The Combination of rTMS and Pharmacotherapy on In Vitro Models: A Mini-Review.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique that is being actively explored as a potential therapeutic modality in various neuropsychiatric disorders, such as depression, neuropathic pain, epilepsy, multiple sclerosis, and neurodegenerative disorders, including the Parkinson's and Alzheimer's disease. The Food and Drug Administration (FDA) approved rTMS for the treatment of major depression, migraine-associated headaches, and Obsessive Compulsive Disorder (OCD). The fact that a significant proportion of patients suffering from these disorders fail to respond to current pharmacological interventions indicates the need for alternative therapies like rTMS. OBJECTIVE: The objective was to find and summarize all studies combining the use of rTMS and pharmacological interference in vitro, in order to facilitate future studies. METHODS: The results of studies combining the use of rTMS with pharmacological interference in vitro were focused on. The PubMed database was searched using the terms "rTMS", "repetitive", "transcranial", "magnetic", "stimulation", "in vitro", "in vivo", "cell cultures" untilMarch 2019 and 7 eligible studies were found. RESULTS: Overall results show a synergistic effect of rTMS and pharmacotherapy in vitro with additive effectiveness, better prognosis, and superior potential management. CONCLUSION: The limited amount of knowledge denotes the need for additional in vitro studies on the combination of rTMS and pharmacotherapy, which could be extended to in vivo studies and ultimately help design clinical trials so as to improve the therapeutic management of patients with a wide array of neuropsychiatric disorders.

Apathy, cognitive dysfunction and impaired social cognition in a patient with bilateral thalamic infarction.

We describe the case of a patient with bilateral thalamic lesions due to brain infarcts in the paramedian thalamic artery territories. The patient demonstrated symptoms of apathy (e.g., loss of initiative and interest in others, poor motivation, flattened affect). Neuropsychological assessment 3 and 5 years post-infarct revealed severe deficits in verbal and non-verbal immediate and delayed memory, attention, and executive functioning, with minimal improvement over time. Also, he demonstrated difficulties in social cognition (i.e., perception of facial expressions of others and of sarcasm). These findings are discussed and interpreted in light of current theories regarding the neurobiological substrate of apathy.

An open-label, add-on study of pregabalin in patients with partial seizures: a multicenter trial in Greece.

INTRODUCTION: Pregabalin efficacy and safety as an adjunctive treatment for partial seizures was evaluated using an open-label, flexible-dose. STUDY DESIGN: In 98 adults with refractory partial epilepsy taking 1-3 anti-epileptic drugs with ≥2 seizures during an 8-week baseline period. METHODS: Pregabalin was increased to ≤600 mg/day during a 9-week dose optimization period with dosage maintained for 12 additional weeks. Primary endpoint was the percentage change in partial seizure frequency between the 8-week baseline and 12-week observation period. RESULTS: Pregabalin treatment was associated with a significant reduction in partial seizure frequency: median percent change in partial seizure frequency from baseline to 12 weeks was -33% and -22% in patients with a baseline seizure frequency of ≤3 and >3 per 28 days, respectively. The 50% and 75% responder rates were 41.94% (95% CI: 31.91-51.96) and 30.11% (95% CI: 20.78-39.43), respectively. Nineteen percent of subjects were seizure-free throughout the last 12 weeks. Pregabalin administration resulted in a significant reduction in anxiety (mean reduction in Hospital Anxiety and Depression Scale scores of 1.68 units, 95% CI: -2.60 to -0.76). Most patients were much improved or very much improved on Patient Global Impression of Change (53.8%) and Clinical Global Impression of Change (53.8%). The most frequently self-reported adverse events (AEs) were mild or moderate somnolence (20.4%) and dizziness (5.1%) with a low AE discontinuation rate (5.1%). CONCLUSIONS: The efficacy and side-effect profile of pregabalin were similar to previous pregabalin double-blind, controlled studies. Additionally, pregabalin, as an add-on treatment for partial epilepsy, exhibits significant anti-anxiety properties.

The effect of valproate on silent period and corticomotor excitability.

OBJECTIVE: To investigate, by transcranial magnetic stimulation, the effects of valproate on silent period and corticomotor excitability. METHODS: thirty patients with generalized epilepsy were studied at baseline, and re-examined 4 (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 +/- 284 mg). Transcranial magnetic stimulation was performed with a figure of eight coil (recording, first dorsal interosseous). Threshold was measured at 1% steps. Silent period was measured using a recently described protocol. Briefly, silent periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity. At each stimulus intensity, 4 silent periods were obtained and the average value of silent period duration was used to construct a stimulus/response curve of stimulus intensity versus silent period. The resulting curves were then fitted to a Boltzman function and were statistically compared. The motor-evoked potential recruitment curve was constructed under active conditions and analyzed in a similar way. RESULTS: Valproate increased threshold from 36.5 +/- 5.99% at baseline to 41.02 +/- 7.84% at S1 (p < 0.0001, paired t-test). The maximum value of the silent period curve decreased from 257.5 +/- 3.9 ms at baseline to 230.3 +/- 3.9 ms at S1 (p < 0.0001, F-test and AIC) while the other best-fit values (V(50), slope, threshold) were not significantly affected. Regarding the motor-evoked potential recruitment curve, the maximum value decreased significantly post-drug (from 0.449 +/- 0.007 to 0.392 +/- 0.009, p < 0.01, F-test and AIC test), whereas the rest of the best-fit values remained unaffected. CONCLUSION: In patients with idiopathic generalized epilepsy, valproate increases threshold and reduces the maximum values of the silent period curve and the motor-evoked potential recruitment curve. These findings probably reflect valproate's effects on voltage-dependent Na(+) channels, as well as an activation of GABA(A) receptors.