Physical Therapy and Nusinersen Impact on Spinal Muscular Atrophy Rehabilitative Outcome.

INTRODUCTION: Spinal muscular atrophy (SMA) is a progressive neurological disease with autosomal recessive transmission that affects motor neurons, causing their loss and resulting in muscle waste and motor deficiency. Nusinersen, the first SMN2 pre-mRNA targeted therapy approved by the Food and Drug Administration and the European Medicines Agency, has demonstrated high efficacy in improving motor function, as well as respiratory and nutritional statuses. MATERIALS AND METHODS: We observed 55 patients (children/adolescents) diagnosed with spinal muscular atrophy (SMA), who received nusinersen therapy. To investigate the benefits of physical therapy on rehabilitation outcomes, we compared the motor evolution of patients who received nusinersen and performed daily physical therapy (study group) to those of the control group, who received only nusinersen therapy. RESULTS: Motor skill improvements were statistically significantly (p < 0.001) higher in the study group, being almost four times better (12.66%), effect size, in comparison to the control group (3.18%). CONCLUSIONS: Physical therapy has provided superior results for those who receive it on a regular basis. These results include the correction of posture, reduction in stiffness, expansion of the range of motion and strengthening of muscles, thus allowing patients to do more movements and boosting their ability to perform everyday tasks.

Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke.

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that "non-pharmacological" approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.

Translation of the Fugl-Meyer assessment into Romanian: Transcultural and semantic-linguistic adaptations and clinical validation.

Purpose: The Fugl-Meyer Assessment (FMA) scale, which is widely used and highly recommended, is an appropriate tool for evaluating poststroke sensorimotor and other possible somatic deficits. It is also well-suited for capturing a dynamic rehabilitation process. The aim of this study was to first translate the entire sensorimotor FMA scale into Romanian using the transcultural and semantic-linguistic adaptations of its official afferent protocols and to then validate it using the preliminary clinical evaluation of inter- and intra-rater reliability and relevant concurrent validity. Methods: Through three main steps, we completed a standardized procedure for translating FMA's official afferent evaluation protocols into Romanian and their transcultural and semantic-linguistic adaptation for both the upper and lower extremities. For relevant clinical validation, we evaluated 10 patients after a stroke two times: on days 1 and 2. All patients were evaluated simultaneously by two kinesi-physiotherapists (generically referred to as KFT1 and KFT2) over the course of 2 consecutive days, taking turns in the roles of an examiner and observer, and vice versa (inter-rater). Two scores were therefore obtained and compared for the same patient, i.e., being afferent to an inter-rater assay by comparing the assessment outcomes obtained by the two kinesi-physiotherapists, in between, and respectively, to the intra-rater assay: based on the evaluations of the same kinesi-physiotherapist, in two consecutive days, using a rank-based method (Svensson) for statistical analysis. We also compared our final Romanian version of FMA's official protocols for concurrent validity (Spearman's rank correlation statistical method) to both of the widely available assessment instruments: the Barthel Index (BI) and the modified Rankin scale (mRS). Results: Svensson's method confirmed overall good inter- and intra-rater results for the main parts of the final Romanian version of FMA's evaluation protocols, regarding the percentage of agreement (≥80% on average) and for disagreement: relative position [RP; values outside the interval of (-0.1, 0.1) in only two measurements out of the 56 comparisons we did], relative concentration [RC; values outside the interval of (-0.1, 0.1) in only nine measurements out of the same 56 comparisons done], and relative rank variation [RV; all values within an interval of (0, 0.1) in only five measurements out of the 56 comparisons done]. High correlation values were obtained between the final Romanian version of FMA's evaluation protocols and the BI (ρ = 0.9167; p = 0.0002) for FMA-upper extremity (FMA-UE) total A-D (motor function) with ρ = 0.6319 and for FMA-lower extremity (FMA-LE) total E-F (motor function) with p = 0.0499, and close to the limit, with the mRS (ρ = -0.5937; p = 0.0704) for FMA-UE total A-D (motor function) and (ρ = -0.6615; p = 0.0372) for FMA-LE total E-F (motor function). Conclusions: The final Romanian version of FMA's official evaluation protocols showed good preliminary reliability and validity, which could be thus recommended for use and expected to help improve the standardization of this assessment scale for patients after a stroke in Romania. Furthermore, this endeavor could be added to similar international translation and cross-cultural adaptations, thereby facilitating a more appropriate comparison of the evaluation and outcomes in the management of stroke worldwide.

Non-invasive, non-pharmacological/bio-technological interventions towards neurorestoration upshot after ischemic stroke, in adults-systematic, synthetic, literature review.

Considering its marked life-threatening and (not seldom: severe and/or permanent) disabling, potential, plus the overall medico-psycho-socio-economic tough burden it represents for the affected persons, their families and the community, the cerebrovascular accident (CVA)-including with the, by far more frequent, ischemic type-is subject to considerable scientific research efforts that aim (if possible) at eliminating the stroke induced lesions, and consist, as well, in ambitious-but still poorly transferable into medical practice-goals such as brain neuroregeneration and/or repair, within related corollary/upshot of neurorestoration. We have conducted, in this respect, a systematic and synthetic literature review, following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" concept. Accordingly, we have interrogated five internationally renowned medical data bases: Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science (the last one to check whether the initially identified articles are published in ISI indexed journals), based on a large (details in the body text) number of most appropriate, to our knowledge, key word combinations/"syntaxes"-used contextually-and subsequently fulfilling the related, on five steps, filtering/selection methodology. We have thereby selected 114 fully eligible (of which contributive: 83-see further) papers; at the same time, additionally, we have enhanced our documentation-basically, but not exclusively, for the introductive part of this work (see further)-with bibliographic resources, overall connected to our subject, identified in the literature within a non-standardized search. It appears that the opportunity window for morph-functional recovery after stroke is larger than previously thought, actually being considered that brain neurorestoration/repair could occur, and therefore be expected, in later stages than in earlier ones, although, in this context, the number of cases possibly benefitting (for instance after physical and/or cognitive rehabilitation-including with magnetic or direct current transcranial stimulation) is quite small and with more or less conflicting, related outcomes, in the literature. Moreover, applying especially high intense, solicitating, rehabilitation interventions, in early stages post (including ischemic) stroke could even worsen the functional evolution. Accordingly, for clarifications and validation of more unitary points of view, continuing and boosting research efforts in this complex, interdisciplinary domain, is necessary. Until finding (if ever) effective modalities to cure the lesions of the central nervous system (CNS)-including post ischemic stroke-it is reasonable and recommendable-based on rigorous methodologies-the avail of combined ways: physiatric, pharmacologic, possibly also bio-technologic. On a different note, but however connected to our subject: periodic related systematic, synthetic literature reviews reappraisals are warranted and welcome.

Modulated Neuroprotection in Unresponsive Wakefulness Syndrome after Severe Traumatic Brain Injury.

BACKGROUND: We aimed to assess the effects of modulated neuroprotection with intermittent administration in patients with unresponsive wakefulness syndrome (UWS) after severe traumatic brain injury (TBI). METHODS: Retrospective analysis of 60 patients divided into two groups, with and without neuroprotective treatment with Actovegin, Cerebrolysin, pyritinol, L-phosphothreonine, L-glutamine, hydroxocobalamin, alpha-lipoic acid, carotene, DL-α-tocopherol, ascorbic acid, thiamine, pyridoxine, cyanocobalamin, Q 10 coenzyme, and L-carnitine alongside standard treatment. MAIN OUTCOME MEASURES: Glasgow Coma Scale (GCS) after TBI, Extended Glasgow Coma Scale (GOS E), Disability Rankin Scale (DRS), Functional Independence Measurement (FIM), and Montreal Cognitive Assessment (MOCA), all assessed at 1, 3, 6, 12, and 24 months after TBI. RESULTS: Patients receiving neuroprotective treatment recovered more rapidly from UWS than controls (p = 0.007) passing through a state of minimal consciousness and gradually progressing until the final evaluation (p = 0.000), towards a high cognitive level MOCA = 22 ± 6 points, upper moderate disability GOS-E = 6 ± 1, DRS = 6 ± 4, and an assisted gait, FIM =101 ± 25. The improvement in cognitive and physical functioning was strongly correlated with lower UWS duration (-0.8532) and higher GCS score (0.9803). CONCLUSION: Modulated long-term neuroprotection may be the therapeutic key for patients to overcome UWS after severe TBI.

Motor demyelinating tibial neuropathy in COVID-19.

Ten patients suffering from residual symptoms after the resolution of COVID-19, which manifested as fatigue in the lower limbs, have been submitted to nerve conduction studies. Motor demyelinating neuropathy features mainly of the tibial nerves but also the peroneal, median, and ulnar nerves were objectified. These findings might be considered as new neurological characteristics of SARS-CoV-2 infection.

Radial Extracorporeal Shockwave Therapy versus Ultrasound Therapy in Adult Patients with Idiopathic Scoliosis.

BACKGROUND: This study aimed to compare the effectiveness of radial extracorporeal shockwave and ultrasound therapies in adult patients with idiopathic scoliosis in terms of pain, disability, and quality of life. METHODS: Forty-eight patients with idiopathic scoliosis were randomly divided into three groups of 16: shockwave, ultrasound, and control. The patients were evaluated at admission (day one) and at discharge (day 14) for pain, by using the visual analogue scale; for disability, by using the Oswestry disability index; and for the quality of life, with short form-36. RESULTS: Radial extracorporeal shockwave therapy was more effective than ultrasound in reducing pain (p = 0.004) and increasing quality of life, bringing extra vitality (p = 0.003) and emotional comfort (p = 0.007) to the patient. Both shockwave therapy (p = 0.001) and ultrasound therapy (p = 0.003) were effective in reducing pain. In terms of disability, both treatments had similar effects (p = 0.439). CONCLUSION: Radial shockwave was significantly more effective than ultrasound in reducing pain and increasing the quality of life, bringing additional vitality and emotional comfort to the patient with idiopathic scoliosis. In terms of disability, both treatments had similar effects when associated with kinesitherapy.

Interferential electrical stimulation for improved bladder management following spinal cord injury.

Patients with spinal cord injury (SCI) with neurogenic bladder (NB) represent a major medical problem, which initiated the search for a non-invasive and effective treatment that is easy to apply and without side effects. A study was performed using interferential medium frequency current electrical stimulation (IMFC ES) on 332 patients shortly after SCI diagnosed with NB dysfunction. All subjects received standard care and patients of the experimental group additionally received IMFC ES. Urinary management results included volitional control of voiding, intermittent catheterization, post-voidance residuum (PVR) quantity and quantity of urine lost (LOSS). Results were assessed based on the American spinal cord injury association impairment scale (AIS). The IMFC ES included two channels of medium frequency stimulation that were marginally different. Within the body, a low frequency field was generated through the interaction of the medium frequencies, which stimulated the urinary structures. In the IMFC ES group, interference stimulation was applied for 10 min with frequencies cycling from 0-100 Hz and back in 10 sec intervals. The strength of the low frequency stimulation, achieved by the interference of the two medium-frequency fields, was adjusted to the patients' vibration sensation. The intensities triggering vibration sensation were between 20-80 mA for patients with AIS levels B, C and D. For patients with AIS level A intensities <20 mA were used for therapeutic effects without causing skin injuries. Safety of IMFC ES was based on occurrence of adverse events of which none were recorded in the experimental group. IMFC ES was effective in patients with AIS levels B and C, significantly decreasing PVR and LOSS compared with patients receiving standard care No significant improvements in urinary management were observed following IMFC ES treatment of patients with AIS level A. Patients with SCI and NB classed as AIS levels B and C that exhibit preserved sensitivity were the best beneficiaries of IMFC ES therapy.

Mobile Mechatronic/Robotic Orthotic Devices to Assist-Rehabilitate Neuromotor Impairments in the Upper Limb: A Systematic and Synthetic Review.

This paper overviews the state-of-the-art in upper limb robot-supported approaches, focusing on advancements in the related mechatronic devices for the patients' rehabilitation and/or assistance. Dedicated to the technical, comprehensively methodological and global effectiveness and improvement in this inter-disciplinary field of research, it includes information beyond the therapy administrated in clinical settings-but with no diminished safety requirements. Our systematic review, based on PRISMA guidelines, searched articles published between January 2001 and November 2017 from the following databases: Cochrane, Medline/PubMed, PMC, Elsevier, PEDro, and ISI Web of Knowledge/Science. Then we have applied a new innovative PEDro-inspired technique to classify the relevant articles. The article focuses on the main indications, current technologies, categories of intervention and outcome assessment modalities. It includes also, in tabular form, the main characteristics of the most relevant mobile (wearable and/or portable) mechatronic/robotic orthoses/exoskeletons prototype devices used to assist-rehabilitate neuromotor impairments in the upper limb.

Evolution of traumatic spinal cord injury in patients with ankylosing spondylitis, in a Romanian rehabilitation clinic.

The ankylosing spondylitis (AS) is a systemic, multi-factorial, chronic rheumatic disease. Patients are highly susceptible to vertebral fractures with or without spinal cord injury (AS-SCI), even after a minor trauma. The study is a retrospective descriptive survey of post-acute, traumatic AS-SCI patients, transferred from the neurosurgical department and admitted in a Romanian Neurorehabilitation Clinic, during 2010-2014. There were 11 males associating AS-SCI (0.90% of all consecutive SCI admitted cases), with an average age of 54.6 years (median 56, limits 42-73 years). The average duration between the medically diagnosed AS and the actual associated spinal fracture(-s) moment was 21.4 years (median 23; limits 10-34 years). Low-energy trauma was incriminated in 54.5% cases. The spinal level of fracture was: cervical (four cases), thoracic (three), lumbar (four), assessed at admission as: American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (four subjects), C (five) and D (two). By the time of discharge, neither patient has neurologically deteriorated; five patients (45.5%) improved of at least grade 1 (AIS). The overall complications were mainly infections: symptomatic urinary tract infections (seven patients; 63.6%), pulmonary (three subjects; 27.3%) and spondylodiscitis (one case; 9%). The average follow-up period was 15.3 months (median 12; limits 1-48 months) after discharge; three subjects gained functional improvement to AIS-E. The clinical profile (different risk factors, mechanisms, types and levels of spinal fractures, additional encephalic and/or cord lesions, co-morbidities), different post-surgical and/or general complications acquired during admission in our rehabilitation ward, served us for future prevention strategies and a better therapeutic management.