Atypical Huntington's disease with the clinical presentation of behavioural variant of frontotemporal dementia.

Huntington's disease is an incurable, adult-onset, autosomal dominant inherited disorder caused by an expanded trinucleotide repeat (CAG). In this study, we describe a Huntington's disease patient displaying clinical symptoms of the behavioural variant of frontotemporal dementia in the absence of tremor and ataxia. The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeats in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid ß (Aß) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. Confocal microscopy revealed that the majority of p62 intranuclear lesions co-localised with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington's disease. The presented proband suffered from Huntington's disease showed atypical distribution of FUS positive intranuclear aggregates in the cortical areas with concomitant Alzheimer's disease pathology.

Multi-infarct dementia and Alzheimer disease, contribution of cerebral circulation ultrasonography to pathogenesis and differential diagnosis. Value of microembolisation.

OBJECTIVES: Dementias are one of the most serious health and socioeconomic issues. Multi-infarct dementia (MID) and Alzheimer´s type dementia (AD) exhibit differences in cerebrovascular blood flow velocity profiles and in presence of microemboli, detected by transcranial Doppler sonography. MATERIAL AND METHODS: A group of 77 persons was divided into 4 subgroups: 1. subgroup of patients with MID (n=19; 10 male and 9 female, mean age was 74.32±8.30 years); 2. subgroup of patients with AD (n=19; 11 male and 8 female, mean age was 70.37±87.85 years); 3. subgroup of patients with hypertension (n=19; 11 male and 8 female, age adjusted) and 4. sex and age adjusted control group (CG) of 20 persons without hypertension or other serious risk factors. The duplex ultrasonographic examination of extracranial and intracranial circulation was preceded by neurologic, neuropsychological and psychiatric examination. The presence of microemboli was determined using Multi Dop X2 device (maker DWL), 60 minutes monitoring. All patients underwent brain computer tomography (CT) or magnetic resonance imaging (MRI). RESULTS: We found significantly higher incidence (68.4%, p=0.5267) of asymptomatic microemboli in ACM in the group of patients with MID compared to the AD group, the group of patients with hypertension and CG. CONCLUSION: The occurrence of "asymptomatic" emboli in the middle cerebral artery in patients with multi-infarct dementia is higher in the current study. Although these microemboli do not cause immediate symptoms, the evidence suggests, that they may be a risk factor for cognitive impairment, especially for multi-infarct dementia.

Impairment of endothelial function in patients with multiple sclerosis.

OBJECTIVE: Large epidemiological studies suggest higher risk of vascular events in patients with multiple sclerosis (MS). Chronic inflammatory response and oxidative stress, key-players in a process of atherogenesis, are also suspected to play a role in pathophysiology of MS. Prospective studies elucidating risk of atherosclerosis in MS patients are currently missing. The aim of the study was to assess endothelial function in patients with MS and in healthy controls. METHODS: We enrolled 46 patients with diagnosis of relapsing-remitting MS and age-matched population of 31 healthy subjects. Endothelial function was assessed using peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). RESULTS: RHI in MS population was significantly lower than in controls (1.77 vs 2.30; p=0.001), even though control population seemed to have higher burden of known vascular risk factors (significantly higher portion of male sex and significantly higher body mass index; p ≤ 0.001 for both parameters). The presence of MS was the only significant independent variable associated with the RHI (beta=0.396, p<0.001) in multiple linear regression model. CONCLUSION: Results of our study suggest significant impairment of endothelial function in MS population compared to age matched control population with low burden of vascular risk factors.

Impairment of endothelial function in Parkinson's disease.

OBJECTIVE: There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function in patients with PD and matched controls. In PD subjects, we searched for factors contributing to endothelial dysfunction as well. Traditional vascular risk factors, PD characteristics, and PD medication were considered. RESULTS: We prospectively enrolled 41 patients with PD and 41 controls matched for age, sex, body mass index, and vascular risk factors. Endothelial function (EF) was assessed using peripheral arterial tonometry (EndoPAT 2000 device) and expressed as reperfusion hyperemia index (RHI). Clinical characteristics including PD medication were recorded. RHI was non-significantly lower in the PD group than in controls (1.8 ± 0.5 vs. 1.9 ± 0.5, p = 0.478). In PD patients, in linear regression analysis, smoking (beta = -0.453, p = 0.008) and use of dopamine agonists (beta = -0.365, p = 0.030) were significant contributors in a model predicting RHI. Despite non-significant differences in endothelial dysfunction between PD patients and controls, our results suggest an association between smoking, dopamine agonists, and impaired EF in PD patients. The small sample size, as well as the absence of an extended search for traditional and non-traditional vascular risk factors, are the most important factors limiting the interpretation of the current results.

Decreased baroreflex sensitivity in Parkinson's disease is associated with orthostatic hypotension.

BACKGROUND: Autonomic dysfunction is a substantial part of extrapyramidal diseases, including Parkinson's disease (PD). Baroreflex is an important determinant of short-term blood pressure regulation and cardiovascular variability. Impaired baroreflex sensitivity (BRS) in PD has been a subject of investigation in several studies, however the relationship between BRS and orthostatic hypotension (OH) is still poorly understood. OBJECTIVE: To compare the BRS of Parkinson's disease patients with those of an age-matched control population, and to determine BRS association with blood pressure, orthostatic hypotension and antiparkinson treatment. PATIENTS AND METHODS: The study included 52 patients with Parkinson's disease and 52 controls. We assessed autonomic dysfunction with a Finometer device using the method of spontaneous fluctuations of blood pressure (BP) and the R-R interval in time domain, expressed as baroreflex sensitivity. Supine and standing blood pressure were measured under standard conditions. RESULTS: BRS values were significantly lower in the PD group as compared to the control group: 4.0±2.0 vs. 6.4±3.8ms/mmHg (p=0.001). We determined a significant correlation between decreased BRS values and increased systolic BP (p=0.003) as well as between decreased BRS values and orthostatic hypotension (OH), in the PD group (p=0.048). Moreover, patients with PD and OH had significantly lower BRS as compared with patients with PD without OH (3.2±2 versus 4.5±2, p=0.045). We also determined that BRS values were significantly lower in the PD population treated with LDOPA+COMTI as compared to the LDOPA+COMTI untreated patients (3.0±1.5 vs. 4.8±2.0, p<0.001). CONCLUSION: BRS was significantly lower in the PD group, supine hypertension and orthostatic hypotension was strongly associated with low BRS. We determined for the first time that orthostatic hypotension strongly correlates with decreased baroreflex sensitivity in PD patients. Moreover, orthostatic hypotension was associated with low BRS not only qualitatively but also quantitatively. We also revealed a strong association between LDOPA+COMTI therapy and decreased BRS in the literature for the first time.