Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome.

OBJECTIVE: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI). Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI. METHODS: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity. RESULTS: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected. CONCLUSIONS: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients. SIGNIFICANCE: This study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Experimental Protocol to Assess Neuromuscular Plasticity Induced by an Exoskeleton Training Session.

Exoskeleton gait rehabilitation is an emerging area of research, with potential applications in the elderly and in people with central nervous system lesions, e.g., stroke, traumatic brain/spinal cord injury. However, adaptability of such technologies to the user is still an unmet goal. Despite important technological advances, these robotic systems still lack the fine tuning necessary to adapt to the physiological modification of the user and are not yet capable of a proper human-machine interaction. Interfaces based on physiological signals, e.g., recorded by electroencephalography (EEG) and/or electromyography (EMG), could contribute to solving this technological challenge. This protocol aims to: (1) quantify neuro-muscular plasticity induced by a single training session with a robotic exoskeleton on post-stroke people and on a group of age and sex-matched controls; (2) test the feasibility of predicting lower limb motor trajectory from physiological signals for future use as control signal for the robot. An active exoskeleton that can be set in full mode (i.e., the robot fully replaces and drives the user motion), adaptive mode (i.e., assistance to the user can be tuned according to his/her needs), and free mode (i.e., the robot completely follows the user movements) will be used. Participants will undergo a preparation session, i.e., EMG sensors and EEG cap placement and inertial sensors attachment to measure, respectively, muscular and cortical activity, and motion. They will then be asked to walk in a 15 m corridor: (i) self-paced without the exoskeleton (pre-training session); (ii) wearing the exoskeleton and walking with the three modes of use; (iii) self-paced without the exoskeleton (post-training session). From this dataset, we will: (1) quantitatively estimate short-term neuroplasticity of brain connectivity in chronic stroke survivors after a single session of gait training; (2) compare muscle activation patterns during exoskeleton-gait between stroke survivors and age and sex-matched controls; and (3) perform a feasibility analysis on the use of physiological signals to decode gait intentions.

Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom.

More than half of patients who recover from COVID-19 experience fatigue. We studied fatigue using neuropsychological and neurophysiological investigations in post-COVID-19 patients and healthy subjects. Neuropsychological assessment included: Fatigue Severity Scale (FSS), Fatigue Rating Scale, Beck Depression Inventory, Apathy Evaluation Scale, cognitive tests, and computerized tasks. Neurophysiological examination was assessed before (PRE) and 2 min after (POST) a 1-min fatiguing isometric pinching task and included: maximum compound muscle action potential (CMAP) amplitude in first dorsal interosseous muscle (FDI) following ulnar nerve stimulation, resting motor threshold, motor evoked potential (MEP) amplitude and silent period (SP) duration in right FDI following transcranial magnetic stimulation of the left motor cortex. Maximum pinch strength was measured. Perceived exertion was assessed with the Borg-Category-Ratio scale. Patients manifested fatigue, apathy, executive deficits, impaired cognitive control, and reduction in global cognition. Perceived exertion was higher in patients. CMAP and MEP were smaller in patients both PRE and POST. CMAP did not change in either group from PRE to POST, while MEP amplitudes declined in controls POST. SP duration did not differ between groups PRE, increased in controls but decreased in patients POST. Patients' change of SP duration from PRE to POST was negatively correlated to FSS. Abnormal SP shortening and lack of MEP depression concur with a reduction in post-exhaustion corticomotor inhibition, suggesting a possible GABAB-ergic dysfunction. This impairment might be related to the neuropsychological alterations. COVID-19-associated inflammation might lead to GABAergic impairment, possibly representing the basis of fatigue and explaining apathy and executive deficits.

Use of injectable collagen in partial-thickness tears of the supraspinatus tendon: a case report.

Management of partial-thickness rotator cuff tears is actually controversial. We treated a patient with a partial-thickness tear of the supraspinatus tendon by a series of four type I porcine collagen ultrasound-guided injections, at weekly intervals. At the same time the patient underwent physical therapy, consisting of motor re-education and proprioceptive exercises. The patient was assessed before the treatment and up to 18 months after the last injection by the Constant-Murley score, the Disability of Arm, Shoulder and Hand questionnaire and ultrasonography. Shoulder pain and functional limitation progressively improved and they almost completely disappeared at the last follow-up. Ultrasonography showed a gradual healing of the partial-thickness tear and a regeneration of the tendon structure. This is the first study on ultrasound-guided injections of type I porcine collagen for the treatment of partial-thickness rotator cuff tears. Future research should confirm the excellent result achieved in this case report.