The Language of Pain in the Hypermobile Ehlers-Danlos Syndrome: Metaphors as a Key to Understanding the Experience of Pain and as a Rehabilitation Tool.

Ehlers-Danlos syndromes are a heterogeneous group of Heritable Connective Tissue Disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile Ehlers-Danlos syndrome is the most frequent and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hypermobile Ehlers-Danlos syndrome is often associated with pain that does not always allow the use of effective pain-reducing treatments. Patients with hEDS constantly describe their pain in detail. Eighty-nine patients with hEDS diagnoses were recruited and evaluated. They were asked to describe their pain in writing. The texts were examined through Linguistic Inquiry and Word Count. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and the quality of metaphors was carried out. The results showed that language quality varies depending on how much pain is perceived. The greater the pain is perceived, the lesser the positive effects and the greater the negative effects and dehumanizing metaphors are being used. Moreover, a greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for examining illness experience and may help clinicians in the rehabilitation program.

Investigating the Effects of a Focal Muscle Vibration Protocol on Sensorimotor Integration in Healthy Subjects.

Background: The ability to perceive two tactile stimuli as asynchronous can be measured using the somatosensory temporal discrimination threshold (STDT). In healthy humans, the execution of a voluntary movement determines an increase in STDT values, while the integration of STDT and movement execution is abnormal in patients with basal ganglia disorders. Sensorimotor integration can be modulated using focal muscle vibration (fMV), a neurophysiological approach that selectively activates proprioceptive afferents from the vibrated muscle. Method: In this study, we investigated whether fMV was able to modulate STDT or STDT-movement integration in healthy subjects by measuring them before, during and after fMV applied over the first dorsalis interosseous, abductor pollicis brevis and flexor radialis carpi muscles. Results: The results showed that fMV modulated STDT-movement integration only when applied over the first dorsalis interosseous, namely, the muscle performing the motor task involved in STDT-movement integration. These changes occurred during and up to 10 min after fMV. Differently, fMV did not influence STDT at rest. We suggest that that fMV interferes with the STDT-movement task processing, possibly disrupting the physiological processing of sensory information. Conclusions: This study showed that FMV is able to modulate STDT-movement integration when applied over the muscle involved in the motor task. This result provides further information on the mechanisms underlying fMV, and has potential future implications in basal ganglia disorders characterized by altered sensorimotor integration.

Habituation deficit of visual evoked potentials in migraine patients with hypermobile Ehlers-Danlos syndrome.

Objectives: Migraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described in migraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine. Methods: We enrolled 22 hEDS patients with migraine (hEDS) and 22 non-hEDS patients with migraine (MIG), with and without aura (according to ICHD-3), as well as 22 healthy controls (HC). Repetitive pattern reversal (PR)-VEPs were recorded in basal conditions in all participants. During uninterrupted stimulation, 250 cortical responses were recorded (4,000 Hz sample rate) and divided into epochs of 300 ms after the stimulus. Cerebral responses were divided into five blocks. The habituation was calculated as the slope interpolating the amplitudes in each block, for both the N75-P100 and P100-N145 components of PR-VEP. Results: We observed a significant habituation deficit of the P100-N145 component of PR-VEP in hEDS compared to HC (p = 0.002), unexpectedly more pronounced than in MIG. We observed only a slight habituation deficit of N75-P100 in hEDS, with a slope degree that was intermediate between MIG and HC. Discussion: hEDS patients with migraine presented an interictal habituation deficit of both VEPs components like MIG. Pathophysiological aspects underlying the pathology could account for the peculiar pattern of habituation in hEDS patients with migraine characterized by a pronounced habituation deficit in the P100-N145 component and a less clear-cut habituation deficit in the N75-P100 component with respect to MIG.

Congenital Defects in a Patient Carrying a Novel Homozygous AEBP1 Variant: Further Expansion of the Phenotypic Spectrum of Ehlers-Danlos Syndrome Classical-like Type 2?

In 2018, a new clinical subtype, caused by biallelic variants in the AEBP1 gene, encoding the ACLP protein, was added to the current nosological classification of the Ehlers-Danlos Syndromes (EDS). This new phenotype, provisionally termed EDS classical-like type 2 (clEDS2), has not yet been fully characterized, as only nine cases have been reported to date. Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant (NM_001129.5 c.2123_2124delTG (p.Val708AlafsTer5)), whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations. Furthermore, we briefly summarize the current principal clinical manifestations of clEDS2 and the molecular evidence surrounding the role of AEBP1 in the context of extracellular matrix homeostasis and connective tissue development. Although a different coexisting etiology for the multiple congenital malformations of our patient cannot be formally excluded, the emerging role of ACLP in TGF-ß and WNT pathways may explain their occurrence and the phenotypical variability of clEDS2.

Neuromuscular taping for chronic non-specific low back pain: a randomized single-blind controlled trial.

BACKGROUND: Low-back pain is a worldwide pain syndrome causing important limitations to daily activity. Common treatment guidelines recommend drugs and exercise. AIM: To evaluate the efficacy of a standardized NeuroMuscular Taping (NMT) lumbar application in reducing pain and improving function associated with back-school therapy (BST). METHODS: Single-blind randomized controlled trial. The experimental group was treated with BTS followed by three applications of NMT over 8 days and the control group who underwent only BST. All patients were evaluated before and at the end of treatment, after 4 and 8 weeks from the end of BST and with a follow-up at distance of three months from the last evaluation, with pain numeric scale, Oswestry disability index and Schober test. RESULTS: Significant pain reduction and functional improvement have been observed in the follow-up evaluations in the experimental group. CONCLUSION: Association of a standardized NMT application to BTS was seen to significantly improve function and reduce pain with longer time efficacy.

Italian Version of the YQOL-DHH Questionnaire: Translation and Cross-cultural Adaptation.

OBJECTIVE: To translate and cross-culturally adapt into Italian the YQOL-DHH (Youth Quality of Life Instrument-Deaf and Hard of Hearing Module), an instrument to evaluate the health-related quality of life in young deaf people. It could be useful for professionals, teachers, and parents to take care of deaf adolescents' needs. STUDY DESIGN: Forward-backward translation, cross-cultural adaptation, and cognitive debriefing. SETTING: The cognitive debriefing was performed online with professionals and during clinical practice with deaf adolescents. METHODS: A methodological study was conducted according to the guidelines provided by the development team. The study consisted of a forward-backward translation and a cross-cultural adaptation. After the original authors' confirmation, a cognitive debriefing was conducted with 30 professionals who work with deaf young people and with 10 deaf adolescents aged 11 to 18 years. RESULTS: For the linguistic translation and cross-cultural adaptation, some variations to the original instrument were made to obtain equivalence, such as the expression "deaf or hard of hearing" translated only with the Italian word "sordo." During the cognitive debriefing, the clarity and comprehensibility of the items were reported by professionals and deaf adolescents. Eventually, the authors approved the final version. CONCLUSION: The YQOL-DHH was translated and culturally adapted into Italian. The translated items were pertinent to the Italian culture and equivalent to the original ones. A validation study is suggested to make the instrument feasible for use in different clinical or educational contexts. In addition, to guarantee accessibility and autonomy for young deaf signers, Italian Sign Language translation of the questionnaire is suggested.

Pain Management through Neurocognitive Therapeutic Exercises in Hypermobile Ehlers-Danlos Syndrome Patients with Chronic Low Back Pain.

BACKGROUND: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management. METHODS: In this nonrandomized clinical trial, eighteen hEDS patients (4 males and 14 females) with mean age 21 years (range 13-55) were recruited and evaluated before and after three months of rehabilitation treatment. RESULTS: The outcome scores showed significant statistical results after treatment in reducing pain symptoms (numerical rating scale, P = 0.003; McGill (total score), P = 0.03), fatigue (fatigue severity scale, P = 0.03), fear of movement (Tampa scale, P = 0.003), and pain-associated disability (Oswestry disability index, P = 0.03). CONCLUSION: The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers-Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.

Attention-Demanding Cognitive Tasks Worsen Postural Control in Patients With Cervical Dystonia: A Case-Control Study.

Background: Patients with cervical dystonia (CD) show impaired postural control, balance, and gait, likely due to abnormal head postures and sensorimotor disturbances. However, until now no study has investigated whether attention-demanding activity worsens postural control and balance in CD patients. Objective: To investigate whether patients with CD show cognitive-motor interference (CMI), a specific kind of dual-task interference that occurs during the simultaneous execution of a cognitive and motor task. This information may be useful to determine whether performing activities of daily living worsens postural control and balance in CD patients. Methods: We performed a pilot case-control study. Twenty-two patients affected by CD and 19 healthy controls were enrolled in order to test CMI. Each subject was evaluated during the execution of a cognitive task while postural stability was assessed through a stabilometric platform. Results: CD patients showed impaired postural control compared to healthy controls, with instability increasing with increasing cognitive task complexity. No relationships were found between stabilometric parameters and clinical characteristics of CD. Conclusions: Our hypothesis is that CMI in CD patients derives from deranged network connectivity when activated simultaneously during the performance of two tasks that interfere with each other and "compete" for the same resources within the cognitive system.

Motor Recovery After Stroke: From a Vespa Scooter Ride Over the Roman Sampietrini to Focal Muscle Vibration (fMV) Treatment. A 99mTc-HMPAO SPECT and Neurophysiological Case Study.

Focal repetitive muscle vibration (fMV) is a safe and well-tolerated non-invasive brain and peripheral stimulation (NIBS) technique, easy to perform at the bedside, and able to promote the post-stroke motor recovery through conditioning the stroke-related dysfunctional structures and pathways. Here we describe the concurrent cortical and spinal plasticity induced by fMV in a chronic stroke survivor, as assessed with 99mTc-HMPAO SPECT, peripheral nerve stimulation, and gait analysis. A 72-years-old patient was referred to our stroke clinic for a right leg hemiparesis and spasticity resulting from a previous (4 years before) hemorrhagic stroke. He reported a subjective improvement of his right leg's spasticity and dysesthesia that occurred after a30-min ride on a Vespa scooter as a passenger over the Roman Sampietrini (i.e., cubic-shaped cobblestones). Taking into account both the patient's anecdote and the current guidelines that recommend fMV for the treatment of post-stroke spasticity, we then decided to start fMV treatment. 12 fMV sessions (frequency 100 Hz; amplitude range 0.2-0.5 mm, three 10-min daily sessions per week for 4 consecutive weeks) were applied over the quadriceps femoris, triceps surae, and hamstring muscles through a specific commercial device (Cro®System, NEMOCOsrl). A standardized clinical and instrumental evaluation was performed before (T0) the first fMV session and after (T1) the last one. After fMV treatment, we observed a clinically relevant motor and functional improvement, as assessed by comparing the post-treatment changes in the score of the Fugl-Meyer assessment, the Motricity Index score, the gait analysis, and the Ashworth modified scale, with the respective minimal detectable change at the 95% confidence level (MDC95). Data from SPECT and peripheral nerve stimulation supported the evidence of a concurrent brain and spinal plasticity promoted by fMV treatment trough activity-dependent changes in cortical perfusion and motoneuron excitability, respectively. In conclusion, the substrate of post-stroke motor recovery induced by fMV involves a concurrently acting multisite plasticity (i.e., cortical and spinal plasticity). In our patient, operant conditioning of both cortical perfusion and motoneuron excitability throughout a month of fMV treatment was related to a clinically relevant improvement in his strength, step symmetry (with reduced limping), and spasticity.

Fifteen Years of Wireless Sensors for Balance Assessment in Neurological Disorders.

Balance impairment is a major mechanism behind falling along with environmental hazards. Under physiological conditions, ageing leads to a progressive decline in balance control per se. Moreover, various neurological disorders further increase the risk of falls by deteriorating specific nervous system functions contributing to balance. Over the last 15 years, significant advancements in technology have provided wearable solutions for balance evaluation and the management of postural instability in patients with neurological disorders. This narrative review aims to address the topic of balance and wireless sensors in several neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and other neurodegenerative and acute clinical syndromes. The review discusses the physiological and pathophysiological bases of balance in neurological disorders as well as the traditional and innovative instruments currently available for balance assessment. The technical and clinical perspectives of wearable technologies, as well as current challenges in the field of teleneurology, are also examined.

A new insight on postural tachycardia syndrome in 102 adults with hypermobile Ehlers-Danlos Syndrome/hypermobility spectrum disorder.

There is an association between joint hypermobility, hypermobile Ehlers-Danlos syndrome (hEDS) and different forms of orthostatic intolerance. Objective: to explore autonomic profile in a large cohort of adults with hEDS and hypermobility spectrum disorder (hEDS/HSD) with a multimodal approach. In this observational retrospective study, heart rate, blood pressure and baroreflex sensitivity were estimated in 102 hEDS/HSD subjects during deep breathing, Valsalva maneuver, standing up: 30-15 ratio, Head-Up Tilt and sustained handgrip. Abnormal results and head-up tilt test were common and included postural orthostatic tachycardia syndrome (POTS; 48%), orthostatic intolerance (25.5%) and hypotension (3.9%). Baroreflex sensitivity was significantly different in individuals with POTS compared to the others. This study confirms the high rate and heterogeneity of abnormal autonomic regulation in hEDS/HSD, and suggests the baroreflex sensitivity might distinguish comorbid POTS from other profiles in this subgroup of patients. Abnormal autonomic regulation is common in adults with hEDS/HSD and should be regularly assessed for tailoring the management approach.

Pain due to Ehlers-Danlos Syndrome Is Associated with Deficit of the Endogenous Pain Inhibitory Control.

OBJECTIVES: Although pain is a common complication of the hypermobile type of Ehlers-Danlos syndrome, its underlying mechanisms are still an issue of controversy. In this psychophysical study, we aimed at testing small-fiber function and the endogenous pain inhibitory control in patients with pain due to Ehlers-Danlos syndrome. METHODS: In 22 patients with pain due to Ehlers-Danlos syndrome and 22 healthy participants, matched for age and sex, we tested small-fiber function using quantitative sensory testing and the endogenous pain inhibitory control using the conditioned pain modulation (CPM) protocol. As quantitative sensory testing methods, we included thermal pain and mechanical pain thresholds and the wind-up ratio. The CPM protocol consisted of two heat painful stimuli, that is, a test stimulus and a conditioning stimulus. RESULTS: All patients complained of widespread pain. Quantitative sensory testing revealed no small-fiber deficit; in the area of maximum pain, we found an increased wind-up ratio. Whereas in the healthy participants the CPM protocol showed that the test stimulus rating was significantly reduced during conditioning, in patients with pain due to hEDS, the test stimulus rating increased during conditioning. CONCLUSIONS: Our psychophysical study showing that patients with pain due to hEDS have an increased wind-up ratio in the area of maximum pain and abnormal CPM protocol suggests that in this condition, pain is associated with central sensitization, possibly due to deficit of the endogenous pain inhibitory control. These data might be relevant to pharmacological treatment.

Functional Evaluation Using Inertial Measurement of Back School Therapy in Lower Back Pain.

Lower back pain is an extremely common health problem and globally causes more disability than any other condition. Among other rehabilitation approaches, back schools are interventions comprising both an educational component and exercises. Normally, the main outcome evaluated is pain reduction. The aim of this study was to evaluate not only the efficacy of back school therapy in reducing pain, but also the functional improvement. Patients with lower back pain were clinically and functionally evaluated; in particular, the timed "up and go" test with inertial movement sensor was studied before and after back school therapy. Forty-four patients completed the program, and the results showed not only a reduction of pain, but also an improvement in several parameters of the timed up and go test, especially in temporal parameters (namely duration and velocity). The application of the inertial sensor measurement in evaluating functional aspects seems to be useful and promising in assessing the aspects that are not strictly correlated to the specific pathology, as well as in rehabilitation management.

Promoting post-stroke recovery through focal or whole body vibration: criticisms and prospects from a narrative review.

OBJECTIVE: Several focal muscle vibration (fMV) and whole body vibration (WBV) protocols have been designed to promote brain reorganization processes in patients with stroke. However, whether fMV and WBV should be considered helpful tools to promote post-stroke recovery remains still largely unclear. METHODS: We here achieve a comprehensive review of the application of fMV and WBV to promote brain reorganization processes in patients with stroke. By first discussing the putative physiological basis of fMV and WBV and then examining previous observations achieved in recent randomized controlled trials (RCT) in patients with stroke, we critically discuss possible strength and limitations of the currently available data. RESULTS: We provide the first systematic assessment of fMV studies demonstrating some improvement in upper and lower limb functions, in patients with chronic stroke. We also confirm and expand previous considerations about the rather limited rationale for the application of current WBV protocols in patients with chronic stroke. CONCLUSION: Based on available information, we propose new recommendations for optimal stimulation parameters and strategies for recruitment of specific stroke populations that would more likely benefit from future fMV or WBV application, in terms of speed and amount of post-stroke functional recovery.

Short-Term Effects of Focal Muscle Vibration on Motor Recovery After Acute Stroke: A Pilot Randomized Sham-Controlled Study.

Repetitive focal muscle vibration (rMV) is known to promote neural plasticity and long-lasting motor recovery in chronic stroke patients. Those structural and functional changes within the motor network underlying motor recovery occur in the very first hours after stroke. Nonetheless, to our knowledge, no rMV-based studies have been carried out in acute stroke patients so far, and the clinical benefit of rMV in this phase of stroke is yet to be determined. The aim of this randomized double-blind sham-controlled study is to investigate the short-term effect of rMV on motor recovery in acute stroke patients. Out of 22 acute stroke patients, 10 were treated with the rMV (vibration group-VG), while 12 underwent the sham treatment (control group-CG). Both treatments were carried out for 3 consecutive days, starting within 72 h of stroke onset; each daily session consisted of three 10-min treatments (for each treated limb), interspersed with a 1-min interval. rMV was delivered using a specific device (Cro®System, NEMOCO srl, Italy). The transducer was applied perpendicular to the target muscle's belly, near its distal tendon insertion, generating a 0.2-0.5 mm peak-to-peak sinusoidal displacement at a frequency of 100 Hz. All participants also underwent a daily standard rehabilitation program. The study protocol underwent local ethics committee approval (ClinicalTrial.gov NCT03697525) and written informed consent was obtained from all of the participants. With regard to the different pre-treatment clinical statuses, VG patients showed significant clinical improvement with respect to CG-treated patients among the NIHSS (p < 0.001), Fugl-Meyer (p = 0.001), and Motricity Index (p < 0.001) scores. In addition, when the upper and lower limb scales scores were compared between the two groups, VG patients were found to have a better clinical improvement at all the clinical end points. This study provides the first evidence that rMV is able to improve the motor outcome in a cohort of acute stroke patients, regardless of the pretreatment clinical status. Being a safe and well-tolerated intervention, which is easy to perform at the bedside, rMV may represent a valid complementary non-pharmacological therapy to promote motor recovery in acute stroke patients.

The effects of rotator cuff tear on shoulder proprioception.

PURPOSE: To evaluate the effects of rotator cuff tear (RCT) and its severity on shoulder proprioception. METHODS: We studied 132 consecutive patients (67 M-65 F; mean age ± SD, 66.03 ± 9.04; range, 43-78) who underwent arthroscopic rotator cuff repair. Tear size was determined intra-operatively. The control group included 82 subjects (38 M-44 F; mean age ± SD, 65.87 ± 8.06; range, 41-75) with no RCT. All participants, wearing an eye mask, were submitted to the evaluation of the joint position sense (JPS) at 30°, 60°, 90°, 120°, and 150° of shoulder forward flexion during the sitting position, using a digital inclinometer securely attached to the subject's arm using hook-and-loop straps. The passive placement and active replacement method was used; the order of the tested angles was randomly selected. The entire test was repeated three times. The error score, by averaging the three trials, was measured as the absolute difference between the target angle and the observed angle. Statistics were performed. RESULTS: The intraclass correlation coefficient for all degrees of flexion movement measured was > 0.90, exhibiting a very high correlation. We found significant differences between cases and controls regarding the results of joint position sense error at all measurements (p < 0.05). According to RCT size, we found significant differences between groups at 30° (F = 27.27, p < 0.001), 90° (F = 5.37, p = 0.006), 120° (F = 10.76, p < 0.001), and 150° (F = 30.93, p < 0.001) of shoulder flexion; in details, patients with massive RCT showed greater absolute error value than those with both small and large RCT at 30°, 90°, 120°, and 150° of shoulder flexion (p < 0.05). CONCLUSIONS: RCT provokes an alteration of shoulder proprioception, evaluated as the loss of joint position sense, and the impairment is related to tear severity.

Plasticity Induced in the Human Spinal Cord by Focal Muscle Vibration.

The spinal cord spinal cord has in the past been considered a hardwired system which responds to inputs in a stereotyped way. A growing body of data have instead demonstrated its ability to retain information and modify its effector capabilities, showing activity-dependent plasticity. Whereas, plasticity in the spinal cord is well documented after different forms of physical exercise, whether exogenous stimulation can induce similar changes is still a matter of debate. This issue is both of scientific and clinical relevance, since at least one form of stimulation, i.e., focal muscle vibration (fMV), is currently used as a treatment for spasticity. The aim of the present study was to assess whether fMV can induce plasticity at the SC level when applied to different muscles of the upper limb. Changes in different electrophysiological measures, such as H-reflex testing homonymous and heteronymous pathways, reciprocal inhibition and somatosensory evoked potentials were used as outcomes. We found that fMV was able to induce long-term depression-like plasticity in specific spinal cord circuits depending on the muscle vibrated. These findings helped understand the basic mechanisms underlying the effects of fMV and might help to develop more advanced stimulation protocols.

Gait evaluation using inertial measurement units in subjects with Parkinson's disease.

We investigated whether a wearable system based on a commercial Inertial Measurement Unit (IMU) can reliably provide the main spatiotemporal gait parameters in subjects with Parkinson's disease (PD), compared to a gold-standard optoelectronic motion capture system. The gait of 22 subjects with PD (Age: 69.4 (6.1) years; UPDRS-III: 28.0 (9.2)) was recorded simultaneously with an optoelectronic system and a commercial IMU-based wearable system. Eight spatiotemporal parameters describing the step cycle (cadence, velocity, stride length, stride duration, step length, stance, swing and double support duration) were compared between the two systems. The IMU and the optical system reported comparable gait parameters, with the exception of walking velocity (optical system, 0.72 (0.27) m∙s-1 vs. IMU: 0.86 (0.26) m∙s-1, p < 0.05). Although most parameters detected by the two systems were not statistically different, some of them like stride length, double support and step duration showed notable root mean square and mean absolute errors. In conclusion, the algorithm embedded in the current release of the commercial IMU requires further improvements to be properly used with subjects with PD. Overall, the IMU system was sufficiently accurate in the assessment of fundamental gait spatiotemporal parameters. The fast and simplified data recording process allowed by wearables makes this technology appealing and represents a possible solution for the quantification of gait in the clinical context, especially when using a traditional 3D optoelectronic gait analysis is not possible, and when subjects are not fully cooperative.