bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotype and Phenotype in Cystic Fibrosis
Authors: Zielenski Julian
Published: April 2003

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene which encodes a protein expressed in the apical membrane of exocrine epithelial cells. CFTR functions principally as a cAMP-induced chloride channel and appears capable of regulating other ion channels. Besides the most common mutation, ΔF508, accounting for about 70% of CF chromosomes worldwide, more than 850 mutant alleles have been reported to the CF Genetic Analysis Consortium. These mutations affect CFTR through a variety of molecular mechanisms which can produce little or no functional CFTR at the apical membrane. This genotypic variation provides a rationale for phenotypic effects of the specific mutations. The extent to which various CFTR alleles contribute to clinical variation in CF is evaluated by genotype-phenotype studies. These demonstrated that the degree of correlation between CFTR genotype and CF phenotype varies between its clinical components and is highest for the pancreatic status and lowest for pulmonary disease. The poor correlation between CFTR genotype and severity of lung disease strongly suggests an influence of environmental and secondary genetic factors (CF modifiers). Several candidate genes related to innate and adaptive immune response have been implicated as pulmonary CF modifiers. In addition, the presence of a genetic CF modifier for meconium ileus has been demonstrated on human chromosome 19q13.2. The phenotypic spectrum associated with mutations in the CFTR gene extends beyond the classically defined CF. Besides patients with atypical CF, there are large numbers of so-called monosymptomatic diseases such as various forms of obstructive azoospermia, idiopathic pancreatitis or disseminated bronchiectasis associated with CFTR mutations uncharacteristic for CF. The composition, frequency and type of CFTR mutations/variants parallel the spectrum of CFTR-associated phenotypes, from classic CF to mild monosymptomatic presentations. Expansion of the spectrum of disease associated with the CFTR mutant genes creates a need for revision of the diagnostic criteria for CF and a dilemma for setting nosologic boundaries between CF and other diseases with CFTR etiology.
Self-Adjusting Continuous Positive Airway Pressure Therapy Based on the Measurement of Impedance
Authors: Randerath W. , Parys K. , Lehmann D. , Sanner B. , Feldmeyer F. , Rühle K.-H.
Published: April 2003

Background: Measurement of impedance using forced oscillation technique is a sensitive means of detecting airway obstructions, including the obstructive sleep apnea syndrome (OSAS). Objective: The present study was conducted to determine whether treatment with an automated impedance-controlled continuous positive airway pressure (CPAP) device (APAPFOT) is possible in patients with OSAS, and which is the best range of pressure variation in automatical CPAP treatment. We investigated two modes of APAPFOT with different pressure ranges: (1) the widest technically possible pressure range and (2) a range with individually defined minimum pressure. Methods: Ten patients [9 men, age 56.6 ±10.5 years, BMI 32.0 ± 4.5 kg/m2, apnea/hypopnea index (AHI) 18.2 ± 13.3 /h] had a diagnostic polysomnography (baseline). After manual titration of positive airway pressure they were submitted, in randomized order, to two modes of the APAPFOT device, namely pressure range of 4.0– 15.5 mbar (mode 1 free range) and an individually fixed higher minimum pressure with a maximum pressure of 15.5 mbar (mode 2). Results: While the manually titrated pressure was 8.0 ± 1.3 mbar, in mode 1 it was 5.6 ± 2.1 mbar (p < 0.01); in mode 2 7.3 ± 1.6 mbar (p < 0.05). Both of these modes suppressed abnormal respiratory events (baseline AHI 18.2 ± 13.3/h; mode 1: 2.5 ± 1.9; mode 2: 1.8 ± 0.7, p < 0.01 in each case), and increased slow wave sleep (baseline: 10.6 ± 8.0%, mode 1: 20.2 ± 10.4%, p < 0.05; mode 2: 22.3 ± 9.3%, p < 0.01). In mode 1, the pressure was lower than that titrated manually in 73.2% of total sleep time, in mode 2 in 48.6%, while pressures higher than those derived manually were observed in 13.0% in mode 1 and in 19.1% in mode 2. Conclusions: The data indicate that impedance-controlled CPAP (APAPFOT) allows adequate treatment of OSAS patients at significantly lower pressures as compared with manually titrated pressure. Differences between the two modes are only minor.
Comparison of the Effect on Bronchial Hyperresponsiveness of Beclomethasone Dipropionate Administered via a Novel Multidose Dry-Powder Inhaler or a Conventional Pressurised Metered Dose Inhaler
Authors: Morice A.H. , Andrews B. , Taylor M.
Published: April 2003

Background: Treatment with inhaled corticosteroids improves symptoms and reduces bronchial hyperresponsiveness (BHR) associated with asthma. Delivery of drugs into the lung is dependent on the inhaler device. Furthermore, environmental concerns regarding the use of chlorofluorocarbon propellants in pressurised inhalers and patient acceptability of inhaler devices both influence the extent of use of different delivery systems. Objectives: To compare the efficacy of beclomethasone dipropionate (BDP) administered via a novel multidose dry-powder inhaler (DPI) and a conventional pressurised metered-dose inhaler (pMDI) with spacer in patients with BHR. Methods: A randomised, double-blind, crossover study was carried out in a group of 27 patients (aged 19–55 years) with a clinical diagnosis of reversible airway disease, who demonstrated BHR to methacholine (PD20 ≤6.4 mg). Each patient received BDP (≤2 mg/day) via the DPI or pMDI, for periods of 4 weeks. The randomised treatment periods were preceded by 3-week washout periods when no corticosteroid was used. Five clinic visits marked the start and end of each study phase. The primary efficacy endpoint was BHR as defined by the pharmacodynamic parameter, PD20, which was determined at the start and end of each treatment period. Clinical endpoints including lung function, symptoms and adverse events were also evaluated. Results: Both treatments caused a significant decrease in BHR (p < 0.05 vs. pre-treatment values). Mean ± SD changes in log PD20 were: DPI 0.59 ± 1.29; pMDI 0.59 ± 0.94 mg. There was no statistically significant difference between treatments and no evidence of a carry-over effect between treatments on BHR. Clinical efficacy and safety parameters also demonstrated no statistically significant treatment differences, and patients found the DPI easier to use. Conclusion: Efficacy of BDP in reducing BHR is comparable via the DPI and pMDI plus spacer.
Tracheobronchial Involvement in Relapsing Polychondritis
Authors: Tsunezuka Yoshio , Sato Hideo , Shimizu Hiroshi
Published: April 2003

Relapsing polychondritis (RPC) is a multisystem disorder of chondromalacia involving any cartilage. Respiratory tract involvement is the greatest threat to life. We report a patient with stenosis of the subglottic trachea and left main bronchus who suddenly ceased breathing. As this patient did not have any other clinical features of RPC, the diagnosis was difficult. CT showed circumferential worm-eaten-like thickening suggesting a deformity and edema of the tracheal mucosa. Biopsy of the tracheal and thyroid cartilage revealed mild cartilage degeneration and infiltration with inflammatory cells. Therefore, the patient was diagnosed as having RPC. She is currently well 24 months after Montgomery T tube intubation with systemic steroids. Narrowing of the left main bronchus has not worsened.
Future Pharmacological Treatment of Cystic Fibrosis
Authors: Zeitlin Pamela L.
Published: April 2003

Cystic fibrosis (CF) is an autosomal recessive disorder that is caused by over 850 different mutations in the CF gene. It is useful to group these mutations according to the defect that results in the CFTR mRNA or protein. New pharmacological treatments targeted towards specific mutations that are relatively common are being developed. Class I mutations do not produce CFTR protein because of a premature stop signal in the CFTR DNA. These null mutations can be corrected by certain aminoglycosides which cause the aberrant stop signal to be skipped. Mutations leading to a CFTR protein that attains an unstable structure shortly after translation in the endoplasmic reticulum form class II. Class II mutations can be restored to the protein trafficking pathway by manipulation of chaperone protein/CFTR interactions with chemical chaperones or drugs that affect gene regulation such as the butyrates. Production of a CFTR with reduced Cl– transport on the basis of abnormal regulation of the chloride channel is the basis of class III. Genistein can overcome this block in regulation. Mutations that partially reduce chloride conductance through CFTR (class IV) can be stimulated with milrinone, which is a phosphodiesterase inhibitor. Finally, mutations that lead to a severe reduction in normal CFTR protein form class V. Increased levels of CFTR could be generated with the butyrates or supplemented with gene therapy. Although most of the reported mutations in CFTR are rare and unclassified, it may be possible to use genotype-phenotype correlations to determine the best approach.
Left Ventricular Function in Patients with Obstructive Sleep Apnoea Syndrome before and after Treatment with Nasal Continuous Positive Airway Pressure
Authors: Alchanatis Manos , Paradellis George , Pini Helen , Tourkohoriti Georgia , Jordanoglou John
Published: April 2003

Background: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. Objectives: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). Methods: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean ± SD = 52 ± 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12–14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. Results: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 ± 11.6 ms, p < 0.05; E/A = 0.94 ± 0.26, p < 0.02; SF = 39.9 ± 4.1%, not significant (NS); IVST = 9.9 ± 1.2 mm, NS; PWT = 8.3 ± 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 ± 9.2 mm Hg, BP/diastolic/night-time = 90.3 ± 10.7 mm Hg). After 12–14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 ± 8.8 ms, p < 0.05; E/A = 1.07 ± 0.3, p < 0.05; BP/diastolic/daytime = 86.3 ± 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 ± 8.6 mm Hg, p < 0.05) in our patient group. Conclusions: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.
Circulating Cytokeratin 8:Anti-Cytokeratin 8 Antibody Immune Complexes in Sera of Patients with Pulmonary Fibrosis
Authors: Dobashi Naomi , Fujita Jiro , Ohtsuki Yuji , Yamadori Ichiro , Yoshinouchi Takeo , Kamei Tadashi , Tokuda Michiaki , Hojo Satoko , Bandou Shuji , Ueda Yutaka , Takahara Jiro
Published: April 2003

Background: It has been suggested that the humoral immune system plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). Although circulating immune complexes in patients’ sera have been suggested, none of the antigens have been characterized. Objectives: The purpose of this study is to characterize the antigen of the immune complexes in patients’ sera of pulmonary fibrosis. Methods: As we previously established that one of the antibodies against A549 cells (lung alveolar type II cells) was anti-cytokeratin 8 (CK8), we confirmed the existence of anti-CK8 antibody in patients’ sera by Western immunoblot. In addition, we tried to demonstrate circulating CK8:anti-CK8 immune complexes in patients’ sera by Western immunoblot. Furthermore, we established an enzyme-linked immunosorbent assay to quantitate CK8:anti-CK8 immune complexes. Results: In patients with pulmonary fibrosis, anti-CK8 antibodies were clearly demonstrated in sera by Western immunoblot. In addition, circulating CK8:anti-CK8 immune complexes were also clearly demonstrated by Western immunoblot. It was possible to establish ELISA to quantitate CK8:anti-CK8 immune complexes. If the cutoff value, which was determined based on the highest value of normal volunteers, was introduced, high CK8:anti-CK8 antibody complexes were demonstrated in 9 of 31 patients (29.0%) with IPF and PF-CVD. Conclusions: This is the first study to clarify the antigen of the circulating immune complex in sera of patients with IPF. These results suggest that circulating CK8:anti-CK8 immune complexes may have played a role in the process of lung injury in pulmonary fibrosis.
Placebo-Controlled Study of Inhaled Budesonide on Indices of Airway Inflammation in Bronchoalveolar Lavage Fluid and Bronchial Biopsies in Cross-Country Skiers
Authors: Sue-Chu Malcolm , Karjalainen Eeva-Maija , Laitinen Annika , Larsson Lars , Laitinen Lauri A. , Bjermer Leif
Published: April 2003

Background: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. Objective: To investigate the effect of inhaled budesonide, 400 μg twice daily, on indices of airway inflammation in ‘ski asthma’, defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. Methods: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16–20) years for a mean (range) treatment period of 22 (10–32) weeks over the competitive season. Results: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV1. Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. Conclusions: We were unable to show any clear beneficial effect of budesonide in ‘ski asthma’. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.
Deciduoid Pleural Mesothelioma Affecting a Young Female without Prior Asbestos Exposure
Authors: Gloeckner-Hofmann Katharina , Zhu Xiong-Zeng , Bartels Heinrich , Feller Alfred C. , Merz Hartmut
Published: April 2003

Pleural mesothelioma is commonly associated to asbestos exposure. A 40-year-old woman is described who presented with shortness of breath. She had a smoking history but no history of asbestos exposure. Chest radiography and computed tomography showed a large tumour on the right lower lung. An open pleural biopsy was performed. A metastatic adenocarcinoma of the pleura was primarily diagnosed. The tumour progressed and after surgical excision an accurate histological and immunohistochemical examination was performed. It revealed a pleural mesothelioma with a deciduoid differentiation that has not been described before.
Nasal Continuous Positive Airway Pressure and Weight Loss Improve Swallowing Reflex in Patients with Obstructive Sleep Apnea Syndrome
Authors: Okada Seiko , Ouchi Yasuyoshi , Teramoto Shinji
Published: April 2003

We have recently reported that swallowing reflex is impaired in patients with obstructive sleep apnea syndrome (OSAS). However, the effects of OSAS treatment on swallowing function in these patients have not been reported. Here we report 2 cases of OSAS in whom swallowing reflex was impaired before the start of nasal continuous positive airway pressure (NCPAP) and improved 1 year after NCPAP. These cases suggest that impaired swallowing reflex may be reversible by OSAS treatment.
Pergolide-Induced Dyspnea, Bilateral Pleural Effusion and Peripheral Edema
Authors: Varsano Shabtai , Gershman Marina , Hamaoui Eric
Published: April 2003

A patient with severe Parkinson’s disease presented with increasing dyspnea, bilateral pleural effusion and peripheral edema that were refractory to diuretic therapy and were first misdiagnosed as signs of right-sided heart failure. Pergolide was the only culprit for this devastating condition and on its discontinuation all signs of fluid retention resolved. In this report, drug reactions to ergots and dopamine agonists are discussed.
Surgical Management of Intractable Epilepsy
Authors: Chung, Sang Sup , Lee, Kyung Hoe , Chang, Jin Woo , Park Yong Gou
Published: April 2003

Cortical resective surgery (including amygdalohippocampectomy) and corpus callosotomy are the most widely accepted modes of surgical treatment for intractable epilepsy. Between July 1989 and May 1996, 146 surgeries for epilepsy were done at Severance Hospital, Yonsei University. Resective surgery was performed in 126 patients and corpus callosotomy in 20 patients. Of the 126 patients who underwent resective surgery, surgery for the removal of the epileptic lesion (lesionectomy) was performed in 21 patients (16.7%) while 105 patients (83.3%) underwent surgery without a structural lesion. Current surgical therapy for intractable epilepsy requires the precise localization of a resectable zone of epileptogenesis. Unfortunately, finding a localized focus in an extratemporal region is far more difficult than in the temporal lobe. Surgeries for extratemporal lobe epilepsy without lesions have been less successful than surgeries for temporal lobe epilepsy. Although surgery for intractable epilepsy has been increasingly successful, we still need to refine our techniques to further improve the success rate and to reduce complications of surgery such as language and memory impairment.
An Algorithm for the Empirical Determination of Intracranial Stereotactic Targets
Authors: Ott Kenneth
Published: April 2003

The determination of empirical targets for functional brain lesions is usually made with graphical techniques using CT or MR software. Geometrical errors occur in the method when the intercommissural line and plane of the third ventricle are not parallel and orthogonal to transaxial images. A mathematical algorithm can be used to calculate target coordinates from the coordinates of the anterior commissure, the posterior commissure, and the position of a third point within the inferior, third ventricle. These coordinates may be determined in any image plane in stereotactic space. By supplying the distance of the target from the mid-point of the intercommissural line, the distance lateral and inferior to the line, target coordinates are computed. This overcomes geometrical errors of previous graphical methods.
Anatomical Targeting in Functional Neurosurgery by the Simultaneous Use of Multiple Schaltenbrand-Wahren Brain Atlas Microseries
Authors: Nowinski Wieslaw L.
Published: April 2003

This paper presents a novel approach for the use of the Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren [Stuttgart, Thieme, 1977] for anatomical targeting in functional neurosurgery. We propose to use simultaneously all three electronic axial, coronal and sagittal mutually coregistered Schaltenbrand-Wahren brain atlas microseries. The printed atlas microseries are digitized, extended to cover both hemispheres, contoured, labeled, organized into atlas volumes, and mutually coregistered. The electronic atlas is interactively registered with the data by using the three-dimensional Talairach proportional grid system transformation, followed up by local warping in the region of interest based on any clearly visible landmarks. The detailed targeting steps for pallidotomy, thalamotomy and subthalamotomy are formulated. The potential of this approach is to increase the accuracy of target definition, to decrease the time of the procedure by reducing the number of microelectrode tracts, and to give an extra degree of confidence to the neurosurgeon. The advantages of the approach and the limitations of the Schaltenbrand-Wahren atlas are discussed.
Lesion Volume and Clinical Outcome in Stereotactic Pallidotomy and Thalamotomy
Authors: Goodman Scott H. , Wilkinson Steve , Overman John , Koller William C. , Tröster Alex , Pahwa Rajesh , Lyons Kelly , Kieltyka Jennifer , Burns Jeffrey , Gordon Michael
Published: April 2003

Postoperative lesion volume and clinical outcome were assessed in 19 Parkinson’s disease (PD) patients who received posteroventral pallidotomy, and in 14 essential tremor (ET) patients who received ventrolateral thalamotomy. Before and after surgery, PD patients were evaluated using the Unified PD Rating Scale (UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Inner and total lesion volumes were determined with postoperative MR imaging and three-dimensional data segmentation. Lesion volumes were compared to percent improvement in UPDRS and FTM scores, using Spearman’s rank-order correlation test. No rank-order correlations were found between lesion volume and clinical improvement in either the PD or the ET patients. In performing stereotactic surgery for movement disorders, any lesion volume within a prescribed range may be equally effective in relieving symptoms associated with PD or ET.
Direct Spinal Cord Electrical Stimulations during Surgery of Intramedullary Tumoral and Vascular Lesions
Authors: Duffau Hugues , Capelle Laurent , Sichez Jean-Pierre
Published: April 2003

Despite the use of somatosensory evoked potentials during surgery for spinal cord tumors or vascular lesions, postoperative neurological disorders, particularly motor deficits, frequently occur after aggressive surgery with an attempt of gross total resection. We report the use of peroperative direct spinal cord electrical stimulation to decrease morbidity while improving the quality of resection. Three patients with intramedullary lesions (1 ependymoma and 2 cavernomas), initially revealed by pain and followed by neurological deficit, were operated at our institution using peroperative direct medullary electrical stimulations (60 Hz, biphasic square wave pulses with 1 ms/phase, 0.9 mA) under general anesthesia without curare. In all cases, gross total resection was performed until motor responses to stimulation, which indicated anterior and lateral boundaries between the lesion and the functional tissue, were obtained. There was no postoperative neurological worsening, but an immediate partial improvement of sensory and bladder disorders in the patient with ependymoma. Postoperative MRI confirmed total resection in the 3 patients. These cases demonstrate that direct medullary electrical stimulation is a safe, easy, precise and reliable method to reduce morbidity during spinal cord surgery.
Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus for Control of Tremors in Parkinson’s Disease and Essential Tremor
Authors: Kumar Krishna , Kelly Michael , Toth Cory
Published: April 2003

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson’s disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 ± 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 ± 8.1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.
History of the American Society for Stereotactic and Functional Neurosurgery
Authors: Gildenberg Philip L.
Published: April 2003

The field of human stereotactic neurosurgery has just passed the half-century mark. Soon after its inception, the pioneers in the field began to meet to exchange information and ideas, which led to an international forum for stereotactic surgery. In 1973, the organization was expanded to form both the World Society for Stereotactic and Functional Neurosurgery, as well as the European and American Societies for Stereotactic and Functional Neurosurgery. Reviewing the programs of the meetings of those Societies permits one to review the nature of the information that was exchanged through the years, and, in doing so, to monitor the pulse of the field as it has developed. The first independent meeting of the American Society for Stereotactic and Functional Neurosurgery took place in Houston in 1980, at which there were 27 papers, 40% of which were on the newly emerging field of image-guided neurosurgery and the rest on classical functional neurosurgery. The five meetings since, occurring at approximately 4-year intervals, have documented the progress in epilepsy surgery, the reemergence of stereotactic surgery for movement disorders, the growth of stereotactic radiosurgery, and the genesis of frameless stereotactic techniques which have now become widespread.
Magnetic Source Imaging in Stereotactic and Functional Neurosurgery
Authors: Orrison Jr. William W.
Published: April 2003

Magnetic source imaging (MSI) combines the unique spatial and temporal functional accuracy of magnetoencephalography (MEG) with the anatomic and pathologic detail of magnetic resonance (MR). This relatively new method of evaluating brain function provides a preoperative mapping of brain function and brain structure by integrating the functional information of MEG with the structural information of MR. This results in data on actual neuronal interactions in clinical patients. The temporal and spatial accuracy of the MEG data, combined with the anatomic and pathologic specificity of MRI, results in the magnetic source image, which offers accurate knowledge of cortical functional organization, and is important in the surgical treatment of brain neoplasms, vascular malformations, and epilepsy. MSI allows the tracking of neuronal activity on the scale of milliseconds with millimeter accuracy, and continues to lead to new understanding of many functional brain disorders.
Accuracy and Availability of the Computed Assisted Neurosurgery Navigation System during Epilepsy Surgery
Authors: Hirabayashi Hidehiro , Chitoku Shiro , Hoshida Tohru , Sakaki Toshisuke
Published: April 2003

The magnetic-force-based Computed Assisted Neurosurgery System was used for epilepsy surgery to localize targets accurately in the operative field. The correlation between X components of target coordinates in the axial plane and the coronal plane for the same target was strong in all cases. Concerning Y components, there were statistically significant differences in 2 cases. There was a case that showed statistically significant differences only in the Z dimension. The interdisk distance by data sets of coordinates obtained from neuronavigation was calculated to quantify localization error, and the measuring error ranged from –5 to 13.3 mm (1.3 ± 3.2 mm). The magnitude of the application errors in this study tended to be large in the frontal and vertex regions.
Audit of Neurophysiological Recording during Movement Disorder Surgery
Authors: Forster A. , Eljamel M.S. , Varma T.R.K. , Tulley M. , Latimer M.
Published: April 2003

Sixty-two cases of thalamic pallidal and subthalamic surgery in Dundee were audited to assess the influence of physiological localisation on the procedure. Methods included microelectrode recording, evoked potential and stimulation techniques. Although anatomical localisation is improving with modern techniques, the physiological information is still modifying the surgery in 67% of cases.
Unilateral Pallidal Stimulation in Cervical Dystonia
Authors: İşlekel Sertaç , Zileli Mehmet , Zileli Berna
Published: April 2003

Cervical dystonia (spasmodic torticollis) is a focal dystonia of the cervical region. Various treatment modalities have been performed with variable success rates. We present a 42-year-old woman complaining of involuntary head rotation for the last 3 years. Different medical treatments had been used for 3 years. Botulinum toxin injections resulted in temporary and moderate improvement for periods of 3–4 months. Pallidal stimulation was performed using a quadripolar electrode and a battery-operated programmable pulse generator. We conclude that a unilateral pallidal lesion or stimulation is an effective method of treatment in focal dystonia. The target must be the pallidum contralateral to the contracted sternocloidomastoid muscle. Deep brain stimulation is superior to lesioning because of the capability of manipulating the stimulation parameters which can modify the pallidotomy effect.
Multimodality Stereotactic Brain Tissue Identification: The NASA Smart Probe Project
Authors: Andrews R. , Mah R. , Aghevli A. , Freitas K. , Galvagni A. , Guerrero M. , Papsin R. , Reed C. , Stassinopoulos D.
Published: April 2003

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of ‘optical biopsy’ by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2.7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures.
Functional Magnetic Resonance Image-Guided Surgery of Tumors in or near the Primary Visual Cortex
Authors: Schulder Michael , Holodny Andrei , Liu Wen-Ching , Gray Allison , Lange Gudrun , Carmel Peter W.
Published: April 2003

Objective: To assess the accuracy of functional magnetic resonance imaging (fMRI) of the primary visual cortex in patients undergoing surgery for tumors in the occipital lobe. Methods: Two patients with nondominant occipital lobe tumors were studied, one with a solitary lung metastasis and another with radiation necrosis after radiosurgery for a low-grade astrocytoma. At surgery, visual evoked potentials (VEPs) were stimulated using Light-emitting-diode goggles and recorded using cortical grids placed immediately after brain exposure. The location of the peak VEP was compared to that predicted by the registered functional scan. Results: In each case, the epicenter of visual activation as represented on the registered fMRI corresponded to the site of peak VEP recording. Prediction error for the visual cortex, measured in patient 1, was 1.0 mm. Visual confirmation showed the registration in the second patient to be accurate as well. Conclusion: As previously demonstrated for sensorimotor fMRI, visual fMRI accurately predicts the location of the primary visual cortex. Additional confirmation is expected with more clinical experience.
Functional Magnetic Resonance Imaging and Radiosurgical Dose Planning
Authors: Schulder Michael , Vega Jose , Narra Venkat , Jacobs Alexander , Kalnin Andrew , Lange Gudrun , Liu Wen-Ching
Published: April 2003

Objective: To assess the effect of functional magnetic resonance imaging (fMRI) on stereotactic radiosurgical (SRS) dose planning. Methods: Patients included those undergoing SRS whose lesions were in or near areas that could be identified with fMRI. After processing, an fMR scan was registered to the anatomic scan, and this dataset was registered to a stereotactic CT scan. The imaged functional areas were contoured along with standard anatomical targets. Dose planning was done at first with the functional volumes rendered invisible; the plans were then adjusted as needed using the functional targets. Doses were measured using a dose-volume histogram tool. Results: SRS was performed in 12 patients, 1 of whom also underwent SRT. Functional volumes studied included motor cortex in 8 patients, visual in 6 and language in 3; a total of 33 functional targets were imaged. Prescription doses ranged from 12 to 22.5 Gy (mean 19.5 Gy), and the maximum dose to functional volumes from 8 cGy to 18.5 Gy (mean 2.9 Gy). In 6 patients, arc adjustment using functional targets yielded a >50% reduction in dose to at least one functional volume; in all patients, the dose reduction to 50 and 75% of functional volumes averaged 4% (12 cGy) and 13% (30 cGy), respectively, while the reduction of maximal dose averaged 24% (50 cGy). Conclusions: fMRI can be used in SRS to reduce irradiation of eloquent brain using standard prescription doses. Appropriate arc adjustment may allow for escalation of the dose to the targeted lesion.
Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations: Appearance of Perinidal T2 Hyperintensity Signal as a Predictor of Favorable Treatment Response
Authors: Mobin Fardad , De Salles Antonio A.F. , Abdelaziz Osama , Cabatan-Awang Cynthia , Solberg Timothy , Selch Michael
Published: April 2003

The purpose of this study was to analyze the significance of perinidal T2 hyperintensity appearance after radiosurgery of arteriovenous malformations (AVMs), as a predictor of treatment response. Our initial experience with linear accelerator (LINAC) radiosurgery at University of California, Los Angeles, between 1990 and 1997 involved treatment of 129 patients affected by cerebral AVMs. Based upon availability of neuroimaging follow-up, 48 patients with 50 AVMs were selected for review. Forty (80%) of the AVMs underwent complete obliteration or significant reduction on follow-up MRI, on average 20 months after radiosurgery. Thirteen (72%) of 18 obliterated AVMs were associated with perinidal T2 hyperintensity signal, on average 18 months (6–49) after radiosurgery. Ten (20%) of 50 AVMs (average volume 23.1 cm3, ranging 7.5–46.5) were unchanged. Furthermore, only 3 AVMs in this group showed reversible T2 signal changes. In patients with complete nidal obliteration, appearance of T2 hyperintensity signal achieves 72% sensitivity in predicting successful treatment response.
Long-Term Seizure Outcome following Corpus Callosotomy in Children
Authors: McInerney James , Siegel Adrian M. , Nordgren Richard E. , Williamson Peter D. , Thadani Vijay M. , Jobst Barbara , Reeves Alexander G. , Roberts David W.
Published: April 2003

Introduction: The long-term outcome of pediatric patients undergoing corpus callosotomy (CC) for palliative control of medically intractable seizures is presented. Methods: During a 27-year period, 43 patients, 20 years of age or younger, underwent CC for seizure palliation and had a minimum of 1 year follow-up. Seizure reduction and stability of that outcome for individual seizure types and for most disabling seizure were reviewed. Results: Overall, 63% of the seizures documented showed a good response. For the most disabling seizure, 56% of the patients had good outcomes. Changes in outcome status occurred within the first 6 months, and outcome was largely maintained after that point. Conclusion: Callosotomy achieves the goal of seizure palliation in more than half of the patients, with stable, good outcomes being maintained in the majority of patients.
Long-Term Multicenter Experience with Vagus Nerve Stimulation for Intractable Partial Seizures
Authors: Amar Arun Paul , DeGiorgio Christopher M. , Tarver W. Brent , Apuzzo Michael L.J.
Published: April 2003

Objective: Intermittent stimulation of the left cervical vagus nerve trunk (VNS) with the NeuroCybernetic Prosthesis (NCP) is emerging as a novel adjunct in the management of medically refractory epilepsy. We review the safety and efficacy of VNS 1 year after completion of the E05 study, the largest controlled clinical trial of VNS to date. Methods: One hundred and ninety-nine patients with intractable epilepsy and at least 6 complex partial or secondarily generalized seizures per month enrolled in a randomized, double-blinded, partial crossover trial of high versus low parameters of stimulation (E05). After 3 months, all patients received high stimulation during an open-label, nonblinded extension trial (XE5). Seizure frequency, adverse events and multiple physiologic variables were monitored at regular intervals. Results: At 3 months, the mean reduction in seizure frequency among patients receiving high stimulation during E05 was 28%. Of the 199 subjects participating in this acute-phase trial, 195 continued in the long-term protocol. Among the latter patients, 21 subsequently exited the study due to lack of efficacy, and 2 others died from causes unrelated to VNS. Complete data were obtained for 164 of the remaining subjects. Using a declining N analysis, the mean and median reduction in seizure frequency at 15 months was 37 and 45%, respectively. A last visit carried forward analysis, which controls for dropouts and incomplete follow-up, yielded comparable results (34 and 45%, respectively), indicating little potential for selection bias. At 15 months, 39% of the subjects had a greater than 50% reduction in seizures, including 21% who had a greater than 75% reduction, and 2% have remained seizure free. Few serious adverse events, physiological perturbation or device failures were reported. Conclusions: The long-term multicenter safety, efficacy, feasibility and tolerability of VNS, as well as the durability of the NCP device have been confirmed. Unlike chronic therapy with antiepileptic medication, the efficacy of VNS is maintained during prolonged stimulation, and overall seizure control continues to improve with time.
Efficacy of Transverse Tripolar Stimulation for Relief of Chronic Low Back Pain
Authors: Slavin Konstantin V. , Burchiel Kim J. , Anderson Valerie C. , Cooke Beverly
Published: April 2003

The goal of this study was to evaluate the efficacy of the transverse tripolar spinal cord stimulation system (TTS) in providing relief of low back pain in patients with chronic non-malignant pain. Transverse tripolar electrodes were implanted in the lower thoracic region (T8–9 to T12–L1) in 10 patients with chronic neuropathic pain, all of whom reported a significant component of low back pain in combination with unilateral or bilateral leg pain. One patient reported inadequate pain relief during the trial and was not implanted with a permanent generator. A visual analogue scale of low back pain showed a nonsignificant decrease from 64 ± 19 to 47 ± 30 (p = 0.25; paired t test) after 1 month of stimulation. Similarly, functional disability evaluated using Oswestry Low Back Pain Questionnaire was not improved (p = 0.46; paired t test). We conclude that chronic low back pain is not particularly responsive to the transverse stimulation provided by the TTS system.
Gamma Knife Radiosurgery for Trigeminal Neuralgia
Authors: Han Patrick P. , Shetter Andrew G. , Smith Kris A. , Fiedler Jeffrey A. , Rogers C. Leland , Speiser Burton , Feiz-Erfan Iman
Published: April 2003

Forty-three patients with trigeminal neuralgia (TN) unresponsive to pharmacologic treatment and/or prior invasive procedures underwent stereotactic radiosurgery with the Gamma Knife (GK). Outcome was evaluated by a standardized questionnaire mailed to each patient. The mean follow-up was 9 months. Fifteen patients (35%) reported no trigeminal pain and were no longer taking medication. Three patients (7%) experienced occasional pain, but were no longer taking medication. In 15 patients (35%), pain improved and was adequately controlled by medication, often in lower dosages than preoperatively. Pain was reduced in 9 patients (21%), but their symptoms were still inadequately controlled by drug therapy, and 1 patient (2%) reported no pain relief after treatment. Three patients (7%) described new facial numbness, but in none was this bothersome. GK radiosurgery for TN appears to have minimal morbidity, although the success rate may be slightly lower than that of other operative procedures. More patients and longer follow-up are needed before drawing final conclusions regarding efficacy and complications.
Image Guidance: The Foundation for the Future Design of Neurosurgical Procedural Facilities
Authors: Heilbrun Peter
Published: April 2003

Today’s image guidance systems are the foundation of minimally invasive diagnosis and therapy and are the basis for the rational design of the neurosurgical operating room of the future. The building blocks of this procedural arena will be (1) high-resolution MR/CT anatomic imaging supplemented with (2) functional imaging using MR and magnetoencephalography, (3) real-time image monitoring using ultrasound probes, open MR and portable CT adapted to image guidance systems and (4) conformal radiosurgery systems. Although the initial investment in such facilities may be high, eventual cost saving through added precision and safety will result in shorter inpatient stays, lower morbidity and more complete realization of treatment goals.
Comparison of Stereotactic Brain Biopsy to Interventional Magnetic-Resonance-Imaging-Guided Brain Biopsy
Authors: Hall Walter A. , Liu Haiying , Martin Alastair J. , Truwit Charles L.
Published: April 2003

Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance (MR) imaging now allows neurosurgeons to interactively investigate specific regions with exquisite visualization. We compared the safety and efficacy of this new surgical approach with stereotaxis. From February 1991 to June 1998, 134 stereotactic and 35 interventional MR-guided brain biopsies were performed. Stereotactic biopsies utilized preoperative scanning. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathologic examination of biopsy material was performed to verify the presence of diagnostic tissue in both biopsy groups. Intra- and postoperative MR imaging was obtained to exclude the presence of intraoperative hemorrhage. Recently, MR spectroscopic targeting has been utilized in 6 patients. In the stereotactic group, 129/134 (96%) biopsies were diagnostic. One patient had a transient hemiparesis after a brain stem biopsy and another suffered a fatal hemorrhage for a morbidity rate of 0.7% and a mortality rate of 0.7%. In reviewing 7,471 stereotactic biopsies, the morbidity was 3.5%, mortality 0.7% and diagnostic yield 91%. All 35 MR-guided brain biopsies were diagnostic (100%). MR spectroscopy was accurate in all cases in distinguishing recurrent tumor (5 cases) from radiation necrosis (1 case). One patient (3%) suffered a transient hemiparesis following a pontine biopsy and another patient (3%) developed a postoperative scalp cellulitis. No patient sustained a clinically or radiologically significant hemorrhage as determined by the immediate postbiopsy, intraoperative MR imaging. Interventional MR-guided brain biopsy is a safe and effective technique for evaluating lesions of the brain with morbidity and mortality rates comparable to those of stereotaxis. MR-guided biopsy appears to have a higher diagnostic yield than stereotaxis, which may reflect the ability to perform interactive, intraoperative scanning with that technique.
Histometric Assessment of the Age-Related Skin Response to 2-Hydroxy-5-Octanoyl Benzoic Acid
Authors: Avila-Camacho Mabel , Montastier Christiane , Piérard Gérald E.
Published: April 2003

Only a handful of topical products have been shown to limit or improve age-related skin damage. 2-Hydroxy-5-octanoyl benzoic acid, also designated β-lipohydroxyacid (β-LHA), is among the active molecules claiming such effects. The present randomized placebo-controlled double-blind study was undertaken to evaluate the effects of β-LHA in young and older women. Both groups responded to the β-LHA-containing formulation, although to different degrees according to age and the biologic parameter considered. Topically applied 1% β-LHA formulation was associated with several changes, the most conspicuous ones being epidermal thickening and dendrocytic hyperplasia. The constellation of biologic modifications remained within physiological limits, close to the characteristics of young skin. It is inferred that topical β-LHA can cause a significant improvement in some epidermal and dermal manifestations of ageing.