Technology Assisted Rehabilitation Patient Perception Questionnaire (TARPP-Q): development and implementation of an instrument to evaluate patients' perception during training.

BACKGROUND: The introduction of technology-assisted rehabilitation (TAR) uncovers promising challenges for the treatment of motor disorders, particularly if combined with exergaming. Patients with neurological diseases have proved to benefit from TAR, improving their performance in several activities. However, the subjective perception of the device has never been fully addressed, being a conditioning factor for its use. The aims of the study were: (a) to develop a questionnaire on patients' personal experience with TAR and exergames in a real-world clinical setting; (b) to administer the questionnaire to a pilot group of neurologic patients to assess its feasibility and statistical properties. METHODS: A self-administrable and close-ended questionnaire, Technology Assisted Rehabilitation Patient Perception Questionnaire (TARPP-Q), designed by a multidisciplinary team, was developed in Italian through a Delphi procedure. An English translation has been developed with consensus, for understandability purposes. The ultimate version of the questionnaire was constituted of 10 questions (5 with multiple answers), totalling 29 items, exploring the patient's performance and personal experience with TAR with Augmented Performance Feedback. TARPP-Q was then administered pre-post training in an observational, feasible, multi-centric study. The study involved in-patients aged between 18 and 85 with neurological diseases, admitted for rehabilitation with TAR (upper limb or gait). FIM scale was run to control functional performance. RESULTS: Forty-four patients were included in the study. All patients answered the TARPP-Q autonomously. There were no unaccounted answers. Exploratory factor analyses identified 4 factors: Positive attitude, Usability, Hindrance perception, and Distress. Internal consistency was measured at T0. The values of Cronbach's alpha ranged from 0.72 (Distress) to 0.92 (Positive attitude). Functional Independence Measure (FIM®) scores and all TARPP-Q factors (Positive attitude, Usability, Hindrance perception, except for Distress (p = 0.11), significantly improved at the end of the treatment. A significant positive correlation between Positive attitude and Usability was also recorded. CONCLUSIONS: The TARPP-Q highlights the importance of patients' personal experience with TAR and exergaming. Large-scale applications of this questionnaire may clarify the role of patients' perception of training effectiveness, helping to customize devices and interventions.

The patient-caregiver dyad: the impact of cognitive and functional impairment.

This study evaluates the cognitive impairment impact on the caregiver's burden and quality of life.Patient-caregiver dyads admitted to dementia Diagnostic-Therapeutic Care Pathway underwent a psychological and neuropsychological assessment. Overall, 30 caregivers (age 58.97 ± 14.68) of patients with dementia and 28 caregivers (age 58.57 ± 12.22) of patients with MCI were recruited. Caregiver's burden is positively correlated to the number (r = .37, p = .003) and severity (r = .37, p = .003) of neuropsychiatric patient's symptoms and with the caregiver's distress (r = .36, p = .004). It is also negatively related to good quality of life perception (r = - .52, p = < .0001), to lower cognitive impairment (r = - .26, p = .05), to higher patient's residual functional abilities in daily living (r = - .32, p = .010) and to positive perception of the physician's communication (r = - .28, p = .026). Moreover, the caregiver's burden is significantly predicted by the patient's low level of instrumental activity of daily living (ß = - .74; p = .043) and by the number of neuropsychiatric symptoms (ß = .74; p = .029). Thus, this study suggests that the autonomy and neuropsychiatric symptoms may determine the caregiver's burden.

Music listening for people living with dementia: a systematic review.

SUMMARY: This review aimed at exploring how music listening-based approach can be effective on physiological, cognitive and behavioural aspects, with specific reference to the domain of dementias. Music listening can be considered one of the most common approaches in dementia care, frequently in combination with other non-pharmacological treatments. This type of intervention may allow persons with dementia to work on the organization and regulation of their emotions thanks to the mediation of the sonorous-musical element. Methods. Two independent researchers performed literature search by consulting the PUBMED database and the Cochrane Register of randomized controlled trials (articles written in English and published from January 1st 2000 to February 28th 2022 were considered as eligible). Results. Twelve articles met the inclusion criteria and were included in this review. The selected studies highlighted some effects of music listening in people with moderate to severe dementia. Assuming a clinical point of view, the results showed how music listening intervention could bring benefits on the behavioural and psychological symptoms of dementia, also if not always statistically significant. Discussion/Conclusion. The study focused on the need to define clear criteria of music listening programs selection and administration, but also on the involvement of trained music therapists in planning and managing the music listening-based interventions. Music listening interventions should be developed by implementing evidence-based practice and integrating research in the field. The identification of specific musical elements connected with the therapeutic outcome is a key point for the music therapy future.

Inhibition of Somatosensory Evoked Potentials During Different Modalities of Spinal Cord Stimulation: A Case Report.

BACKGROUND: Although the number of patients with chronic neuropathic pain treated by spinal cord stimulation (SCS) is continuously increasing, its analgesic mechanism remains to be elucidated. Previous studies have demonstrated that classical SCS (low stimulation frequency evoking paresthesia) inhibits the somatosensory evoked potentials (SEPs). CASE PRESENTATION: We describe here the results of a series of SEPs recordings performed in a female patient with chronic pain, using four different types of SCS: the classical SCS (60 Hz, 250 µsec) and three paresthesia free SCS modalities: high frequency (10 kHz, 20 µsec) and two types of high-density SCS (500 Hz, 500 µsec and 200 Hz, 1000 µsec). All the tested SCS modalities completely inhibited the SEPs cortical responses, with an immediate recovery of the inhibition after turning the stimulator off. CONCLUSIONS: All the tested SCS modalities are able to inhibit SEPs and thus the lemniscal system. In particular, both paresthesia and paresthesia free SCS affect SEPs in the same manner. The presence of this inhibitory effect during paresthesia free modalities suggests that it is independent from the generation of action potentials, with a probable mechanism acting at the stimulation site. Further studies investigating the relationship between the inhibition of the lemniscal system and the analgesic effect of the SCS are, therefore, warranted.

Dynamic Mechanical Allodynia--One Clinical Sign, Several Mechanisms: Five Illustrative Cases.

Pain evoked by tangential movement across the skin is usually defined as dynamic mechanical allodynia (DMA). Some patients complain of DMA as troublesome as spontaneous pain and refer a marked interfering with activities of daily living and sleep. Pathophysiology of DMA is complex and can be related to several mechanisms, both nociceptive and neuropathic. Five exemplificative clinical cases of DMA are presented, each associated to a possible specific mechanism: injured skin DMA, peri-injured skin DMA, far injury DMA, nerve-confined DMA and fear DMA (pseudo allodynia). The identification of these subcategories of DMA can stimulate further studies aimed at evaluating the usefulness of a mechanism-based therapy for the different clinical forms of DMA.

Excessive daytime sleepiness in patients on intrathecal analgesia for chronic pain.

OBJECTIVES: Intrathecal (IT) drug administration is an advanced technique in pain treatment algorithm for patients poorly responsive to systemic pharmacological treatment or less invasive techniques. The aim is to improve analgesia lowering side effects; despite this premise, many side effects of long-term IT therapy have been described, mainly related to opioid administration. We observed, in some of the patients regularly followed for pump refills in our Pain Unit, the appearance of excessive daytime sleepiness (EDS) interfering with daily life and work activity; this study aims to investigate the incidence of EDS in patients on IT analgesia with opioid or non-opioid drugs and its possible relationship with respiratory problems during sleep. MATERIALS AND METHODS: 21 patients on IT therapy for chronic pain answered the Epworth Sleepiness Scale (ESS). The incidence of EDS in patients receiving IT opioids was compared to a control group not receiving opioids. In 10 patients, who performed polysomnography (PSG) and maintenance of wakefulness test (MWT) for sleep complaints, we studied the relationship between PSG data and ESS scores and we verified the concordance of ESS and MWT results. RESULTS: 38% of the patients reported EDS, according to ESS data; all the patients with EDS were receiving an IT opioid. Even if some patients presented sleep apneas, we failed to correlate this data with daytime sleepiness. Subjective sleepiness is confirmed by the results of MWT. CONCLUSION: Our data demonstrate that EDS is a frequent and important side effect of IT analgesia and it seems related to opioids administration.

Pain and thyroid hormones.

The role of endocrine systems in chronic pain mechanisms is slowly getting increasing experimental and clinical consideration. Many painful conditions appear to be directly and/or indirectly induced, reduced or, in some cases, modulated by hormones. We have done much work in trying to understand the relationship between hormones and pain, with particular attention to the hypothalamus-pituitary-gonadal axis. To expand our knowledge of this field, we have directed our attention to another axis, the hypothalamus-pituitary-thyroid (HPT). The literature on thyroid functions is vast but very few studies have focused on the HPT axis and pain. The few available data are considered in the present review to stimulate interest in the possible interactions between the HPT axis and pain.

Allodynic skin in post-herpetic neuralgia: histological correlates.

Most post-herpetic neuralgia (PHN) patients suffer from tactile allodynia (pain evoked by lightly touching the skin) and it is frequently the dominant clinical manifestation. The pathophysiology of tactile allodynia in PHN patients is poorly understood and this is one of the major limits to the development of appropriate therapies. Epidermal nerve fibres (ENFs) are free nerve endings of small-diameter A-delta and C primary afferents, which can easily be assessed by neurodiagnostic skin biopsy (NSB). The aim of this study was to establish the correlation between the residual epidermal innervation of the allodynic skin and the intensity of tactile allodynia in that area. Twenty-five patients (13 males and 12 females) with PHN were enrolled. Eighteen patients had PHN in the thoracic dermatome, four in the cervical, two in the trigeminal and one in the lumbar. The severity of allodynia evoked by a paintbrush was graded according to an eleven-point numerical scale. A skin biopsy was obtained from the maximal allodynia area and from the contralateral skin. Nerve fibres were labelled with indirect immunofluorescence. Results showed that epidermal innervation was lower in the allodynic skin than in the contralateral skin, although there was great variability among patients. There was no correlation between severity of allodynia and epidermal innervation of the PHN skin. In conclusion, the present study further indicates peripheral nervous system involvement in PHN but does not support a direct correlation between epidermal innervation changes and tactile allodynia.

Unusual sensory-motor neuropathies in post-COVID-19 patients admitted in rehabilitation hospitals: a case-series.

BACKGROUND: Several neurological complications occurred in SARS-CoV-2 disease (COVID-19), mainly related to inflammatory and vascular disorders. The involvement of the peripheral nervous system (PNS) has been mostly reported as Guillain-Barré Syndrome, while focal peripheral neuropathies have been rarely described. CASE REPORT: We report the cases of ten patients hospitalized in Rehabilitation Units after COVID-19, who presented severe focal motor involvement. Electrophysiological investigations revealed focal sensory-motor neuropathies, atypical for many aspects: bilaterality, location and contemporary involvement of different nervous districts. We speculate that their pathogenesis is possibly related to prolonged abnormal postures maintained during hospitalization in Intensive Care Unit, virus neurotropism and thrombotic vascular damage involving vasa nervorum. CLINICAL REHABILITATION IMPACT: Motor neuropathies could induce severe disability and their early recognition in post COVID-19 patients is of primary importance for a specific rehabilitation treatment.

Pathological nerve patterns in human basal cell carcinoma.

The peculiar combined, or binary involvement of epithelium and stroma makes basal cell carcinoma (BCC) a unique tumour. Nerve fibres have been shown to play an active role in different cancers. A prospective observational study was carried out on punch biopsies harvested within BCC surgical excision specimens. A total of 10 samples of histologically diagnosed BCC, derived from 10 different patients (five females, five males), was included in the study. Within the BCCs, seven different histological sub-types were identified: morphea-like, basosquamous, micronodular, mixed nodular-micronodular, adenoid, nodular and superficial multifocal. Nerve fibres were stained for indirect immunofluorescence targeting protein gene product 9.5. Three different morphological patterns of nerve fibre distribution within the BCCs were identified. Pattern 1 displayed a normal skin nerve pattern, in which the fibres were dislodged by the growing tumour masses. Pattern 2 featured a ball of curved, tangled nerve fibres close to the tumour masses, slightly resembling piloneural collar nerve fibres, wrapped around hair follicles in the normal anatomical setting. Pattern 3 showed nerve fibres crowding in the sub-epidermal layer with focal epidermal hyperinnervation. Such a pattern is reminiscent of the typical anatomical neuro-epithelial interaction in mechanosensory organs. Our study may disclose a hidden third player, of nerves. Thus, tissue involvement of BCCs may be better represented by the triad of epithelium, stroma and nerves, each component retaining some features associated with its developmental setting.

Vertebral body innervation: Implications for pain.

Vertebral fractures often cause intractable pain. To define the involvement of vertebral body innervation in pain, we collected specimens from male and female patients during percutaneous kyphoplasty, a procedure used for reconstruction of the vertebral body. Specimens were taken from 31 patients (9 men and 22 women) suffering high-intensity pain before surgery. In total, 1,876 histological preparations were obtained and analysed. Immunohistochemical techniques were used to locate the nerves in the specimens. The nerve fibres were labelled by indirect immunofluorescence with the primary antibody directed against Protein Gene Product 9.5 (PGP 9.5), a pan-neuronal marker; another primary antibody directed against type IV collagen (Col IV) was used to identify vessels and to determine their relationship with vertebral nerve fibres. The mean percentage of samples in which it was possible to identify nerve fibres was 35% in men and 29% in women. The percentages varied depending on the spinal level considered and the sex of the subject, nerve fibres being mostly present around vessels (95%). In conclusion, there is scarce innervation of the vertebral bodies, with a clear prevalence of fibres located around vessels. It seems unlikely that this pattern of vertebral body innervation is involved in vertebral pain or in pain relief following kyphoplasty.

Quantitative Sensory Testing (QST) Estimation of Regional Cutaneous Thermal Sensitivity During Waking State, Neutral Hypnosis, and Temperature Specific Suggestions.

This study aimed to determine the effects of neutral hypnosis and hypnotic temperature suggestions in thermal and pain thresholds compared to resting state. Sixteen healthy medium or high hypnotizable volunteers were enrolled. Hypnotizability was assessed with the Hypnotic Induction Profile (HIP); QST was checked in resting state, in neutral hypnosis, after suggestions of heat and cold, and after deinduction. A significant increase in heat threshold was recorded during hypnosis with both cold and heat suggestions compared to neutral hypnosis. HIP induction score showed a linear correlation with changes of temperature thresholds after heat and cold suggestions. Thermal suggestions may result in a significant increase of heat perception thresholds with respect to neutral hypnosis. HIP score is related to thermal threshold changes. QST is a valuable and manageable tool to measure temperature threshold change during hypnosis.

Effect of Botulinum Toxin on Disabling Neuropathic Pain: A Case Presentation Suggesting a New Therapeutic Strategy.

This case presentation describes a 47-year-old woman who developed complex regional pain syndrome type II with severe neuropathic pain following iatrogenic transection of the tibial nerve at the ankle. The pain and disability progressively worsened over time, markedly impaired ambulation, and were not relieved despite various analgesic treatments. After injection of botulinum toxin (abobotulinumtoxinA, BoNT-A) in the leg muscles the tendons of which pass through the tarsal tunnel (together with the tibial nerve), her pain decreased and her walking capacity improved. This case suggests a new therapeutic role for botulin toxin in treating peripheral neuropathic pain caused by movement-evoked ectopic potentials. LEVEL OF EVIDENCE: V.

Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in a patient-specific model of recessive catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse model of the disease homozygous carrier of the R33Q mutation. In the present study, we investigated the efficacy of the virally mediated gene therapy in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs) obtained from a patient carrying the homozygous CASQ2-G112+5X mutation. To this end, we infected cells with an Adeno-Associated Viral vector serotype 9 (AAV9) encoding the human CASQ2 gene (AAV9-hCASQ2). Administration of the human WT CASQ2 gene was capable and sufficient to restore the physiological expression of calsequestrin-2 protein and to rescue functional defects of the patient-specific iPSC-derived CMs. Indeed, after viral gene transfer, we observed a remarkable decrease in the percentage of delayed afterdepolarizations (DADs) developed by the diseased CMs upon adrenergic stimulation, the calcium transient amplitude was re-established and the density and duration of calcium sparks were normalized. We therefore demonstrate the efficacy of the AAV9-mediated gene replacement therapy for CPVT2 in a human cardiac-specific model system, supporting the view that the gene-therapy tested is curative in models with different human mutations of CPVT.

Usefulness of BFB/EMG in facial palsy rehabilitation.

OBJECTIVE: To analyze and to compare the recovery and the development of synkinesis in patients with idiopathic facial palsy (Bell's palsy) following treatment with two methods of rehabilitation, kinesitherapy (KT) and biofeedback/EMG (BFB/EMG). STUDY DESIGN: Retrospective cases--series review. METHODS: Seventy-four patients with Bell' palsy were clinically evaluated within 1 month from onset of palsy and at 12 months after palsy (House scale and synkinesis evaluation). Electromyography (EMG) and Electroneurography (ENG) were performed about 4 weeks after palsy to better evaluate functional abnormalities due to facial nerve lesion. The patients followed two different protocols for rehabilitation: the first 32 patients were treated with therapeutic exercises performed by therapists (KT group), the latter 42 patients were treated using BFB/EMG methods (BFB group) with inhibition of synkinetic movement as the primary goal. RESULTS: KT and BFB patients were evaluated for clinical and neurophysiological characteristics before rehabilitative treatment. BFB patients showed better clinical recovery and minor synkinesis than KT patients. CONCLUSIONS: BFB/EMG seems to be more useful than KT in Bell's palsy treatment. This could be due to the fact that BFB/EMG gives more accurate information than KT on muscle activation with better modulation in voluntary recruitment of motor unit.

Where is hidden the ghost in phantom sensations?

The term phantom sensations (PS) refers to sensations in a missing body part. They are almost universal in amputees and can be both painful and not painful. Although PS have been frequently described in limb amputees, they can also occur in other clinical conditions and several pathophysiological interpretations have been proposed, with a predominance of theories based on a central origin. Actually, different mechanisms are able to create a phantom sensation. After an amputation, PS are frequently generated by the genesis of ectopic action potentials in the interrupted nerve fibers but the PS generator can also be more proximal. Sometimes PS are not created by the stimulation of somatosensory fibers with a missing territory, but they can be the result of central sensitization or neuroplastic changes that allow for the convergence of impulses coming from different body parts (referred sensations), one of which is missing. In conclusion, PS can be generated by both neuropathic and non-neuropathic mechanisms developed in the amputated body part or in other parts of the nervous system. Since these mechanisms are not pathognomonic of amputation there are no hidden ghosts to look for in phantom sensations. The only interpretative rule is just to follow the pathophysiological principles.

Contralateral antalgic effect of high-frequency transcutaneous peripheral nerve stimulation.

OBJECTIVE: To investigate the analgesic effect of high-frequency transcutaneous peripheral nerve stimulation (HF-TPNS) in the ipsilateral and contralateral skin territory of the stimulated nerve. DESIGN: Prospective, cross-over study. SETTING: Clinical neurophysiology unit, institutional care, rehabilitation center. PARTICIPANTS: Ten healthy volunteers (5 male, 5 female). METHODS: Participants underwent 3 different sessions. In the first, heat pain thresholds (HPTs) were measured on the left dorsal hand skin without stimulation; in the second and third sessions, HPTs were measured, respectively, in the territory of the left and right radial nerve before, during, and after an electrical stimulation (10 minutes, 100 Hz, 0.1 ms) of the left superficial radial nerve. MAIN OUTCOME MEASUREMENT: Heat pain threshold. RESULTS: An increase of HPTs was observed in the skin territory of both right and left radial nerve during and after the left radial nerve stimulation. CONCLUSION: The present study demonstrates an analgesic effect of HF-TPNS not only in the ipsilateral but also in the contralateral side of stimulation, suggesting a possible role of contralateral HF-TPNS in the treatment by physical therapy of patients with unilateral pain syndromes.

The role of ischaemia in the analgesia which follows Bier's block technique.

The effect of 30-min tourniquet ischaemia (Bier's block) on the antidromic homolateral left median nerve sensory potential (SP) and on the bilateral sympathetic skin response (SSR) was studied in 6 healthy volunteers. The SSR was provoked both acoustically and by electrical stimulation of the median nerve; the latter stimulus was also used to provoke the SP. After 28 min of tourniquet ischaemia, the electrical stimulus failed to provoke the SP and bilateral SSR, indicating blockade of the afferent limb of the reflex. The acoustic SSR was unaffected by ischaemia, and thus the efferent limb of the SSR was not blocked, indicating that ischaemia does not affect the post-ganglionic efferent C fibres. These findings confirm that 30 min of ischaemia blocks A beta afferent fibres but does not block efferent C fibres. Thus the analgesia following Bier's block alone, in some patients with sympathetically maintained pain, most likely results from the ischaemic blockade of sensory A beta fibres, confirmed both acoustically and by electrical stimulation of the median nerve.

Unilateral peripheral neuropathic pain: The role of neurodiagnostic skin biopsy.

According to the current definition of neuropathic pain ("pain arising as a direct consequence of a lesion or disease affecting the somatosensory system"), the demonstration of a lesion or disease involving the somatosensory system is mandatory for the diagnosis of definite neuropathic pain. Although several methods are currently available for this aim, none is suitable for every type of disease (or lesion). Neurodiagnostic skin biopsy (NSB) is a relatively new technique for the diagnosis of peripheral nerve lesions. It is an objective method, completely independent from the patient's complaining, based on immunohistochemical staining techniques that allow measurement of the density of the epidermal nerve fibers, currently considered the free nerve endings of small diameter (A-delta and C) afferent fibers. NSB has the important property of being used to investigate the skin, allowing obtaining a diagnosis of small fiber axonal neuropathy of peripheral nerves supplying every body part covered by skin. This feature appears to be very important, particularly in cases of unilateral nerve lesions, because it allows going beyond the possibilities of neurophysiological tests which are available only for a limited number of peripheral nerves. All these characteristics make NSB a precious instrument for the diagnosis of peripheral unilateral neuropathic pain.