Influence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing's syndrome.

BACKGROUND: Asymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing's syndrome (CS). OBJECTIVE: To assess the influence of IPS drainage patterns on detection of an adenoma in CS. METHODS: Retrospective single-center cohort analysis reviewing records of patients with CS and negative MRI findings who subsequently underwent BIPSS. RESULTS: BIPSS was performed in 38 patients with a mean age of 45±15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing's disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6±2.7 versus 16.4±6.0; P=0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0±2.5 versus 35.7±22.5; P=0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P=0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS. CONCLUSIONS: Bearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome.

Iatrogenic Vessel Dissection in Endovascular Treatment of Acute Ischemic Stroke.

PURPOSE: Knowledge about the localization and outcome of iatrogenic dissection (ID) during endovascular treatment of acute ischemic stroke (AIS) is limited. We aimed to determine the frequency, clinical aspects and morphology of ID in endovascular AIS treatment and to identify predictors of this complication. METHODS: Digital subtraction angiography (DSA) of ID carried out during endovascular treatment between January 2000 and March 2012 have been re-evaluated. The ID localization and morphology were analyzed and related to the interventional techniques. Baseline clinical and radiological findings, treatment modality and outcome were compared with patients without ID. RESULTS: Out of 866 patients 18 (2%) suffered an ID (44% female, median age 64 years). Localization was extracranial in 15 (83%, 14 internal carotid artery and 1 vertebral artery) and intracranial in 3 (17%; 1 vertebrobasilar dissection and 2 in the anterior circulation). Of the IDs 5 (28%) resulted in a high-degree, 3 (17%) in a moderate, 5 (28%) in a mild and 5 (28%) in no stenosis and 8 IDs were stented in the acute phase. At 3 months 7 (42%) patients had a favorable outcome (modified Rankin score mRS ≤ 2) and 6 (33%) patients had died. Patients with ID had a different stroke etiology (p = 0.041), were more likely to be smokers (44% versus 19%, p = 0.015) and were more likely to be treated with mechanical thrombectomy (100% versus 60%, p < 0.001). Although two ID patients had relevant complications, the outcome did not differ between the groups. CONCLUSION: The occurrence of ID is a rare complication of endovascular AIS treatment associated with smoking and mechanical thrombectomy.

Limitations of Current Near-Infrared Spectroscopy Configuration in Detecting Focal Cerebral Ischemia During Cardiac Surgery: An Observational Case-Series Study.

Cerebral oximetry using near-infrared spectroscopy (NIRS) allows for continuous monitoring of cerebral perfusion and immediate treatment of hemodynamic perturbations. In configurations used in current clinical practice, NIRS optodes are placed on the patient`s forehead and cerebral oxygen saturation (ScO2 ) is determined in bilateral frontal cortical samples. However, focal cerebral ischemic lesions outside of the NIRS field of view may remain undetected. The objective of this observational case-series study was to investigate ScO2 measurements in patients with acute iatrogenic stroke not located in the frontal cortical region. Adult patients undergoing cardiac surgery with cardiopulmonary bypass or interventional cardiology procedures and suffering stroke in the early postoperative period were identified from the Bernese Stroke Registry and analyzed for their intraoperative ScO2 values and brain imaging data. Main outcome measures were the ScO2 values, computed tomography and magnetic resonance imaging findings. In six patients, the infarct areas were localized in the vascular territories of the posterior and/or dorsal middle cerebral arteries. One patient had watershed stroke and another one excellent collaterals resulting in normal cerebral blood volume and only subtle decrease of cerebral blood flow in initially critically perfused watershed brain areas. Intraoperative ScO2 values were entirely unremarkable or nonindicative for brain damage. Our results indicate that uneventful intraoperative NIRS monitoring does not exclude severe cerebral ischemia due to the limited field of view of commercially available NIRS devices. False negative NIRS may occur as a consequence of stroke localized outside the frontal cortex.

Spatially extended versus frontal cerebral near-infrared spectroscopy during cardiac surgery: a case series identifying potential advantages.

Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac surgery, but early detection and treatment could protect patients from an unfavorable postoperative course. Hypoperfusion and emboli can be detected with transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow velocity correlates with cerebral oxygenation determined clinically by near-infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential advantage of a spatially extended NIRS in detecting critical events in three cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000 continuous-wave NIRS system. Principle components analysis was performed to differentiate between global and localized hypoperfusion or ischemic territories of the middle and anterior cerebral arteries. In one patient, we detected a critical hypoperfusion of the right MCA, which was not apparent in the frontal channels but was accompanied by intra- and postoperative neurological correlates of ischemia. We conclude that spatially extended NIRS of temporal and parietal vascular territories could improve the detection of critically low cerebral perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain normal because the anterior cerebral artery can be supplied by the contralateral side directly or via the anterior communicating artery.

Stereolithographic models in the interdisciplinary planning of treatment for complex intracranial aneurysms.

BACKGROUND: Treatment of complex intracranial aneurysms requires strategic pre-interventional or preoperative planning. In addition to modern three-dimensional (3D) rotational angiography, computed tomography angiography (CTA) or magnetic resonance angiogram (MRA), a solid, tangible 3D model may improve anatomical comprehension and treatment planning. A 3D rapid prototyping (RP) technique based on multimodal imaging data was evaluated for use in planning of treatment for complex aneurysmal configurations. METHODS: Six patients with complex aneurysms were selected for 3D RP based on CTA and 3D rotational angiography data. Images were segmented using image-processing software to create virtual 3D models. Three-dimensional rapid prototyping techniques transformed the imaging data into physical 3D models, which were used and evaluated for interdisciplinary treatment planning. RESULTS: In all cases, the model provided a comprehensive 3D representation of relevant anatomical structures and improved understanding of related vessels. Based on the 3D model, primary bypass surgery with subsequent reconstruction of the aneurysm was then considered advantageous in all but one patient after simulation of multiple approaches. CONCLUSIONS: Preoperative prediction of intraoperative anatomy using the 3D model was considered helpful for treatment planning. The use of 3D rapid prototyping may enhance understanding of complex configurations in selected large or giant aneurysms, especially those pretreated with clips or coils.

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature. METHODS: From 1998 to 2009 we treated 586 consecutive patients with CEA. CEA was performed, under general anesthesia, with a surgical microscope using a non-patch technique. Somatosensory evoked potential and transcranial Doppler were continuously monitored. Cross-clamping was performed under EEG burst suppression and adaptive blood pressure increase. Follow-up was performed by an independent neurologist. Mortality at 30 days and morbidity such as major and minor stroke, peripheral nerve palsy, hematoma and cardiac complications were recorded. The restenosis rate was assessed using duplex sonography 1 year after surgery. RESULTS: A total of 439 (75%) patients had symptomatic and 147 (25%) asymptomatic stenosis; 49.7% of the stenoses were on the right-side. Major perioperative strokes occurred in five (0.9%) patients [n = 4 (0.9%) symptomatic; n = 1 (0.7%) asymptomatic patients]. Minor stroke was recorded in six (1%) patients [n = 4 (0.9%) symptomatic; n = 2 (1.3%) asymptomatic patients]. Two patients with symptomatic stenoses died within 1 month after surgery. Nine patients (1.5%) had reversible peripheral nerve palsies, and nine patients (1.5%) suffered a perioperative myocardial infarction. High-grade (>70%) restenosis at 1 year was observed in 19 (3.2%) patients [n = 12 (2.7%) symptomatic; n = 7 (4.7%) asymptomatic patients]. CONCLUSIONS: The midterm rate of restenosis was low when using a microscope-assisted non-patch endarterectomy technique. The 30-day morbidity and mortality rate was comparable or lower than those in recently published surgical series.

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing's syndrome.

INTRODUCTION: Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma. METHODS: We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation. RESULTS: In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing's disease patients. CONCLUSION: BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor.

Incidence, clinical presentation and imaging findings of cavernous malformations of the CNS. A twenty-year experience.

QUESTIONS UNDER STUDY: Up to 88% of cavernous malformations (CMs) of the central nervous system can become symptomatic and cause long-term disability. The aim of this study was to document the characteristics of CMs in the catchment area of our institution. METHODS: We retrospectively analysed newly discovered CMs over a 20-year observation period, as well as the frequency of familial forms in the catchment area. RESULTS: In the period from 1985-2004, a total of 347 patients were investigated. The cohort included about 75% symptomatic CM cases. A total of 1.31 and 0.55 symptomatic and asymptomatic cases, respectively, were newly diagnosed per annum per 100'000 inhabitants. Symptomatic CMs were diagnosed on average at the age of 36 years (range: newborn to 79 years old). There were slightly more patients who presented with evidence of acute bleeding (28%) than those with seizures (26%). Most intracranial lesions were supratentorial in location (54%). Lesion size was predominately below 3 cm (range: 0.2 to 8 cm). Symptomatic CMs (average: 1.75 cm) were significantly larger (p <.0001) than asymptomatic ones (average 0.91 cm). When compared to medical literature, there was a relatively high frequency of multiple CMs (18.9%), which were more common in the familial form (62%). CONCLUSIONS: The observed frequency of CM, including multiple lesions in a single individual and the familial form of this pathological entity appears relatively high compared to medical literature.

Decompressive craniectomy after intra-arterial thrombolysis: safety and outcome.

OBJECTIVES: Data on decompressive craniectomy (DC) after intra-arterial thrombolysis (IAT) for treatment of malignant middle cerebral artery (MCA) stroke are lacking. METHODS: The authors compared consecutive patients with middle cerebral artery (MCA) strokes who underwent decompressive craniectomy (DC) after IAT with DC patients without prior thrombolysis. RESULTS: Thirty of 2395 consecutive patients with acute ischaemic stroke or transient ischaemic attack were treated with DC because of space-occupying oedema 12-72 h after symptom onset. Fifteen patients underwent intra-arterial thrombolysis (IAT) prior to DC. Baseline characteristics did not differ between thrombolysed and non-thrombolysed patients except for lower National Institute of Health Stroke Scale score in non-thrombolysed patients (median National Institute of Health Stroke Scale 17 vs. 14, p=0.033). The outcome at 3 months was favourable (modified Rankin scale 0-3) in seven (47%) thrombolysed patients and in four (27%) non-thrombolysed patients (p=0.45). Mortality and major complications after DC did not differ between the two groups (p>0.05). Older age (p=0.037) and previous hypertension (p=0.047) independently predicted unfavourable outcome in DC patients, but not IAT prior DC. CONCLUSIONS: There was no difference of outcome of patients with DC with or without prior IAT. DC after IAT did not cause any more complications than DC without prior thrombolysis.

Predictors of early mortality after acute ischaemic stroke.

BACKGROUND: The study set out to identify clinical, laboratory and radiological predictors of early mortality after an acute ischaemic stroke (AIS) and to analyse medical and neurological complications that caused death. METHODS: A total of 479 consecutive patients (mean age 63+/-14 years) with AIS underwent stroke examination and treatment. Examination included clinical evaluation, laboratory tests, and brain CT and/or MRI. Follow-up data at 30 days were available for 467 patients (93%) who were included in the present analysis. RESULTS: The median National Institute of Health Stroke Study (NIHSS) score on admission was 6. A total of 62 patients (13%) died within 30 days. The cause of death was the initial event in 43 (69%), pneumonia in 12 (19%), intracerebral haemorrhage in 9 (15%), recurrent stroke in 6 (10%), myocardial infarction in 2 (3%), and cancer in 1 (2%) of the patients. In univariate comparisons, advanced age (p<0.001), hypertension (p=0.013), coronary disease (p=0.001), NIHSS score (p<0.001), undetermined stroke etiology (p=0.031), relevant co-morbidities (p=0.008), hyperglycemia (p<0.001), atrial fibrillation (p<0.001), early CT signs of ischemia (p<0.001), dense artery sign (p<0.001), proximal vessel occlusion (p<0.001), and thrombolysis (p=0.008) were associated with early mortality. In multivariate analysis, advanced age (HR=1.12; 95% CI 1.05-1.19; p<0.001) and high NIHSS score on admission (HR=1.15, 95% CI 1.05-1.25; p=0.002) were independent predictors of early mortality. CONCLUSIONS: We report 13% mortality at 30 days after AIS. More than two thirds of the deaths are related to the initial stroke. Advanced age and high NIHSS score are the only independent predictors of early mortality in this series.

Orbital venous malformation: percutaneous treatment using an electrolytically detachable fibred coil.

PURPOSE: To report the efficacy of percutaneous treatment of an orbital venous malformation with an electrolytically detachable fibred coil. METHODS: We report an instance of radiography-guided percutaneous treatment with an electrolytically detachable fibred coil in a 16-year-old boy with acute, spontaneous, painless proptosis on the left side, which progressed with time. RESULTS: Magnetic resonance imaging, angiography and orbitophlebography revealed a low-flow, intraorbital venous malformation. Percutaneous puncture and drainage were followed by a short remission. Following an acute recurrence, a single detachable fibred coil was deployed via a percutaneous approach under angiographic guidance. No radiological or clinical recurrences were observed over 4 years. CONCLUSIONS: Embolization of a deep orbital venous malformation with detachable fibred coils via a percutaneous approach can be highly effective, and may be considered before proceeding with open surgery.

A novel method for analyzing DSCE-images with an application to tumor grading.

OBJECTIVES: (a) The development of a novel analysis method, named Dynamic pixel intensity Histogram Analysis (DHA) allowing for pixel intensity-histogram-model-parameter fitting of arbitrary-shaped regions defined in dynamic-susceptibility-contrast-enhanced (DSCE) difference MR-image time-series, and (b) its prospective application and evaluation for glioma grading. MATERIALS AND METHODS: For each difference-image, pixel intensity histograms of arbitrary-shaped ROIs were computed and fitted using the Levenberg-Marquardt algorithm. Time-dependent histogram center-position- and width-parameters are computed during bolus-passage. The method was applied to 25 patients with low and high grade gliomas. RESULTS: During bolus outflow-time, histogram-center-position-parameter and histogram-width-parameter reach highest significance levels and discriminate gliomas of different grades. The histogram center-position-parameter discriminated grade-II from grade-III, grade-II from grade-IV but not grade-III from grade-IV. The observed histogram width-parameters discriminated grade-II from grade-III (P < 0.00022), grade-II from grade-IV (P <8.3 10), and grade-III from grade-IV (P < 0.00063). CONCLUSIONS: DHA is a easy-to-use method for glioma grading; the histogram width parameter is best indicator for histologic grade.

Endovascular and surgical treatment of spinal dural arteriovenous fistulas.

INTRODUCTION: The aim of this retrospective study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas (SDAVFs) that were treated with surgery, catheter embolization, or surgery after incomplete embolization. METHODS: The study included 21 consecutive patients with SDAVFs of the thoracic, lumbar, or sacral spine who were treated in our institution from 1994 to 2007. Thirteen patients were treated with catheter embolization alone. Four patients underwent hemilaminectomy and intradural interruption of the fistula. Four patients were treated by endovascular techniques followed by surgery. The clinical outcome was assessed using the modified Aminoff-Logue scale (ALS) for myelopathy and the modified Rankin scale (MRS) for general quality of life. Patient age ranged from 44 to 77 years (mean 64.7 years). RESULTS: Surgical as well as endovascular treatment resulted in a significant improvement in ALS (-62.5% and -31.4%, respectively, p < 0.05) and a tendency toward improved MRS (-50% and -32%, respectively) scores. Patients that underwent surgery after endovascular treatment due to incomplete occlusion of the fistula showed only a tendency for improvement in the ALS score (-16.7%), whereas the MRS score was not affected. CONCLUSION: We conclude that both endovascular and surgical treatment of SDAVFs resulted in a good and lasting clinical outcome in the majority of cases. In specific situations, when a secondary neurosurgical approach was required after endovascular treatment to achieve complete occlusion of the SDAVF, the clinical outcome was rather poor. The best first line treatment modality for each individual patient should be determined by an interdisciplinary team.

Intra-arterial thrombolysis of acute iatrogenic intracranial arterial occlusion attributable to neuroendovascular procedures or coronary angiography.

BACKGROUND AND PURPOSE: For selected stroke patients, intra-arterial thrombolysis (IAT) has been shown to be an effective treatment option. However, knowledge of safety and efficacy of IAT in patients with acute stroke as a complication of arterial catheter interventions is limited. METHODS: We analyzed clinical radiological findings and functional outcomes in consecutive patients 3 months after treatment with IAT for peri-procedural strokes occurring during neuroendovascular or cardiac catheter interventions. To measure outcome, the modified Rankin scale score was used. RESULTS: Of a total of 432 patients treated with IAT, 12 (4 women and 8 men; mean age, 60 years) were treated because of an ischemic stroke after a neuro-endovascular procedure (n=6) or coronary angiography (n=6). The median baseline National Institutes of Health Stroke Scale score was 15. Recanalization was complete (thrombolysis in myocardial infarction grade 3) in 6, partial (thrombolysis in myocardial infarction 2) in 5, and minimal (thrombolysis in myocardial infarction 1) in 1. Nine patients (75%) had a favorable outcome (modified Rankin scale score, 0 to 2), and 3 had a poor outcome (modified Rankin scale score, 3 or 4). All patients with complete recanalization had a favorable outcome, whereas only 3 of 6 patients with partial or minimal recanalization (P=0.18) had a favorable outcome. Follow-up brain imaging was normal in 2 and showed new ischemic lesions in 10 patients. Two patients (17%) had a symptomatic intracerebral hemorrhage. CONCLUSIONS: In acute stroke attributable to arterial catheter interventions, IAT is feasible and has the potential to improve outcome in these patients. A high recanalization rate could be achieved.

Expanded polytetrafluoroethylene graft for bypass surgery using the excimer laser-assisted nonocclusive anastomosis technique.

OBJECT: Patients with complex craniocerebral pathophysiologies such as giant cerebral aneurysms, skull base tumors, and/or carotid artery occlusive disease are candidates for a revascularization procedure to augment or preserve cerebral blood flow. However, the brain is susceptible to ischemia, and therefore the excimer laser-assisted nonocclusive anastomosis (ELANA) technique has been developed to overcome temporary occlusion. Harvesting autologous vessels of reasonable quality, which is necessary for this technique, may at times be problematic or impossible due to the underlying systemic vascular disease. The use of artificial vessels is therefore an alternative graft for revascularization. Note, however, that it is unknown to what degree these grafts are subject to occlusion using the ELANA anastomosis technique. Therefore, the authors studied the ELANA technique in combination with an expanded polytetrafluoroethylene (ePTFE) graft. METHODS: The experimental surgeries involved bypassing the abdominal aorta in the rabbit. Ten rabbits were subjected to operations representing 20 ePTFE graft-ELANA end-to-side anastomoses. Intraoperative blood flow, followup angiograms, and long-term histological characteristics were assessed 75, 125, and 180 days postoperatively. Angiography results proved long-term patency of ePTFE grafts in all animals at all time points studied. Data from the histological analysis showed minimal intimal reaction at the anastomosis site up to 180 days postoperatively. Endothelialization of the ePTFE graft was progressive over time. CONCLUSIONS: The ELANA technique in combination with the ePTFE graft seems to have favorable attributes for end-to-side anastomoses and may be suitable for bypass procedures.

Repeated laser-assisted high-flow bypass for recurrent giant intracranial aneurysm.

The treatment of intracranial aneurysms is changing as endovascular obliteration possibilities and long-term results are being published in regard to outcome. However, not all aneurysms are amenable to direct endovascular or surgical treatment. In such situations, a high flow bypass for flow preservation can be considered as indirect treatment alternative, enabling a trapping of the aneurysm or occlusion of the feeding artery. We present the case history of a 57 year-old patient suffering of a recurrent giant intracranial carotid aneurysm. The aneurysm could be excluded using a new cerebral high-flow bypass technique for which no temporary occlusion of any intracranial vessels is required. This technique reduces the risks of perioperative neurological complications.

Contrast-enhanced 3-D MRA in decision making for carotid endarterectomy: a 6-year experience.

BACKGROUND: Systematic need for angiography in diagnosis of carotid artery stenosis and indication of surgical therapy is still debated. Noninvasive imaging techniques such as MR angiography (MRA) or CT angiography (CTA) offer an alternative to digital subtraction angiography (DSA) and are increasingly used in clinical practice. In this study, we present the radiological characteristics and clinical results of a series of patients operated on the basis of combined ultrasonography (US)/MRA. METHODS: This observational study included all the patients consecutively operated for a carotid stenosis in our Department from October 1998 to December 2004. The applied MRA protocol had previously been established in a large correlation study with DSA. DSA was used only in case of discordance between US and MRA. The preoperative radiological information furnished by MRA was compared with intraoperative findings. The outcome of the operation was assessed according to ECST criteria. RESULTS: Among 327 patients, preoperative MRA was performed in 278 (85%), DSA in 44 (13.5%) and CT angiography in 5 (1.5%). Most of DSA studies were performed as emergency for preparation of endovascular therapy or for reasons other than carotid stenosis. Eleven additional DSA (3.3%) complemented US/MRA, mostly because diverging diagnosis of subocclusion of ICA. No direct morbidity or intraoperative difficulty was related to preoperative MRA. Combined mortality/major morbidity rate was 0.9% (3 patients) and minor morbidity rate 5.5% (18 patients). CONCLUSIONS: This observational study describes a well-established practice of carotid surgery and supports the exclusive use of non invasive diagnostic imaging for indicating and deciding the operation.

Comparison of voxel-based 3-D MRI analysis and subtraction ictal SPECT coregistered to MRI in focal epilepsy.

While voxel-based 3-D MRI analysis methods as well as assessment of subtracted ictal versus interictal perfusion studies (SISCOM) have proven their potential in the detection of lesions in focal epilepsy, a combined approach has not yet been reported. The present study investigates if individual automated voxel-based 3-D MRI analyses combined with SISCOM studies contribute to an enhanced detection of mesiotemporal epileptogenic foci. Seven consecutive patients with refractory complex partial epilepsy were prospectively evaluated by SISCOM and voxel-based 3-D MRI analysis. The functional perfusion maps and voxel-based statistical maps were coregistered in 3-D space. In five patients with temporal lobe epilepsy (TLE), the area of ictal hyperperfusion and corresponding structural abnormalities detected by 3-D MRI analysis were identified within the same temporal lobe. In two patients, additional structural and functional abnormalities were detected beyond the mesial temporal lobe. Five patients with TLE underwent epileptic surgery with favourable postoperative outcome (Engel class Ia and Ib) after 3-5 years of follow-up, while two patients remained on conservative treatment. In summary, multimodal assessment of structural abnormalities by voxel-based analysis and SISCOM may contribute to advanced observer-independent preoperative assessment of seizure origin.

Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ARSA). Clinically, the disease is heterogeneous with respect to the age of onset, affection of peripheral and central nervous systems, and progression. OBJECTIVES: To analyze mutations in the ARSA gene of a patient with adult-onset MLD with no signs of peripheral polyneuropathy and to emphasize the clinical, neuroradiologic, neuropathologic, and genetic features of the disease. DESIGN: Case study of a patient clinically presenting with rapidly progressive dementia and behavioral abnormalities. We report the findings of clinical evaluation and neurophysiologic and neuropathologic studies of peripheral nerves; we also performed DNA sequence analysis, transfections, metabolic labeling, and immunoprecipitation of mutant ARSA polypeptides. SETTING: Genetic research and clinical unit, university hospital. RESULTS: Genetic analysis revealed homozygosity for a novel mutation in exon 3 of ARSA (F219V). This substitution leads to a misfolded unstable enzyme with a specific activity less than 1% of normal. There were no clinical or neurophysiologic signs of peripheral nervous system dysfunction. Typical neuropathologic signs for MLD were absent from nerve biopsy specimens. CONCLUSIONS: This novel mutation is associated with progressive psychocognitive impairment without clinical or electrophysiologic signs and only minor morphologic signs of peripheral nerve affection. The F219V substitution causes reduction in enzyme activity to an extent unexpected for an adult patient with MLD.