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Cyclic nucleotides (cAMP & cGMP) are critical intracellular second messengers involved in the transduction of a diverse array of stimuli and their catabolism is mediated by phosphodiesterases (PDEs). We previously detected focal genomic amplification of PDE1C in >90 glioblastoma multiforme (GBM) cells suggesting a potential as a novel therapeutic target in these cells. In this report, we show that genomic gain of PDE1C was associated with increased expression in low passage GBM-derived cell cultures. We demonstrate that PDE1C is essential in driving cell proliferation, migration and invasion in GBM cultures since silencing of this gene significantly mitigates these functions. We also define the mechanistic basis of this functional effect through whole genome expression analysis by identifying down-stream gene effectors of PDE1C which are involved in cell cycle and cell adhesion regulation. In addition, we also demonstrate that Vinpocetine, a general PDE1 inhibitor, can also attenuate proliferation with no effect on invasion/migration. Up-regulation of at least one of this gene set (IL8, CXCL2, FOSB, NFE2L3, SUB1, SORBS2, WNT5A, and MMP1) in TCGA GBM cohorts is associated with worse outcome and PDE1C silencing down-regulated their expression, thus also indicating potential to influence patient survival. Therefore we conclude that proliferation, migration, and invasion of GBM cells could also be regulated downstream of PDE1C.

The heterogeneity of tumours and uncertainties surrounding derived short-term cell cultures and established cell lines fundamentally challenge the research and understanding of tumour growth and development. When tumour cells are cultured, changes are inevitably induced due to the artificial growth conditions. Several recent studies have questioned how representative established cell lines or derived short-term cell cultures are of the tumour in situ. We have characterised gene expression changes induced by short-term culture in astrocytoma in order to determine whether derived short-term cell cultures are representative of the tumour in situ. In comparison to the majority of studies, paired biopsies and derived short-term cultures were investigated to reduce the effects of long-term culture and inter-tumour variability when comparing biopsies and derived cultures from tumours with the same histology from different individuals. We have used the Affymetrix GeneChip® U133A to generate gene expression profiles of 6 paediatric pilocytic astrocytoma (PA) biopsies and derived short-term cell cultures and 3 adult glioblastoma multiforme (GBM) biopsies and derived short-term cultures. Significant differential gene expression is induced by short-term culture. However, when the biopsy and derived short-term cell culture samples were grouped according to tumour type (PA and GBM) a molecular signature of 608 genes showed significant differential expression between the groups. This gene cohort can distinguish PA and GBM tumours, regardless of the sample source, suggesting that astrocytoma derived short-term cultures do retain key aspects of the global tumour expression profile and are representative of the tumour in situ. Furthermore, these genes are involved in pathways and functions characteristic of adult GBM including VEGF signalling, hypoxia and TP53 signalling.

A 75-year-old man presented with a 3-month history of progressive paraparesis due to an extradural mass causing cord compression at the T7 level of the thoracic spine. He underwent decompressive surgery, and later vertebrectomy and cage fixation. Histologically, the lesion was a localized mass of amyloid associated with a clonal plasma cell infiltrate. Localized 'amyloidomas' of the spine are rare, evolve slowly and often have a good prognosis following surgery.

Cyclic nucleotides (cAMPcGMP) are critical intracellular second messengers involved in the transduction of a diverse array of stimuli and their catabolism is mediated by phosphodiesterases (PDEs). We previously detected focal genomic amplification of PDE1C in90 glioblastoma multiforme (GBM) cells suggesting a potential as a novel therapeutic target in these cells. In this report, we show that genomic gain of PDE1C was associated with increased expression in low passage GBM-derived cell cultures. We demonstrate that PDE1C is essential in driving cell proliferation, migration and invasion in GBM cultures since silencing of this gene significantly mitigates these functions. We also define the mechanistic basis of this functional effect through whole genome expression analysis by identifying down-stream gene effectors of PDE1C which are involved in cell cycle and cell adhesion regulation. In addition, we also demonstrate that Vinpocetine, a general PDE1 inhibitor, can also attenuate proliferation with no effect on invasion/migration. Up-regulation of at least one of this gene set (IL8, CXCL2, FOSB, NFE2L3, SUB1, SORBS2, WNT5A, and MMP1) in TCGA GBM cohorts is associated with worse outcome and PDE1C silencing down-regulated their expression, thus also indicating potential to influence patient survival. Therefore we conclude that proliferation, migration, and invasion of GBM cells could also be regulated downstream of PDE1C.

Although the treatment of colloid cysts remains controversial, high viscosity and small volume are poor prognostic indicators for successful burr hole aspiration and cortical incision via craniotomy may be associated with postoperative epilepsy. The anterior transcallosal approach provides a direct and adequate pathway to the lateral ventricles, where the foramen of Monro serves as a natural entrance into the anterior third ventricle, especially when the foramen is dilated by a lesion. When the midsuperior portion of the IIIrd ventricle cannot be reached, the interforniceal or the subchoroidal exposures have been advocated. Stereotactic techniques contribute to a minimal invasive approach and reduce morbidity. Nine patients harbouring anterior third ventricular cysts (seven colloids and two intrinsic craniopharyngiomas) underwent anterior transcallosal microsurgical excision assisted by an interactive infrared-based image guided system (EasyGuide, Neuro, Philips). There were 4 men and 5 women ranging in age from 15 to 42 years (mean 28.5). Transcallosal transforaminal (5 cases) or interforniceal (4 cases) approaches allowed total excision in eight patients and subtotal in one. Postoperative morbidity included a case of transient hemiparesis and a case of transient short-term memory disturbances; both resolved in the first months. Mortality was zero. Particular advantages of the method were accurate trajectory and position of callosotomy incision determination, visualisation and avoidance of superior saggital sinus, retraction of bridging veins and the often variable pericallosal arteries, spatial orientation within the ventricular system, and identification of the periventricular anatomical structures.

The activity of temozolomide, which has shown clinical activity against malignant glioma, has been assessed in vitro against short-term cultures derived from these tumors using an intermediate duration microtitration assay with MTT reduction as the end-point This assay has previously been shown to correlate closely with a monolayer clonogenic assay. Sensitivity was assessed in 15 short-term cultures (passage levels 3-9) derived from WHO grade III and IV astrocytomas. These cultures had a median ID50 value of 258 microM for temozolomide and 16.13 microM for CCNU. Maximum serum concentrations of temozolomide are of the order of 75 microM but only three of 15 (20%) cultures had ID50s below this value. Fourteen of 15 (93%) cultures displayed cross-resistance between temozolomide and CCNU, although one line which was extremely resistant to CCNU retained sensitivity to temozolomide. Comparative studies of published clonogenic survival curves indicate that the short-term glioma cell lines used in this study have similar sensitivities to established glioma cell lines, whilst colon carcinoma cell lines and bladder carcinoma are often more resistant to these drugs. Cell lines from testicular teratoma cell lines may show exquisite sensitivity to temozolomide and this level of sensitivity is seen only occasionally in short-term cultures derived from malignant glioma.

Technical advances and pioneering surgeons have established neuroendoscopy as an accepted diagnostic and therapeutic tool. The clinical indications for endoscopy, variety of operative techniques and number of endoscopic surgeons continue to increase steadily. However, there are fundamental limits to the scope of freehand endoscopy principally governed by the need for direct vision of anatomical and pathological structures. In addition, whilst the expert neuroendoscopist is only occasionally disorientated by complex distorted anatomy, the rising number of novices are likely to be mislead relatively often. We report the integration of neuroendoscopy with an optical neuronavigation system to provide interactive image-guided neuroendoscopy. This combination both removes the constraining requirement for direct vision and provides accurate localisation to guide the surgeon during surgery. We describe the clinical application of this method to two cases where image-guided endoscopy was essential to the safe completion of the procedure.

Because of the methodological difficulties associated with the MTT assay in screening short-term cultures derived from human malignant glioma, a chemosensitivity assay based on the protein staining using sulforhodamine B (SRB) has been optimized for use with these cells. SRB at a fixed dye concentration achieved maximal staining density at 20 min for most cell lines and this intensity was not further increased by using dye concentrations above 0.2%. A delay in staining after fixation did not significantly decrease staining intensity, but delay in dye extraction after fixation and staining did. There was an excellent quantitative and qualitative linear relationship between cell number determined by either the SRB assay or by cell counting, but not with the MTT assay which consistently underestimated the number of cells in assay plates. The MTT assay appeared to be incapable of detecting less than about 150 cells/well, while these small numbers of cell were readily detectable by either cell counting or SRB staining. There was a close correlation between chemosensitivity values derived from the MTT and SRB assays for procarbazine, CCNU and vincristine when the endpoint is taken as either the ID25, ID50 or ID75. The results indicate that the SRB is capable of producing broadly similar results to the MTT assay, but is more sensitive in the detection of small numbers of cells with a linear relationship between cell number and SRB staining intensity over a wide range of cell numbers. It is capable of producing data from short-term cultures from malignant glioma and offers technical advantages over the MTT assay in that plates may safely be stored at certain points during the assay without the need for immediate processing. The SRB assay provides a useful alternative to the MTT assay for determining the sensitivity of short-term cultures of human glioma to cytotoxic drugs.

Twenty nine patients with gliomas were investigated for loss of heterozygosity for 40 DNA polymorphisms in tumour DNA, particularly concentrating on those mapping to chromosomes 10 and 17. Eight of 18 grade IV gliomas showed loss of sequences from chromosomes 10, 17, or both. The data suggested total loss of one copy of chromosome 10, but there were interstitial deletions of the short arm of chromosome 17 in three of five tumours. Heterogeneous interstitial deletions of chromosome 17 were also found in two lower grade astrocytomas and one benign oligodendroglioma. The striking finding of this study was that patients with high grade gliomas whose tumours exhibited loss of heterozygosity for chromosomes 10, 17, or both survived significantly longer after surgery (median 17.4 months) than those whose tumours did not show loss of these chromosomes (median 6.7 months). These findings suggest that there is a subset of particularly aggressive high grade gliomas with no currently known molecular genetic abnormalities.

Selective removal of the medio-basal temporal structures has been introduced as an alternative to standard temporal lobectomy in the treatment of intractable temporal lobe epilepsy not related to gross structural lesions. Various approaches have been described for the surgical excision of the amygdalo-hippocampal complex, each of them presenting advantages and limitations. The recently introduced computer-assisted technique of volumetric stereotactic excision of deep-seated intracerebral lesions combines precision of targeting with elimination of unnecessary cortical trauma and may potentially provide an alternative method in the treatment of temporal lobe epilepsy. We present our experience of stereotactic volumetric selective amygdalo-hippocampectomy in six patients with medically intractable temporal lobe epilepsy. The criteria for selection, the pre-operative evaluation and the operative technique are discussed. All patients had a cessation or considerable reduction in seizure frequency while the morbidity was minimal.

The concept of stereotactic neurosurgery was introduced by Horsley and Clarke [4] on an experimental basis to explore the primate brain in 1905. This technology was adapted to the human brain by Spiegel and Wycis in 1947 [13] and subsequently stereotactic neurosurgical techniques have been applied not only for examination in the treatment for movement disorders and of chronic pain syndromes, but also in the management of brain tumors. With the development of CT scanning in the 1970s and of MRI scanning in the 1980s the use of stereotactic brain biopsy increasingly became widespread and was found to improve diagnostic yield of histological diagnosis with low morbidity and mortality, even in deep seated and highly eloquent areas.

We have examined a series of 13 benign and 27 malignant human gliomas for evidence of molecular abnormalities of proto-oncogene and putative tumour suppressor gene loci. The results indicated that specific molecular lesions were associated with increasing grades of malignancy. Thus, loss of genetic material on chromosome 17 was present with approximately equal frequency in both benign and malignant gliomas, whereas loss of loci on chromosome 10 was seen only in malignant gliomas. Only the most malignant tumours, known as glioblastoma multiforme, had more than one molecular abnormality in the same tumour. These findings may contribute to our understanding of glial tumour development, as well as improve the accuracy of tumour diagnosis. Images Figure 1 Figure 2 Figure 3

A non-invasive head fixation system is described which is accurately relocatable and enables the transfer of stereotactic positions between a variety of radiodiagnostic images and therapeutic procedures. The system can be simply and repeatedly applied for planning stereotactic radiation therapy from one or more diagnostic images and for repeated treatment with a conventional linear accelerator. In addition, the long-term effects of therapy can be objectively monitored by relocating the frame and repeating images in an identical way, months or years later.

The Gill-Thomas-Cosman (GTC) repeat stereotactic localiser allows frame-based stereotaxy to be performed in a minimally invasive manner by using dental fixation rather than traditional skull pins. The GTC enables accurate relocation in the same stereotactic space so that image acquisition and surgery can be separated if necessary. The device is especially suitable for fractionated stereotactic radiotherapy where it conveniently provides both patient-frame and frame-couch fixation on a repeatable basis.

In recent years, advances in computer technology and a significant increase in the accuracy of medical imaging have made it possible to develop systems that can assist the clinician in diagnosis, planning, and treatment. This paper deals with an area that is generally referred to as computer-assisted surgery, image-directed surgery, or image-guided surgery. We report the research, development, and clinical validation performed since January 1996 in the European Applications in Surgical Interventions (EASI) project, which is funded by the European Commission in their "4th Framework Telematics Applications for Health" program. The goal of this project is the improvement of the effectiveness and quality of image-guided neurosurgery of the brain and image-guided vascular surgery of abdominal aortic aneurysms, while at the same time reducing patient risks and overall cost. We have developed advanced prototype systems for preoperative surgical planning and intraoperative surgical navigation, and we have extensively clinically validated these systems. The prototype systems and the clinical validation results are described in this paper.

MRI is being increasingly used for the detection of intracranial lesions. MRI-guided stereotactic brain biopsy is infrequently performed. We audited our recent experience of this procedure, and demonstrated that it is feasible and comparable to CT-guided biopsy in terms of diagnostic accuracy with a low procedural morbidity. We critically analyse its future role in the presence of more recent developments.

A total of 15 patients with relapsed high-grade glioma were treated with carboplatin (400 mg/m2) or iproplatin (300 mg/m2). All had received previous radiotherapy, and 12 had previously undergone chemotherapy. One of the ten patients treated with carboplatin and one of the five treated with iproplatin achieved a partial remission as determined by repeat computerised tomographic (CT) scan. Myelosuppression was considerable, as three patients developed grade IV neurotoxicity, which was fatal in one case. Although carboplatin and iproplatin showed activity against malignant glioma, the study was closed because of unacceptable toxicity.

Paroxysmal exercise induced dystonia is a rare disorder classified as one of the paroxysmal dyskinesias.1 2 In this condition patients develop dystonia, mostly involving their feet, after prolonged exercise, usually walking or swimming.1-3Treatment response is poor to both antieplileptic drugs and drugs given for dystonia—for example, anticholinergic drugs, muscle relaxants, or acetazolamide.3 We recently noted the dramatic benefit of unilateral pallidotomy in completely abolishing attacks of paroxysmal exercise induced dystonia of the contralateral foot in one patient. This 47 year old woman was followed up over 2 years for a 10 year history of attacks of dystonia affecting her right foot, induced by exercise. At onset the attacks were mild and were induced by walking long distances. During an attack her right foot would invert for a few minutes making it difficult for her to continue walking or stand. The attack would subside within 2–3 minutes on resting. …

Malignant intracranial neoplasms are one of the most distressing conditions which present to the neurosurgeon. The management of these tumours is multidisciplinary, with surgery having a central role. Surgical options that are generally available include biopsy, be it freehand or stereotactically guided and open procedures. Conventional external beam radiotherapy is widely available as an adjuvant following surgery and is the only therapy to have consistently improved survival. Brachytherapy and focused radiation are available in specialized centres.

Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

The incidence of primary brain tumours is difficult to assess accurately as the frequency of different tumour types depends on the source of the series which is analysed, but ranges from 4.2 per 100 000 to 12.8 per 100 000 (Brewis et al., 1966; Liebowitz and Atler, 1969). Of these, approximately 30% are astrocytomas (Percy et al. 1972).

Six patients, with recurrent high grade glioma, receiving intralesional 131I labeled Mab, had a total of 36 SPECT, 6 CT and 3 NMR scans during their treatment. For each patient the image sets were registered with a combination of surface markers (SM) and stereotactic head frames (SF). Registration enabled the radioactivity on SPECT to be correlated on the anatomical features of CT and MRI, displaying its distribution within tumour and improving the confidence of tumour to background ratio calculation. Phantom and patient studies demonstrated comparable registration accuracy for the two techniques but strongly dependent on slice separation. In patients undergoing SPECT the SF took longer to prepare, patients had longer times in the scanning unit and it was more uncomfortable. Patient movement was eliminated using the SF as it attached to all the scanning couches but the resolution of SPECT was worse than SM as there was a wider radius of rotation of the camera head. Other various merits of the two systems are discussed but this study demonstrates that image registration in nuclear medicine is now feasible and despite its complexities, will have an advantageous impact on a multitherapy approach to cancer care.

Precision resection of stereotactically defined volume presents one of the current applications of “volumetric stereotaxis”. Computer-assisted reconstruction of serial outlines of the volume for resection obtained with modern computerised neuroimaging methods defines the spatial coordinates of that volume and allows its interpolation in a three-dimensional matrix (Kelly et al., 1984). Information derived from stereotactically performed computerised imaging allows the suspension of the given volume into a stereotactic three-dimensional space and its precise resection using a stereotactic technique. Experience with CT-directed volumetric resections indicates that the method is satisfactory. The ability of magnetic resonance imaging (MRI) to define the boundaries of most intracranial structures more accurately and its superior diagnostic image sensitivity make its use in stereotactic volumetric resections highly desirable. The use of MRI, however, in computerised volumetric stereotactic surgery presents considerable difficulties. Problems concerning the construction of stereotactic hardware materials such as fiducials, frame and stabilising devises have now been successfully addressed. Computer software compatible with current imaging and stereotactic hardware has also been developed and used in clinical practice and although the problem of linear distortion still remains, especially in the periphery of the image, it is now possible to use MRI-derived information in volumetric stereotactic resections either indirectly by registration of the stereotactic coordinates or directly through specially developed software (Kelly et al, 1987).

Four hundred and seventy five patients with trigeminal neuralgia underwent cryotherapy (145), radiofrequency thermocoagulation (265) or microvascular decompression 65) and were then followed up for mean time of 45 months. Outcome of treatment was assessed not only by the clinicians but also by a postal questionnaire. The presence of anxiety and depression was determined and compared to 51 patients due to undergo surgery. The median time to recurrence for the cryotherapy patients and the radiofrequency thermocoagulation patients were 6 and 24 months, respectively. At 5 years 38% of the microvascular decompression patients had had a recurrence of neuralgia. There was one operative death in the radiofrequency thermocoagulation group. Patients in all three groups were satisfied with their treatment but the questionnaires showed that clinicians under-report the recuccrence of pain and post operative complications. Pre-operatively depression and anxiety are high but post-operatively only 15% were depressed. Patients need careful pre-operative assessment which includes the McGill Pain Questionnaire and they should be given a choice about which surgical method would be most suitable in their case. Printed information should be available to supplement the consultation. This would ensure the patients' expectations matched up with the results as they would be aware of possible outcomes.

A computer program is described for planning accurate positioning of catheters containing radioactive Iodine-125 seeds for the treatment of recurrent malignant brain tumours. A stereotactic reference frame is fitted to the patient’s head and cross-sectional images acquired using a CT scanner. Images are transferred onto a computer and a three dimensional model of the head, tumour and frame constructed. A 3D cursor is used to mark catheter trajectories. The radiation dose distribution is calculated and displayed in two and three dimensions for various combinations of seed activity and position. The interactive 3D graphics and fast computation enables efficient optimization of plans.

The clinical results of six cases of open stereotactic amygdalohippocampectomy for medically intractable epilepsy are presented. Outcome in terms of seizure control (highly satisfactory in five patients) and neuropsychological sequelae (all cases had poor functioning of the contralateral temporal lobe pre-operatively) are detailed. In addition the use of post-operative Magnetic Resonance Imaging (MRI) is demonstrated and shown to be a valuable tool in providing the crucially accurate baseline that is required for more meaningful follow-up outcome studies.

Subcutaneous and intracranial VMDk tumours were treated with photodynamic therapy (PDT) using a new sensitiser, m-THPP. Subcutaneous tumours were highly sensitive to PDT but intracranial tumours were much more resistant, requiring a 30-fold increase in sensitiser dose to produce equivalent levels of necrosis. Resistance of intracerebral tumours was not due to failure of the sensitiser to enter tumours. Necrosis of intracranial tumours was increased when mice breathed 100% oxygen during PDT while subcutaneous tumour necrosis was unaffected.

Treatment of glioblastoma multiforme and other malignant cerebral gliomas by surgery combined with adjuvant methods remains relatively ineffective. The prognosis of an individual patient with a cerebral glioma depends more on precise tumour type and grade, as well as on the patient’s age and his performance score after surgery, than on operative, radiotherapeutic or chemotherapeutic interventions, However, the evidence from numerous empirical clinical trials confirms that chemotherapy, particularly with nitrosoureas or procarbazine, does have a significant biological effect in glioma, producing modest increases in median survival and in the rate of longterm survival.

Positron Emission Tomography (PET) employs tracers labelled with the shortlived positron emitting isotopes of biologically important elements like oxygen, and carbon or the analogue of hydrogen, fluorine, to study non-invasively the pathophysiology of gliomas in man.

Proton magnetic resonance spectroscopy (1H MRS) was used to investigate intracranial tumours in vitro and in vivo. Biopsy specimens were studied from 47 patients, 11 of whom were also examined in vivo. Analysis was based on the signals from N-acetylaspartate (NAA), phosphocreatine plus creatine (Cr), choline-containing compounds (Cho), alanine (Ala), and lactate. Biopsy data from 26 astrocytomas showed that the NAA/Cr ratio differs significantly in all grades from its value in normal white matter and that the Cho/Cr ratio differs significantly in grade IV tumours from its value in the other grades. Meningiomas have an unusually high Ala/Cr ratio. Spectra obtained in vivo are consistent with in vitro results from the same patients, and their lactate signal provides additional information about abnormal metabolism. We conclude that 1H MRS has a clear role in the diagnosis and biochemical assessment of intracranial tumours and in the evaluation and monitoring of therapy.

5In the UK abuse has also reached epidemic proportions, with the abuse of Ecstasy in particular being associated with the “rave culture”. In the past 7 months we have treated 13 patients with a positive history of abuse of one or more of these substances leading to ICH. Of these patients, 11 were well enough to undergo cerebral angiography. To our surprise this revealed seven intracranial aneurysms and three arteriovenous malformations. In only one case was the angiogram reported as normal. These ten patients subsequently went to have surgical or interventional radiological treatment of these abnormalities. The average age of patients was 31 (19–43) years. In this series, five of the seven aneurysm patients had successful surgery and were discharged home with no neurological deficit, one patient was discharged with a residual hemiplegia and one patient died before treatment. Of the three patients with arteriovenous malformations, one underwent successful surgical treatment, one had successful coil embolisation, and one was referred for longterm rehabilitation with severe neurological impairment following surgical intervention. The two-patients who were unfit for cerebral angiography died. Despite their young age, the mortality and morbidity of patients presenting with ICH following substance abuse appears to be substantially greater than similar patients without this aetiological factor. This usually reflects the fact that they are neglected in the initial phase of their illness, presenting in a dehydrated state and often have serious underlying illness such as AIDS and malnutrition. In addition it has been suggested that the intensity and duration of vasospasm is worsened by cocaine. Linking any neurological event with ingestion of a particular drug is, however, difficult because of inaccurate drug histories or because the substances bought on the street are frequently mixed with a variety of compounds before sale. We suggest that a thorough history focusing on the use of illicit substances and toxicological screening of urine and serum should be part of the evaluation of any young patient with a stroke. Contrary to historical opinion, drug-related ICH is frequently related to an underlying vascular malformation. Neurosurgical or neurological referral for cerebral angiography should be part of the evaluation of most young patients with ICH. Drug abuse is likely to represent the most common cause of stroke in young adults.

Twenty-four cases have been operated upon using a prototype Brown-Roberts-Wells, CT-guided stereotactic neurosurgical system. This device has proved to be practical and flexible in clinical use. No CT scanner modifications were required, a fact which simplified its use in more than one hospital. Multiple targets can be biopsied with ease and relative safety. Drainage and other therapeutic procedures can be carried out with minimal hazard. Future applications of this system may include its use with NMR and PET images.

Rapid T2 dependent field echo [partial saturation (PS)] sequences were used in 38 patients with brain tumors, intracerebral hematomas, and cerebral infarction as well as other neurological and abdominal disease. Reduction in the radiofrequency excitation angle (alpha) from 90 to 30 degrees produced an increase in lesion contrast as did change of echo time (TE) from 33 to 59 or 120 ms using repetition time (TR) values in the range of 120-500 ms. The PS sequence showing most lesion contrast was compared with conventional spin echo (SE 1,500/80 and SE 1,500/120) and inversion recovery (IR 1,500/500/44 and IR 1,500/100/44) sequences. Although PS sequences with TE = 39 ms were usually inferior to conventional SE sequences, those with TE = 59 or 120 ms were comparable and in some cases (particularly hematomas) superior. The PS sequences with alpha of approximately 30 degrees, TR of 80-250 ms, and TE of 60-120 ms offer considerable savings in time compared with conventional sequences although more work will be required to explore the limits of this approach and to optimize sequences at different field strengths.

Two cases of Aspergillus infection of the nervous system are reported. In the first case it occurred in a healthy individual and presented as a space occupying lesion mimicking a tuberculous granuloma. In the second case it was an opportunistic infection in a patient with predisposing conditions and manifested as chronic meningitis with fatal arteritis.