Spontaneous intracranial hypotension and single entry multi-site epidural blood patch.

The syndrome of spontaneous intracranial hypotension is often difficult to treat. Unfortunately, cerebrospinal fluid leaks are often numerous and difficult to detect radiologically. Multiple entries to the spinal epidural space, in an effort to alleviate symptoms, are therefore sometimes necessary. This case report details two patients treated successfully with a single lumbar entry point and the administration of a continuous multi-site epidural blood patch via a mobile catheter and their subsequent follow-up. These procedures are based on that first published by Ohtonari et al. in 2012. It is, to our knowledge, the first undertaken in Australasia.

A comparison of adult outcomes for males compared to females following pediatric traumatic brain injury.

OBJECTIVE: To identify the association between traumatic brain injury (TBI) and internalizing and externalizing problem behaviors and determine if these apply equally to males and females. METHOD: The association between adult psychosocial functioning and childhood TBI for males and females was examined using groups with a history of childhood TBI (mild or moderate/severe) or orthopedic injury (injury age, 1-17, assessed 18-31 at >5 years postinjury), including rates of depression and anxiety disorders, substance abuse/dependence and offending behavior. Repeated-measures logistic regression was used to determine if the rates of internalizing and externalizing problem behaviors varied by group and sex. RESULTS: Overall rates of problem behaviors were significantly greater for both moderate/severe TBI (OR = 4.00) and mild TBI (OR = 3.60) groups compared with orthopedic controls. Females were significantly more likely than males to report a history of internalizing problems (OR = 2.22), whereas males were more likely than females to report externalizing problems (OR = 2.10). The sex difference in internalizing/externalizing problems was found consistently across TBI groups and controls. CONCLUSIONS: Childhood TBI is associated with psychosocial problems in adulthood, regardless of injury severity. How deficits are expressed differs between the sexes, with important implications for interventions strategies.

Increased paired box transcription factor 8 has a survival function in glioma.

BACKGROUND: The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis. METHODS: PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression. RESULTS: Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death. CONCLUSIONS: PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.

Predicting adult offending behavior for individuals who experienced a traumatic brain injury during childhood.

OBJECTIVES: To examine whether individuals who experienced a childhood traumatic brain injury (TBI) are at increased risk for subsequent offending behavior, to identify the emotional characteristics of adults who experienced childhood TBI, and to examine whether these predict offending behavior. PARTICIPANTS: Individuals from the Canterbury region who had experienced a childhood (<18 years of age) injury event and were now 18 years or older and more than 5 years postinjury (between 18 and 30 years of age). Three groups were formed: (1) moderate/severe TBI (n = 62); (2) mild TBI (n = 58); and (3) fracture control group (n = 38). SETTING: University of Canterbury. MAIN MEASURES: A semistructured interview assessed lifetime involvement in offending behavior; the Emotional Behavior Scale measured internalizing and externalizing behaviors, including malevolent aggression, social anxiety, and social self-esteem. RESULTS: Compared with controls, there was an increased risk of offending behavior (mild TBI: odds ratio = 8.7; moderate/severe TBI odds ratio = 20.4). Binary logistic regression analysis revealed that the strongest predictors of offending behavior were TBI status, higher levels of malevolent aggression, and age at injury. CONCLUSIONS: Individuals who experienced childhood TBI are at increased risk of offending behavior. Emotional behavior measures were useful predictors of offending behavior, offering opportunity for intervention.

Patterns of hearing loss following retrosigmoid excision of unilateral vestibular schwannoma.

Objectives To determine the pattern of auditory responses, time-course of hearing deterioration, and possible site of lesion following retrosigmoid excision of unilateral vestibular schwannomas. Design Prospective, nonrandomized, observational pilot study. Setting Tertiary referral medical center. Main outcome measures Preoperative and postoperative pure-tone and speech audiometry, auditory brainstem response testing, and distortion product otoacoustic emissions were performed in 20 patients. Testing was conducted every 24 hours for the duration of hospitalization. Transtympanic electrocochleography was performed if delayed deterioration of auditory responses was documented. Results Of the 20 patients, 7 had no discernible cochlear nerve at the end of the procedure. Of the 13 patients with an intact nerve, 6 retained hearing, 3 with evidence of reduced neural function. Of the 7 who lost hearing despite an intact nerve, 5 lost at least cochlear and possibly also neural function, and 1 had reduced neural function but retained cochlear function. There were two examples of delayed deterioration of cochlear nerve responses. Conclusions Hearing loss following retrosigmoid removal of vestibular schwannomas most often involves loss of at least cochlear function, possibly in addition to neural damage. In a smaller number of cases anacusis or hearing deterioration can be attributed to purely neural trauma.

Spinal cord stimulation for intractable chronic upper abdominal pain: a case report of the first patient in New Zealand.

We present the first patient in New Zealand to undergo Spinal Cord Stimulation (SCS) for intractable upper abdominal pain. The patient was a 53-year-old man with a 20-year history of debilitating upper abdominal pain associated with chronic pancreatitis secondary to pancreatic divisum. Prior to the SCS, he was prescribed 680 mg of morphine sulphate equi-analgesia a day. Despite the intense analgesia, he still suffered monthly attacks of upper abdominal pain requiring hospitalisation. Nine months after implanting a Spinal Cord Stimulator, the monthly attacks ceased, his background pain was effectively controlled and the need for opioids decreased to 510 mg of morphine sulphate equi-analgesia a day.

The CDKN2A G500 allele is more frequent in GBM patients with no defined telomere maintenance mechanism tumors and is associated with poorer survival.

Prognostic markers for glioblastoma multiforme (GBM) are important for patient management. Recent advances have identified prognostic markers for GBMs that use telomerase or the alternative lengthening of telomeres (ALT) mechanism for telomere maintenance. Approximately 40% of GBMs have no defined telomere maintenance mechanism (NDTMM), with a mixed survival for affected individuals. This study examined genetic variants in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene that encodes the p16(INK4a) and p14(ARF) tumor suppressors, and the isocitrate dehydrogenase 1 (IDH1) gene as potential markers of survival for 40 individuals with NDTMM GBMs (telomerase negative and ALT negative by standard assays), 50 individuals with telomerase, and 17 individuals with ALT positive tumors. The analysis of CDKN2A showed NDTMM GBMs had an increased minor allele frequency for the C500G (rs11515) polymorphism compared to those with telomerase and ALT positive GBMs (p = 0.002). Patients with the G500 allele had reduced survival that was independent of age, extent of surgery, and treatment. In the NDTMM group G500 allele carriers had increased loss of CDKN2A gene dosage compared to C500 homozygotes. An analysis of IDH1 mutations showed the R132H mutation was associated with ALT positive tumors, and was largely absent in NDTMM and telomerase positive tumors. In the ALT positive tumors cohort, IDH1 mutations were associated with a younger age for the affected individual. In conclusion, the G500 CDKN2A allele was associated with NDTMM GBMs from older individuals with poorer survival. Mutations in IDH1 were not associated with NDTMM GBMs, and instead were a marker for ALT positive tumors in younger individuals.

Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres.

Telomere maintenance by either telomerase activity or the recombination-mediated alternative lengthening of telomeres (ALT) mechanism is a hallmark of cancer. Tumors that use ALT as their telomere maintenance mechanism are characterized by long telomeres of great heterogeneity in length and by specific nuclear structures of co-localized promyelocytic leukemia protein and telomere DNA, called ALT-associated promyelocytic leukemia bodies (APBs). Recent advances have revealed a direct role for APBs in telomere recombination in ALT-positive cells. In this study, we investigated the possibility that APBs could occur before the long 'alternatively' lengthened telomeres arise, particularly in low-grade tumors. We measured APBs, telomere length, and telomerase activity in 64 astrocytomas inclusive of grade 1-4 tumors. Almost all grade 1-3 tumors (93%) were APB-positive using published criteria. Grade 2-3 APB-positive tumors also had long telomeres and were confirmed as ALT positive. However, grade 1 tumors lacked long telomeres and were therefore classified as ALT negative, but positive for telomere-associated promyelocytic leukemia bodies (TPB). This is the first report of a TPB-positive but ALT-negative tumor, and suggests that low-grade tumors have the foundation for recombinational telomere repair, as in ALT. Further work is warranted to characterize the TPB-positive phenotype in other early malignancies, as well as to determine whether TPBs predispose to telomere maintenance by ALT.

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: genotoxicity. A COLIPA analysis.

For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat to the use of these assays is their relatively low specificity and high rate of false or misleading positive results. Due to the 7th amendment to the EU Cosmetics Directive ban on in vivo genotoxicity testing for cosmetics that was enacted March 2009, it is no longer possible to conduct follow-up in vivo genotoxicity tests for cosmetic ingredients positive in in vitro genotoxicity tests to further assess the relevance of the in vitro findings. COLIPA, the European Cosmetics Association, has initiated a research programme to improve existing and develop new in vitro methods. A COLIPA workshop was held in Brussels in April 2008 to analyse the best possible use of available methods and approaches to enable a sound assessment of the genotoxic hazard of cosmetic ingredients. Common approaches of cosmetic companies are described, with recommendations for evaluating in vitro genotoxins using non-animal approaches. A weight of evidence approach was employed to set up a decision-tree for the integration of alternative methods into tiered testing strategies.

Occipital expansion without osteotomies in Apert syndrome.

INTRODUCTION: Cranial expansion has been the mainstay of initial management of children with Apert syndrome. Surgical timing is a balance between the risk of relapse if performed too early and the possibility of raised intracranial pressure and ossification defects if performed later. Primary occipital expansion has been proposed as a method to delay the timing of frontal surgery. We have applied the principal of spring expansion of patent sutures to expand the posterior cranial fossa without a cranial osteotomy. PATIENTS AND METHODS: All new Apert syndrome patients seen during the 3-year period December 2004-December 2007 underwent initial occipital expansion without osteotomy using spring expansion of the patent lambdoid suture. RESULTS: Four new Apert syndrome patients underwent posterior spring expansion of the patent lambdoid suture. Good occipital expansion was achieved in all cases. Standard frontal advancement was performed 5-18 months later. No relapse after frontal advancement has been seen after mean follow-up of 41 months. CONCLUSIONS: Spring expansion of the patent lambdoid suture is an alternative technique to expand the posterior cranial fossa. Compared to current techniques it has very low morbidity. Occipital expansion is thought to treat several of the mechanisms responsible for raised intracranial pressure in Apert syndrome. When performed at 6 months of age it has enabled us to delay the time at which we would normally perform frontal advancement surgery until a time when the surgical result is likely to be more stable.

Adolescent psychiatric symptoms following preschool childhood mild traumatic brain injury: evidence from a birth cohort.

OBJECTIVE: To determine whether childhood mild traumatic brain injury (MTBI) is associated with behavioral problems in adolescence. PARTICIPANTS: Children from a longitudinal birth cohort (initial N = 1265) were assigned to 1 of 3 groups: (1) inpatient group (n = 19) comprised children admitted to hospital for MTBI before age 5 years; (2) outpatient group (n = 57), children with any incidence of MTBI before age 5 seen by a general practitioner or at an accident and emergency department and sent home; (3) reference control group (n = 839). OUTCOME MEASURES: Maternal and self-report regarding attention deficit/hyperactivity disorder, conduct disorder, anxiety disorder, mood disorder, and alcohol or illicit substance abuse/dependence obtained using Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria. RESULTS: At age 14 to 16 years, children who had been hospitalized for MTBI during preschool years were significantly more likely to show symptoms of attention deficit/hyperactivity disorder (odds ratio = 4.2), conduct disorder/oppositional defiant disorder (odds ratio = 6.2), substance abuse (odds ratio = 3.6), and mood disorder (odds ratio = 3.1) but not anxiety disorder. CONCLUSIONS: Preschool MTBI is associated with persistent negative effects on psychosocial development. These continuing problems are consistent with the view that preschool years represent a period of particular vulnerability following MTBI.

Ten-year review of extradural spinal abscesses in a New Zealand tertiary referral centre.

Despite being a well-understood pathology, patients with an extradural spinal abscess (ESA) still experience delays in diagnosis, with associated morbidity and mortality. This 10-year retrospective audit aimed to define the presentation, findings and prognosis of ESA in a New Zealand tertiary referral centre. Forty-two patients were diagnosed and treated between 1 May 1997 and 30 June 2007. The mean age was 55 years, with a male predominance of 1.6:1. Staphylococcus aureus was identified in 67% of patients. On presentation, 27/38 patients with back pain were afebrile and 2/37 patients had a normal C-reactive protein (CRP) level in the first 24 hours. Ten patients were discharged with neurological dysfunction and one died. One reason for the delays in diagnosis and appropriate referral could be the lack of "red flag" symptoms at the time of presentation. Attention needs to be paid to the history and nature of a patient's back pain. We recommend routine CRP and full blood count to help raise clinical suspicion.

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: skin irritation.

Evaluation of the skin irritancy and corrosivity potential of an ingredient is a necessity in the safety assessment of cosmetic ingredients. To date, there are two formally validated alternatives to the rabbit Draize test for skin corrosivity in place, namely the rat skin transcutaneous electrical resistance (TER) assay and the Human Skin Model Test using EpiSkin, EpiDerm and SkinEthic reconstructed human epidermal equivalents. For skin irritation, EpiSkin, EpiDerm and SkinEthic are validated as stand-alone test replacements for the rabbit Draize test. Data from these tests are rarely considered in isolation and are evaluated in combination with other factors to establish the overall irritating or corrosive potential of an ingredient. In light of the deadlines established in the Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. In conclusion, the safety assessments for skin irritation/corrosion of new chemicals for use in cosmetics can be confidently accomplished using exclusively alternative methods.

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: eye irritation.

The need for alternative approaches to replace the in vivo rabbit Draize eye test for evaluation of eye irritation of cosmetic ingredients has been recognised by the cosmetics industry for many years. Extensive research has lead to the development of several assays, some of which have undergone formal validation. Even though, to date, no single in vitro assay has been validated as a full replacement for the rabbit Draize eye test, organotypic assays are accepted for specific and limited regulatory purposes. Although not formally validated, several other in vitro models have been used for over a decade by the cosmetics industry as valuable tools in a weight of evidence approach for the safety assessment of ingredients and finished products. In light of the deadlines established in the EU Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision-tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. Furthermore, recommendations are given on how remaining data gaps and research needs can be addressed.

Evolution of surgery for sagittal synostosis: the role of new technologies.

BACKGROUND: Techniques for sagittal synostosis correction continue to evolve to improve outcomes and minimize morbidity. The techniques now used by our craniofacial service are spring-assisted cranioplasty for younger children (generally up to 9 months of age) and biparietal barrel staving with cross-struts using bioabsorbable plates for older children. We evaluate the evolution of, and rationale for, our current methods of treatment. METHOD: All patients who underwent surgery for craniosynostosis over the period 1982 to 2007 were retrospectively reviewed. Patients with sagittal synostosis were analyzed according to the type of operative procedure performed. Blood loss, operative time, and hospital stay were compared between techniques using analysis of variance. RESULTS: Seventy-one patients had a cranial vault remodeling procedure for craniosynostosis. Thirty-four patients had sagittal synostosis with scaphocephaly. During the period 1982 to 2000, 13 patients had a strip craniectomy, and 5 patients had a barrel stave and morcellation procedure. Since 2001, the cross-strut technique using bioabsorbable plates has been used in 7 patients. In 2005, the spring cranioplasty technique was introduced and has been used in 9 patients. There were no deaths and no serious complications. One patient treated with springs had a second spring procedure performed to further increase biparietal width. Spring-assisted cranioplasty had a significantly shorter operating time than other techniques (P < 0.01). CONCLUSION: The availability of both absorbable plates and expansile cranial springs has revolutionized the techniques our unit uses for scaphocephaly correction. Our early experience with these techniques has shown that the techniques are reliable and give good cranial shape and form with minimal treatment morbidity.

Pontomedullary ganglioglioma: a rare tumour in an unusual location.

Gangliogliomas are rare low-grade tumours composed of neoplastic glial and neuronal cell elements. Although they may arise within any part of the neuraxis, involvement of the brainstem is rarely encountered. The distinct nature of gangliogliomas means that they have a comparatively better prognosis than other tumours in this location following subtotal resection. We present the case of an infant with a pontomedullary ganglioglioma and discuss the relevant literature.

Correction of nonsynostotic scaphocephaly without cranial osteotomy: spring expansion of the sagittal suture.

BACKGROUND: Scaphocephaly is usually due to sagittal synostosis. Scaphocephaly may also be seen in the presence of a nonsynostosed sagittal suture. In this situation traditional surgery is controversial due to the altered risk-benefit profile. This paper reports the first known series of patients with nonsynostotic scaphocephaly treated using spring assisted expansion of the sagittal suture. METHODS: All patients referred to our craniofacial program over the period February 2005-February 2008 were retrospectively reviewed. Eleven patients were seen with nonsynostotic scaphocephaly. Seven patients underwent spring expansion of the sagittal suture without osteotomy. RESULTS: Four female and three male patients had spring expansion of a patent sagittal suture. Four patients were born prematurely. Two patients had Beckwith-Weidemann syndrome. The ages ranged from 6 to 26 months (mean 12 months). The average preoperative cranial index was 66 (range 63-67). This improved to 76 at the time of spring removal (range 73-78). Springs were kept in situ for an average of 7.25 months. The mean blood loss was 7 ml and the mean operative time 36 min. CONCLUSION: Spring cranioplasty for sagittal synostosis is ideally performed before 6 months of age however in nonsynostotic scaphocephaly older children can be considered due to the absence of frontal bossing. Significant aesthetic improvement was achieved in all cases and normalization of the cranial index was achieved in 86% of cases with minimal morbidity and no significant complications. This technique is an alternative for nonsynostotic cases that were previously either untreated or undergone major remodelling surgery.

Conductive hearing loss after removal of acoustic neuroma.

OBJECTIVE: To report 4 patients who have developed a conductive and/or mixed hearing loss due to dehiscence of the inner ear after retrosigmoid approach for removal of acoustic neuroma. PATIENTS: Four patients who presented with conductive and/or mixed hearing loss after retrosigmoid approach for removal of acoustic neuroma. MAIN OUTCOME MEASURE: Evidence of inner ear dehiscence on postoperative computed tomographic scan of the temporal bones. CONCLUSION: The occurrence of conductive hearing loss after the surgical removal of an acoustic neuroma has not previously been documented. Computed tomographic scan of the temporal bones showing inner ear dehiscence may explain this finding. Formal documentation of such cases may allow techniques to be developed to reduce its occurrence or reconstruction of the defect at the time of primary surgery.