Das Restless-legs-Syndrom (RLS) ist ein häufiges neurologisches Krankheitsbild. Studien zeigten, dass es mit internistischen und neurologischen Erkrankungen assoziiert auftritt.

BackgroundRestless legs syndrome (RLS) is acommon neurological disease. Studies have shown that RLS is associated with avariety of medical and neurological disorders.ObjectivesUsing the example of three associated neurological diseases, the significance for everyday therapy decisions is assessed.Material and methodsAsystematic search was carried out in PubMed for all studies with the keyword RLS in combination with polyneuropathies (PNP), Parkinson's disease (PD) and multiple sclerosis (MS) and classified according to the methodology in high, medium or low study quality.ResultsOf 16studies on RLS and MS, 10 were rated as high. The high association frequency of RLS in MS between 13.3% and 65.1% (the variability possibly originates from different methods) prevents further statements about the prevalence. Within 30studies on Parkinson's disease 17 were classified as having a high quality. In patients with Parkinson disease RLS occurs most frequently during therapy and is related to the duration of dopaminergic treatment. In patients with polyneuropathy, only 5 out of 24studies were classified as being of high quality and an increased RLS prevalence was detected for acquired polyneuropathies with heterogeneous data for hereditary forms.ConclusionThere is an increased prevalence of association with RLS for the diseases discussed. This prevalence is possibly determined by the pathophysiology of these disorders. These diseases are possibly characterized by genetic predispositions as well, which can hopefully be classified more accurately in the future.

Background In absence of a positive family history, the diagnosis of fatal familial insomnia (FFI) might be difficult because of atypical clinical features and low sensitivity of diagnostic tests. FFI patients usually do not fulfil the established classification criteria for Creutzfeldt-Jakob disease (CJD); therefore, a prion disease is not always suspected.Objective To propose an update of diagnostic pathway for the identification of patients for the analysis of D178-M129 mutation.Design and methods Data on 41 German FFI patients were analysed. Clinical symptoms and signs, MRI, PET, SPECT, polysomnography, EEG and cerebrospinal fluid biomarkers were studied.Results An algorithm was developed which correctly identified at least 81% of patients with the FFI diagnosis during early disease stages. It is based on the detection of organic sleep disturbances, either verified clinically or by a polysomnography, and a combination of vegetative and focal neurological signs and symptoms. Specificity of the approach was tested on three cohorts of patients (MM1 sporadic CJD patients, non-selected sporadic CJD and other neurodegenerative diseases).Conclusions The proposed scheme may help to improve the clinical diagnosis of FFI. As the sensitivity of all diagnostic tests investigated but polysomnography is low in FFI, detailed clinical investigation is of special importance.

Results: Compared with classical sporadic CreutzfeldtJakob disease, the disease duration was prolonged (median, 14 months). All patients had dementia and early and prominent neuropsychological signs such as spatial disorientation, aphasia, or apraxia. Alzheimer disease was the most frequent initial diagnosis (33%). Increased S100B protein in the cerebrospinal fluid was found in 100%; the 14-3-3 protein test was positive in 91%. Electroencephalograms revealed periodic sharp wave complexes in 42%. T2-weighted magnetic resonance imaging showed basal ganglia hyperintensities in only 1 patient, and cortical hyperintensities were not necessarily present. Severe cortical damage was the most prominent histological feature.

Background: Recently, six molecular subtypes of sporadic CJD ( sCJD) have been identified showing differences regarding the disease course, neuropathologic lesion patterns, and sensitivity to diagnostic tools. Only isolated cases of the rare VV1 type have been reported so far. Objective: To describe the clinical characteristics and neuropathologic lesion profiles in nine cases.Methods: In the years 1993 until late 2003, 571 definite neuropathologically confirmed cases of sporadic CJD were identified in Germany. Of these, nine were homozygous for valine and displayed type 1 of the pathologic PrPSc in the brain ( VV1 type).Results: The authors describe eight men and one woman belonging to the VV1 type. All patients were relatively young at disease onset ( median 44 years vs 65 years in all sCJD) with prolonged disease duration ( median 21 months vs 6 months in all sCJD). During the initial stages, their main clinical signs were personality changes and slowly progressive dementia as well as focal neurologic deficits. None of the nine VV1 patients had periodic sharp- wave complexes ( PSWCs) in the EEG. Only two out of seven displayed the typical signal increase of the basal ganglia on MRI, whereas signal increase of the cortex was seen in all patients. The 14- 3- 3 protein levels were elevated in CSF in all cases tested.Conclusions: The clinical diagnosis of the VV1 type of sCJD can be best supported by the 14- 3- 3 test and cortical signal increase on MRI. Because of the young age at onset vCJD is sometimes suspected as a differential diagnosis. MRI plays an important role in differentiating these two disease types and should be performed early during the disease course.

Sporadic Creutzfeldt–Jakob disease (sCJD) is a rare neurodegenerative disease with the greatest incidence occurring in patients between 60 and 70 years old. Younger patients may also be affected. In this study, we used all case material available from 52 patients with sCJD aged 50 years or younger at disease onset, who were identified between 1993 and 2003 in Germany. The objective of this study was to describe the psychiatric and neurological features of these young patients with emphasis on the different codon 129 genotypes and PrP types, and to compare them with elder patients with sCJD and patients with variant CJD. We also gave particular attention to electroencephalogram, magnetic resonance imaging, and 14‐3‐3 results, as well as to the neuropathological lesion profile. The clinical syndrome in young patients differs from elder patients with CJD with respect to clinical signs, disease duration, technical investigations, and neuropathological lesion profile. The psychiatric symptoms in young patients with sCJD are similar to the psychiatric symptoms expressed by patients with variant CJD; however, in contrast with the variant cases, young patients with sCJD experience development of prominent dementia early in the disease course. Ann Neurol 2005

Background: Creutzfeldt-Jakob disease (CJD) is a rare and fatal disease caused by prions. Recently, 6 molecular subtypes of sporadic CJD (sCJD) have been identified showing differences regarding the disease course, neuropathological lesion patterns and sensitivity to diagnostic tools. In the literature, only isolated cases of the rare VV1 subtype have been reported so far. We describe the clinical characteristics and neuropathological lesion profiles in 9 of our cases and review the literature on former VV1 case reports.

Background: Recently, six molecular subtypes of sporadic CJD (sCJD) have been identified showing differences regarding the disease course, neuropathologic lesion patterns, and sensitivity to diagnostic tools. Only isolated cases of the rare VV1 type have been reported so far. Objective: To describe the clinical characteristics and neuropathologic lesion profiles in nine cases. Methods: In the years 1993 until late 2003, 571 definite neuropathologically confirmed cases of sporadic CJD were identified in Germany. Of these, nine were homozygous for valine and displayed type 1 of the pathologic PrPSc in the brain (VV1 type). Results: The authors describe eight men and one woman belonging to the VV1 type. All patients were relatively young at disease onset (median 44 years vs 65 years in all sCJD) with prolonged disease duration (median 21 months vs 6 months in all sCJD). During the initial stages, their main clinical signs were personality changes and slowly progressive dementia as well as focal neurologic deficits. None of the nine VV1 patients had periodic sharp-wave complexes (PSWCs) in the EEG. Only two out of seven displayed the typical signal increase of the basal ganglia on MRI, whereas signal increase of the cortex was seen in all patients. The 14-3-3 protein levels were elevated in CSF in all cases tested. Conclusions: The clinical diagnosis of the VV1 type of sCJD can be best supported by the 14-3-3 test and cortical signal increase on MRI. Because of the young age at onset vCJD is sometimes suspected as a differential diagnosis. MRI plays an important role in differentiating these two disease types and should be performed early during the disease course.

Introduction: Psychiatric symptoms are regarded as a main and early feature of the new variant of Creutzfeldt-Jakob disease (vCJD). In contrast, few studies address psychiatric findings in sporadic Creutzfeldt-Jakob disease (CJD). Methods: We present two studies with 50 autopsy-proven (definite) and 49 probable cases of sporadic CJD assessing 12 psychiatric symptoms along with clinical data as well as genetic polymorphisms. In 72 of these patients (definite: 39; probable: 33) the evaluation was based on medical records held in the CJD Surveillance Unit at the University of Goettingen. 27 patients (definite: 11; probable: 16) were investigated by interviewing their relatives with the Neuropsychiatric Inventory. Results and conclusions: Our findings provide a detailed description of the psychopathology in the course of sporadic CJD compared to other dementias like Alzheimer`s disease, Lewy body dementia and dementia with Parkinson`s disease. Correlations between the different psychiatric symptoms and other clinical features such as age at onset, duration of illness and neurological symptoms are presented. The results elucidate the questions whether specific psychiatric symptoms in sporadic CJD could be related to genotype and gender or may be useful in the differential diagnosis of the disease.

Background In neurodegenerative diseases, increasing attention has been focused on inflammatory mediators such as pro-inflammatory and anti-inflammatory cytokines and their potential influence in the process of neurodegeneration. In prion diseases, much data has been gained on the cell culture and animal disease models level, but only limited information is available on humans affected by Creutzfeldt-Jakob disease (CJD). Objective To obtain data on anti-inflammatory cytokines interleukin 4 and interleukin 10 in the cerebrospinal fluid of patients with CJD, patients with other dementia, and nondemented neurological patients and controls. Design Cerebrospinal fluid samples were collected from CJD patients and control subjects, and concentrations of the anti-inflammatory cytokines interleukin 4 and interleukin 10 were determined using an enzyme-linked immunosorbent assay. Patients Cerebrospinal fluid samples from 61 patients were analyzed. The group was composed of patients with CJD (n = 20), patients with other forms of dementia (n = 10), patients with motoneuron disease (n = 6), patients with normal pressure hydrocephalus (n = 5), and control subjects (n = 20). Results Interleukin 10 levels were significantly elevated in the cerebrospinal fluid of CJD patients (median, 9.8 pg/mL). The elevation was significant to other dementia (median, 7.9 pg/mL,P<.05), motoneuron disease (median, 7.9 pg/mL,P<.05), normal pressure hydrocephalus (median, 7.0 pg/mL,P<.05), and controls (median, 1.3 pg/mL,P<.001). Levels of interleukin 4 were significantly elevated in cerebrospinal fluid of patients with CJD (median, 26.4 pg/mL) compared with control subjects (median, 6.2 pg/mL,P<.001) and patients with a motoneuron disease (median, 10.5 pg/mL,P<.001) Conclusions Elevated levels of the anti-inflammatory cytokines interleukin 4 and interleukin 10 in cerebrospinal fluid of patients with CJD are new findings. The data of the present study provide a clue toward the possible role of cytokines as immunological modifiers in the neurodegenerative process of CJD.