Vitamin D in mild cognitive impairment and Alzheimer's disease. A study in older Greek adults.

BACKGROUND: In recent years, accumulating evidence has linked vitamin D deficiency to cognitive dysfunction and dementia. This study aimed at determining the relevance of serum 25-hydroxyvitamin D concentrations in mild cognitive impairment (MCI) and Alzheimer's disease (AD) in older Greek adults. It also examined whether the vitamin D level could be considered a predisposing factor for conversion from MCI to AD. METHODS: The study enrolled 350 subjects aged 65 years and over, allocated into three groups consisting of 103 healthy subjects (HS), 109 individuals with MCI, and 138 patients with AD, respectively. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, measured in ng/ml, were determined by electrochemiluminescence, and we used the Mini-Mental State Examination (MMSE) and the Cambridge Cognition Examination (CAMGOG) to evaluate the subjects' cognitive status. One follow-up examination was performed for the MCI patients 30 months ± three months after the initial evaluation. RESULTS: Compared to HS, serum 25(OH)D levels were significantly decreased in individuals with MCI (p =0.012) and patients with AD (p <0.001). Moreover, serum 25(OH)D concentrations were significantly decreased in patients with AD compared to individuals with MCI (p =0.003) and also significantly lower in individuals with MCI who progressed to AD compared to those who remained MCI (p =0.028). After adjusting for confounders, multivariate analysis revealed that an increase of vitamin D concentration by one ng/mL reduces the risk of MCI by 4 % (OR =0.96, 95 % CI =0.92-0.99, p =0.006), the risk of AD by 8 % (OR =0.92, 95 % CI =0.89-0.95, p <0.001), and in an individual with MCI reduces the risk of conversion to AD by 10 % (OR =0.90, 95 % CI =0.83-0.96, p =0.003). CONCLUSIONS: The present study reveals that serum vitamin D levels are significantly decreased in subjects with MCI and patients with AD compared to HS. Additionally, individuals with MCI who progressed to AD presented significantly lower vitamin D levels than those who remained MCI. These results suggest that preserving adequate vitamin D status in older adults could delay or prevent cognitive decline. HIPPOKRATIA 2020, 24(3): 120-126.

The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS. RESULTS: Thirty-five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%-74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%-50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%-18.9%) and 19.5% (16.6%-22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%-18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63-2.54, P < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%-8.3%)] and spontaneous echo contrast [3.8% (2.3%-6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%-0.7%)]. Significant heterogeneity was identified (I(2) > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut-off of 50 years, PFO was significantly (P = 0.001) more prevalent in younger than in older patients. CONCLUSION: Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Extracranial venous hemodynamics in multiple sclerosis: a case-control study.

OBJECTIVES: A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of multiple sclerosis (MS). We performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria. METHODS: We prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva maneuver. RESULTS: We recruited 42 patients with MS (mean age 39 ± 11 years, 17 men) and 43 control individuals (mean age 38 ± 12 years, 16 men). Very good/excellent intrarater and interrater agreement (κ values 0.82-1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. After performing Valsalva maneuver, we documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999). CONCLUSIONS: With established reproducibility of venous ultrasound testing, our data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.

The sural sensory/radial motor amplitude ratio for the diagnosis of peripheral neuropathy in type 2 diabetic patients.

BACKGROUND AND AIM: The diagnosis of peripheral diabetic neuropathy is based on clinical examination. Nerve conduction study (NCS) enables earlier diagnosis, but it is demanding and requires specialised personnel. In an attempt to simplify the procedure, this study aimed to identify a new electrophysiological index, which might correlate with results obtained on standardised NCS in patients with long-standing type 2 diabetes. PATIENTS AND METHODS: Medical records of type 2 diabetic patients evaluated for neuropathy by NCS were reviewed retrospectively. This analysis included 104 patients (50 men, 54 women) with a mean age of 67.1±5.5 years and mean diabetes duration of 13.1±2.7 years. NCS was performed on radial, ulnar, sural, and peroneal nerves. Neuropathy was defined as impaired NCS. Ratios of neurophysiological parameters from these nerves were calculated and each of them was compared with diagnosis of neuropathy. RESULTS: The sural sensory/radial motor amplitude ratio had the best combination of sensitivity (85%) and specificity (71%) for neuropathy. It also remained the strongest independent predictor of neuropathy in multivariate regression analysis: low levels of this ratio yielded an odds ratio of 7.7 for neuropathy. CONCLUSIONS: The sural sensory/radial motor amplitude ratio has a high sensitivity and a moderately high specificity for the diagnosis of neuropathy, low levels being associated with a nearly eightfold increase in the risk for neuropathy. These results encourage further evaluation of this and other electrophysiological indices to enable wider availability of NCS.

Multicenter external validation of the ABCD2 score in triaging TIA patients.

OBJECTIVES: A simple clinical score (ABCD(2) score) has been introduced to triage TIA patients with a high early risk of stroke. External validation studies have yielded inconsistent results regarding the predictive ability of the ABCD(2) score. We aimed to prospectively validate the former score in a multicenter case series study. METHODS: We prospectively calculated the ABCD(2) score (age [> or = 60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10-59 minutes: 1, > or = 60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). RESULTS: The 7-day and 90-day risks of stroke in the present case series (n = 148) were 8% (95% CI 4%-12%) and 16% (95% CI 10%-22%). The ABCD(2) score accurately discriminated between TIA patients with high 7-day (c statistic 0.72, 95% CI 0.57-0.88) and 90-day (c statistic 0.75, 95% CI 0.65-0.86) risks of stroke. The 90-day risk of stroke was 7-fold higher in patients with an ABCD(2) score >3 points (28%, 95% CI 18%-38%) than in patients with an ABCD(2) score < or = 3 points (4%, 95% CI 0%-9%). After adjustment for stroke risk factors, race, history of previous TIA, medication use before the index TIA and secondary prevention treatment strategies, an ABCD(2) score of >2 was associated with a nearly 5-fold greater 90-day risk of stroke (hazard ratio 4.65, 95% CI 1.04-20.84, p = 0.045). CONCLUSION: Our findings externally validate the usefulness of the ABCD(2) score in triaging TIA patients with a high risk of early stroke in a multiethnic sample of hospitalized patients. The present data support current guidelines endorsing the immediate hospitalization of patients with an ABCD(2) score >2.

Incidence and case fatality of subarachnoid haemorrhage in Northern Greece: the Evros Registry of Subarachnoid Haemorrhage.

BACKGROUND: Epidemiological data on subarachnoid haemorrhage incidence and case-fatality rates are scarce in the south-eastern Mediterranean region. We conducted a population-based study in Evros Province, located in north-eastern Greece, to determine subarachnoid haemorrhage incidence over a 5-year period (2001-2005). METHODS: Evros Province has a well-defined, largely homogeneous population with healthcare organised around a single tertiary-care University Hospital. We organised a prospective computerised registry of permanent Evros residents admitted or transferred to our hospital with a diagnosis of subarachnoid haemorrhage. Standard World Health Organization definitions and overlapping case-finding methods were used to identify all cases of first ever in a lifetime subarachnoid haemorrhage in all age groups, occurring during the study period. The diagnosis was confirmed by computed tomography scan in all hospitalised cases. Sudden deaths attributable to subarachnoid haemorrhage were systematically recorded province-wide by our forensic department and are included in the study. RESULTS: During the 5-year period, 51 cases of subarachnoid haemorrhage were recorded (28 men, 23 women; mean age 59+/-17 years). The crude annual incidence rates were 8.3/100,000 persons (95% confidence interval: 5.5-12.0) for men, 7.5/100,000 (4.8-11.3) for women and 7.9/100,000 (5.9-10.4) for all subjects. The standardised incidence rates for groups aged 45-84 years in the European population were 9.3/100,000 (5.8-12.8) for men, 6.5/100,000 (3.7-9.4) for women and 7.9/100,000 (5.7-10.2). The 28-day case-fatality rates for men, women and all subjects were 36% (21-54%), 35% (19-55%) and 35% (24-49%), respectively. CONCLUSIONS: The incidence and case-fatality rate of subarachnoid haemorrhage haemorrhage in Greece appear to be similar to other developed countries. No gender differences in subarachnoid haemorrhage incidence and case-fatality rate were documented.

Sleep architecture in stroke and relation to outcome.

The aim of this study was to investigate sleep architecture in stroke patients, and correlate possible disturbances with the topography, severity and outcome of stroke and the presence of sleep-disordered breathing (SDB). In total, 62 acute stroke patients and 16 age- and gender-matched hospitalised controls underwent polysomnographic studies. Sleep architecture was analysed according to the topography of lesion, severity (National Institutes of Health Stroke Scale) and outcome (Barthel Index) of stroke. We found that sleep architecture is disturbed in stroke patients, regardless of SDB. Stroke patients (without SDB) have reductions in total sleep time and sleep efficiency, reduced stage II and slow wave sleep, increased wakefulness during sleep and increased sleep latency. Rapid eye movement (REM) sleep is reduced when SDB is also present. REM sleep is relatively preserved in cerebellar strokes, as opposed to other topographies. Sleep stages I and REM are negatively associated with stroke severity, and the latency to REM sleep is positively correlated with a good outcome. Sleep architecture is impaired in stroke patients (with fragmentation, increased wakefulness and reduced slow wave sleep), and this correlates with severity and outcome. Sleep disturbances should be investigated and addressed in these patients. Further studies are needed to confirm these findings and assess the clinical and therapeutic implications.

Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes.

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa=0.229, p=0.074) but was 90.2% (kappa=0.782, p<0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.

Carotid plaque echomorphology and serum vascular endothelial growth factor levels.

Neovascularization in atherosclerotic plaques plays an essential role in the progression and rupture of plaques. Vascular endothelial growth factor (VEGF) is an important angiogenic factor. Echomorphologic evaluation of carotid plaques using computer-assisted imaging was found to have a good correlation with the histology of the lesion. The aim of this study was to investigate whether the serum VEGF level could be a determinant of the echomorphology of the carotid plaque. In 28 carotid plaques causing 60-99% stenosis, serum VEGF levels and the mean gray value (MGV) of three-dimensional image of the carotid plaques were measured. A statistically significant inverse correlation was found between serum VEGF concentrations and MGVs (Spearman's correlation coefficient: -0.415, p = 0.028). Our finding indicates that in patients with > or =60% carotid stenosis the serum VEGF levels are associated with the echogenicity of the atherosclerotic plaque.