精神障碍和治疗

Abstract

Demyelination affects highly myelinated structures like corpus callosum (CC). CC is exclusive in function that it connects right and left brain and it synchronises bimanual or bipedal activities. Affecting CC can disturb synchrony between the 2 hemispheres and can affect bimanual and bipedal tasks. The aim is to ascertain if speed of clapping (bimanual activity) can reflect the involvement of CC in MS. Succeeding 70 multiple sclerosis patients from outpatient clinics and home visits were tests for bimanual hand function (clapping). Exclusion criteria are upper limb power MRC scale, pain, visual impairment, intentional tremors, stroke or cognitive impairment. Study period started from 01.09.2016. Comparison of speed between rapid supination/pronation of left and right separately then clapping of both hands (supination/pronation of every hands alternatively) were conducted. Patients had to try to as fast as they might and noticeable slowing of clapping comparing to single hand supination/pronation was taken as a symbol slowing down of conduction through CC. 31 patients were excluded, 34 patients showed no noticeable difference, 2 patients were difficult to make conclusions and 3 patients showed definite slowing down in clapping. Positive patients will have difficulties in doing bimanual activities like using two sticks for mobility, typing using keyboard, and pushing wheel chair bimanually etc. It is possible to detect CC involvement by doing above bedside test and may be utilized in rehabilitation setting. Sample size isn't large enough and bigger studies got to follow to validate the finding.

Background:

The main feature of Multiple Sclerosis (MS) is demyelination which slows down the conduction of Axons in the Central Nervous System. All the signs and symptoms of MS are result of this feature. Corpus Callosum (CC) is one of the biggest myelinated structures in the brain and often involved in the demyelination process.

 Objectives:

1. To develop a bedside test that reflects CC involvement in MS and tests it on MS patients

2. To work out prevalence of positive CC bedside test in MS sufferers

 Methods:

Clapping with alternative supination/pronation needs synchronisation of both hemispheres through CC. This will be used as a bedside test reflecting integrity of CC. The speed of clapping is compared with the speed of single hand shakings. 70 consecutive patients, suffering from MS, were seen in clinics and home visits starting from 01 09 2016. Exclusion criteria were Upper limb strength MRC scale, Impaired position sense in the upper limbs, Pain including neuropathic sensation, visual impairment, Stroke, Cognitive impairment, intentional tremor, muscular-skeletal conditions affecting hand movement and movement disorder involving upper limb(s).

Results:

Out of 70 patients, 31 patients were excluded, 34 patients showed no difference in the speed between the clapping and single hand shaking and 3 patients showed noticeable difference between the clapping and single hand shakings. Comparison of CC thickness on MRI scan between three positive patients and three negative matched patients clearly showed marked thinning of CC within the three positive patients.

Conclusions:

The study showed at 4.2% of the patients showed dyes synchronisation of the hand movements (clapping) all of whom showed marked thinning on MRI scans.

Introduction

Corpus Callosum (CC) is the structure that connects both hemispheres in both directions. If there is deficiency in the connection, there will be dyssynchronisation in bimanual and bipedal activities. There is a bedside sensory test for CC developed by Kazuo Satomi. Sensory tests are not generally applicable in MS as many of the MS sufferers have variety of sensory impairments. Motor bedside test would be more appropriate and the author has designed the motor test for upper limbs.

Findings

3 (4.2%) patients showed noticeable slowing of speed of clapping and two patients finding were questionable due to functional overlay, 34 (48%) patients showed no noticeable difference in the speed of hand shakings and clapping. It is difficult to determine in 2 patients (3%) due to functional overlay. MRI images of the three positive patients were then reviewed. Thinnest segments of their CC were measured. The three positive patients were then matched with three negative patients from the sample (age & duration of MS) for comparison. The average thickness of CC in positive patients is 2.1mm and for the three matched negative patients is 3.6mm. The finding support that there is correlation between thickness of CC and dys-synchrony between the two sides

Representativeness of the Sample

Sample Frame was taken from filing cabinets. There were 367 MS patients under our team caseload which covers North Lincolnshire and Northeast Lincolnshire in UK (Total population 329420 in 2015). There are two outliers (Age 18 & 87) in the Sample Frame and they are excluded to match the Sample. Sample Frame is now 365. Mean age of Sample Frame is 55.56 as shown in the Age Distribution Graph. Maximum Prevalence is between 50 to 59 years. Female to Male ratio of Sample Frame is 2.04. In the sample, Female to Male ratio is 2.18. Age range is from 20 to 74 with the mean age of 55.5. Maximum prevalence is between 50 to 59 years Both Graphs are Negative Skewed as Maximum Prevalence is between 50 to 59 in both Sample and Sample Frame. Although Sample size is only 19% of Sample Frame, it is found to be representative of the Sample Frame.

Extension study

As an extension of the above study, further sampling was taken from clinics and home visits in July, August and September 2017. All the exclusion criteria from the first study still applied. In addition, the patients must not be from the first sample and their MRI scans must be accessible and the measurement of thinnest segment must be greater than 2.5mm (the author have arbitrarily chosen 2.5 mm thickness a cut-off point as the average CC of positive patients from the first study is 2.1mm). MRI scans were reviewed the day before the clinic, and bedside clapping test was performed in clinics or home visits the next day

Finding of Extension Study

There were 17 MS patients who met the criteria and none of the patients showed dys-synchrony in Bedside Clapping Test.

Conclusion of the Extension Study

The finding showed that if the CC is thick enough (>2.5mm), synchrony of bimanual activity is intact.

Discussion

Dys-synchrony of bimanual activity like clapping reflects dyssynchrony between the two hemispheres which reflects CC deficiency unless proven otherwise. MRI scan measurements support the correlation between the thinness of CC and dys-synchrony of left and right in bimanual activities. The author also has video evidence of how these positive patients struggled to do clapping despite being strong enough upper limbs (at least 4/5 MRC scale) which has never seen before until the author looked for it. The author has experienced with hundreds of neurological patients with a variety of neurological conditions in the last twenty years. Although MS can have complex manifestation of signs and symptoms, CC deficiency can cause specific clinical sign (another example of dys-synchrony is observed in Intern clear Opthalmoplegia where the deficiency lies in Medial Longitudinal Fasciculus and this was accepted without Imaging or Neurophysiology evidence)

Note: This work is partly presented at 5th International Conference on Brain Disorders and Therapeutics November 29-30, 2017 held at Madrid, Spain.

Abstract

Objective: The aim of this study was to evaluate the nutritional status and macronutrients adequacy of traumatic brain injury (TBI) patients and controls, attending treatment from an exclusive unit in Qatar. Research Design  

Methods: This study was conducted among male (TBI) in-patients admitted in Rumailah Hospital Rehabilitation Unit, Hamad Medical Corporation-Doha, Qatar from August 2014 to June 2015 (21 cases and 21 healthy volunteers). The attendees were consecutive patients with TBI. Demographic variables were solicited via medical evidence or directly from the attendees with TBI. Anthropometric evaluation and dietary intake (24- hour recall) were collected and assessed by the super tracker.

 Results: Half of the members (52.4%) were of age 30 -38 years range. Around 23.8% of cases were classified as having ‘mild TBI’ while 28.6% and 47.6% were classified as average and severe TBI respectively. In terms of nutritional parameters, three fourth (76.2%) of the cases were at high or average risk of malnutrition, 23.8% of cases were underweight, while 66.7% in the normal range and 9.5% were overweight. TBI patients were noted to have a insufficiency in energy (30.2%), carbohydrate (43.0%), protein (24.8%), and fibre (54.1%) intake.

Conclusion: Despite the high currency of TBI in emerging economies such as Qatar, to our knowledge, there is a dearth of studies inspect the nutritional status and it’s agree among the TBI population. This study specifies that TBI patients in Qatar are at a high risk of developing malnutrition, and macronutrients insufficiency. Therefore, nutritional assessment, involvement, and support are highly essential to improve TBI patient’s health status beyond the brain injury.

INTRODUCTION

TBI can be explained as a disturbance in the normal function of the brain caused by a blow or jolt to the head or a penetrating head injury (Sueur et al., 2013). Traumatic brain injury (TBI) is the leading causes of deaths and disability, accounting annually for 50,000 deaths and 235,000 hospitalizations (Global Burden of Disease Paediatrics Collaboration, USA, 5.3 million individuals are suffering from T problems (Al-Reesi et al., 2013) and similar high rate has been noted to occur in other developed countries economies such as those country in the Arabian Gulf, due to increased motorization, TBI is common due to high number of road traffic accident. Therefore, in the regions, there are urgent needs to quantify the sequel as well to contemplate remedial intervention among the victim of TBI. The first stage of cerebral injury after TBI is direct tissue damage and impaired regulation of Cerebral Blood Flow Before (CBF) metabolism which, in turn, has direct bearing to functionality of the individual affected by the TBI Victim of TBI have been documented to incur energy and protein deficits which, in turn has been postulated to have direct bearing on poor functional prognosis. Some studies have suggested that mechanisms specific to pathology entailed in TBI contribute energy and protein deficits while other studies have indicated that functional sequel of TBI renders the victim of TBI to be incapable to consume required energy and protein Peripheral amino acids (from skeletal muscle) and glycerol/free fatty acids (from adipose tissue) was ignites an inflammatory response that supports acute-phase functions after TBI. The total amount of visceral protein actually produced is less than the amount of skeletal muscle catabolized. Approximately 10% loss of skeletal muscle within one week, if caloric intake was inadequate for 2-3 weeks, which results in increased risk of mortality The brain-injured patient also oxidizes fatty acids at an increased rate, in addition to using muscle protein stores for fuel Catabolism of protein has various implications for patients with TBI, it may be affected by decreased nitrogen efficiency, immobility steroid administration, and decreased nutrient intake. Weight loss, muscle wasting, and lowered levels of visceral proteins (prealbumin, albumin, and transferrin) are commonly evidenced signs after TBI (Ott et al., 1994; Cerra et al., 1987). Previous studies have indicated that nutritional status could play an important role for heightening functional recovery of people with TBI. To our knowledge, such studies have not been forthcoming from Arabian Gulf countries where TBI constitute a leading burden of disability and dependency (Bener et al., 2010). In order to fill the gap in the literature, the present current case control study aim to find out the link between nutrition and TBI. For this we evaluated the nutritional status, macronutrient adequacy among TBI and the influence of trauma severity on nutrient intake among patients with TBI attending Rumailah Hospital, Doha, Qatar. METHODS Patients This study was conducted in rehabilitation ward at Rumailah Hospital, Doha - Qatar from August 2014 to June 2015. Twenty five post traumatic brain injury patients, aged 18 – 65 years, males, free of any chronic diseases and 21 healthy participants as control group were recruited. Comparative normal healthy subjects were recruited from the community. Cognitive assessment for all patients was conducted using the Montreal Cognitive Assessment (MOCA) (Nasreddine et al., 2015). Four patients were excluded from the study due to incomplete nutritional assessment or refused to continue

 Demographic characteristics

 Demographic information, including age, sex, education level, marital and smoking status were collected using a structured questionnaire Weight, height and body mass index (BMI) were measured and for patients who were unable to stand, height was estimated by using knee height, ulna length and demi - span equations as detailed elsewhere (Lohman et al., 1988; Cheng et al., 2001; Gauld et al., 2004; Bassey, 1986; Organization, 2012) Energy (Kcal), carbohydrate (gm), protein (gm), fat (gm) and fibre (gm) intakes were assessed by using the 24 – hour recall method (Lim et al., 2012) through face–to–face interview with each subject. Household utensils with different portion size of common foods were used to assist the patients to report the accurate amount of food consumed. Food intake was analysed electronically using electronic program the percentage of carbohydrate, protein, and fat was calculated as calories of each nutrient divided by the actual energy intake. Macronutrients adequacy was calculated based by dividing the actual intake by Recommended Daily Allowances (RDA) (Report of the Panel on Macronutrients, 2005).

 Nutritional Status and TBI Severity

“Malnutrition Universal Screening Tool” (MUST) (Henderson et al., 2008) was used to assess the nutritional status of all subjects and it was classified as: no risk, moderate risk and high risk of malnutrition when MUST score was 0, 1 and ≥ 2 respectively. Severity of TBI was classified into mild, moderate, and severe based on Glasgow Coma Scale (GCS) when it ≥13, 9 -12 and ≤ 8 respectively (Kondrup et al., 2003).

Ethical approval

The written informed consent was obtained from each participant. The study was approved by Ethical Committee of Medical Research Centre - Hamad Medical Corporation.

Note: This work is partly presented at 5th International Conference on Brain Disorders and Therapeutics Nov 29-30, 2017 held at Madrid, Spain

Abstract

In the present study, we examined the effect of acoustic range of electromagnetic field (EMF) on the behavioural manifestation of seizure in genetically epilepsy-prone rats (GEPRs) of Krushinsky Molodkina strain. A five days exposure to EMF (10000 -15000 Hz frequency, 1, 5 m/Tesla, during 20 min) resulted in partial or complete suppression of behaviour activity in GEPRs. Besides, on the background of EMF the latency stage of first wild run was increased and on equivalent conditions, duration of untamed run was decreased. The anxiety degree in irradiated GEPRs versus the controls (GEPRs without magnetic stimulation) was decreased, whereas the locomotion/exploratory activity were increased. Audio genic stimuli obtained in GEPRs changed the Eco activity of sensomotoral cortex only in audiogenally kindled animals. Findings of this study suggest that the regulation of the behavioural manifestation of seizure in GEPRs doesn't involve the cortex; mainly, it's regulated by brainstem structures. The EMF can modulate Ponto-geniculo-occipital (PGO) waves. On the other hand, PGO waves have a possible inhibitory influence on EEG seizure activity. Increased number of PGO spikes in animals exposed to auditory stimulation attributed to the anatomical proximity of the structures involved in acoustic signal processing. Besides, acoustic stimulation could promote the discharge of acetylcholine within the brainstem structures involved within the initiation of PGO waves. Perhaps, these influences mediated by changing in membrane ion channel permeability, which occur under the effect of low-frequency EMF. Also, we propose that EMF exposure on brain results changes in electric and current density fields, amid modification of synaptic activity, modes of synchronous bursts of neuronal populations, ion dynamics, and other phenomena. Thus, acoustic range of EMF can apply for suppression of behavioural manifestation of seizure.

Introduction

Epilepsy is one of the most common disorders. According to the WHO (World health Organization) fact sheet, epilepsy affects about 50 million people of all ages worldwide. Despite the fact that it is possible to treat epilepsy using pharmacological substances, about 30- 40% of the patients are resistant to such treatment (WHO, media Centre 2016). In addition, a long-term consumption of the drugs negatively affects the patients’ cognitive functions. The effectiveness of pharmacological agents, used for epilepsy treatment is limited due to incomplete understanding of the mechanisms involved in the pathogenesis of the disease. Therefore, a goal of modern psychiatric research is to find the new ways for anti-epilepsy therapy, which will give the opportunity to cure this group of patients. The EMF exposure is a non-invasive treatment method; it used as a complementary to the drugs, for treating different neurodegenerative diseases (Parkinson's disease, schizophrenia, depression, tinnitus, etc.). EMF exposure also can be used as a separate treatment therapy. Furthermore, repetitive TMS Trans cranial Magnetic Stimulation) is seen as a secure treatment method, without enduring side effects: no long-term neurological, cognitive, or cardiovascular side effects are reported. The EMF appears to be biologically active, penetrating into the living tissue with none impediments. However, it is unclear how the low-frequency EMF can block seizure activity. One of the basic provisions underlying the given research is the assumption that the macromolecules which constitute the living organism are subjected to the conformational fluctuations under the conditions of EMF impact. In our opinion the artificially created EMF may change the tonic activity of the cells located in the local area of its action and because of it the mode of neural impulses formation. Because of it, the tonic activity is also changed in the central nuclei, through which the various sensory afferent ways coming from the various parts of the body are passing. On the other hand, oscillations of acoustic range (which belong to low frequency oscillations) due to their activity can cause the intensification of chemical processes. Then, oscillations of this range can be used both for process stimulation, intensification and optimization and for their attenuation. It will depend on impact mode and selection of duration. Both a change in membrane ion channel permeability and oriented redistribution of radicals, liquid-crystalline macromolecular structures, metalloproteinase (haemoglobin, vitamins) and molecular water fragments may occur under influence of low frequency magnetic fields

The goal of this study was to explore the potential mechanisms underlying the impact of EMF exposure on the epilepsy. In GEPRs and inbred white rats, we examined the effect of EMF exposure on ECoG activity in sensomotoral cortex. We attempted identify the optimal parameters of repeated EMF exposure, which fully or partially depress the ECoG and behavioural seizure manifestations.

Methods

 Subjects and Surgical Procedures

 Experiments were conducted on male white, inbred rats and GEP of Krushinsky-Molodkina (KM) strain rats (n=14). This strain of rats manifests short lasting seizure activity in neonatal age and fully-fledged seizure activity after hierarchical implication of brainstem structures. In response to a strong sound (the bell -90-dB, during 60 sec), GEPRs display either fear reaction accompanied by facial muscle clonus (group a) or fear reactions with elevated motor act responses (wild running, jumps), which are accompanied with tonic-clonic behavioural seizures (group b). The present study was conducted on animals of group b. Under ketamine (5-10 mg/kg intraperitoneally) Anesthesia, the rats were implanted with stainless bipolar electrodes (8IE3633SPCXE ELEC 0.05-125 MM SS Plastics One) into sensomotoral area of neocortex.

Experimental Paradigm

At the beginning of experiments, both control (Inbred, white male rats n=7) and experimental (GEPRs n=14) rats were placed into coil for EMF exposure with defined parameters of magnetic field (see below) for a 20-min session. 10 min after the session of EMF exposure, the animals were re-tested. The GEPRs (with or without exposure) were given audio genic stimuli, for 60 secs, before and after testing in open field for monitoring behaviour correlates of seizure activity.

EMF Exposure

For EMF exposure (carried for five consecutive days), we used the coil designed at Tbilisi Technical University, Georgia. Parameters of magnetic field (stimulus frequency, its intensity and train duration), which partially or fully depressed ECoG and behaviour manifestation of seizure activity, were established during pilot experiments. For repetitive (5-days) EMF exposure, we used the following parameters: (10000- 15000 Hz, 1-1.5 m/Tesla).

The Open Field Test

Emotional-motivational status of the rats was tested in a chamber of 80 cm in diameter surrounded by 30 cm height walls, Open Field. The floor of the chamber was divided into 32 squares and lighted with 200 W lamps. The rats were video-recorded for initial 5 minutes after the placement into the Open Field, for three consecutive days (the same time of day). We registered the following parameters: entering the centre, numbers of crossed squares, head raise, vertical stands, the frequency and duration of grooming, number of faecal boluses and urination. After each trial, the chamber was cleaned with 30 % ethanol solution.

Data Analysis

We determined the parameters of locomotors and emotional-motivated activity in Open field (see above), the parameters of behavioural (latency of the first wild run, duration of the first wild run, duration of pause, and duration of second wild run, duration of tonic-clonic seizure and of post-ictal activity) and ECoG seizure activity were determined as well.

Note: This work is partly presented at 5th International Conference on Brain Disorders and Therapeutics November 29-30, 2017 held at Madrid, Spain.

Abstract

The nucleus accumbens (NAc) and therefore the ventral tegmental area (VTA) are two major areas for the mesolimbic dopaminergic system which are strongly involved within the development of behavioral sensitization. In the present study, we investigated the role of D1/D2 dopaminergic receptors within the NAc or VTA in response to sensitization to morphine by the tail-flick test as a model of acute pain. Sensitization was induced by subcutaneous (SC) injection of morphine (5 mg/kg), once daily for 3 days followed by five days freed from drug. After the sensitization period, ant nociceptive responses induced by an ineffective dose of morphine (1 mg/kg; SC) were obtained by the tail-flick test, and represented as maximal possible effect (%MPE). In experimental groups, D1 and D2 receptor antagonists, SCH-23390 and sulpiride (0.25, 1 and 4 µg/rat), were separately microinjected into the NAc or VTA, 10 min before morphine administration during the sensitization period, respectively. Results showed that injection of morphine during the sensitization period (development of sensitization) increased %MPE of the ineffective dose of morphine from 2.43±1.4% in naive to 47.75±4.01% in sensitized animals. Unilateral microinjections of various doses of the D1/D2 receptor antagonists, SCH-23390 and sulpiride, into the NAc dose-dependently decreased %MPEs in morphine-sensitized animals. Nonetheless, %MPEs were only suffering from intra-VTA administration of SCH-23390 in morphine-sensitized animals. Our findings suggest that both the D1/D2 dopamine receptors in the NAc and the D1 receptors in the VTA may be of more important in the development of sensitization to in rats.

Introduction

While the precise role for dopamine has been debated, dopamine is thought to be a key ingredient in both the development and expression of behavioral sensitization to repeated drug administration (Lodge and Grace, 2008; Pierce and Kalivas, 1997; Robinson and Berridge, 1993). It was found earlier that long-term opioid treatment leads to antinociceptive tolerance and causes a paradoxical sensitization (opioid-induced hyperalgesia) toward mildly painful (hyperalgesia) and normally innocuous (allodynia) stimuli. Prolonged morphine administration was also found to up-regulate pain neurotransmitter (such as calcitonin gene-related peptide; CGRP) levels in primary sensory neurons (Tumati et al., 2011; Zarrindast et al., 2007). Anatomical and pharmacological evidence indicates that the nucleus accumbens (NAc) is involved in opioid sensitization (Azizi et al., 2009; Kalivas and Duffy, 1995; Robinson and Kolb, 2004). The common circuitry in behavioral sensitization includes dopamine projections from the ventral tegmental area (VTA) to the NAc and glutamate projections from the medial prefrontal cortex (mPFC) to the NAc (Pierce and Kalivas, 1997). The NAc is a complex forebrain structure (Jongen‐Rêlo et al., 1994), which receives massive dopaminergic input from the VTA and glutamatergic input from structures such as the hippocampus, amygdala and mPFC (Heyman et al., 1989). In rats, dopamine-mediated ant nociception has been reported in many studies (Altier and Stewart, 1998; Morgan and Franklin, 1991). The binding of dopamine to its receptors causes a change in the release of neurotransmitters which plays a key role in behavioral sensitization. For example, enhanced excitability of the VTA dopaminergic neurons that occurs with repeated cocaine is associated with a decrease in dopamine D2 auto receptor sensitivity (White and Wang, 1984). Moreover, repeated intra-VTA injections of low doses of the D2 receptor antagonist, eticlopride, which is presumably an auto receptor-selective, enhanced subsequent stimulant response to amphetamine (sensitization). Blockade of the dopamine D1 receptors in the VTA during the initiation phase prevents the development of amphetamine, but not cocaine sensitization (Vezina, 1996). Morphine and amphetamine-induced analgesia are involved in increasing dopamine levels in the NAc. In a study by Altier and Stewart (1998), dopamine receptor antagonists injected into the NAc blocked the analgesic effects of intra-NAc or -VTA of substance P, morphine and amphetamine. This study suggests that tonic pain is inhibited, at least in part, by enhanced dopamine released from terminals of mesolimbic neurons. Human and animal imaging data also suggest that the NAc is an important neural substrate of pain modulation, and intra-accumbal injection of D2 receptor agonist inhibits persistent on-going nociception in the formalin test (Magnusson and Fisher, 2000; Taylor et al., 2003). Considering the above-mentioned findings and the interaction of opiate-mediated pain modulation and sensitization, in the present study, we tried to find out the role of dopamine D1 and D2 receptors within the NAc and VTA in the sensitization to morphine by the tail-flick test as a model of acute pain in rats.

2. Materials & methods

 2.1. Animals

 One hundred and thirty eight adult male albino Wistar rats (Pasteur Institute, Tehran, Iran) weighing 200–220 g were used in these experiments. Animals were housed in groups of three per cage a 12/12 h light/dark cycle (light on between 7:00 a.m. and 7:00 p.m.) with free access to chow and tap water. The animals were randomly allocated to different experimental groups. Each animal was used only once. Rats were habituated to their new environment and handled for one week before the experimental procedure started. All experiments were executed in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publication No. 80-23, revised 1996) and were approved by the Research and Ethics Committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2.2. Drugs

 In the present study, the following drugs were used: morphine sulphate (Temad, Tehran Iran) and SCH-23390 (Tocris Bioscience, Bristol, UK), a D1 receptor antagonist, which were dissolved in sterile saline (0.9%). Sulpiride (Tocris Bioscience, Bristol, UK), a D2 receptor antagonist, was dissolved in 10% dimethyl sulfoxide (DMSO). In separate groups, control animals received either saline or 10% DMSO as a vehicle into the NAc or VTA.

 2.3. Stereotaxic surgery

Rats were anesthetized by intraperitoneal injection of xylazine (10 mg/kg) and ketamine (100 mg/kg), and placed into a stereotaxic device (Stoelting, USA). An incision was made along the midline, the scalp was retracted, and the area surrounding bregma was cleaned and dried. In addition, lidocaine with epinephrine (0.2 ml) was injected in several locations around the incision. In separate groups of animals, a stainless steel 23-gauge guide cannula was unilaterally implanted 1 mm above the intended site (NAc or VTA) of drug injections according to the rat brain atlas (Paxinos and Watson, 2007). Stereotaxic coordinates for the NAc were 1–1.2 mm anterior to the bregma, ±0.8–1 mm lateral to the sagittal suture and 6.8–7.8 mm ventral to the skull surface; and those for the VTA were 4.7–5 mm posterior to the bregma, ±0.8–0.9 mm lateral to sagittal suture and 8.2–8.4 mm from the skull surface. The guide cannula was secured in place using two stainless steel screws anchored to the skull and dental acrylic cement. After the cement completely dried and hardened, one stainless steel stylet was used to occlude the guide cannula during recovery period. Penicillin-G200000 IU/ml (0.2–0.3 ml/rat, single dose, intramuscular) was administered immediately after surgery. Animals were individually housed and allowed to recover for 5–7 days before experiments.

2.4. Drug administration

Microinjections were performed by lowering a stainless steel injector cannula (30-gauge needle) with a length of 1 mm longer than the guide cannula into the NAc or VTA. The injector cannula was connected to a 1-μl Hamilton syringe by polyethylene tubing (PE-10). Drug solution or vehicle was infused over 60 s and left in place for 60 s to facilitate drug diffusion, which was followed by replacement of the obdurator. Different doses of SCH-23390 and sulpiride were slowly administered in a total volume of 0.5 or 0.3 μl into the NAc or VTA, respectively. The microinjection time for 0.1 μl volume of drugs was 10 s to prevent lesions in these areas. All drug solutions were freshly prepared on the test day, and all microinjections were unilaterally administered into the NAc or VTA.

Note: This work is partly presented at 5th International Conference on Brain Disorders and Therapeutics November 29-30, 2017 held at Madrid, Spain.

Abstract

Objectives: 

To determine the prevalence, predictors, triggers and educational outcome of migraine among medical students and interns in King Abdulaziz University, Jeddah, Saudi Arabia.

Methods: 

A cross-sectional study was completed among 566 participants selected through a multistage stratified random sample method. A validated, confidential, self-administered data collection sheet was utilized. It contained ID Migraine test™, Numeric Pain Rating Scale (NPRS). Questions about possible predictors, triggers and impact of migraine were asked. Descriptive, inferential statistics and multiple logistic regression analysis were conducted.

Results:

Quite one-half (54.9%) of the participants had ≥ 2 headache attacks during the three months preceded the study. The prevalence of migraine was 26.3%, and 41.6% of the cases suffered from severe pain. The main migraine predictors were Functional Gastrointestinal Disorders (FGIDs), case history of migraine, female gender, and enrolment within the second school year . Exam stress and sleep disturbances were the foremost typical triggers. The majority of the participants reported that their educational performance and skill to attend sessions were affected during migraine attacks.

Conclusion: 

A relatively high prevalence of migraine was seen among our participants. FGIDs, gender and academic year were the predictors. Screening and management of migraine among medical students are required. Conduction of relaxation programs and stress management courses also are recommended.

INTRODUCTION

Nowadays, headache has been considered together of the highest global disabling medical conditions.1 Migraine is a crucial sort of headache, and one among the chronic multifaceted neuro-inflammatory disorders. It is characterized by recurrent throbbing headache pain that typically affects one side of the top, and is usually amid nausea and disturbed vision. Migraine headache accounts for 1.4% of all neurological and mental disorders. It was reported that the estimated lifetime prevalence of migraine ranged 12%-18%.

Migraine is taken into account a crucial ill health among university students. This is due to its high prevalence, associated morbidities, disability and decreasing academic performance. Medical student are usually working hard and requiring constant concentration and studying, which may cause much stresses and sleep disturbances, subjected to high stressful conditions.

There is inadequate number of recent studies done about migraine headache among medical students in Jeddah, Saudi Arabia. Hence, such study was required. The objective of the study was to work out the prevalence, predictors, triggers and academic outcome of migraine headache among medical students and interns in King Abdulaziz University (KAU) in Jeddah, Saudi Arabia.

METHODS

A cross sectional study was conducted during the educational year 2014/2015. The study population included medical students who completed the freshman year (2nd – 6th year), and interns at KAU. A multistage stratified random sample method was used. Stratification put into account the educational level and gender. The sample size was calculated according to the following pre-established formula.

The calculated sample size to achieve a precision of ± 0.04%, at a 95% Confidence Interval (CI) was 600 participants. A validated, confidential, self-administered data collection sheet was used. The face and content validity of the instrument was assessed by two experts. Internal consistency reliability was assessed by Cronbach’s alpha test and found to be 0.8. The data collection sheet asked about personal, socio-demographic data, habits, Grade Point Average (GPA), and history of ≥ 2 general headache attacks during three months preceded the study. History of chronic diseases, Functional Gastrointestinal Disorders (FGIDs) other than Irritable Bowel Syndrome (IBS), and IBS were asked. Anxiety and depression were assessed. Weight and height were determined.

The English version of ID Migraine™ test (with good sensitivity and specificity)6 was used. The detected migraineurs were asked about migraine regarding the age onset, frequency, duration of attacks, associated symptoms, triggers, etc. In addition, the Numeric Pain Rating Scale (NPRS) (7) was used to assess severity of migraine during attacks. For females, the effect of menstrual period on migraine was asked. Drugs utilized for relieving migraine headache was determined. Educational outcomes of migraine were assessed.

Statistical analysis

The data was analysed using SPSS (21). Body Mass Index (BMI) was calculated. The severity of migraine pain was classified by NPRS into mild, moderate and severe degrees.7 Descriptive statistics were done. Pearson’s Chi-square (X2), Odds Ratios (ORs) and 95% CIs were calculated. A multiple logistic regression analysis model was done. All P-values < 0.05 were considered statistically significant.

Ethical statement

The research was conformed to Helsinki Declaration. The protocol of the study was approved by the Institutional Review Board (IRB) of King Abdulaziz University Hospital (KAUH), with a Reference Number of 334-14. A written consent was taken from each student accepted participant. Administrative approvals were also taken.

RESULTS

Out of 600 invited medical students and interns, 566 completed the questionnaire (acceptance rate= 94.3%). Their mean age was 21.5 ± 1.6 years. The prevalence of getting ≥ 2 headache episodes during the three months preceded study was 54.9%. Furthermore, the prevalence of migraine headache was 26.3% (47.9% of all types of headache). The mean age of start of migraine attacks was 16.9±3.6 years, and the mean number of attacks was 4.6± 1.5 per month. About one-third (34.8%) of female sufferers reported that their migraine headache is suffering from cycle . NPRS revealed that 14.8%, 43.6% and 41.6% of migraines suffered from mild, moderate and severe degrees of pain, respectively.

DISCUSSION

The current study illustrated that more than one-half of the participants suffered from ≥ 2 headache attacks during the three months preceded the study. This coincides with other study done among medical students from Isfahan, Iran. Results from an Indian study showed that migraine constituted 42% of all types of headache, which agrees with our findings.

The prevalence of migraine headache among our participants was 26.3%, which agrees with recent similar studies from Kuwait, USA and India. On the other hand, much lower rates were reported from other studies done in Iran, Turkey and Nigeria. On the other hand, a higher prevalence was reported from Peshawar, Pakistan. The causes of such discrepancies could be attributed to cultural differences between countries, difference in the time of conduction of their studies, the amount of educational stress and the instrument used for diagnosis of migraine. In the current work, the mean number of migraine attacks was 4.6 attacks / month, which is in line with the results from Kuwait and Pakistan.

Our findings revealed that presence of migraine headache was associated with female gender. This was supported by results from many other studies. In addition, about one-third of female migraineurs in our study reported that migraine was affected by their menstrual cycle, which agrees with the results from Croatia. Endogenous sex steroid hormones may have a relevant role in explaining of such findings.

 The second year students in our study reported significantly higher rate of migraine compared to others. This can be explained by numerous stressors that face medical students during the first medical education year (after freshman year). However, our results disagree with the Croatian study. The cause of discrepancy may be attributed to cultural differences or the amount of faced stresses.

Results of the present study revealed presence of an association between migraine headache and the family history of it. This finding agrees also with the results of other studies. FGIDs was the first predictor of migraine in the current study and this is in line with other studies. The possible physiological pathways of migraine may be associated with the brain-gut axis, neuro-immunity, and neuro-endocrine interactions.

Our results showed that stresses, and sleep disturbance were the commonest reported triggers, which agree with results from India and Kuwait. Furthermore, smoking was reported as a trigger of migraine among approximately 16% of migraineurs which is in line with results from Spain.

 The commonest accompanying symptoms of migraine in our study were difficulty in concentration and photophobia. Similarly, results from the Indian study reported that photophobia was the commonest manifestation.9

Paracetamol was the most frequently used analgesic for migraine in the current study. On the other hand NSAIDs were the most commonly used by US students. This discrepancy may be due to widespread use of Paracetamol in Saudi Arabia.

The present study showed that educational performance and the ability to attend educational classes were affected to a certain degree among the majority of migraines during migraine attacks. These findings are in line with findings from a study from the USA.

Biography

Afnan Khalid Alotaibi has completed her MMBS from King Abdulaziz University School of Medicine. Currently, she is a Medical Intern at King Abdullah University Hospital (KAUH).

Note: This work is partly presented at 5th International Conference on Brain Disorders and Therapeutics November 29-30, 2017 held at Madrid, Spain

Introduction

The theoretical framework The driving force behind this research idea are the current funding cuts within mental health services instigated by municipal councils in Belgium and in the Netherlands that have an effect on the availability of day activity services, raising the possible question if the lack of services has an effect on the recovery process of people with a serious mental illness. Another underlying reason and concern behind the need for this investigation are the recent figures that show an increase of forced admissions in Psychiatric Hospitals. This has been attributed to a decline in supportive strategies and admission possibilities that assist in the recovery process. Clinical and community relevance in regard to day activities has been a long-time supporting strategy in caring for people with a serious mental illness, either in a hospital or community setting. These services have been around since the dawn of psychiatric care. In large psychiatric hospitals activities were and are organised as part of the treatment and nursing processes. These days participating in activities outside the confines of home can stimulate community participation, create an exchange mechanism between service users and promote a more positive self-esteem. Furthermore, the possible therapeutic benefits of reducing relapses of psychiatric symptoms, community acceptance and participation have been documented

Methods:  There is a substantial amount of literature dealing with the issue of activities and the issues related to the recovery process. The principal researcher has found articles that touched on the subject in the database PubMed, Google Scholar, and the International Journal of Mental Health Nursing, Community Mental Health Journal, International Journal of Mental Health, International Journal of Mental Health Systems and Quality of Life Research. For example, key articles by Happell et al. and Borg et al. were used. The databases PubMed and Cochrane Library were considered for multiple searches using various combinations of key words as: day activity, recovery, ACT (Assertive Community Treatment), serious mental illness, schizophrenia, psychosis, psychiatric hospital admission, service users, local community and Ghent.

Ethical issues in the planned data collection Ethics approval will be sought from the Ethics Committee of the Ghent University Hospital, to start interviewing patients in the day activity center in Ghent. Participants will be provided with information of the study and asked to sign a consent form. Identifying information will be removed from any reported material. De-identification of participant’s names and their socio-demographics will occur, with a pseudonym allocated to each participant to preserve their confidentiality. The recordings of interviews will only be heard by the principal researcher, the transcribing in Dutch will be completed by the principal researcher to increase his experience of familiarity with the data. The recordings will not be used for any other purpose.

Results:  The literature defines day activities as all activities that participants are involved in to fill in her or his day. Therefore, the first aim of these activities is to be occupied. These activities vary from active employment to hobbies and anything in-between. The literature shows, by entering keywords in the databases, that day activities have an important role in recovery. By using the search engines, the following concepts have been identified by the principal researcher:

• Relaxation is a model identified by the literature. Within this concept the participant is involved in activities that will relax them, like listening to music.

 • Feeling fit is also a component. It serves the feeling of wellbeing and energy. It can assist to gain physical health after a period of i.e. illicit drug use.

 • Self-expression are all the activities that can fall under the concept of creativity. Examples are acting, drawing, painting and photography.

• Self-development. This entails all activities that are aimed at the process of recovery. The fourth item can be marked as the umbrella of the concepts that have been identified. The literature shows a variety of definitions of recovery. Aside from the official Macquarie dictionary (online) definition: “Repair, reinstate, salvage and salvation”.

 • Something that is broken that needs to be mended

• Conscious thought and less occupied with problems

 • Cured from drugs and

• Being part of the community again.

Discussion:  In order to understand the full scoop of the issue at hand, one will have to realise that the fairly recent introduction of the Mobile Teams and FACT (Flexible Assertive Community Treatment) model changed the care for people with a serious mental illness significantly, thus needing new parameters to evaluate this care. Extended admission to a psychiatric hospital is now replaced by active social psychiatry. Their strength is that they work with the local partners in their subsequent municipal council. These partners also include the organised day activities delivery of care. The core business is recovery and focusses on recovery supporting care and methodology.

Strength of this pilot study is the qualitative approach. Qualitative approaches offer flexibility. Qualitative research is “multi-method in focus, involving an interpretive, naturalistic approach to its subject matter”. This means that qualitative researchers study issues in their natural settings, attempting to make sense of, or interpret, phenomena in terms of the meanings people bring to them.

Note: This work is partly presented at 2^nd International Congress on Mental Health on June 13-15, 2019 held in Amsterdam, Netherlands

Background

Service providers throughout Europe have recognized the need to describe how high-quality community-based mental health care looks to establish their own services and to update governments, commissioners and funders. In 2016, councils of mental health care service providers, networks, umbrella organizations and knowledge organizations in Europe came together to found the European Community Mental Health Services Provider (EUCOMS) Network. This network advanced a shared vision on the ideologies and key elements of community mental health care in different circumstances. The result is a comprehensive agreement paper, of which this location paper is an outline.

With this paper the network wants to contribute to the conversation on how to recover structures in mental healthcare, and to narrow the gap between evidence, policy and exercise in Europe.

Main text

The progress of the consensus paper started with an skillful workshop in April 2016. An allocated writing group on behalf of the workshop contributors built upon the outcomes of this meeting and developed the harmony paper with the input from 100 European counterparts through two additional work groups, and two structured feedback rounds via email.

High quality community-based mental health care: 1) protects human rights; 2) has a public health focus; 3) supports service users in their recovery journey; 4) makes use of effective interventions based on evidence and client goals; 5) promotes a wide network of support in the community and; 6) makes use of peer expertise in service design and delivery. Each principle is illustrated with good practices from European service providers that are members of the EUCOMS Network.

Conclusions

Dialogue among EUCOMS network members resulted in a blueprint for a regional model of integrated mental health care based upon six principles.

Aim

This paper defines a shared vision in the form of a position paper outlining six values behind the organization of good community-based mental health care in a separate geographically defined region or catchment area. The practical implications of these principles have been exemplified with good practices from European service providers that are members of the EUCOMS Network. With this shared vision EUCOMS aims to contribute to the conversation on how to narrow the gap between evidence, policy and practice in Europe supporting the regional application of quality public mental health care taking into account the diverse contexts. The main inquiry addressed in the position paper is: “what are the principles and key elements of high-quality community-based mental health care according to memberships of the EUCOMS network?”

Methods

Setting the scope

Consultation and integration

Finalization

Principles and key elements of community-based mental health care

This position paper abstracted health as the lively ability to adapt and self-manage one’s own well-being to address the physical, emotional and social tests of life. This definition shifts the stress from ill-health to resilience and well-being stressing that the focus of community-based mental health care is on the promotion of mental health, integrating cure, care and anticipation of mental illness. The position paper defines what high quality municipal mental health care looks based on six principles each outlined below:

1. Human rights

2. Public health

3. Recovery

4. Effectiveness of interventions

5. Community network of care

6. Peer expertise

Conclusions: Discussion among European professional-, scientific- and peer- experts and members of the EUCOMS network resulted in an impression of six principles that help as a foundation for a national, regional and local model of integrated mental health care. High quality community-based mental health care: 1) protects human rights; 2) has a public health focus; 3) supports service users in their recovery journey; 4) makes use of effective interventions based on evidence and client goals; 5) promotes a wide network of support in the community, and; 6) makes use of peer expertise in service design and delivery.

The six principles can be explained from three consistent perspectives. The first combines the human rights and public health principle in the citizenship or societal viewpoint, which claims for the protection of human rights for all, including people with mental illness. The second is the personhood or the facility user perspective, which combines the retrieval and peer know-how principle. This perspective puts emphasis on the centrality of the service user in care and the use of their expertise in service design and establishment. The last viewpoint is the quality of care or the professional perspective, uniting the effectiveness of interferences and the community network of care principles. This last viewpoint argues that interventions are effective when they take into account local realities and work with the network, both formal and informal, of the facility users.

Limitations: Although the authors tried to develop a agreement based on the viewpoint of a broad variety of stakeholders both in terms of their role within the mental health system and country of origin, it must be noted that not all investor groups have been equally signified. This article presents the view of EUCOMS members on what the principles and key-elements are of high-quality community-based mental health care. EUCOMS members are mental health service managements, umbrella organization directors, mental health care professionals, peer experts, researchers and policy advisors who are mostly in favor of community-based mental health care, as they became member of the network to endorse its implementation. In the development of the shared vision professionals from Western European countries were overrepresented. Relatively little service users and careers, and respondents from Southern and Eastern European countries provided input. This could have resulted in a view that does not sufficiently reflect counterarguments for community-based mental health care, the perspective of the service users and careers, and the socio-cultural and economic context in Southern and Eastern European countries.

Note: This work is partly presented at 2^nd International Congress on Mental Health on June 13-15, 2019 held in Amsterdam, Netherlands