Spinal cord clinical trials and the role for bioengineering

There is considerable need for bringing effective therapies for spinal cord injury (SCI) to the clinic. Excellent medical and surgical management has mitigated poor prognoses after SCI; however, few advances have been made to return lost function. Bioengineering approaches have shown great promise in preclinical rodent models, yet there remains a large translational gap to carry these forward in human trials. Herein, we provide a framework of human clinical trials, an overview of past trials for SCI, as well as bioengineered approaches that include: directly applied pharmacologics, cellular transplantation, biomaterials and functional neurorehabilitation. Success of novel therapies will require the correct application of comprehensive preclinical studies with well-designed and expertly conducted human clinical trials. While biologics and bioengineered strategies are widely considered to represent the high potential benefits for those who have sustained a spinal injury, few such therapies have been thoroughly tested with appreciable efficacy for use in human SCI. With these considerations, we propose that bioengineered strategies are poised to enter clinical trials.     

娱乐疗法对脑卒中患者社会交往能力的影响

目的探讨娱乐疗法对脑卒中患者社会交往能力的影响。方法将脑卒中患者分为治疗组28例和对照组30例,在接受常规康复的同时,治疗组接受经个体化设计的娱乐康复活动。分别在治疗前和治疗结束时进行功能独立性评定。结果两组患者治疗后功能独立性评分均有改善(P<0.05),治疗组社会交往能力评分较对照组改善更多(P<0.01)。结论娱乐康复活动有助于提高脑卒中患者社会交往能力。     

Influence of chronic kidney disease and haemodialysis on stroke outcome

INTRODUCTIONStroke patients with underlying chronic kidney disease (CKD) and those on haemodialysis have complex rehabilitation needs, and their survival and functional outcomes are limited. This study aimed to review post-stroke survival and functional outcomes following rehabilitation in patients with CKD and those on haemodialysis.METHODSWe conducted a retrospective analysis of consecutive stroke patients with underlying CKD (Stages G3b, G4 and G5; n = 30) and those on dialysis at the time of stroke (n = 7), who underwent in-patient rehabilitation between June 2008 and May 2017. The mean duration of follow-up was 56 months. Demographic details, associated comorbidities and laboratory parameters were reviewed. Baseline and follow-up scores of the National Institute of Health Stroke Scale (NIHSS) and Functional Independence Measure (FIM), and dates of death of the patients were analysed.RESULTSOf the 37 consecutive stroke patients (mean age 64.7 years), 34 had ischaemic stroke and three had haemorrhagic transformation. Significant improvements in NIHSS and FIM scores were observed from the time of admission to after discharge. Older age, longer duration of hospital stay, lower estimated glomerular filtration rate and low haemoglobin levels were all significantly related to mortality.CONCLUSIONDespite significant functional and neurological improvements following rehabilitation, stroke patients with underlying CKD had higher average duration of hospital stay, more recurrent hospitalisations and poorer survival outcomes than those without underlying CKD. This could be attributed to the complications associated with CKD rather than stroke. Multidisciplinary community rehabilitation may be an alternative to reduce recurrent hospitalisations and morbidity in this group of patients.     

On the outcome in stroke patients one year later: the role of atrial fibrillation

The post-stroke aftermath of patients suffering from atrial fibrillation (AF) is investigated. A total of 104 consecutive patients (80 with AF and 24 without AF) were referred to a rehabilitation centre and enrolled. They underwent a rehabilitative programme. Disability was assessed by using the Functional Independence Measure (FIM), at the time of admission, discharge and after 1 year. Death was more frequent over the 1-year interval in AF group. Ten patients died (42%), whereas in the non-AF group death occurred in 15 cases (19%). By using chi-square test, the difference was significant (P < 0.02). The logistic regression analysis indicated that the unique variable affecting the FIM at follow-up was the FIM at discharge (P < 0.0001). AF was not a significant variable in the equation. The result can be attributed to subject attrition in the AF group, as the most severe patients died and survivors could benefit from a better functional status.     

The influence of age on length of stay,functional independence and discharge destination of rehabilitation inpatients in Italy

Advanced age in itself does not predict a poor functional outcome or a longer length of stay in rehabilitation units. Seven hundred and sixty-four adult cases were analysed, from 14 post-acute rehabilitation facilities throughout Italy. Data came from the national database run by the agency distributing the Italian version of an internationally validated scale of disability, the FIM©^sm (Functional Independence Measure). The FIM is an 18-item scale rating independence in the domains of selfcare, sphincter control, mobility, locomotion, communication and social cognition. The total FIM score may range from 18 to 126 (higher score = greater independence). Patients were classified with respect to the cut-off age of 75 years (76+ and 75?, mean age 82 and 57 years, n = 203 and 561, 27% and 73% of the cases, respectively). The median interval between onset of disability and admission to the facility (onset-to- admission delay, OAD) was 36 and 45 days in the 76+ and the 75? group, respectively (p < 0.001). Mean admission FIM score was 70 (±28) in the 76+ and 71 (±27) in the 75? group. Discharge FIM scores were 84±29 and 93±26, respectively (p < 0001). Median length of stay (LOS) was 34 days in the 76+ and 41 days in the 75? group, respectively (p < 0.005). The 76+ and 75? groups were discharged home in 86% and 90% of the cases, respectively (p = 0.053). The results suggest that inpatient rehabilitation is substantially effective and efficient for older as well as for younger patients.     

Immunogenicity and safety of a booster dose of diphtheria,tetanus, acellular pertussis and inactivated poliomyelitis vaccine (Tdap-IPV; Repevax) administered concomitantly versus non-concomitantly with an influenza vaccine (Vaxigrip) to adults aged ≥60 years: An open-label,randomised trial

Background

Annual influenza vaccination provides an opportunity to administer a booster dose of diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine (Tdap-IPV) to the elderly. This study evaluated immune responses to and safety of the two vaccines administered concomitantly or sequentially to elderly individuals in France and Germany.

Methods

Individuals aged ≥60 years who had received a diphtheria/tetanus booster within 5–15 years were randomised (1:1) to receive either Tdap-IPV and an inactivated influenza vaccine concomitantly (Group 1) or inactivated influenza vaccine then Tdap-IPV 28–35 days later (Group 2). Antibody titres were measured before and 28–35 days after each vaccination.

Results

The mean age of randomised individuals (n = 954) was 68.8 years. Post-vaccination seroprotection rates (≥0.1 IU/mL for diphtheria/tetanus and ≥8 1/dilution for polio) for Group 1 were non-inferior to Group 2 for diphtheria (85.4% vs. 87.5%), tetanus (both 100%), polio type 1 (99.8% vs. 100%), polio type 2 (both 100%) and polio type 3 (99.3% vs. 99.8%). Similarly, percentages of individuals with pertussis antibodies ≥5 EU/mL for Group 1 were non-inferior to Group 2: pertussis toxin (94.3% vs. 98.1%), filamentous haemagglutinin (99.8% vs. 100%), pertactin (97.3% vs. 96.0%), fimbriae 2 and 3 (91.7% vs. 89.5%). Post-vaccination geometric mean titres of anti-influenza haemagglutinin antibodies for Group 1 were non-inferior to Group 2. Adverse events following administration of Tdap-IPV were similar in both study groups, with no vaccine-related serious adverse events.

Conclusion

Tdap-IPV and inactivated influenza vaccine can be administered concomitantly in the elderly without impairing tolerability or the immune response to either vaccine.     

Cautious Use of Intrathecal Baclofen in Walking Spastic Patients: Results on Long‐term Follow‐up

Intrathecal baclofen is presently the most effective treatment for diffuse spasticity whatever the cause. The fact that both spasticity is always accompanied by a degree of muscle weakness and that any antispastic treatment causes a decrease in muscle strength indicate that major attention must be paid in treating spasticity in ambulant patients. Methods. We present here a retrospective study, approved by the insitutional ethics committee, of 22 ambulant spastic patients, selected as homogeneous for disease and disease duration, who were treated with intrathecal baclofen at the Istituto Nazionale Neurologico “C.Besta” in Milan. These patients were followed‐up for to 15 years of treatment and their clinical assessment was enriched by the evaluation of their functional independence measurement (FIM) before and during treatment. Results. There was improvement in quality of life as measured by the FIM scale; however, an increase in the patient's motor performance could not be detected. Conclusion. Although we did not show any improvement in muscle performance, intrathecal baclofen did improve daily quality of life, even in spastic patients who were able to walk.     

Rehabilitation outcome of patients with severe and prolonged disorders of consciousness after aneurysmal subarachnoid hemorrhage (aSAH)

Objectives

Our objectives were to evaluate rehabilitation outcome of aSAH survivors with severe disorders of consciousness (DOC) and to examine potential predictors of long-term outcome. Severe DOC includes patients in a vegetative state (VS) and in a minimally conscious state (MCS).

Patients and methods

This is a retrospective single-center cohort study of consecutive aSAH patients with severe and prolonged DOC upon admission to neurorehabilitation. Clinical assessments started right after discharge from ICU, a median of 26 days after the aSAH. Two different outcome criteria were used, one addressing the functional aspect (assessed by the Functional Independence Measure [FIM]) the other one addressing the level of consciousness (“behavioral outcome”, assessed by the Coma Remission Scale [CRS]). Improved outcome was defined by an increase in FIM scores of at least 22 points (minimal clinically important difference) or by reaching a full score of 24 points on the CRS. Separate least square linear regression models were calculated to examine potential predictors for functional and behavioral outcome.

Results

Out of 63 patients, 19.0% and 39.7% of the patients achieved an improved functional and behavioral outcome, respectively. Age and level of consciousness upon admission to neurorehabilitation were independent prognostic factors for both outcome definitions. Both groups reached the better outcome category after a median of 11 and 9 weeks, respectively. In an individual patient, the longest delay to achievement of improved functional outcome was 30 weeks and to favorable behavioral outcome was 22 weeks after rehabilitation admission.

Conclusion

About one-third of severely affected aSAH patients with DOC regained at least a favorable behavioral status during early neurorehabilitation. It is interesting to note that in our study population, the beginning of clinical improvement took up to 6 months after aSAH.     

Early rehabilitation outcome in patients with middle cerebral artery stroke

Although important data on the prognosis and rehabilitation outcome in stroke patients have been reported, data on functional recovery according to stroke subtypes are limited. This retrospective study aimed to evaluate functional outcome in patients with middle cerebral artery (MCA) stroke-the most common subtype of ischemic stroke. The records of stroke patients that underwent the rehabilitation program at our brain injury rehabilitation service between January 2007 and December 2008 were reviewed, and those with MCA stroke were included in the study. Patient demographic and clinical data, and Barthel Index (BI) and Functional Independence Measure (FIM) scores at admission and discharge were collected. The study included 80 MCA stroke patients with a mean age of 63.54 years. FIM and BI scores improved significantly post rehabilitation (P < 0.05). Age was negatively correlated with both BI and FIM scores at admission and discharge. Length of stay was not correlated with improvement in BI or FIM scores during hospitalization. The patients that had ≤1 month of inpatient rehabilitation had similar outcomes as those that had >1 month of inpatient rehabilitation (P > 0.05). Length of time after stroke onset was not correlated with BI or FIM scores at admission. Regardless of initial functional status, prediction of discharge functional status was misleading. Physiatrists should keep in mind that functional improvement does not always increase with duration of inpatient therapy.