Pharyngeal electrical stimulation for neurogenic dysphagia following stroke, traumatic brain injury or other causes: Main results from the PHADER cohort study

BackgroundNeurogenic dysphagia is common and has no definitive treatment. We assessed whether pharyngeal electrical stimulation (PES) is associated with reduced dysphagia.MethodsThe PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) was a prospective single-arm observational cohort study. Participants were recruited with neurogenic dysphagia (comprising five groups – stroke not needing ventilation; stroke needing ventilation; ventilation acquired; traumatic brain injury; other neurological causes). PES was administered once daily for three days. The primary outcome was the validated dysphagia severity rating scale (DSRS, score best-worst 0–12) at 3 months.FindingsOf 255 enrolled patients from 14 centres in Austria, Germany and UK, 10 failed screening. At baseline, mean (standard deviation) or median [interquartile range]: age 68 (14) years, male 71%, DSRS 11·4 (1·7), time from onset to treatment 32 [44] days; age, time and DSRS differed between diagnostic groups. Insertion of PES catheters was successfully inserted in 239/245 (98%) participants, and was typically easy taking 11·8 min. 9 participants withdrew before the end of treatment. DSRS improved significantly in all dysphagia groups, difference in means (95% confidence intervals, CI) from 0 to 3 months: stroke (n = 79) –6·7 (–7·8, –5·5), ventilated stroke (n = 98) –6·5 (–7·6, –5·5); ventilation acquired (n = 35) –6·6 (–8·4, –4·8); traumatic brain injury (n = 24) -4·5 (–6·6, –2·4). The results for DSRS were mirrored for instrumentally assessed penetration aspiration scale scores. DSRS improved in both supratentorial and infratentorial stroke, with no difference between them (p = 0·32). In previously ventilated participants with tracheotomy, DSRS improved more in participants who could be decannulated (n = 66) –7·5 (–8·6, –6·5) versus not decannulated (n = 33) –2·1 (–3·2, –1·0) (

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration. If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results. Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS

Effects of intrathecal baclofen therapy in subjects with disorders of consciousness: a reappraisal

Baclofen is a structural analogue of gamma-amino-butyric acid (GABA), which reduces spastic hypertonia of striated muscle due to a mechanism of GABAB-ergic inhibition of mono- and polysynaptic reflexes at the spinal level. There are reports of patients with severe disorders of consciousness that presented a substantial improvement following intrathecal baclofen (ITB) administration for severe spasticity. The neural mechanisms underlying the clinical recovery after ITB have not yet been clarified. Baclofen could modulate sleep-wake cycles that may be dysregulated and thus interfere with alertness and awareness. The diminished proprioceptive and nociceptive sensory inputs may relieve thalamo-cortical neural networks involved in maintaining the consciousness of the self and the world. ITB treatment might also promote the recovery of an impaired GABAergic cortical tone, restoring the balance between excitatory and inhibitory cortical activity. Furthermore, glutamatergic synapses are directly or indirectly modulated by GABAB-ergic receptors. Neurophysiological techniques (such as transcranial magnetic stimulation, electroencephalography, or the combination of both) can be helpful to explore the effects of intrathecal or oral baclofen on the modulation of neural cortical circuits in humans with disorders of consciousness

Effects of repetitive transcranial magnetic stimulation in subjects with sleep disorders

In this review, we aimed at identifying the studies that have employed repetitive transcranial magnetic stimulation (rTMS) in patients with sleep disorders. Low-frequency (LF) rTMS stimulating the right dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) was found to be effective to reduce cortical hyperexcitability and improve the sleep quality in subjects with chronic primary insomnia (PI). Both high-frequency (HF) and LF rTMS applied over the primary motor cortex or the supplementary motor cortex seem to have transient beneficial effects in patients with restless legs syndrome (RLS). Stimulation of upper airway muscles during sleep by isolated TMS and by rTMS twitch can improve airflow dynamics in obstructive sleep apnea syndrome (OSAS) patients without arousal. A single case report study indicates that HF rTMS over the left DLPFC might represent an alternative choice for symptom control in narcoleptic patients with cataplexy, and a pilot study also raises the possibility of therapeutic benefits from rTMS in patients with sleep bruxism. rTMS may also exert intrinsic effects on hypersomnia in depressed adolescents. In conclusion, rTMS may contribute to the development of new non-pharmacological therapeutic options for several sleep disorders. rTMS might be useful as therapeutical tool in particular in patients with PI, RLS, OSAS and narcolepsy, while its effect in other sleep disorders (ie, parasomnias) has not yet been explored. rTMS integrated with clinical, sleep-related, and neuroimaging data may represent an effective tool in modulating cortical excitability and inducing short-term synaptic plasticity. Further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up warranted to verify the initial findings, and to expand clinical and research interest towards neuromodulation in the different sleep disorders

Facilitation of auditory comprehension after theta burst stimulation of Wernicke's area in stroke patients: a pilot study

Introduction: Single-pulse transcranial magnetic stimulation (TMS) and high-frequency repetitive TMS (rTMS) over Wernicke's area were found to facilitate language functions in right-handed healthy subjects. We aimed at investigating the effects of excitatory rTMS, given as intermittent theta burst stimulation (iTBS) over left Wernicke's area, on auditory comprehension in patients suffering from fluent aphasia after stroke of the left temporal lobe. Methods: We studied 13 patients with chronic fluent aphasia after an ischemic stroke involving Wernicke's area. iTBS was applied in random order to Wernicke's area, the right-hemisphere homologous of Wernicke's area, and the primary visual cortex. Auditory comprehension was blind assessed using the Token test before (T0), 5 (T1), and 40 min (T2) after a single session of iTBS. Results: At the first evaluation (T1) after iTBS on left Wernike's area, but not on the contralateral homologous area nor on the primary visual cortex, the scores on the Token test were significantly increased. No significant effects were observed at T2. Conclusion: We demonstrated that a single session of excitatory iTBS over Wernicke's area was safe and led to a transient facilitation of auditory comprehension in chronic stroke patients with lesions in the same area. Further studies are needed to establish whether TBS-induced modulation can be enhanced and transformed into longer-lasting effects by means of repeated TBS sessions and by combining TBS with speech and language therapy

On the recovery of disorders of consciousness under intrathecal baclofen administration for severe spasticity—An observational study

Abstract Background Occasionally, patients show dramatic recovery from disorders of consciousness (DOC) under intrathecal baclofen (ITB), an established treatment option for severe supraspinal spasticity. Anecdotal explanations for ITB‐related recovery of cognition include modulation of afferent impulses at the spinal level, thereby reducing spasticity‐related proprioceptive information overload within cortico–thalamo–cortical connections. Objective In this retrospective patient chart analysis, we assessed whether a reduction in spasticity would be associated with an increase in Coma Recovery Scale revised (CRS‐R) scores in a larger sample of patients than previously published. Methods From a hospital‐based ITB treatment register, we extracted data from 26 patients with DOC and severe supraspinal spasticity who improved by >2 points on the Coma Recovery Scale revised (CRS‐R) within 6 months after ITB treatment initiation. We assessed Modified Ashworth scale (MAS) scores and CRS‐R scores on admission (PRE) and 3 and 6 months after initiation of ITB treatment (3M, 6M). We performed correlation analysis of the scores and their respective changes (PRE to 3M, 3M to 6M). We also correlated the time from acute event until ITB initiation to CRS‐R scores at 3M and 6M. Results ITB led to significant improvement in spasticity based on MAS scores, which did not correlate to the improvements seen in CRS‐R total and subscale scores. Daily ITB dose did neither correlate to MAS scores nor to CRS‐total scores in the whole patient group, but after 3 months, ITB dose correlated to some CRS‐R subscale scores in some patient subgroups. Time until ITB treatment did not correlate to CRS‐R scores later on. Conclusions Our data confirm that ITB may exert beneficial effects in selected DOC patients with respect to improved cognitive functions, which, however, do not correlate to its antispastic effect. The lack of correlation between time to ITB and CRS‐R outcome, but significant CRS‐R improvements following pump implantation, renders spontaneous remissions unlikely and leaves room for alternative pharmacological mechanisms