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Original Article


The relationship between hormone replacement therapy (HRT) and memory performance in women: influences of HRT type and APOE E4 allele status - read full article

By: Donna Spooner, Ada Ho Yan Lo, Soo Keat Khoo, Sheila O’Neill, and Nancy A. Pachana

Objective: To investigate the relationship between hormone replacement therapy (HRT) and performance on the Wechsler Memory Scale-III (WMS-III) after controlling for confounders, and to determine the impact of different types of HRT and the effect of APOE E4 allele status on memory performance.

Methods: A sample of 223 postmenopausal women aged 44-80 years enrolled in the Longitudinal Assessment of Women (LAW) study participated in this study. Participants were administered tests of verbal memory, auditory memory, visual memory, attention and working memory from the WMS-III. Information on their HRT use, and a range of demographic and health variables were also collected.

Results: After controlling for covariates, HRT use contributed unique variance to performance on the Spatial Span subtest of the WMS-III and estrogen-only users performed more poorly on this task than nonusers. APOE E4 contributed unique variance to the Letter-Number Sequencing Subtest of the WMS-III. No significant HRT use by APOE interaction was found.

Conclusion: In summary, HRT use was observed to have minimum effect overall on the performance of postmenopausal women on the WMS-III. The APOE E4 allele was also demonstrated to have minimal influence on cognitive functioning, and it did not interact significantly with HRT to affect test performance.

Keywords: APOE E4, HRT, memory, cognitive, women’s health

International Journal of Clinical Neurosciences and Mental Health 2014; 1:2


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Original Article


Neurovascular coupling and EEG band distribution in patients with chronic obstructive pulmonary disease - read full article

By: Bernhard Rosengarten, Melanie Schmid, Anna Steinmann, Tobias Gessler, and Stefan Kuhnert

Background: Chronic obstructive pulmonary disease (COPD) patients often complain of neurological symptoms which were usually referred to oxygen deficit or neurovascular dysfunction. To address this issue we studied neurofunctional and neurovascular parameters in COPD patients without chronic oxygen treatment.

Methods: Severity of the COPD disease was classified according to the BODE score. Besides body plethysmography and capillary blood gas analysis, vascular risk factors, medication, CRP, and nitric oxide levels were obtained. Using a visual stimulation paradigm evoked potential amplitudes over the occipital cortex as well as hemodynamic responses in the posterior cerebral artery were obtained with a simultaneous EEG-Doppler technique. EEG frequency bands as well as flow velocity were also obtained during resting conditions.

Results: As expected a significant decline in the pO2 level (Bode 0: 77±11 vs. Bode 7-10: 61±5 mmHg; p<0.005), and increase in the pCO2 level (Bode 0: 35±3 vs. Bode 7-10: 43±7 mmHg; p<0.05) was found with disease progression. However, resting flow velocity levels, neurovascular coupling responses, potential amplitudes, or EEG band distribution were similar between groups. The pH levels were similar between groups showing complete metabolic compensation of hypercapnia. Hemoglobin, CRP, and NO levels were also similar between groups.

Conclusion: According to the present study there seems to be no simple association between COPD disease severity, reported neurological complaints, and neuronal or neurovascular parameters. Further investigations are warranted to investigate this issue in patients with stronger hypoxia or induced inflammation.

Keywords: Chronic obstructive pulmonary disease, Neurovascular coupling, Transcranial Doppler, Electroencephalogram

International Journal of Clinical Neurosciences and Mental Health 2014; 1:3


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Original Article


Screening of cerebrovascular diseases in Stroke Prevention Centres in Latvia - read full article

By: Galina Baltgaile, Tatjana Timofejeva, Ženija Kovaldina, Anita Raita, and Jelena Pecherska

Background: To improve stroke prevention, the observation of patients suspected on having cerebrovascular disease (CVD) or stroke risk factors has been carried out in Stroke Prevention Centres (SPC) in Riga. The analysis of the incidence of CVD, correlations of clinical symptoms with diagnostic findings and risk factors was performed.

Methods: 1102 outpatients aged 7-89 years (65% female, 35 % male) underwent color- coded duplex sonography of precerebral and cerebral blood vessels (CCDS), had checked brachial blood pressure and blood test. Vascular pathology detected by CCDS was confirmed by CT angiography. Some of patients underwent X-ray, EEG, CT scan or MRI examination.

Results: Isolated dyslipidemia was the reason for observation in 2% of cases only, although 56% of surveyed had registered high level of cholesterol at the moment of observation or in the past. Patients with arterial hypertension (14% of all) had atherosclerotic lesions in arteries in 42% of cases. From 22% of patients with vertiginous syndromes and tinnitus CVD was proved in 5% of cases. Vascular pathology in cases of headache (18% of all) was found in only 11%. Silent atherosclerotic process in pre-cerebral arteries was suspected in 15% of patients but proved in 27% of all surveyed.

Conclusion: The underestimation of dyslipidemia and arterial hypertension as a stroke risk factors and the mismatch of diagnoses in patients with unspecified vestibular disorders and headache was found. The prevalence of detected silent carotid stenoses from all suspected proved the efficacy of US vascular screening in prevention, detection and follow-up of CVD.

Keywords: Stroke prevention, Stroke risk factors, Cerebrovascular diseases, Stenosis of precerebral and cerebral arteries, Vascular ultrasound screening, Vestibular disorders, Headache.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S10


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Original Article


Carotid ecodoppler and transesophageal echocardiography: complementary methods for evaluation of atherosclerosis? - read full article

By: Joana Chin, Ana Camacho, Patrícia Guilherme, Pedro Sousa, Vasco Marques, Paula Gago, Nelson Tavares, Rui Ferrinha, Sandra Cunha, Ana P. Silva, and Ilídio Jesus

Background: The purpose of this study was to assess the relationship between carotid ultrasonography (CU) and transesophageal echocardiography (TEE), regarding atherosclerotic disease findings, the presence of carotid plaques (CP), proximal aortic plaques (AP), carotid intima-media thickness (CIM), and the aortic intima-media thickness (AIM).

Methods: Sixty one patients (57.4% men, mean age 62.7 ± 14 years) were evaluated with CU and TEE with an interval inferior to one month. CIM was measured at the common carotid artery (CCA); CP was defined as a localizaed protrusion in the arterial lumen larger than 1.5 mm, in the CCA or the internal carotid, without uniform wall involvement. AIM was measured at the aortic arch; AP was defined as a hyperechogenic area with >2 mm of thickness.

Results: Thirty seven patients had CP and 19 had AP. Seventeen patients had plaques in both locations (p=0.002). There was a difference between the medians of AIM (1.4; IQR=0.5) and CIM (1.0; IQR=0.3) (p<0.001). There was a linear correlation between CIM and AIM (coef =0.378, p=0.003). The presence of CP was a predictor (OR 6.28, p=0.03) of AP. CIM (coef=0.52, p=0.05) and gender (coef=0.22, p=0.02) were predictors of AIMs.

Conclusion: The presence of CP was related to the presence of AP. There was a positive association between CIM and AIM. CU results can be used as surrogate markers of aortic atherosclerotic disease. Evaluation of thoracic aorta with TEE is important, since it provides additional information on the extent of atherosclerotic disease.

Keywords: Atherosclerosis, Transesophageal echocardiography, Carotid, Aorta, Intima-media, Plaque.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S11


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Original Article


Modifying effect of aortic atheroma on ischemic events recurrence in stroke patients with cervical and intracranial steno-occlusive disease - read full article

By: Liliana Pereira, Carina Fernandes, and Miguel Rodrigues

Background: Large artery atherosclerosis is a major cause of ischemic stroke. Ultrasound can assess aortic, supra-aortic and intracranial vessels. We describe the recurrence rate in patients with cervical/intracranial disease and aortic atheroma.

Methods: We performed a retrospective review of patients’ charts admitted to a Neurology ward with ischemic stroke/transient ischemic attack in a 5- year period. We collected clinical data, aortic, supra-aortic, and intracranial atherosclerotic changes whenever transesophageal echocardiogram was also available. Follow-up data was obtained from charts. Group comparison and recurrence risk estimates were done by Kaplan-Meier curves with Log Rank (LR) and Cox regression with Hazard Ratio (HR), with 95% confidence intervals (95% CI).

Results: Of 1300 patients, 337 underwent transesophageal echocardiogram (mean age 55.7 years; 62.9% male). Stenosis >50% or occlusion was found in 8.0% of carotid arteries, 4.2% of vertebral arteries, and 14.2% of intracranial vessels. Aortic complex plaques were found in 18.2%. Recurrence rate was 10.3% and lethality 1.3%, in 604.7 days of mean follow-up. No difference was found between risk factors of patients with or without recurrence. After 1-year of follow-up more events were seen with cervical/intracranial disease (11.7% vs 2.8%, LR p=0.006). However, cervical/intracranial disease is not predictive of recurrent events in patients without aortic atheroma (LR p=0.607), while the association is strong if aortic atheroma is present (LR p=0.013; HR=4.9; 95% CI 1.2-19.5).

Conclusion: In stroke patients investigated with transesophageal echocardiogram, cervical/intracranial disease had higher 1-year recurrence risk, but not in subjects without aortic atheroma. Presence of aortic atheroma slightly further increases recurrences.

Keywords: Ischemic stroke, Stroke recurrence, Aortic atherosclerosis, Carotid atherosclerosis, Intracranial atherosclerosis.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S12


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Original Article


Internal carotid artery stenosis: validation of Doppler velocimetric criteria - read full article

By: Ana Monteiro, Rosa Santos, Carmen Ferreira, Andreia Costa, and Elsa Azevedo

Background: Carotid endarterectomy is effective in reducing recurrent stroke in patients with carotid stenosis. Duplex sonography is widely used for diagnosing internal carotid artery (ICA) stenosis. Surgeons often base management decisions solely on this technique. Published velocimetric criteria should be validated in each laboratory. This study aims to validate Doppler velocimetric criteria for different grades of ICA stenosis and evaluate intracranial collateralization circuits.

Methods: Duplex scans from 10,435 consecutive patients routinely referred to our Neurosonology Unit from 2003 to 2011 were reviewed. Cases with ICA stenosis ?50% (ultrasonographic morphologic criteria) were grouped by percentage of stenosis (ECST method). Mean ICA peak-systolic (PSV) and end-diastolic velocities (EDV), carotid index and presence of collateral flow were recorded. Pearson’s coefficient was used to correlate percentage of stenosis and velocity parameters. One-way ANOVA was performed for the presence of collateralization.

Results: Nine-hundred and sixty cases of ICA stenosis ?50% were identified. The Pearson’s correlation values were R=0.802, p<0.001; R=0.724, p<0.001 and R=0.769, p<0.001 for the PSV, EDV and carotid index, respectively. The presence of collateral flow increased significantly for a stenosis ?70% (p<0.001). For stenosis ?70%, PSV >182 cm/s showed a sensibility of 80%, specificity of 82% and accuracy of 88%, EDV >61 cm/s showed a sensibility of 76%, specificity of 80% and accuracy of 86%, and carotid index >2.3 showed a sensibility of 82%, specificity of 82% and accuracy of 89%. These velocities were superior to the recently published consensus criteria for diagnosing stenosis ?70%. Collateral blood flow increased significantly for stenosis ?70% (p<0.001).

Conclusion: This work defined optimal velocimetric criteria for ICA stenosis in our laboratory, enabling the correct diagnosis when morphological criteria are lacking. The presence of collateralization was important to identify hemodinamically significant stenosis.

Keywords: Internal carotid artery stenosis, Velocimetric criteria, ECST, NASCET; Endarterectomy, Collateral blood flow.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S13


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Original Article


Reversal of ophthalmic artery blood flow direction and severe ipsilateral carotid stenosis - read full article

By: Miguel Grilo, Ana Monteiro, Rosa Santos, Carmen Ferreira, Andreia Costa, and Elsa Azevedo

Background: The assessment of ophthalmic artery flow direction by transcranial Doppler sonography has become part of the cerebrovascular routine examination in stroke patients. It provides helpful information for the investigation of collateral circulation and can evaluate the hemodynamic significance of high-grade internal carotid artery (ICA) stenosis. Our aim was to determine the value of assessing the direction of ophthalmic artery blood flow in the setting of routine color flow duplex ultrasonography examination of patients with ipsilateral carotid disease.

Methods: We reviewed 967 ultrasound carotid scans performed in our Neurosonology Unit from January 2003 to December 2011 with ICA stenosis ?50%, and assessed ophthalmic artery flow direction.

Results: Ophthalmic artery flow reversal was seen in 73 cases, 62 (85%) of which were in cases of ICA stenosis ?80%. Flow reversal in ophthalmic artery had a sensitivity of 43%, specificity of 99%, negative predictive value of 91% and positive predictive value of 85% for ICA stenosis ?80%.

Conclusion: We found a significant association between reversal of ophthalmic artery flow and carotid stenosis ? 80% with an excellent specificity and negative predictive value. Assessing ophthalmic artery can be especially important in patients with difficult duplex scans or with stenosis in the pre-ophthalmic artery intracranial segment of internal carotid artery, where duplex scan may fail to detect the lesion. Evaluation of ophthalmic artery blood flow direction is therefore feasible and accurate with Doppler ultrasound, and it brings very useful information to better assess intracranial hemodynamic status that can influence treatment decisions.

Keywords: Carotid stenosis, Ophthalmic artery, Reversed ophthalmic artery flow, Cerebral collateral flow pathways, Transcranial Doppler, Carotid duplex ultrasonography.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S14


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Original Article


Simulated hemodynamics in human carotid bifurcation based on Doppler ultrasound data - read full article

By: Luísa C. Sousa, Catarina F. Castro, Carlos C. António, João M.R.S. Tavares, André M.F. Santos, Rosa M. Santos, Pedro Castro, and Elsa Azevedo

Background: Atherosclerotic lesions commonly develop at arterial branch sites. Non-invasive carotid artery ultrasound is a well-established and effective method that allows real-time imaging and measurement of flow velocities. We aimed to develop a methodology for patient-specific computational 3D reconstruction and blood flow simulation based on ultrasound image data.

Methods: Subject-specific studies based on the acquisition of a set of longitudinal and sequential cross-sectional ultrasound images and Doppler velocity measurements at common carotid artery (CCA) bifurcation were performed at a university hospital. A developed simulation code of blood flow by the finite element method (FEM) that includes an adequate structured meshing of the common carotid artery bifurcation was used to investigate local flow biomechanics.

Results: Hemodynamic simulations of CCA bifurcations for six individuals were analyzed. Comparing pairs (Doppler, FEM) of velocity values, Lin’s concordance correlation coefficient analysis demonstrated an almost perfect strength of agreement (?c = 0.9911), in patients with different degrees of internal carotid artery (ICA) stenosis. Numerical simulations were able to capture areas of low wall shear stress correlated with stagnation zones.

Conclusion: Simulated hemodynamic parameters can reproduce the disturbed flow conditions at the bifurcation of CCA and proximal ICA, which play an important role in the development of local atherosclerotic plaques. This novel technology might help to understand the relationship between hemodynamic environment and carotid wall lesions, and have a future impact in carotid stenosis diagnosis and management.

Keywords: Doppler image-based analysis, Carotid bifurcation, Computational fluid dynamics, Wall shear stress.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S15


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Original Article


Transcranial color coded sonography: advanced approach using ultrasound fusion imaging - read full article

By: Stephan J. Schreiber, José M. Valdueza, and Florian Doepp

Background: Transcranial color-coded sonography (TCCS) is a well established method to study intracranial parenchymal and vascular structures. It is, however, limited by the need to insonate through available bone windows, resulting in oblique imaging planes, which can hinder easy allocation, particularly within the brain parenchyma and limit the opportunity for direct comparison with other imaging techniques. The objective of this study was to analyze the diagnostic yield of the ultrasound fusion imaging (UFI) technique using standard diagnostic approaches.

Methods: UFI is a new technique, permitting an online matching and comparison of live ultrasound images with preregistered CT or MRI images by means of a local electromagnetic field. The principles and setup of the technique for transcranial UFI is demonstrated and examples of its use in assessing established insonation planes given.

Results: UFI is suitable for transcranial insonation and allows easy combination of live ultrasound with routine diagnostic CT or MRI image datasets in the classical TCCS transtemporal and transforaminal insonation planes. System setting and matching is fast and movement artifacts are eliminated by the use of a motion tracker correction. First application in patients demonstrates easy identification and comparison of structural lesions like dilated ventricles, arachnoid cyst, or subdural hematoma.

Conclusion: UFI offers a unique opportunity to study transcranial ultrasound and CT or MRI anatomy simultaneously. It seems therefore particularly promising to be further analyzed concerning its potentials in teaching and education as well as in any intracranial condition in which repetitive intracranial imaging is required.

Keywords: Ultrasound, Virtual navigation, Transcranial color-coded sonography, Duplex ultrasound, Imaging planes.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S16


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Original Article


Clinical predictors of increased middle cerebral artery pulsatility - read full article

By: Ana Gouveia, João Sargento-Freitas, João Madaleno, Joana Penetra, Fernando Alves-Silva, Cristina Machado, Gustavo Cordeiro, and Luís Cunha

Background: Transcranial Doppler Pulsatility Index (PI) has traditionally been interpreted as a descriptor of distal cerebrovascular resistance. Many authors have investigated its usefulness in the context of traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and hydrocephalus. Nonetheless, many doubts remain about its interpretation in cerebrovascular prevention. The aim of our study is to identify the clinical predictors of increased PI.

Methods: We conducted an analysis of a prospective database including all patients undergoing cerebrovascular ultrasonographic evaluation during 2011. We excluded patients with ?70% stenosis or occlusion in any intra or extracranial artery, stenosis in middle cerebral artery (MCA), atrial fibrillation, patients without transtemporal sonographic window and all evaluations performed in context of TBI, SAH, acute ischemic stroke or intracranial hypertension. The mean PI of both MCA, measured in its middle third after a minimum of 10 minutes of rest in the supine position, was registered. Vascular risk factors and clinical conditions were analyzed.

Results: Of the 947 patients analyzed, 446 were included, of which 287 (64.3%) were male. The mean age was 62.7 years (SD = 14.92) and the mean PI was 0.995 (SD = 0.240). In multivariate analysis, age (regression coefficient Beta (B):0.007, 95% CI: 0.005-0.009, p<0.001), hypertension (B:0.056, 95% CI: 0.003-0.108, p=0.037) and diabetes mellitus (B:0.064, 95% CI: 0.006-0.121, p=0.030) were identified as predictors of increased PI.

Conclusion: These results suggest that PI is associated with vascular risk factors classically responsible for small vessel disease. We discuss the pathophysiology of elevation of PI and its possible usefulness in cerebrovascular prevention.

Keywords: Pulsatility Index, Transcranial Doppler, Cerebrovascular resistance, Small vessel disease, Cerebrovascular prevention.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S17


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Original Article


Impaired autoregulation is associated with mortality in severe cerebral diseases - read full article

By: Bernhard Schmidt, Jens J. Schwarze, Marco Weinhold, Vesna Lezaic, Marek Czosnyka, and Jürgen Klingelhöfer

Background: Small cerebral vessels respond to variations of cerebral perfusion pressure (CPP) by changes of vessel diameter inducing changes of blood flow resistance and keeping cerebral blood flow constant. This mechanism is called cerebral autoregulation (CA). An index Mx, observing correlation between cerebral blood flow velocity (CBFV) and CPP has been recently introduced for assessment of state of CA during spontaneous changes of CPP. In the current study, the relationship between lethal outcome during hospitalization and Mx index was investigated.

Methods: Thirty patients (18-77 years, mean 53±16 years) with severe cerebral diseases were studied. CBFV, arterial blood pressure (ABP,) and intracranial pressure (ICP) were simultaneously recorded. Assessments were repeated at days 2, 4 and 7. Mx was calculated retrospectively, as averaged correlation between CBFV and CPP (=ABP-ICP). Positive values of Mx indicated impairment of CA.

Results: Six of the patients died in-hospital. In this group Mx was significantly higher than in the group of survivors (0.28±0.40 versus 0.03±0.21; p<0.05). Changes of Mx during days of monitoring (Mx last day - Mx first day) were not significantly related to mortality. Nine patients showed an Mx >0.2, four of them died, whereas from the 21 patients with Mx <0.2 only two died . The association between increased Mx and death was significant (p<0.05, Fisher’s exact test). Mx correlated significantly with Glasgow Outcome Score (GOS) in the subgroup of patients with known GOS (N=21; R=-0.56, p<0.05).

Conclusion: Increased Mx indicates impairment of CA and is associated with risk of death in patients with severe cerebral diseases.

Keywords: Cerebral autoregulation, Cerebral perfusion pressure, Intracranial pressure, Cerebral disease.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S18


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Capability of cerebral autoregulation assessment in arteriovenous malformations perinidal zone - read full article

By: Vladimir Semenyutin, Grigory Panuntsev, Vugar Aliev, Andreas Patzak, Dmitry Pechiborsch, and Alexandr Kozlov

Background: Cerebral autoregulation (CA) in the region of an intracranial artery involved in blood supply of arteriovenous malformations (AVM) is impaired. This could be due to pathologic shunting, disguising real state of CA, or brain lesion in perinidal area. It is quite difficult to define the influence of both factors on CA. The purpose of this study was to assess dynamics of CA in patients with AVM in perioperative period.

Methods: The radicality of AVM embolization (Hystoacryl or Onyx) was evaluated in 47 patients by cerebral angiography and blood flow index in precerebral arteries with a Vivid E ultrasound scanner. We monitored blood flow velocity (BFV) in basal cerebral arteries with Multi Dop X and blood pressure (BP) with Finapres-2300. CA was assessed with cuff test (autoregulation index – ARI) and phase-shift (PS) between spontaneous oscillations of BP and BFV within the range of Mayer’s waves.

Results: Preoperative values of ARI and PS were 1.8±0.7 and 0.3±0.2 rad, respectively. In 15 cases with total embolization a significant (p<0.005) increase of rate of CA (ARI: 6.0±1.1, PS: 0.9±0.1 rad) was noted. In other two cases with total embolization, CA didn’t change significantly after operation. In 14 cases with subtotal embolization postoperative ARI and PS were 3.6±0.5 and 0.7±0.1 rad, respectively (p<0.05), and in cases with partial elimination were 2.1±0.6 and 0.4±0.1 rad (p>0.05).

Conclusion: CA assessment could be used for detection of its real impairment in perinidal zone of AVM during the staged endovascular treatment and for prognostication of postoperative complications.

Keywords: Cerebral autoregulation, Cerebral blood flow volume, Arteriovenous malformation, Embolization.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S19


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Convergent cross mapping: a promising technique for cerebral autoregulation estimation - read full article

By: Linda Heskamp, Aisha S.S. Meel-van den Abeelen, Joep Lagro, and Jurgen A.H.R. Claassen

Background: Cerebral autoregulation (CA) is the physiological mechanism that keeps the cerebral blood flow velocity (CBFV) relatively constant despite changes in arterial blood pressure (ABP). Currently, transfer function analysis (TFA) is widely used to assess CA non-invasively. TFA is based on the assumption that CA is a linear process, however, in reality CA is a non-linear process. This study explores the usability of convergent cross mapping (CCM) as a non-linear analysis technique to assess CA.

Methods: CCM determines causality between variables by investigating if historical values of a time-series X(t) can be used to predict the states of a time-series Y(t). The Pearson correlation is determined between the measured Y(t) and the predicted Y(t) and increases with increasing time-series length to converge to a plateau value. When used for CA, normal and impaired CA should be distinguishable by a different plateau value. With impaired CA, ABP will have a stronger influence on CBFV, and therefore the CBFV signal will contain more information on ABP. As a result, the correlation converges to a higher plateau value compared to normal CA. The CCM method was validated by comparing normal CA (normocapnia: breathing 0-2% CO2) with a model of impaired CA (hypercapnia: breathing 6-7% CO2).

Results: CCM correlation was higher (p=0.01) during hypercapnia (0.65 ± 0.16) compared to normocapnia (0.51 ± 0.18).

Conclusion: CCM is a promising technique for non-linear cerebral autoregulation estimation.

Keywords: Cerebral autoregulation, Convergent cross mapping, Non-linear analysis.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S20


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Original Article


Continuous monitoring of vertebrobasilar hemodynamics utilizing TCDS transducer holder Sonopod during postural changes - read full article

By: Toshiyuki Shiogai, Mayumi Yamamoto, Yuka Arima, Daichi Yamasaka, Kenji Yoshikawa, Toshiki Mizuno, and Masanori Nakagawa

Background: The objective was to evaluate continuous monitoring in the vertebrobasilar arteries (VBA), utilizing the transducer holder Sonopod for transcranial color duplex sonography (TCDS), vertebrobasilar hemodynamics and autoregulation, during postural changes.

Methods: Subjects were five normal controls and seven patients: two patients with arterial hypertension, three with dizziness (peripheral neuropathy, hepatic cirrhosis, and unknown), one with lacunar infarction and diabetes mellitus (LI/DM), and one with spino-cerebellar degeneration (SCD). TCDS utilizing the transducer holder Sonopod was used to continuously monitor the intracranial VA and BA. Blood pressure (BP), heart and respiration rates were also monitored. During two series of postural changes (supine or sitting to/from standing), a) clinical symptoms, b) BP: systolic, mean, and diastolic pressures (SBP, MBP, and DBP), c) TCDS: time-averaged maximum velocity (Vmax) and pulsatility index (PI), estimated cerebrovascular resistance (eCVR) = MBP/Vmax, and autoregulation index (ARI) = %?eCVR/%?MBP, were all calculated on the basis of maximum and minimum values during both series and of separate values from sitting to standing.

Results: a) Severe dizziness resulted in an inability to remain standing in two patients (LI/DM and SCD). b) BP: 1) ?DBP >10mmHg in all cases. 2) ?SBP>20mmHg in 2 controls and all but one patient (LI/DM). c) TCDS: 1) ?PI and ?eCVR tended to increase in the two severe dizziness patients. 2) ARI for both normal control subjects and patients fluctuated in all series and during individual standing.

Conclusion: Continuous TCDS monitoring in the VBA during postural changes is capable of evaluating vertebrobasilar autoregulation associated with autonomic regulation.

Keywords: Transcranial color duplex sonography, Transducer holder sonopod, Vertebrobasilar artery, Autoregulation, Postural changes.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S21


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Transcranial targeting low frequency ultrasound thrombolysis system: evaluation of the probe fixation devices for blood flow monitoring - read full article

By: Jun Shimizu, Hidetaka Mitsumurab, Ayumi Arai, Jun Kubotaa, Takashi Azuma, Takeki Ogawa, and Hiroshi Furuhata

Background: We developed the transcranial targeting low frequency ultrasound thrombolysis system (TCTLoFUT) which will be used for an acute ischemic stroke (AIS). TCT-LoFUT can emit the T beam (500 kHz continuous waveform, 0.72 W/cm2) for thrombolysis to a target thrombus with the D beam (2 MHz pulsed waveform, 0.72 W/cm2) for diagnostic TC-CFI. We report the in vitro thrombolytic efficacy by TCTLoFUT and estimate the blood flow monitoring in human with a newly developed head-fixture for TCT-LoFUT using a same aspect of commercial probe.

Methods: A) Sonothrombolysis experiment: The 1.25 ml of blood was extracted by the healthy volunteer. The blood in a syringe for 40 min and created a fresh thrombus with a centrifuge (4500 rotation / 5 min). The alteplase concentration in a syringe solution was made to be 358 IU/ml. The intermittent T/D beams were applied under the 60 min of protocol which was described in our studies. The rt-PA independent group (rt-PA, n=39) and the rt-PA + TCT-LoFUT group (rt-PA+US, n=13) were compared. The sound intensity in a syringe was 0.05 W /cm2. B) Blood-flow monitoring evaluation: We evaluated the blood flow monitoring by middle cerebral artery (MCA) detection in 10 healthy volunteers for 30 min. We used the 2.5 MHz TCCFI probe with the fixture which was developed for same aspect of the TCT-LoFUT.

Results: A) Sonothrombolysis experiment: The recanalization rate of 60 min after were 64.1% in rt-PA group and 92.3% in rt-PA+US group. Average recanalization time was shortened from 27.2 min in rt-PA group to 21.4 min in rt-PA+ US group ( p < 0.01). B) Blood-flow monitoring evaluation: The MCA could be detected using the fixture for TCT-LoFUT.

Conclusion: TCT-LoFUT has a function of the blood-flow monitoring simultaneously with a thrombolysis accelerating effect which will be used for AIS patients.

Keywords: Sonothrombolysis, Low frequency, Color flow imaging, Fixation.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S22


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Original Article


Improving uniformity of intensity distribution of ultrasound passing through a human-skull fragment by random modulation - read full article

By: Osamu Saito and Hiroshi Furuhata

Background: Transcranial ultrasound irradiation can enhance the effect of a thrombolytic-agent tissue plasminogen activator (tPA), depending on the intensity. Because of the ultrasound’s interference, its intensity distribution near a transducer is not uniform, i.e., there are low-intensity cold spots and high-intensity hot spots. Furthermore, the distribution can be more inhomogeneous when the ultrasound passes through a human skull. At the cold spots, the enhancement of the tPA effect is less than in other areas, whereas at the hot spots, the risk of hemorrhages is higher. Therefore, the reduction of the difference in the intensity between the cold and hot spots, i.e., improving the uniformity of the ultrasound field, is important for effective and safer ultrasound irradiation. The purpose of this study is to show that the uniformity of the ultrasound field can be improved by random modulation of the activating signal used for the ultrasound emission.

Methods: A hydrophone measurement of the distribution of ultrasound passing through a human skull fragment in water was performed for each of the sinusoidal activations (500 kHz) and random modulation. To quantify the degree of uniformity of an intensity distribution, the term uniformity index is newly defined in this paper. This index is smaller for more homogeneous distribution.

Results: It was shown that ultrasound radiation was more homogeneous during random modulation. The uniformity index was smaller for sinusoidal activation than for random modulation in the near-field region.

Conclusion: This technique is expected to be useful for developing effective and safer therapeutic equipment.

Keywords: Sonothrombolysis, Uniformity, Random modulation, Transcranial ultrasonication.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S23


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Collateral cerebral venous outflow by scalp veins in patients with parasagittal meningiomas - read full article

By: Vladimir Semenyutin, Dmitry Pechiborsch, Vugar Aliev, Andreas Patzak, Grigory Panuntsev, and Alexandr Kozlov

Background: Invasion of the superior sagittal sinus (SSS) by parasagittal meningiomas (PSM) causes formation of collateral pathways of venous outflow (including scalp veins) from the cranial cavity. However their importance, considering this function, is still under question. The purpose of this study was to determine the importance of scalp veins in collateral cerebral venous outflow in patients with PSM.

Methods: Eight patients with PSM (52-73 year-old) with invasion of the SSS and 4 healthy volunteers were examined, in supine position, with bilateral transcranial Doppler monitoring (MultiDop X, DWL) of blood flow velocity (BFV) in both middle cerebral arteries (MCA), and with blood pressure (BP) monitoring using photoplethysmography (Ohmeda, Finapres 2300). In patients circular compression of scalp veins with pneumatic cuff around glabella and inion during 3 minutes was performed, while in volunteers a simultaneous transient complete compression of both internal jugular veins controlled by ultrasound in B-mode (Vivid E, GE) was performed.

Results: Significant changes of BFV, pulsatility index (PI) and BP were not detected during the whole period of compression of scalp veins. These data indicate a low importance of scalp veins in collateral venous outflow from the cranial cavity. Simultaneous compression of both internal jugular veins in all 4 volunteers caused BFV decrease by 9±4% (p<0.05) and PI increase by 18±12% (p<0.05) associated presumably with intracranial hypertension and impairment of venous outflow from the cranial cavity.

Conclusion: Temporary circular compression of scalp veins in patients with invasion of the SSS does not cause impairment of venous outflow from the cranial cavity, which presumably indicates their low importance.

Keywords: Scalp veins, Cerebral venous outflow, Parasagittal meningiomas, Collateral venous pathways.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S24


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Original Article


The effect of clinical, demographic and lifestyle factors on executive functions in middle aged and older women - read full article

By: Matthew Currell, Gerard J. Byrne, and Nancy A. Pachana

Objective: Global population ageing has contributed to an increased prevalence of cognitive dysfunction. The current study investigated the psychological, health, lifestyle and demographic factors later in life that are associated with executive function.

Methods: AThe data for this project were collected as part of the Longitudinal Assessment of Women (LAW) study. A neuropsychological test battery was administered to 376 women and this was augmented by self-report data from a postal questionnaire covering psychological, lifestyle and sociodemographic factors.

Results: Investigation of variables influencing a composite measure of executive functioning demonstrated that increasing age and higher self-reported depression had a negative relationship with executive abilities while higher levels of education, mild alcohol consumption and higher BMI had a positive relationship with executive functioning.

Conclusion: These findings suggest that treating depression, and encouraging a healthy diet, which may include mild alcohol consumption, may positively affect executive performance in older adults.

Keywords: Executive functioning, Depression, Anxiety, Diabetes, Obesity, Alcohol.

International Journal of Clinical Neurosciences and Mental Health 2014; 1:9


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Original Article


Differences between ethnic and non ethnic-specific clinics for Portuguese-speaking mental health patients explained by providers - read full article

By: Marta Gonçalves, Diana Farcas, and Benjamin Cook

Background: A previous quantitative study conducted in a health care system in a Northeastern U.S. metropolitan area identified greater adequacy of mental health care for Portuguese-speaking patients at a ethnic-specific Portuguese Mental Health Program (PMHP) compared to non ethnic-specific clinics. The objective of the present study was to understand, from a provider perspective, the disadvantages and difficulties of treating Portuguese-speaking immigrants with mental illness, and to elicit recommendations for improving care for this population.

Methods: We conducted three interviews with providers using a structured interview guide that elicited questions related to the clinic, its patients, provider’s work, and ways in which the providers tailored mental health services to the Portuguese-speaking population. Responses were analyzed using content analysis, recording the frequency and saliency of particular words and phrases, and identifying keywords or repeated ideas.

Results: Providers reported that the PMHP clinic is successful because it offers a unique set of services, provides services in the Portuguese language 100% of the time, and has existed for a long time in their community. Important differences between patients from Portugal and patients from Brazil include demographic characteristics, and patients’ and relatives’ feelings about seeking mental health treatment.

Conclusion: This study supports policy recommendations to expand the availability of ethnic specific clinics. These clinics may play an especially important role in cost reduction and quality enhancement efforts being undertaken in urban safety net hospitals that serve a large number of individuals of racial/ethnic minority background.

Keywords: Retention, Mental health care, Ethnic specific, Qualitative, Providers perspective.

International Journal of Clinical Neurosciences and Mental Health 2014; 1:13


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Original Article


Mental health representations, help-seeking behaviors, and perceived access barriers of expatriate adolescent children - read full article

By: Marta Gonçalves and Diana Farcas

Background: Currently, due to globalization and the world’s economic situation, international organizations tend to remain competitive by acquiring employees with global management skills, the so called expatriates. Usually, family members accompany expatriates in the international relocation experience. Expatriate adolescent children (EAC) may suffer additional psychological distress. In order to better assist them it is important to understand their mental health representations, help-seeking behaviors, and pWe conducted an online survey, which was completed by 51 students aged 12–16 years of an international school in Portugal, 35.3% of which EAC.

Results: Results show similarities and differences in the way mental health is perceived by EAC and non-EAC. Both perceive a good mental health as "not using drugs", while not feeling well psychologically is understood as "something that has to be taken seriously". The most predominant help-seeking behavior is distraction (e.g. reading), while talking with someone presents high average values and significant differences between the two groups of students. EAC mostly refer that problems should be solved in the family context. The ones who have already sought a mental health professional while in the host country, refer problems related to classmates and family.

Conclusion: An improved understanding of representations and behaviors for expatriate adolescent children, as well as knowledge of current interventions involving the family-school-primary care triangle among expatriate families will lead to a better adjustment of expatriates in international assignments. 


Keywords: Mental health representations, Help-seeking behaviors, Perceived access barriers, Expatriate adolescent children.

International Journal of Clinical Neurosciences and Mental Health 2014; 1:17


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Original Article


Welcome (one) more child: perspectives from mothers of large and non-large families - read full article

By: Marta Gonçalves and Rosário Boavida

Background: In many countries around the world we are currently witnessing a large decrease in the fertility rate. This phenomenon brings several social sustaining problems. Large families (families with three or more children) seem therefore essential on contradicting this tendency. The aim of this study is to explore attitudes towards conception in large (LFM) and non-large families mothers (NLFM).

Methods: We used a quantitative approach (N=210 LFM; 170 NLFM) and we analyzed how the family type relates to variables such as satisfaction with life, religiosity, attitudes towards contraception, and attitudes towards abortion. These variables were accessed in each participant through an online survey.

Results: We found evidence supporting the hypothesis that LFM have higher levels of satisfaction with life and religiosity; they have more negative attitudes towards contraception and abortion. We have also tested the hypotheses of the relationship between family type and attitudes towards contraception and abortion being moderated by the strength of different types of religiosity, finding some supportive data, at least for the attitudes towards contraception.

Conclusion: Although we conclude that additional research on large families and reproductive behavior is needed, this study emphasizes some of the factors that differentiate the specific population that contributes to an increase the fertility rate.

Keywords: Large families, Satisfaction with life, Religiosity, Conception.

International Journal of Clinical Neurosciences and Mental Health 2015; 2:2


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Original Article


Vulnerability to stress and psychopathology among third year medical students - read full article

By: João Gama Marques, Daniel Machado, Sílvia Ouakinin, and Maria Luísa Figueira

Background: Some studies describe high prevalence of psychological disturbances among 3rd year medical students. The specific nature of factors like perceived stress, medical identity formation, and psychodynamic features are usually pointed as responsible for triggering factors of emotional disturbances but there is resistance among medical student to search for help. The objective of the study was to assess stress vulnerability and psychopathology risk among 3rd year medical students in Portugal.

Methods: The authors conducted a cross-sectional, survey of medical students at the biggest Portuguese medical school, through an anonymous self-report questionnaire, including sociodemographic data, psychiatric history illness, plus stress vulnerability, with 23 Questions on Vulnerability to Stress (23QVS), and psychopathology, with Symptom Checklist 90 Revised (SCL-90-R).

Results: A 56% response rate was obtained among 228 students (70.1% women), with mean age of 20.82+1.27 years (mean ± standard deviation). Main stress factor was academic issues (50%), with female being more vulnerable than male. Stress vulnerability’s mean value was 33.88 ± 9.28 (cut-off point 23QVS > 43) and SCL90R’s Global Severity Index mean value was 0.389 (cut-off point SCL-90-R > 1.5). In a subsample of 24 students, with levels of stress vulnerability above cut-off point (23QVS > 43), a positive correlation was found with interpersonal sensitivity (r=0.517; p=0.1), depression (r=0.497; p=0.13), phobic anxiety (r=0.443; p=0.03), psychoticism (r=0.427; p=0.038) and SCL-90-R’s Global Severity Index (r=0.47; 0.02).

Conclusion: Low mean values for stress vulnerability and psychopathology were found, and among vulnerable subjects, there was a strong correlation between both dimensions.

Keywords: Stress, Psychopathology, Medicine, Students.

International Journal of Clinical Neurosciences and Mental Health 2015; 2:3


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Original Article


The “Clinical Interview for Psychotic Disorders” (CIPD): Development and expert evaluation - read full article

By: Maria João Martins, Célia Carvalho, Paula Castilho, Ana Telma Pereira, and António Macedo

Background: New treatment approaches for psychosis indicate that effective interventions require a therapeutic focus on emotional regulation, cognitive appraisals, and functioning. Efficacy of psychotherapeutic interventions’ evaluation has changed from exclusively assessing symptom frequency/severity to a comprehensive and functional assessment of interference, functioning, and the relationship people have with symptoms. This shift led to new needs in clinical assessment. This study aimed to develop and submit to expert evaluation a new clinical interview for psychotic disorders which considers the new needs of the field.

Methods: CIPD was developed by a multidisciplinary team considering the DSM-5 criteria for psychotic and affective disorders. Relevant information was retrieved from leading research in the area of assessment and evaluation of interventions in psychosis. An expert panel of recognized professionals in the main areas of mental health evaluated each question of the interview (5-point Likert scale) regarding pertinence and clarity.

Results: A detailed description of CIPD is presented. Results from the experts’ evaluation showed that, overall, the CIPD questions were evaluated as pertinent and clear for the target population.

Conclusion: CIPD assesses both diagnosis or presence of psychotic symptoms and symptoms’ psychosocial correlates. Psychotherapy and pharmacotherapy may benefit from CIPD since it may detect subtle changes caused by intervention and changes in areas other than symptom reduction.

Keywords: Assessment, CIPD, Clinical Interview, Psychosis.

International Journal of Clinical Neurosciences and Mental Health 2015; 2:7


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Mindfulness-based intervention in cancer recovery: a pilot feasibility study in a Portuguese sample - read full article

By: José Carlos Lopes, Sandra Vilarinho, Vera Afreixo, Luís Almeida, Francisco Luís Pimentel, and David Shannon

Objectives: The aim of the present study was to assess, through a pilot randomised controlled trial, the feasibility and efficacy of a mindfulness-based intervention in oncology (MBIO) with Portuguese cancer patients, considering that such kind of interventions can be conditioned by cultural factors and that most studies have been carried out in countries with a different ethos. 
Methods: A Portuguese version of an eight-week MBIO was delivered to 26 ambulatory cancer patients, aged between 46 and 64 years, attending two hospital centres in Portugal. Patients’ health-related quality of life (QoL) and mindfulness processes were assessed before (T1), just after (T2), and 12 weeks following the programme (T3), with self-reported measures, using validated Portuguese versions of two scales: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the Mindful Attention Awareness Scale. 
Results: At T2, the attrition rate was null for the intervention group and 36% for the control group. Compared to controls and in reference to base-line (T1), participants in the intervention group had significantly (p ? 0.05) improved (a) QoL function score at T2, and (b) QoL global health status, total score and symptom score at T3. Mindfulness approached a significant (p = 0.12) positive change at T2. 
Conclusion: Overall, findings indicate that MBIOs may be feasible and effective in a Portuguese sample, opening up perspectives for larger scale studies, with more representative samples of the Portuguese population. 

Keywords: Cancer; Oncology; Mindfulness; Mindfulness-Based Intervention; Quality of Life.

International Journal of Clinical Neurosciences and Mental Health 2016; 3:4
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3.4

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Original Article


A comparative study of innate immunity markers in Alzheimer's disease, Mixed dementia and Vascular dementia - read full article

By: Liubov Androsova, Nataliya Mikhaylova, Svetlana Zozulya, Aleksandr Dupin, and Tatyana Klyushnik

Background: Innate immunity is currently considered to be an important component of pathological cascade in old age dementia. The aim of this study was to evaluate activity of inflammatory markers such as leukocyte elastase and alpha-1 proteinase inhibitor, as well as concentration of C-reactive protein and interleukin-6 in blood plasma of patients with pure’ AD, mixed dementia and VaD of varying severity. 
Methods: Several parameters of innate immunity such as leukocyte elastase activity (LE), the functional activity of ?1-proteinase inhibitor, the concentration of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in blood plasma of elderly patients with main forms of dementia including: Alzheimer’s disease (AD), mixed dementia (MD) and vascular dementia (VaD).
Results: A total of 161 in-patients and 39 control subjects were included in the study. The levels of innate immunity markers were found to depend on the severity of dementia. The decreased activity of LE in AD and MD is suggested to be due to the alteration of neutrophils degranulation activity or to changes in enzyme properties. A negative correlation between the level of IL-6 and degree of cognitive impairment in AD (Spearman r= -0.43; p<0.05) indicates significantly that levels of proinflammatory cytokines may characterize the severity of the process having the great impact on (lower) total MMSE score. Elevated level of CRP is likely to be a biological marker of an early stage of disease in VaD. 
Conclusions: Our results confirm the presence of an inflammatory component in the pathological cascade of AD, MD and VaD. 

Keywords: Alzheimer’s disease, Mixed dementia, Vascular dementia, Innate immunity, Leukocyte elastase activity, Functional activity of ?1-proteinase inhibitor; C-reactive protein, Interleukin-6 


Special Issue on Controversies in Neurology. From the 10th World Congress on Controversies in Neurology (CONy), Lisbon, Portugal. 17–20 March 2016.

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 1):S03 

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Chronic obstructive pulmonary disease as a risk factor for dementia - read full article

By: Saule T. Turuspekova, Dmitriy Mitrokhin, Almaz Zhanayev, Aigerim Ablayeva, Gaukhar Zhilkibayeva, and Asiya Umarbayeva

Introduction: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. According to data released by the World Bank and the World Health Organization (WHO), it is expected that in 2020 it will be on the 5th place on the damage caused by diseases globally. Pulmonary pathology leads to disruption of cerebral blood flow. Insufficient oxygen supply to the brain at bronchial obstruction negatively affects the brain functions such as memory, attention, thinking. This study aims to identify the state of higher brain functions in patients with chronic obstructive pulmonary disease. 
Methods: There were studied 40 patients aged 26 to 87 years (28 men and 12 women) with COPD II, III and IV. Pulse oximetry was used to determine blood oxygen saturation. The study was conducted using the Montreal Cognitive Assessment Scale. 
Results: The study showed a significant reduction of memory, attention, thought in 14 patients (35% -<19 points), moderate decline of higher brain functions in 14 patients (35% -20 and 23 points ), a slight decrease - in 8 patients (20% -<25 points), and the norm– in 4 patients (10%). At the same time found a direct correlation between cognitive impairment and peripheral oxygen saturation: <95% saturation correlated with cognitive impairment and <85% saturation correlated with dementia. 
Conclusion: The present study indicates a significant impact of COPD on higher brain functions. 

Keywords: Chronic obstructive pulmonary disease (COPD), Mild Cognitive Impairment, Dementia

Special Issue on Controversies in Neurology. From the 10th World Congress on Controversies in Neurology (CONy), Lisbon, Portugal. 17–20 March 2016.

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 1):S04 

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The effects of intrathecal methylene blue and glyceryl trinitrate administration on orofacial pain in mice - read full article

By: Catalina Bohotin, Teodora Alexa, Andrei Luca, Andrei Dondas, Adriana Negru, and Radu Iliescu

Background: Nitric oxide (NO) is involved in several types of painful conditions. In patients with chronic migraine, glyceryl trinitrate, a pro-drug for NO, can induce a delayed migraine episode. In this study, we decided to assess the effects of intrathecal administration of a NO pro-drug (glyceryl trinitrate-GTN) and a NO scavenger (methylene blue–MB) on orofacial pain (OFP). 
Methods: 24 BALB/c mice were divided into three groups as follows: GTN group (0.1mg/kg, n=8), MB group (0.05mg/kg, n=8) and control group (NaCl, n=8). All groups received the substance by the intrathecal route. Two hours after drug/saline administration, formalin was injected into the upper lip and the time mice spent rubbing/liking the injected area was recorded. 
Results: Intrathecal administration of MB and NTG had no effect on the acute phase of OFP when compared with control. In the second phase, however, both drugs had an analgesic tendency; for GTN, this was statistically significant (p=0.025), and for MB the effect was less important (p=0.083). 
Conclusions: By centrally administering a NO pro-drug and a NO scavenger, we expected to modulate NO production in formalin-induced OFP. Our results demonstrated that the acute phase of OFP does not depend on NO (neither of the drugs had any effect) and that both substances diminish pain perception in the persistent/inflammatory phase but only the NO pro-drug has a clear-cut antinociceptive effect. 

Keywords: Orofacial Pain, Nitric Oxide, Nitroglycerin, Methylene Blue, Analgesia, Intrathecal Injections

Special Issue on Controversies in Neurology. From the 10th World Congress on Controversies in Neurology (CONy), Lisbon, Portugal. 17–20 March 2016.

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 1):S17 

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