Iris Zavoreo

Carotid artery disease and cognitive impairment

The term neurologic symptom usually relates to the loss of motor or sensory functions; cognitive deficit is mostly unrecognized in patients with severe carotid stenosis. In large population studies carotid stenosis has been shown as independent risk factor for mild cognitive impairment (MCI) and it was not due to underlying vascular risk factors. The term MCI refers to a transitional stage between cognitive changes of normal aging and vascular dementia. At this stage, cognitive decline is not severe enough to constitute dementia, but also it is beyond the cognitive functioning deficit which is expected in normal aging. Carotid stenosis detected in population older than 65 is 75% for men and 62% for women, with prevalence of stenosis ≥ 50% in this population 7% for men and 5% for women. There are two possible underlying pathomorphological mechanisms of cognitive changes in patients with carotid disease - cerebral emboli and hypoperfusion with or without silent brain infarctions. In both cases loss of regional cerebral autoregulation can be recognized by means of neurosonology (transcranial Doppler ultrasonography). Most of the studies which evaluated cognitive functions before and after CEA/CAS have shown improvement or no changes in cognitive functions, but no deteriorations. There are still no clear recommendations about using CEA/CAS in treating cognitive deficit in otherwise asymptomatic patients. It is important to recognize cognitive changes as a symptom of carotid disease in order to follow up such patients and include cognitive deficit as one of the criteria in calculating perioperative risk and benefit from CEA/CAS.

Evaluation of aging vs dementia by means of neurosonology

Aging is often associated with some cognitive impairment. Greater population life expectancy is one explanation for increased incidence of cognitive impairment cases. Large number of people with cognitive impairment and dementia is becoming one of the most important medical and social problems worldwide. Therefore, prevention of Alzheimer disease is becoming an imperative. Dementia includes a heterogeneous group of disorders, the most common being Alzheimer dementia (AD) and vascular dementia (VD). Most cardiovascular risk factors, such as hypertension, diabetes mellitus, hypercholsterolemia, atrial fibrillation, and smoking are not exclusively risk factors for VD, but also for AD. Intracranial hemodynamics of the aging brain can be assessed by Transcranial Doppler Sonography (TCD), functional TCD with various functional tests, and TCD detection of cerebral emboli. Extracranial circulation can be assessed by means of color Doppler flow imaging (CDFI). New neurosonology techniques and possibilities provide information necessary to closer determine the relation between cognitive deterioration and vascular risk factors, so that the evolution towards dementia could be prevented or at least postponed.

The Role of Classic Risk Factors and Prothrombotic Factor Gene Mutations in Ischemic Stroke Risk Development in Young and Middle-Aged Individuals

BACKGROUND In young individuals, a genetically predisposing hypercoagulability and classic modifying risk factors can act synergistically on the ischemic stroke risk development. The aim of the study was to compare the prevalence of classic vascular risk factors and polymorphisms of the G20210A coagulation factor II (prothrombin), Arg506Glu coagulation factor V Leiden, C677T methylenetetrahydrofolate reductase (MTHFR), and 4G/5G plasminogen activator inhibitor-1 (PAI-1) and the impact of these gene mutations and classic vascular risk factors on the overall stroke risk in individuals aged 55 years or younger. METHODS The study included 155 stroke patients aged 55 years or younger and 150 control subjects. Stroke prevalence and odds ratio (OR) were assessed for the following parameters: G20210A prothrombin, Arg506Glu factor V Leiden, C677T MTHFR, and 4G/5G PAI-1 polymorphisms; total number of study polymorphisms in a particular subject (genetic sum); and classic vascular risk factors of hypertension, obesity, diabetes mellitus, cigarette smoking, hypercholesterolemia, hypertriglyceridemia, and elevated levels of low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein cholesterol. RESULTS The prevalence of hypertension (P < .001), smoking (P < .001), decreased HDL cholesterol levels (P < .001), obesity (P = .001), elevated LDL cholesterol (P = .036), C677T MTHFR polymorphism (P < .001), and genetic sum was significantly higher in the group of stroke patients. The following parameters were found to act as independent risk factors for ischemic stroke: decreased HDL cholesterol level (P < .001; OR 4.618; 95% confidence interval [CI] 2.381-8.957); hypertension (P = .001; OR 2.839; 95% CI 1.519-5.305); obesity (P = .040; OR 2.148; 95% CI 1.036-4.457); smoking (P = .001; OR 2.502; 95% CI 1.436-4.359); and genetic sum as a continuous variable (P < .01; OR 2.307; 95% CI 1.638-3.250). CONCLUSIONS Gene mutations of the procoagulable and proatherosclerotic factors investigated exerted a synergistic action in the development of overall risk of ischemic stroke in young and middle-aged individuals.

Breath holding index in detection of early cognitive decline

The aim of the study was to evaluate role of breath holding index (BHI) as a functional parameter for intracranial subclinical atherosclerotic changes in recognizing patients who are at risk for developing cognitive impairment of the vascular type. We included 60 volunteers divided into 3 groups according to age and presence of cognitive impairment (healthy subjects 30-40 years old, controls 60-70 years old and subjects with mild cognitive impairment 60-70 years old). We excluded individuals with moderate and severe carotid stenosis. There was a decreasing trend in the mean blood flow velocities of the intracranial blood vessels due to age increase, but it was not statistically significant. BHI values were 1.66±0.20 in the first group, 1.35±0.31 in the second and 0.69±0.30 in the third group. There was a statistically significant difference between the first two groups and the group with a mild cognitive impairment (MCI) in Montreal cognitive assessment (MoCA) score (29±1, 27±1 and 19±1 respectively), no statistically significant difference was found in Mini mental state exam (MMSE) score (29±1, 28±1, and 28±1 respectively). After regressing out age and conventional vascular risk factors, we found a good correlation between the decreasing trend in BHI values and MoCA score, and no statistically significant correlation between the BHI values and MMSE score. Results of our study show that BHI test as a parameter of impaired cerebrovascular reactivity (intracranial small vessel wall dysfunction) might differentiate individuals with early cognitive decline from healthy subjects.

Breath holding index and arterial stiffness as markers of vascular aging

BACKGROUND The aim of the study was to evaluate correlation of breath holding index (BHI) as functional parameter for intracranial subclinical atherosclerotic changes - we have shown in our previous works and arterial stiffness (AS-functional parameter for extracranial subclinical atherosclerotic changes) in normal population. PATIENTS AND METHODS We included 120 healthy volunteers (conventional risk factors for cerebrovascular disease were excluded) who were examined at our Neurology Department. They were divided into 6 age groups-(25-35, 36-45, 46-55, 56-65, 66-75, 76+ years). We performed standard laboratory workup, body weight and height measurements, Color Doppler and Power Doppler of the main head and neck vessels and Transcranial Doppler, (measured by means of e-Tracking software). RESULTS There was decline of BHI, and increase in AS - in correlation with age increase (p<0.01). There was statistically significant negative correlation between BHI and AS (r= -0,931, p<0.01 right and r = -0,938, p<0.01 left). CONCLUSION These results show that decline in BHI as parameter for intracranial microvessel dysfunction is in good correlation with increase of AS as functional parameter of extracranial vascular aging.

The effectiveness of acupuncture versus clonazepam in patients with burning mouth syndrome

Objective Burning mouth syndrome (BMS) is a chronic oral condition, characterised by burning symptoms, which mainly affects perimenopausal and postmenopausal women. Neuropathy might be the underlying cause of the condition. There are still insufficient data regarding successful therapy. The aim of this study was to compare the effectiveness of acupuncture and clonazepam. Methods Forty-two patients with BMS (38 women, 4 men) aged 66.7±12.0 years were randomly divided into two groups. Acupuncture was performed on 20 participants over 4 weeks, 3 times per week, on points ST8, GB2, TE21, SI19, SI18 and LI4 bilaterally as well as GV20 in the midline, each session lasting half an hour. Twenty-two patients took clonazepam once a day (0.5 mg in the morning) for 2 weeks and, after 2 weeks, two tablets (0.5 mg in the morning and in the evening) were taken for the next 2 weeks. Prior to and 1 month after either therapy, participants completed questionnaires: visual analogue scale, Beck Depression Inventory, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale, 36-item Short Form Health Survey (SF-36) and Montreal Cognitive Assessment (MoCA). Results There were significant improvements in the scores of all outcome measures after treatment with both acupuncture and clonazepam, except for MoCA. There were no significant differences between the two therapeutic regimens regarding the scores of the performed tests. Conclusions Acupuncture and clonazepam are similarly effective for patients with BMS.

Neurosonology: a means of evaluating normal aging versus dementia

The aging of the population and higher life expectancy have led to an increase in the incidence of cognitive changes and dementia. It is important to differentiate between cognitive changes associated with normal aging and those associated with dementia. Dementia is a syndrome caused by a heterogeneous group of disorders, the most common being Alzheimer’s disease and vascular dementia. While cardiovascular risk factors, such as diabetes mellitus, hypertension, hypercholesterolemia, atrial fibrillation and smoking, are particularly relevant in the development of vascular dementia, they may also play a role in Alzheimer’s disease. The control of these risk factors at an early stage may help to delay the onset and reduce the severity of vasculopathy. Cognitive changes and vasculopathy are correlated with decreased mean blood flow velocities in the main arteries of the brain. Intracranial hemodynamics of the aging brain can sucessfully be assessed by a number of methods, including transcranial Doppler sonogra...

Targeted Mass Spectrometry-Based Assays for Relative Quantification of 30 Brain-Related Proteins and Their Clinical Applications

Cerebrospinal fluid (CSF) is a promising clinical sample for identification of novel biomarkers for various neurological disorders. Considering its direct contact with brain tissue, CSF represents a valuable source of brain-related and brain-specific proteins. Multiple sclerosis is an inflammatory, demyelinating neurological disease affecting the central nervous system, and so far there are no diagnostic or prognostic disease specific biomarkers available in the clinic. The primary aim of the present study was to develop a targeted mass spectrometry assay for simultaneous quantification of 30 brain-related proteins in CSF and subsequently to demonstrate assay feasibility in neurological samples derived from multiple sclerosis patients. Our multiplex selected reaction monitoring assay had wide dynamic range (median fold range across peptides = 8.16 × 103) and high assay reproducibility (median across peptides CV = 4%). Candidate biomarkers were quantified in CSF samples from neurologically healthy individuals (n = 9) and patients diagnosed with clinically isolated syndrome (n = 29) or early multiple sclerosis (n = 15).

The First Hospital-Based Registry of Patients with Multiple Sclerosis in Croatia

The first hospital-based registry of patients with multiple sclerosis (MS) was established at the University Department of Neurology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, in 2014. The aim of the registry was to continuously provide data on the number of hospital-managed MS patients, patterns of disease progression, predictors of disability progression, changes in lifespan and long-term outcomes. Relevant medical data included age and gender of MS patients, family history of MS, data on previous immunization, disease course, Expanded Disability Status Scale (EDSS) score, cerebral magnetic resonance imaging (MRI) lesion load quantification, and cerebrospinal fluid analysis. Lifestyle habits in MS patients including smoking and alcohol consumption were also analyzed. All data were obtained from primary medical records between January 1, 2014 and January 1, 2015, and entered into the database. Data were evaluated retrospectively according to age and gender differences. Results showed that the majority of patients enrolled in the registry had the remitting relapsing course of disease, with low EDSS score indicating no disability or minimal disability. Cerebrospinal fluid analysis showed that oligoclonal bands were present in the majority of MS patients, with affected blood-brain-barrier permeability. According to the remitting relapsing course of the disease, cerebral MRI quantitative analysis demonstrated a significant lesion load in the majority of patients. When stratified by lifestyle habits, smokers and alcohol consumers were more prevalent among male patients. Our hospital-based registry might be considered as a prototype for the national MS registry and should be improved for reliable statistical analysis.

Uloga elektromiografskog refleksa treptaja u procjeni pojavnosti glavobolja

Migraine and tension type headache are the most common disabling primary headache disorders. Epidemiological studies have documented their high prevalence and high socioeconomic and personal impacts. According to recent data, migraine ranks as the third most prevalent disorder and seventh-highest specific cause of disability worldwide. Tension-type headache has lifetime prevalence in the general population ranging between 30% and 78% in different studies. According to the International Classification of Headache Disorders, 3rd edition, there also are many other headaches but their incidence in general population is lower than the previously mentioned headaches. Trigeminal nerve and upper cervical segments (C1-C3) are included in pain control of the head region and often evaluated in headache studies in order to improve differential diagnosis and headache treatment. In our study, we evaluated the potential role of electromyographic (EMG) blink reflex in establishing diagnosis of headache and evaluation of trigeminal nerve dysfunction as the possible underlying pathomorphological headache mechanism. Our study included 60 patients with different types of primary headaches and 30 control subjects. Statistical analysis was performed by use of χ2-test and statistical significance was set at p<0.001. Study results showed that patients with trigeminal dysfunction in EMG blink reflex had a 5.6-fold higher risk of developing headache in comparison to subjects with normal EMG blink reflex finding.