Botulinum Toxin-A High-Dosage Effect on Functional Outcome and Spasticity-Related Pain in Subjects with Stroke.

Stroke patients can develop spasticity and spasticity-related pain (SRP). These disorders are frequent and can contribute to functional limitations and disabling conditions. Many reports have suggested that higher doses than initially recommended of BTX-A can be used effectively and safely, especially in the case of severe spasticity; however, whether the treatment produces any benefit on the functional outcome and SRP is unclear. Studies published between January 1989 and December 2022 were retrieved from MEDLINE/PubMed, Embase, and Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA, (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term "high dosage" indicates ≥600 U. Nine studies met the inclusion criteria. Globally, 460 subjects were treated with BTX-A high dose, and 301 suffered from stroke. Studies had variable method designs, sample sizes, and aims. Only five (55.5%) reported data about the functional outcome after BTX-A injection. Functional measures were also variable, and the improvement was observed predominantly in the disability assessment scale (DAS). SRP pain was quantified by visual analog scale (VAS) and only three studies reported the BTX-A effect. There is no scientific evidence that this therapeutic strategy unequivocally improves the functionality of the limbs. Although no clear-cut evidence emerges, certain patients with spasticity might obtain goal-oriented improvement from high-dose BTX-A. Likewise, data are insufficient to recommend high BTX dosage in SRP.

Recovery and long term functional outcome in people with critical illness polyneuropathy and myopathy: a scoping review.

BACKGROUND: Intensive care unit acquired weakness (ICUAW), embraces an array of disorders labeled "critical illness polyneuropathy" (CIP), "critical illness myopathy" (CIM) or "critical illness polyneuromyopathy" (CIPNM). Several studies have addressed the various characteristics of ICUAW, but the recovery is still unclear. OBJECTIVE: The present review investigated the recovery and the long-term functional outcome of subjects with ICUAW, whether the types of ICUAW have different outcomes and whether there is any supporting evidence. METHODS: Literature search was performed from MEDLINE/PubMed, CINAHL, EMBASE, PeDro, Web of Science and Scopus. Inclusion criteria were: i) sample size including five or more subjects; ii) subjects who suffered from ICUAW and/or CIP, CIM and CIP/CIM; iii) ICUAW ascertained by EMG. Follow-ups longer than one year were defined as long-term. RESULTS: Twenty-nine studies met the inclusion criteria. In total, 788 subjects with ICUAW were enrolled: 159 (20.1%) died and 588 (74.6%) were followed. Of all the included patients, 613 (77.7%) had CIP, 82 (10.4%) CIM and 56 (7.1%) CIP/CIM. Overall, 70.3% of the subjects with ICUAW fully recovered. Seven (24.1%) studies had a follow-up longer than 1 year (range 2-8) with 173 (21.9%) subjects enrolled globally and 108 followed. Of these subjects, 88.8% gained full recovery. Most of the studies did not use proper functional scales and only 4 and 3 studies employed the Barthel scale and the Functional Independence Measure (FIM) scale. Differentiation between the types of ICUAW was performed in 7 studies, but only 3 studies reported that subjects with CIM had a better prognosis and earlier recovery than subjects with CIP/CIM. CONCLUSIONS: Subjects with ICUAW could achieve good recovery and could improve at follow-up. However, the quality of the published studies due to short follow-ups and the paucity of defined outcome measures require confirms.

Critical Illness Polyneuropathy and Functional Outcome in Subjects with Covid-19: Report on Four Patients and a Scoping Review of the Literature.

Patients with COVID-19 may develop a range of neurological disorders. We report here 4 COVID-19 subjects with intensive care unit-acquired weakness and their functional outcome. In addition, a scoping review of COVID-19 literature was performed to investigate this issue. Of the post-COVID-19 patients admitted to our Neuro-Rehabilitation Unit, 4 (3 males, 1 female; mean age 59.2 ± 8.62 years) had intensive care unit-acquired weakness, diagnosed with electromyography. Muscle strength and functional evaluation were performed on all patients with Medical Research Council, Disability Rating Scale and Functional Independence Measure, respectively, at admission, discharge and 6-month follow-up after discharge. Electromyography revealed that 3 subjects had critical illness polyneuropathy and 1 had critical illness polyneuropathy/critical illness myopathy. At follow-up, the 3 subjects with critical illness polyneuropathy reached full recovery. The patient with critical illness polyneuropathy/critical illness myopathy showed moderate disability requiring bilateral ankle foot-orthosis and support for ambulation. The scoping review retrieved 11 studies of COVID-19 patients with intensive care unit-acquired weakness, concerning a total of 80 patients: 23 with critical illness myopathy (7 probable), 21 with critical illness polyneuropathy (8 possible), 15 with critical illness polyneuropathy and myopathy (CIPNM) and 21 with intensive care unit-acquired weakness. Of 35 patients who survived, only 3 (8.5%) reached full recovery. All 3 had critical illness myopathy, but 2 of these had a diagnosis of probable critical illness myopathy. Intensive care unit-acquired weakness commonly occurred in subjects with COVID-19. Recovery was variable and a low percentage reached full recovery. However, the heterogeneity of studies did not allow definitive conclusions to be drawn.

High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at?

Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term "high dosage" indicated ≥ 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable.

Vitamin D serum level in subjects with critical illness polyneuropathy and myopathy.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a disabling neuropathy that occurs in intensive care unit (ICU) subjects. It was hypothesized that a low serum level or deficiency of 25(OH)D might be associated with CIPNM. The aim of the present study was to ascertain the 25(OH)D serum level in subjects with CIPNM. METHOD: Consecutive ICU patients admitted to neuro-rehabilitation were prospectively enrolled. At admission, vitamin D serum levels were measured and EMG examination was performed to ascertain those with CIPNM. 25(OH)D was stratified as sufficient (≥30 ng/mL) insufficient (20-29.9 ng/mL), and deficient (<20 ng/mL). RESULTS: Eighty-four patients (31 F, 53 M; mean age 51.7±12.6) were identified and 63 (21 F, 42 M) enrolled. CIPNM was detected in 38 (9 F, 29 M) patients. A deficient mean serum level of vitamin D was observed in the whole population: 18.1 ± 9.2 ng/mL. No difference of vitamin D serum levels was detected in subjects with and without CIPNM: 17.5 ± 8.4 and 19.0 ± 10.5 ng/mL (p=0.58), respectively. CONCLUSION: Almost all subjects showed Vitamin D deficiency. No difference was detected between those with and without CIPNM. The condition might represent a secondary phenomenon resulting from the inflammatory process as well as from conditions that could interfere with vitamin D metabolism.

The Role of Rehabilitation in Patients With Progressive Supranuclear Palsy: A Narrative Review.

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder caused by the deposition of abnormal proteins in neurons of the basal ganglia that limit motor ability, resulting in disability and reduced quality of life. So far, no pharmacologic therapy has been developed, and the treatment remains symptomatic. The aim of the present study is to perform a systematic investigation of the literature, and to determine the types and effects of rehabilitative interventions used for PSP. A search of all studies was conducted in MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL, and EMBASE. Twelve studies were identified, including 6 case reports, 3 case series, one case-control study, one quasi-randomized trial (i.e. not truly random) with crossover design, and one randomized controlled trial, with 88 patients investigated overall. Rehabilitative interventions varied in type, number, frequency, and duration of sessions. The most commonly used clinical measures were the Progressive Supranuclear Palsy Rating Scale (PSPRS) and Unified Parkinson's Disease Rating Scale (UPDRS). Physical exercises were the main rehabilitative strategy but were associated with other interventions and rehabilitative devices, in particular treadmill and robot-assisted gait training. All studies showed an improvement in balance and gait impairment with a reduction of falls after rehabilitation treatment. Because of poor methodological quality and the variety of rehabilitative approaches including different and variable strategies, there was insufficient evidence of the effectiveness of any specific rehabilitation intervention in PSP. Despite this finding, rehabilitation might improve balance and gait, thereby reducing falls in PSP patients. LEVEL OF EVIDENCE: IV.

Functional outcome of critical illness polyneuropathy in patients affected by severe brain injury.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) frequently occur in intensive care unit (ICU) critically ill subjects; about 55-70% of subjects achieve full recovery. CIPNM can occur in ICU subjects with severe acquired brain injury (sABI), but no data have been reported regarding their outcome. AIM: The aim of the present study was to investigate the functional recovery in subjects suffering from both CIPNM and sABI and whether they had poorer outcome than those with sABI only. DESIGN: Prospective cohort study. SETTING: Dedicated rehabilitation setting. POPULATION: Adult ICU subjects with sABI causing a disorder of consciousness graded 3-8 on the Glasgow Coma Scale admitted to a dedicated rehabilitative setting were enrolled from January 2015 to June 2016. METHODS: The enrolled sample was divided in two groups: patients with CIPNM and coexistent sABI (CIPNM+sABI) and patients with sABI. Electromyography was performed in all subjects to ascertain CIPNM occurrence, at admission. Functional outcome was investigated using the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS), at admission and discharge. Mortality and length of stay (LOS) were recorded. RESULTS: One-hundred and thirty-one patients (59 F, 72 M; mean age 54.7±15.8) were admitted to the rehabilitation setting, and 111 (47 F, 64 M; mean age: 53.6±18.4 years) were enrolled. Thirty-six (31.8%) had CIPNM+sABI, and 75 patients had isolated sABI. Significant functional outcomes in all assessment measures were observed after rehabilitation in all samples. The estimated mean scores (95% confidence interval) of LCF, DRS, GOS and mRS from a multivariate model adjusted for age, sex and time of ICU stay were: 2.85 (2.53-3.21) and 5.24 (4.81-5.71), 23.94 (22.37-25.62) and 16.04 (14.77-17.41), 2.86 (2.70-3.04) and 3.46 (3.28-3.65), and 4.91 (4.67-5.17) and 3.79 (3.58-4.02), at admission and at discharge, respectively. Despite functional improvement, CIPNM+sABI patients showed lesser improvement than those with sABI only. Furthermore, patients with both disorders had significantly higher median LOS than sABI subjects: 107 (q1-q3: 65-146), and 65 (q1-q3: 38-105) days (P=5.5x10-83), respectively. No statistically significant difference in mortality rates was found between groups. CONCLUSIONS: Subjects with CIPNM and coexistent sABI improved after rehabilitation, but had poorer recovery than those with solely sABI requiring a longer LOS. CLINICAL REHABILITATION IMPACT: The rehabilitation process in subjects suffering from CINPM is challenging and no evidence support the use of specific rehabilitative approaches to improve function and activities of daily living.

Readmission to the acute care unit and functional outcomes in patients with severe brain injury during rehabilitation.

BACKGROUND: Medical and surgical complications are common after brain lesions and may require acute care unit readmission (ACUR) during the rehabilitation stay. This clinical phenomenon has not been explored in subjects with severe brain injury (sBI). AIM: Because sBI patients come from the intensive care unit (ICU), patients may be transferred to rehabilitation before complete clinical stabilization. We investigated ACUR and causes as well as whether those who required ACUR had different functional outcomes. DESIGN: Prospective cohort study. SETTING: Dedicated rehabilitation setting. PARTICIPANTS: Adult subjects with sBI causing a disorder of consciousness graded 3-8 on the Glasgow Coma Scale admitted to a dedicated rehabilitative setting were prospectively enrolled from January 2014 to December 2015. METHODS: Functional outcome was investigated using the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS), in subjects with and without ACUR, at admission and discharge. Mortality and length of stay (LOS) were recorded. RESULTS: One hundred-thirty (53 F, 77 M; mean age: 55.7±17.8) subjects were admitted to the rehabilitation setting, and 97 were enrolled (43 F, 54 M; mean age: 54.7±18.2). Thirty-six ACUR were detected that involved 29 (29.8%) patients. There were 20 and 16 referrals to acute medical and surgical care, respectively. Significant functional outcomes in all assessment measures were observed after rehabilitation, but subjects without ACUR showed significant improvement in all measurements: LCF (P=0.001), DRS (P<0.001), GOS (P=0.003), and mRS (P<0.001), compared to those who required ACUR. At baseline, patients with ACUR were more disabled than those without ACUR, and they had significant lower LCF scores: 2.60 (95% CI: 2.15-3.14) and 3.47 (95% CI: 3.07-3.91) (P=0.013), respectively. Significant longer LOS was observed in subjects with ACUR as compared to those without ACUR: 120 (q1-q3:93-165) vs. 63 (q1-q3: 38-93) days (P<0.001), respectively. The intra-hospital mortality rate was higher in patients who required ACUR (8.1 events per 100 person-months) as compared to those who did not require ACUR (2.8 events per 100 person-months). CONCLUSIONS: Readmission to acute care was common in subjects with sBI during rehabilitation. Subjects who required ACUR had poorer functional outcomes, higher risk of mortality and longer LOS than subjects without ACUR. CLINICAL REHABILITATION IMPACT: Careful control of these subjects and more strict collaboration and communication among physicians on the rehabilitative team are required to plan proper care pathways.

Effect of electrical stimulation as an adjunct to botulinum toxin type A in the treatment of adult spasticity: a systematic review.

OBJECTIVE: To investigate whether electrical stimulation (ES) as an adjunct to BTX-A boosts botulinum activity and whether the combined therapeutic procedure is more effective than BTX-A alone in reducing spasticity in adult subjects. DATA SOURCES: A search was conducted in PubMed, EMBASE, Cochrane Central Register, and CINAHL from January 1966 to January 2016. STUDY SELECTION: Only randomized controlled studies (RCT) involving the combination of BTX-A and ES were considered. RCTs were excluded if BTX plus ES was investigated in animals or healthy subjects; certain techniques were used as an adjunct to BTX-A, but ES was not used; BTX-A or ES were compared but were not used in combination. ES was divided into neuromuscular stimulation (NMS), functional electrical stimulation (FES), and transcutaneous electrical nerve stimulation (TENS). Two authors independently screened all search results and reviewed study characteristics using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Fifteen RCTs were pinpointed and nine studies were included. Trials varied in methodological quality, size, and outcome measures used. ES was used in the form of NMS and FES in seven and two studies, respectively. No study investigating BTX-A plus TENS was found. BTX-A plus ES produced significant reduction in spasticity on the Ashworth Scale (AS) and on the modified AS in seven studies, but only four showed high quality on the PEDro scale. Significant reduction in compound muscular action potential (CMAP) amplitude was detected after BTX-A plus ES in two studies. CONCLUSIONS: ES as an adjunctive therapy to BTX-A may boost BTX-A action in reducing adult spasticity, but ES variability makes it difficult to recommend the combined therapy in clinical practice. Implications for rehabilitation Electrical stimulation (ES) as adjunct to botulinum toxin type A (BTX-A) injections may boost neurotoxin action in treating adult spasticity. Given the variability of ES characteristics and the paucity of high-quality trials, it is difficult to support definitively the use of BTX-A plus ES to potentiate BTX-A effect in clinical practice. A vast array of rehabilitation interventions combined with BTX-A have been provided in reducing spasticity, but the present evidence is not sufficient to recommend any combined therapeutic strategy.

Early rehabilitation for severe acquired brain injury in intensive care unit: multicenter observational study.

BACKGROUND: The increased survival after a severe acquired brain injury (sABI) raise the problem of making most effective the treatments in Intensive Care Unit (ICU)/Neurointensive Care Unit (NICU), also integrating rehabilitation care. Despite previous studies reported that early mobilization in ICU was effective in preventing complications and reducing hospital stay, few studies addressed the rehabilitative management of sABI patients in ICU/NICU. AIM: To collect clinical and functional data about the early rehabilitative management of sABI patients during ICU/NICU stay. DESIGN: Prospective, observational, multicenter study. SETTING: Fourteen facilities supplied by intensive neurorehabilitation units and ICU/NICUs. POPULATION: Consecutive sABI patients admitted to ICU/NICU. METHODS: Patients were evaluated at admission and then every 3-5 days. Clinical, functional and rehabilitative data, including Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), The Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome scale (GOS) and Functional Independence Measure (FIM) were collected. RESULTS: One hundred and two patients (F/M 44/58) were enrolled. The mean duration of ICU stay was 24.7±13.9 days and the first rehabilitative evaluation occurred after 8.7±8.8 days. Regular postural changes and multijoint mobilization were prescribed in 63.7% and 64.7% cases, respectively. The mean session duration was 38±11.5 minutes. Swallowing evaluation was performed in 14.7% patients, psychological support was provided to 12.7% of patients' caregivers, while 17.6% received a psycho-educational intervention, and 28.4% were involved in interdisciplinary team meetings. The main discharge destinations were Severe Acquired Brain Injury rehabilitation units for 43.7%, intensive neurorehabilitation units for 20.7%. CONCLUSIONS: Data showed that early rehabilitation was not diffusely performed in sABI subjects in ICU/NICU and rehabilitative interventions were variable; one-third of subjects were not referred to dedicated rehabilitation unit at discharge. CLINICAL REHABILITATION IMPACT: The study stresses the need to spread and implement a rehabilitative culture also for critical ill patients due to neurological diseases.

Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation.

Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post-traumatic neuralgia, phantom limb, and complex regional pain syndrome with focal dystonia. The use of BTX-A could represent a novel therapeutic strategy in caring for neuropathic pain whenever common pharmacological tools have been ineffective. However, large and well-designed clinical trials are needed to recommend BTX-A use in the relief of neuropathic pain.

Thrombocytosis after hip and knee surgery in the rehabilitation setting: is it an occasional phenomenon? Relationship with deep venous thrombosis and functional outcome.

BACKGROUND: Thrombocytosis can follow surgery and has occasionally been observed after major orthopaedic surgery. The aim of the present study was to ascertain the platelet count (PLTC) change in patients admitted to a rehabilitation unit after major joint surgery and whether deep venous thrombosis (DVT) and poor outcomes occurred in those who had thrombocytosis. METHOD: PLTC, red blood cells (RBC), haemoglobin (Hb), fibrinogen, and D-dimers were assessed in patients on admission and at discharge after major joint surgery. Functional outcomes were ascertained using the Barthel Scale (BS), the Functional Independence Measure (FIM) and gait evaluation. Thrombocytosis was considered to have occurred when PLTC was greater than or equal to 500 × 100(9)/L. All subjects with thrombocytosis had ultrasonography to assess DVT occurrence. The patients were divided into "young" and "old" groups according to an age cut-off of 75 years to investigate potential age-related differences. RESULTS: Two hundred and seventy-five patients were identified and 142 (36 M and 106 F, mean age 77.2 ± 10.7) were enrolled. Seventy-six (53.5%) underwent total hip arthroplasty (THA), 40 (51.1%) underwent hip internal fixation and 26 (18.3%) subjects underwent total knee arthroplasty (TKA). The young and old groups included 60 and 82 patients, respectively. Fifty-nine (42.4%) patients had PLTC above 400 × 100(9)/L. Of these, 28 (20.1%) had thrombocytosis with PLTC above 500 × 100(9)/L, and 15 of them (10.7%) had very high values above 600 × 100(9)/L. Increased levels of fibrinogen and D-dimers were also detected. No subject with thrombocytosis had DVT. Outcome was not affected by PLTC. At discharge, significant improvement in all functional assessments was observed in young compared to old people; gait: 2.9 ± 0.2 vs. 2.2 ± 0.8; BS: 97 ± 6.9 vs. 70.5 ± 25.6; and FIM: 116.4 ± 10.9 vs. 83.6 ± 31.2 (p < 0.004), respectively. BS and FIM mean scores were positively correlated with Hb level. CONCLUSION: Elevated PLTC and thrombocytosis were not uncommon in patients after major joint surgery, but no subject developed DVT. Platelet count change did not affect the outcome. Higher age and lower haemoglobin level correlated with poorer functional recovery.

Efficacy of botulinum toxin type B for the treatment of primary palmar hyperhidrosis: a prospective, open, single-blind, multi-centre study.

Primary palmar hyperhidrosis is a distressing and disabling condition that can produce social, psychological and occupational problems. Although the use of botulinum toxin type A (BoNT-A) has been reported as an efficacious and safe intervention to improve palmar hyperhidrosis, only one study concerned botulinum toxin type B (BoNT-B) in this disorder. The aim of study was to evaluate the efficacy and safety of BoNT-B in treating primary palmar hyperhidrosis. Participants were injected with 5,000 IU of BoNT-B in each palm. Visual analogue test (VAS) to evaluate the intensity of decrease in sweat production, Minor's iodine starch test and measurement of paper towels' weight were used to ascertain palmar sweating at baseline, 4, 12 and 24 weeks after BoNT-B injections by a blind examiner. Thirty-two subjects (12 males, 20 females, mean age 31 ± 11) were enrolled. Significant reduction of palmar sweating was detected after BoNT-B injection: 2.9 ± 1.4, 0.3 ± 0.4, 0.9 ± 0.8, and 2.1 ± 1.5 g (p < 0.001) of paper towels' weight for the right palm at baseline, 4, 12 and 24 weeks; and 2.8 ± 1.7, 0.5 ± 0.6, 0.8 ± 0.7, and 1.8 ± 1.25 g (p < 0.001) at same time, respectively for the left palm. Significant reduction of mean VAS values were also detected after BoNT-B injections: 8.6 ± 1.1, 0.6 ± 0.8, 3.5 ± 2.5, and 7.1 ± 2.4 (p < 0.0001) at baseline, 4, 12 and 24 weeks, respectively. Mild side effects consisting in local pain and hand weakness were observed in 4 (12.5%) subjects. The findings indicated that the use of 5,000 IU BoNT-B injection in each palm was safe and significantly improved the severity of palmar hyperhidrosis.

High doses of a new botulinum toxin type A (NT-201) in adult patients with severe spasticity following brain injury and cerebral palsy.

BACKGROUND: Spasticity can be a severe disabling disorder requiring high-dose injections of botulinum toxin type A (BoNT-A). Efficacy and safety of high BoNT-A doses in reducing multi-level spasticity of subjects with brain injury and cerebral palsy were investigated. Pain and functional outcome were also assessed. METHOD: High doses (up to 840 IU) of incobotulinumtoxinA were injected in adult subjects with severe spasticity of the upper and lower limbs due to brain injury (BI) and cerebral palsy (CP). The Modified Ashworth Scale, Visual Analogue scale, Glasgow Outcome Scale, Franchay Arm Test (FAT) and Barthel Scale were employed to assess spasticity, pain and functional outcome at baseline, and 4 and 16 weeks after BoNT-A injection. RESULTS: Twenty-two (12 M, 10 F; mean age 38.1 ± 13.7 years) subjects - 16 subjects with BI and 6 with CP - were enrolled. Elbow, wrist, fingers and ankle muscles showed significant spasticity reduction after BoNT-A injections. The mean FAT score improved, but the benefit was not significant. Three (13.6%) subjects complained of mild adverse events. CONCLUSION: High-dose BoNT-A injections were effective and safe in reducing spasticity of BI and CP subjects. A significant reduction of the pain was also observed, but global functionality and arm dexterity were unchanged.

Rehabilitation strategy in the elderly.

The population is getting older. Rehabilitation can play an essential strategic role to counteract impairments and disability which characterize the elderly. Correct rehabilitative programmes have to be approached on the functional limitation and residual abilities of elders. Leading a more active lifestyle and regular physical activity including aerobic and resistance exercises have been demonstrated to improve cardiovascular, respiratory, musculoskeletal, and cognitive wellbeing in older adults. Occupational therapy, prescription of assistive devices, environmental, and home living adaptation, and family or caregiver educational training represent an essential rehabilitative strategy in elders developing disability. In these people, falls are dramatic events that lead to hospitalization, functional decline, decreased social activity, and poor quality of life. Rehabilitation incorporating balance, gait, and strength training exercise interventions can reduce the risk of falls. Frailty refers to a condition characterized by a gradual physiologic decline in multiple body systems, loss of physiologic reserve, and increased vulnerability to disease and death. Several therapeutic strategies have been proposed including exercises, multi-component training and approaches, all aimed at decreasing the need for nursing home placement, hospitalization, and reducing dependence and death. In these subjects, geriatric comprehensive assessment and the multi-disciplinary team have recently been demonstrated to be more effective than usual care.

Botulinum toxin type B for sialorrhoea in children with cerebral palsy: a randomized trial comparing three doses.

AIM: The aim of the present study was to evaluate the efficacy and safety of three doses of botulinum toxin type B (BoNT-B) in reducing persistent sialorrhoea in children with cerebral palsy (CP). METHOD: Children with CP and refractory sialorrhoea were randomized to one of four groups: a control group and three experimental groups receiving a low (1500 mouse units [MU]), medium (3000 MU), or high (5000 MU) dose of BoNT-B respectively, into bilateral salivary glands. Drooling was measured using the Thomas-Stonell rating scale, and the weight and the number of bibs used per day were counted in all children at baseline, 4, and 12 weeks after BoNT-B injection. RESULTS: Twenty-seven children (15 males, 12 females; mean age 7 y 10 mo, SD 1 y 6 mo; range 5-15 y) were randomized into a control (seven children: four males, three females) and experimental groups receiving low (six children: four males, two females), medium (seven children: four males, three females), and high (seven children: three males, four females) doses of BoNT-B respectively. All children had mixed neurological disorders consisting of spastic paraparesis, tetraparesis, dystonic movements, and ataxia. Gross Motor Function Classification System levels ranged from III to V, and all children had moderate or severe intellectual disability. Estimated means with their standard errors (SEM) of drooling were at baseline, 4, and 12 weeks respectively, as follows: control group, 12.1 (2.1), 11.9 (2.1), 11.8 (2.2), p for trend 0.992; low dose group, 13.8 (2.3), 11.4 (2.3), 13.9 (2.3), p for trend 0.952; medium dose group, 13.9 (2.1), 6.7 (2.1), 7.1 (2.1) p for trend 0.008; and for the high dose group 14.4 (2.1), 5.0 (2.1), 5.6 (2.1), p for trend 0.002. Side effects included dense saliva, xerostomia, and difficulty in swallowing, and were more frequent in the high-dose group. INTERPRETATION: A 3000 MU injection of BoNT-B into the salivary glands significantly improved the frequency and severity of sialorrhoea in children with CP. The lower dose was ineffective, and the higher dose produced no greater benefit and more side effects.

Long-term outcome and health status in decompressive craniectomized patients with intractable intracranial pressure after severe brain injury.

OBJECTIVE: Decompressive craniectomy (DC) in severe traumatic brain injury (TBI) remains a controversial therapeutic strategy. The long-term functional recovery and health status in a sample of decompressive craniectomized TBI are reported. METHODS: Patients with TBI who underwent DC were retrospectively investigated. Patients with cerebral haemorrhage (CH) and DC were considered as control group. In all survival patients admitted to a neuro-rehabilitation setting, the modified Rankin (mRS), Glasgow Outcome scale (GOS) and Barthel Scales (BS) were administered at admission, discharge, 1 year and follow-up. The quality-of-life was evaluated with the SF-36 questionnaire at follow-up (41.1±16.6 months). RESULTS: Seventy (33 F, 37 M, mean age=46.8, SD=18.8) patients were enrolled: 46 (20 F, 26 M) subjects with TBI and 24 (13 F, 11 M) with CH. After surgery, 11 (23.9%) and 10 (41.6%) subjects in the TBI and CH group, respectively, died. The mean Barthel scores were 4.0 (SD=5.9), 60.9 (SD=37.5), 63.7 (SD=35.1) and 67.3 (SD=38.2) (p<0.001) and median GOS was 3, 4, 4 and 4 at admission, discharge, 1 year and follow-up, respectively, in TBI patients. Seventeen (36.9%) patients with TBI and four (16.6%) with CH made a full recovery. The SF-36 questionnaire showed significant abnormalities in all domains of health status in both groups. CONCLUSION: Craniectomized patients with TBI achieved good long-term outcome, although they experienced significant difficulties in health status.

Functional outcome and health status of injured patients with peripheral nerve lesions.

BACKGROUND: Peripheral nerve lesions (PNLs) can complicate the clinical course and outcome of multiply injured patients. Since this often impedes recovery, it can be a significant burden for both patients and clinicians. The objective of the present study was to investigate the long-term outcome and health status of patients with PNL. SUBJECTS AND METHODS: Multiply injured patients admitted to an intensive rehabilitation setting were identified. The Barthel and modified Rankin scales (mRS) were administered to all patients at admission, discharge and follow-up. The short form (SF)-36 questionnaire was used at follow-up (mean: 25.3+/-6.5 months). RESULTS: Seventy-seven multiply injured patients were identified, and 45 (22 male, 23 female; mean age: 59.7+/-21.7 years; range: 19-83 years) were enrolled. Of the injured patients, 22 subjects (10 male and 12 female) had no PNL, while 23 (12 male, 11 female) did. In the PLN group, the mean Barthel scores at admission, discharge and follow-up, respectively, were 33.4+/-17.9, 85.3+/-3.8 and 93.0+/-6.9 (p<0.001) and the median mRS scores were 4 (interquartile range (IQR): 3-5), 3 (IQR: 1-3) and 1 (IQR: 0-2), respectively. In the group without PLN, the mean Barthel scores at admission, discharge and follow-up, respectively, were 30.4+/-14.5, 86.6+/-9.8 and 96.6+/-4.9 (p<0.001) and the median mRS scores were 4 (IQR: 3-5), 2 (IQR: 1-3) and 0.5 (IQR: 0-2). The mean length of hospital stay was 86.7+/-10.8 and 65.6+/-14.6 days in patients with and without PNL, respectively. The SF-36 did not show significant differences between the groups, but the patients with and without PNL reported significant lower mean scores on all items compared to national population norms. CONCLUSION: Multiply injured patients with and without PNL showed significant improvement and a good long-term outcome after rehabilitation. However, those with PNL had a longer hospital stay and needed more rehabilitation than patients without PNL. Both the groups of patients experienced significant difficulties in the health status.

Botulinum toxin type A in the healing of ulcer following oro-mandibular dyskinesia in a patient in a vegetative state.

OBJECTIVE: Use of botulinum toxin is expanding as clinical studies demonstrate new potential therapeutic applications. In rehabilitation, botulinum toxin is predominantly used as adjunct therapy for the treatment of spasticity, but it may prove useful for other atypical clinical situations. CASE HISTORY: A 73-year-old man had a severe sub-arachnoid haemorrhage following the rupture of a giant aneurism of the middle left cerebral artery. Clinically, the patient presented a vegetative state and an oro-mandibular dyskinesia that produced a chronic ulcer on the lower lip. As treatment for this dyskinesia, a total of 320 U botulinum toxin type A were injected into the upper and lower orbicularis oris and masseter muscles. RESULTS AND DISCUSSION: This treatment allowed for application of topical medication and subsequently, ulcer healing. Botulinum toxin type A may be an important therapeutic aid for clinicians faced with treating persistent pathological conditions caused by dyskinesia.