MULTIDIMENSIONALITY AND MULTIDISCIPLINARITY OF CHRONIC NEUROPATHIC NONODONTOGENIC OROFACIAL PAIN.

This study compared the self-assessed health-related quality of life (HRQoL) and degree of depression between patients with chronic neuropathic nonodontogenic orofacial pain (NOFP) and healthy controls using the Short Form Survey (SF-36) health status questionnaire and Beck Depression Inventory II (BDI-II). This controlled cross-sectional study included 100 patients and 119 healthy controls. The diagnostic protocol recorded the following: 1) pain intensity using a visual analog scale for the time of examination and during the one-month prior; 2) evidence for neuropathic pain using the Leeds questionnaire for neuropathic signs and symptoms (LANSS); 3) emotional status using the BDI-II; and 4) HRQoL using the SF-36 questionnaire. The mean LANSS score was 17.18 in the patient group and 0.0 in the control group. The mean BDI-II score was 18.31 in the patient group and 5.87 in the control group. The SF-36 scores were shown with Mann-Whitney U testing to have statistically significant differences between the patient and healthy control groups in all categories. Vitality was the only SF-36 category in which the patient group scored higher than the control group. In conclusion, NOFP significantly reduces the self-reported HRQoL. NOFP is also related to the development of depression, but does not affect its severity. There is a significant correlation between depression and low quality of life in patients with NOFP.

THE CONCENTRATION OF INTERLEUKIN 6 AND TUMOR NECROSIS FACTOR ALPHA IN SALIVA AND BLOOD OF PATIENTS WITH INACTIVE MULTIPLE SCLEROSIS AND COEXISTING HASHIMOTO'S THYROIDITIS.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto's thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

Treatment of relapsing multiple sclerosis - recommendations of the Croatian Neurological Society.

Untreated multiple sclerosis (MS) irretrievably leads to severe neurological impairment. In European health care systems, patient access to disease modifying therapies (DMT) is often confined to more advanced stages of the disease because of restrictions in reimbursement. A discrepancy in access to DMTs is evident between West and East European countries. In order to improve access to DMTs for people with MS (pwMS) living in Croatia, the Croatian Neurological Society issued new recommendations for the treatment of relapsing MS. The aim of this article is to present these recommendations. The recommendations for platform therapies are to start DMT as soon as the diagnosis is made. If poor prognostic criteria are present (≥9 T2 or FLAIR lesions on the initial brain and spinal cord magnetic resonance imaging [MRI] or ≥3 T1 lesions with postcontrast enhancement on the initial brain and spinal cord MRI or Expanded Disability Status Scale after treatment of the initial relapse ≥3), high-efficacy DMT should be initiated. If pwMS experience ≥1 relapse or ≥3 new T2 lesions while on platform therapies, they should be switched to high-efficacy DMT. Further efforts should be made to enable early and unrestricted access to high-efficacy DMT with a freedom of choice of an appropriate therapy for expert physicians and pwMS. The improvement of access to DMT achieved by the implementation of national treatment guidelines in Croatia can serve as an example to national neurological societies from other Eastern European countries to persuade payers to enable early and unrestricted treatment of pwMS.

SPINAL SUBDURAL HEMATOMA ASSOCIATED WITH LUMBAR PUNCTURE - A CASE REPORT.

Spinal subdural hematoma caused by lumbar puncture is a rare state of acute blood clot in spinal subdural space, and in some cases, it can be the cause of local compression and consecutive neurological symptoms. We present a 36-year-old female patient who was hospitalized due to persistent headache despite pharmacological therapy. Therefore, we performed lumbar puncture in order to measure intracranial pressure and evaluate cerebrospinal fluid. After lumbar puncture, the patient was complaining of pain in the lumbar region. Emergency magnetic resonance imaging (MRI) of the lumbosacral (LS) region was performed to show acute subdural hematoma of up to 7.3 mm in the dorsal part of the spinal canal at the level of L1 vertebra to the inferior endplate of L4 vertebra. Repeat LS MRI after 3 hours showed unchanged finding. The patient reported gradual regression of pain in the LS region over the next few days, therefore conservative treatment was applied. Patients with a previously known blood clotting disorder and patients on anticoagulation therapy have worse outcome as compared with patients without such disorders. During treatment, it is necessary to monitor patient clinical state and consider the need of surgical treatment.

SIALORRHEA AND XEROSTOMIA IN PARKINSON'S DISEASE PATIENTS.

Parkinson's disease (PD) is generally considered as a primary movement disorder, but the majority of patients also suffer from non-motor oral, salivary symptoms. The most common salivary symptoms, sialorrhea and xerostomia, have a considerable negative impact on the quality of life. Although these symptoms are completely opposite ones, both significantly impair oral health of patients. Sialorrhea is defined as an increased amount of the retaining saliva. It is related to salivary overproduction, or it may be associated with impaired clearance of saliva. Opposed to sialorrhea, xerostomia is subjectively defined as dryness of mouth and it is related to insufficient salivary secretion. Xerostomia promotes imbalance of oral microflora and oral pathology that often leads to malnutrition in PD patients. It is mostly related to autonomic dysfunction, or it might be considered as a side effect of dopaminergic or anticholinergic medication. In PD, different assessments are used for evaluation of sialorrhea and xerostomia, including validated scales for non-motor symptoms and standardized questionnaires on oral health. Consequently, treatment of salivary symptoms includes pharmacological and nonpharmacological approach, and surgical interventions. A multidisciplinary approach in clinical neurology and dental medicine, which includes accurate evaluation of salivary symptoms and effective treatment, indicates successful management of PD patients.

EVAULATION OF BLINK REFLEX BETWEEN PATIENTS WITH IDIOPATHIC TRIGEMINAL NEURALGIA AND HEALTHY VOLUNTEERS.

The purpose of the study was to find differences in the parameters of the response to the blink reflex (BR) between patients with idiopathic trigeminal neuralgia (TN) and health volunteers. A prospective cohort study was conducted over 2 years. The TN-subgroup included 15 patients (mean age / SD 62.3 ± 10.7 years). Pain-free and healthy volunteers as a HV-subgroup (mean age / SD: 30.8 ± 8.1 years) were recruited from asymptomatic students of dental medicine. Diagnostic parameters were determined by measuring latency to the onset of the BR components from electric stimulation. The following branches of the trigeminal nerve were affected: maxillary branch only (26.7%), mandibular branch only (20%), combined: ophthalmic branch with maxillary branch (6.7%), and ophthalmic branch with mandibular branch (6.7%) respectively, combined maxillary and mandibular branch (26.7%) and affected all three branches (13.4%). The latencies of the BR, left and right side together, between subgroups were significantly higher for values R1 (homolateral early response), R2 (homolateral late response), R2c latency (contralaterally expressed response) in the TN-subgroup (p < 0.05). On the basis of the presence of R1c and R3 latencies and upon considering the abnormal findings of the BR, no statistically significant differences were found between the examined subgroups (p > 0.05). Blink-reflex parameters (R1, R2 and R2c) were significantly abnormal comparing TN-patients with healthy volunteers. The R3 component of the BR was related to noxious stimuli, likewise by innocuous stimuli.

The Effect of Transcoutaneous Electrical Nerve Stimulation on Pain Control during Dental Procedure in Children 9-14 Years Old.

INTRODUCTION: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological method widely used by medical specialists to manage acute and chronic pain in different circumstances. It can be used to manage pain during many dental procedures, as well as pain due to various conditions affecting the maxillofacial region. The aim of this study was to provide insight into the clinical research evidence for the analgetic application of TENS in pediatric patients. The hypothesis was that TENS device will achieve analgetic effect on teeth during dental procedure. METHODS: This study included 125 patients treated at the School of Dental Medicine, University of Zagreb clinic during two-year period. After diagnosis of caries and need for restorative treatment, patients were randomly selected in three groups. Group 1 received local anesthesia, group 2 had no anesthesia and group 3 used TENS device. Level of pain was measured with Visual Analogue Scale (VAS). Research was conducted by one therapist that was calibrated. RESULTS: We found no statistically significant difference between TENS group and group without anesthesia(p>0.05). CONCLUSION: TENS device is not as efficient in achieving analgetic impact during dental procedure as local anesthesia.

ASSOCIATION BETWEEN APOLIPOPROTEIN E POLYMORPHISMS AND EPILEPSY IN CHILDREN.

Apolipoprotein E (APOE) plays an important role in lipid metabolism and is a proven risk factor for development of dementia and other neurodegenerative diseases. The aim of the study was to determine the possible connection between particular APOE alleles, blood lipid profile and different types of epilepsy in children. Alleles of the APOE gene, blood cholesterol (total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were analyzed in blood samples of 111 children with epilepsy and 118 age- and sex-matched children without epilepsy. Distribution of APOE genotypes was the same in children of both groups. Significantly increased levels of total cholesterol and LDL cholesterol were found in control group (Z=3.49 and 3.52 respectively, p<0.01). No statistically significant difference was found between the genotypes of children with idiopathic and symptomatic epilepsy (χ2=1.96; df=2; p>0.05). There were statistically significant differences in the levels of total cholesterol (Z=2.09; p<0.05) and LDL cholesterol (Z=2.05; p<0.05) according to the type of epilepsy in favor of symptomatic epilepsy. The study confirmed that there was no connection between APOE and type of epilepsy in children and showed the children with epilepsy to have lower total cholesterol and LDL cholesterol levels. Interestingly, this also held true for children with idiopathic epilepsy compared to those with symptomatic condition.

Genetic and lifestyle predictors of ischemic stroke severity and outcome.

BACKGROUND: Different models that include clinical variables and blood markers have been investigated to predict acute ischemic stroke treatment course and recovery. AIM: The aim of the study was to investigate associations between lipid levels, lifestyle factors, hemostatic (F5, F2, SERPINE1, F13A1, and FGB), and atherogenic (APOA5 and ACE) gene variants and acute ischemic stroke (AIS) severity. MATERIALS AND METHODS: This study included 250 patients with AIS in which F5, F2, SERPINE1, F13A1, FGB, APOA5, and ACE genotypes were determined. Total cholesterol (TC), high-density cholesterol, low-density cholesterol, and triglycerides concentrations were measured within 24 h of the AIS onset. Examination of the neurological deficit was done using National Institutes of Health Stroke Scale/Score (NIHSS). RESULTS: APOA5 genotype [TC + CC] was more frequent (P = 0.026) in patients with the NIHSS score ≥ 21. Univariate regression analysis has shown that triglycerides (OR 0.55, 95% CI 0.34-0.91; P = 0.019), obesity (0.28, 95% CI 0.10-0.73; P = 0.010), age (OR 1.08, 95% CI 1.04-1.13; P < 0.001), and APOA5 genotype (TC + CC) (OR 2.40, 95% CI 1.10-5.25; P = 0.034) are significantly associated with a severe stroke. When all variables were included in model age (OR 1.06, 95% CI 1.01-1.11; P = 0.018), obesity (OR 0.25, 95% CI 0.08-0.77; P = 0.016) and APOA5 genotype (TC + CC) (OR 3.26, 95% CI 1.29-8.23; P = 0.012) remained significant for the risk of severe AIS. CONCLUSION: APOA5 genotype (TC + CC), age, and obesity could be used as prognostic risk factors for a very severe stroke (NIHSS ≥ 21).

RECURRENT ATYPICAL OPTIC NEURITIS AS THE LEADING SIGN OF FABRY DISEASE.

Acute optic neuritis has the age and sex adjusted incidence of 1-5/100,000 in general population. It is mostly a disorder affecting young Caucasian women (31-32 years). Patients present to a wide range of clinicians including general practitioner, emergency physician, ophthalmologist, neurologist, etc. There are two main clinical presentations of optic neuritis, typical and atypical. It is of great importance to distinguish these two types of optic neuritis in order to detect the underlying etiology and plan appropriate and timely treatment. We present a young female patient (36 years) admitted to Department of Ophthalmology due to visual loss on the left eye. Magnetic resonance imaging showed demyelinating lesions in frontal and parietal lobe, periventricularly, in mesencephalon and right cerebellar hemisphere, and left optic neuritis; magnetic resonance angiography was normal. The patient's history revealed renal dysfunction, hypothyroidism, and miscarriage in the 6th month of pregnancy due to eclampsia, and Fabry disease in family (mother and two sisters). She was transferred to the Department of Neurology for further evaluation of the demyelinating disorder of the central nervous system. The patient received corticosteroid therapy (methylprednisolone 1 g) for 5 days with regression of visual disturbances on the left eye. After this acute treatment, the question of definitive diagnosis remained, along with further treatment of the underlying cause. Considering renal dysfunction, miscarriage, arterial hypertension, positive genetic and biochemical testing for Fabry disease in close relatives (mother), we suspected that she also had Fabry disease. She was tested and the results were positive. We concluded that optic neuritis was the first sign of Fabry disease in this case, reflecting acute atypical neuroinflammatory disease.

OROFACIAL PAIN - DIAGNOSTIC AND THERAPEUTIC CHALLENGES.

The concept of diagnostics and therapy of musculoskeletal and neuropathic diseases of the stomatognathic system, which are the subject of this paper, has been developing for decades. It can be said that in order to avoid misunderstanding, the orofacial pain as a clinical problem, in the narrower sense, involves non-odontogenic and non-malignant causes of orofacial region. In this study, the results of clinical diagnosis of the population of 557 consecutive patients with orofacial pain based on multidisciplinary diagnostics were evaluated. 15.6% of patients have given up on the participation in the study. It has been shown that the patients who dropped out of the study were significantly older (p=0.0411) than those who agreed to participate, but there was no difference in gender ratio (p=0.185) since the proportion of female patients prevailed. In an analysis of 84.4% of patients participating in the study, the elevated anxiety values were established (mean value on STAI 1 was 39.2 and STAI 2 was 41.1) and statistical significance was found in correlation between elevated anxiety and intensity of pain as shown on visual analogue scale on open mouth (p<0.0001). Compared to the age, the statistical significance was for STAI 1 (p=0.0097) but not for STAI 2 (p=0.5599). The most common form of therapy is Michigan stabilization splint: for disc displacement of temporomandibular joint (TMJ) in 38.9% of patients and in combination with physiotherapy in 18.7% of patients; for osteoarthritis of TMJ in 28.4% and in combination with physiotherapy in 26.4% of patients. The treatment with anticonvulsant drugs for trigeminal neuralgia predominates in 54.3% of patients, which is combined with acupuncture in 25.7% of patients and only acupuncture in 17.1% of patients. In this study, a multidisciplinary co-operation in initial diagnostics and differential was designed to develop subspecialist knowledge on orofacial pain.

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

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

MULTIPLE SCLEROSIS OR FABRY DISEASE - PROS AND CONS.

- Fabry disease is a rare X-linked inherited lysosomal storage disease affecting multiple organ systems, presenting in the central nervous system (CNS) as white matter lesions with underlying cerebral vasculopathy and autoinflammatory changes of the choroid plexus and leptomeninges. We present a young female patient (age 36 years) admitted to our department due to visual loss on the left eye. Magnetic resonance imaging (MRI) showed demyelinating lesions in the frontal and parietal lobe, periventricularly, in mesencephalon and right cerebellar hemisphere, and left optic neuritis; MR angiography was normal. Her medical history revealed renal dysfunction, hypothyroidism, and miscarriage in the 6th month of pregnancy due to eclampsia and Fabry disease in the family (mother). Cerebrospinal fluid analysis showed mild pleocytosis, normal blood brain barrier function and oligoclonal bands type 3. Visual evoked potentials showed prechiasmal dysfunction of the left optic nerve. Genetical testing for Fabry disease was positive (two heterozygous mutations), with decreased alpha galactosidase activity values and increased Lyso GB3 values. The patient received corticosteroid therapy (methylprednisolone) 1 g for 5 days, which led to regression of visual disturbances on the left eye. After this acute treatment, there was a question of definitive diagnosis and further treatment of the underlying cause. Considering renal dysfunction, miscarriage, arterial hypertension, positive genetic and biochemical testing for Fabry disease, as well as MRI findings showing lesions in posterior circulation, we concluded that the patient probably had Fabry disease with autoinflammatory changes in the CNS and should be treated with enzyme replacement therapy. Still, there was a question of optic neuritis on the left eye and positive oligoclonal bands favoring the diagnosis of multiple sclerosis. Therefore, further clinical and neuroradiological follow up was needed to distinguish multiple sclerosis and Fabry disease in this patient.

Accommodation to Diagnosis of Trigeminal Neuralgia

Trigeminal neuralgia is one of the most common causes of facial pain. It implies short lasting episodes of unilateral electric shock-like pain with abrupt onset and termination, in the distribution of one or more divisions of the trigeminal nerve that are triggered by innocuous stimuli. Most cases of trigeminal neuralgia are caused by compression of the trigeminal nerve root. Depending on the etiology, trigeminal neuralgia can be classified as classic trigeminal neuralgia or painful trigeminal neuropathy. It may be precipitated by some actions at trigger zones. The diagnosis of trigeminal neuralgia is based on diagnostic criteria for classic trigeminal neuralgia, neuroimaging and electrophysiologic trigeminal reflex testing. Treatment of classic trigeminal neuralgia for most patients is pharmacological therapy, while surgical approach is reserved for patients that are refractory to medical therapy and in cases of painful trigeminal neuropathy.

Restless Legs Syndrome in Multiple Sclerosis Patients ­ Patient Experience at Lipik Special Hospital for Medical Rehabilitation

The study included 60 patients with multiple sclerosis (MS) hospitalized at our institution from September 1 to December 31, 2014. The aim of the study was to assess the prevalence of restless legs syndrome (RLS) in MS patients and RLS relationship with patient age, sex, degree of disability, form of MS, time elapsed from MS diagnosis and use of antidepressants. The diagnosis of RLS was made according to the criteria set by the International Restless Legs Syndrome Study Group. Of the 60 patients, 24 (40%) met the criteria for the existence of RLS. In the group of patients with RLS, there was a significantly higher proportion of women and those that were taking antidepressants. There were no statistically significant between-group differences according to age, duration of illness, degree of disability and clinical course of MS. In the study, 37.5% of patients that met the criteria for RLS diagnosis had not informed the neurologists about their difficulties. The high prevalence of RLS and the fact that a large proportion of patients did not inform the neurologists about their difficulties related to RLS point to the need of an active approach to diagnosis and treatment.

The Role of Electromyographic Blink Reflex in the Evaluation of Headache Incidence

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

Effects of Trigeminal Nerve Dysfunction in Various Types of Headaches.

Headaches are one of the most common ailments in modern society, leading to severe diminishing of general activities and they result in significant impact on the patient's quality of life. Blink reflex is an objective neurophysiological method for determining the status of the trigeminal system, facial nerve and the lateral part of medulla oblongata. The aim of this study was to examine the connection between trigeminal nerve dysfunction and various types of headaches using functional electrophysiological assessment of blink reflex tests in patients and controls. The sample comprised 60 subjects with headache attacks, 44 females, and 16 males). The control group consisted of 30 healthy subjects (19 females, and 11 males) who did not suffer from headaches. The age of subjects ranged from 20 years to 76 years with the mean of 42.81 years. Trigeminal nerve function was assessed by using blink reflex tests in patients suffering from headaches and in controls, applying the standard procedure described by Kimura et al. Pathological findings of blink reflex were observed in 58.3 % of patients suffering from headaches and in only 20 % of cases in the control group. The application of Yates' χ2 test showed a significant correlation between pathological blink reflex and headache occurrence (χ2 = 10.354; P = 0.001). Normal blink reflex was found in 41.7 % of patients suffering from headaches and in 80 % of control group subjects. Females with pathological blink reflex have 4 times higher risk for headaches than controls (OR = 4.107; 95% CI = 1.036 - 17.565). Males with pathological blink reflex have a considerably higher risk for headaches, and it was 13 times higher than in controls (OR = 13.500; 95% CI = 1.555 - 153.646). There is a strong correlation between pathological blink reflex and the occurrence of headaches in both genders, indicating significant association of trigeminal nerve dysfunction with the occurrence of headaches. The use of blink reflex testing could be of help to detect patients with an increased risk for headaches.

Sexual Dysfunction and Incidence of Depression in Multiple Sclerosis Patients

Multiple sclerosis (MS) is one of the most common diseases of the central nervous system and usually occurs at the age when people would be expected to be in the prime of their sexual lives. In everyday practice, sexual dysfunction is underestimated because clinicians mostly concentrate on the classic neurologic deficits and often overlook symptoms that can seriously affect the quality of life. Our study included 98 patients (42 men and 56 women, mean age 35±12 years) with relapse from our MS register, with established diagnosis of relapsing remitting multiple sclerosis according to McDonald criteria. Patients completed the questionnaires (Sexual Satisfaction Scale, SSS and Beck Depression Scale BDS), and underwent neurological assessment (Expanded Disability Status Scale, EDSS). All patients were in the group with EDSS 2 to 4 points (mobile patients). There was no statistically significant difference in BDS and SSS values according to EDSS score. Correlation coefficients were calculated (BDS and SSS) for men (p=0.42) and women (p=0.44), yielding positive correlation. There was no statistically significant difference in BDS and SSS values according to gender, disease duration or immunomodulatory therapy. In our group of patients, despite low EDSS score (fully ambulatory without aid, self sufficient patients) we found positive correlation between sexual dysfunction and depression, showing that even in such patients the quality of life can be decreased. In conclusion, sexual dysfunction and depression are mostly under-recognized by neurologists because they are not part of routine testing; therefore, some additional questionnaires should be used in the evaluation in MS patients, even those with low EDSS score, in order to improve their quality of life.

The Impact of Sleep Deprivation on the Brain

Each sleep phase is characterized by specific chemical, cellular and anatomic events of vital importance for normal neural functioning. Different forms of sleep deprivation may lead to a decline of cognitive functions in individuals. Studies in this field make a distinction between total sleep deprivation, chronic sleep restriction, and the situation of sleep disruption. Investigations covering the acute effects of sleep deprivation on the brain show that the discovered behavioral deficits in most cases regenerate after two nights of complete sleep. However, some studies done on mice emphasize the possible chronic effects of long-term sleep deprivation or chronic restriction on the occurrence of neurodegenerative diseases such as Alzheimer's disease and dementia. In order to better understand the acute and chronic effects of sleep loss, the mechanisms of neural adaptation in the situations of insufficient sleep need to be further investigated. Future integrative research on the impact of sleep deprivation on neural functioning measured through the macro level of cognitive functions and the micro molecular and cell level could contribute to more accurate conclusions about the basic cellular mechanisms responsible for the detected behavioral deficits occurring due to sleep deprivation.

The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

Epilepsy is the most common neurological complication in pregnancy. Women with epilepsy have a higher risk of complications in pregnancy. In Croatia, women with epilepsy are treated by neurologists at tertiary centers according to the place of residence. We prospectively followed-up pregnancies in women with epilepsy and healthy controls, and analyzed the factors responsible for their delivery outcomes and development of their babies. Healthy pregnant women had a higher level of education and economic status, but pregnant women with epilepsy took folic acid in a higher proportion than controls, possibly due to timely preconception counseling. Complications during pregnancy depended on the number of antiepileptic drugs and epilepsy control. We noticed some behavioral and cognitive aspects in children exposed in utero to valproic acid, which required follow up. The rate of congenital malformations was not increased. In conclusion, women with epilepsy should receive preconception counseling about the risk for pregnancy, but also about the possibilities to minimize that risk. We have introduced a model of integrative management of pregnancy and epilepsy based on close collaboration among different clinical experts in Croatia, in order to provide prompt counseling and timely intervention.