Value of delayed MRI in angiogram-negative subarachnoid haemorrhage.

AIM: To assess the efficacy of delayed magnetic resonance imaging (MRI) in identifying a structural cause for angiogram-negative subarachnoid haemorrhage. MATERIALS AND METHODS: All patients presenting with spontaneous subarachnoid haemorrhage who had negative computed tomography (CT) angiography and catheter angiography between 2006 and 2012 were reviewed. RESULTS: During the 6 year period, 1023 angiograms were performed for a new presentation of subarachnoid haemorrhage. Of these, 242 (23.7%) did not show a cause for the haemorrhage. A second catheter angiogram was performed in 48 patients, and aneurysms were identified in two patients. Of the remaining 240 patients, 131 underwent a subsequent MRI brain. One hundred and five (80.2%) MRI examinations were performed 4 or more weeks after angiography. In two patients, cavernomas were identified as the likely bleeding source. In both patients, the pattern of subarachnoid haemorrhage surrounding a small intraparenchymal haemorrhage on the initial CT suggested the diagnosis. Thirty-nine patients underwent MRI of the cervical spine, none of which identified a cause for the haemorrhage. None of the patients re-presented to our centre during the 6 year study period. CONCLUSION: Delayed MRI following angiogram-negative subarachnoid haemorrhage has a low (1.5%) yield and is not routinely necessary. MRI may be useful to characterize the diagnosis in patients with clinical or radiological features of an underlying abnormality such as a cavernoma.

Pituitary apoplexy in non-functioning pituitary adenomas: long term follow up is important because of significant numbers of tumour recurrences.

OBJECTIVES: The frequency of pituitary tumour regrowth after an episode of classical pituitary apoplexy is unknown. It is thus unclear whether regrowth, if it occurs, does so less frequently than with non-apoplectic non-functioning pituitary macroadenomas that have undergone surgery without postoperative irradiation. This has important repercussions on follow up protocols for these patients. DESIGN: Retrospective cohort study of patients diagnosed with classical pituitary apoplexy in Oxford in the last 24 years. MEASUREMENTS: MRI/CT scans of the pituitary were performed post-operatively and in those patients who did not receive pituitary irradiation, this was repeated yearly for 5 years and 2 yearly thereafter. RESULTS: Thirty-two patients with non-functioning pituitary adenomas who presented with classical pituitary apoplexy were studied. There were 23 men and the mean age was 56·6 years (range 29-85). The mean follow up period was 81 months (range 6-248). Five patients received adjuvant radiotherapy within 6 months of surgery and were excluded from further analysis. In this group, there were no recurrences during a mean follow up of 83 months (range 20-150). In the remaining 27 cases there were 3 recurrences, with a mean of 79 months follow up (range 6-248) occurring 12, 51 and 86 months after surgery. This gives a recurrence rate of 11·1% at a mean follow up of 6·6 years post surgery. All recurrences had residual tumour on the post operative scan. CONCLUSIONS: Patients with classical pituitary apoplexy may show recurrent pituitary tumour growth and therefore these patients need continued post-operative surveillance if they have not had post-operative radiotherapy.

Intraoperative, imaging and pathological features in spinal cord vasculitis.

The surgical intraoperative findings in spinal cord vasculitis have not been previously described. The imaging appearances can mimic intramedullary spinal cord tumours. We present a patient with spinal cord vasculitis and mixed intraoperative findings of spinal vascular lesion and intramedullary tumour. Based on the absence of a confirmatory intraoperative smear, vessel obliteration and tumour debulking was avoided, preventing a catastrophic surgical complication. The limited literature and management options are also reviewed.

Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotide.

BACKGROUND: Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case. OBJECTIVE: We carried out a prospective study to assess whether surgical debulking of pituitary macroadenomas causing acromegaly improved the subsequent control of acromegaly by the somatostatin analogue lanreotide. PATIENTS AND METHODS: We treated 26 consecutive patients [10 males and 16 females--median age 53.5 years (range 22-70)] with macroadenoma causing acromegaly unselected for somatostatin response for 16 weeks with lanreotide, maximizing GH and IGF-I suppression, if necessary, by incremental dosing. Surgical resection was carried out and the patients were re-assessed off medical treatment at 16 weeks following surgery. Those with nadir GH > 2 mU/l in the oral glucose tolerance test (OGTT) and a mean GH in the GH day curve (GHDC) > 5 mU/l were subsequently restarted on lanreotide and the responses were assessed at the same time points as during the preoperative lanreotide treatment. RESULTS: GH values fell on lanreotide treatment and prior to surgery they were considered 'safe' (mean GH in GHDC < 5 mU/l) in eight patients (30.7%). After surgery, they were 'safe' in 18 patients (69.2%). The figures for normal IGF-I were 11 (42.3%) before surgery and 23 (88.5%) after surgery. After surgery, six patients had nadir GH > 2 mU/l in the OGTT and 'unsafe' GH levels (mean GH in GHDC > 5 mU/l); on re-exposure to lanreotide, GH levels fell in all patients and at the end of 16 weeks postsurgery, they were 'safe' in three of them (50%) (P < 0.05). Pituitary tumour volume was also assessed prospectively, preoperatively on lanreotide and showed a mean fall of 33.1%. Eighty-three percent of patients had > 20% shrinkage. CONCLUSIONS: In this first prospective study using lanreotide, surgical debulking of pituitary tumours causing acromegaly improved subsequent postoperative control by the somatostatin analogue lanreotide. Surgery should, therefore, be considered in patients with macroadenoma causing acromegaly, even if there is little prospect of surgical cure. Lanreotide causes significant pituitary tumour shrinkage in the majority of patients.

Nonsurgical cerebrospinal fluid rhinorrhea in invasive macroprolactinoma: incidence, radiological, and clinicopathological features.

CONTEXT: Macroprolactinomas (MPRLs) may result in nonsurgical (spontaneous or dopamine agonist induced) cerebrospinal fluid (CSF) rhinorrhea; however, the incidence of and mechanisms underlying this phenomenon are poorly understood. OBJECTIVE: The objective of the study was to determine the incidence of nonsurgical rhinorrhea and identify biochemical, radiological, and histopathological factors associated with leakage. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of MPRL patients (n = 114) was compared with patients with nonfunctioning pituitary adenoma (NFA) (n = 181) seen over a 19-yr period (1985-2004). MAIN OUTCOME MEASURES: Incidence of CSF rhinorrhea, factors predictive of leakage, and differential expression of candidate markers of invasiveness were measured. RESULTS: Nonsurgical CSF rhinorrhea occurred in 8.7% of MPRLs (10 of 114) [2.6% spontaneous (three of 114), 6.1% dopamine agonist induced (seven of 114)], whereas no NFAs developed nonsurgical rhinorrhea. There was a clear male preponderance in MPRLs with nonsurgical rhinorrhea (males to females, 9:1, P = 0.008). Dopamine agonist resistance was more frequent in MPRLs with rhinorrhea than with MPRLs without rhinorrhea [30% (n = 10) vs. 5% (n = 104) P = 0.003]. Baseline prolactin levels, rate of prolactin decline in response to dopamine agonists, and tumor volume at diagnosis did not predict CSF leakage. Candidate markers of invasiveness, specifically the protease-activated receptor 1 and e-cadherin expression scores and tumor macrophage density, were not significantly different between groups; MPRL+CSF rhinorrhea (n = 6), MPRL without CSF rhinorrhea (n = 9), and NFAs (n = 9). CONCLUSIONS: The incidence of nonsurgical CSF rhinorrhea in MPRL patients (8.7%) is higher than expected. Dopamine agonist resistance is more common in MPRLs with CSF rhinorrhea; however, whether this is a mechanistic relationship requires further study. Protease-activated receptor 1 expression, e-cadherin expression, and macrophage infiltration rates do not distinguish tumors with from those without CSF rhinorrhea.

What is the natural history of nonoperated nonfunctioning pituitary adenomas?

BACKGROUND: Series of patients systematically investigating the outcome of clinically nonfunctioning pituitary adenomas (NFAs) not treated by surgery or radiotherapy during long follow-up periods are limited. Most reports involve the follow-up of selected cases of incidentally found lesions, rendering their results unreliable on the assessment of the pros and cons of a 'watch and wait' policy. OBJECTIVE: To investigate the outcome of a series of consecutive patients with presumed NFA (microadenoma or macroadenoma), who were not offered treatment at presentation (for a number of reasons) and were regularly followed up, and to identify possible factors predicting subsequent increase in tumour size. PATIENTS AND METHODS: All patients presenting to the Department of Endocrinology in Oxford between 1989 and 2005 with presumed NFA were studied retrospectively. Inclusion criteria were: (i) imaging features suggestive of a pituitary adenoma, (ii) no clinical and/or biochemical evidence of hormonal hypersecretion by the tumour, (iii) monitoring being the initial choice of management, and (iv) at least one repeat scan during the follow-up period. Subjects presenting with acute apoplexy were excluded. Follow-up management included clinical evaluation, assessment of the visual acuity and fields and imaging at regular intervals. The duration of observation was estimated from the dates of first and last scan. RESULTS: Forty subjects were included in the study [18 males/22 females, median age 52 years (range 18-89), 16 with microadenoma/24 with macroadenoma]. The mean follow-up period was 42 months (range 8-128). During the observation interval, 12.5% of the microadenomas and 50% of the macroadenomas increased in size. The 48-month probability for enlargement was 19% for the microadenomas and 44% for the macroadenomas. Among the subjects with tumour enlargement, 57% showed new or worse visual field defects (all had macroadenomas) and 21% showed chiasmatic involvement on imaging without visual deterioration (all had macroadenomas). New or worse visual field defects were found in 67% of the macroadenomas showing increase in size. No microadenoma enlarged to cause visual deterioration. In microadenomas, sex and age at presentation were not predictors of enlargement. In macroadenomas, sex, age, visual field defects or cavernous sinus invasion at presentation were not predictors of enlargement. CONCLUSIONS: The 'watch and wait' policy seems reasonable for microadenomas but is probably not a safe approach for macroadenomas, which appear to have a significant growth potential; in these cases, given the lack of established medical treatment, the decision for surgical intervention should balance the presence of significant comorbidities and the anaesthetic/peri-operative risks at presentation against the probability of tumour enlargement and its consequences, as well as the possible loss of advantages associated with early operation.

Subaxial cervical synovial cyst presenting with myelopathy. Report of three cases.

Synovial cysts occur infrequently in the spinal canal and are most often associated with degenerative facet joints. Despite the prevalence of degenerative spinal disease, symptomatic synovial cysts are extremely uncommon. There have been only two previously reported cases of subaxial degenerative synovial cysts of the cervical spine in patients who presented with a clinical picture of spinal cord compression. The authors report three additional patients treated for degenerative cervical synovial cysts who presented with myelopathy. In all three patients the cyst was successfully excised and a good clinical outcome achieved.

Outcome in surgically treated Rathke's cleft cysts: long-term monitoring needed.

OBJECTIVE: To clarify the outcome of all cases of Rathke's cleft cysts (RCC) treated surgically and followed up in Oxford during a long-term period. SUBJECTS AND METHODS: The records of all patients with RCC seen in the Department of Endocrinology between January 1978 and June 2009 were reviewed. RESULTS: A total of 33 patients (20 females, median age 43 years) were identified. At presentation, major visual field defects were detected in 58% of patients and gonadotrophin, ACTH and TSH deficiency in 60, 36 and 36% of patients respectively. Desmopressin treatment was required in 18% of patients. Treatment consisted of cyst evacuation combined with or without biopsy/removal of the wall. Post-operatively, visual fields improved in 83% of patients with impairment, whereas there was no reversal of ACTH or TSH deficiency or of diabetes insipidus. All but one subject had imaging follow-up during a mean period of 48 months (range 2-267). Cyst relapse was detected in 22% of patients at a mean interval of 29 months (range 3-48 months); in 57% of them, the recurrence was symptomatic. Relapse-free rates were 88% at 24-months and 52% at 48-months follow-up. At last assessment, at least quadrantanopia was reported in 19% of patients, gonadotrophin, ACTH and TSH deficiency in 50, 42 and 47% of patients respectively. Desmopressin treatment was required in 39% of patients. CONCLUSIONS: In this study of patients with RCC and long-term follow-up, we showed a considerable relapse rate necessitating long-term monitoring. Surgical intervention is of major importance for the restoration of visual field defects, but it does not improve endocrine morbidity, which in the long-term affects a substantial number of patients.

Awake craniotomy using stealth frameless stereotaxy without rigid skull fixation.

The authors describe a technique using the Medtronic Stealth spinal reference array allowing awake craniotomy to be performed without cranial fixation in the Mayfield pin head rest. A Medtronic spinal reference array (four-point H-shaped LED array) is fitted to a Yasargil footplate via a three-jointed swingarm. The Yasargil footplate is directly attached to the cranium after craniotomy and following stereotactic registration the patient is awakened. The patient is free to move his head during the procedure as the reference array does not move in relation to the cranial contents and the fiducials, preserving accuracy.

Endoscopic removal of a third ventricular cysticercal cyst.

We report the case of a young man who presented with acute obstructive hydrocephalus previously treated with bilateral ventriculo-peritoneal shunts. Previous magnetic resonance imaging studies were consistent with aqueduct stenosis; no intraventricular pathology was identified. Neuroendoscopy was performed in order the third ventricle and perform a third ventriculostomy. This revealed a cysticercal lesion of the third ventricle which was removed endoscopically. In addition, a third ventriculostomy was performed and both shunt systems removed. Following a course of albendazole the patient went on to make a full recovery, and currently remains shunt independent.

High and low pressure states associated with posterior sacral meningocele.

We describe the rare cases of a 44-year-old woman and a 28-year-old woman each presenting with a large posterior sacrococcygeal mass and alternating symptoms of high and low intracranial pressure. The first patient underwent excision of her large sacral meningocele and simple ligation of the neck, resulting in resolution of all her associated symptoms. The second patient suffered traumatic rupture of the meningocele; she underwent excision of the redundant sac and repair of the dural defect using a musculofascial flap, also resulting in resolution of her symptoms.

Wrapping of solitary ruptured intracranial aneurysms, outcome at five years.

Previous follow up studies of patients who have had ruptured intracranial aneurysms treated by a wrapping technique have largely been in the pre-microsurgical era. Our objective was to ascertain whether wrapping aneurysms with the aid of the operating microscope provides protection against rebleeding in the short and long term. The study involved retrospective analysis of patients with ruptured aneurysms treated by wrapping over a six-year period. Twenty-nine patients were identified with wrapped aneurysms, of these 15 had wrapping of a solitary ruptured aneurysm, the remainder were excluded because of clip/wrap combination, multiple aneurysms, and unruptured aneurysms. Of the 15 patients who had a solitary ruptured aneurysm wrapped, none had rebled at one year follow up. One patient died of a myocardial infarction at 4 years, the remaining 14 patients had no episodes of rebleeding with all patients achieving Glasgow outcome scores of four or five at 5 years follow-up. Although surgical clipping of intracranial aneurysms is the definitive method of treatment, our findings suggest that wrapping of ruptured intracranial aneurysms with the aid of the operating microscope confers good protection against both early and late rebleeding in those cases considered 'unclippable'.

Posterior fossa meningiomas: surgical experience in 52 cases.

BACKGROUND: Early reports of the surgical management of posterior cranial fossa meningiomas (PCFM) yielded poor results with high rates of mortality and morbidity. With the advent of modern neuroimaging and microsurgical techniques the results of surgery have improved markedly, but despite these advances removal of these lesions remains a challenge. METHODS: The results of the surgical treatment of PCF meningiomas were examined with the aim to identify particular features associated with increased mortality and morbidity. RESULTS: Of 713 patients with meningioma, 52 patients were identified with PCFM. Total macroscopic excision was achieved in 44 patients (84%). Postoperative complications occurred in 28 patients (54%) with permanent sequelae in 18 (35%). There were no mortalities in the immediate postoperative period. Follow-up ranged from 14 to 174 months (mean 42), tumour has recurred in 11 patients (21%) with a long-term mortality of 11%. At their latest follow-up 41 (79%) of patients achieved Glasgow outcome scores of 4 or 5. CONCLUSIONS: Total excision of tumour should remain the goal of treatment in patients with PCFM. Despite the recent advances in preoperative planning and surgical techniques, the morbidity associated with surgery remains significant. Notwithstanding, the majority of patients achieve a good outcome with surgical treatment.

The contribution of proton magnetic resonance spectroscopy (1HMRS) to clinical brain tumour diagnosis.

Proton magnetic resonance spectroscopy (1HMRS) provides biochemical information from tissue non-invasively, and has an evolving role in brain tumour diagnosis and management. We present 100 consecutive patients with brain tumours who had single voxel 1HMRS as part of their preoperative investigations. We report the histopathological findings and the diagnostic contribution of spectroscopy in an adjunctive role. On the basis of clinical and radiological information the preoperative diagnosis was unclear or inaccurate in 26 out of 100 cases. The discrepancy was of lesion grade in 17 cases and lesion type in 9 cases. In 6 of 100 patients with brain tumours 1HMRS could have made a significant contribution to the preoperative diagnosis if used as part of the routine assessment. There is therefore a useful role for 1HMRS in the evaluation of intracranial mass lesions.

Comparison of in vivo 1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samples in vitro.

High resolution magic angle spinning (MAS) 1H nuclear magnetic resonance (NMR) spectroscopy has been employed to study intact human brain tumour tissue and comparison with the corresponding in vivo spectrum has been made. Two dimensional 1H MAS-NMR measurements, including J-resolved and homonuclear shift correlation spectra, were obtained to aid metabolite signal assignment. MAS gave greatly improved line-shape and reduced line-width in comparison to conventional high resolution in vivo 1H MRS of intact tissue, permitting the simultaneous detection of cellular lipids and metabolites. The technique provides the most direct method for comparison of in vivo spectra with high resolution spectra in vitro and hence allows more reliable peak assignment of in vivo 1H MRS spectra.

Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy.

Proton spectroscopy can noninvasively provide useful information on brain tumor type and grade. Short- (30 ms) and long- (136 ms) echo time (TE) (1)H spectra were acquired from normal white matter (NWM), meningiomas, grade II astrocytomas, anaplastic astrocytomas, glioblastomas, and metastases. Very low myo-Inositol ([mI]) and creatine ([Cr]) were characteristic of meningiomas, and high [mI] characteristic of grade II astrocytomas. Tumor choline ([Cho]) was greater than NWM and increased with grade for grade II and anaplastic astrocytomas, but was highly variable for glioblastomas. Higher [Cho] and [Cr] correlated with low lipid and lactate (P < 0.05), indicating a dilution of metabolite concentrations due to necrosis in high-grade tumors. Metabolite peak area ratios showed no correlation with lipids and mI/Cho (at TE = 30 ms), and Cr/Cho (at TE = 136 ms) best correlated with tumor grade. The quantified lipid, macromolecule, and lactate levels increased with grade of tumor, consistent with progression from hypoxia to necrosis. Quantification of lipids and macromolecules at short TE provided a good marker for tumor grade, and a scatter plot of the sum of alanine, lactate, and delta 1.3 lipid signals vs. mI/Cho provided a simple way to separate most tumors by type and grade.