Spinal direct current stimulation (tsDCS) in hereditary spastic paraplegias (HSP): A sham-controlled crossover study.

Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP.Design: A double-blind, randomized, crossover and sham-controlled study.Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan.Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15.Interventions: tsDCS (anodal or sham, 2.0 mA, 20', five days) delivered over the thoracic spinal cord (T10-T12).Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T0), at the end of the stimulation (T1), after one week (T2), one month (T3) and two months (T4).Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T1, P = .0137; T4, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time.Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.

Role of Intraoperative Neurophysiologic Monitoring in the Resection of Thalamic Astrocytomas.

BACKGROUND: The thalamus is a deep-seated and crucial structure for the sensorimotor system. It has been long considered a surgically inaccessible area because of the morbidity associated with surgical resections. Astrocytomas of the thalamus are usually treated with bioptic procedures followed by adjuvant treatments. Intraoperative neurophysiologic monitoring (IONM) allows safe and satisfactory resections of lobar gliomas, but few data are available for thalamic lesions. The aim of this study was to review the outcome of a small series of patients with thalamic astrocytomas that were treated with surgical resection with the aid of IONM. METHODS: Surgical resection with IONM was performed in 5 patients with thalamic astrocytomas (1 grade I, 1 grade II, 2 grade III, 1 grade IV). Two astrocytomas were in the dominant hemisphere. Preoperative and postoperative neuropsychological assessments were performed in 3 patients. IONM was tailored to the individual patient and consisted of transcranial motor evoked potential monitoring, cortical motor evoked potential monitoring, somatosensory evoked potential monitoring, direct electrical stimulation, electroencephalography, and electrocorticography. RESULTS: None of the patients experienced permanent motor deficits; 2 patients had a transient hemiparesis requiring rehabilitation; 1 patient had a transient aphasia, and 1 patient had permanent aphasia. None of the patients had intraoperative seizures, but 1 patient experienced postoperative transient status epilepticus. The extent of resection on postoperative volumetric magnetic resonance imaging was >70% in all cases. CONCLUSIONS: Surgical resection of thalamic astrocytomas appeared to be effective and relatively safe when guided by IONM. Larger series of patients are required to confirm these preliminary data.

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans.

BACKGROUND: Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord. NEW METHOD: We studied the effects of tsDCS on interhemispheric motor connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before (T0) and at a different intervals following sham, anodal and cathodal tsDCS (T9-T11 level, 2.0 mA, 20'). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating with the display positioned in the right hemifield. RESULTS: Anodal tsDCS increased TCT (p < 0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p < 0.0001), dampening at the same time iSP duration (APB: p < 0.0001; AH: p = 0.0005; deltoid: p < 0.0001), while cathodal stimulation elicited opposite effects (p < 0.0001). DISCUSSION: tsDCS modulates interhemispheric processing in a polarity-specific manner, with anodal stimulation leading to a functional disconnection between hemispheres. tsDCS would be a new promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric balance, or an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques (NIBS) are not indicated due to safety concerns.

Transcutaneous spinal direct current stimulation modulates human corticospinal system excitability.

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.

Cathodal transcutaneous spinal direct current stimulation (tsDCS) improves motor unit recruitment in healthy subjects.

Transcutaneous spinal direct current stimulation (tsDCS) is a new promising technique for modulating spinal cord function in humans. However, its effects on corticospinal pathways and lower motorneuron excitability are poorly understood. We studied the effects of tsDCS on motor unit recruitment by evaluating changes in motor unit number (MUNE) and peripheral silent period (PSP) after sham (s-tsDCS), anodal (a-tsDCS) and cathodal (c-tsDCS) tsDCS applied either over the cervical or the lower thoracic spinal cord in healthy subjects. For the calculation of MUNE we used the multipoint incremental technique recording from either the ulnar nerve innervated abductor digiti minimi (ADM) or the median nerve innervated abductor pollicis brevis (APB) muscle. c-tsDCS dramatically increases MUNE values following cervical polarization, while sham and anodal polarization have no significant effect (APB: F(4,99)=26.4, p<0.001, two-way repeated measures ANOVA with "time" and "stimulation" as factors; ADM: F(4,99)=22.1, p<0.0001). At the same time, c-tsDCS dampened PSP respect to sham and anodal conditions (p<0.0001). Interestingly, also thoracic c-tsDCS significantly improved motor unit recruitment compared with both s-tsDCS and a-tsDCS (APB: F(4,99)=20.1, p<0.0001; ADM: F(4,99)=16.6, p<0.0001). Our data in healthy subjects suggest that tsDCS, possibly also through supraspinal effects, could provide a novel therapeutic tool in managing several pathological conditions characterized by reduced motor unit recruitment, such as stroke and spinal cord injuries.

Modeling the current density generated by transcutaneous spinal direct current stimulation (tsDCS).

OBJECTIVE: Non-invasive transcutaneous spinal direct current stimulation (tsDCS) induces changes in spinal cord function in humans. Nonetheless, the current density (J) spatial distributions generated by tsDCS are unknown. This work aimed to estimate the J distributions in the spinal cord during tsDCS. METHODS: Computational electromagnetics techniques were applied to realistic human models, based on high-resolution MRI of healthy volunteers (a 26-years-old female adult model "Ella"; a 14years-old male adolescent model "Louis"; an 11years old female adolescent model "Billie"). Three electrode montages were modeled. In all cases, the anode was always over the spinal process of the tenth thoracic vertebra and the cathode was placed: (A) above the right arm; (B) over the umbilicus; (C) over Cz. The injected current was 3mA. The electrodes were conductors within rectangular sponges. RESULTS: Despite inter-individual differences, the J tends to be primarily directed longitudinally along the spinal cord and cauda equina with the region of higher amplitude influenced by the reference electrode position; on transversal sections, the J amplitude distributions were quite uniform. CONCLUSIONS: Our modeling approach reveals that the J generated by tsDCS reaches the spinal cord, with a current spread also to the muscle on the back and the spinal nerve. SIGNIFICANCE: This study is a first step in better understanding the mechanisms underlying tsDCS.

Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis.

BACKGROUND: The debilitating fatigue that patients with multiple sclerosis (MS) commonly experience during day-to-day living activities responds poorly to current therapeutic options. Direct currents (DC) delivered through the scalp (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor cortical excitability that persist for almost an hour after current offset and depend on current polarity. tDCS successfully modulates cortical excitability in various clinical disorders but no information is available for MS related fatigue. OBJECTIVE: In this study we aimed to assess fatigue symptom after five consecutive sessions of anodal tDCS applied over the motor cortex in patients with MS. METHODS: We enrolled 25 patients with MS all of whom experienced fatigue. We delivered anodal and sham tDCS in random order in two separate experimental sessions at least 1 month apart. The stimulating current was delivered for 15 minutes once a day for 5 consecutive days. In each session the Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were administered before the treatment (baseline), immediately after treatment on day five (T1), one week (T2) and three weeks (T3) after the last tDCS session. RESULTS: All patients tolerated tDCS well without adverse events. The fatigue score significantly decreased after anodal tDCS in 65% of the patients (responders). After patients received tDCS for 5 days their FIS scores improved by about 30% and the tDCS-induced benefits persisted at T2 and T3. CONCLUSION: Our preliminary findings suggest that anodal tDCS applied over the motor cortex, could improve fatigue in most patients with MS.

Transcranial direct current stimulation (tDCS) and language.

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.

Increased short latency afferent inhibition after anodal transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS), a technique for central neuromodulation, has been recently proposed as possible treatment in several neurological and psychiatric diseases. Although shifts on focal brain excitability have been proposed to explain the clinical effects of tDCS, how tDCS-induced functional changes influence cortical interneurones is still largely unknown. The assessment of short latency afferent inhibition (SLAI) of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), provides the opportunity to test non-invasively interneuronal cholinergic circuits in the human motor cortex. The aim of the present study was to assess whether anodal tDCS can modulate interneuronal circuits involved in SLAI. Resting motor threshold (RMT), amplitude of unconditioned MEPs and SLAI were assessed in the dominant hemisphere of 12 healthy subjects (aged 21-37) before and after anodal tDCS (primary motor cortex, 13min, 1mA). SLAI was assessed delivering electrical conditioning stimuli to the median nerve at the wrist prior to test TMS given at the interstimulus interval (ISI) of 2ms. Whereas RMT and the amplitude of unconditioned MEPs did not change after anodal tDCS, SLAI significantly increased. In conclusion, anodal tDCS-induced effects depend also on the modulation of cortical interneuronal circuits. The enhancement of cortical cholinergic activity assessed by SLAI could be an important mechanism explaining anodal tDCS action in several pathological conditions.

Transcutaneous spinal cord direct current stimulation inhibits the lower limb nociceptive flexion reflex in human beings.

Aiming at developing a new, noninvasive approach to spinal cord neuromodulation, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in the central pain pathways in human beings. A double-blind crossover design was used to investigate the effects of anodal direct current (2mA, 15min) applied on the skin overlying the thoracic spinal cord on the lower-limb flexion reflex in a group of 11 healthy volunteers. To investigate whether transcutaneous spinal cord DC stimulation (tsDCS) acts indirectly on the nociceptive reflex by modulating excitability in mono-oligosynaptic segmental reflex pathways, we also evaluated the H-reflex size from soleus muscle after tibial nerve stimulation. In our healthy subjects, anodal thoracic tsDCS reduced the total lower-limb flexion reflex area by 40.25% immediately after stimulation (T0) and by 46.9% 30min after stimulation offset (T30). When we analyzed the 2 lower-limb flexion reflex components (RII tactile and RIII nociceptive) separately, we found that anodal tsDCS induced a significant reduction in RIII area with a slight but not significant effect on RII area. After anodal tsDCS, the RIII area decreased by 27% at T0 and by 28% at T30. Both sham and active tsDCS left all the tested H-reflex variables unchanged. None of our subjects reported adverse effects after active stimulation. These results suggest that tsDCS holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain. Thoracic transcutaneous direct current stimulation induces depression of nociceptive lower limb flexion reflex in human beings that persists after stimulation offset; this form of stimulation holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain.

Novel nonpharmacologic perspectives for the treatment of task-specific focal hand dystonia.

NARRATIVE REVIEW: The pathophysiology of focal hand dystonia (FHD) has not yet been completely clarified. Although there is a loss of inhibition at multiple levels of the central nervous system, maladaptive plasticity of the cerebral cortex as well as impairments in sensory and motor representations have also been reported. All of these abnormalities can be viewed as an epiphenomenon of the primary--still unknown--abnormality underlying focal dystonia. The purpose of this review is to describe the underlying constructs of novel nonpharmacologic approaches for the treatment of FHD. Alternative or complementary approaches to botulinum toxin injections such as behavioral training strategies and brain stimulation techniques are reviewed. None of the proposed treatments appears to be definitive and applicable to all patients with FHD. Each treatment strategy elicited some benefit in a fraction of patients. The combination of more than one approach (retraining, immobilization, botulinum toxin, neuromodulation, etc.) could lead to a better control of FHD.