches: cerebellar venous insufficiency.

The infratentorial supracerebellar approach is a popular technique for exposure of lesions of the superior vermis and pineal region. The cerebellomedullary fissure approach is enjoying increasing application as a technique for exposure of the fourth ventricle. Occasionally, a tumor that arises in the quadrigeminal plate or the superior vermis grows to fill the fourth ventricle, and for such a case a combination of the infratentorial supracerebellar approach and the cerebellomedullary fissure approach might be considered. We report a grave hazard of this combination. Two patients with tumors involving the superior vermis and filling the fourth ventricle were managed with a combined infratentorial supracerebellar/cerebellomedullary fissure approach. The first patient, who underwent a bilateral exposure, died on the sixth postoperative day due to massive hemorrhagic venous infarction of the cerebellum. The second patient, who was explored on one side only, suffered a protracted postoperative course characterized by suboccipital pain, torticollis, feeding difficulties and persisting hydrocephalus. Postoperative imaging showed swelling of the inferior vermis and ipsilateral hemisphere of the cerebellum with unilateral tonsillar herniation. Simultaneous compromise of the galenic and tentorial bridging veins and interruption of collateral pathways between these systems and the petrosal bridging veins, as in the combined infratentorial supracerebellar/cerebellomedullary fissure approach, may cause cerebellar venous insufficiency with venous congestion and possible venous infarction.

Some hypothalamic hamartomas contain transforming growth factor alpha, a puberty-inducing growth factor, but not luteinizing hormone-releasing hormone neurons.

Activation of LH-releasing hormone (LHRH) secretion, essential for the initiation of puberty, is brought about by the interaction of neurotransmitters and astroglia-derived substances. One of these substances, transforming growth factor alpha (TGFalpha), has been implicated as a facilitatory component of the glia-to-neuron signaling process controlling the onset of female puberty in rodents and nonhuman primates. Hypothalamic hamartomas (HH) are tumors frequently associated with precocious puberty in humans. The detection of LHRH-containing neurons in some hamartomas has led to the concept that hamartomas advance puberty because they contain an ectopic LHRH pulse generator. Examination of two HH associated with female sexual precocity revealed that neither tumor had LHRH neurons, but both contained astroglial cells expressing TGFalpha and its receptor. Thus, some HH may induce precocious puberty, not by secreting LHRH, but via the production of trophic factors--such as TGFalpha--able to activate the normal LHRH neuronal network in the patient's hypothalamus.

Subdural empyema complicating cerebrospinal fluid shunt infection.

Subdural empyema has not been reported previously as a complication of cerebrospinal fluid (CSF) shunt surgery. An infant submitted to CSF shunt insertion for congenital hydrocephalus developed subdural empyema after a failed attempt to treat a superficial scalp wound infection with oral antibiotics. Enterobacter cloacae was isolated from the empyema. Temporizing management of the preceding superficial wound infection with oral antibiotics probably was the cause of this exotic pathogen. The treatment of infected scalp wounds contiguous with shunt hardware must be surgical.

The Chiari II malformation: lesions discovered within the fourth ventricle.

Structural lesions associated with the Chiari II malformation have been identified within the fourth ventricle in 8 patients. During the 42-month period encompassing the operations of the 7 patients treated surgically, only 9 other patients were explored without the discovery of some associated structural lesion. The patients ranged in age from 2 to 26 years. The following lesions were identified: glial or arachnoidal cysts (3 patients), glial or choroidal nodules (3 patients) and subependymoma (2 patients). These lesions were all situated in the roof of the fourth ventricle adjacent to or interspersed with the choroid plexus. Only the cystic lesions were identified by preoperative imaging. In only 1 case did the associated lesion, a 2-cm cyst, seem to contribute to the patient's clinical presentation. Structural lesions of the fourth ventricle associated with the Chiari II malformation are common in patients who are submitted to decompression. These lesions may be dysplasias of developmental origin, or they may be reactive lesions related to chronic compression and ischemia. They do not necessarily required biopsy or excision.

A pitfall in the diagnosis of child abuse: external hydrocephalus, subdural hematoma, and retinal hemorrhages.

External hydrocephalus has been associated with subdural hematomas in infancy, and the hematomas have been noted to be secondary to minor trauma or have even been described as spontaneous. The author reports the case of an infant with external hydrocephalus who developed retinal as well as subdural hemorrhages after sustaining a minor head injury. Although retinal hemorrhage in infancy has been considered virtually pathognomonic of child abuse, in the setting of external hydrocephalus a more cautious interpretation may be appropriate.