Special Issue : Trends and Innovations in Neurology and Neuroscience


Trends and Innovations in Neurology and Neuroscience


Aaron I. Vinik, M.D., Ph.D.1, Etta J. Vinik, MEd.1, Ying-Chuen Lai, M.D.2, Steven Morrison, Ph.D.3, Sheri R. Colberg, Ph.D.4, Serina Neumann, Ph.D.5, Joshua Edwards, MS.6, Scott Gerwe, M.D1, Carolina Casellini, M.D.1, Henri Parson, Ph.D.1

1Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA
2Department of Internal Medicine, National Taiwan University Hospital Yun Lin Branch, Taiwan
3School of Physical Therapy and Athletic Training, Old Dominion University, Norfolk, VA
4Human Movement Sciences Department, Old Dominion University, Norfolk, VA
5Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA
6Health Care Analytic Institute Eastern Virginia Medical School

*This work was performed at Eastern Virginia Medical School and Old Dominion University, Norfolk, VA


Aims To explore the impact of the autonomic nervous system function in “disease-free” people for testing and appropriate therapies in different age-groups.

Methods Seventy-five disease-free volunteers who participated in a previous study were randomly selected from five age-groups (30-79 years) for a cross/sectional study to assess the impact of fatigue on cardiac/autonomic function by analysis of heart rate variability (HRV) and measures of cognitive and physical fatigue on quality-of-life-fatigue (QOLF) scores. Written informed consent was obtained and protocol approved. To induce fatigue, three 5-minute walking trials were performed on an instrumental treadmill, increasing the incline in increments of 2°/min to measure perceived exertion (RPE) at the beginning and end of each trial. Polar monitors measured heart rate (HR); a modified Borg 10-point scale measured RPE. Cardiac autonomic reflex tests (CART) with time/frequency domains analyzed HRV. QOLF scores were measured and analyzed for correlation with sympathetic/parasympathetic function on the Norfolk QOL-F fatigue scale.

Results QOL-F scores were not significantly different among 5 age groups, likely due to wide standard deviations and small subject numbers. Significant correlations between overall fatigue severity and several indices of HRV were found, independent of age, gender, and body mass index (p<0.05). Self-rated physical fatigue and compromised activities of daily living (ADLs) were related to sympathetic hyperactivity and autonomic imbalance (p=0.04). Participants in the (70–79-year-olds) category had impaired scores.

Conclusions The study identifies a relationship between autonomic nervous system function and cognitive and physical fatigue even in “disease-free” people in different age- groups and suggests that fatigue is impacted by somatic and autonomic nerve function. Higher self-ratings of perceived fatigue were associated with sympathovagal hyperactivity. Impaired HR response to exercise in older people corresponding with vagal over-activity, and paradoxically, best self-rated QOL-F, mandates clinical autonomic dysfunction testing and lifestyle therapies to prevent catastrophic events.

C. (Linda) M.C. van Campen1, MD; Frans C. Visser, MD, PhD1

1Stichting CardioZorg, Planetenweg 5, 2132 HN Hoofddorp, Netherlands


Introduction: In patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a higher-than-normal resting heart rate has been reported in a number of studies. As heart rate is linked to stroke volume, the present study explored the relationship between the supine heart rate and stroke volume index in healthy controls and in ME/CFS patients. Moreover, as patients with a postural orthostatic tachycardia syndrome (POTS) during tilt testing, have a higher supine heart rate than patients with a normal heart rate and blood pressure response during tilting, these two patient groups were also compared.

Methods and results: From a database of individuals who had undergone tilt-testing, including supine Doppler measurements for stroke volume index calculation, we selected ME/CFS patients and healthy controls without evidence of hypotension or syncope. 474 ME/CFS patients were analyzed, 314 with a normal heart rate and blood pressure response and 160 with POTS during tilt-testing, and 56 healthy controls. Resting stroke volume indices were similar between the 3 groups. All 3 groups had an inverse relation between the resting stroke volume index and resting heart rate (all p<0.0001). The slope of the relation was not significantly different between the 3 groups. Using the upper limit of the 95% prediction interval for the heart rate of healthy controls, 46 (15%) of patients with a normal heart rate and blood pressure response had a resting heart rate above the upper limit, 248 (85%) a heart rate between the upper and lower limit. In 47 (29%) patients developing POTS the resting heart rate was above the upper limit, and in 113 (71%) patients within the upper limit and lower limit. This distribution was significantly different between the two patient groups (p=0.0001).

Conclusion: Patients and healthy controls showed a significant and inverse relation between the SVI and heart rate at rest. Already at rest heart rate in patients developing POTS during tilt-testing were higher compared to the patients with a normal heart rate and blood pressure response per unit of SVI, but the heart rate of the majority of all patients fell within the limits of normal of healthy controls. The difference of patients with heart rate above the upper limit versus between the upper limit and lower limit deserves further investigation and may have therapeutic implications.

Edgar Friederichs1,2 & Petra Friederichs2

1University of Bamberg, Business and Economic Education, Germany
2Center of Learning and Development, Bamberg, Germany


Cerebral visual impairment (CVI) in children is, to our knowledge, a very common but until now very often neglected outcome of, among other things, a) a stressful pregnancy, b) preterm birth and c) stressful term birth with pre- and perinatal injuries. The entire visual system includes both the eyes and the brain, and damage can affect one or both of these organs. The visual brain-focused aim is that children gain precise visual access to their surroundings, linking visual information with the appropriate language and motor skills to both enable them to understand what they see and guide movements along the visual acuity. Thus, vision, language and motor skills typically evolve together during the first months of life.

The meaning of the so called ‘seeing sense’ is still not considered enough to understand its contribution to normal developmental stages and vision-related deterioration in childhood. A systematic diagnostic approach to CVI in the medical system is missing. Consequently, experimental interventions are very rare. However, due to the demographic development (e.g. the increase in preterm births) there is an increase in the prevalence and cerebral visual dysfunctions and the need for its treatment.

Early insult to the visual system affects more than visual brain perception. As visual brain processing is related to cognition, emotion, motivation and the motor system, early visual impairments could negatively influence the development of all these functional systems. Thus, human brain development depends on structural and functional visual conditions and can be significantly disturbed by cerebral visual impairment. This article emphasizes the influence of possible early damage to the visual pathways on general development and academic achievement and the implication of CVI in the development of affected children.

Philip H.C. Kremer1,2, Geert Jan Groeneveld1,2

1Center for Human Drug Research, Leiden, The Netherlands
2Leiden Academical Medical Center, Leiden, The Netherlands


With aging populations in many countries, the prevalence of neurodegenerative diseases is expected to increase in the upcoming decades. Currently, no disease modifying therapies for these conditions exist. Advances in genetics and proteomics have identified novel druggable targets for neurodegenerative diseases. Compounds modulating these targets have recently entered clinical trials. These compounds can be orally administered small drug molecules, intravenously dosed antibodies, intrathecally injected antisense oligonucleotides (ASOs), gene therapies, stem cells or viral vectors. For the development of these compounds to be successful, multiple challenges have to be overcome. In this review we discuss advances in drug development for each of the major neurodegenerative diseases, which, when applied to early phase drug studies, increase the chance of successful clinical development. Here we will limit ourselves to: 1) the use of biomarkers for understanding target and pathway engagement at an early stage of development, 2) novel approaches for increasing blood-brain barrier penetration and 3) advances in understanding cerebrospinal fluid flow dynamics in relation to neurodegeneration and target site distribution for intrathecally administered compounds.

Professor Colin Pritchard, Research Professor, Dr. Anne Silk, Senior Public Health Fellow, Faculty of Health & Social Sciences, Bournemouth University and Dr. Lars Hansen, Consultant Psychiatrist, Dept of Psychiatry, University of Southampton


Aims: To examine whether increased neurological deaths during 21st Century are predominately due to elderly demographics, or major influences of interactive-multiple environmental contributory factors? We examine WHO Early-Adult-Deaths (55-74yearolds), which is below Western life-expectancy, and total Age-Standardised-Death-Rates (ASDR) controlled by age, sex, and population, to challenge the demographic assumption.


Based upon WHO latest global neurological mortality categories, Nervous-Disease-Deaths and Alzheimer’s & Other Dementias, which provides the Combined Neurological Death, rates per million (pm), for the twenty-one West-Developed-Nations (WDN) over the period.

Early-Adult-Death rates based upon numbers of deaths, divided by 55-74 population and WHO total ASDR during the 21st Century. Increases between Over 75’s population and Over 75’s neurological mortality is compared using Odds Ratios. Numbers of deaths are indicative of family and services pressures.

Results: Every country’s 55-74yearolds Nervous-Disease-Deaths rates were higher than Alzheimer’s & Dementia Deaths, ten countries Nervous-Disease-Deaths rose higher than Alzheimer’s & Dementias during Century.

Highest Combined Deaths and increases were Finland 1006 per million (pm) up 44%, USA 710pm, rose 39% and UK 653pm a rise of 32%, countries average of 25%, though Belgium, Canada and France rates fell.

Highest ASDR were Finland 973pm, up 104%, USA 592pm, rose 76%, UK 553pm, increase 170%. Lowest were Japan 112pm, yet up 90%, Greece 184pm, rose 64% and Austria 214pm increased 102%, average nation’s 62%.

Belgium at 387pm up 34%, Canada 401pm, increased 13% and France ASDR 336pm up 11%.

Population compared with total neurological amongst Early-Adult-Deaths and Over 75’s, ratios of change, were respectively 1:1.34 and 1:2.21, yielding an Odds ratios of 1:1.65

French total neurological numbers were 40,594 rose to 71,543, up 76%, UK 24,601 to 103,550 increased 321% and the USA 174,708 to 436,438 rising 150%.

Discussion: We reject the hypothesis that neurological increases were mainly dues to demographics. Our results support by new studies across the continents, with their findings of significant causal multiple-interactive-environmental pollutants, including, endocrine disruptive chemicals, air pollution, organophosphates, plastics, petrochemicals, impact of low ubiquitous prolonged electro-magnetism, etc, associated with neuro-degenerative disease, especially Early-Onset-Dementia, below Western life-expectancy.

Conclusions: Governments should seek urgent research to explain this new epidemic.

Marco Righi1,2, Stefano Morara1,2, Giulia Petrillo1,2, Andrea Perota3, Giulia Cagnotti4, Cristiano Corona5

1CNR-Institute of Neuroscience, Milan, Italy
2NeuroMI, Milan Center for Neuroscience, University of Milano Bicocca, Milan, Italy
3Laboratory of Reproductive Technologies, Avantea, Cremona, Italy
4Department of Veterinary Science, University of Turin, Grugliasco, Italy
5Istituto Zooprofilattico Sperimentale Piemonte Liguria e Valle d’Aosta, Turin, Italy


Amyotrophic Lateral Sclerosis is still a poorly understood neurological syndrome showing muscle impairment and leading to death because of respiratory failure. Recently, a new, transgenic swine model overexpressing the human superoxide-dismutase 1 gene, promised the chance to investigate animals before disease onset, and we planned to investigate vascular alterations that we recently learned to quantify. In order to address for feasibility, we checked angioarchitectures in spinal cord samples of at least one animal for each of three health conditions: healthy, asymptomatic, clear motor symptoms. Furthermore, analyses were carried out in three different regions: cervical, thoracic and lumbar districts.

In our approach, we relied on described ImageJ automatic routines, measuring amounts and dispersion of microvascular structures, classified according to their calibers and in spite of the low height of the sample slice. As in previous papers, we investigated amount and volume dispersion of 7 progressively reconstructed angioarchitectures, built from larger calibers through addition of vessels or voxels of smaller and smaller caliber. Results were processed by linear regression to depict a 2D summary pattern, specific for that micro-angioarchitecture.

Healthy samples presented well dispersed vascular layouts, depicted by near-flat linear regressions. However, they were characterized by large dispersion variances, apparently due to district of origin of the sample itself. On the contrary, results from pathological samples presented lines with increased slopes while retaining the observed inter-sample dispersion variances. Absence of samples from different animals in the same health status prevented us to observe inter-animal variances. Therefore, we could not derive significant biological conclusions on reduced vascularization. Nevertheless, results demonstrated the success of our image analysis approach and provided a “tantalizing” observation of vascular alterations in a swine model for Amyotrophic Lateral Sclerosis.

Selbi Myradova Research and Development. Medical Center Foltra, Teo, Spain. (Current Address and Affiliation: Health advisor services. European Union Delegation to Turkmenistan, Ashgabat, Turkmenistan).
Pablo Devesa Research and Development. Medical Center Foltra, Teo, Spain. (Current Address and Affiliation: Coordination and Research, School of Medicine, University Univalle, Cochabamba, Bolivia).
Joaquín Guerra Otolaryngology. Medical Center Foltra, Teo, Spain.
Jesús Devesa Scientific Direction. Medical Center Foltra, Teo, Spain.


A common problem in children affected by cerebral palsy, independently of its etiology, is the existence of visual impairment. In this retrospective study we analyzed the effects of Growth hormone (GH) administration (0,04 mg/kg/day, 5 days/week) together with visual stimulation with a tachistoscope in 42 children with cerebral palsy (22 boys, 20 girls, aged 2,48 ± 1,5 years [mean ± SD) in whom there was an evident lesion of the visual pathway. In 17 of these cases, prematurity was the responsible factor, while in the other 25 children, ischemic encephalopathy due to pre/perinatal problems was the origin of visual impairment. In addition, we analyzed three other children (1, 2 months and 1 year of age) in whom multicystic encephalopathy (due to severe hypoxia-ischemia at delivery) mainly affecting the occipital lobes was the responsible factor. Visual evoked potentials were recorded before beginning and after treatment, assessing the latency in ms of the N75, P100 and N140 waves, as well as the amplitude of the waves (µV). Treatment duration (mean ± SD) was 5.20 + 2.05 months. Completion of treatment was established by clinical criteria. The statistical significance of the data was carried out using the Wilcoxon test.

The treatment induced a significant decrease in the latency of N75, P100 and N140 (p < 0.001), as well as a clear tendency to increase the amplitude of the waves (p < 0.05). Of special interest is the case of a child affected by Multicystic Encephalopathy in which the cystic cavities in the occipital lobes detected by MRI before starting treatment (15 days of age) completely disappeared in a new MRI performed 1 year later. That child is now totally independent for activities of daily living. GH treatment did not produce any adverse effects. In summary, from our results we can conclude that the administration of GH added to visual stimulation with a tachistoscope is an effective and safe method for the repair of visual deficiencies in children with cerebral palsy, regardless of the existence or not of GH deficiency.

Pétur Sigurjónsson, MD Msc. Landspitali University Hospital, Department of Anesthesia and Intensive Care, Reykjavik, Iceland
Asta Dogg Jonasdottir, MD Msc. Landspitali University Hospital, Department of Endocrinology,, Reykjavik, Iceland
Ingvar H Olafsson, MD Landspitali University Hospital Department of Neurosurgery, Reykjavik, Iceland
Sigurbergur Karason, MD, PhD, professor Landspitali University Hospital Department of Anesthesia and Intensive Care, Reykjavik, Iceland
Gudmundur Sigthorsson, MD Msc PhD Landspitali University Hospital Department of Clinical Chemistry, Reykjavik, Iceland
Helga A Sigurjonsdottir, MD, PhD, professor Landspitali University Hospital, Department of Endocrinology,, Reykjavik, Iceland


Background and aims of the study: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) can cause death and long-term morbidity. Studies indicate that both TBI and SAH may affect pituitary function in both the acute and the chronic phase. The aims of this study were firstly to evaluate the nature of neuroendocrine changes in the acute phase of moderate and severe TBI and all SAH, to evaluate association between neuroendocrine disturbance and indicators of severity of insult as well as hypotension, desaturation and anemia and to evaluated the incidence of neuroendocrine changes after moderate and severe TBI and SAH in the acute phase. Purpose: To explore neuroendocrine disturbances in moderate traumatic brain injury (mTBI), severe TBI (sTBI) and subarachnoid hemorrhage (SAH) in the acute phase.

Methods: The study was a prospective single-center study. Anterior hypothalamic-pituitary (HP) hormone axis were assessed on admission (day 0) with baseline hormone levels and on day 6 post insult with baseline hormone levels and a Synacthen test. From patient charts we recorded for all patients GCS, APACHEII score, length of ICU stay, pupil dilatation, documented hypotension, desaturation and hemoglobin value <80 g/dL. Hunt and Hess grade for SAH group and Injury severity score for TBI group. S100b was measured in all patients on admission. We included 21 TBI patient, 6 moderate TBI and 15 severe TBI, and 19 SAH patients. Anterior hypothalamic-pituitary (HP) hormone axis were assessed on day 0 and 6 post insult in Twenty-one TBI patient and 19 SAH patients.

Results: HP-adrenal axis: The TBI group had significantly lower mean cortisol than the SAH group on day 0, 23.8% of TBI patients had low cortisol and 0% of SAH patients. On day 6, one patient in each group had low cortisol, 6.7% of TBI and 9.1% of SAH. HP-gonadal axis: In males on day 0, 52.9% of TBI patients and 57.1% of SAH patients had suppressed HP-gonadal axis and on day 6, 84.6% of TBI patients and 90% of SAH patients. There was a greater suppression of LH/FSH in the TBI group. HP-thyroid axis: Only one TBI patient (5.9%) had secondary hypothyroidism on day 6. HP-somatotroph axis: On day 0, 52.4% of TBI patients and 35.7% of SAH patients had low IGF-1. On day 6 all but one TBI patient (5.9%) had normalized their IGF-1 but 25% of SAH patients still had low IGF-1. In general, when evaluating association there seemed to more suppression of the hypothalamic-pituitary (HP) gonadal and thyroid axis with more severe insult and adequately more activation of the hypothalamic-pituitary adrenal axis.

Conclusion: Neuroendocrine disturbances in the acute phase of TBI and SAH are common and seem to differ between the two groups. The clinical significance of these disturbances is uncertain.

Sergei Viktorovich Karnup1, William De Groat1, Jonathan Beckel1, Changfeng Tai1

1University of Pittsburgh


Electrical stimulation in the kilohertz-frequency range has been successfully used for treatment of various neurological disorders. Nevertheless, the mechanisms underlying this stimulation are poorly understood. To study the effect of kilohertz-frequency electric fields on neuronal membrane biophysics we developed a reliable experimental method to measure responses of single neurons to kilohertz field stimulation in brain slice preparations. In the submerged brain slice pyramidal neurons of the CA1 subfield were recorded in the whole-cell configuration before, during and after stimulation with a biphasic charge balanced electric field at 2kHz, 5kHz or 10 kHz. The slice was placed in a 1 mm gap between two parallel 2 mm long platinum-iridium 0.1 mm diameter wire electrodes. Whole-cell recordings lasted for an hour or longer. Typically, a few 5-10 min long sessions of kHz-field stimulation (kHz-FS) with various frequency/amplitude combinations were applied to assess the type of neuronal response and possible changes of its membrane characteristics. It was found that kHz-field stimulation at all frequencies elicited reproducible excitatory neuronal responses lasting throughout stimulation period, but not after cessation of kHz-FS. During kHz-FS the rheobase usually decreased. In addition, spontaneous firing might be initiated in some silent neurons or became more intense in previously spontaneously active neurons. Response thresholds were in the range of 0.5-2 mA and were higher at higher frequencies. Blockade of glutamatergic synaptic transmission did not alter the magnitude of responses. Inhibitory synaptic input was not changed by kilohertz field stimulation. We conclude that kHz-frequency current applied in brain tissue has an excitatory effect on pyramidal neurons during stimulation. This effect is more prominent and occurs at a lower stimulus intensity at a frequency of 2kHz as compared to 5kHz and 10kHz.

Bjørn A. Nexø1

1Biomedicine, Bartholin Building, Vilhelm Meyers Allé 4, Aarhus University, 8000, Aarhus C, Denmark


Most, if not all, animals have endogenous viruses i.e., copies of parts of or complete retro-viral genomes in their chromosomes. Man, for example, has in the order of 100 000 bits and pieces of retrovirus, distributed on all chromosomes. Most of these bits are grossly defective but in man about 50 can encode a protein. There is evidence several coding endogenous viruses can recombine and start an infection. I believe these coding endogenous viruses contribute to human disease. Indeed I speculate, they are the most important limitation on size and longevity of the members of a species: both these parameters are roughly proportional to the chance of making a replicating virus. In the following I will try to argue for the importance of coding endogenous viruses.

If the presence of retroviral sequences does not lead to replicating virus the situation is mostly fine. However, as soon as a virus starts replicating in an individual, the mutational level in the animal increases dramatically, by way of insertion of viral genomes at unusual places, and the animal in part loses control of its genome. This is known to result in cancer, and I believe in autoimmune disease.

Shahir Mazaheri1, Yazdan Heshmati1, Mohsen Vazifehdaryazd1, Mojtaba Khazaei1, Masoud Ghiasian1, Ashkan Rasouli-Saravani2, Mehrdad Hajilooi2, Ghasem Solgi2&3

1Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3Psoriasis Research Centre, Hamadan Univers ity of Medical Sciences, Hamadan, Iran


Backgrounds: Environmental factors such as bacterial infections, as well as genetic factors—in particular the human leukocyte antigen (HLA) alleles—have been implicated in the etiology of multiple sclerosis (MS). This study aims to explore the relationship between Helicobacter pylori infection, HLA alleles, and disease severity in Iranian MS patients.

Methods: The study population comprised 125 MS patients and 153 ethnically matched healthy controls. Stool antigen test was used to detect H. pylori, and the expanded disability status scale (EDSS) scores were assessed in the patients. HLA-DRB1 and DQB1 alleles and haplotypes were determined in both the patients and the controls. The relationships between H pylori infection, HLA alleles, and EDSS were also analyzed.

Results: HLA-DRB1*15 and DQB1*06 alleles families and the DRB1*15~DQB1*06 haplotype were significantly more frequent in MS patients, whereas HLA-DRB1*14 and DRB1*14~DQB1*05 haplotype were less frequent. Of the 125 MS patients, 38 were diagnosed with active H. pylori infection. We found lower frequencies of HLA-DRB1*15 (P = .08) and DRB1*16 (P = .05) alleles and a higher frequency of DQB1*02 (P = .06) in the H. pylori-positive patients. HLA-DRB1*07 was more prevalent in patients with EDSS≤3.0 (P = .06). More severe MS cases (EDSS>3.0) were linked to H pylori positivity (P = .02), disease chronicity (P = .001), receiving non-steroidal anti-inflammatory drugs (P = .02), and female gender (P = .05).

Conclusion: These preliminary findings suggest a link between H. pylori infection and the severity of MS H. pylori-positive patients regardless of the type of HLA carriage.

Keywords: multiple sclerosis, Helicobacter pylori, HLA-DRB1, HLA-DQB1, EDSS


A Robert Spitzer1

1Mackinac Neurology


The treatment of sleep disorders is problematic because the diagnoses consist of an array of unrelated terms, there is little knowledge or link to disease processes, and progression from the patient presentation to effective therapy is not systematic. The purpose of this paper is to provide a coherent framework for understanding sleep disorders, based on anatomy and pathophysiology.

A classification of sleep disorders based on classical neurological diagnosis is presented. First, the diagnostic process in classical, clinical neurology is reviewed. In this traditional approach, diagnoses are not inferred directly from symptoms. Rather, symptoms are used to identify putative anatomic localizations, and pathophysiological mechanisms. Diagnoses are inferred as a second step from the localizations and mechanisms of disease. Subsequently, testing may be applied as necessary, using a probabilistic interpretation to guide treatment. Treatment for diseases classified in this manner is more likely to be successful. In addition, be generating alternative hypotheses during this process, if initial treatments are not successful, alternative approaches may be considered.

The anatomy and physiology of sleep disorders is briefly reviewed. The process of diagnosis is then presented, starting with specific symptoms, including insomnia, hypersomnia, limb movement disorders, fatigue and pain syndromes. Groups of symptoms, as syndromes, are considered. By relating the symptoms to the localizations and pathophysiology, a more ordered approach to management is presented. The distinction of etiology from diagnosis is discussed. Etiologies that have resolved are typically not treatable.

Prior research on fibromyalgia is summarized, including possible anatomic and pathophysiological substrates, and underlying sleep disorders. Other forms of fatigue are contrasted, with implications for different treatments.

Daniel S. Levine1

1Department of Psychology, University of Texas at Arlington, Arlington, TX 76019-0528


The traditional idea of emotion and cognition in Western culture is that emotion is separate from, and inferior to, cognition. This article reviews results from experimental neuroscience that refute this notion and support the idea that emotion and cognition are partners that depend on each other for organized decision making. Cooperation between cortical and subcortical parts of the brain is essential for behavior that adapts successfully to the environment in pursuit of goals. Concurrently, there has been a rich development of computational neural network theories that combine emotion as a source of values with reason as a process of discerning the actions that will best implement those values. Incorporating the partnership view of emotion and cognition encourages integration of those two aspects of the psyche, with benefit both for mental illness treatment and for making society more cooperative.

Sergey Rusanov1



The article is presented in the form of a review and analysis of the literature, which additionally helps to reveal the mechanisms of the pathogenesis of the development of atherosclerosis in humans. A contemporary vision is refuted that animal models of atherosclerosis are completely similar to the two types of human atherosclerotic lesions. The use of incorrect information about the etiology and pathogenesis of atherosclerotic lesions in humans reduces and even completely interferes with the possibility to carry out effective treatment and prevention of cardiovascular diseases associated with atherosclerosis. The two types of human atherosclerotic plaques have very different characteristics compared to atherosclerotic plaques in animals. They have a completely different etiology, pathogenesis, have a completely different appearance and location relative to the artery wall, have a different structure of the fibrous cap, a different pathway of LDL and macrophages, a different location of lipid core, a different way and time of arterial occlusion, a different type of endothelial dysfunction, they interact in totally different way with the walls of the artery and still have many additional differences that make both human atherosclerotic lesions completely different from atherosclerotic lesion in animals. Types IV atherosclerotic lesions consist of one lipid core with molten extracellular lipid. Type V atherosclerotic lesions type is a long, concentric, soft, strong, elastic, yellow, uniform structure. Due to the large number of inconsistencies between atherosclerotic lesions in animals and the two types of atherosclerotic lesions in humans, it is neither possible nor reasonable to use animal models to study the development of atherosclerotic lesions in humans. The plaques appear in the lumen of the artery in just a few days, in places of a sharp narrowing of the artery caused by hyperstimulation of the nervous system. The plaques consist of LDL, which were glued together with fibrin filaments. It also doesn’t allow to detect a very simple mechanism accountable for the pathological increase in LDL levels in people who do not have genetic abnormalities. This mechanism proposed by the author is described in the first article dedicated to the type V atherosclerotic lesions (“Cylindrical cholesterol plaque”).


Dimitrios Panagopoulos1, Georgios Stranjalis1, Maro Gavra1, Efstathios Boviatsis1, Stefanos Korfias1, Ploutarchos Karydakis1, Marios Tmemistocleous1

1Consultant Pediatric Neurosurgeon, Neurosurgical Department, Pediatric Hospital of Athens, Agia


Introduction: The entity of the trapped fourth ventricle represents a clinical challenge, as it is a rare entity associated with a wide spectrum of underlying pathologic conditions and the proposed treatment options are restricted and frequently associated with complications and unfavorable long-term outcome. The majority of the affected individuals report a medical history of previous ventriculo-peritoneal shunt infection, as well as a precipitating factor for the entrapment (central nervous system infection, intraventricular hemorrhage, trauma). They come to clinical attention due to symptomatology attributed to mass effect that is exerted by the ballooned fourth ventricle on the brainstem and cerebellum.

Materials and Methods: We present our results, extracted from data derived from our medical center 20 years surgical experience and relevant outcomes in 120 pediatric patients diagnosed and managed with entrapped fourth ventricle. They were treated either with fourth ventricle-peritoneal shunt insertion or with an endoscopic approach. The relative efficacy of both techniques was recorded one year and five years after the initial operation and the data underwent statistical analysis. All patients who failed the initial therapeutic option were managed again with the aforementioned techniques, and their long-term results were recorded.

Conclusions: We recorded that after one year of follow-up, there were no significant differences in outcome when these two techniques were compared. However, when the results of five-year follow-up were compared between two groups, there was superiority, regarding the functional outcome, of the procedure involving the insertion of a fourth ventricular-peritoneal shunt. The outcome of patients that underwent a salvage procedure of any type did not seem to be different after a one-year follow-up period, being unable to verify the superiority of one technique over the other. However, there seems to be a superiority of the shunt procedure over the endoscopic technique regarding the functional outcome of these patients, five years after their second operation. Nevertheless, these results are only indicative and our data are insufficient to establish a statistical level of significance, probably due to the restricted number of patients that were incorporated in our survey.

Damian Leitner1, Megan Udala1, Harry Miller1, Maya Libben1

1Department of Psychology, Kelowna General Hospital, 2268 Pandosy Street, Kelowna, B.C., V1Y-1T2 Canada


Accurate assessment of memory following a stroke is important for patient rehabilitation. The Buschke Selective Reminding Test (SRT) is a test of verbal learning and memory that can be used to assess many clinical populations. The current study investigated the criterion validity of the SRT by comparing scores from patients with stroke to healthy controls, and identified scores on the SRT that best differentiate between these two groups. Participants included 65 patients with stroke and 65 age-and education-matched healthy controls. The control group differed significantly from patients with stroke on all scores (p <.01). Spearman’s rho correlations revealed potential multicollinearity between multiple SRT measures. Binomial logistic regression suggested SRT scores differentiated patients with stroke from controls, and correctly classified 76% of cases. Lower continuous long-term retrieval (CLTR) scores were more likely among patients with stroke. Results supported the SRT as useful for identifying verbal learning and memory impairment in acute stroke inpatients.

Dimitrios Panagopoulos1, Georgios Strantzalis1, Maro Gavra1, Efstathios Boviatsis1, Stefanos Korfias1, Ploutarchos Karydakis1

1Consultant Pediatric Neurosurgeon, Neurosurgical Department, Pediatric Hospital of Athens, Agia


Chiari malformations comprise a group of disorders, which share in common inherent anatomical abnormalities that involve the region of the brain stem and cerebellum, eventually coexisting with entities such as hydrocephalus, spina bifida, syringomyelia and tethered cord syndrome.In the mean-time, from the original description of this syndrome, several researchers have focused on an effort to elucidate the pathogenesis of Chiari malformation from a point of view that it is a primary neural anomaly.

The aim of the current review is to investigate the time course of our knowledge regarding Chiari malformation, which has expanded significant in the past decades. As new insight has occurred regarding the pathophysiology and natural history of Chiari I malformation (CIM), in association with the widespread availability of MRI,the treatment modalities and algorithm for this patient population has been substantially evolved.Our purpose is to present a review of CIM and its most significant associated comorbidities,comment on techniques for surgical intervention and their expected outcomes.

There is a bulk of literature reviews centered on Chiari malformations· in this context, we attempted a literature review, including a discussion centered onthe historical background, anatomical forms, pathophysiology, clinical presentation, relationships with other diseases and diagnostic procedures for these abnormalities. Moreover, a bibliographic search was performed, using Thomson Reuters web of Science and Pubmed databases, in order to identify the most noteworthy papers about Chiari Syndrome. The following parameters were recorded: article titles, number of total citations and citations per year, authors’ names, authors’ h-index, institution and country where the research took place, year of publication, the journal of publication and journal’s impact factor. In addition, we reviewed the journals’ Impact Factor and SCImago Journal Rank (SJR). To obtain all those parameters, besides Web of sciences, we utilized Scopus, SCimago Journal and Country rankings, and In Cites Journal Citation Reports.

Our search resulted in 9.972 articles, published from 1855 until now (March2022). All articles are in English. The 50 most cited papers are presented in Table S1. All of them combined have been cited 8.999 times, in 3.262 different articles, with an average citation per item of 179.98.

We have attempted to present a thorough overview of this group of disorders, as well as to trace the evolution of our knowledge regarding the anatomical abnormalities associated with this condition, imaging and treatment gold standards and future perspectives.

The real pathophysiology, embryological background and natural history of CM have still not been entirely elucidated. This is in concordance with the fact that new suggestions have been submitted for the management of this malformation and more sophisticated imaging techniques have been introduced, in order to investigate in more details, the diagnosis. However, a lot of controversies remain, mainly centered on the optimum strategy which should be selected for selection of the appropriate surgical candidates and most efficacious treatment protocols, in order to obtain efficient decompression of the cranio-cervical junction.


Dimitrios Panagopoulos1, Georgios Strantzalis1, Maro Gavra1, Stefanos Korfias1, Ploutarchos Karydakis1

1Consultant Pediatric Neurosurgeon, Neurosurgical Department, Pediatric Hospital of Athens, Agia


In an effort to maximize extent of resection (EOR) regarding gliomas, intraoperative MRI (i-MRI) and 5-aminolevulinic acid (5-ALA) have been developed. Our study aimed to investigate the comparative contribution of 5-aminolevulinic acid and i-MRI in maximizing EOR in gliomas.

We searched the PubMed and ScienceDirect services for randomized controlled trials, controlled trials and interrupted time series studies evaluating the effect of i-MRI on gross total resection (GTR) rates and on overall survival in glioma patients. Our primary study endpoint was the definition of the percentage of patients who were offered GTR. Other relevant points of interest included the determination of overall and progression-free survival and subgroup analyses for level of evidence.
I-MRI aids in achieving GTR (odds ratio 2.71, p<0.0001). Magnet field strength does not affect significantly either GTR rates (p=0.08). The cost of the procedure is dependent on the workload of the i-MRI system. These data suggest that i-MRI or 5-ALA improves progression-free and overall survival, although there are several restrictions related to their effectiveness and reliability.
I-MRI and 5-ALA are considered to be effective adjuncts in the achievement of GTR of gliomas. When these methods are compared, there is no definite conclusion regarding which method is more effective.


Bruggen van Rufi Monique1,2, Benkmil Farid1, Jansen Mijke1, Karpati Rita1, Lawa Linda1, Magnus Regina1, Mol Wouter1, Serrano Irene1

1Saffier Domus Nostra, Korsakoff Expertise Center, The Hague, Netherlands
2ArtEZ University of the Arts, Professorship/Lectoraat Music-based Therapies and Interventions, Music Therapy Department, Enschede, Netherlands


This article reports about the beneficial effects of creative arts therapy on memory and cognition for patients with Korsakoff Syndrome, residing in a long term care facility specialized in the care of people with Korsakoff. Creative arts therapy is an umbrella term for healthcare professions who use the creative and expressive process of art-making to improve and enhance the psychological and social well-being of individuals of all ages and health conditions. It is a non-pharmaceutical intervention, using the power of the experience by doing rather than by speaking about the struggles in daily life.

There is still little knowledge on how creative arts therapy may contribute to improving the quality of life of patients with Korsakoff, or reducing the impairments they suffer.

In this article several case examples from the field of creative arts therapy, specifically music therapy, arts therapy and dance/movement-therapy, are described. These case examples portrait different persons with Kosakoff who benefit greatly from creative arts therapy while they are struggling with their physical and mental problems.

Typical characteristics of persons suffering from Korsakoff are memory impairment, confabulation and problems with executive functions, caused by their chronic alcohol abuse which led to developing Korsakoff. The aim of this article is to provide greater insight into how to treat patients with Korsakoff through creative arts therapy. The different case vignettes, describing the authors lived experiences, give the reader insight in the real-world context in which creative arts therapy is practiced. By giving the patients a face and a voice and showing their artistic skills, we hope to break the stigma that is chasing them: the low-life-drunks who made a big mess of their life.

Paba Dotes Ana Beléna, De Torres-García Irenea

aPhysical Medicine and Rehabilitation Department, Hospital Regional Universitario de Málaga, Spain.
Civil Hospital, Plaza del Hospital Civil, s/n, 29009, Malaga, Spain


Case: Acquired brain damage is one of the most complex pathologies that affect the central nervous system, there is great variability in its pathophysiology, from traumatic focal injuries to diffuse axonal injuries, including spasticity. It supposes a great comorbidity and functional repercussion in patients, hindering their subsequent recovery. We report a case of a young patient with a history of quadriplegia due to acquired brain damage secondary to thrombosis of the dural sinus. The patient presented sensorimotor deficit, restricted function, and a great situation of dependency. He required three cycles of high doses of incobotulinumtoxinA (IncoBoNT) according to his specific need, the first infiltration was 800 U, the second 800 U, and the last 500 U over a period of 14 weeks. Thanks to the previous objectives agreement with the patient the results were satisfactory and relevant for him, presenting a great functional improvement of spasticity and associated pain, as assessed by the visual analog scale score.Conclusion: IncoBoNT at high doses and short intervals has been shown to be an effective and valuable tool for personalized treatment adapted to the needs of severely affected neurological patients.