Clinical Neuroscience

Unanswered questions in the transcranial magnetic stimulation treatment of patients with depression

MORVAI Szabolcs1, NAGY Attila1, KOVÁCS Attila1, MÓRÉ Csaba1, BERECZ Roland1, FRECSKA Ede1

JANUARY 30, 2016

Clinical Neuroscience - 2016;69(01-02)

DOI: https://doi.org/10.18071/isz.69.0004

According to the WHO fact sheet depression is a common mental disorder affecting 350 million people of all ages worldwide. Transcranial Magnetic Stimulation (TMS) is a technique which allows the investigator to stimulate and study cortical functions in healthy subjects and patients suffering from various mental and neurological disorders. In the early 1990s, studies revealed that it is possible to evoke long term mood changes in healthy volunteers by rapid rate repetitive, TMS (rTMS) over the frontal cortex. Subsequent studies involving depressed patients found frontal cortical rTMS administered daily to be clinically effective. In the past two decades, numerous trials examined the therapeutic potential of rTMS application in the treatment of mood disorders with constantly evolving treatment protocols. The aim of this paper is to review the literature of the past two decades, focusing on trials addressing the efficacy and safety of rTMS in depressed patients. Our primary goal is to evaluate the results in order to direct future studies which may help investigators in the development of treatment protocols suitable in hospital settings. The time is not far when TMS devices will be used routinely by practitioners primarily for therapeutic purpose rather than clinical research. To our knowledge, a widely accepted “gold standard" that would offer the highest efficacy, with the best tolerability has not been established yet. In order to approach this goal, the most important factors to be addressed by further studies are: localization, frequency, intensity, concurrent medication, maintenance treatments, number of pulses, trains, unilateral, or bilateral mode of application.

AFFILIATIONS

  1. University of Debrecen, Department of Psychiatry, Debrecen

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Clinical Neuroscience

[Financing of medicines for treatment of rare diseases of the nervous system. orphan drugs in rare neurological diseases]

MOLNÁR Mária Judit, BONCZ Imre, KOSZTOLÁNYI György, SZEGEDI Márta

[Objectives – Nervous system involvement is expected up to 60-70% in case of rare diseases. This article aims to present the financial methods and expenditures of rare neurological diseases’ orphan medicinal products being financed in the frame of Hungarian social insurance system in 2012. Methods – The subsidized orphan medicines were selected on the Orphanet portal 2012 while orphans financed by compessionate use were provided by the Hungarian National Insurance Fund Administration (OEP) database. Three products exist without orphan designation, however those are intended for the treatment of rare neurological ailments. The medicines were categorized by financial methods and determined by costs. Results – Numerically, out of 36 pieces of subsidized orphan or orphan criteria fulfilled medicines 17 were authorized for the treatments of rare neurological diseases in the year of 2012. Most of the drugs (14 pieces) were to be financed in the frame of compassionate use by the reimbursement system. The cost amount of social insurance for 387 rare neurological disease patients reached more than 4.5 billion HUF (1.4% of the total pharmaceutical budget in outpatient care). Conclusions – In Hungary half of the subsidized orphans are intended for the treatments of rare neurological ailments. 30% of the total amount of social insurance for rare diseases’ medicinal treatments were used to subsidizing rare neurological disease patients in 2012. Most of the orphan medicines were to be financed in the frame of compassionate use by the reimbursement system for outpatient care. Consequently, a great deal of crucial problems occurred in relation with the unconventional subsidizing method. At the end of 2012 new financial methods have been elaborated and introduced in a pilot phase from 1 January 2013. In spite of the high cost commitment, nearly the entire diagnosed rare disease subpopulation have been provided with subsidized treatments in Hungary. In order to facilitate the acces to orphan medicines, collaboration shall be achieved by financing authority and professionals for identificating the descently sustainable, affordable and viable financial method. ]

Clinical Neuroscience

Comparison of hospitalized acute stroke patients’ characteristics using two large central-eastern european databases

CSIBA László, BERECZKI Dániel, MIHÁLKA László, SZŐCS Ildikó, SZATMÁRI Szabolcs, FEKETE Klára, ORBÁN-KIS Károly

Objectives – Stroke is the third leading cause of death in the European region. In spite of a decreasing trend, stroke related mortality remains higher in Hungary and Romania when compared to the EU average. This might be due to higher incidence, increased severity or even less effective care. Methods – In this study we used two large, hospital based databases from Targu Mures (Romania) and Debrecen (Hungary) to compare not only the demographic characteristics of stroke patients from these countries but also the risk factors, as well as stroke severity and short term outcome. Results – The gender related distribution of patients was similar to those found in the European Survey, whereas the mean age of patients at stroke onset was similar in the two countries but lower by four years. Although the length of hospital stay was significantly different in the two countries it was still much shorter (about half) than in most reports from western European countries. The overall fatality rate in both databases, regardless of gender was comparable to averages from Europe and other countries. In both countries we found a high number of risk factors, frequently overlapping. The prevalence of risk factors (hypertension, smoking, hyperlipidaemia) was higher than those reported in other countries, which can explain the high ratio of recurring stroke. Discussion – In summary, the comparatively analyzed data from the two large databases showed several similarities, especially regarding the high number of modifiable risk factors, and as such further effort is needed regarding primary prevention.

Clinical Neuroscience

[Event-related potentials and clinical symptoms in schizophrenia]

JANKA Zoltán, CSIFCSÁK Gábor, DOMJÁN Nóra

[The investigation of schizophrenia’s aetiology and pathomechanism is of high importance in neurosciences. In the recent decades, analyzing event-related potentials have proven to be useful to reveal the neuropsychological dysfunctions in schizophrenia. Even the very early stages of auditory stimulus processing are impaired in this disorder; this might contribute to the experience of auditory hallucinations. The present review summarizes the recent literature on the relationship between auditory hallucinations and event-related potentials. Due to the dysfunction of early auditory sensory processing, patients with schizophrenia are not able to locate the source of stimuli and to allocate their attention appropriately. These deficits might lead to auditory hallucinations and problems with daily functioning. Studies involving high risk groups may provide tools for screening and early interventions; thus improving the prognosis of schizophrenia. ]

Clinical Neuroscience

Long term follow-up of lesional and non-lesional patients with electrical status epilepticus in slow wave sleep

HALÁSZ Péter, FOGARASI András, BARSI Péter, HEGYI Márta, SIEGLER Zsuzsa

Objectives – A retrospective study has been done at the Bethesda Children’s Hospital Epilepsy Center with those patients whose EEG records fulfilled in one or more records the criteria of electrical status epilepticus in slow wave sleep (ESES) pattern, occupying at least 75% of NREM sleep with bilateral discharges, and had detailed disease history and long term follow-up data, between 2000 and 2012. Patients and methods – Thirty-three patients (mean 11.1±4.2 years of age) were studied by 171 sleep EEG records. Sleep was recorded after sleep deprivation or during spontaneous sleep at least for one hour length of NREM. From the 492 EEGs, 171 sleep records were performed (average five/patient). Average follow-up time was 7.5 years. Eighty-two ESES records have been analyzed in 15 non-lesional and 18 lesional (11 with dysgenetic and seven with perinatal - asphyxic or vascular origin) patients. Variability of seizure types, seizure frequency and frequency of status epilepticus was higher in the lesional group. Impairment of the cognitive functions was moderate and partial in the non-lesional, while severely damaged in the lesional group. Results – EEG records of 29 patients showed unihemispherial spike fields with a perpendicular axis (in anterior, medial and posterior variants) to the Sylvian fissure, regardless their lesional or non-lesional origin. Only three (1one non-lesional and two lesional) patients had bilateral synchronous spike-wave discharges with bilateral symmetric frontocentral spike fields. The individual discharges of the sleep EEG pattern were very similar to the awake interictal records except their extension in time and field, their increased number, amplitude, and continuity of them and furthermore in the increased trans-hemispheral propagation and their synchronity. Conclusions – Assumed circuits involved in the pathomechanism of discharges during NREM sleep in ESES are discussed based on our findings.

Clinical Neuroscience

Internet and stroke awareness in the young hungarian population

TÓTH Anna, BARI Ferenc, NYÁRI Tibor, PRIBOJSZKI Magda, FORCZEK Erzsébet

Background – Although stroke mortality rate in Hungary has tapered off over the last years, it is still twice the European average. This statistic is alarming and a coordinated response is needed to deal with this situation when considering new ways of communication. There are currently more than 300 websites in Hungarian related to stroke prevention, acute stroke treatment, recovery and rehabilitation. Aims and/or hypothesis – We sought to identify base level of stroke knowledge of the Hungarian students and the efficiency with which the knowledge disseminated by internet is actually utilized. Methods – We surveyed 321 high-school and university students to determine their ability to extract specific information regarding stroke from Hungarian websites. The base level of knowledge was established by asking 15 structured, close-ended questions. After completing the questionnaire, students were asked to search individually on stroke in the internet where all the correct answers were available. After a 25-min search session they answered the same questionnaire. We recorded and analyzed all their internet activity during the search period. Results – The students displayed a fair knowledge on the basics of stroke but their results did not change significantly after the 25-min search (53±13% vs. 63±14%). Only correct information given on demographic facts improved significantly. Most of the students used very simple search strategies and engines and only the first 5-10 web-pages were visited. Conclusion – Analysis of the most often visited web-pages revealed that although stroke-related Hungarian web-based resources contain almost all the important and required information the unsuitable structure, lack of simplicity and verbosity hinder their effective public utilization.

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The effects of 30 Hz, 50 Hz AND 100 Hz continuous theta burst stimulation via transcranial magnetic stimulation on the electrophysiological parameters in healthy individuals

ACAR Erkan, OZDEMIR Zeynep, SOYSAL Aysun

Transcranial magnetic stimulation is a non-invasive procedure that uses robust magnetic fields to create an electrical current in the cerebral cortex. Dual stimulation consists of administering subthre­shold conditioning stimulation (CS), then suprathreshold test stimulation (TS). When the interstimulus interval (ISI) is 1-6 msec, the motor evoked potential (MEP) decreases in amplitude; this decrease is termed “short interval intracortical inhibition” (SICI); when the ISI is 7-30 msec, an increase in MEP amplitude occurs, termed “short interval intracortical facilitation” (SICF). Continuous theta burst stimulation (cTBS), often applied at a frequency of 50 Hz, has been shown to decrease cortical excitability. The primary objective is to determine which duration of cTBS achieves better inhibition or excitation. The secondary objective is to compare 50 Hz cTBS to 30 Hz and 100 Hz cTBS. The resting motor threshold (rMT), MEP, SICI, and SICF were studied in 30 healthy volunteers. CS and TS were administered at 80%-120% and 70%-140% of rMT at 2 and 3-millisecond (msec) intervals for SICI, and 10- and 12-msec intervals for SICF. Ten individuals in each group received 30, 50, or 100 Hz, followed by administration of rMT, MT-MEP, SICI, SICF immediately and at 30 minutes. Greater inhibition was achieved with 3 msec than 2 msec in SICI, whereas better facilitation occurred at 12 msec than 10 msec in SICF. At 30 Hz, cTBS augmented inhibition and suppressed facilitation, while 50 Hz yielded less inhibition and greater inter-individual variability. At 100 Hz, cTBS provided slight facilitation in MEP amplitudes with less interindividual variability. SICI and SICF did not differ significantly between 50 Hz and 100 Hz cTBS. Our results suggest that performing SICI and SICF for 3 and 12 msec, respectively, and CS and TS at 80%-120% of rMT, demonstrate safer inhibition and facilitation. Recently, TBS has been used in the treatment of various neurological diseases, and we recommend preferentially 30 Hz over 50 Hz cTBS for better inhibition with greater safety and less inter-individual variability.

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[Psychometric properties of the Hungarian Adult Attachment Scale]

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Clinical Neuroscience

Evaluation of anxiety, depression and marital relationships in patients with migraine

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Aim - The aim of this study was to evaluate the frequency and characteristics of attacks in patients with migraine, to determine the effects of anxiety or depressive symptoms, and to evaluate the marital relationships of patients with migraine. Method - Thirty patients who were admitted to the neurology outpatient clinic of our hospital between July 2018 and October 2018 and were diagnosed with migraine according to the 2013 International Headache Society (IHS) diagnostic criteria were included in this cross-sectional study. Age, sex, headache frequency and severity, depressive traits, marital satisfaction and anxiety status were examined. We used the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Maudsley Marital Questionnaire (MMQ) and Visual Analogue Scale (VAS) for measuring relevant parameters. Results - The mean severity of migraine pain according to VAS scale was 6.93 ± 1.41 and the mean number of migraine attacks was 4.50 ± 4.24. The mean BDI score of the patients was 12.66 ± 8.98, the mean MMQ-M score was 19.80 ± 12.52, the mean MMQ-S score was 13.20 ± 9.53, the mean STAI-state score was 39.93 ± 10.87 and the mean STAI-trait score was 45.73 ± 8.96. No significant correlation was found between age, number of migraine attacks, migraine duration, migraine headache intensity, and BDI, STAI and MMQ scores (p>0.05). But there was a positive correlation between MMQ-S and scores obtained from the BDI and STAI-state scales (p<0.05). Conclusion - In this study more than half of the migraine patients had mild, moderate or severe depression. A positive correlation was found between sexual dissatisfaction and scale scores of depression and anxiety.

Clinical Neuroscience

Validation of the Hungarian PHQ-15. A latent variable approach

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Somatic symptoms without a clear-cut organic or biomedical background, also called “medically unexplained” or “somatoform” symptoms, are frequent in primary and secondary health care. They are often accompanied by depression and/or anxiety, and cause functional impairment. The Patient Health Question­naire Somatic Symptom Scale (PHQ-15) was developed to measure somatic symptom distress based on the frequency and bothersomeness of non-specific somatic symptoms. The study aimed to (1) evaluate the Hungarian version of the PHQ-15 from a psychometric point of view; (2) replicate the bifactor structure and associations with negative affect described in the literature; and (3) provide the Hungarian clinical and scientific community with reference (normal) values split by sex and age groups. PHQ-15, depression (BDI-R), and subjective well-being (WHO-5) scores obtained from a large (n = 5020) and close to representative community sample (Hun­garostudy 2006) were subjected to correlation analysis and linear structural equation modeling. The PHQ-15 showed good internal consistency (Cronbach’s α = 0.810; McDonald’s ω = 0.819) and moderate to strong correlation with the BDI-R (rs = .49, p < 0.001) and WHO-5 (rs = -.48, p < 0.001). Fit of the bifactor structure was excellent; in independent analyses, the general factor was strongly associated with depression (β = 0.656±0.017, p < 0.001) and well-being (β = -0.575±0.015, p < 0.001), whereas the symptom specific factors were only weakly or not related to these constructs. The PHQ-15 score was higher in females and showed a weak positive association with age. The Hungarian PHQ-15 is a psychometrically sound scale which is positively associated with depression and ne­gatively related to subjective well-being. The bifactor structure indicates the existence and meaningfulness of a gene­ral factor representing the affective-motivational component of somatic symptom distress. The Hungarian version of the PHQ-15 is a brief and usable tool for the pre-screening of somatization disorder (DSM-IV) or somatic symptom disorder (DSM-5). The reported reference values can be used in the future for both clinical and research purposes.

Clinical Neuroscience

[Diabetes, dementia, depression, distress]

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[The number of people living with diabetes continues to rise. Therefore neurologists or other health care practitioners may be increasingly faced with comorbid neuropsychiatric disorders commonly presented by diabetic patients. More recently there has been an increasing research interest not only in the interactions between diabetes and the nervous system, the fine structure and functional changes of the brain, but also in the cognitive aspects of antidiabetic treatments. Patients with both types of diabetes mellitus may show signs of cognitive decline, and depression. Comorbid insomnia, anxiety, and distress may also occur. The bi-directional relationships between all these phenomena as well as their connection with diabetes can lead to further health and quality of life deterioration. Therefore it is important that all practitioners involved in the care of diabetic patients recognize the presence of comorbid neuropsychiatric disturbances early on during the healthcare process. Identifying higher risk patients and early screening could improve the prognosis of diabetes and may prevent complications.]