Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma) in the setting of cowden syndrome: a case report and literature review on COLD syndrome.

Lhermitte-Duclos Disease is a rare clinical entity involving a dysplastic lesion of the cerebellum. The dysplastic cerebellar ganglioblastoma is often seen in association with Cowden Syndrome, an autosomal dominant disorder consisting of a mutation in the phosphatase and homologous tensin (PTEN) gene. Characteristic findings on neuroimaging allow for a pre-operative diagnosis to be made, which guides further management of the condition. This report describes the diagnosis and management of Lhermitte-Duclos Disease in a 51-year-old lady, spanning a period of almost seven years. The characteristic radiological and histological findings are presented, along with the clinical features associated with Cowden Syndrome. This patient ultimately underwent surgical intervention for symptomatic relief, which is described here.

Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant.

BACKGROUND: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. METHODS: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. RESULTS: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. CONCLUSIONS: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment.

A review of major trauma admissions to a tertiary adult referral hospital over a ten year period: fewer patients, similar survival.

BACKGROUND: Trauma is an important cause for presentation to the emergency department, representing a significant number of emergency surgical admissions. Societal changes result in alterations in the epidemiology of trauma. OBJECTIVES: This study aimed to review patients admitted to a tertiary referral hospital as a result of traumatic injuries, assessing for changes in admission epidemiology. METHODS: Trauma admissions over two year-long periods a decade apart were reviewed. The Trauma Audit and Research Network (TARN) audit system identified admissions and transfers between June 2006 and May 2007. The Hospital In-Patient Enquiry (HIPE) system identified those fulfilling TARN criteria a decade earlier. Comparative analysis was performed on the dataset. RESULTS: There were 367 trauma admissions between June 2006 and May 2007: 88 road traffic accidents (RTAs), 201 falls and 77 other injuries, with 627 admissions a decade earlier: 286 RTAs, 247 falls and 94 others. Males comprised 72% and 69% of RTA admissions in both periods respectively. Firearm-related injuries increased significantly (p = 0.015). Neurosurgical transfers decreased from 256 to 150 with a slight increase in unadjusted overall mortality from 8.5% to 10.9%. Admissions of patients aged less than 19 reduced from 150 to 59 (p = 0.0031) with a similar trend in those aged between 20 and 29 years from 149 to 78. CONCLUSION: Admissions resulting from RTAs and of patients aged under 30 reduced significantly, however, young males remain the most affected sub-group. Firearm injuries increased significantly, a worrying trend in view of the severity of injury sustained by these victims.

An outcome analysis of seventeen patients treated surgically for intractable extratemporal epilepsy.

We studied the outcomes of seventeen patients treated surgically for extratemporal lobe epilepsy. A retrospective case review of medical charts was performed. Seizure freedom post surgery was appraised using the Engel classification system. Post-operatively seven patients (41%) were seizure free (Engel class I), four patients were class II (23.5%), two in class III (11.76%) and four in class IV (23.5%). Three patients (17.6%) suffered traumatic injuries due to seizures. The mean duration of epilepsy prior to surgery was 12.2 years and the mean number of anti-epileptic medications given was 6.5. Seizure freedom rates for surgical treatment of extratemporal epilepsy in this centre are similar to those of other centres. Post-operative morbidity in this centre was similar to other centres. Any complications resolved with no lasting impairment.

Spontaneous resolution of a small extradural haematoma in a child.

We report the rapid spontaneous resolution of a small extradural haematoma (EDH) in a 19-month-old child. The haematoma was managed conservatively. The child went on to make a full recovery. The authors discuss the significance of this surprising clinical finding.

Intraparenchymal pericatheter cyst following ventriculoperitoneal shunt insertion: does it always merit shunt revision?

Intraparenchymal pericatheter cyst is a rare complication of shunt surgery. It occurs as a consequence of increased CSF outflow resistance distal to a patent ventricular catheter. Treatment has traditionally consisted of shunt revision. We report on two such cases managed conservatively. The role of shunt revisions in cases with asymptomatic intraparenchymal pericatheter cyst is debatable.

Extraskeletal myxoid chondrosarcoma of the cerebellopontine angle presenting during pregnancy.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma, which usually occurs in the lower extremities. It is often associated with chromosomal translocations. The clinical, radiological and pathological findings in extraskeletal myxoid chondrosarcoma, with an origin in the cerebellopontine angle, are described along with the issues associated with management of this tumour presenting acutely in a 26-year-old woman who was 20 weeks pregnant.

Familial occurrence of oligodendroglial tumours.

Two non-identical brothers were diagnosed with anaplastic oligoastrocytoma within 4 months of each other and a maternal grandmother was diagnosed with oligodendroglioma 21 years previously. Familial clustering of oligodendrogliomas is rare.

The Children's Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours.

Dysembryoplastic neuroepithelial tumours (DNETs) were incorporated into the new World Health Organization classification of brain tumours as part of the group of glioneuronal tumours in 1993. Large series of patients with DNETs and pharmaco-resistant epilepsy have been reported. DNETs are most often located in the temporal lobe, occurring in both mesial and lateral temporal locations. DNETs have also been reported in the insular cortex, brain stem, cerebellum, occipital lobe and striatum. Approximately 40% of DNETs are cystic, and solitary nodular, multinodular or diffuse forms have been recognized. Approximately 30% of DNETs are associated with subtle cortical dysplastic changes in the adjacent cortex. DNET nodules usually look like oligodendroglioma, whilst between the nodules it may be possible to recognize vertical columns of neurons surrounded by oligodendrocyte-like cells. Cytologically, oligodendroglial-like cells of DNETs are distinguished from oligodendroglioma by larger nuclei with frequent nuclear indentations and multiple, small nucleoli, whilst oligodendrogliomas consistently show nuclear roundness with one or two occasional nucleoli. Very rare cases of malignant transformation have been reported. DNETs are hypodense on CT and demonstrate decreased signal on the T1-weighted images and a hyper-intense signal on T2-weighted MRI. DNETs associated with pharmaco-resistant epilepsy should be removed early to achieve seizure freedom and prevent tumour progression. The surgical approach should be that of an extended lesionectomy, i.e. excision of the lesion and the abnormal dysplastic cortex around it. Use of MRI-based image guidance (neuronavigation) as a surgical tool to identify this area of abnormal cortex is very helpful to ensure that the extended lesionectomy includes any visibly dysplastic cortex. It is not advocated to use a stereotactic biopsy only, as this may generate an unrepresentative tissue sample consisting of an oligodendroglial component only and may lead to an incorrect diagnosis.

The role of endoscopic third ventriculostomy in the management of hydrocephalus associated with cerebellopontine angle tumours.

BACKGROUND: Progressive hydrocephalus secondary to cerebellopontine angle tumours has been traditionally managed with ventriculo-peritoneal shunting. Endoscopic third ventriculostomy provides an alternative treatment option and the success rate in this patient group has not previously been reported. METHODS: We report a retrospective series of 11 patients with cerebello-pontine angle tumours who presented with symptomatic hydrocephalus, or developed hydrocephalus following radiosurgery, who underwent endoscopic third ventriculostomy. RESULTS: Seven patients (63.6%) remain shunt free. There were no complications following endoscopy in any patient. Where the ventriculostomy failed there was no additional morbidity. CONCLUSIONS: Endoscopic third ventriculostomy is a low morbidity procedure, which avoids the inherent problems of shunts, particularly infection and should be considered for patients with hydrocephalus and cerebello-pontine angle tumours.

Paraganglioma of the cauda equina: a case report and literature review.

A 26-year-old man presented with left leg pain and progressive paraparesis. Imaging revealed a large intradural tumour compressing the cauda equina. The lesion was radically resected and histological analysis revealed it to be a paraganglioma. The clinical features of this rare tumour are described with a review of the literature.

Combined nasal and skull base pathology: adjacent nasal schwannoma and olfactory groove meningioma.

A 55-year-old woman presented with a longstanding history of headache and personality change. Preoperative imaging suggested an olfactory groove meningioma invading the posterior nasal space. Following surgical removal of the lesion histopathology confirmed the presence of both a nasal schwannoma and an olfactory groove meningioma. This dual pathology may represent a variation of neurofibromatosis type 2 (NF-2).

Role of mRNA transcript stability in modulation of expression of the gene encoding thrombin activable fibrinolysis inhibitor.

Regulation of mRNA stability has emerged as a major control point in eukaryotic gene expression. The abundance of a particular mRNA can be rapidly regulated in response to a stimulus by altering the stability of existing translatable transcripts rather than by altering the rate of transcription initiation. Alternative polyadenylation of transcripts during mRNA processing can be important in determining transcript abundance if the different forms of mRNA possess different stabilities or translatability. The mRNA transcript encoding thrombin activable fibrinolysis inhibitor (TAFI) is an attractive candidate for regulation of mRNA stability because of the relatively long length of its 3'-untranslated region and because the transcript can be polyadenylated at three different sites. As well, we have previously reported that treatment of HepG2 cells with interleukins (IL) - 1beta and - 6 destabilizes the endogenous TAFI mRNA expressed in this cell line. In the current study, we report that the TAFI 3'-untranslated region contains cis-acting instability element(s) and that these elements in fact determine the intrinsic stability of the TAFI transcript. Moreover, we found that the three different polyadenylated mRNA forms have different intrinsic stabilities, with the mRNA half-life increasing from the longest to the shortest transcript. Interestingly, treatment with IL-1beta plus IL-6 not only resulted in a 2-fold decrease in stability of the transcript produced using the 3'-most polyadenylation site but also resulted in profound shifts in the relative abundances of the respective polyadenylated forms through changes in the frequency of utilization of the three polyadenylation sites. As such, in the presence of IL-1beta and IL-6, the longest transcript is over a thousand times more abundant than the two shorter transcripts whereas in the absence of the stimulus it comprises only 1% of the total TAFI transcripts.

Should airguns be banned?

In this article, we express concerns regarding the availability of airguns, the injuries that they cause and their abuse as weapons of assault. We wish to stimulate debate on this topic and report a 5-year retrospective analysis of all airgun injuries to the head and neck, presenting to Alder Hey Children's Hospital, Liverpool, from June 1998 to June 2003. We identified 16 patients who suffered such injuries with ages ranging from 5 to 15 years. The majority of cases were violent assaults, which is not in accordance with previous published reports. All of these occurred in public places outside the home. Most incidents occurred through the spring and summer period. Six patients required overnight stay in hospital. Nine patients required operative procedures to remove the airgun pellets. Two patients had serious eye injuries resulting in loss of vision. Two patients had penetrating neck injuries requiring exploration of the wound. The remaining group had either skin-penetrating injuries with lodgement of fragments in subcutaneous tissues or non-skin penetrating injuries. This study highlights serious injuries arising from the abuse of airguns as weapons of assault. Airguns are readily available to people without license. Recent legislation has increased the minimum age at which airguns can be carried in a public place, but we believe that stricter legislation is required to produce a reduction in the number of airgun-related injuries.

Diffuse primary non-Hodgkin's lymphoma of the cranial vault.

Primary non-Hodgkin's lymphoma of the skull vault is a rare disease. We describe a case occurring in a 72-year-old woman presenting with generalized tonic clonic seizures on a background of a 1-year history of headaches and progressively enlarging scalp masses. Imaging showed diffuse infiltration of the skull vault with multifocal intra- and extracranial soft tissue masses, causing compression and probably infiltration of the cerebral cortex. Further investigation failed to identify any other evidence of systemic lymphoma. Biopsy of one of the scalp masses showed a small to intermediate cell B cell lymphoma. The other nine reported cases of primary skull vault lymphoma are reviewed. The diffuse vault infiltration as well as the multiple intracranial, scalp and temporalis muscle masses renders this case unique.

The anatomical distribution of cerebral gliomas in mobile phone users.

We analysed the association between mobile phone use and the anatomical distribution of glial brain tumours in Irish neurosurgical patients. All patients with unilateral histologically proven glioma were enrolled over a 12 month period. We hypothesised that were a cellular phone to cause a glioma then it would do so on the dominant hand side. Fifty mobile phone users and twenty three non-users were identified. The vast majority of patients (69/73) were right handed and the right side of the brain was more common as the tumour site (48/73). Fisher's exact test revealed no statistical significance for glioma location based on the handedness of the patient in the mobile phone user group and location of the tumour in both user and non-user groups. We discuss our findings and the stable trend in the incidence of reported glioma cases.

Schwann cell invasion of the conus medullaris: case report.

As Schwann cells possess regenerative capabilities there is intense interest concerning their role in central nervous system (CNS) regeneration. We report on a case of an intramedullary schwannoma involving the conus medullaris and spinal cord above it. We discuss the possible origin of these cells and the mechanisms by which these cells may invade the CNS. We offer imaging and discuss experimental studies to support our hypothesis. This case concerns a 48-year-old man, who presented with a 6-month history of bilateral lower extremity weakness. Magnetic resonance imaging (MRI) revealed an intramedullary tumour extending from the conus to T11. At operation, following laminectomy and durotomy, a schwannoma was dissected free from the conus. Total gross resection of tumour was achieved. The patient made an uneventful and full recovery. This case shows that Schwann cells can invade the CNS. Manipulation of the transitional zone astrocytic barrier may offer a potential avenue for Schwann cells to enter the CNS in pathological states.

Effect of peptide conformation on membrane permeability.

The effect of peptide conformational constraint on the peptide permeation across the model membranes was examined by determining the permeability of pairs of cyclic and acyclic peptides related to c[d-Pen2, d-Pen5] enkephalin (DPDPE). The peptides were cyclized by formation of an intramolecular disulfide bridge between the second and fifth residues composed of either d-penicillamine or cysteine. In each case the acyclic peptide was three to seven times more permeable than corresponding cyclic peptide. The possibility that the differences in permeability of cyclic and acyclic peptides is based on the greater conformational freedom of the acyclic peptides in the presence of membrane was examined in more detail by isothermal titration calorimetric studies of Trp6-DPDPE and its acyclic analog. The membrane binding of the acyclic peptide is a more exothermic process than binding of its cyclic Trp6-DPDPE. The transfer of acyclic peptide from water to membrane is an enthalpy driven process, whereas the transfer of the cyclic peptide is driven by entropy.