[Von Hippel-Lindau disease. Interdisciplinary patient care]. / Von-Hippel-Lindau-Erkrankung. Interdisziplinäre Patientenversorgung.

Von Hippel-Lindau disease is an important hereditary tumor syndrome with a clear option for effective treatment if diagnosed in time. Interdisciplinary cooperation is the key to successful management. Major components of the disease are retinal capillary hemangioblastomas, hemangioblastomas of cerebellum, brain stem and spine, renal clear cell carcinomas, pheochromocytomas, multiple pancreatic cysts and islet cell carcinomas, tumors of the endolymphatic sac of the inner ear, and cystadenomas of the epididymis and broad ligament. A well structured screening program should be performed at yearly intervals.

Benefits and limitations of image guidance in the surgical treatment of intracranial dural arteriovenous fistulas.

BACKGROUND: Despite major advances in endovascular embolization techniques, microsurgical resection remains a reliable and effective treatment modality for dural arteriovenous fistulas (DAVF). However, intraoperative detection of these lesions and identification of feeding arteries and draining veins can be challenging. In a series of 6 patients who were not candidates for definitive treatment by endovascular embolization we evaluated the benefits and limitations of computer-assisted image guidance for surgical ablation of DAVF. METHODS: Of the 6 patients, 5 presented with haemorrhage and one with seizures. Diagnosis of DAVF was made by conventional angiography and dynamic contrast enhanced MR angiography (CE-MRA). All patients were surgically treated with the assistance of a 3D high resolution T1-weighted MR data set and time-of-flight MR angiography (MRA) obtained for neuronavigation. Registration was based on cranial fiducials and image-guided surgery was performed with the navigation system. FINDINGS: Four of the 6 patients suffered from DAVF draining into the superior sagittal sinus, one fistula drained into paracavernous veins adjacent to the superior petrosal sinus and one patient had a pial fistula draining in the straight sinus. DAVF diagnosed with conventional angiography could be located on CE-MRA and MRA prior to surgery. MRI and MRA images were combined on the neuronavigation workstation and DAVF were located intraoperatively by using a tracking device. In 4 out of 6 cases neuronavigation was used for direct intraoperative identification of DAVF. Brain shift prevented direct tracking of pathological vessels in the other 2 cases, where navigation could only be used to assist craniotomy. Microsurgical dissection and coagulation of the fistulas led to complete cure in all patients as confirmed by angiography. CONCLUSIONS: Neuronavigation may be used as an additional tool for microsurgical treatment of DAVF. However, in this small series of 6 cases, surgical procedures have not been substantially altered by the use of the neuronavigation system. Image guidance has been beneficial for the location of small, superficially located DAVF, whereas a navigated approach to deep-seated lesions was less accurate due to the familiar problem of brain shift and brain retraction during surgery.

Familial horizontal gaze palsy with progressive scoliosis maps to chromosome 11q23-25.

Horizontal gaze palsy with progressive scoliosis (HGPS) is a rare, autosomal recessive disorder characterized by a congenital absence of conjugate horizontal eye movement, with progressive scoliosis developing in childhood or adolescence. The authors identified two unrelated consanguineous families with HGPS. Genomewide homozygosity mapping and linkage analysis mapped the disease locus to a 30-cM interval on chromosome 11q23-25 (combined maximum multipoint lod score Z = 5.46).

Loss-of-function EA2 mutations are associated with impaired neuromuscular transmission.

OBJECTIVE: To examine the functional consequences of episodic ataxia type 2 (EA2)-causing nonsense and missense mutations in vitro and to characterize the basis of fluctuating weakness in patients with E2A. BACKGROUND: Mutations in CACNA1A encoding the Ca(v)2.1 calcium channel subunit cause EA2 through incompletely understood mechanisms. Although the Ca(v)2.1 subunit is important for neurotransmission at the neuromuscular junction, weakness has not been considered a feature of EA2. METHODS: The disease-causing mutations in three unrelated patients with EA2 and fluctuating weakness were identified by mutation screening and sequencing. Mutant constructs harboring mutations R1281X, F1406C, R1549X were transfected into COS7 cells and expressed for patch clamp studies. Single-fiber electromyography (SFEMG) was performed in patients to examine synaptic transmission at the neuromuscular junction. RESULTS: Functional studies in COS7 cells of nonsense and missense EA2 mutants demonstrated markedly decreased current densities compared with wild type. SFEMG demonstrated jitter and blocking in these patients with EA2, compared with normal subjects and three patients with SCA-6. CONCLUSION: EA2-causing missense and nonsense mutations in CACNA1A produced mutant channels with diminished whole cell calcium channel activity in vitro due to loss of function. Altered biophysical properties or reduced efficiency of plasma membrane targeting of mutant channels may contribute to abnormal neuromuscular transmission, manifesting as myasthenic syndrome.

Stereological estimates of total neuron numbers in the hippocampus of adult reeler mutant mice: Evidence for an increased survival of Cajal-Retzius cells.

The cytoarchitecture of the brain is disrupted severely in reeler mice. This is caused by a deficiency in the protein, Reelin, which is essential for the normal migration and positioning of neurons during development. Although cell migration is clearly affected by the reeler mutation, it is believed that the total number of neurons is not. Thus, we were surprised to find an unusually large number of calretinin-immunopositive cells, presumably Cajal-Retzius cells, in the molecular layer of the adult reeler hippocampus (Deller et al. [1999]; Exp. Neurol. 156:239-253). This suggested that the reeler mutation affects the number of neurons in the hippocampus. In order to verify this hypothesis, unbiased stereological methods were employed. Calretinin immunostaining was used as a marker for Cajal-Retzius cells in control as well as reeler mice and Nissl staining was used to identify hippocampal principal neurons. Total numbers of calretinin-immunopositive cells, calretinin-immunoreactive Cajal-Retzius cells, and Nissl-stained neurons were estimated in different subfields of the reeler and the control hippocampus. Stereological estimates (P < 0.05) revealed that the total number of calretinin-immunopositive and Cajal-Retzius cells in reeler mice are 1.5 and 2.1 times that of controls, respectively. No significant difference in total neuron number was found in any hippocampal subfield. These data demonstrate that the reeler mutation affects the number of calretinin-immunoreactive Cajal-Retzius cells in the adult hippocampus, probably due to a reduced excitatory innervation by entorhinal terminals in the absence of reelin. However, the reeler mutation does not affect mechanisms that determine total hippocampal neuron number.

[Ductus thoracicus drainage in man. Changes of the lymph cells and protein fractions]. / Ductus Thoracicus-Drainage beim Menschen. Veränderungen der Lymphzellen und Proteinfraktionen

1. During thoracic duct drainage a significant decrease of serum beta- and gammaglobulins can be found. 2. The withdrawn lymphprotein can be sufficiently substituted by human serum albumin. 3. The number of small lymphocytes decreases significantly during thoracic duct drainage, while the number of large lymphocytes and lymphoid cells increases. 4. The drainage of thoracic duct in humans is a highly immuno-suppressive procedure without major risks.