Daniel Rawluk

Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas

One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology.

Idiopathic intracranial hypertension: lumboperitoneal shunts versus ventriculoperitoneal shunts – case series and literature review

Objectives: Idiopathic intracranial hypertension (IIH) is an uncommon but important cause of headache that can lead to visual loss. This study was undertaken to review our experience in the treatment of IIH by neuronavigation-assisted ventriculoperitoneal (VP) shunts with programmable valves as compared to lumboperitoneal (LP) shunts. Methods: A retrospective chart review was conducted on 25 patients treated for IIH between 2001 and 2009. Age, sex, clinical presentation, methods of treatment and failure rates were recorded. Results: Seventy-two per cent were treated initially with LP shunts. Failure rate was 11% in this group. Neuronavigation-assisted VP shunts were used to treat 28%. In this group, the failure rate was 14%. Conclusion: Our experience indicates that both LP shunts and VP shuts are effective in controlling all the clinical manifestations of IIH in the immediate postoperative period. Failure rates are slightly higher for VP shunts (14%) than LP shunts (11%). However, revision rates are higher with LP shunts (60%) than with VP shunts (30%).

Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients

Background: Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented. Objective: To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions. Methods: All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium <130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis. Results: Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p<0.001), intracranial neoplasm (56/355, 15.8%; p<0.001) and subarachnoid haemorrhage (62/316, 19.6%; p<0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p<0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12–28)) than normonatraemic patients (median 12 days (IQR 10.5–15)) (p<0.001). Conclusions: Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.

Acute Glucocorticoid Deficiency and Diabetes Insipidus Are Common After Acute Traumatic Brain Injury and Predict Mortality

CONTEXT Published data demonstrates that hypopituitarism is common after traumatic brain injury (TBI). Hormone deficiencies are transient in many, but the natural history of the acute changes after TBI has not been documented. In addition, it is not clear whether there are any early parameters that accurately predict the development of permanent hypopituitarism. OBJECTIVES There were 3 main objectives of this study: 1) to describe the natural history of plasma cortisol (PC) changes and sodium balance after TBI; 2) to identify whether acute hypocortisolemia or cranial diabetes insipidus (CDI) predict mortality; and 3) to identify whether the acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism. DESIGN Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality, and fluid balance after TBI. All other anterior pituitary hormones were measured on day 10 after TBI. The results from 15 surgical comparisons defined a PC less than 300 nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to standard criteria. Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months after TBI. SETTING The patients were recruited from the Irish National Neurosurgery Centre. PATIENTS One hundred sequential TBI patients were recruited. Fifteen patients admitted to Intensive Therapy Unit (ITU) after major surgery were recruited as comparison patients. MAIN OUTCOME MEASURES PC in TBI patients was compared with that of comparison patients. The mortality rate was compared between TBI patients with and without acute hypocortisolemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolemia. RESULTS Most of the TBI patients (78%) developed inappropriately low PC after TBI. Low PC and CDI were predictive of mortality. Thirty-nine percent of the patients who had follow-up testing had at least 1 pituitary hormone deficit, all of whom had had previous acute hypocortisolemia or CDI. CONCLUSIONS Acute hypocortisolemia and CDI are predictive of mortality and long-term pituitary deficits in TBI.

Superficial siderosis of the central nervous system following cervical nerve root avulsion: the importance of early diagnosis and surgery

SummarySuperficial siderosis (SS) of the central nervous system is an insidious, progressive, irreversible and debilitating neurological disorder caused by recurrent haemorrhage within the subarachnoid space. The subsequent deposition of haemorrhagic breakdown products in the spinal cord and nervous tissues leads to the loss of neurones and myelin, and to the development of a neurological deficit. In a small number of patients, the source of haemorrhage is related to traumatic cervical nerve root avulsion occurring several years prior to the onset of symptoms. Surgical ablation of the source has been shown to halt the progression of the disease, at least in the short term. We review the literature on SS secondary to cervical nerve root avulsion and report a further case in which surgical management was successful in halting disease progression. We emphasize that early detection and recognition of the initial non-progressive symptoms related to this poorly known disease, coupled with timely surgical management, minimizes the degree of neurological disability.

Foramen magnum decompression for Chiari I malformation: A procedure not to be underestimated

Abstract Objective. Chiari I malformation may be treated with foramen magnum decompression (FMD). We aim to describe the symptoms with which patients initially present, and to determine the number and type of complications occurring after FMD for Chiari I malformation. Methods. Retrospective review of medical records for patients who had FMD performed for Chiari I malformation between January 2009 and December 2011. Post-operative outcomes were recorded and analysed. Patient demographic details and other relevant medical conditions were also noted. Results. Between January 2009 and December 2011, 54 FMDs were performed for Chiari I malformation. Among them, 40(74%) patients were female and 14 patients (26%) were male. The majority of patients (42.6%) were aged 16–39 years and 24.07% of patients were children aged < 16 years. A total of 30(55.6%) patients had documented evidence of a syrinx pre-operatively. 18(33.3%) patients developed complications. Nine of these developed multiple complications while nine had a single problem. One mortality was reported. Ten (18.5%) patients developed hydrocephalus requiring shunting. Two patients developed subdural collections requiring evacuation associated with hydrocephalus. Six (11.1%) patients developed post-operative infections: two CNS infections; one wound infection; and three other infections. Conclusions. FMD for Chiari I malformation is a procedure which carries risk. In particular, the risk of developing post-operative hydrocephalus requiring permanent shunting is relatively high. ICP monitoring prior to FMD may be required to definitively rule out raised intracranial pressure.

Acromegaly associated with gangliocytoma

BackgroundAcromegaly secondary to growth hormone-releasing hormone (GHRH) excess is rare.Aims/case descriptionWe report two patients with acromegaly who were diagnosed with sellar gangliocytomas that were immunopositive for GHRH. Tumour tissue persisted after debulking surgery and in the second case this was associated with persistent growth hormone hypersecretion, successfully suppressed by a somatostatin analogue.ConclusionsThe development of functional pituitary adenomas in association with sellar gangliocytomas is poorly understood. We present a brief discussion of the possible aetiology of these unusual pituitary tumours.

Atypical clinical presentations of vestibular schwannomas.

A significant number of patients with vestibular schwannomas present atypically, with none of the classical symptoms of unilateral sensorineural hearing loss, tinnitus, and/or dysequilibrium. The aim of this study is to highlight those patients with unusual clinical symptoms. Study Design: The clinical data of all patients who presented to the vestibular schwannoma clinic at Beaumont Hospital over the past 12 years was prospectively recorded in a computerized database. This paper reviews the atypical presenting symptoms. Results: Three hundred ninety-eight patients were included in this study. A total of 3.7% of patients presented with atypical symptoms only. Conclusion: A significant subgroup, 3.7% in our study, did not present with the audiovestibular symptoms classically associated with vestibular schwannoma. Clinician awareness of the atypical clinical symptoms may lead to earlier detection of these lesions.

Cavernous angioma of the internal auditory canal

Cavernous angiomas of the internal auditory canal are rare lesions. The authors present a case of a 29-year-old lady with multiple infratentorial cavernous angiomas, whose sister had previously undergone surgery for a similar supratentorial lesion. She initially presented with an acute brainstem haematoma, secondary to a pontine cavernous angioma. Three years later she developed progressive right-sided sensorineural hearing loss and facial nerve paresis due to an internal auditory canal lesion. This was removed via the translabyrinthine approach and was found to be a cavernous angioma. This report underlines the multiple and dynamic nature of familial cavernous angiomas, as well as the importance of follow up to determine whether new symptoms are due to the enlargement of known angiomas or the development of new ones. As far as the authors are aware, this is the first report describing a cavernous angioma of the internal auditory canal in the context of familial and multiple infratentorial angiomas.

Non-surgical treatment of meningioma: a case report and review

A woman initially presented with a right hemiparesis and subsequently underwent subtotal resection of a left parietal meningioma arising from the lateral wall of the sagittal sinus. She again presented 18 months after surgery with a hemiparesis and repeat MRI showed tumour spreading into the sagittal and the transverse sinuses. She had a therapeutic abortion at 8 weeks gestation 3 weeks prior to her representation. Gestrinone, a synthetic steroid and an antiprogesterone was commenced. Two months later she stopped her medication and is asymptomatic at 16 months. A follow-up MRI revealed that the tumour had shrunk dramatically. This case is the first of its kind with tumour size reduction to less than 20%. We feel that the future of meningioma treatment will be multi-disciplinary and non-surgical options should be considered.