[Cerebrospinal fluid-based diagnostics of CT-negative subarachnoid haemorrhage]. / Liquordiagnostik bei CT-negativer Subarachnoidalblutung.

The diagnostic investigation of CT-negative subarachnoid haemorrhage (SAH) is a particular challenge in clinical neurology. Cerebrospinal fluid (CSF) analysis via lumbar puncture is the method of choice. The diagnosis of SAH in CSF is based on a bloody or xanthochromic discoloration of the CSF as well as on findings in non-automated CSF cytology including the detection of erythrophages and siderophages. The automated determination of CSF ferritin concentrations or spectrophotometric detection of xanthochromia may contribute to the diagnosis but are only useful with regard to the overall clinical picture. Generally, the knowledge of the time flow of CSF changes associated with SAH is essential for a correct interpretation of CSF findings.

Localization of creatine kinase isoenzymes in myofibrils. II. Chicken heart muscle.

Chicken heart muscle contains almost exclusively the BB isoenzyme of creatine kinase (CK), its myofibrils, moreover, lack an M-line. This tissue thus provides an interesting contrast to skeletal muscle, in which some of the MM-CK present as predominant CK isoenzyme is bound at the myofibrillar M-line. Approx. 2% of the total CK activity in a chicken heart homogenate remains bound to the myofibrillar fraction after repeated washing cycles; both the fraction and the absolute amount of CK bound are about threefold lower than in skeletal muscle. Almost all of the bound enzyme is located within the Z-line region of each sarcomere, as revealed by indirect fluorescent-antibody staining with antiserum against purified chicken BB-CK. After incubation with exogenous purified MM-CK, positive immunofluorescent staining for M-type CK at the H-region of heart myofibrils was observed, along with weaker fluorescence in the Z-line region. Chicken heart myofibrils may thus possess binding sites for both M and B forms of CK.

[Wilson's disease]. / Morbus Wilson.

Wilson's disease is a rare autosomal recessive disorder of hepatic copper transport leading to a biliary excretion inhibition of copper. Overload of the metal mainly in liver and basal ganglia leads to hepatic but also to extrapyramidal motor as well as psychiatric clinical symptoms. Diagnosis is based on clinical suspicion, parameters of copper metabolism, ophthalmic examination and a liver biopsy. A radiocopper test is able to identify patients even with inconsistent laboratory results. For initial assessment and follow-up neurophysiological investigation and MRI are recommended additionally. Genetic analysis can be helpful to detect asymptomatic relatives of the index patient. Dependent on the stage of the disease for therapy chelating drugs and zinc are possible but must be given lifelong without longer interruptions. With early diagnosis and consequent treatment the prognosis of Wilson's disease is excellent and usually the need for liver transplantation can be prevented.

Pattern of cell death during optic cup formation in the tree shrew Tupaia belangeri.

Developmental cell death during optic cup formation was investigated in the tree shrew Tupaia belangeri. Twenty-six embryos from days 12 to 16 of prenatal ontogenesis were studied by light microscopy. Prior to the optic vesicle stage, a dorsal area of cell death surrounded the lumen of the V-shaped optic evagination (phase 1). A ventral band of dead cells, found in the optic vesicle (phase 2), preceded a dorsal focus of cell death (phase 3) previously described as a characteristic avian feature. During further invagination (phase 4), a peak of cell death was represented by a ventrodorsal band extending from the diencephalon over the complete optic anlage. The main areas of cell death found in phases 2 to 4 were, topographically, segments of this band. Also, the distinct areas of cell death reported in the literature for the vertebrate species studied so far fit well into this ventrodorsal band found in Tupaia. Thus, most probably, a common spatio-temporal sequence of cell death exists in all of them. In Tupaia, dead cells concentrated at the diencephalic insertion of the optic stalk, the suboptic necrotic center (SONC) reported by several authors, were part of the early ventral band of cell death originating from the median floor of the prosencephalon (phase 2). During optic cup formation, the SONC was part of the ventrodorsal band and, thus, was not secondarily formed by the subdivision of a pre-existing distal ventral area of cell death as reported for several other vertebrates.

Pattern of calretinin immunoreactivity in the main olfactory system and the vomeronasal system of the tree shrew, Tupaia belangeri.

The distribution of the calcium-binding protein calretinin was studied in peripheral and central parts of the main olfactory system (MOS) and the vomeronasal system (VNS) of adult tree shrew Tupaia belangeri. The calretinin immunoreaction was carried out with a peroxidase-coupled polyclonal antibody. In the VNS, complete labeling of all receptor cells and vomeronasal nerve fibers was observed, whereas only a subset of the somata and dendrites of receptor cells and of the olfactory nerve fibers of the MOS was immunoreactive. From the immunoreactive dendritic clubs of vomeronasal receptor cells, calretinin-labeled structures, presumably clumps of microvilli, arose that terminated within immunopositive portions of the mucus. In the main olfactory bulb, the neuropil of some of the glomeruli was immunoreactive. All periglomerular and many mitral cells were labeled. The external plexiform layer was subdivided into a faintly immunoreactive superficial half and a strongly immunoreactive deep half. Immunoreactive basal dendrites of mitral cells could be followed into either the deep half or the superficial half. In the laminated internal granular layer, a subset of immunopositive granule cells extended dendrites into the external plexiform layer. Mitral cells and granule cells with dendrites ascending to different levels of the external plexiform layer may represent functional subclasses. In the accessory olfactory bulb, all vomeronasal nerve fibers, glomeruli, and mitral/tufted cells were labeled, whereas immunoreactive periglomerular cells and internal granule cells were only scattered. In Tupaia, calretinin immunoreactivity is a more general property of the primary projecting neurons of the VNS than of the MOS and possibly indicates the involvement of calretinin in the perception of certain of the olfactory qualities.

The morphogenesis of the arteries of the pelvic extremity. A comparative study of mammals with special reference to the tree shrew Tupaia belangeri (Tupaiidae, Scandentia, Mammalia).

The ontogeny of the arteries of the pelvic extremity of Tupaia belangeri was investigated by light microscopy on the basis of serial sections of 30 embryos, dating from day 17 to day 42 post-copulation. In Tupaia, the gestational period takes approximately 43 days. Additionally, a 3-D reconstruction of the pelvic region and the right leg of a 22-day embryo was prepared. The arteries of an adult Tupaia were studied on the basis of a corrosion cast. The results were compared with the ontogeny of the arterial system of other mammals. In the 17-day embryo, the anlage of the pelvic extremity is penetrated by a capillary plexus. In the 18-day embryo, the a. ischiadica reaches the pelvic limb bud, representing the primary axial artery. On day 19, its r. perforans tarsi extends from the plantar to the dorsal aspect of the foot plate. The a. ischiadica is the main artery of the leg until the stage of the 22-day embryo. Afterwards, the peripheral arteries supplied by it are taken over by the a. iliaca externa and its extension, the a. femoralis. The a. iliaca externa springs from the a. iliaca communis in the 19-day embryo. From day 21 to day 22, the capillary plexus, which is nourished by the a. femoralis, closely approaches the a. ischiadica, and finally, a connecting branch joins the a. ischiadica. The a. ischiadica is then reduced to the a. glutea caudalis, and the aa. femoralis, poplitea profunda (at the cranial aspect of the m. popliteus), and interossea become the main arteries of the pelvic extremity. The a. poplitea superficialis, lying at the caudal aspect of the m. popliteus, and its continuation in the crural region, the a. peronea, develop until the 25-day embryo. The a. peronea gives rise to an r. perforans which penetrates the membrana interossea towards the dorsum of the foot. As a result of a shift of the origin of the a. iliaca externa in the proximal direction, the length of the a. iliaca communis gradually decreases until, on day 24, the a. iliaca externa springs directly from the lateral wall of the aorta. In the 20-day embryo, the a. iliaca externa gives rise to an a. circumflexa ilium profunda towards the lateral pelvic wall, and in 23-day embryos, to the a. profunda femoris. The main branches of the a. profunda femoris develop until day 24. At the same time, the aa. circumflexa femoris lateralis and nutricia ossis femoris arise from the a. femoralis. The a. saphena, which is already recognizable in the 23-day embryo, gives rise to the a. genus descendens, and as an a. plantaris medialis, to four aa. digitales plantares communes (I-IV) at the planta pedis. The development of the a. tibialis cranialis on day 25 takes place independently and without any topographic relation to the a. saphena, which functionally replaces the a. tibialis cranialis in some other mammals. In the 26-day embryo, the aa. peronea and tibialis cranialis extend to the dorsum of the foot where they continue as the aa. dorsales pedis profunda and superficialis. The fourth main artery of the lower leg, the a. caudalis femoris, which is first observed in the 20-day embryo, reaches the lateral aspect of the foot on day 24. Its r. calcaneus runs to the planta pedis. In 30-day embryos, the aa. digitales plantares propriae have differentiated. The corresponding dorsal arteries and the superficial plantar vascular are develop until day 35, so that all important arteries of the pelvic extremity, which are seen in the corrosion cast of the adult, are recognizable. Among the embryos and the adult Tupaia studied, individual variation is minimal. The developmental stage at which the arteries of the leg acquired a secondary vascular wall was ascertained. Only a vessel with a primary vascular wall can dissolve into a capillary plexus later on (e.g., a. interossea). In contrast, the course of an artery which has acquired a secondary vascular wall is determined, because modifications of the course of a vessel often need a capillary plexus as an intermediate st

FMRFamide immunoreactivity and the invasion of adenohypophyseal cells into the neural lobe in the developing pituitary of the tree shrew Tupaia belangeri.

Ontogenetic development of FMRFamide immunoreactivity in the cells and nerve fibers of the pituitary was studied in the tree shrew Tupaia belangeri. Up to the 26th day of gestation (E26), no FMRFamide immunoreactivity was visible. From E27 onwards it increased continuously until prenatally, on E41, the adult pattern was reached in the adenohypophysis, although at a lower intensity. In the adult Tupaia, as in the other mammals studied so far, a finely stained FMRFamide-immunoreactive fiber network was visible in the neural lobe and the infundibular stalk. As in several other adult mammals including man, endocrine cells in the pars intermedia and numerous scattered cells in the pars distalis were labeled, in contrast to several reports on rats and our studies on Galago, showing no FMRFamide-immunoreactive cells in these locations of the pituitary. With reference to the 'basophil invasion', we found FMRFamide-immunoreactive endocrine cells invading the neural lobe from the pars intermedia during the pituitary development. The distribution pattern of FMRFamide immunoreactivity in Tupaia indicates that the mammalian counterparts of FMRFamide may function as neuromodulators, neurotransmitters or as hormones already in defined prenatal stages.

Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions.

In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients. Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated 37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain and thalamic area) by using (18)F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [(18)F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least) two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined by a disturbed consumption in the striatal area.

Serum neuron-specific enolase levels do not increase after electroconvulsive therapy.

BACKGROUND: Cognitive disorders occurring after electroconvulsive therapy (ECT) are regarded as an expression of brain damage, despite computed tomography (CT) and magnetic resonance imaging (MRI) showing no signs of structural brain damage. Serum neuron-specific enolase (NSE) is a sensitive marker of neuronal damage (i.e., after stroke or cardiac arrest). The objective of this study was to investigate whether ECT leads to a rise in the serum NSE level as an expression of neuronal damage. METHODS: We investigated seven patients (four women, three men; mean age 6212 years) with major depressive disorder, who were treated with ECT for the first time. ECT was administered every 2 days, three times a week under standard conditions (anaesthesia: thiopental, succinylcholine, 100% oxygen, unilateral ECT, seizure duration more than 20 s). Blood samples were drawn at the following times. For the first ECT: 15 and 1 min before ECT, and 1, 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, 105, 120 min, and 8, 12, 24 h after ECT. For all subsequent ECT: 1 min before and 4 h after every ECT. Serum NSE was measured by means of enzyme immunoassay (Cobas Core NSE, EIA, Hoffmann-La Roche). RESULTS: On average, each patient underwent ECT 10 times (range 5-20). In the first ECT there was no difference in serum NSE levels before and at all times following ECT. A comparison of serum NSE levels before and after each subsequent bout of ECT revealed no differences. Moreover, comparing the baseline serum NSE levels (before the first ECT) with the values after final ECT showed no differences either. CONCLUSION: ECT did not increase serum NSE values, indicating that electroconvulsive therapy does not cause neuronal damage.

"Lens mitochondria" in the retinal cones of the tree-shrew Tupaia belangeri.

In all mammals, the mitochondria of the cones of the retina are concentrated in the inner segment. Uniquely in tree-shrews (Tupaia, Scandentia, Mammalia), a "megamitochondrion" exhibiting highly specialized systems of densely packed cristae and a very electron dense matrix, is located apically in the inner segment. The ellipsoid is a solid body containing several megamitochondria and, towards its base, a large number of smaller mitochondria. The refractive index of isolated, but not oriented, inner segments of Tupaia belangeri is higher (XA = 1.405) than in any other mammal studied so far. The consistent geometrical pattern of the multilamellar crista-matrix systems, oriented longitudinally towards the outer segment, suggests an additional optical function of the megamitochondria.

The early development of the heart of Tupaia belangeri, with reference to other mammals.

The development of the heart of Tupaia belangeri from the first endothelial-lined lumina to the cardiac loop is described in 20 embryos with 2 to 14 somites, from ontogenetic days 11 and 12. Bilateral endocardial tubes transporting blood are found in the 8-somite embryo; in the middle cardiac plate, angioblasts and angiocysts are located between them. In the 9-somite embryo, formation of the cardiac loop has started, the endocardial tubes approach each other closely, most of the angiocysts have been incorporated by the expanding endocardial tubes, and fusion of the endocardial lumina has started in the cono-truncal area. Apparently, much of the endocardial cardiac loop found in the 9-somite embryo has been produced by the disproportionate lengthening of a segment of the endocardial tubes, which is very short in the 8-somite embryo. In the 13-somite embryo the endocardial tubes have largely fused, but tube-like strands of endothelia, remnants of the original endothelial walls separating them, form a "palisade" and mark the original boundary between them. Myoepicardial differentiations of the splanchnopleure begin separately on both sides of the embryo and gradually spread craniad until they coalesce in the midline, in front of the anterior intestinal portal. The caudal portions of the endocardial tubes with initial myoepicardial and cardiac jelly differentiations do not contribute to the definitive heart. The anterior intestinal portal is very broad in Tupaia. Contradictions in the literature as to the bilaterality of cardiac primordia of eutherian mammals are discussed. The hypothesis is developed that bilateral endocardial tubes and bilateral myoepicardial differentiations of the splanchnopleure develop in species with a large yolk-sac, relatively late closure of the foregut, and a broad anterior intestinal portal (e.g., Tupaia, ferret, and cat, etc.). This is probably the primitive condition in eutherian mammals. In species with a small yolk-sac and/or reversal of germ layers (man, rodents), the foregut and anterior intestinal portal are formed earlier, the heart primordium reaches its median position ventral to the foregut in the angiocyst-stage, and the first endocardial lumina appear close to the midline. In these species, the primordium of the endocardium seems to be plexiform and without clear evidence for bilaterality.

The early development of the epicardium in Tupaia belangeri.

Development of the epicardium was studied in embryos of Tupaia belangeri from the 13th to 15th day of ontogeny. The greater part of the epithelium of the epicardium does not differentiate locally from the myoepicardium (cardiac splanchnopleure, splanchnic mesoderm), but rather from the coelomic epithelium of the septum transversum. The myoepicardium of the future atria and ventricles differentiates into myocardial cells only. On ontogenetic day 13, bulbar protrusions (the "villi" of Kurkiewicz 1909) are formed on the surface of the septum transversum and extend into the pericardial cavity, primarily between the sinoatrial and the ventricular regions of the embryonic heart. These protrusions are covered by flattened interdigitating cells, and they are filled with intercellular fluid of the mesenchyme of the septum transversum. Many mitoses are found among the cells. From these protrusions free vesicles are formed which are discharged into the pericardial cavity. The vesicles attach to the surface of the myoepicardium, i.e. to the developing myocardial cells. The vesicles open, and their cells spread out onto the surface of the heart to form the primary epicardium. This process begins on the dorsal surface of the heart, close to the protrusions of the septum transversum, there are, however, further isolated patches of primary epicardium in other regions of the surface of the heart. After the epicardial cells have settled onto the myocardium, mitoses become rare among them. On day 15, most of the myocardium is coated by the primary epicardium and the protrusions on the septum transversum disappear. A "bare" myocardium, as found on ontogenetic days 12 and 13 in Tupaia, might be a primitive (plesiomorphic) condition among chordates. In adult Branchiostoma, the coelomic epithelium which coats the contractile blood vessels had been found to differentiate into muscle cells that remain uncoated on the side facing the coelomic cavity (Franz 1933; Joseph 1914, 1928).

Ciliogenesis in photoreceptor cells of the tree shrew retina.

Transmission electron microscopy of the retinal cones from several prenatal, young postnatal and adult tree shrews (Tupaia belangeri) reveals that the centrioles, from which the ciliary precursors of the outer segments grow out, are not transported into a pre-existing inner segment, but are positioned under the apical plasma membrane of cone precursor cells all through the inner segment formation. Ciliogenesis starts before or on embryonic day 20 and thus precedes initial formation of the inner segment by 20 days, which is half the gestation period. Thus, the maturation of the outer segment covers a considerably longer period than has been previously described. Published observations from other mammals can be interpreted as conforming with the situation in Tupaia. In other vertebrates, compared to mammals, marked heterochronies do occur. In Tupaia, the centrioles and the cilium are located close to the central longitudinal axis of the photoreceptor precursor cell from the 20-day-old embryo to the 5-day-old juvenile. In this position the microtubule apparatus originating from the centrioles should be most effective in transporting the mitochondria into the inner segment. In the 12-day-old tree shrew, when transport of the mitochondria into the inner segment has been completed, centrioles and cilium have shifted into an eccentric position and the light-collecting megamitochondria have approached the disks of the outer segment. This eccentric position is maintained in all later developmental stages. In certain of the retinal areas of the adult Tupaia, the connecting cilia of neighbouring cones are always positioned on the same side of the inner segments.

The patterns of cell death and of macrophages in the developing forebrain of the tree shrew Tupaia belangeri.

The patterns of cell death and of macrophages were investigated in the forebrain and eyes of the tree shrew Tupaia belangeri during five phases of optic cup formation. Seventeen embryos were studied. Three- dimensional reconstructions were made from one embryo of each phase. In phase 1 (V-shaped optic evagination) a midline band of cell death passes through the closing anterior neuroporus. From phases 2 (optic vesicle) to 5 (far-advanced invagination) the midline band of cell death extends in the dorsal wall of the forebrain to its rostral pole and, further, into its ventral wall. At the approximate future position of the optic chiasm this ventral pycnotic area, predicted but so far unidentified by others, is connected to a previously described second band of cell death passing through the optic anlagen. Recently, evidence has been presented that chicken embryos develop holoprosencephaly and cyclopia when ventral forebrain structures are lost secondary to experimentally induced apoptosis. Our findings in Tupaia suggest that, in cases of spontaneous malformations of this kind, such an atypical pycnotic area in the ventral telencephalon might result from the defective regulation of cell death processes during optic cup formation. In the forebrain and eyes of Tupaia, the occurrence of bands of cell death precedes the appearance of the earliest intraepithelial macrophages. From phase 3 (onset of invagination) onwards almost all of them are concentrated along the band of cell death.

Expression patterns of erythropoietin and its receptor in the developing midbrain.

The expression patterns of erythropoietin (EPO) and its receptor (EPOR) were investigated in the midbrain and in adjacent parts of the synencephalon and hindbrain of embryonic C57Bl mice. On embryonic (E) day 8 (E8), virtually all neuroepithelial cells expressed EPOR. After neural tube closure, subsets of these cells downregulated EPOR. In contrast, radial glial cells were EPOR-immunolabeled from E11 onwards. Simultaneously, subpopulations of early developing neurons upregulated EPO and expressed HIF-1, known to transcriptionally activate EPO. Three-dimensional reconstructions revealed subpopulations of EPO-expressing neurons: (1) in the trigeminal mesencephalic nucleus (TMN), (2) at the rostral transition of the midbrain and synencephalon, (3) in the basal plate of the midbrain, (4) in the trigeminal motor nucleus, and (5) in the trigeminal principal sensory nucleus. In the rostral midbrain and synencephalon, EPO-immunoreactive neurons were attached to EPOR-expressing radial glial cells. The identity of radial glial cells was proven by their immunoreactivity for antibodies against astrocyte-specific glutamate transporter, brain lipid-binding protein, and nestin. From E12.5 onwards EPOR was downregulated in radial glial cells. Viable neurons of the TMN continued to express EPO and upregulated EPOR. Our findings provide new evidence that components of the EPO system are present in distinct locations of the embryonic brain and, by interactions between neurons and radial glial cells as well as among clustered TMN neurons, may contribute to its morphogenesis. Whether the observed expression patterns of EPO and EPOR may reflect EPO-mediated trophic and/or antiapoptotic effects on neurons is discussed.

Tension transients in skinned muscle fibres of insect flight muscle and mammalian cardiac muscle: effect of substrate concentration and treatment with myosin light chain kinase.

Glycerinated single fibres from the dorsal longitudinal muscle of Lethocerus maximus were isometrically contracted in MgATP-salines (10 microM Ca2+; 1.5 mM Mg2+; pH 6.7; 22 degrees C and 20 mM PEP; 100 U/ml pyruvate kinase). The ratio of ATPase activity to tension decreased by a factor of 2 after reducing the ATP-concentration from 15 to 0.5 mM. At all ATP-concentrations (0.5-15 mM), the fibres showed tension adjustments in response to small step changes in length characteristic to an actively contracting muscle: i) an elastic phase which did not depend on ATP-concentration ii) a quick phase of stress relaxation with at least two exponential components; iii) a phase of delayed tension generation. An increase in size of the length step and/or a decrease of ATP-concentration slowed the quick phase and the delayed phase. Similar results have been obtained with skinned cardiac muscle (pig right ventricle). To see, how the isolated contractile system is affected by an increase in the light chain phosphorylation, tension transients were studied in skinned right ventricular muscle fibres before and after incubation with ATP gamma S (2 mM), pure myosin light chain kinase (9 micrograms/ml), Calmodulin (1 microM) and Ca2+ (0.8 microM). While isometric tension development elicited by 20 microM Ca2+ in the ATP salt solution was barely affected in presence of the enzyme, the ATPase activity was decreased by about 25% of the control. There was also a marked decrease (about 50%) in the contraction velocity as determined by the recovery of tension following a quick release. Quick stretches cause an immediate increase in tension followed by a rapid fall and a subsequent rise in tension. The velocity of this tension rise decreased by approximately 30% after incubation with myosin light chain kinase.

The vomeronasal organ of the New World monkey Saguinus fuscicollis (Callitrichidae). A light and transmission electron microscopic study.

The vomeronasal organ (VNO) of the New World monkey Saguinus fuscicollis (Callitrichidae) is located at the base of the most distal portion of the nasal septum opening into the nasal portion of the ductus nasopalatinus which also communicates with the oral cavity. The lumen of the VNO is limited medially and laterally by a neuroepithelium which is devoid of intraepithelially located blood vessels and composed of receptor, supporting and basal cells. Ultrastructural analysis of the VNO of Saguinus fuscicollis reveals morphological features which lead one to postulate the functional capacity of this organ in these primates. A possible mechanism through which scent marks may be incorporated into the VNO is discussed.

[Correlation of clinical aspects as well as genotype and phenotype in Wilson's disease on the basis of epidemiologic, clinical and cranial MRI findings]. / Klinische und Genotyp-Phänotyp-Korrelation epidemiologischer, bildgebender und neurologischer Befunde bei Patienten mit Morbus Wilson.

Wilson's disease, a rare autosomal recessive disorder of hepatic copper transport, is characterized by a varying pattern of hepatic, neurologic and psychiatric symptoms. Currently, about 250 causative mutations of the ATP 7B gene are known. However, a correlation between genotype and phenotype according to these mutations is not yet clear. To elucidate a possible correlation in this study 39 patients with Wilson's disease were subdivided into three groups according to the underlying mutation in group I for homocygote respectively group II for compound heterocygote mutation in H1069Q and group III for other mutations. Clinical subtype and extent of neurologic disturbance as well as epidemiologic aspects, presence of psychiatric symptoms, results of acustically evoked potentials (Wave III, interpeak latency III-V) and findings of cranial MRI were considered. While psychopathological symptoms, the results of acustically evoked potentials and cranial MRI show a correlation to the clinical subtype of Wilson's disease there was no genotype-phenotype correlation on the basis of the mutation in H1069Q. The qualitative and quantitative pattern of results do not show any significant differences in the three groups of genotype. Thus, the time of treatment onset still has most influence on the extent of clinical manifestation and reversibility of the toxic copper accumulation.