Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease.

Pentosan polysulphate, delivered by chronic intraventricular infusion, has been proposed as a potential therapy for human prion disease. The first treated patient is still alive several years after treatment started. Here we describe in detail a case of variant Creutzfeldt-Jakob disease in which this treatment was started at a relatively early stage but had no definite clinical benefit. The patient died from disease progression 16 months after diagnosis and 5 months after pentosan polysulphate treatment was commenced.

Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma.

BACKGROUND AND PURPOSE: The mechanisms by which the glucocorticoid dexamethasone produces its therapeutic action in patients with intracranial tumors still remain unclear. The purpose of this study was to investigate whether dexamethasone affects cerebral perfusion and water molecule diffusion by using quantitative dynamic susceptibility contrast perfusion MR imaging (DSC-MR imaging) and diffusion tensor MR imaging (DT-MR imaging). METHODS: Ten consecutive patients with glioblastoma multiforme underwent DSC-MR imaging and DT-MR imaging before and 48-72 hours after dexamethasone treatment (16 mg/day). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and water mean diffusivity () were measured for enhancing tumor, nonenhancing peritumoral edematous brain, and normal-appearing contralateral white matter before and after steroid therapy. The percentage change in CBF, CBV, MTT, and for the 3 tissue types was calculated for each patient, a mean value obtained for the population, and the statistical significance determined by using a paired-samples Student t test. RESULTS: After dexamethasone treatment, there was no significant change in tumor CBF, CBV, or MTT. Edematous brain CBV and MTT were also unchanged. There was, however, an increase in edematous brain CBF (11.6%; P = .05). was reduced in both enhancing tumor (-5.8%; P = .001) and edematous brain (-6.0%; P < .001). There was no significant change in CBF, CBV, MTT, or for normal-appearing contralateral white matter after treatment. CONCLUSION: These data suggest that dexamethasone does not significantly affect tumor blood flow but may, by reducing peritumoral water content and local tissue pressure, subtly increase perfusion in the edematous brain.

Patient perceptions of "awake" brain tumour surgery.

BACKGROUND: Awake brain tumour surgery allows intraoperative patient assessment and is done to optimise safe tumour removal. It is an established technique but little is known about patient perceptions of the procedure. METHOD: Fifteen adult patients filled out a dedicated questionnaire to assess 10 aspects of patient perceptions of the procedure. FINDINGS: All patients, who were awake for a median of 45 minutes (range 10-105), stated they were adequately prepared for the operation. Most recollected various aspects of the procedure, although 3 patients (20%) had little memory of actually being awake during the surgery despite being cooperative. A minority reported more than minor discomfort (20%), fear (15%) or anxiety (29%), and most felt they coped with the cortical stimulations and functional testing well. Sources of discomfort and pain were the cranial pin holding device, operative position, inadequate infiltration of the cranial wound with local anesthetic, a full bladder causing a desire to micturate and a hard and uncomfortable operating table. CONCLUSIONS: These results, are very similar to a previous American report using a different anesthetic technique, in that most patients tolerate awake craniotomy remarkably well if the procedure is explained to them and some simple precautions are taken. Additionally between 8%-37% of patients (95% Confidence Interval, summing data from the two studies, n = 35) will have no recollection of being awake. Ways of minimising discomfort and problems of anxiety in this patient cohort are discussed.

Costs of thalamic deep brain stimulation for movement disorders in patients with multiple sclerosis.

Several studies have shown that thalamic deep brain stimulation (DBS) reduces tremor and improves hand performance in patients with multiple sclerosis (MS). The purpose of this paper is to describe the cost implications of DBS in MS patients and to highlight postoperative medical requirements that can be associated with this therapy. In a prospective study of thalamic DBS in MS patients the mean equipment costs were pounds 4769 (median pounds 7010, Medtronic, 1998 prices); mean neurosurgical inpatient costs per operated patient (n = 15) were pounds 4848 (range pounds 1982-8920, median pounds 5110); and mean in-patient postoperative rehabilitation cost pounds 4602 (range pounds 0-32,225, median pounds 1783). In addition there were transport and follow up costs. Mean neurosurgical inpatient stay following stereotactic DBS implantation was 15 days (median 12 days); and mean inpatient, postoperative rehabilitation stay 54 days (median 25 days). Although there were significant improvements in hand function and tremor reduction at 12 months postoperation, the level of patient performance in activities of daily living, their perception of their handicap and ipse facto the amount of home support required were unchanged from preoperative levels. This study has highlighted significant unforeseen medical requirements and costs that can occur in MS patients who have thalamic DBS surgery.

A prospective study of thalamic deep brain stimulation for the treatment of movement disorders in multiple sclerosis.

The place for neurosurgical management of movement disorders in multiple sclerosis is unclear. To evaluate the potential benefits of unilateral thalamic deep brain stimulation (DBS) a prospective study was performed. Fifteen patients with confirmed MS and chronic, severe, drug-resistant movement disorders underwent stereotactic surgery to implant a thalamic DBS electrode using CT image guidance and intra-operative neurophysiological testing. The primary outcome measures were reduction in tremor severity and improvement in tests of hand function when the DBS electrode was turned on, 12 months after surgery. Secondary outcome measures included indices of disability, handicap, neuropsychological function and independence. Thirty-seven patients were assessed for treatment, but only 15 underwent surgery. In the 10 patients in whom implantation of the complete DBS system was carried out there was a significant reduction in the severity of tremor (p = 0.02) and improvement in hand function (p = 0.02). There were no benefits in any of the secondary outcome measures. Two patients had thalamocapsular haemorrhages at the site of electrode implantation and two had seizures in the follow-up period. Thalamic stimulation significantly reduced the tremor associated with MS and improved hand function in the targeted upper limb. However, there can be difficulties with identifying an optimal implantation site during operation, significant procedural morbidity and difficulty in predicting immediate outcome. It is also likely that the insignificant benefits of DBS on disability and handicap reflect persisting cerebeller dysmetria, and both the severity and diffuse nature of the disease process in this patient cohort.

Chronic posttraumatic movement disorder alleviated by insertion of meso-diencephalic deep brain stimulating electrode.

Incapacitating and drug-resistant posttraumatic movement disorders have successfully been treated by stereotactic thalamotomy. We describe the case of a young man with a posttraumatic hemiballismoid type movement disorder of the left arm, persistent for 2 years, who was selected for treatment with a thalamic deep brain stimulator. However, placement of the stimulating electrode tip at the junction of the zona incerta and subthalamic regions caused abolition of the movement disorder, and the pulse generator was not required. Reassessment over a 44-month period using multiple clinical and functional tests has confirmed continued benefit. This case adds to the reports of alleviation of movement disorders following either stereotactic thalamic mapping or placement of stimulating electrodes without macroscopic thalamic lesioning.

Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels.

OBJECT: Intracranial infusions of gamma-linolenic acid (GLA), an essential fatty acid, have been used as an adjuvant therapy following malignant glioma resection; however, little is known about the dose response of glioma cells to this therapy. In this in vitro study the authors address this important pharmacological question. METHODS: Glioma spheroids derived from U87, U373, MOG-G-CCM, and C6 cell lines were grown in collagen gel and exposed to a range of GLA concentrations (0-1 mM) for 5 days. The diameter of glioma spheroids was measured, the apoptotic index was assessed using both the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and cell morphological testing, and the levels of proliferating cell nuclear antigen were also measured. CONCLUSIONS: The dose-response patterns were similar for all four glioma spheroids. Low concentrations of GLA (<100 microM) increased both apoptosis and proliferation with a net increase in tumor growth and invasion, whereas high-dose GLA (>100 microM) significantly impaired spheroid cell growth. The proliferative effects of low-dose GLA could be a hazard in the clinical treatment of malignant glioma; however, because of the low toxicity of GLA against normal cells, local delivery of millimolar doses of GLA could significantly reduce tumor size.

CT-guided stereotactic antero-medial pulvinotomy and centromedian-parafascicular thalamotomy for intractable malignant pain.

A quick and safe CT image-guided stereotactic thalamotomy technique that has proved ideal for alleviating medically refractory intractable pain due to malignant disease is described. A simple method of deriving cartesian coordinates for target points that facilitates functional neurosurgery using CT images and the Brown-Roberts-Wells stereotactic system is also described.

Teaching image-guided stereotactic methodology and functional neuroanatomy of the thalamus and pallidum: a simple ex vivo technique.

A simple and cheap model that enables on site, ex vivo, but very practical, learning of frame-based image-guided stereotactic technique and methodology, and the functional anatomy of the pallidum and thalamus is described. Using a cadaver skull, a specially prepared, formalin-fixed cadaver brain, and a modified stereotactic probe application of a stereotactic frame to the cranium, fiducial point acquisition, target point acquisition, computation of both arc and probe depth settings, and verification of target point accuracy can all be practiced. If diencephalic targets are selected for targeting with ball bearings then section of the cadaver brains, and study of a human thalamic stereotactic atlas provides an excellent and clinically relevant method of learning functionally important thalamic and pallidal anatomy. The method and techniques are described for CT imaging using the Brown-Roberts-Wells frame, but they are equally applicable to other frame types.

Epileptogenic anaplastic astrocytoma imaged only by T2-weighted magnetic resonance studies: clinical and surgical implications.

The case of a 28-year-old woman who presented with focal sensory seizures and later developed mild sensory loss in the face and hand is described. An EEG, two contrast-enhanced CT and non-enhanced T1-weighted magnetic resonance (MR) scans were normal, but T2-weighted MR scans revealed a lesion measuring 3 x 2 cm in the mid-rolandic region. This lesion did not enlarge over a 6-month period. Resection of the abnormal gyrus was guided by electrocorticography and histology revealed an anaplastic astrocytoma. Although there was resolution of the facio-digital sensory loss postoperatively the frequency and pattern of the partial sensory seizures was unchanged. The neuroradiological and histological findings in this case highlight the difficulties concerning the indications for surgical intervention in adult patients who present with epilepsy and have lesions visualized only on magnetic resonance imagery.

CT-guided stereotactic neurosurgery using the Brown-Roberts-Wells system: experience with 125 procedures.

Experience with a consecutive series of 125 computerized tomographic (CT) image guided stereotaxic neurosurgical procedures, performed using the Brown-Roberts-Wells (BRW) system is described. Operative objectives included tissue sampling for diagnostic purposes, intra-operative localization of craniotomy flaps and intracerebral lesions, cyst and abscess aspiration and lesion to modulate tremor. A neuropathological diagnosis was possible in 96% of the biopsies, and lesions were precisely localized in all patients undergoing microsurgical stereotaxic craniotomy. Two patients (2.2%) undergoing stereotaxic biopsy died as a result of the procedure and one patient's hemiparesis was permanently worsened (0.8%). In only one of three patients undergoing stereotaxic thalamotomy was tremor abolished. This report confirms that CT image guided stereotaxic neurosurgery is safe, accurate and versatile. There is, however, a moderate incidence (7.2%) of lesser complications that can occur with this type of surgery. These complications, which are emphasized in this paper, are related to both the site of surgery and the neuropathology.

The contribution of secondary mediators to the etiology and pathophysiology of brain oedema: studies using a feline infusion oedema model.

Secondary mediator compounds are postulated to have a role in vasogenic oedematogenesis. They may also cause focal brain dysfunction due to their neuronal, axonal and glial modulating properties. Using the feline model of infusion brain oedema the effects of right frontal intracerebral infusion (200 microliters/hr for 3 hrs) of saline, bradykinin (10(-4) to 10(-6) M), arachidonic acid (10(-2) to 10(-3) M), 20% protein and four human glioma cyst fluids were evaluated. Somatosensory evoked potentials (SSEP), motor evoked potentials (MEPs), rCBF and rCBF CO2 reactivity (Hydrogen clearance). ICP, craniospinal compliance, local brain tissue water content (microgravimety), brain histology and BBB function (Evans Blue 2%) were measured. Brain water content increased locally from 69% to 79%, ICP increased (by mean 14 mmHg) and compliance decreased (mean 70%) and there were the histological features of brain oedema with all infusates. BBB opening occurred with Bradykinin (+), arachidonic acid (++), 20% protein ( ) and glioma cyst fluid (4+). Polymorphic and macrophage infiltrates were seen with all infusions but rCBF and MEPs remained normal. SSEPs changed with high dose bradykinin and some glioma cyst infusates whilst CBF CO2 reactivity was locally impaired by all infusates except saline and arachidonic acid. This study suggests that certain compounds in brain oedema fluid could mediate local brain dysfunction.