Aging affects the phase coherence between spontaneous oscillations in brain oxygenation and neural activity.

The risk of neurodegenerative disorders increases with age, due to reduced vascular nutrition and impaired neural function. However, the interactions between cardiovascular dynamics and neural activity, and how these interactions evolve in healthy aging, are not well understood. Here, the interactions are studied by assessment of the phase coherence between spontaneous oscillations in cerebral oxygenation measured by fNIRS, the electrical activity of the brain measured by EEG, and cardiovascular functions extracted from ECG and respiration effort, all simultaneously recorded. Signals measured at rest in 21 younger participants (31.1 ± 6.9 years) and 24 older participants (64.9 ± 6.9 years) were analysed by wavelet transform, wavelet phase coherence and ridge extraction for frequencies between 0.007 and 4 Hz. Coherence between the neural and oxygenation oscillations at ∼ 0.1 Hz is significantly reduced in the older adults in 46/176 fNIRS-EEG probe combinations. This reduction in coherence cannot be accounted for in terms of reduced power, thus indicating that neurovascular interactions change with age. The approach presented promises a noninvasive means of evaluating the efficiency of the neurovascular unit in aging and disease.

Early isolated subarachnoid hemorrhage versus hemorrhagic infarction in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare cerebral vascular disease, the presentation of which is highly variable clinically and radiologically. A recent study demonstrated that isolated subarachnoid hemorrhage (iSAH) in CVT is not as rare as thought previously and may have a good prognostic significance. Hemorrhagic venous infarction, however, is an indicator of an unfavorable outcome. We therefore hypothesized that patients who initially suffered iSAH would have a better clinical outcome than those who suffered hemorrhagic cerebral infarction. PATIENTS AND METHODS: We selected patients hospitalized due to CVT, who presented either with isolated SAH or cerebral hemorrhagic infarction at admission or during the following 24 hours: 23 (10 men) aged 22-73 years. The data were extracted from hospital admission records, our computer data system, and the hospital radiological database. RESULTS: The iSAH group consisted of 8 (6 men) aged 49.3 ± 16.2 and the hemorrhagic infarction group included 15 (4 men) aged 47.9 ± 16.8. Despite having a significantly greater number of thrombosed venous sinuses/deep veins (Mann-Whitney Rank Sum Test, p = 0.002), the isolated SAH group had a significantly better outcome on its modified Rankin Score (mRs) than the hemorrhagic infarction group (Mann-Whitney Rank Sum Test, p = 0.026). Additional variables of significant impact were edema formation (p = 0.004) and sulcal obliteration (p = 0.014). CONCLUSIONS: The patients who suffer iSAH initially had a significantly better outcome prognosis than the hemorrhagic infarction patients, despite the greater number of thrombosed sinuses/veins in the iSAH group. A possible explanation might include patent superficial cerebral communicating veins.

Heart Rate Variability in Huntington Disease: A Long-Term Longitudinal Study.

INTRODUCTION: The aim of the study was to follow tonic and phasic autonomic nervous activity in Huntington disease (HD) mutation carriers and patients. METHODS: Evaluation of motor functions and total functional capacity was performed in 30 HD mutation carriers or patients at the beginning and in 22 subjects after 8-10 years. Continuous arterial blood pressure, heart rate (HR), and ECG at rest were measured, and HR variability analysis was performed in four different ways. A group of matched controls was also evaluated. RESULTS: Eighteen subjects were assorted in 3 groups: 6 HD mutation carriers without motor symptoms (PHD) who remained so (PHD-PHD); 6 early symptomatic patients (EHD) who remained so (EHD-EHD); and 6 early symptomatic patients who deteriorated to a late symptomatic (LHD) (EHD-LHD). At the beginning, sympathetic tonic activity in PHD was elevated, according to mean arterial pressure (99 ± 10.6 mm Hg) higher than in controls (85 ± 8.7 mm Hg) and EHD (82 ± 9.9 mm Hg) (Dunnett's test, p < 0.05) and higher HR (78 ± 16 beats/min) than after 8-10 years (64 ± 11.3 beats/min) (paired t test, p < 0.05). There was also a decreased phasic sympathetic activity in EHD patients compared controls at the beginning (219 ± 106 vs. 664 ± 466 s2/Hz) and after 8-10 years (182 ± 136 vs. 1,012 ± 1,369 s2/Hz) (Dunnett's test, p < 0.05). In patients who deteriorated from EHD to LHD, there was a drop in phasic parasympathetic activity from 887 ± 433 to 230 ± 235 s2/Hz (paired t test, p < 0.05). CONCLUSIONS: Our long-term observational study provides important information on the timeline of ANS activity in HD progress. There was a temporary increase in cardiac and vascular sympathetic activity in PHD subjects. The normalization of HR in PHD subjects might indicate the approach of an outbreak of clinical disease phase.

Stroke and antiphospholipid syndrome-antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event.

Testing for antiphospholipid antibodies could be an important part in determining the cause of a cerebrovascular event (CVE). Currently, it is also unknown whether antiphospholipid antibodies represent a risk factor for the development of a CVE and whether the selected therapy options are efficacious. So, this study aimed at (1) determining the frequency of patients experiencing a CVE and fulfilling the laboratory criterion for an antiphospholipid syndrome (APS), (2) investigating whether the persistent presence of antiphospholipid antibodies represented a risk factor for a CVE, and (3) focusing on the efficacy of the selected treatment strategy in the first year after the CVE. Eighty-nine patients with an acute CVE were prospectively followed for 1 year. At least two sera from each were tested for lupus anticoagulants, anticardiolipin, anti-ß2-glycoprotein I, anti-phosphatidylserine/prothrombin and anti-annexin V antibodies. Twenty out of eighty-nine (22%) of CVE patients fulfilled the criteria for APS (17/20 for definitive and 3 for probable APS). There was a significant association between persistently present antiphospholipid antibodies and the CVE (OR, 4.62). No statistically significant difference was found in the CVE recurrence rate between APS-CVE and non-APS-CVE patients being treated mainly with acetyl salicylic acid. Antiphospholipid antibodies represent an independent risk factor for a CVE. In the first year after the CVE, antiplatelet therapy seemed to be sufficient in secondary CVE thromboprophylaxis in most APS patients.

Evidence of cardiac electrical remodeling in patients with Huntington disease.

OBJECTIVE: Although Huntington's disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a major cause of death. Cardiac dysfunction in HD might be a primary consequence of peripherally expressed mutant huntingtin or secondary to either a general decline in health or the onset of neurological dysfunction. The aim of the study was to clarify the heart muscle involvement. MATERIALS AND METHODS: We measured conventional and advanced resting ECG indices. Thirty-one subjects with a confirmed huntingtin gene mutation and 31 age- and gender-matched controls were included. The HD subjects were divided into four groups based on their Unified Huntington Disease Rating Scale (UHDRS) motor score. RESULTS: We detected changes in advanced ECG variables connected with electrical ventricular remodeling (t test, p < 0.01). The increase in the unexplained part of both QT variability and the standard deviation of normal-to-normal QT intervals, presumably reflecting beat-to-beat changes in repolarization, was most pronounced. Further, both variables correlated with the product of the cytosine-adenine-guanine (CAG) triplets' repeat length and the subjects' age (CAP), the former R = 0.423 (p = 0.018) and the latter R = 0.499 (p = 0.004). There was no correlation between the CAP score and any of variables representing autonomic nervous system activity. CONCLUSIONS: Both autonomic nervous system dysfunction and cardiac electrical remodeling are present in patients with HD. The changes in advanced ECG variables observed in the study evolve with HD progression. The increased values of QT unexplained variability may be a marker of temporal inhomogeneity in ventricular repolarization associated with malignant ventricular arrhythmias.

Anorectal Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington's Disease.

BACKGROUND: Huntington's disease (HD) patients often report anorectal dysfunction; however, in HD research no detailed analysis of these complaints has been published. OBJECTIVE: To report anorectal dysfunction in a systematically studied cohort of HD subjects. METHODS: In 54 HD patients (24 men) and 10 presymptomatic HD mutation carriers (2 men) and in 99 controls (44 men) a history of anal incontinence and constipation was obtained and data was compared accordingly. In HD mutation carriers a clinical neurologic assessment and in some cases anorectal manometry were performed. RESULTS: Defecation urgency was reported by 28% of our HD mutation carriers, soiling in 18% and fecal incontinence in 28%. Severe anal incontinence (solid stools) was found in 0% men / 10% women, moderate (liquid stools) in 21% / 13%, and mild (flatus only) in 67% / 47% of our HD subjects. Compared to controls, anal incontinence was significantly more common in HD subjects (p < 0.001). Severe chronic constipation was found in 4.2% men / 0.0% women, moderate in 8.3% / 0.0%, and mild in 21% / 27% of HD subjects. Constipation was more common in HD men (p = 0.02) than in HD women (p = 0.144). Anorectal dysfunction was not reported by 54% of our HD subjects. Patients reporting incontinence or constipation were significantly more depressed (r = 0.53, p = 0.001). Upon anorectal manometry reduced resting anal pressure was found in 4 of 6 HD women. CONCLUSIONS: Our study demonstrated significant bowel dysfunction in HD patients. We propose these symptoms to be of central autonomic origin, although we cannot exclude effects of medication. These often neglected symptoms in HD subjects require greater attention from physicians.

Female Sexual Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington's Disease.

BACKGROUND: Although in Huntington's disease (HD) movement, cognition, and personality are most significantly affected, autonomic dysfunction should not be neglected. In women with HD sexual dysfunction has not been adequately studied yet. OBJECTIVE: To report sexual dysfunction in a systematically studied cohort of female HD patients and compare it with controls of a similar age. METHODS: In female HD patients and presymptomatic HD mutation carriers, we compared the Female Sexual Function Index (FSFI) questionnaire, neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC). RESULTS: Of 44 female HD patients and 9 presymptomatic HD mutation carriers, 30 HD patients and 8 HD mutation carriers responded our invitation to complete FFSI questionnaire. Finally, 23 HD women with a partner were compared to 47 controls with a partner. HD patients had more problems with sexual arousal, lubrication, orgasm and sexual satisfaction. By contrast, we found no difference in sexual desire and pain. Sexual dysfunction progressed in parallel with the decline in the TFC; severe sexual dysfunction occurred with TFC <7/13. CONCLUSIONS: Our study demonstrated a significant impact of HD on female sexual function that progressed with patients' functional decline and impaired patients' quality of life. Sexual dysfunction may be caused by progression of the disease itself, side effects of medication, and comorbidities like depression or dementia.

Functional impairment of precerebral arteries in Huntington disease.

BACKGROUND: Cardiovascular pathology of Huntington disease (HD) appears to be complex; while microvascular dysfunction seems to appear early, deaths from cardiomyopathy and stroke might occur in the late phase of HD. METHODS: Our study evaluated global risk factors for coronary heart disease (CHD), structure and function of precerebral arteries in 41 HD subjects and 41 matched controls. HD subjects were divided into groups by the United Huntington disease rating scale (presymptomatic-PHD, early-EHD, midstage-MHD and late-LHD). CHD risk factors assessment and Doppler examination of precerebral arteries were performed, including measurements of the carotid artery intima-media thickness (IMT), and parameters indicating local carotid artery distensibility (stiffness index ß, pulse wave velocity, pressure strain elasticity module and carotid artery compliance). RESULTS: In the HD and controls we identified a comparable number of non-obstructive plaques (<50% lumen narrowing). No obstructive plaques (>50% lumen narrowing) were found. There was significantly increased IMT in MHD. In PHD and EHD the parameters of arterial stiffness were significantly higher and the carotid artery compliance was significantly lower. CONCLUSIONS: Our results reveal functional vascular pathology in PHD, EHD, and MHD. Precerebral arteries dysfunction in HD therefore appears to be mostly functional and in agreement with recently described autonomic nervous system changes in HD.

Male sexual function in presymptomatic gene carriers and patients with Huntington's disease.

AIMS: To report sexual dysfunction in a systematically studied cohort of men with Huntington's disease (HD), and compare them with control men of a similar age. METHODS: In men with HD and asymptomatic HD gene carriers, the male sexual dysfunction questionnaire (International Index of Erectile Function--IIEF, covering erectile and orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction), neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC) Score were utilized. RESULTS: Responses were obtained from 23 HD patients and 2 HD gene carriers. HD patients reported more problems with erection, intercourse satisfaction and overall satisfaction (p<0.05) compared to 41 controls. HD patients generally reported reduced sexual desire and performance. Sexual dysfunction progressed in parallel with patients' decline in motor (UHDRS) and TFC, but was not related to patients' age and duration of disease. CONCLUSIONS: Our study demonstrated a significant impact of HD on male sexual function that progressed in parallel with motor and total patient (TFC) dysfunction. Physicians helping HD patients should also consider this largely neglected aspect of the disease.

Bladder dysfunction in presymptomatic gene carriers and patients with Huntington's disease.

The objective of this study was to report bladder dysfunction and cystometric findings in a systematically studied cohort of Huntington's disease (HD) patients. In HD patients and asymptomatic HD gene carriers a urinary function questionnaire, neurologic assessment using the Unified Huntington's Disease Rating Scale, and postvoid residual volume measurement were applied. All patients were also invited to cystometric studies. Urinary function data were compared to control men and women. The most common symptoms in 54 HD patients (24 men) were those of bladder overactivity (men/women 54%/40%), followed by urinary incontinence (29%/43%) and symptoms of disturbed bladder emptying (25%/40%). Using urinary function questionnaires severe bladder dysfunction was found in 4%/0%, moderate in 21%/23%, and mild in 25%/30% of HD men/women. Urinary symptoms interfered with daily life in 21%/37% and sexual life in 21%/33% of sexually active HD men/women. In 5 HD men and 1 woman, increased postvoid residual volume (>100 ml) was found. Compared to 49/55 control men/women urinary incontinence, and urgency were more common in HD men, but not in HD women (urinary incontinence reported 10%/38% of control men/women). Cystometry, performed in 12 HD patients and 1 of 10 asymptomatic HD gene carriers, demonstrated detrusor-sphincter dyssynergia in 5 (42%), detrusor overactivity in 2 (17%), and reduced detrusor capacity in 2 (17%) HD patients. Our study demonstrated significant urinary symptoms in HD patients, which reduced their quality of life. Physicians helping HD patients should also consider this largely neglected aspect of the disease.

Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

BACKGROUND: In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. SUBJECTS AND METHODS: Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. RESULTS: No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. CONCLUSIONS: Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

Chorea-acanthocytosis presenting as dystonia.

The aim of this article is to present two Slovenian chorea-acanthocytosis (ChAc) siblings with an unusual predominantly dystonic ChAc phenotype. For diagnostic purposes, the genomic DNA was screened for VPS13A mutations. Movement disorder was evaluated and scored according to the Dystonia Movement and Disability Scale (DMDS) in order to evaluate the effects of L-dopa on dystonia. Brain imaging was performed with the use of magnetic resonance imaging scan and 99m Tc-ethyl cysteinate dimmer single photon emission computed tomography (Tc-ECD SPECT). Clinical neurological examination disclosed gait dystonia. Marked swallowing difficulty due to tongue and feeding dystonia was observed. Both siblings were found to be heterozygous for a substitution in exon 22 (c.2191C>T) and for a deletion in exon 35 (c.3995_3996delinsA) leading to mutation in VPS13A. After being administered L-dopa for three months, both subjects showed significant symptomatic improvement documented by reduced DMDS scores. It is concluded that VPS13A mutation testing may improve diagnosis of dystonia and recognition of atypical ChAc phenotypes. It seems that L-dopa could be effective in the treatment of dystonia due to VPS13A mutations.

Cognitive and autonomic dysfunction in presymptomatic and early Huntington's disease.

Huntington's disease is characterized by disorders of movement, cognition and behavior. Individuals with Huntington's disease display aberrant changes in the autonomic nervous system that are detected even before the onset of other symptoms. Subtle cognitive dysfunction may start before other clinical manifestations. The aim of the present study was to investigate the autonomic nervous system response to mental arithmetic and the relationship between the autonomic and cognitive/motor function in presymptomatic and early Huntington's disease. We examined 15 presymptomatic Huntington's disease gene carriers (PHD), 15 early Huntington's disease patients (EHD) and 30 healthy controls. PHD and EHD groups were determined according to Unified Huntington's Disease Rating Scale (UHDRS) motor score. ECG, heart rate, systolic and diastolic blood pressure, and cutaneous laser Doppler flux were measured during rest and during a simple mental arithmetic test. UHDRS cognitive test battery was applied to determine cognitive dysfunction. During mental arithmetic, the heart rate of PHD/EHD increased significantly less than that of controls. Decreased microvascular response to mental arithmetic was found in EHD. Significant correlations for the PHD/EHD group were found between laser Doppler flux response and Symbol Digit Modalities Test score, and between laser Doppler flux response and UHDRS motor score. It seems that central autonomic dysregulation of cardiovascular system in Huntington's disease goes along with the degeneration of other central neuronal systems. This finding is relevant as it could enable simple and noninvasive testing of disease progression.

No electrophysiological evidence for Onuf's nucleus degeneration causing bladder and bowel symptoms in Huntington's disease patients.

AIMS: In several degenerative neurologic diseases degeneration of Onuf's nucleus has been demonstrated using histologic and electromyographic (EMG) methods. Although Huntington's disease (HD) patients also frequently complain of bladder and bowel symptoms, degeneration of Onuf's nucleus has not been systematically studied in this group. METHODS: From our inventory of patients with genetically confirmed HD, all patients willing and capable of participating in the study, which utilized several standard questionnaires, were included. The patients reporting bladder/bowel symptoms were also asked to participate in anal sphincter EMG and sacral reflex studies. RESULTS: Of 52 patients (23 men) with genetically confirmed HD, 34 reported bladder/bowel symptoms, and 16 (8 men) of them consented to anal sphincter EMG and sacral reflex studies. Complete pattern of urinary and fecal urgency with incontinence reported 6 (38%), and incomplete 3 (19%) patients, accompanied with episodic diarrhea in another 3 (19%) patients. No patient exhibited quantitative anal sphincter EMG or sacral reflex abnormalities. However, in 81% of patients, decreased tonic anal sphincter activity and/or decreased voluntary activation were found on qualitative EMG. Lower sacral sensory thresholds and shorter reflex latencies were also found in HD patients compared to controls. CONCLUSIONS: We found no EMG signs of Onuf's nucleus degeneration in HD patients. The observed decreased anal sphincter tonic activity and voluntary activation, lower sacral sensory thresholds and shorter reflex latencies as well as the reported bladder/bowel symptoms, are probably caused by degeneration of other central nervous system structures. Neurourol. Urodynam. 33:524-530, 2014. © 2013 Wiley Periodicals, Inc.

Microcirculation response to local cooling in patients with Huntington's disease.

Altered autonomic nervous system (ANS) functioning in early stages of Huntington's disease (HD) has been suggested, presumably due to distorted high-order autonomic control. ANS functioning in the early stages of HD was further investigated. Laser-Doppler (LD) flux in the skin of the fingertips, heart rate (HR), HR variability, systolic and diastolic blood pressure were measured during rest and during a 6 min cooling of one hand at 15°C. Data of 15 presymptomatic gene mutation carriers (PHD), 15 early symptomatic HD patients (EHD), and two groups of 15 age- and sex-matched controls were compared. The area under the low frequency (LF) and high frequency (HF) bands of the HR variability spectrum were calculated. An augmented reduction of cutaneous LD flux was found in response to the direct cooling in the PHD group (37.5 ± 8.5% of resting value) compared to the PHD controls (67.27 ± 8.4%) (p < 0.05). In addition, the PHD group had higher (LF/(LF + HF) index of primary sympathetic modulation of the HR at rest (53.6 ± 3.3) compared to the EHD patients (39.7 ± 4.2) (p < 0.05). In the EHD group, a significantly smaller change of HR during cooling (100.26 ± 1.2%) was found compared to the EHD controls (95.9 ± 1.0%) (p < 0.05). The results are in line with the hypothesis that ANS dysfunction occurs even in PHD subjects. Further, they support the hypothesis that dysfunction of the high-order autonomic centres are involved in HD.

Novel pathogenic mutations and copy number variations in the VPS13A gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc.

Gene expression changes in blood as a putative biomarker for Huntington's disease.

Several studies demonstrated alterations of gene expression in blood in various neurological disorders including Huntington's disease (HD). Using microarray technology, a recent study identified a large number of significantly altered mRNAs in HD blood, from which a 12-gene set was selected as classifier for discriminating controls and HD patients. The aim of our study was to validate expression changes of these 12 genes in an independent cohort of HD patients and evaluate their sensitivity and specificity. Four different subject groups were included--patients with HD, Parkinson's disease (PD), acute ischemic stroke (AS) and healthy controls. Although the previous results were successfully validated, gene expression changes in HD blood partly overlapped with those observed in blood from PD and AS patients. Predictive value of the selected biomarker set for HD group was 78%, with 82% sensitivity and 53% specificity. Further gene expression analyses in longitudinal studies are needed to validate and refine possible transcriptomic blood biomarkers in HD.

Hemochromatosis-causing mutations C282Y and H63D are not risk factors for atherothrombotic cerebral infarction.

BACKGROUND: It has been suggested that iron metabolism may be involved in the pathogenesis of atherothrombotic cerebral infarction (ACI). The C282Y and H63D mutations in the hemochromatosis (HFE) gene are associated with increased serum iron levels and net iron accumulation. The aim of this study was to test the hypothesis that the C282Y and H63D mutations in the HFE gene are risk factors for ACI in a Slovene population. MATERIAL/METHODS: The C282Y and H63D HFE gene mutations were tested in 96 Caucasian patients who had suffered an acute cerebral infarction, later confirmed as ACI, and 115 control subjects. Genotypes were determined by electrophoresis of the DNA digestion products from RsaI (C282Y) and MboI (H63D). RESULTS: We failed to demonstrate that the C282Y and H63D mutations were risk factors for ACI in Caucasians. The percentage of C282Y and H63D genotypes (dominant model) in ACI-cases (C282Y: 7.3%, n=7; H63D: 28.1%, n=27) did not differ significantly (P=0.9 and P=0.7 respectively) from that of the controls (C282Y: 7.0%, n=8; H63D: 26.1%, n=30). Logistic regression analysis revealed that arterial hypertension, diabetes, and cigarette smoking are independent risk factors for ACI, whereas the C282Y and H63D HFE gene mutations are not. CONCLUSIONS: We provided evidence that the C282Y and H63D HFE gene mutations were not risk factors for ACI in this Slovene population.

Derivation by prefixation in Slovenian: two aphasia case studies.

The present study is concerned with two Slovenian-speaking patients who were asked to produce, in various tasks, verbs, nouns, and adjectives derived by prefixation with prepositions. Despite differences due to their specific linguistic difficulties, both patients' performance was characterized by the differential processing of prefixes and remaining components of complex words. Prepositions in prefixation were mostly preserved, and less frequently substituted, regardless of the numerous errors produced in the remaining portion of the words. These errors seem clearly determined by the morphological structure of the words and therefore appear to be authentic morphological errors. These findings contribute to the theoretical debate on mental lexical representation, speaking in favor of a morphological decomposition in processing of prefixed complex words at different processing levels.

DD Genotype of the angiotensin - converting enzyme gene and stroke in Slovenian population.

The angiotensin-converting enzyme (ACE) is a rate-limiting enzyme in the renin angiotensin system, the enzyme is involved in the vascular remodelling and atherosclerosis. Its significance in pathogenesis of ischemic cerebrovascular insults (CVI) is not known. We analysed 124 Slovenian patients with CVI and compared them with 161 healthy controls for I/D polymorphism. Under a recessive model (χ2 = 1.76, p= 0.1, OR = 1.40, 95% CI: 0.85 - 2.34) we found no significant difference in I/D genotypes between patients with CVI and controls. This study shows that in a group of Slovenian CVI patients the DD genotype is not an important risk factor for the development of stroke.