Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Arteriovenous malformations.

Arteriovenous malformations (AVMs) represent one of the most complex lesions encountered by the vascular neurosurgeon. They are thought to arise by a developmental aberration early in fetal life leading to structurally abnormal vessels, characterised by arteriovenous shunting. AVMs may present in a number of ways, the most devastating being hemorrhage. Their natural history, particularly hemorrhage risk, has been extensively studied and is crucial in informing management decisions. The primary goal of treatment is to eliminate hemorrhage risk. Success in treating these lesions involves comprehensive evaluation of the lesions to balance the risk of haemorrhage against the risk of treatment. Thus, first the decision whether to treat is made followed by selecting the optimum modality of treatment. Successful surgical treatment of AVMs requires extensive preoperative planning and meticulous microsurgical technique.

Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we practising evidence-based medicine?

Although increasingly used, the precise role of radiotherapy in the management of meningiomas is still disputed. The objective of this study, therefore, was to appraise the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, and to compare and contrast it with the current opinion and practice of neurosurgeons in the United Kingdom and the Republic of Ireland. The use of radiotherapy as a primary treatment strategy or its use in the treatment of recurrence was not considered. We performed a systematic review of the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, surveyed current opinion amongst neurosurgeons involved in such cases and ascertained local practice using data from the regional cancer registry. Overall, 10 cohorts were identified that fulfilled our eligibility criteria. Four studies showed significantly improved local control in patients receiving adjuvant radiotherapy for incompletely resected grade I meningiomas. Our survey demonstrated that the vast majority (98%) of neurosurgeons would not recommend adjuvant radiotherapy in grade I meningioma. In grade II meningioma, most (80%) would not advocate adjuvant radiotherapy if completely excised, but the majority (59%) would recommend radiotherapy in cases of subtotal resection. Significant variation in opinion between centres exists, however, particularly in cases of completely resected atypical meningiomas (p = 0.02). Data from the Eastern Cancer Registration and Information Centre appears to be in line with these findings: less than 10% of patients with grade I meningiomas, but almost 30% of patients with grade II meningiomas received adjuvant radiotherapy in the Eastern region. In conclusion, our study has highlighted significant variation in opinion and practice, reflecting a lack of class 1 evidence to support the use of adjuvant radiotherapy in the treatment of meningiomas. Efforts are underway to address this with a randomized multicentre trial comparing a policy of watchful waiting versus adjuvant irradiation.

A second biopsy?--Tandem lesion.

This is a rare case of synchronous pituitary adenoma and PNET in an adult and first of this sort in the literature. The MR appearances suggest a single pathological entity causing the changes in the different anatomical location which can occur in cases of germ cell tumours, PNET and glioblastoma. In certain cases, histological confirmation may be warranted for the different lesions. Both pathologies have different treatment strategy and outlook depending on the age, extent of the disease and Karnofsky score.

Papillary tumour of the pineal region.

Papillary tumour of the pineal region (PTPR) is a relatively new and rare pathological entity, which appears to run a spectrum of clinical courses. We add another case with detailed description of the clinical course documented with serial imaging over the total of 7 years. In accordance with previous reports we recommend total surgical resection with subsequent focal radiotherapy. Clinical and radiological follow up of the entire cerebrospinal axis is mandatory.

Sporadic malignant nerve sheath tumour of the oculomotor nerve.

Malignant peripheral nerve sheath tumours (MPNST) are exceedingly rare in an intracranial location. In this report clinical and pathological evidence for the diagnosis of a MPNST arising from of the oclumotor nerve is presented. To our knowledge this is the first such case reported in the medical literature.

Primary intradural classic chondrosarcoma: case report and literature review.

OBJECTIVE AND IMPORTANCE: The exact origin of rare intradural chondrosarcomas remains obscure. We present a case report of an intradural classic chondrosarcoma (a very rare subtype of chondrosarcoma in this location), with a review of the literature, in an attempt to clarify the histogenesis of these tumors. CLINICAL PRESENTATION: A 48-year-old man presented with a 12-month history of progressive right hemiparesis. Computed tomography and magnetic resonance imaging demonstrated a left parietal space-occupying lesion. INTERVENTION: The patient underwent an image-guided, left parietal parasagittal craniotomy. An extrinsic tumor, which seemed to arise from the dura, was macroscopically removed. There was no bone involvement. The histological examination revealed a Grade II classic chondrosarcoma with tumor infiltration into the dura. Adjuvant radiotherapy was administered. CONCLUSION: Intradural chondrosarcomas are rare tumors, the majority of which are mesenchymal. Classic chondrosarcomas in this location are much rarer. Their histogenesis is uncertain. In this case, the origin seems to be from the dura. Because of the malignant potential of these tumors, radical extirpation whenever possible, followed by radiotherapy, is indicated.

Endoscopic treatment of suprasellar and third ventricle-related arachnoid cysts.

OBJECTIVE: To evaluate the role of neuroendoscopy in the treatment of rare suprasellar and other third ventricle-related arachnoid cysts. METHODS: A review of supratentorial midline arachnoid cysts treated by endoscopic fenestration. RESULTS: Ten cases were identified. The median age of these ten patients was 7.5 years. In three a cysto- or ventriculoperitoneal shunt had previously been inserted. Six cysts were located in the suprasellar/prepontine area, one was a combined suprasellar/middle fossa cyst, and three were complex cysts arising mainly in the quadrigeminal cistern and extending into the third ventricle. Successful endoscopic fenestration to both the ventricular system and the basal cisterns ("bipolar" fenestration) was achieved in all cases. In seven cases a cystoventriculostomy and cystocisternostomy was performed, while in three a cystoventriculostomy was combined with a third ventriculostomy, achieving additional communication to the subarachnoid space. The previously inserted shunts were removed at the end of the procedure. The median follow-up period was 17 (range 1-30) months. The clinical outcome was excellent in all cases, despite only marginal reduction in the cyst size and persistence of ventriculomegaly in some cases. No further treatment to the cyst was required during the period of follow-up. CONCLUSION: Third ventricle-related arachnoid cysts can be satisfactorily and safely treated by endoscopy. This approach leaves the patient shunt independent.

Management of spontaneous cerebellar hematomas: a prospective treatment protocol.

OBJECTIVE: To identify easily applicable guidelines for the surgical and conservative management of spontaneous cerebellar hematomas. METHODS: A treatment protocol was developed and prospectively applied for the management of 50 consecutive cases of cerebellar hematomas. The appearance of the fourth ventricle, adjacent to the hematoma, on computed tomographic scans was divided into three grades (normal, compressed, or completely effaced). The degree of fourth ventricular compression was correlated with the size and volume of the hematoma and the presenting Glasgow Coma Scale (GCS) score. The hematoma was surgically evacuated for all patients with Grade III compression and for patients with Grade II compression when the GCS score deteriorated in the absence of untreated hydrocephalus. Patients with Grade I or II compression were initially treated with only ventricular drainage in the presence of hydrocephalus and clinical deterioration. RESULTS: The degree of fourth ventricular compression was classified as Grade I in 6 cases, Grade II in 26, and Grade III in 18. The degree of fourth ventricular compression was significantly correlated with the volume of the hematoma (r(s) = 0.67, P < 0.0001), hydrocephalus (r(s) = 0.44, P = 0.001), the preoperative GCS score (r(s) = 0.43, P = 0.001), the maximal diameter of the hematoma (r(s) = 0.43, P = 0.001), and a midline location of the hematoma (chi(2) = 6.84, P < 0.009). Acute deterioration in GCS scores occurred for 6 (43%) of 14 patients with Grade III ventricular compression who were conscious at presentation. Thirteen patients with Grade I or II ventricular compression and stable GCS scores of more than 13 were treated conservatively. Nine patients were treated with ventricular drainage only, and 28 underwent posterior fossa craniectomy and evacuation of the hematoma with ventricular drainage. The mortality rate at 3 months was 40%. None of the patients with Grade III fourth ventricular compression and GCS scores of less than 8 at the time of treatment experienced good outcomes. Overall, 15 (60%) of 25 patients with hematomas with maximal diameters of more than 3 cm and Grade I or II compression did not require clot evacuation. CONCLUSION: Conscious patients with Grade III fourth ventricular compression should undergo urgent clot evacuation before deterioration. Surgical evacuation of the clot may not be required for large hematomas (>3 cm) if the fourth ventricle is not totally obliterated at the level of the clot.

A preliminary experimental in vivo study of the effect of photodynamic therapy on human pituitary adenoma implanted in mice.

As surgery alone may prove inadequate to effect a cure for invasive pituitary adenomas, photodynamic therapy (PDT) was investigated as a possible adjuvant treatment for this group of tumours. Different subtypes of human pituitary adenoma cells were implanted subcutaneously into nude mice to study the in vivo effect of PDT on such lesions. The photosensitizer used in this study was polyhaematoporphyrin at a dose of 10 mg/kg b.w., followed by light irradiation at a wavelength of 630 nm with varying light doses between 10 and 75 J/cm2. Histopathological examination of the treated implants consistently showed tumour vascular changes with acute inflammatory reaction, interstitial haemorrhage, and evidence of cell death at higher doses of light. These changes were absent in the control groups. These findings indicate that the cytotoxic effect of PDT demonstrated in vitro in previous studies, is also present in vivo.

Muslin induced granuloma following wrapping of intracranial aneurysms: the role of infection as an additional precipitating factor. Report of two cases and review of the literature.

Two patients who developed what appeared to be a granulomatous reaction following muslin wrapping of unclipped aneurysms are reported. They presented with cranial nerve palsies and at operation were found to have an abscess around the wrapped aneurysms. In one of these two patients Staphylococcus epidemidis was isolated from the pus. This, together with further evidence from reported cases in the literature, would suggest that infection may play an additional role at least in some cases in the onset of a foreign-body granulomatous reaction seen following wrapping of aneurysms.

Endoscopy-assisted burr hole evacuation of subdural empyema.

A 71-year-old man developed a large multi-loculated subdural empyema following the evacuation of a chronic subdural haematoma. The pockets of pus were successfully evacuated endoscopically via the burr holes resulting in good recovery and no re-accumulation. The advantages of this technique and the difficulties encountered during this procedure are discussed.

Tuberculous osteitis of the skull: a case report and review of the literature.

A 13-year-old girl of Pakistani origin presented with a non-tender, fluctuant swelling over her left parietal area and an underlying skull defect. At the apex of the swelling there was a sinus. Cultures of the discharge were positive for Mycobacterium tuberculosis. We present a case report of tuberculosis of the skull and review of the literature. We highlight the difficulty which still exists in establishing a diagnosis of tuberculosis in countries where it is uncommon.

Evaluation of surgery for the tethered cord syndrome using a new grading system.

A new grading system is presented to assess the degree of untethering achieved at surgery for the 'tethered cord syndrome' based on intraoperative observation at the end of the procedure. Various pathophysiological mechanisms responsible for the 'tethered cord syndrome', as well as possible factors causing retethering were considered in developing this grading system. In Grade I the cord is considered to be fully untethered and the factors potentially responsible for retethering are eliminated, in Grade II partial untethering is performed and in Grade III untethering is unsuccessful. This grading system was used to assess the results of 22 consecutive operations performed to release a tethered cord between June 1991 and February 1995. The tethering factors encountered at surgery were: spinal lipoma in 14, diastematomyelia in five, a tight filum terminale in 10 and intradural adhesions in three instances. The grade of untethering was correlated with the type of pathology encountered, postoperative results, and whether previous surgery was performed or not. Previous surgery was found not to affect the rate of subsequent successful untethering.

Cerebellar mutism following posterior fossa tumour surgery.

Two cases of transient mutism following operative removal of cerebellar medulloblastoma are reported. These add to the few cases reported in the literature of this rare complication of posterior fossa tumour surgery in children.

Posttraumatic cerebellar infarction.

We report an 18-year-old patient who presented with delayed neurological deterioration secondary to posttraumatic cerebellar infarction. Management by ventricular drainage and posterior fossa decompression resulted in a good outcome. The absence of a demonstrable structural vascular lesion makes this case apparently unique. The possible aetiology, pathogenesis and management of this condition are discussed.