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Objective: The epsilon4 allele of the apolipoprotein E (ApoE) gene has been defined as a critical factor for early onset neurodegeneration in Pick's, Parkinson's, and Alzheimer's disease. Unexpectedly, the epsilon4 allele appeared to delay the age of onset in Huntington's disease (HD) patients. Furthermore, sex specific effects were reported on earlier age of onset due to the ApoE epsilon2epsilon3 genotype in males with HD. The age of onset of HD is known to be negatively correlated with increasing lengths of pathogenetic CAG expansions in the huntingtin gene.Methods: In order to examine the effects of CAG block lengths, we have correlated ApoE genotypes with the age of onset in 145 patients symptomatic for HD with psychiatric and somatic symptoms (depression, psychosis, dementia, choreic, and other movement disorders) harbouring only modestly expanded huntingtin alleles (41-45 CAGs).Results: The negative correlation between age of onset and CAG block length was established in our HD cohort. Statistically significant effects of the epsilon4 allele were not obvious regarding clinical characteristics including age of onset, nor were any sex differences for the epsilon2epsilon3 genotype observed.Conclusion: The ApoE genotype does not affect the course of HD significantly. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether Huntington's disease (HD) affects autonomic nervous system (ANS) functioning.Methods: Twenty patients with HD who had positive genetic test results underwent standardised ANS function tests including sympathetic skin responses (SSRs) of the hands and feet, measurements of heart rate variability (HRV), both during five minutes of resting and deep respiration, and an orthostatic blood pressure test. Patients were classified according to the motor subscale of the unified Huntington's disease rating scale (UHDRS; mean (SD) score 26.4 (13.6)) and divided into two subgroups: UHDRS <25 points (early stages, E-HD) and UHDRS > or =25 points (mid stages, M-HD). Autonomic indices were compared with those obtained for a group of well matched healthy controls (n=60).Results: Overall, patients showed lower HRV indices than controls. Multivariate analysis with the independent factor of "group" (controls, E-HD, M-HD) showed a significant group effect on both the high frequency power (F=4.32, p=0.017) and the coefficient of variation (F=4.23, p=0.018), indicating a significant reduction in vagal modulation in the M-HD group. There was a shift in autonomic neurocardiac balance towards sympathetic predominance in the M-HD group compared with controls (F=2.89, p=0.062). Moreover, we found an inverse correlation between the severity of clinical HD symptoms (assessed by the UHDRS) and the modulation of cardiovagal activity (p=0.028). Vagal dysregulation was present in two patients; one of them also showed a pathological blood pressure test and a latency prolongation in the SSRs of the hands. Two other patients had pathologically reduced SSR amplitudes. Only patients of the M-HD group were affected.Conclusion: Autonomic dysfunction is present even in the middle stages of HD and affects both the sympathetic and parasympathetic branch of the ANS. [ABSTRACT FROM AUTHOR]

Objectives and Methods: Transcranial real time sonography (TCS) was applied to 49 patients with Huntington's disease and 39 control subjects to visualise alterations in the echotexture of the basal ganglia. For comparison T1 weighted, T2 weighted, and fast spin echo MRI was performed in 12 patients with Huntington's disease with and in nine patients without alterations of the basal ganglia echotexture as detected by TCS and T1 weighted, T2 weighted, and fast spin echo MRI. Furthermore, the widths of the frontal horns, third ventricle, and the lateral ventricles were depicted in TCS examinations and correlations examined with corresponding CT slices.Results: Eighteen out of 45 (40%) of the patients with Huntington's disease with adequate insonation conditions showed hyperechogenic lesions of at least one basal ganglia region. In 12 patients TCS depicted hyperechogenic lesions of the substantia nigra; in six patients the head of the caudate nucleus was affected. The lentiform nucleus (n=3) and the thalamus (n=0) were less often affected or spared. Hyperechogenic lesions were significantly more frequent in patients with Huntington's disease than in 39 control subjects, who had alterations of the echotexture in 12.8% (4/39) of the examinations. The number of CAG repeats and the clinical status correlated with the identification of hyperechogenic lesions of the substantia nigra (p<0.01). Hyperechogenic lesions of the caudate nucleus were associated with an increased signal intensity in T2 weighted MR images (p<0.05). All TCS parameters indicating brain atrophy correlated with CT findings (p<0.0001).Conclusions: TCS detects primarily abnormalities of the caudate nucleus and substantia nigra in Huntington's disease. These changes in the echotexture may represent degenerative changes in the basal ganglia matrix and are partially associated with CAG repeat expansion and the severity of clinical findings. [ABSTRACT FROM AUTHOR]

Objective: The ϵ4 allele of the apolipoprotein E (ApoE) gene has been defined as a critical factor for early onset neurodegeneration in Pick's, Parkinson's, and Alzheimer's disease. Unexpectedly, the ϵ4 allele appeared to delay the age of onset in Huntington's disease (HD) patients. Furthermore, sex specific effects were reported on earlier age of onset due to the ApoE ϵ2ϵ3 genotype in males with HD. The age of onset of HD is known to be negatively correlated with increasing lengths of pathogenetic CAG expansions in the huntingtin gene. Methods: In order to examine the effects of CAG block lengths, we have correlated ApoE genotypes with the age of onset in 145 patients symptomatic for HD with psychiatric and somatic symptoms (depression, psychosis, dementia, choreic, and other movement disorders) harbouring only modestly expanded huntingtin alleles (41-45 CAGs). Results: The negative correlation between age of onset and CAG block length was established in our HD cohort. Statistically significant effects of the ϵ4 allele were not obvious regarding clinical characteristics including age of onset, nor were any sex differences for the ϵ2ϵ3 genolype observed. Conclusion: The ApoE genotype does not affect the course of HD significantly. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of transient response second harmonic imaging (HI) by means of ultrasound to assess abnormalities of cerebral echo contrast agent enhancement in patients with acute stroke.Methods: The study comprised 25 patients with acute onset of hemispheric stroke (<24 h) with sufficient insonation conditions and 14 control subjects without cerebrovascular disease. All stroke patients had HI, extracranial and transcranial colour coded duplex examinations of the arteries supplying the brain, and clinical examinations (European stroke scale) performed in the acute phase, on day 2, and within 1 week. Acute CT was repeated within 1 week and facultatively accompanied by angiography. Examinations using HI were performed in an axial diencephalic plane of section using the transtemporal acoustic bone window. After bolus application of galactose based microbubbles, 61 ultrasound images with a cardiac cycling triggering frequency of once every 2 seconds were recorded and evaluated off line. Focal perfusion deficit was identified if no contrast enhancement was visualised in a circumscribed region of interest and insufficient temporal bone window was excluded. In cases of reappearance of contrast enhancement reperfusion was assessed.Results: Adequate cerebral contrast enhancement could be seen in 21 subjects. In seven, a large hemispheric deficit of contrast enhancement affecting the entire middle cerebral artery (MCA) territory was detectable; the lentiform nucleus was affected in three subjects. Assessment of cerebral contrast abnormalities was possible in two patients with superficial MCA infarctions but in none of the patients with lacunar ischaemias. None of the control persons had focal deficits of cerebral echo contrast enhancement. In all patients with complete MCA infarction and striatocapsular infarction, presumed ischaemic areas in HI examinations correlated with final CT findings. Overall sensitivity and specifity of HI examinations for predicting size and localisation of the infarction were 75 and 100%, respectively. During follow up, reappearance of contrast enhancement was determined in three patients, in two patients circulatory arrest due to malignant brain oedema with missing contrast enhancement in the entire cerebral hemisphere could be seen. Extent of contrast enhancement deficits significantly correlated with the clinical status on admission and after 1 week (p<0.01).Conclusions: Second harmonic imaging is the first ultrasonic technique that enables visualisation of pathological cerebral echo contrast enhancement. Because this method identifies deficits of focal contrast enhancement in patients with acute stroke and allows estimation of the final infarct size and clinical prognosis, it may help to select and monitor patients for invasive therapies. [ABSTRACT FROM AUTHOR]

Objective: Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia (ADCA) of which the mutation causing the disease has recently been characterised as an expanded CAG trinucleotide repeat in the gene coding for the alpha1A-subunit of the voltage dependent calcium channel. The aim was to further characterise the SCA6 phenotypeMethods: The SCA6 mutation was investigated in 69 German families with ADCA and 61 patients with idiopathic sporadic cerebellar ataxia and the CAG repeat length of the expanded allele was correlated with the disease phenotype.Results: Expanded alleles were found in nine of 69 families as well as in four patients with sporadic disease. Disease onset ranged from 30 to 71 years of age and was significantly later than in other forms of ADCA. Age at onset correlated inversely with repeat length. The SCA6 phenotype comprises predominantly cerebellar signs in concordance with isolated cerebellar atrophy on MRI. Non-cerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Neither these clinical signs nor progression rate correlated with CAG repeat length.Conclusions: This study provides the first detailed characterisation of the SCA6 phenotype. Clinical features apart from cerebellar signs were highly variable in patients with SCA6. By comparison with SCA1, SCA2, and SCA3 no clinical or electrophysiological finding was specific for SCA6. Therefore, the molecular defect cannot be predicted from clinical investigations. In Germany, SCA6 accounts for about 13% of families with ADCA. However, up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadic disease due to late manifestation in apparently healthy parents. Genetic testing is therefore recommended for the SCA6 mutation also in patients with putative sporadic ataxia. [ABSTRACT FROM AUTHOR]

Objective: Machado-Joseph disease (MJD) is an autosomal dominant cerebellar ataxia with extensive phenotypic variability originally described in families of Portuguese ancestry. Recently, the mutation causing the disease has been identified as an expanded CAG trinucleotide repeat. In this study relations between genotype and phenotype were investigated.Methods: A series of 180 German patients with degenerative forms of ataxia were clinically and genetically examined. Patients bearing the MJD mutation were assigned to three phenotypes: phenotype 1 characterised by early onset and dystonia or pronounced rigidity associated with ataxia and spasticity. Main symptoms in phenotype 2 were ataxia and spasticity. In phenotype 3 onset was relatively late and peripheral neuropathy accompanied ataxia. Clinical and molecular data were correlated.Results: An expanded CAG array was found in 42 patients from 22 families. Repeat length of CAG varied between 67 and 80 CAG motifs and showed an inverse correlation with the age of onset. For the development of phenotype 1 early onset (< 20 years) seemed more decisive than extensive repeat length. Phenotype 2 was present in all patients with more than 73 CAG motifs and onset between 20 and 40. Phenotype 3 developed in most patients with less than 73 CAG motifs and onset was regularly beyond the age of 40. Intrafamilial variability of both repeat length and phenotype was large reflecting meiotic instability of the expanded CAG repeat.Conclusions: The MJD mutation is the most frequent cause of dominantly inherited ataxia in Germany. Variations in repeat lengths substantially influence age of onset as well as phenotype but cannot explain why MJD characteristics of Portuguese families such as "bulging eyes", dystonia, and rigidity are essentially missing in German families. Despite the genotypic and phenotypic relations found in this study a reliable individual prognosis of the course of the disease is not possible at a presymptomatic stage. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether electroconvulsive therapy (ECT) induces brain tissue damage expressed as an increase in neuron specific enolase and protein S-100.Methods: A total of 179 serial measurements of S-100 and NSE serum concentrations were performed on 14 patients during the course of a bilaterally stimulated ECT series. Cognitive performance was assessed by psychometric testing carried out on the day before the start of ECT as well as on the days after the third, sixth, and last ECT. Pre-ECT and post-ECT concentrations of NSE and S-100 were compared by non-parametric tests.Results: On average, 9.5 (SD 2.9) (range 3-12) ECTs were applied; 13 of 14 patients received at least six ECTs. The average duration of convulsion (computed for all ECTs) was 29.0 (SD 10.5) seconds. At no point during the ECT series was there a significant increase in the average NSE or S-100 concentrations compared with the baseline investigation before the start of the ECT series. The maximal measured post-ECT values of NSE and S-100 were 26.6 ng/ml and 0.46 ng/ml, respectively. The cumulative energy doses applied, seizure durations, and ECT induced changes in cognitive performance scores were never significantly correlated with the NSE or S-100 serum concentrations.Conclusion: This pattern of findings suggests that a modern ECT, fulfilling current quality standards, induces no brain tissue damage detectable by changes in NSE or protein S-100. [ABSTRACT FROM AUTHOR]

Ten hours after onset of an anterior spinal artery syndrome (ASAS) F-waves could not be obtained from the paralysed left hand muscles. F-waves in the right hand were present and motor nerve conduction studies were normal on both sides. One week later paralysis of the right hand together with paraparesis occurred. Two days later F-waves from the right hand had disappeared. Three weeks later MRI confirmed the diagnosis of ischaemic spinal cord infarction. [ABSTRACT FROM AUTHOR]

A neurogenic bladder is seldom described as the first manifestation of syringomyelia. A patient is reported with an extensive syrinx along the entire spinal cord and a Chiari type I malformation, who experienced dysaesthesia and weakness during shooting practice and presented with urinary retention. [ABSTRACT FROM AUTHOR]