Birk Eggers

The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease.

Abstract.Objective: One of the most frequent psychiatric symptoms in patients with Wilsons disease (WD) is depression. It has been suggested that depression is associated with deficits in serotonergic neurotransmission, but, hitherto, no measurements have been performed in WD. Methods: We prospectively examined 23 adult patients (12 women, 11 men, mean age 40 years) with WD for symptoms of depression using the Hamilton rating scale for depression (HAMD). We correlated the data with the presynaptic serotonin transporter density (SERT density) in the thalamus–hypothalamus and the midbrain–pons regions measured with high resolution single-photon emission computed tomography (SPECT) 24 hours after the application of 180 MBq 2β-carbomethoxy-3β-(4 [123I]iodophenyl)tropane ( [123I]b-CIT). The regions of interest were determined by coregistration with a standard MRI dataset. Results: A significant negative correlation was found between HAMD and SERT density in the thalamus–hypothalamus region (r = −0.49, p = 0.02), but not in the midbrain–pons (r = −0.31, p = 0.15). Conclusions: We conclude that depression in patients with Wilsons disease is correlated with alterations of serotonergic neurotransmission in the thalamus–hypothalamus region.

Regional serotonin transporter availability and depression are correlated in Wilson's disease.

Summary. In patients with Wilson’s disease (WD), depression is a frequent psychiatric symptom. In vivo neuroimaging studies suggest that depression and other neuropsychiatric disorders are associated with central serotonergic deficits. However, in vivo measurements of serotonergic neurotransmission have not until now been performed in patients with this copper deposition disorder. The present prospective study revealed that depressive symptomatology is related to an alteration of presynaptic serotonin transporters (SERT) availability as measured by [123I]-2β-carbomethoxy-3β-(iodophenyl)tropane ([123I]β-CIT) and high-resolution single-photon emission computed tomography (SPECT). SERT imaging with [123I]β-CIT-SPECT could therefore become a useful tool for diagnosis and therapy monitoring in depressed WD patients.

The indication for liver transplant to improve neurological symptoms in a patient with Wilson's disease.

Sirs: Wilson’s disease is an autosomal recessive condition in which a defective copper-transporting P-Typ-ATPase causes a disorder in the excretion of copper from the liver. The resulting copper build-up affects first the liver and then the brain. The earlier medical therapy is started, the more effective it is. Should conservative therapy fail, another option is to perform a liver transplant. Accepted indications that a liver transplant is necessary in a patient with Wilson’s disease are fulminant hepatic failure and chronic, progressive liver disease in its final stage [3, 4, 7]. The good results of liver transplants with symptomatic improvement have generated increasing discussion over whether liver transplants are suitable for patients with progressive neurological symptoms [6, 8]. Wilson’s disease was diagnosed in a 19-year-old patient with behavioural disorder and progressive extrapyramidal motor symptoms (see Tab. 1) in 1994. The disease had manifested a year previously with epigastric discomfort, jaundice, ascites, hepatosplenomegaly and tissue oedema, but had not been recognised. As these findings were initially non-progressive, liver cirrhosis of uncertain genesis was assumed. Neurological symptoms occurred half a year later. Typical features included reduced ceruloplasmin and serum copper levels as well as a KayserFleischer corneal ring. The diagnosis of Wilson’s disease was confirmed by the intravenous radio copper test. Despite treatment with D-penicillamine being started immediately (initially 300 mg/d and gradually increased to 1,500 mg/d over a period of 8 months), the neurological symptoms – especially tremor, bradykinesia and dysarthrophonia – progressed during the following two years. In the end the patient was unable to dress himself. Oral food intake was impossible owing to a severe swallowing disorder. Symmetrical hypointense areas in the basal ganglia were observed in cerebral magnetic resonance imaging (T2 weighted) from 1994 (Fig. 1). In July 1996 an orthotopic liver transplant was carried out. Over the next few months, the neurological symptoms diminished. The patient regained his independence. The main residual symptoms were dysarthria and facial dystonia. Repeat MRI in 1999 indicated the reduction of the hypodense signals in the basal ganglia (Fig. 2). This case is characterised by a progressive deterioration of the neurological symptoms despite medical therapy. After the possible initial temporary deterioration of the symptoms owing to copper mobilisation caused by D-penicillamine, the extrapyramidal motor symptoms normally decline. Moreover, the gradually increasing dosage prevents rapid copper mobilisation. It was only after the liver transplant – which was carried out in response to the liver symptoms – that the neurological symptoms were reversed. Schumacher et al. also reported an improvement in the neurological symptoms of 13 patients with LETTER TO THE EDITORS

Correlation between automated writing movements and striatal dopaminergic innervation in patients with Wilson's disease

Abstract Handwriting defects are an early sign of motor impairment in patients with Wilsons disease. The basal ganglia being the primary site of copper accumulation in the brain suggests a correlation with lesions in the nigrostiatal dopaminergic system. We have analysed and correlated striatal dopaminergic innervation using [123I]β-CIT-SPECT and automated handwriting movements in 37 patients with Wilsons disease. There was a significant correlation of putaminal dopaminergic innervation with fine motor ability (p < 0,05 for NIV [number of inversion in velocity], NIA [number of inversion in acceleration], frequency). These data suggest that loss of dorsolateral striatal dopaminergic innervation has a pathophysiological function for decreased automated motor control in Wilsons disease. Furthermore analysis of automated handwriting movements could be useful for therapy monitoring and evaluation of striatal dopaminergic innervation.

Genotype Correlation with Fine Motor Symptoms in Patients with Wilson’s Disease

Wilson’s disease, an autosomal recessive disorder of copper metabolism, is caused by about 200 different mutations of the ATP7B gene. Using a genotype-phenotype correlation, 36 patients were examined to see whether the disorder of the automatic handwriting movement depends on the genotype. The findings of this study indicated that no such link exists. Neither the profile of the impairment of the fine motor parameters nor the severity and frequency of pathological findings were different among the three genotype groups (homozygous for H1069Q, compound homozygous for H1069Q and other mutations). By contrast, fine motor disorders were found to correlate with the clinical symptoms recorded when therapy began. The pathophysiology of the basal ganglia and the cerebellar loop therefore cannot be directly attributed to the genotype of the mutation in the ATP7B gene.

Zerebrales MRT und evozierte Potenziale bei Morbus Wilson

ZusammenfassungDer Morbus Wilson ist gekennzeichnet von einer toxischen Kupferakkumulation mit bevorzugter hepatischer und basalganglionärer Schädigung. Im Fall einer neurologischen Symptomatik konnten charakteristische Befunde im kranialen MRT und bei den elektrophysiologischen Untersuchungen gefunden werden.In der vorliegenden Studie werden bei 28 Patienten mit einer neurologischen Verlaufsform die Befundmuster im kranialen MRT denen der evozierten Potenziale (FAEP, MSEP, T-VEP, MEP) gegenübergestellt. Regelmäßig liegen im MRT basalganglionäre Signalveränderungen (Putamen und Gl. pallidus) in Kombination zu einer Groß- und Kleinhirnatrophie vor. Variabel treten Signalveränderungen mesenzephal (46%) und im Nc. dentatus (36%) auf, pontine Veränderungen sind nur diskret. Bei 71% der Patienten bestehen gestörte FAEP und bei 46% gestörte MSEP. In 39% treten pathologische FAEP und MSEP kombiniert auf. Weniger häufig sind die T-VEP (36%) und die MEP (39%) betroffen.Im individuellen Vergleich der beiden Befundmuster findet sich keine strenge gegenseitige Bedingtheit. Damit ist der Wert beider Untersuchungsmethoden in einer Ergänzung zu interpretieren und die simultane morphologische und funktionelle Überwachung zu empfehlen.SummaryWilsons disease is caused by toxic copper accumulation, which leads predominantly to hepatic and basal ganglia damage. Characteristic findings in MRI and electrophysiologic examinations are described according to the occurrence of neurological symptoms. In the present study, 28 patients suffering from Wilsons disease (neurological type) were investigated. The results of MRI are compared with abnormalities of evoked potentials (BAEP, MSEP, T-VEP, MEP). All patients show hypodensities in the basal ganglial area (putamen and Gl. pallidus) regularly combined with atrophy of the cerebrum and cerebellum in MRI. Signal abnormalities in the mesencephalic region (46% occurrence) and Nc. dentatus (36% occurrence) are combined with the other findings in variable patterns. Only slight changes are found in the pontine region. BAEP are disturbed in 71% of all cases and MSEP in 46%. Combined abnormalities of BAEP and MSEP were found in 39%. Pathological values occurred with a lower frequency in T-VEP (36%) and MEP (39%). The comparison of MRI findings with electrophysiological data done separately for each patient reveals no strong correlation between both methods. Individual MRI findings do not correspond with the patterns of disturbed evoked potentials and vice versa. Therefore we conclude that these methods, MRI and electrophysiological evaluation, supplement each other. Magnetic resonance imaging and electrophysiological evaluation should be performed simultaneously for therapy monitoring.

P1-285: First results toward in vivo quantification of cerebral β-amyloid plaque load in Alzheimer's disease by means of BAY 94-9172-PET

patients had significantly higher DVR reflecting greater AV-45 binding estimates in the following brain regions: frontal, temporal, fusiform gyrus, cingulate, insula, putamen, globus pallidus, as well as a summary measure of whole-cortex DVR. MMSE, WMS, and category fluency were not correlated with DVR in any brain region after controlling for diagnosis. However, regional DVR in frontal, temporal, occipital, fusiform gyrus, cingulate, parahippocampus, insula, putamen, and cortex correlated significantly with ADAS-Cog Word Recall after controlling for diagnosis (r .84-.92 for model). Similarly, regional DVR in thalamus and caudate nucleus correlated significantly with ADAS-Cog Constructional Praxis after controlling for diagnosis (r .61-.77 for model). Conclusions: DVR of [F] AV-45, a novel ligand for PET imaging of amyloid plaques, was significantly higher in AD in many cortical regions implicated in early AD. This suggests the utility of this ligand for AD diagnosis. Interestingly enough, DVR in hippocampus was not elevated reflecting the observation that neurofibrillary tangles are a more sensitive marker than plaques for early hippocampal involvement in AD. In two cognitive domains there was further evidence for correlation of cognitive performance with DVR after controlling for diagnosis, suggesting that [F] AV-45 may also be useful as a marker of AD severity.