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Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely... more
Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-...
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Background/Aim. Diagnosis of amyotrophic lateral sclerosis (ALS) is based on combination of clinical signs and electrophysiological correlates of pathological process which takes place in general. New electrophysiological criteria... more
Background/Aim. Diagnosis of amyotrophic lateral sclerosis (ALS) is based on combination of clinical signs and electrophysiological correlates of pathological process which takes place in general. New electrophysiological criteria Awaji-Shima (AS) additionally qualify the complex fasciculations and neurogenically modified potentials of motor units as signs of active lesions of peripheral motor neuron, contrary to previously valid revised El Escorial criteria (rEE). The objective of this research was to determine the clinical significance and advantages of using the AS criteria in patients with ALS. Methods. Thirty patients (59.2 ? 10.9 years, 57% of them with spinal form of the disease) with clinically suspected ALS were monitored from the time of diagnosis until reaching the category of definitive diagnosis or death. The clinical evaluation and electromyographic (EMG) examinations were carried out at 3-month intervals. Results. By applying the AS criteria, the category of probable ...
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Stroke is a leading cause of serious long-term disability worldwide. Functional outcome depends on stroke location, severity, and early intervention. Conventional rehabilitation strategies have limited effectiveness, and new treatments... more
Stroke is a leading cause of serious long-term disability worldwide. Functional outcome depends on stroke location, severity, and early intervention. Conventional rehabilitation strategies have limited effectiveness, and new treatments still fail to keep pace, in part due to a lack of understanding of the different stages in brain recovery and the vast heterogeneity in the poststroke population. Innovative methodologies for restorative neurorehabilitation are required to reduce long-term disability and socioeconomic burden. Neuroplasticity is involved in poststroke functional disturbances and also during rehabilitation. Tackling poststroke neuroplasticity by non-invasive brain stimulation is regarded as promising, but efficacy might be limited because of rather uniform application across patients despite individual heterogeneity of lesions, symptoms, and other factors. Transcranial direct current stimulation (tDCS) induces and modulates neuroplasticity, and has been shown to be able...
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Background/Aim. 123I-FP-CIT brain single-photon emission computed tomography (SPECT), DaTSCAN imaging, offers a possibility to study structural and biochemical integrity of presinaptic dopaminergic neurotransmitter system. The aim of this... more
Background/Aim. 123I-FP-CIT brain single-photon emission computed tomography (SPECT), DaTSCAN imaging, offers a possibility to study structural and biochemical integrity of presinaptic dopaminergic neurotransmitter system. The aim of this study was to evaluate the usefulness of 123I-FP-CIT brain SPECT scintigraphy in patients with extrapyramidal diseases. Methods. Fifteen patients (8 males and 7 females), aged 26-81 years, presenting with extrapyramidal symptoms entered the study. Out of them, 7 patients were diagnosed with definite clinical form of idiopathic Parkinson?s disease (PD) or clinical probable for PD clinical stage 2-4 using the Hoehn&Yahr scale (H&Y); 6 patients were with atypical parkinsonism (AP), 1 patient with essential, and 1 with psychogenic tremor. SPECT was performed 180 min after injection of 185 MBq 123IFP- CIT using a dual head Gamma camera. Sixty four one minutes? frames were acquired using a noncircular rotation mode into a 128 ? 128 image matrix. Transvers...
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Introduction. Bipolar depression is often unrecognized and difficult to treat because of two opposite problems: treatment resistance and risk of manic switch. Case report. A 53-year-old female was suffering from unipolar depressive... more
Introduction. Bipolar depression is often unrecognized and difficult to treat because of two opposite problems: treatment resistance and risk of manic switch. Case report. A 53-year-old female was suffering from unipolar depressive disorder since the age of 36. During a recent major depressive episode pervasive feelings of sadness, lost of interest in activities, severe insomnia and highly expressed somatic anxiety dominated 7 months. After unsuccessful tries with two different antidepressants of adequate doses and duration, slow rate repetitive trascranial magnetic stimulation (rTMS) was started, but the patient stayed at the fixed dose of antidepressant. Partial sleep deprivation (PSD) was additionally applied twice during these 2 weeks with the idea to boost up, or enhance rTMS treatment response. At the last two rTMS sessions depression obviously meliorated, but the patient also expressed symptoms of hypomania. The therapy of rTMS was stopped, hypomanic symptoms gradually vanish...
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Background/Aim. Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymetrical weakness of limbs without sensory loss. The objective of this study was to investigate the involvement of... more
Background/Aim. Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymetrical weakness of limbs without sensory loss. The objective of this study was to investigate the involvement of brachial plexus using combined cervical magnetic stimulation and magnetic resonance imaging (MRI) of plexus brachialis in patients with MMN. We payed special attention to the nerve roots forming nerves inervating weak muscles, but without detectable conduction block (CB) using conventional nerve conduction studies. Methods. Nine patients with proven MMN were included in the study. In all of them MRI of the cervical spine and brachial plexus was performed using a Siemens Avanto 1.5 T unit, applying T1 and turbo spinecho T1 sequence, axial turbo spin-echo T2 sequence and a coronal fat-saturated turbo spin-echo T2 sequence. Results. In all the patients severe asymmetric distal weakness of muscles inervated by radial, ulnar, median and peroneal nerves was ...
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Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in... more
Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections with the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitude in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of ...
Research Interests: Skeletal muscle biology, Transcranial Magnetic Stimulation, Medicine, Germany, Startle Reflex, and 15 moreHumans, Cerebral Cortex, Female, Male, Physiological, Electromyography, Medical Physiology, Motor Evoked Potentials, Adult, Analysis of Variance, Time Factors, Lower Extremity, Spinal Nerves, Acoustic Stimulation, and Motor Neurons
Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning.... more
Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, Motor evoked potential (MEP) amplitude inhibition is observed, the paradigm known as short-latency afferent inhibition (SLAI). Aiming to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of evoked response of somatosensory cortex (N(20)) (PAS(LTP)), and at ISI of N(20) shortened ...
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Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate... more
Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate success. Experimental autoimmune encephalomyelitis (EAE) is currently the most commonly used experimental model for MS and for studying various therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique with multiple beneficial effects on healthy as well as CNS with pathology. However, the molecular and cellular mechanisms of rTMS on acute EAE are scarce. Our study demonstrated beneficial effects of theta-burst stimulation (TBS), an experimental paradigm of rTMS, on disease course of acute EAE. TBS treatment attenuated reactive gliosis, restored myelin sheet and down-regulated expression of vimentin in EAE rats. These effects were reflected through reduced clinical parameters, shorter dura...
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Bipolar depression is common disorder characterized by substantial comorbidity, mortality, the highest suicide rate among psychiatric illnesses and severe social impairment, but is still often misdiagnosed. The real prevalence of bipolar... more
Bipolar depression is common disorder characterized by substantial comorbidity, mortality, the highest suicide rate among psychiatric illnesses and severe social impairment, but is still often misdiagnosed. The real prevalence of bipolar depression could be much higher than is thought, because the problem of misdiagnosis. A percentage of undiagnosed bipolar patients is especially high in population of treatment resistant depression. These patients are most frequently misdiagnosed as having unipolar depression and treated with anitidepressant monotherapy, that result in worsening of the course of the illness and often lead to rapid cycling. Two independent studies 1, 2 in population of 203 and 250 patients with major depression found 40–49% of bipolar disorder. In 1994, the results of survey of National Depressive and Manic-Depressive Association showed that 73% of 500 bipolar patients were misdiagnosed as having unipolar major depression . Unfortunately, 10 years later the same asso...
Background: Synaptic overload with glutamate aggravates neurotransmission and worsen the progression of the neurodegenerative disease, such as multiple sclerosis (MS). The experimentally induced autoimmune encephalomyelitis (EAE) in rats... more
Background: Synaptic overload with glutamate aggravates neurotransmission and worsen the progression of the neurodegenerative disease, such as multiple sclerosis (MS). The experimentally induced autoimmune encephalomyelitis (EAE) in rats is a well-established animal model to study MS. Glutamate reuptake occurs by glial glutamate transporter (GLT-1), and glutamate-aspartate transporter (GLAST) localized predominantly in astrocytes terminals. The focus of the study addressing the expression of these transporters in EAE rats and those subjected to theta burst stimulation (TBS), that promotes long-lasting modulation of neuronal activity in rats/humans. Leading by the reported outcomes of TBS, we examined if TBS underlying mechanisms refer to astroglial glutamate transporters status.Methods : We studied changes in the expression of glial glutamate transporter GLT-1 and glutamate-aspartate transporter (GLAST), and glial fibrillary acidic protein (GFAP), in the spinal cord of EAE rats, sub...
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Cortical theta burst stimulation (TBS) structured as intermittent (iTBS) and continuous (cTBS) could prevent the progression of the experimental autoimmune encephalomyelitis (EAE). The interplay of brain antioxidant defense systems... more
Cortical theta burst stimulation (TBS) structured as intermittent (iTBS) and continuous (cTBS) could prevent the progression of the experimental autoimmune encephalomyelitis (EAE). The interplay of brain antioxidant defense systems against overproduction of reactive oxygen, nitrogen, and thiol species induced by EAE has not been entirely investigated, just as the effect of iTBS or cTBS on oxidative-nitrogen stress (ONS) in EAE rats. Dark Agouti strain female rats were tested for the effects of EAE and TBS. The rats were randomly divided into the following groups: C - control, EAE - rats immunized for EAE, CFA - rats immunized with Complete Freund's adjuvant; iTBS and cTBS groups, and EAE+iTBS and EAE+cTBS - health and EAE rats exposed to iTBS and cTBS, respectively; EAE+iTBSsh and EAE+cTBSsh - sham stimulated EAE rats with the same noise artifacts of iTBS and cTBS, respectively. Superoxide dismutase activity, levels of superoxide anion (O2•-), lipid peroxidation, glutathione (GS...
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Backgroun/Aim. Constant production of free radicals and antioxidants (AO) in cells is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinson?s disease (PD).... more
Backgroun/Aim. Constant production of free radicals and antioxidants (AO) in cells is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinson?s disease (PD). Evaluation of the disease status, prooxidant-antioxidant balance (PAB) and antioxidants are being widely estimated. The aim of this study was to examine potential interaction between several AO variables: glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and PAB, and clinicopathologic features of patients with PD, particularly the Hoehn and Yahr (H&Y) stage. Methods. A multivariate analysis of variance (MANOVA) was conducted to analyze mean differences between clinicopathologic characteristics (gender, age at examination, duration of the disease, and the H&Y stage) and AO variables of PD patients and those of age/sex matched healthy controls. The study included 91 patients with idiopatic PD patients and 20 healthy persons. Results. The multivaria...
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This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal... more
This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS, n = 27) received tDCS over the left primary motor cortex for five days, whereas patients assigned to the control group (sham-tDCS, n = 28) received sham tDCS stimulations. All patients received postoperative PCA-IV morphine. For cost-effectiveness analysis we used data about total amount of PCA-IV morphine and maximum visual analog pain scale with cough (VASP-Cmax). Direct costs of hospitalization were assumed as equal for both groups. Cost-effectiveness analysis was performed with the incremental cost-effectiveness ratio (ICER), expressed as the incremental cost (RSD or US$) per incremental gain in mm of VASP-Cmax reduction. Calculated ICER was 510.87 RSD per VASP-C...
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Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being... more
Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity. The aim of study was to evaluate the levels of above mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status. Results The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant/antioxidant balance (p = 0.02). Relation between oxidant/antioxidant st...
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A growing body of evidence supports the effectiveness of using transcranial direct current stimulation (tDCS) in patients with chronic hand motor impairment resulting from stroke. In this study, we investigate and compare the combined... more
A growing body of evidence supports the effectiveness of using transcranial direct current stimulation (tDCS) in patients with chronic hand motor impairment resulting from stroke. In this study, we investigate and compare the combined effects of anodal tDCS and occupational therapy (OT) to sham stimulation with OT (control) on fine motor skill deficits of chronic stroke patients. A total of 26 stroke patients (at ≥ 9 months) were randomly assigned to an active treatment or a control group in a double-blinded, sham-controlled, parallel design study. Each group received OT for 45 min/day (10 sessions for 2 weeks). Treatment was preceded by either 20 minutes of 2 mA anodal tDCS over ipsilesional M1 or sham tDCS. A modified Jebsen-Taylor Hand Function Test (mJTHFT) was administered as primary outcome measure, and handgrip dynamometer and upper limb Fugl-Meyer (ULFM) assessments were performed as secondary outcomes. The assessment was done at baseline (T0), after the interventions on day 1(T1), day 10 (T2) and day 40 (T3). We observed a statistically significant effect in the tDCS group when the results were compared to the sham group. The mJTHFT times were significantly shorter immediately after treatment and at day 40. The intervention had no effect on handgrip strength or ULFM score. Fine motor skill deficits in chronic stroke survivors can be improved when intensive OT is primed with anodal tDCS over the ipsilesional hemisphere.
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Background/Aim. Adaptive control and fingertip force synchronization of precise grasp stability during unimanual manipulation of small objects represents an illustrative example of highly fractionated movements that are foundation of fine... more
Background/Aim. Adaptive control and fingertip force synchronization of precise grasp stability during unimanual manipulation of small objects represents an illustrative example of highly fractionated movements that are foundation of fine motor control. It is assumed that this process is controlled by several motor areas of the frontal lobe, particularly applicable to the primary motor (M-1) and dorsal premotor cortex (PMd). Aiming to examine the role of PMd during fine coordination of fingertip forces we applied theta burst repetitive magnetic stimulation (TBS) to disrupt neural processing in that cortical area. Methods. Using a single-blind, randomized, crossover design, 10 healthy subjects (29 ? 3.9 years) received single sessions of continuous TBS (cTBS600), intermittent TBS (iTBS600), or sham stimulation, separate from one another at least one week, over the PMd region of dominant hemisphere. Precision grasp and lift were assessed by instrumented device, recording grip (G) and ...
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Ilić NV, Petronić I, Grajić M, Ilić TV. Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: a TMS study. [Efekti pojedinačnih doza diazepama i levodope na modulaciju plasticiteta motornog korteksa kod zdravih osoba - TMS studija]. Srp Arh...more
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Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in... more
Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections with the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitude in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of ...
Research Interests: Skeletal muscle biology, Transcranial Magnetic Stimulation, Medicine, Germany, Startle Reflex, and 15 moreHumans, Cerebral Cortex, Female, Male, Physiological, Electromyography, Medical Physiology, Motor Evoked Potentials, Adult, Analysis of Variance, Time Factors, Lower Extremity, Spinal Nerves, Acoustic Stimulation, and Motor Neurons
Parkinson’s disease (PD) represents a clearly defined neurodegenerative disorder with unique clinical features. In spite of enormous efforts directed toward understanding the etiology and pathogenesis of PD, the cause of this disorder is... more
Parkinson’s disease (PD) represents a clearly defined neurodegenerative disorder with unique clinical features. In spite of enormous efforts directed toward understanding the etiology and pathogenesis of PD, the cause of this disorder is still unknown. Among numerous causative agents, various hypotheses presume that the illness may be due to hereditary factors (Markopoulou et al., 1995; Ward et al., 1983), intrauterine events (Mattock et al., 1988), viral infection (Poskanzer et al., 1963), or environmental factors such as exogenous toxins, including l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) (Snyder et al., 1986; Jovanovic et al., 1994). Intensive research over the last decade has generated several lines of evidence from both human and experimental studies, which support the possibility that free radical mechanisms may initiate cell damage (Jovicic et al., 1995).
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Parkinson’s disease (PD) represents a clearly defined neurodegenerative disorder with unique clinical features. In spite of enormous efforts directed toward understanding the etiology and pathogenesis of PD, the cause of this disorder is... more
Parkinson’s disease (PD) represents a clearly defined neurodegenerative disorder with unique clinical features. In spite of enormous efforts directed toward understanding the etiology and pathogenesis of PD, the cause of this disorder is still unknown. Among numerous causative agents, various hypotheses presume that the illness may be due to hereditary factors (Markopoulou et al., 1995; Ward et al., 1983), intrauterine events (Mattock et al., 1988), viral infection (Poskanzer et al., 1963), or environmental factors such as exogenous toxins, including l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) (Snyder et al., 1986; Jovanovic et al., 1994). Intensive research over the last decade has generated several lines of evidence from both human and experimental studies, which support the possibility that free radical mechanisms may initiate cell damage (Jovicic et al., 1995).
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Research Interests: Skeletal muscle biology, Transcranial Magnetic Stimulation, Medicine, Germany, Startle Reflex, and 15 moreHumans, Cerebral Cortex, Female, Male, Physiological, Electromyography, Medical Physiology, Motor Evoked Potentials, Adult, Analysis of Variance, Time Factors, Lower Extremity, Spinal Nerves, Acoustic Stimulation, and Motor Neurons
Abstract The paper describes a new model of an ideal switch, which can be used in standard circuit simulation algorithms. There are no restrictions on network topology and switch connections. The switches can be both externally and... more
Abstract The paper describes a new model of an ideal switch, which can be used in standard circuit simulation algorithms. There are no restrictions on network topology and switch connections. The switches can be both externally and internally controlled. The ...