Lambert-Eaton myasthenic syndrome IgG depletes presynaptic membrane active zone particles by antigenic modulation

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that can be transmitted from human to mouse with immunoglobulin G (IgG). Electrophysiological studies indicate that LEMS IgG acts on presynaptic voltage-sensitive calcium channels, probably reducing their number, and freeze-fracture electron microscopy demonstrates that LEMS IgG has an effect on the presynaptic active zone particles, which represent putative voltage-sensitive calcium channels. The active zone particles, normally arranged in double parallel rows, move closer together, form clusters, and are reduced in number. The morphological data suggest modulation of the active zone particles crosslinked by LEMS IgG. If this were the case, then only divalent LEMS IgG and F(ab')2 should alter the deployment of active zone particles and monovalent Fab should be without effect. To test this hypothesis, mouse diaphragms were exposed to control and LEMS IgG and IgG fragments in organ culture for 24 hours and then studied by quantitative freeze-fracture electron microscopy. Divalent LEMS IgG and F(ab')2 aggregated and depleted the active zone particles, whereas monovalent Fab had no effect. The findings reconfirm that the active zone particles are targets of LEMS IgG and are direct evidence for modulation of the particles by LEMS IgG. The findings are in harmony with parallel electrophysiological studies of the effects of LEMS IgG fragments on transmitter release in the same diaphragm muscles (Lang et al, J Physiol 1987;390:173P).     

Zentrale Gallengangskarzinome

Surgical resection provides the only chance of cure for patients suffering from hilar cholangiocarcinoma. Due to the central anatomic localization within the liver hilum, established guidelines of oncologic surgery are difficult to apply. Resection of the hilar bifurcation alone or in combination with limited hepatic resection can be performed with low morbidity and low mortality but shows a high rate of local tumor recurrence. Usually, extended resection is required to achieve adequate safety margins. Right trisectionectomy complies best with the basic rules of oncologic surgery while allowing the maximum safety margin. The 5-year survival rates reported after right trisectionectomy range between 20% and 40% and reach 59% in selected patients. The increasing experience with living donor transplantation and recent advances in neoadjuvant tumor therapy may lead to renewed discussion of liver transplantation in hilar cholangiocarcinoma.     

Coronary-like revascularization for atherosclerotic renal artery stenosis

AIMS: The aim of this study was to document the early outcome of coronary-like revascularization for atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS: A total of 181 consecutive patient, 102 men, mean age 66.1 (+/- 9.2) years and 79 females, mean age 68.4 (+/- 9.2) years and 198 lesions were treated between February 1999 and May 2004 for ARAS and retrospectively analyzed. At least one major cardiovascular risk factor was present in 179 (98.9%) patients. Pre-dilatation ARAS was 81.3+/-9.6%, 27 ARAS were 50-70% and no ARAS was <50%. 135 (68.2%) of the ARAS lesions were ostial and 63 (31.8%) were non-ostial. In 17 (9.4%) patients bilateral ARAS were present. Technical success defined as residual stenosis < or =30% was achieved in 178 (98.3%) of patients and 195 (98.5%) of lesions. In one patient (0.5%) the target ARAS could not be crossed, in two (1.1%) patients residual stenosis was >30%. No major adverse cardiac or cerebral effects were observed. In 3.9% of patients minor local complications of the access site occurred; 4 (2.2%) inguinal hematoma, 3 (1.7%) pseudoaneurysm were documented. Serum creatinine concentrations and systolic and diastolic blood pressure before and after the intervention were not statistically different. CONCLUSIONS: Coronary-like approach to ARAS revascularization is technically feasible and associated with a very low complication rate.     

Lipofibrom des Nervus medianus

The following article presents two new cases of a lipofibroma of the median nerve. This formation is a very rare benign tumor of peripheral nerve tissue. Up to now 30 cases have been reported in the literature and are reviewed in this article and are compared with the two cases reported. Besides the operative treatment, which made the neuropathological diagnosis possible, preoperative diagnosis has been extended by MNT-scans of the involved parts of the nerve. The noninfiltrating character of the tumor could be well recognized on these scans. The signal quality and the anatomical proximity to the median nerve made the diagnosis of a lipofibroma likely. By the postoperative histological reviews the diagnosis was confirmed in classic manner. The immunological marking of the S-100 protein showed a remarkable reduction of this protein in these peripheral nerve tumors. The two cases reported by us recapitulate the clinical history typically and describe symptoms and our treatment for the lipofibroma of the median nerve.     

Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.