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Clinical Neuroscience

JANUARY 30, 2021

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

OZDEMIR Zeynep, ACAR Erkan, 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.

Clinical Neuroscience

MARCH 30, 2016

[The therapeutic use of transcranial magnetic stimulation in major depression]

NÉMETH Viola Luca, CSIFCSÁK Gábor, KINCSES Zsigmond Tamás, JANKA Zoltán, MUST Anita

[The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention.]

Clinical Neuroscience

JANUARY 30, 2016

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

MORVAI Szabolcs, NAGY Attila, KOVÁCS Attila, MÓRÉ Csaba, BERECZ Roland, FRECSKA Ede

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.

Clinical Neuroscience

MARCH 30, 2016

The electrophysiological changes after 1 hz RTMS in ALS patients. A pilot study

MAJOR Zsigmond Zoltán, VACARAS Vitalie, MARIS Emilia, CRISAN Ioana, FLOREA Bogdan, MAJOR Andrea Kinga, MURESANU Fior Dafin

Motor neuron diseases are disabling poor prognostic conditions, with no successful treatment. Repetitive transcranial magnetic stimulation might offer a temporary functional improvement. Objective - We intended to evaluate the extent of the functional improvement using electrophysiological and clinical tests. Methods - Patients with motor neuron disease (amyotrophic lateral sclerosis) were included. Muscle strength and respiratory function assessment represents the clinical approach, and central motor conduction time, motor unit number estimation, blink reflex and H-reflex stands for electrophysiology. Two tests were performed using the whole battery prior and after low frequency repetitive transcranial magnetic stimulation, using 1 Hz stimulation frequency for five consecutive days, 20 minutes daily, at 80% of the individual resting motor threshold. Results - Central motor conduction time, muscle strength and pulmonary function showed no statistically significant differences, but a tendency towards improvement. Motor unit number estimation, blink reflex and H-reflex showed a significantly better outcome after the five day repetitive transcranial magnetic stimulation treatment. Conclusion - Low frequency repetitive transcranial magnetic stimulation influences beneficially electrophysiological parameters in amyotrophic lateral sclerosis, but with little clinical impact; further studies are needed to validate the extent of the effect.

Clinical Neuroscience

NOVEMBER 30, 2018

[Comparison of subthalamic nucleus planning coordinates in 1Tesla and 3Tesla MRI for deep brain stimulation targeting ]

JUHÁSZ Annamária, KOVÁCS Norbert, PERLAKI Gábor, BÜKI András, KOMOLY Sámuel, KÖVÉR Ferenc, BALÁS István

[Backgroud - Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. Methods - In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. Results - The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). Conclusion - Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.]

Clinical Neuroscience

NOVEMBER 30, 2020

The applications of transcranial Doppler in ischemic stroke


Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

Clinical Neuroscience

JULY 30, 2020

[Recurrent inhibition during Jendrassik maneuver]


[Objective – Conflicting theoretical models exist regarding the mechanism related to the ability of the Jendrassik maneuver to reinforce reflex parameters. Our objective was to investigate if vigorous handgrip would induce changes in recurrent inhibition of soleus motoneurons. Method – Soleus H reflex was evoked by stimulating the tibial nerve at rest and during bilateral vigorous handgrip, alternating single (H1) and paired stimulation (H2). At paired stimulation we used interstimulus intervals of 10, 15, 20 and 25 ms and supramaximal test stimulus. H1- and H2-wave amplitudes were expressed as percentage of maximal M-wave amplitude. Conditioned H2 wave maximal (H2max) and minimal (H2) amplitudes evoked at rest and expressed as a percentage of the unconditioned H1max amplitude were compared with the corresponding values obtained during handgrip by means of paired Student test and Bonferroni correction. Subjects – At the study participated 28 healthy volunteers. Results – The H1max/Mmax × 100 values obtained during handgrip (37.5±10.1) were significantly higher than those obtained at rest (27.1±7.4). The H2max/H1max × 100-va­lues obtained at paired stimulation were significantly higher during handgrip than at rest, while no significant diffe­rence was found between the H2/H1max × 100-values obtained during handgrip and at rest respectively. Discussion – The H2max/H1max is determined by both the excitability of the motoneurons and the recurrent inhibition elicited by the conditioning stimulus, while H2/H1max indicates only the level of recurrent inhibition. According to our results the Renshaw cells retain their inhibitory effect on the soleus alpha motoneurons during remote muscle contraction. Conclusion – Soleus H reflex enhancement during Jendrassik maneuver is not due to decrease of recurrent inhibition. ]

Clinical Neuroscience

NOVEMBER 20, 2015

[Sleep disordered breathing and epilepsy: relationships and therapeutic considerations]

FALUDI Béla, BÓNÉ Beáta, KOMOLY Sámuel, JANSZKY József

[The importance of the sleep related breathing disorders (obstructive sleep apnea syndrome, central sleep apnea, and Cheyne-Stokes breathing) in the pathophysiology crebro- and cardiovascular disorders is well known. The relationship of sleep related breathing abnormalities and epilepsy is also important but underestimated in the daily practice. The relation is bidirectional. The breathing abnormalities in sleep may play important role in generating epileptic seizure, but the adverse effect of seizure and antiepileptic therapy (generation of apneas and hypopneas) may worsen the seizure control. The effect of new therapies (vagal nerve and deep brain stimulation) on the sleep architecture and sleep disordered breathing must be examined and discussed. Here we present a brief case of epileptic patient with deep brain stimulation therapy on sleep as well. The examination of the sleep related breathing abnormalities in epilepsy patient may help improve the effectiveness of antiepileptic therapy.]

Clinical Neuroscience

NOVEMBER 20, 2015

[Earlier and more efficiently: the role of deep brain stimulation for parkinson’s disease preserving the working capabilities]

DELI Gabriella, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ASCHERMANN Zsuzsanna, NAGY Ferenc, BOSNYÁK Edit, KOVÁCS Norbert

[Background – The recently published “EarlyStim” study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. Methods – We reviewed the data of 39 young (<60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job (“Job+” group, n=15) and retired patients (without active job, “Job-” group, n=24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. Results – As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p<0.01, McNemar test). Conclusion – Although our retrospective study has several limitations, our results fit well with the conclusions of “EarlyStim” study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.]

Clinical Neuroscience

MAY 30, 2018

[Relationship between patent foramen ovale and cryptogenic stroke in a retrospective hospital-based study]


[Objective - After routine workup, 23-25% of ischemic strokes etiology remains unknown, i.e. cryptogenic. However, according to international results pathogenic patent foramen ovale (PFO) reveals in 25% of these cases. Aim of our retrospective study to prove the substantial etiological role of PFO-related stroke (PFO-RS) in cryptogenic strokes (CS), and to identify age related differences in stroke etiology. Methods - All new ischemic strokes of 2014-2015 were classified by ASCOD (Atherosclerosis, Small-vessel disease, Cardiac pathology, Other, Dissection) phenotyping. CS was defined when the etiology was unknown. With the help of special ultrasound techniques and RoPE (Risk of Paradoxical Embolism) score the portion of PFO-RS were determined in the examined CS population. Moreover, etiological distribution and differences between age groups (<40, 40-60, >60 years) were described. Results - During the examined period, 8.12% of 985 new ischemic strokes were categorized as CS. 41.38% of examined CS were found to be PFO-related. PFO-RS were considerably more frequent in the younger age groups than in the older age groups. The probability of appearance of PFO-RS were significantly higher in younger age than in case of age independency. Our results verify the substantial etiological role of PFO-RS in CS, and confirm the essential role of contrast enhanced functional transcranial Doppler in the routine diagnostic workup. Age related differences in stroke etiology were found to be statistically significant (p=0.000, df=14), in which small-vessel disease, cardiac pathology, dissection, other pathologies, CS and PFO-RS were contributed significantly. Based on our results, till in young age rare etiologies are typical, while in older age classical etiologies are mainly characteristic.]