Cuplarea stimulării magnetice transcraniene (TMS) cu electroencefalografia de densitate înaltă (hdEEG) în formele generalizate de epilepsie

Background. In recent years, connectivity and brain plasticity have been vigorously addressed through new techniques for stimulating and monitoring brain activity such as TMS-EEG, TMS-fMRI or TMS-Spectroscopy. Nevertheless, many of them remain underused in the field of epilepsy. Objective of the study. To assess the available literature and the diagnostic and therapeutic accuracy of TMS-hdEEG stimulation in generalized forms of epilepsy. Material and Methods. We searched the PubMed, Scopus and EMBASE databases using the keywords „epilepsy”, „neuromodulation”, „TMS”, „high density EEG”, „magnetic”. Only articles written in English were analyzed. The time period covered was 2015 - 2022. At the same time, we studied the efficacy of coupling TMS stimulation with hdEEG in patients with generalized epilepsy by means of a pilot experimental randomized control trial. Results. In generalized forms of epilepsy, TMS-hdEEG provides an in-depth pathophysiological perspective elucidating clustering events and semi-stable, modified states of excitability that are directly associated with the generation of subsequent epileptiform discharges (EDs) leading to spatial spread. In addition to diagnostic values, TMS stimuli applied during EDs can suppress abnormal electrical activity and apparently restore the effective connectivity of the altered brain networks. These combined TMS actions of addressing cortical excitability on EDs may serve as a biomarker of therapeutic response to both pharmacological and non-pharmacological agents. Conclusion. New functional study paradigms by coupling TMS-hdEEG may provide a new perspective on the underlying mechanisms of generalized forms of epilepsy and the effectiveness of antiepileptic medication, serving as potential biomarkers of diagnosis, therapeutic response, and future prognosis in these patients.Introducere. În ultimii ani, conectivitatea și plasticitatea cerebrală au fost abordate viguros prin intermediul tehnicilor noi de stimulare și monitoring a activității creierului precum TMS-EEG, TMS-fMRI sau TMS-Spectroscopie. Însă toate ele rămân subutilizate în domeniul epilepsiei. Scopul lucrării. A evalua literatura disponibilă și acuratețea diagnostică și terapeutică a stimulării TMS – hdEEG în formele generalizate de epilepsie. Material și Metode. Am efectuat o căutare in bazele de date PubMed, Scopus și EMBASE folosind cuvintele cheie „epilepsie”, „neuromodulare”, „TMS”, „EEG de densitate înalta”, „magnetic”. Am analizat articole scrise în limba engleză. Perioada de timp acoperită a fost 2015 – 2022. În același timp, am studiat eficacitatea cuplării stimulării TMS cu hdEEG la pacienții cu epilepsie generalizata prin prizma unui studiu experimental randomizat pilot. Rezultate. În formele generalizate de epilepsie, TMS-hdEEG oferă o perspectivă fiziopatologică aprofundată elucidând evenimente de clustering și stări semi-stabile, ascunse, de excitabilitate care sunt asociate nemijlocit cu generarea de descărcări epileptiforme (DE) ulterioare și răspândire spațială. Adițional la valoarea diagnostică, stimularea TMS aplicată în timpul acestor DE le poate suprima și aparent poate restabili conectivitatea efectivă a rețelei cerebrale modificate. Acest efect combinat terapeutico-diagnostic de abordare a excitabilității corticale al TMS asupra DE poate servi ca un biomarker al răspunsului terapeutic la agenți atât farmacologici cât și non-farmacologici. Concluzii. Paradigmele noi de studiere funcțională prin cuplarea TMS-hdEEG pot oferi o perspectivă nouă asupra mecanismelor care stau la baza formelor generalizate de epilepsie, precum și eficacității medicației antiepileptice, servind ca potențiali biomarkeri de diagnostic, răspuns terapeutic și prognostic la acești pacienți

Progrese în managementul modern al epilepsiei: stimularea cerebrală

Laboratory of Neurobiology and Medical Genetics, Nicolae Testemitanu SUMPhBackground. Epilepsy is a major neurological disorder affecting around 65 million people worldwide. In around 30% of cases current pharmacological approaches show limited to no results, thus pointing out the need for alternative treatments such as brain neuromodulation. Objective of the study. To assess available modern options of brain neuromodulation in epilepsy patients presented in the literature. Material and Methods. We have conducted a targeted on PubMed Central and Google Scholar engines, in specialized books, in guides and protocols, using the keywords “epilepsy”, “neuromodulation”, “stimulation”, “brain”, “electric”, “magnetic”, “vagus nerve” and “deep brain stimulation”. We analyzed articles written in English. The time period covered was January 1st, 2000 to May 1st, 2021. Results. From a pathophysiological point of view, epilepsy is a result of abnormal neuronal network activity in the brain due to a pathological increase in excitatory synapses (glutamatergic) with a decrease in inhibitory activity (GABA-ergic). Thus, approaching this paradigm, it is assumed that inhibitory neuromodulation could induce the phenomenon of LTD (long-term excitatory depression) with normalization of the excitation threshold in hyper-excitable area and as a result obtaining the expected therapeutic effect. Modulation of brain activity can be achieved by impacting the peripheral elements of sensitization (TDCS, TENS, VNS) or direct cortical-subcortical activity (TMS, DBS). Conclusion. By reducing cortical-subcortical excitability, targeted neuromodulation has enormous therapeutic potential in the treatment of epilepsy, especially in drug-resistant forms.Introducere. Epilepsia este o tulburare neurologică majoră care afectează global aproximativ 65 de milioane de oameni. În aproximativ 30% dintre cazuri, abordările farmacologice actuale indică rezultate limitate, accentuând necesitatea tratamentelor alternative, precum neuromodularea creierului. Scopul lucrării. Elucidarea opțiunilor moderne de neuromodulare disponibile la pacienții cu epilepsie. Material și Metode. Am cercetat lucrările științifice în limba engleză din bazele de date PubMed Central și Google Scholar, ghiduri și protocoale, folosind cuvintele-cheie: epilepsie, neuromodulare, stimulare, creier, electric, magnetic, nervul vag, stimulare profunda cerebrala, perioada 01 ianuarie 2000 – 01 mai 2021. Rezultate. Din punct de vedere fiziopatologic epilepsia este rezultatul unei activități anormale a rețelelor neuronale în creier cauzate de cresterea patologică a activității sinapselor excitatorii cu o scădere a activității inhibitorii. Astfel, abordând această paradigmă, se presupune că neuromodularea inhibitorie ar putea induce fenomenul LTD (depresie excitatorie pe termen lung) cu normalizarea pragului de excitație în zona hiper-excitabilă și, ca rezultat, obținerea efectului terapeutic așteptat. Modularea activității creierului poate fi realizată prin actiune asupra elementelor periferice de sensibilizare (TDCS, TENS, VNS) sau direct asupra activității cortico-subcorticale (TMS, DBS). Concluzii. Prin reducerea excitabilității cortico-subcorticale, neuromodularea țintită are un potențial terapeutic enorm în tratamentul epilepsiei, în special în formele farmacorezistente

Neuromodulatory approach in paroxysmal neurological disorders

Department of Neurology No 2, Nicolae Testemitanu State University of Medicine and Pharmacy Chisinau, the Republic of Moldova, Emergency Medicine Institute, Chisinau, the Republic of Moldova, The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)Background: Nowadays, neuro-modulation offers different devices and techniques in the treatment of neurological patients suffering from paroxysmal disorders, such as epilepsy and migraine. Among non-pharmacologic therapies, rTMS shows good results. Material and methods: A longitudinal, double-blinded, rTMS-intervention study was conducted on 42 subjects with episodic migraine (with and without aura, 2-14 attacks per month). After a baseline follow-up for 1 month, subjects had 6 sessions of rTMS during 2 weeks and received multifocal rTMS or sham stimulation, with further 3-month assessment via questionnaires on headache frequency . Results: After stimulation, the real rTMS group showed a reduction in the number of attacks – 7.5 ± 3.7 at baseline to 3.8 ± 2.7 attacks at 3 months’ period (p0.05). There was a significant reduction in the intensity of attacks over 4-week therapy in the treatment group (6.7 ± 1.5 at baseline; 5.3 ± 2.5 at 4 weeks (p<0.05). The conducted questionnaires revealed a positive impact on quality of life and functional outcomes. There were no serious adverse events reported. Conclusions: Our study showed evidence that the experimental rTMS protocol significantly reduced the frequency and intensity of migraine attacks compared to placebo treatment with no serious adverse events

Accidentul vascular cerebral repetat la adult după înlăturarea malformației angiocavernoase la nivel pontin. (Caz clinic)

Această lucrare a fost efectuată cu scopul elucidării factorilor etiologici, patogenetici și a manifestărilor clinice ale accidentului vascular cerebral hemoragic dat de malformația cavernoasă la nivel pontin. S-a observat clinica neurologică caracteristică leziunii porțiunii laterale a punții Varolio, manifestată prin afectarea nervului oculomotor, nervului abducens, nervului facial, tractului piramidal și căilor spino-talamice. S-a confi rmat superioritatea rezultatelor Imagisticii prin Rezonanță Magnetică comparativ cu alte metode de investigație

Transcranial magnetic stimulation in the treatment of refractory and superrefractory status epilepticus

Background. Pharmacological treatment of Refractory status epilepticus (RSE) and Super-refractory status epilepticus (SRSE) remains a challenge, while transcranial magnetic stimulation (TMS) is one of non-pharmacological options considered to attempt. Objective of the study. We present two intriguing cases of RSE and SRSE successfully managed by pharmacological approach and TMS. Material and methods. All data were collected from medical database. Patients underwent all pharmacological stages of the treatment of RSE/ SRSE and TMS. Results. A 73-year-old female suspected of ischemic stroke with aphasia and right hemiplegia and a 63-year-old female with generalized tonicclonic seizures evolved to unconscious state, were admitted to ICU. In both cases lab tests, cerebrospinal fluid, brain computed tomographies as well as magnetic resonance imaging were unremarkable. In the first case video-electroencephalography (EEG) monitoring showed pathological patterns and protocoled pharmacological treatment failed. At the third stage, repetitive TMS was associated to continuous midazolam. In the second case, fluctuating lateralized rhythmic delta activity on EEG was not resolved despite phenytoin, phenobarbital, propofol and ketamine administration. Under TMS sessions, diffuse delta slowing and background reactivity were observed. Following days after withdrawal of anesthetic and TMS modulation, clinical status and patients’ EEG improved. Conclusions. Synergistic effects of pharmacological and TMS modulation probably suppressed seizure activity and helped us to acquire favorable outcomes in management of RSE and SRSE

Accidentul vascular cerebral ischemic: protocol clinic naţional PCN-13

USMF „Nicolae Testemiţanu”, IMSP Institutul de Medicină UrgentăAcest protocol a fost elaborat de grupul de lucru al Ministerului Sănătăţii al Republicii Moldova (MS RM), constituit din specialiști neurologi, ai Universității de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, ai Laboratorului Boli Cerebrovasculare şi Epilepsie, în cadrul IMSP Institutul de Medicină Urgentă, Specialiști în NeurologieIMSP Institutul de Medicină Urgentă sub conducerea academicianului, d.h.ș.m., prof. univ., Stanislav Groppa. Pentru elaborarea recomandărilor au fost studiate, analizate si consultate informațiile din literatura de specialitate, Protocolul Clinic National “Accident Vascular Cerebral Ischemic” (2008), bazele de date MEDLINE/PubMed, Cochrane Trials Register, documentele de specialitate, Institutului National de Excelență Clinică, Subcomitetului Standardelor de Calitate al Academiei Americane de Neurologie și al American Heart Association/American Stroke Association, al Academiei Europene de Neurologie. Prezentul protocol se dorește a fi o recomandare în abordarea diagnostică și terapeutică a cazurilor de AVC, dar nu limitează si nu absolvă specialistul de responsabilitatea individualizării cazului

Diagnosis and management of ischemic stroke: time is critical

Department of Neurology No 2, Department of Neurology No 1, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Department of Neurology, Epileptology and Internal Diseases, Department of Neurosurgery, Laboratory of Cerebrovascular Diseases and Epilepsy, National Center of Epileptology Institute of Emergency Medicine, Chisinau, the Republic of Moldova, The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)Background: It is predicted that stroke’s incidence and impact will increase considerably over time. Proper management of stroke depends on a reliable and urgent diagnosis that includes patient / relative - emergency team - hospital chain, so the diagnosis begins with the recognition of the first signs of stroke. In order to act promptly in the acute period and subsequently assess the risk factors, the neurological service needs to be equipped with highperformance neuroimaging and clinical laboratory. The specific treatment of acute ischemic stroke is nowadays the reperfusion procedure, performed by thrombolytic therapy and, since 2015, by the endovascular treatment. Stroke is also a leading cause of severe long-term disability. The rehabilitation of post-stroke patients requires an interdisciplinary approach, in order to prevent recurrences, combat complications and reintegrate the patient into society. Conclusions: Stroke remains one of the leading determinants of death and severe disability worldwide and the Republic of Moldova is not an exception. Considering the narrow window for recognition and administration of outcome-modifying treatment, the management of stroke focuses mainly on rapid reperfusion via intravenous thrombolysis and endovascular thrombectomy. The availability of this specialized treatment in the Stroke Unit could improve the patient’s outcome and decrease the disability’s level and economical burden. There is clear evidence that preventing a stroke is much more effective than treating it, so we should seize the opportunity and act involving not only the medical staff, but also the government, health decision makers, specialists in public health and international agencies