Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Cranial vault unicameral bone cyst.

Introduction: Unicameral bone cysts (UBC), also known as simple bone cysts, are common benign bone lesions filled with fluid, primarily occurring in children and adolescents. Although they can develop in any bone, UBCs usually affect the long bones.Materials & Methods: A 53 year old male patient was found incidentally to have a calvarian lesion in the parietal region overlying the superior sagittal sinus (SSS) (Figure 1). The differential diagnosis included a large arachnoid granulation, haemangioma of bone, a giant cell tumour or tuberculous infection. The patient was planned for elective surgery to remove the lesion and establish the diagnosis. Surgery was uneventful.Conclusion: To the best of our knowledge we describe the first case of UBC affecting the cranial vault. The patient underwent surgery.

Spontaneous intracranial hypotension caused by cervical CSF fistulae mimicking subarachnoid haemorrhage - a case report.

We describe an unusual and rarely documented site of SIH supported by clear radiological evidence: a case of spontaneous cerebrospinal fluid (CSF) fistulae involving the C7 and C8 nerve root sheaths, presenting with sudden onset headache and requiring surgical intervention to seal the leaks. Investigations confirmed the leaks and the typical MRI findings of meningeal enhancement, which were resolved after surgery.

Long-term outcomes of children treated for Cushing's disease: a single center experience.

PURPOSE: Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. METHODS: Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). RESULTS: Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. CONCLUSIONS: The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

Endonasal endoscopic transsphenoidal pituitary surgery: early experience and outcome in paediatric Cushing's disease.

BACKGROUND: Selective adenomectomy remains the first-line treatment for Cushing's disease (CD), until recently by microscopic transsphenoidal pituitary surgery. Endonasal transsphenoidal endoscopic surgery (ETES) is emerging as a novel, less invasive treatment for pituitary adenomas and has become the optimal surgical approach. OBJECTIVE: There are no published series for the treatment of paediatric CD by ETES, and we report our centre's preliminary results. DESIGN: Retrospective analysis. PATIENTS: Six paediatric patients (median age 15·8 years; range 11·7-17·0 years) fulfilled standard diagnostic criteria for CD. Preoperatively, no abnormality was identified on pituitary MR scanning in 3 (50%) patients, one had a macroadenoma. Bilateral petrosal sinus sampling demonstrated central ACTH secretion (IPS/P ACTH ratio ≥3·0, post-CRH) in 3/6 (50%) patients. The same neurosurgeon and endoscopic nasal surgeon undertook all the operations. OUTCOME MEASURES: Therapeutic outcome and rate of complications. RESULTS: Clinical recovery and biochemical 'cure' were achieved in 5 (83%) patients, and a corticotroph adenoma was confirmed histologically in all cured cases. One case developed post-operative CSF leak requiring lumbar drain insertion and patching. At a mean interval of 4·7 years (0·1-10·8 years) post-operatively, cured patients have shown no recurrence. One patient, with a large diffuse adenoma requiring more extensive surgery, has panhypopituitarism, and another patient has GH and gonadotrophin deficiencies. CONCLUSIONS: Our experience shows that ETES for removing corticotroph adenomas in children, in most cases not visualized on MRI, is minimally invasive and gave excellent post-operative recovery/results. In skilled hands, this technique provides an alternative to conventional transsphenoidal microscopic surgery in managing paediatric CD.

Long-term remission and recurrence rates in Cushing's disease: predictive factors in a single-centre study.

OBJECTIVE: To investigate the early and late outcomes of patients with Cushing's disease (CD) submitted to a neurosurgical procedure as first-line treatment. DESIGN: In this single-centre retrospective case notes study, 131 patients with CD with a minimum follow-up period of 6 years (124 operated by transsphenoidal surgery (TSS) and seven by the transcranial approach) were studied. Apparent immediate cure: post-operative 0900 h serum cortisol level <50 nmol/l; remission: cortisol insufficiency or restoration of 'normal' cortisol levels with resolution of clinical features; and recurrence: dexamethasone resistance and relapse of hypercortisolaemic features. RESULTS: In patients operated by TSS, remission of hypercortisolaemia was found in 72.8% of 103 microadenomas and 42.9% of 21 macroadenomas, with recurrence rates 22.7 and 33.3% respectively with a 15-year mean follow-up (range, 6-29 years). Of 27 patients with microadenomas operated after 1991, with positive imaging and pathology, 93% obtained remission with 12% recurrence. In multivariate analysis, the time needed to achieve recovery of hypothalamo-pituitaryadrenal axis was the only significant predictor of recurrence; all patients who recurred showed recovery within 3 years from surgery: 31.3% of patients had total hypophysectomy with no recurrence; 42% of patients with selective adenomectomy and 26.5% with hemi-hypophysectomy showed recurrence rates of 31 and 13% respectively (χ(2)=6.275, P=0.03). Strict remission criteria were not superior in terms of the probability of recurrence compared with post-operative normocortisolaemia. CONCLUSIONS: Lifelong follow-up for patients with CD appears essential, particularly for patients who have shown rapid recovery of their axis. The strict criteria previously used for 'apparent cure' do not appear to necessarily predict a lower recurrence rate.

Positron emission tomography in the diagnosis and management of intracranial germ cell tumours.

Positron emission tomography (PET) with (18)F-fluorodeoxy-glucose indicates metabolically active tissue. When investigating enhancing intracranial tumours, we have suggested that PET positivity might suggest an intracranial germ cell tumour (IGCT). Here, we present a case with dicentric IGCT where PET was initially discordant between the lesions and where PET then became negative despite clearly aggressive clinical behaviour. A cautionary note is introduced with respect to the interpretation of negative (18)F-FDG PET when investigating enhancing intracranial lesions.

A "growing cause" of diabetic ketoacidosis.

The progress of a young woman presenting with diabetic ketoacidosis is described. She was managed as for a new presentation of type 1 diabetes, but was subsequently diagnosed with acromegaly due to a large pituitary tumour. Following treatment for this, and relative normalisation of growth hormone levels, she was able to stop insulin completely. Subsequently, an oral glucose tolerance test showed no evidence of abnormal glucose tolerance and she remains non-diabetic.

Thoracic arachnoiditis, arachnoid cyst and syrinx formation secondary to myelography with Myodil, 30 years previously.

Spinal arachnoiditis can rarely occur following irritation from foreign body substances, including certain oil based contrast agents used for myelography. We describe a patient with thoracic arachnoiditis, arachnoid cyst and syringomyelia, 30 years following a myelogram with Myodil. A 62-year-old female presented with chronic thoraco-lumbar back pain, a spastic paraparesis and sphincter disturbance. She had undergone a myelogram with Myodil, 30 years previously for investigation of back pain. A MRI scan revealed evidence of arachnoiditis, thoracic syringomyelia (T6-T8) and an anteriorly placed, extramedullary, arachnoid cyst at T10-T12, compressing the cord. At surgery, T7-T10 thoracic laminectomies were carried out and syringo- and cysto-subarachnoid shunts were inserted. At 12 months follow-up, the sphincter disturbance, lower limb weakness and mobility problems had almost resolved. Although, the use of oil based contrast agents such as Myodil has been discontinued, the present case illustrates some of the rare sequelae of its use, manifesting decades later. Aggressive surgical intervention produced symptomatic benefit.

Hypertrophic pachymeningitis and undifferentiated connective tissue disease: a case report and review of the literature.

A 63-year-old man with hypertrophic pachymeningitis (HP) and an undifferentiated connective tissue disease is described. Combined therapy with prednisolone and azathioprine improved his symptoms. The association between an undifferentiated connective tissue disease and HP is discussed.

Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing's disease.

OBJECTIVE: Early diagnosis and effective treatment of paediatric Cushing's disease (CD) is necessary to minimise associated morbidity. Accepted first-line treatment is selective transsphenoidal microadenomectomy (TSS), which can be technically difficult, and cure rates vary considerably between centres. In our paediatric CD patient group we have assessed the possible factors which may influence cure by TSS. SUBJECTS AND METHODS: From 1983-2004, 27 paediatric patients (16 males, 11 females; mean age+/-s.d., 13.1+/-3.2 yr; range, 6.4-17.8 yr) with CD were managed in our centre and underwent TSS. Sixteen patients (59%), seven males and nine females (mean age+/-s.d., 14.2+/-2.5 yr; range, 8.2-17.8 yr), were cured (post-operative serum cortisol < 50 nM). Eleven patients, nine males and two females (mean age+/-s.d., 11.5+/-3.6 yr; range, 6.4-17.8 yr) had post-operative cortisol levels above 50 nM (2-20 days), with mean serum cortisol levels at 09:00 h of 537 nM (range 269-900 nM) indicating a lack of cure. These 11 patients received external beam pituitary radiotherapy (RT). One patient with a pituitary macroadenoma had a post-operative cortisol level of < 50 nM but 0.8 yr later showed an elevated cortisol and residual disease. RESULTS: The patients cured by TSS alone were significantly older than those not cured (P = 0.038; Student's t test). All patients had CT/MRI pituitary imaging: 14 were reported to have microadenomas and one macroadenoma, while 12 were reported as normal. Bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with i.v. corticotropin-releasing hormone (CRH) administration was introduced as a pre-operative investigation in 1986 and was performed in 21 patients (78%), on BSIPSS, 16 (76%) had evidence suggesting pituitary adrenocorticotropic hormone (ACTH) secretion (central to peripheral (IPS:P) ACTH ratio after CRH of > or = 3.0) and 16 (76%) showed lateralisation of ACTH secretion (IPSG of > or = 1.4). There was concordance between the BSIPSS finding and the position of the microadenoma at surgery in 17/21 (81%) patients. Of the 16 patients showing lateralisation of ACTH secretion, 12 (75%) were cured by TSS. Of the four without lateralisation of ACTH, suggesting a midline lesion, 3 (75%) were cured by TSS. Post-operative pituitary hormone deficiencies in the patients cured by TSS were: pan-hypopituitarism 1/16, isolated growth hormone deficiency (GHD) (peak GH on glucagon/ITT < 1-17.9 mU/l) 9/16 and diabetes insipidus 3/16. CONCLUSION: Over a 21-year period selective adenomectomy by TSS cured 59% of all paediatric CD patients, with higher age favouring cure. Introduction of BSIPSS resulted in the demonstration of a high rate of lateralisation of ACTH secretion consistent with the surgical identification of the adenoma, and therefore appears likely to have contributed to the higher surgical cure rate.

Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas.

CONTEXT: Cushing's disease as a result of a pituitary macroadenoma is an uncommon cause of Cushing's syndrome, and reports in the published literature are few and of limited size. OBJECTIVE: Our objective was to establish the clinical and biochemical characteristics of macroadenomas associated with Cushing's disease compared with a large cohort of microadenomas and to assess their response to therapy. DESIGN: We conducted a retrospective case-records study for the years 1964-2001. SETTING: The study occurred at a tertiary referral hospital center. PATIENTS: Patients had Cushing's disease presenting with a pituitary macroadenoma, in comparison with a large group of microadenoma patients. INTERVENTIONS: Interventions included therapy with surgery and radiotherapy. MAIN OUTCOME MEASURES: Outcome measures included basal and dynamically responsive plasma ACTH and cortisol levels and response to treatment. RESULTS: We identified 18 patients with Cushing's disease secondary to a macroadenoma; basal 0900 h plasma ACTH was 135.8 +/- 32.5 and 45.0 +/- 4.3 ng/liter (mean +/- SEM), respectively, in macroadenomas and microadenomas (P = 0.013). Mean 0900 h serum cortisol was significantly increased in the macroadenomas (27.5 +/- 3.0 microg/dl, 759.6 +/- 82.6 nmol/liter, vs. 22.6 +/- 0.6 microg/dl, 624.7 +/- 16.4 nmol/liter) (P = 0.021). Testing with high-dose dexamethasone showed less suppression in the macroadenomas (57.6 +/- 8.7% vs. 74.4 +/- 2.1%; P = 0.02) and an attenuated ACTH response to CRH. For all biochemical variables there was considerable overlap between the two groups. Few patients with macroadenomas were cured by surgery. CONCLUSIONS: Pituitary macroadenomas causing Cushing's disease have biochemical features largely distinct from patients harboring microadenomas but represent one end of a continuum.