Effect of transcranial magnetic stimulation on rectal sensitivity in irritable bowel syndrome: a randomized, placebo-controlled pilot study.

AIM: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. METHOD: In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0 ± 12.6 years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5 days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. RESULTS: There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. CONCLUSION: This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.

Evoked pressure curves from the external anal sphincter following transcranial magnetic stimulation in healthy volunteers and patients with faecal incontinence.

AIM: The hypothesis was tested that evoked pressure curves (EPCs) after transcranial magnetic stimulation (TMS) would provide additional neuropathophysiological information on the descending pathways to the external anal sphincter (EAS) in patients with faecal incontinence (FI). METHOD: Twenty-five healthy subjects and 69 patients with FI were investigated. TMS was applied to the vertex, and EPCs were recorded with a probe placed through the EAS. TMS was performed with the EAS at rest and during contraction (facilitated responses). At least three responses were recorded for each modality. Clinical data and anorectal manometric, electrophysiological perineal and transanal ultrasound recordings were compared with respect to the EPC results. RESULTS: There was no statistically significant difference between the EPCs of healthy subjects and FI patients. Twenty-three per cent of the FI patients had abnormal EPC latencies, with significantly lower voluntary contraction amplitudes (P = 0.03) and significantly higher rectal sensation (P = 0.04) than the other group. We found no significant difference between FI patients with and without abnormal EPC latencies in terms of clinical characteristics and electrophysiological and endoanal ultrasound parameters. There was no difference in the identified causes of the FI between the two groups. CONCLUSION: As abnormal EPC latencies were found in 23% of FI patients with no known central neurological disease, abnormal EPC latencies might reveal undetected lesions of descending pathways in patients with FI.

Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease.

The physiopathology of gait and balance disorders in Parkinson's disease patients is still poorly understood. Levodopa treatment and subthalamic nucleus (STN) stimulation improve step length and walking speed, with less effect on postural instability. These disorders have been linked to dysfunction of the descending basal ganglia outputs to brainstem structures. In this study, we evaluated the effects of stimulation of the substantia nigra pars reticulata (SNr), on locomotion and balance in Parkinson's disease patients. Biomechanical parameters and leg muscle activity were recorded during gait initiation in seven selected patients operated for bilateral STN stimulation, out of 204 stimulated patients, with one contact of each electrode located within the SNr. Step length, anteroposterior and vertical velocities of the centre of gravity were studied, with special reference to the subjects' ability to brake the centre of gravity fall before foot-contact, and compared to seven controls. In Parkinson's disease patients, five treatment conditions were tested: (i) no treatment, (ii) levodopa treatment, (iii) STN stimulation, (iv) SNr stimulation and (v) combined levodopa treatment and STN stimulation. The effects of these treatments on motor parkinsonian disability were assessed with the UPDRS III scale, separated into 'axial' (rising from chair, posture, postural stability and gait) and 'distal' scores. Whereas levodopa and/or STN stimulation improved 'axial' and 'distal' motor symptoms, SNr stimulation improved only the 'axial' symptoms. Compared to controls, untreated Parkinson's disease patients showed reduced step length and velocity, and poor braking just prior to foot-contact, with a decrease in both soleus (S) and anterior tibialis (AT) muscle activity. Step length and velocity significantly increased with levodopa treatment alone or in combination with STN stimulation in both natural and fast gait conditions, and with STN stimulation alone in the fast gait condition. Conversely, SNr stimulation had no significant effect on these measures in either condition. In the natural gait condition, no fall in the centre of gravity occurred as step length was low and active braking was unnecessary. In the fast gait condition, braking was improved with STN or SNr stimulation but not with levodopa treatment, with an increase in the stance leg S muscle activity. These results suggest that anteroposterior (length and velocity) and vertical (braking capacity) gait parameters are controlled by two distinct systems within the basal ganglia circuitry, representing respectively locomotion and balance. The SNr, a major basal ganglia output known to project to pontomesencephalic structures, is postulated as being particularly involved in balance control during gait.

[Gait and balance disorders in patients with atypical parkinsonian syndromes]. / Les troubles de la marche et de l'équilibre dans les syndromes parkinsoniens << plus >>.

The degenerative Parkinsonian "Plus" syndromes form a heterogeneous spectrum of pathologies comprising multiple system atrophy, progressive supranuclear palsy, Lewy body disease and cortico-basal degeneration. Their developmental profile is distinguished from that of Parkinson's disease by the early appearance of gait and balance disorders, isolated freezing of gait, primary progressive freezing of gait or an isolated or "pure" akinesia. The origin of these symptoms however remains poorly understood. The association of nigrostriatal dopamine neuron loss with either cortical lesions, in the case of cortico-basal degeneration and Lewy body disease, and/or of the brainstem, in the case of progressive supranuclear palsy, explains both the severity of the motor symptoms and the lack of, or minimal, improvement following levodopa therapy. Other symptomatic drug and surgical treatments have been proposed, but with generally disappointing results. Physiotherapeutic techniques targeting balance control can bring some temporary improvements.

Practice of stereoelectroencephalography (sEEG) in drug-resistant epilepsy: Retrospective series with surgery and thermocoagulation outcomes.

OBJECTIVE: The aim of this study was to determine the success rate of sEEG in locating the epileptogenic zone (EZ) in patients with pharmaco-resistant epilepsy. Secondary objectives were to analyze sEEG-related morbidity and outcomes for post-sEEG thermocoagulation and cortical resection. METHODS: Data were collected on 49 sEEGs from 46 consecutive patients between 2010 and 2018. Following sEEG, either resective or palliative surgery with vagus nerve stimulation was performed. In 8 patients, EZ thermocoagulation was performed before EEG leads were withdrawn. Outcomes were collected based on the Engel and ILAE outcome scales. RESULTS: sEEG was contributive in 45 of 49 recordings, with a success rate of 92% in locating the EZ. Minor complications, such as transient neurologic deficit and electrode implantation failures, occurred in 6%. One major complication occurred, with death due to atypical late hematoma. Thermocoagulation was performed in 8 patients and stopped or significantly reduced seizure frequency in 7 (88%). Outcome of surgical resection (n=33) was good, with 20 (61%) seizure-free patients and 32 (97%) with definite improvement. CONCLUSIONS: Our findings suggest that sEEG is an effective technique for EZ location in patients with drug-resistant epilepsy. sEEG was contributive in up to 92% of patients, allowing thermocoagulation and/or surgical resection that resulted in seizure-freedom in two-thirds and seizure-reduction in one-third of cases. This study highlights the need for strict selection of implantation candidates, with strong initial hypothesis as to EZ location.

[Medical management of patients with atypical degenerative parkinsonian syndromes]. / Prise en charge médicale des patients atteints de syndromes parkinsoniens atypiques dégénératifs.

Atypical degenerative parkinsonian syndromes (progressive supranuclar palsy, multiple system atrophy, corticobasal degeneration, Lewy body dementia) are an important differential diagnosis to idiopathic Parkinson's disease. However, because these disorders are characterized by the degeneration of multiple neuronal populations, treatment approaches are much less specific than in Parkinson's disease, where dopamimetic drugs represent the mainstay of therapy. Thus, and because the progression of these disorders is usually more aggressive than Parkinson's disease, many physicians face a form of therapeutic resignation when confronted with patients suffering from atypical degenerative parkinsonian syndromes. However, in the present article, we wish to show that a symptom-by-symptom approach can substantially relieve the patients and their caregivers by providing an overview of pharmacologic and non-pharmacologic treatment options.

Usefulness of multidetector-row computerized tomographic angiography for the surgical planning in stereoelectroencephalography.

PURPOSE: Surgical planning of depth electrode implantation in stereo-electro-encephalography (SEEG) routinely uses magnetic resonance imaging (MRI) alone. Accurate visualization of arteries and veins in the vicinity of the electrode is essential to plan a safe trajectory to presumably reduce the risk of intracranial bleeding. The goal of this study was to compare multidetector row computerized tomographic angiography (MDCTA) with MRI for the visualization of vessels along each planned trajectory in patients who undergo SEEG. MATERIALS AND METHODS: Ten consecutive patients who were scheduled to undergo SEEG procedure were included. T1-weighted gadolinium-chelate enhanced MR sequence, stereotactic MDCT and MDCTA were performed after fixation of Leksell's frame. For each of the 106 planned stereotactic trajectories, the number of vessels in a 4.0mm diameter circle around the trajectory from the dura mater to the target that were visible on MDCTA were compared to that of visible vessels in the same areas on MRI. RESULTS: Ten vessels (10/106; 9.4%) were seen on MRI and 66 (66/106; 62.3%) on MDCTA (P<0.0001). All vessels visible on MRI were visible on MDCTA. The difference in number of visible vessels between the two techniques remained significant for the different lobes (i.e., frontal lobe, temporal lobe and parieto-occipital lobe). CONCLUSION: MDCTA enabled visualization of more vessels than MRI based SEEG. MDCTA may help neurosurgeons better define the trajectory of the electrode and reduce the risk of intracranial bleeding.

Impact of deep brain stimulation on pharyngo-esophageal motility: a randomized cross-over study.

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinson's disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study. METHODS: Sixteen humans PD patients (4 women, 12 men; age: 62.4 ± 9.3-years old) who underwent STN stimulation for at least 6 months were randomly evaluated with either stimulator turned OFF then ON, or inversely. Esophageal high resolution manometry was performed at the end of each ON and OFF period, with a 5 min resting period followed by ten swallows of 5 mL. KEY RESULTS: During the ON, an increase in the distal contractility index was found (OFF: 1750 ± 629 vs ON: 2171 ± 755 mmHg/cm/s; p = 0.03), with no difference in the distal front velocity. A decrease in the integrative relaxation pressure of the lower esophageal sphincter (LES) was noted (OFF: 11.1 ± 1.8 mmHg vs ON: 7.2 ± 1.8 mmHg; p < 0.05) in ON. The LES resting pressure remained unchanged during the two periods. This resulted in a decrease in the intrabolus pressure (p = 0.03). No difference was observed for the upper esophageal sphincter, nor the pharyngeal contraction amplitude and velocity. CONCLUSIONS & INFERENCES: In conclusion, STN stimulation in PD patients increased esophageal body contractions and enhanced the LES opening. This suggests that the nigrostriatal-striatonigral loop is involved in the control of esophageal motility.

Large-field repetitive transcranial magnetic stimulation with circular coil in the treatment of functional neurological symptoms.

OBJECTIVE: Patients with functional neurological symptoms (FNS) are frequently encountered by neurologists and are difficult to treat. Symptoms are multiple and may appear concurrently or successively in the same patient. To date, few studies have been published on focal repetitive transcranial magnetic stimulation (rTMS) in FNS. This type of stimulation induces a focal current, vertically in the cortex. Results are contradictory, probably because it is difficult to identify a limited cortical area that triggers these symptoms. We assessed the efficacy of another type of rTMS: large-field stimulation by means of a circular coil covering a surface area approximately 20 times greater and inducing a circular current tangentially to the cortex. PUBLISHED STUDIES: We analysed two studies on the efficacy of large-field rTMS in functional paralysis and in functional movement disorders. The efficacy of large-field rTMS was very marked in these two studies. PERSONAL NON-PUBLISHED STUDIES: We reported several open series, including patients with functional sensory loss, functional visual loss, and non-epileptic seizures. METHOD: For all patients, one or several sessions of 60 stimuli with circular coil were carried out with a protocol depending on the symptoms. RESULTS: The efficacy of large-field rTMS was dramatic in all patient series. Additionally, we discuss the possible involved mechanism: placebo effect, cognitive behavioural effect or neuromodulatory effect. CONCLUSION: According to the data from these different studies, large-field rTMS could be a new therapy for patients with FNS. However, controlled studies are mandatory.

Effect of unilateral subthalamic deep brain stimulation on rat digestive motor activity.

UNLABELLED: A significant proportion of patients with Parkinson's disease suffers from digestive symptoms. Bilateral deep brain stimulation of the subthalamic nucleus has become a reliable therapeutic option for parkinsonian patients, but its effects on digestive motility remain poorly investigated. The aim of our study was to assess whether subthalamic stimulation could induce changes in gastric, colonic, and rectal motility and modulate brain centers involved in gut motility. METHODS: In anesthetized rats, unilateral subthalamic nucleus stereotactic implantation was performed while intra-gastric, -colonic, and -rectal pressures were recorded during the ON and OFF periods of the stimulation. c-Fos protein expression was quantified by immunostaining in the nucleus of the solitary tract, the dorsal motor nucleus of the vagus nerve, the locus coeruleus, and the Barrington's nucleus. RESULTS: Compared to baseline, sham stimulation did not change phasic gastric, colonic or rectal motor activity. Unilateral subthalamic stimulation increased colonic phasic motility (P<0.05) compared to baseline and the OFF period with no change in gastric and rectal motility. Pre-treatment with atropine, or specific D1 and D2 receptors antagonists prevented the rise in colonic motor activity. An increase in c-Fos protein-positive cells within all the studied nuclei was observed in the stimulated group compared to the sham group. CONCLUSIONS: Unilateral subthalamic stimulation impacts on gut motility in anesthetized rats with a significant increase in colonic motility probably via the modulation of several brain centers. These findings warrant further confirmation in parkinsonian rat models before being transposed to clinical conditions.

Influence of sensory inputs and motor demands on the control of the centre of mass velocity during gait initiation in humans.

Human gait requires the simultaneous generation of goal-directed continuous movement (locomotion) and the maintenance of balance (postural control). In adults, the centre of mass (CoM) oscillates in the vertical plane while walking. During the single support phase of gait initiation, its vertical (vCoM) velocity increases as the CoM falls and is actively reversed prior to foot-contact. In this study we investigated whether this active control, which is thought to reflect balance control during gait initiation, is controlled by visual and somatosensory inputs (Experiment 1) and whether it is modified by a change in motor demands, two steps versus one step (Experiment 2). In all healthy adults, the vCoM velocity was braked, or controlled, by contraction of the soleus muscle of the stance leg. The elimination of visual input alone had no effect on braking, although its amplitude decreased when somatosensory inputs were disrupted (-47%), and further decreased when both visual and somatosensory inputs were disrupted (-83%). When subjects performed only one step, with no trailing of the stance foot, the vCoM velocity braking also decreased (-42%). These results suggest that active braking of the CoM fall during the transition to double support, an indicator of balance control, is influenced by both multisensory integration and the demands of the current motor program. The neural structures involved in this mechanism remain to be elucidated.

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up.

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.