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Transcranial magnetic stimulation (TMS) gives rise to muscle responses, known as motor evoked potentials (MEP), through activation of the motor pathways. Voluntary contraction causes facilitation of MEPs, which consists of shortening MEP latency, increasing MEP amplitude and widening MEP duration. While an increase in excitability of alpha motorneurons and the corticospinal tract can easily explain latency shortening and amplitude increase, other mechanisms have to be accounted for to explain the increase in duration.We measured the increase in duration of the MEP during contraction with respect to rest in a group of healthy volunteers and retrospectively assessed this parameter in patients who were examined in a standardized fashion during the past 5 years. We included 25 healthy subjects, 21 patients with multiple sclerosis, 33 patients with acute stroke, 5 patients with hereditary spastic paraparesis, and 5 patients with signs suggesting psychogenic paresis. We found already significant differences among groups in the MEP duration at rest, patients with MS had a significantly longer duration, and patients with stroke had significantly shorter duration, than the other two groups. The increase in MEP duration during voluntary contraction was different in patients and in healthy subjects. It was significantly shorter in MS and significantly longer in stroke patients. It was absent in the five patients with suspected psychogenic weakness. In patients with HSP, an abnormally increase in duration occurred only in leg muscles. Our results suggest that the increase in duration of the MEP during contraction may reveal the contribution of propriospinal interneurons to the activation of alpha motorneurons. This mechanism may be altered in some diseases and, therefore, the assessment proposed in this work may have clinical applicability for the differential diagnosis of weakness. [ABSTRACT FROM AUTHOR]

Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and γ-aminobutyric acid A receptor (GABAAR) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABAAR-mediated inhibition in human motor cortex, to address the question of which GABAAR subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non-selective affinity profile at different α-subunit-bearing subtypes of the GABAAR while zolpidem has a 10-fold greater affinity to the α1-subunit-bearing GABAAR compared with those bearing the α2- or α3-subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an α1-subunit GABAAR-mediated effect. The findings strongly suggest that SICI is not mediated by the α1-subunit-bearing subtype of the GABAAR but by those bearing either the α2- or α3-subunit. This study represents an attempt by means of TMS to identify GABAAR subtype-specific action at the systems level of human cortex, a highly relevant issue because the different α-subunit-bearing subtypes of the GABAAR are differently involved in benzodiazepine-mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion The use of medications by emergency medical services (EMS) is increasing. Conventional scores are time‐consuming and therefore difficult to use in an emergency setting. For early decision‐making, an easy‐to‐use score based on the medications administered by the EMS may have prognostic value. The primary objective of this study was to develop the prehospital drug‐derived score (PDDS) for 2‐day mortality.A prospective, multicenter, ambulance‐based cohort study was conducted in adults with undifferentiated acute diseases treated by EMS and transferred to the emergency department. Demographic data, prehospital diagnosis data, prehospital medication and variables for the calculation of the National Early Warning Score 2 (NEWS2), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) were collected. The PDDS was developed and validated, establishing three levels of risk of 2‐day mortality. The predictive capability of each score was determined by the area under the curve of the receiver operating characteristic curve (AUROC) and compared using the Delong's test (p‐value).A total of 6401 patients were included. The PDDS included age and the use of norepinephrine, analgesics, neuromuscular blocking agents, diuretics, antihypertensive agents, tranexamic acid, and bicarbonate. The AUROC of PDDS was .86 (95% CI: .816–.903) versus NEWS2 .866 (95% CI: .822–.911), p = .828; versus REMS .885 (95% CI: .845–.924), p = .311; versus RAPS .886 (95% CI: .846–.926), p = .335, respectively.The newly developed easy‐to‐use prehospital drug‐derived PDDS score has an excellent predictive value of early mortality. The PDDS score was comparable to the conventional risk scores and therefore might serve as an alternative score in the prehospital emergency setting. [ABSTRACT FROM AUTHOR]

A response from Vincenzo Di Lazzaro et al to a letter to the editor about their article on transcranial magnetic stimulation in the 2005 issue is presented.

This project investigated whether structural changes are present in the subthalamic nucleus (STN) of people with mild-to-moderate severity of Parkinson's disease (PD). Within-subject measures of STN volume and fractional anisotropy (FA) were derived from high-resolution 7Tesla magnetic resonance imaging (MRI) for 29 subjects with mild-to-moderate PD (median disease duration = 2.3±1.9 years) and 18 healthy matched controls. Manual segmentation of the STN was performed on 0.4 mm in-plane resolution images. FA maps were generated and FA values were averaged over the left and right STN separately for each subject. Motor sign severity was assessed using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Linear effects models showed that STN volume was significantly smaller in the PD subjects compared to controls (p = 0.01). Further, after controlling for differences in STN volumes within or between groups, the PD group had lower FA values in the STN compared to controls (corrected p ≤ 0.008). These findings demonstrate that morphological changes occur in the STN, which likely impact the function of the hyperdirect and indirect pathways of the basal ganglia and movement control. [ABSTRACT FROM AUTHOR]

Background: Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease.Methods: This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871.Findings: Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm (one patient, almost resolved by 6 months); on-medication dyskinesia in the treated arm (one patient, resolved after levodopa dose reduction); and subjective speech disturbance (one patient). Four of the adverse events present at 6 months were related to medical management (anxiety and fatigue [one patient each] and weight gain [two patients]). The most frequent adverse events were transient gait ataxia (related to subthalamotomy, six patients), transient pin-site head pain (related to the head frame, six patients), and transient high blood pressure (during the procedure, five patients). Transient facial asymmetry (one patient) and moderate impulsivity (two patients) were also recorded. The mean MDS-UPDRS III score in the treated hemibody improved by 53% from baseline to 6 months in the off-medication state (16·6 [SD 2·9] vs 7·5 [3·9]) and by 47% in the on-medication state (11·9 [3·1] vs 5·8 [3·5]).Interpretation: MRI-guided focused ultrasound unilateral subthalamotomy was well tolerated and seemed to improve motor features of Parkinson's disease in patients with noticeably asymmetric parkinsonism. Large randomised controlled trials are necessary to corroborate these preliminary findings and to assess the potential of such an approach to treat Parkinson's disease.Funding: Fundación de investigación HM Hospitales and Insightec. [ABSTRACT FROM AUTHOR]