Impact of technique on cushing disease outcome using strict remission criteria.

BACKGROUND: Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery. METHODS: A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement. RESULTS: Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031 and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008). CONCLUSIONS: Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

Outcomes of surgically treated giant pituitary tumours.

OBJECTIVE: To evaluate the outcomes of patients with giant pituitary tumours (GPTs) who underwent a purely binasal endoscopic transsphenoidal surgery (BETS) and compare their outcomes with those achieved through craniotomy and microscopic transsphenoidal surgery (MTS). METHODS: Seventy-two consecutive patients with GPTs (greater than 10 cm3 in volume) who were treated surgically with BETS, craniotomy, or MTS from October 1994 to July 2009 were reviewed for clinical outcomes, degree of tumor resection, recurrence rates, and surgical complications. RESULTS: The BETS group had significantly better mean reduction of tumor volume (91%) than the craniotomy (63%, p = 0.001), and the MTS (63%, p = 0.010) groups. Gross total resection rates were also higher for BETS patients than for craniotomy patients (p = 0.010). Improvements in vision and headaches were noted in 96% and 100% of patients in the BETS group, respectively; these rates were similar to those in the craniotomy and MTS groups. Of the four patients with hormone-secreting tumours in the BETS group, three remained in remission. The median length-of-stay (four days) for the BETS group was shorter (p = 0.010), and surgical complications were less frequent (p = 0.037) and less severe compared to the craniotomy group. There were no differences in the recurrence rates: 79% percent of patients in the BETS group, 69% in the craniotomy group, and 79% in the MTS group were recurrence free at last follow-up (p = 0.829). CONCLUSIONS: Treatment of GPT with BETS offers excellent oncologic and clinical outcomes and can frequently obviate the need for craniotomy in these patients.

Surgical treatment of spontaneous intracranial hypotension secondary to degenerative cervical spine pathology: a case report and literature review.

OBJECTIVE AND IMPORTANCE: A rare cause of intracranial hypotension is leakage of cerebrospinal fluid (CSF) through a dural breach from degenerative cervical spine pathology. To our knowledge there have been only four cases described in the English literature. Treatment is challenging and varies from case to case, with complete symptom resolution reported for only one patient. Herein we review the literature and describe our surgical management of a 46-year-old woman with symptomatic intracranial hypotension from the penetration of the cervical thecal sac. CLINICAL PRESENTATION: The patient presented with a 3-month history of progressive orthostatic headaches. Magnetic resonance imaging demonstrated bilateral subdural hematomas and pachymeningeal gadolinium enhancement. An anterior epidural CSF collection commencing at a C4-5 calcified disc protrusion and osteophyte was evident on a computed tomography spinal myelogram. INTERVENTION: After three unsuccessful lumbar blood patches, we elected to attempt surgical removal of the causative pathology with exposure and primary closure of the dural defect by anterior cervical discectomy as described previously. After resection of the disc-osteophyte complex and dural exposure, immediate high volume egression of CSF mixed with blood at the surgical site. The dural defect was not visible but CSF egression promptly ceased. Cervical corpectomy for greater exposure and primary repair of the defect has been described, but we considered this unwarranted and felt the intraoperative blood collection formed a local blood patch. A collagen dural substitute membrane was inserted through the discectomy space for reinforcement. CONCLUSION: Two months after this novel surgical blood patch procedure the patient was asymptomatic and follow-up imaging demonstrated complete resolution.

Cranial neuropathies after intracranial Photofrin-photodynamic therapy for malignant supratentorial gliomas-a report on 3 cases.

BACKGROUND: In an RCT of PDT in the treatment of malignant gliomas, 3 patients developed cranial neuropathies after photoillumination. We are aware of no previous reports on cranial neuropathy after intracranial PDT. METHODS: In a cohort of 80 patients, there were 41 men and 39 women; 47 were newly diagnosed and 33 had recurrent tumors. All patients underwent surgical tumor extirpation. There were 77 malignant gliomas, 2 meningiomas, and 1 metastatic tumor. The tumor locations were as follows: 39 frontal, 25 temporal, 12 parietal, and 4 occipital. Of the 25 patients with temporal lobe tumors, 18 received PDT. RESULTS: Three of the 18 patients with temporal lobe tumors developed cranial neuropathies after PDT. The floor of the middle fossa received photoillumination in all 3 patients. This complication was not seen in any other patient with tumors in the frontal, parietal, or occipital regions, or patients with temporal lobe tumors who did not receive PDT. The first patient developed seventh nerve paresis and hypoesthesia in fifth nerve distribution, which resolved only partially. The second patient developed a seventh nerve paresis that resolved completely. The third patient developed transient neuralgic pain in the trigeminal nerve distribution. CONCLUSIONS: Cranial neuropathies could be the result of photoillumination of fifth and seventh cranial nerves during PDT of the temporal fossa. We recommend shielding of the middle fossa floor during PDT.

History of neurosurgery at University of Toronto: the St. Michael's story.

In this paper, the authors describe the history of neurosurgery at St. Michael's Hospital, University of Toronto. St. Michael's has long been regarded as one of the top teaching and research hospitals in Canada. A detailed literature review of published and unpublished works was performed to formulate a succinct but in-depth review of its development, successes, and challenges. This fascinating 125-year history serves as a reminder of the importance of their institution's origins, and the authors hope that it will be a useful guide for developing programs around the world.

Captive rearing of the deep-sea coral Eguchipsammia fistula from the Red Sea demonstrates remarkable physiological plasticity.

The presence of the cosmopolitan deep-sea coral Eguchipsammia fistula has recently been documented in the Red Sea, occurring in warm (>20 °C), oxygen- and nutrient-limited habitats. We collected colonies of this species from the central Red Sea that successfully resided in aquaria for more than one year. During this period the corals were exposed to increased oxygen levels and nutrition ad libitum unlike in their natural habitat. Specimens of long-term reared E. fistula colonies were incubated for 24 h and calcification (G) as well as respiration rates (R) were measured. In comparison to on-board measurements of G and R rates on freshly collected specimens, we found that G was increased while R was decreased. E. fistula shows extensive tissue growth and polyp proliferation in aquaculture and can be kept at conditions that notably differ from its natural habitat. Its ability to cope with rapid and prolonged changes in regard to prevailing environmental conditions indicates a wide physiological plasticity. This may explain in part the cosmopolitan distribution of this species and emphasizes its value as a deep-sea coral model to study mechanisms of acclimation and adaptation.

Hemorrhagic epidermoid cyst in a patient with generalized tonic clonic seizure.

Epidermoid cysts account for approximately 1% of all intracranial tumors. Hemorrhage into an epidermoid cyst is extremely rare, and has only been reported a few times. To our knowledge, there are no reports of a hemorrhagic epidermoid cyst presenting with a first generalized tonic clonic seizure. We present a 68-year old female with an epidermoid cyst with intracystic hemorrhage who presented with a first time generalized tonic clonic seizure. When complicated with hemorrhage, the diagnosis of an epidermoid cyst is challenging and there is a potential for misdiagnosis.

Electrophysiological correlates of looking at paintings and its association with art expertise.

This study investigated the electrocortical correlates of art expertise, as defined by a newly developed, content-valid and internally consistent 23-item art expertise questionnaire in N=27 participants that varied in their degree of art expertise. Participants viewed each 50 paintings, filtering-distorted versions of these paintings and plain colour stimuli under free-viewing conditions whilst the EEG was recorded from 64 channels. Results revealed P3b-/LPC-like bilateral posterior event-related potentials (ERP) that were larger over the right hemisphere than over the left hemisphere. Art expertise correlated negatively with the amplitude of the ERP responses to paintings and control stimuli. We conclude that art expertise is associated with reduced ERP responses to visual stimuli in general that can be considered to reflect increased neural efficiency due to extensive practice in the contemplation of visual art.

Photodynamic therapy of brain tumors--a work in progress.

BACKGROUND AND OBJECTIVES: PDT has been used in the treatment of malignant brain tumors. This communication updates our series of unselected malignant gliomas treated with Photofrin-PDT. STUDY DESIGN AND METHODS: We examined the records of 112 patients with malignant gliomas, metastatic brain tumors and meningiomas treated with Photofrin-PDT at St. Michael's Hospital, Toronto. These patients were treated prior to the onset of ongoing randomized trials in Photofrin PDT or had pathology that excluded them from such trials. RESULTS: The overall post-PDT survival of 96 patients with supratentorial gliomas was 42 weeks, with a 40 and 22% 1- and 2-year survival, respectively. The greater the degree of oligodendroglial involvement the longer was the survival. Seventy-five percent of patients had no significant post-operative complications. CONCLUSIONS: Photofrin-PDT was safe. However, higher light doses than were used in these patients may be required for improved responses.

Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development.

Fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have previously been investigated separately with the objectives, respectively, of increasing the extent of brain tumour resection and of selectively destroying residual tumour post-resection. Both techniques have demonstrated trends towards improved survival, pre-clinically and clinically. We hypothesize that combining these techniques will further delay tumour re-growth. In order to demonstrate technical feasibility, we here evaluate fluorescence imaging and PDT treatment techniques in a specific intracranial tumour model. The model was the VX2 carcinoma grown by injection of tumour cells into the normal rabbit brain. An operating microscope was used for white light imaging and a custom-built fluorescence imaging system with co-axial excitation and detection was used for FGR. PDT treatment light was applied by intracranially-implanted light emitting diodes (LED). The fluorescent photosensitizer used for both FGR and PDT was ALA-induced PpIX. For PDT, ALA (100 mg kg(-1)) and low light doses (15 and 30 J) were administered over extended periods, which we refer to as metronomic PDT (mPDT). Eighteen tumour bearing rabbits were divided equally into three groups: controls (no resection); FGR; and FGR followed by mPDT. Histological whole brain sections (H&E stain) showed primary and recurrent tumours. No bacteriological infections were found by Gram staining. Selective tumour cell death through mPDT-induced apoptosis was demonstrated by TUNEL stain. These results demonstrate that the combined treatment is technically feasible and this model is a candidate to evaluate it. Further optimization of mPDT treatment parameters (drug/light dose rates) is required to improve survival.

A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative Photofrin-photodynamic therapy of brain tumors.

BACKGROUND AND OBJECTIVES: Intra-operative identification of tumor by fluorescence may improve surgical resection or photodynamic therapy (PDT). A novel instrument was designed, constructed, and tested for this purpose. STUDY DESIGN/MATERIALS AND METHODS: The instrument was designed to provide high-resolution, multi-spectral (five band) fluorescence imaging, and non-contact point spectroscopy, with long working distance ( approximately 50 cm), large field-of-view ( approximately 3 cm diameter), large depth of view ( approximately 2 cm), and 'point-and-shoot' operation. Its performance was determined in tissue-simulating phantoms and in pilot studies in brain tumor resection patients, with or without intra-operative Photofrin-PDT. RESULTS: In phantoms the imaging resolution was approximately 150 microm, while Photofrin concentrations as low as 0.05 or 0.1 microg/g could be detected at the tissue surface or at 0.5 mm depth, respectively. Red Photofrin fluorescence could be clearly visualized post radical resection in all PDT patients, with biopsy confirmation of residual tumor tissue in regions that were not seen as tumor under white light. Photobleaching of Photofrin during PDT was also demonstrated. CONCLUSIONS: The system performed to specification under realistic operating conditions and could reveal unresected residual tumor tissue. It may be used for either PDT dosimetry/monitoring and/or for surgical guidance.

Increased brain tumor resection using fluorescence image guidance in a preclinical model.

BACKGROUND AND OBJECTIVES: Fluorescence image-guided brain tumor resection is thought to assist neurosurgeons by visualizing those tumor margins that merge imperceptibly into normal brain tissue and, hence, are difficult to identify. We compared resection completeness and residual tumor, determined by histopathology, after white light resection (WLR) using an operating microscope versus additional fluorescence guided resection (FGR). STUDY DESIGN/MATERIALS AND METHODS: We employed an intracranial VX2 tumor in a preclinical rabbit model and a fluorescence imaging/spectroscopy system, exciting and detecting the fluorescence of protoporphyrin IX (PpIX) induced endogenously by administering 5-aminolevulinic acid (ALA) at 4 hours before surgery. RESULTS: Using FGR in addition to WLR significantly increased resection completeness by a factor 1.4 from 68+/-38 to 98+/-3.5%, and decreased the amount of residual tumor post-resection by a factor 16 from 32+/-38 to 2.0+/-3.5% of the initial tumor volume. CONCLUSIONS: Additional FGR increased completeness of resection and enabled more consistent resections between cases.