Cardiovagal modulation upon postural change is altered in Huntington's disease.

BACKGROUND: Cardiac autonomic nervous system (ANS) dysfunction in Huntington's disease (HD) might affect both the sympathetic and parasympathetic branch of the ANS. RESULTS AND CONCLUSIONS: The pattern of linear heart rate variability we found in mid stage HD patients points towards a predominately reduced cardiovagal modulation compared with healthy subjects, which might influence HD patients' susceptibility for cardiovascular complications such as syncopes and cardiac arrhythmias.

Chronic subdural haematoma in patients with Huntington's disease.

We studied the frequency of patients who had chronic subdural haematomas (CSDH) and Huntington's disease (HD) in a 1-year study period. In our department a total of 58 patients with CSDH were treated. Four patients (6.9% of them) had HD. Surgical evacuation of the haematoma was performed in all four cases with the use of a twist drill trepanation without a drainage system.

[Segmental dysfunction of sweating in multiple system atrophy]. / Segmentale Schweisssekretionsstörung bei Multisystematrophie.

There are many different causes of anhidrosis. Sweat glands can be absent, atrophic or blocked; sympathetic innervation may be disturbed, or central nervous system damage may prevent perspiration. We present a patient with multiple system atrophy ( MSA) who presented with unilateral anhidrosis of the trunk. MSA is a sporadic neurodegenerative disorder of adults involving the pyramidal, extrapyramidal, cerebellar and/or autonomic system. The findings in our patient could be explained by a depletion of catecholaminergic sympathetic neurons of the thoracic spinal neurons.

Apolipoprotein E genotypes do not influence the age of onset in Huntington's disease.

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.

Methyltetrahydrofolate reductase polymorphism influences onset of Huntington's disease.

Onset of Huntington's disease (HD) negatively correlates with CAG repeat length of the HD gene, which encodes the protein huntingtin. This protein interacts with the homocysteine metabolizing enzyme cystathionine betasynthase (CBS). Objective of this study was to analyze the impact of CAG repeats, polymorphisms of various homocysteine metabolizing enzymes, like CBS, Methyltetrahydrofolate Reductase (MTHTR), Methionine Synthase Reductase (MSR) and methionine synthase (MS) on HD onset in 171 patients. The significant impact of CAG repeats on HD onset (chi2= 25.54, FG = 4, p<0.0001) with a significant correlation between both (R= -0.521, p=0.01) was obvious. HD patients with the homozygous MTHFR-1298-CC significantly (p = 0.024) earlier experienced HD symptoms. There was no influence demonstrable of CBS, MSR and MS. Determination of MTHFR polymorphisms and CAG repeats enables screening for subjects with putative early HD onset in order to study neuroprotective compounds in their efficacy to delay HD symptoms.

Congruent deterioration of complex and simple movements in patients with Huntington's disease.

Rating scales and assessment of simple and complex movements may reflect severity of Huntington's disease (HD). Objectives of our study were to compare scored HD symptoms and outcomes of instrumental tests, which demand for simple (tapping) and complex (peg insertion) movement series, in controls and subjects in various HD stages and to correlate them to each other. Motor test outcomes were significantly worsened in previously untreated and treated HD patients in comparison with HD gene carriers and controls. Peg insertion- and tapping results significantly correlated with the scored HD symptoms. Significant associations appeared between both motor test results in the controls, the previously untreated- and treated HD patients. Results of both instrumental tasks represent no specific diagnostic marker of HD, but the significant associations between both motor test outcomes indicate, that a parallel progress of deterioration of complex and simple movement abilities occurs after start of HD.

Coenzyme Q10 serum levels in Huntington's disease.

Mitochondrial dysfunction contributes to the neurodegenerative process in Huntington's disease (HD). Coenzyme Q10 (CoQ10) enhances mitochondrial complex I activity and may therefore provide a therapeutic benefit in HD. We compared serum CoQ10 levels of previously untreated-and treated HD patients with those of healthy controls. CoQ10 did not significantly (ANCOVA F(dF 2, dF 55) = 2.57; p=0.086) differ between all three groups. However, the post hoc analysis showed no significant (p = 0.4) difference between treated HD patients ([CoQ10]: 88.12 [mean]+/-24.44 [SD], [range] 48.75-146.32 [pg/million platelets]) and controls (93.71+/-20.72, 65.31-157.94), however previously untreated HD patients (70.10+/-21.12, 38.67-106.14) had marked (p = 0.051) lower CoQ10 results than treated HD patients and controls (p = 0.017). Our results support that CoQ10 supplementation in HD patients may reduce impaired mitochondrial function in HD.

Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study.

OBJECTIVES: To analyse grey matter changes in early stages of Huntington's disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM). METHODS: Forty four patients with a molecularly confirmed clinical diagnosis of Huntington's disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington's Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II). High resolution volume rendering MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analysed in comparison to an age matched normal database by VBM, using statistical parametric mapping (SPM99). RESULTS: In Huntington's disease, robust regional decreases in grey matter density (p<0.001, corrected for multiple comparisons)-that is, atrophy-were found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule. The topography of striatal changes corresponded to the dorso-ventral gradient of neuronal loss described in neuropathological studies. Stratification according to clinical severity showed a more widespread involvement extending into the ventral aspects of the striatum in the group of more severely affected patients. CONCLUSIONS: The topography of cerebral volume changes associated with Huntington's disease can be mapped using VBM. It can be shown that cerebral grey matter changes co-vary with clinical severity and CAG repeat length.

Autonomic nervous system function in Huntington's disease.

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.

Relation between electroconvulsive therapy, cognitive side effects, neuron specific enolase, and protein S-100.

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.

Implant-supported denture in a patient with Huntington's disease: interdisciplinary aspects.

Patients with extrapyramidal diseases often cannot maintain independent, efficient oral hygiene due to restricted motor ability of the upper extremities and lack of coordination. The hermetic closure of the mouth and lips, and the associated ability to keep liquid and toothpaste in the mouth, can become so weak that effective oral hygiene cannot be maintained. Over a period of many years, this illness leads to loss of teeth and the need for complete prosthodontic care. Dyskinesia and hyperkinesia of the tongue and the peri-oral musculature, combined with xerostomia and pooling of saliva, make it impossible for the patient to wear a conventional complete denture, despite an anatomically-adequate bearing area. In such cases, an implant-supported prosthesis is a better therapeutic measure, although some aspects of oral hygiene must initially be disregarded. Two ITI implants were inserted into the anterior mandibular region of a patient with Huntington's chorea, because a complete denture could not be retained on the alveolar ridge, despite adequate vestibule depth, due to tongue dyskinesia. A bar joint was used to anchor this mucosal-borne denture. This implant-supported complete denture led to a clear improvement in the patient's chewing function when observed over a period of a year.

Basal ganglia alterations and brain atrophy in Huntington's disease depicted by transcranial real time sonography.

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.