Thyrotropic Axis and Disorders of Consciousness in Acquired Brain Injury: A Potential Intriguing Association?

Purpose: A potential involvement of thyrotropic axis in influencing the state of consciousness could be hypothesized. We aimed at investigating thyroid function tests as predictors of disorders of consciousness (DoC) and relating recovery in a large cohort of patients with DoC secondary to acquired brain injury (ABI). Methods: This retrospective, multicenter, cohort study included 151 patients with DoC following ABI, consecutively admitted for a 6-month neurorehabilitation program. Data on etiology of brain injury, evolution of DoC, disability and rehabilitation assessments, and death during rehabilitation were collected at baseline and on discharge. Thyroid function tests (serum TSH, fT4 and fT3 levels) were assessed on admission in all patients and at final discharge in 50 patients. Results: Lower baseline TSH levels and greater TSH increments (ΔTSH) after neurorehabilitation predicted a favorable change in DoC independent of age, sex, BMI, etiology of brain injury and initial DoC subtype (TSH: OR=0.712, CI 95% 0.533-0.951, p=0.01; ΔTSH: OR=2.878, CI 95% 1.147-7.223, p=0.02). On the other hand, neither fT4 nor fT3 or their variations appeared to play any role on DoC changes after 6-months inpatient neurorehabilitation. A lower magnitude of ΔfT4 acted as a strong predictor of improved functional disability level (ß=0.655, p=0.002) and cognitive functions (ß=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes. Conclusions: Serum TSH levels assessed in the subacute post-ABI phase and its variation during neurorehabilitation could represent a potential biomarker of DoC evolution, while variations in fT4 levels seem to be associated with rehabilitation and cognitive functions. Further studies are needed to investigate the mechanisms underlying these associations.

Peripheral Neuropathy in Patients Recovering from Severe COVID-19: A Case Series.

Background and Objectives: Neurological manifestations have been reported in a significant proportion of coronavirus disease 2019 (COVID-19) patients. We aimed to evaluate the prevalence and severity of peripheral nervous system (PNS) involvement in a large group of convalescent COVID-19 patients undergoing in-hospital multidisciplinary rehabilitation. Materials and Methods: Convalescent COVID-19 patients admitted to a Pulmonary Rehabilitation Unit were consecutively screened for inclusion within 48 h of discharge from an acute care setting. All included patients underwent electrophysiological examinations. Results: Among 102 enrolled patients (mean age 62.0 years, 82.4% males), PNS electrophysiological alterations were detected in 42.2%. Mononeuropathies exclusively involving the peroneal nerve were observed in 8.8% (n = 9), while multiple mononeuropathies were similarly reported in nine patients (8.8%). A symmetric sensorimotor polyneuropathy was documented in 24.5% of participants (n = 25). A significant difference was found for exercise capacity and pulmonary function in post hoc comparisons between the three study groups. Conclusions: The risk of neuropathy in the convalescent phase of COVID-19 is relevant. This should be considered when planning multidisciplinary rehabilitation strategies.

Positive impact of short-term gait rehabilitation in Parkinson patients: a combined approach based on statistics and machine learning.

Parkinson's disease is the second most common neurodegenerative disorder in the world. Assumed that gait dysfunctions represent a major motor symptom for the pathology, gait analysis can provide clinicians quantitative information about the rehabilitation outcome of patients. In this scenario, wearable inertial systems for gait analysis can be a valid tool to assess the functional recovery of patients in an automatic and quantitative way, helping clinicians in decision making. Aim of the study is to evaluate the impact of the short-term rehabilitation on gait and balance of patients with Parkinson's disease. A cohort of 12 patients with Idiopathic Parkinson's disease performed a gait analysis session instrumented by a wearable inertial system for gait analysis: Opal System, by APDM Inc., with spatial and temporal parameters being analyzed through a statistic and machine learning approach. Six out of fourteen motion parameters exhibited a statistically significant difference between the measurements at admission and at discharge of the patients, while the machine learning analysis confirmed the separability of the two phases in terms of Accuracy and Area under the Receiving Operating Characteristic Curve. The rehabilitation treatment especially improved the motion parameters related to the gait. The study shows the positive impact on the gait of a short-term rehabilitation in patients with Parkinson's disease and the feasibility of the wearable inertial devices, that are increasingly spreading in clinical practice, to quantitatively assess the gait improvement.

Sex Differences in Long-Term Mortality and Functional Outcome After Rehabilitation in Patients With Severe Stroke.

Objective: We sought to determine sex differences in outcomes in patients with severe stroke who had been admitted to inpatient rehabilitation. Methods: We studied 1,316 patients aged 18 to 99 (mean 72) classified as case-mix groups 0108, 0109, and 0110 of the Medicare case-mix classification system. These groups encompass the most severe strokes. Three outcomes were analyzed: (1) 3-year mortality from admission to rehabilitation; (2) combined outcome of transfer to acute care or death within 90 days from admission to rehabilitation; (3) functional outcome, including proportional recovery in motor functioning and good functional outcome as defined by achievement of a Functional Independence Measure (FIM)-motor score ≥65 points at discharge. Multivariable regression analyses were used to assess sex-difference in each outcome between women and men. The covariates examined included age, marital status, comorbidities, time from stroke onset to rehabilitation admission <30 days, ischemic stroke, dysphagia, neglect, motor FIM score at admission, and cognitive FIM score at admission. Results: Kaplan-Meier estimated 3-year mortality rate was 20.7% in women and 22.0% in men. The crude hazard ratio (HR) of death for women compared with men was 0.94 (95% CI 0.74-1.20). After adjustment for significant covariates, the HR of 3-year mortality was 0.73 (95% CIs 0.56-0.96; p = 0.025). Comorbidity, including diabetes, anemia, coronary artery disease, atrial fibrillation, and chronic obstructive pulmonary disease, significantly increased mortality risk by 49-88%. The incidence of the combined outcome was 8.3% in women and 8.4% in men. The crude HR of the combined end-point for women compared with men was 1.05 (95% CI 0.72-1.53). After adjustment for significant covariates, the HR was 0.95 (95% CIs 0.65-1.40; p = 0.810). Likewise, no significant difference in proportional recovery or in the rate of achievement of a good functional outcome between women and men was observed. Conclusion: Among patients admitted to inpatient rehabilitation after severe stroke, women and men had comparable crude mortality rates at 3 years. After multivariable adjustment, however, women had lower mortality risk. No sex-differences in the risk of being transferred to acute care or dying within 90 days from admission to rehabilitation or in responsiveness to rehabilitation were observed.

Association Between Malnutrition and Outcomes in Patients With Severe Ischemic Stroke Undergoing Rehabilitation.

OBJECTIVE: To investigate the incremental prognostic significance of malnutrition in patients with severe poststroke disability. DESIGN: Retrospective cohort study. The patients were recruited from 3 specialized inpatient rehabilitation facilities. Nutritional status was assessed using the Prognostic Nutritional Index (PNI), which is calculated from serum albumin and total lymphocyte count. Scores >38 points reflect normal nutrition status, scores of 35-38 indicate moderate malnutrition, and scores <35 indicate severe malnutrition. The association of PNI categories with outcomes was assessed using multivariable regression analyses. SETTING: Inpatient rehabilitation facility. PARTICIPANTS: Patients (N=668) with ischemic stroke admitted to inpatient rehabilitation within 90 days from stroke occurrence and classified as Case-Mix Groups 0108, 0109, and 0110 of the current Medicare case-mix classification system. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Three outcomes were examined: (1) the combined outcome of transfer to acute care and death within 90 days from admission to rehabilitation; (2) 2-year mortality; and (3) FIM motor effectiveness, calculated as (FIM motor change/maximum FIM motor-admission FIM motor score)×100. RESULTS: Overall, the median time to rehabilitation admission was 18 days (range, 12-26 days). The prevalence of moderate and severe malnutrition was 12.7% and 11.5%, respectively. Ninety-one patients (13.6%) experienced the combined outcome. After adjusting for independent predictors including sex, atrial fibrillation, dysphagia, FIM cognitive score, and hemoglobin levels, neither moderate (P=.280) nor severe malnutrition (P=.482) were associated with the combined outcome. Similar results were observed when looking at 2-year mortality. Overall, FIM motor effectiveness was 30%±24%. After adjusting for independent predictors, severe malnutrition (ß coefficient -0.458±0.216; P=.034) was associated with FIM motor effectiveness. CONCLUSIONS: Approximately 1 in every 9 patients presented severe malnutrition. On top of the independent predictors, severe malnutrition did not provide additional prognostic information concerning risk of the combined outcome or 2-year mortality. Conversely, severe malnutrition was associated with poorer functional outcome as expressed by FIM motor effectiveness.

Prognosis of severe acquired brain injury: Short and long-term outcome determinants and their potential clinical relevance after rehabilitation. A comprehensive approach to analyze cohort studies.

BACKGROUND: Accurate prognostic evaluation is a key factor in the clinical management of patients affected by severe acute brain injury (ABI) and helps planning focused therapies, better caregiver's support and allocation of resources. Aim of the study was to assess factors independently associated with both the short and long-term outcomes after rehabilitation in patients affected by ABI in the setting of a single Rehabilitation Unit specifically allocated to these patients. METHODS AND FINDINGS: In all patients (567) with age ≥ 18 years discharged from the Unit in the period 2006/2015 demographic, etiologic, comorbidity indicators, and descriptors of the disability burden (at hospital admission and discharge) were evaluated as potential prognostic factors of both short-term (4 classes of disability status at discharge) and long-term (mortality) outcomes. A comprehensive analytical method was adopted to combine several tasks. Select the factors with a significant independent association with the outcome, assess the relative weights and the "stability" (by bootstrap resampling) of them and estimate the role of the prognostic models in the clinical framework considering "cost" and "benefits". The generalized ordered logistic model for ordinal dependent variables was used for the short-term outcome while the Cox proportional hazard model was used for the long-term outcome. The final short-term model identified 7 factors that independently account for 37% of the outcome variability as shown by pseudo R2 (pR2) = 0.37. The disability status descriptors show the strongest association since they account for more than 60% of the pR2, followed by age (14.8%), the presence of percutaneous endoscopic gastrostomy or nasogastric intubation (14.4%), a longer stay in the acute ward (5.9%) and concomitant coronary disease (1.3%). The final multivariable Cox model identified 4 factors that independently account for 52% of the outcome variability (R2 = 0.52). The disability extent and the disability recovered lead the long-term mortality since they account for the 53% of the global R2. The relevant effect of age (42%) is appreciable only after 2 years given the significant interaction with time. A longer stay in the acute ward explains the remaining fraction (5%). Considering 'cost and benefits', the decision curve analysis shows that the clinical benefit achieved by using both prognostic models is greater than the other possible action strategies, namely 'treat all' and 'treat none. Several less obvious characteristics of the prognostic models are appreciated by integrating the results of multiple analytical methods. CONCLUSION: The comprehensive analytical tool aimed to integrate statistical significance, weight, "stability" and clinical "net" benefit, gives back a prognostic framework explaining a relevant portion of both outcomes' variability in which the strong association of the disability status with both outcomes is comparable to and followed by a time modulated role of age. Our data do not support a differentiated association of traumatic vs non-traumatic etiology. The results encourage the use of integrated approach to analyze cohort data.

Rehabilitation Outcomes of Patients With Severe Disability Poststroke.

OBJECTIVE: To characterize rehabilitation outcomes of patients with severe poststroke motor impairment (MI) and develop a predictive model for treatment failure. DESIGN: Retrospective cohort study. Correlates of treatment failure, defined as the persistence of severe MI after rehabilitation, were identified using logistic regression analysis. Then, an integer-based scoring rule was developed from the logistic model. SETTING: Three specialized inpatient rehabilitation facilities. PARTICIPANTS: Patients (N=1265) classified as case-mix groups (CMGs) 0108, 0109, and 0110 of the Medicare classification system. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Change in the severity of MI, as assessed by the FIM, from admission to discharge. RESULTS: Median FIM-motor (FIM-M) score increased from 17 (interquartile range [IQR] 14-23) to 38 (IQR, 25-55) points. Median proportional recovery, as expressed by FIM-M effectiveness, was 26% (IQR, 12-47). Median FIM-M change was 18 (IQR, 9-34) points. About 38.5% patients achieved the minimal clinically important difference. Eighteen point six percent and 32.0% of the patients recovered to a stage of either mild (FIM-M ≥62) or moderate (FIM-M 38-61) MI, respectively. All between-CMG differences were statistically significant. Outcomes have also been analyzed according to classification systems used in Australia and Canada. The scoring rule had an area under the curve of 0.833 (95% confidence interval, 0.808-0.858). Decision curve analysis displayed large net benefit of using the risk score compared with the treat all strategy. CONCLUSIONS: This study provides a snapshot of rehabilitation outcomes in a large cohort of patients with severe poststroke MI, thus filling a gap in knowledge. The scoring rule accurately identified the patients at risk for treatment failure.

Efficacy of the Regent Suit-based rehabilitation on gait EMG patterns in hemiparetic subjects: a pilot study.

BACKGROUND: The recovery of the functional limb mobility of patients with cerebral damages can take great benefit of the role offered by proprioceptive rehabilitation. Recently have been developed a special Regent Suit (RS) for rehabilitative applications. Actually, there are preliminary studies which describes the effects of RS on gait recovery of stroke patients in acute stage, but none in chronic stage. Moreover, it is known that motor recovery does not always reflect improvements of the muscle activity and coactivity. AIM: To investigate the effects of proprioceptive stimulation induced by the Regent Suit (RS) on the EMG patterns during gait in post-stroke chronic patients. DESIGN: Randomized controlled trial. SETTING: S. Maugeri Foundation, Telese Terme (BN), Italy. POPULATION: Patients have been randomly assigned into two equal groups of 20 patients: experimental group and traditional group. Further, a control group of 20 healthy subjects have been enrolled. METHODS: The traditional group attended a rehabilitation program composed by neuro-motor exercises without the RS, the experimental group performed the same rehabilitation program while wearing the RS. The NIH Stroke Scale (NIHSS), the Barthel Index (BI), the Functional Independent Measure (FIM) and the Berg Balance Scale (BBS) have been evaluated. EMG analysis has been performed considering the muscle activation timing over the gait of the soleus, tibialis anterior, semitendinosus and vastus lateralis muscles by decomposing the EMG signals into Gaussian pulses. Then, the symmetry of muscle activation and the muscle synergy patterns over the gait cycle have been assessed. RESULTS: The proprioceptive stimulation of the RS-based treatment induces higher and remarkable restoration of the normal muscle activation timing, also increasing the muscle symmetry and reducing the pathological muscle coactivation on both affected and non-affected sides. CONCLUSIONS: These results suggest confirm that a RS-based treatment is more effective than usual care in improving the EMG patterns during locomotion and daily living activities in chronic post-stroke subjects. CLINICAL REHABILITATION IMPACT: The proprioceptive rehabilitation Regent Suit based has an impact on motor function in stroke patients during gait.

Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model.

BACKGROUND AND PURPOSE: Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. METHODS: The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. RESULTS: Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913 (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow χ2 was 4.12 (P=0.249) and 1.20 (P=0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model 1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer-Lemeshow χ2 was 8.86 (P=0.115) and 34.50 (P=0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P=0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14-0.68; P=0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81. CONCLUSIONS: This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management.

Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients.

OBJECTIVE: To study small and large fiber pathology in drug-naive and l-dopa-treated patients affected by Parkinson disease (PD) in early phases, before the occurrence of neuropathic electrophysiologic abnormalities. METHODS: We enrolled 85 patients with idiopathic PD (male/female 49/36, age 61.3 ± 9.7 years) without electrophysiologic signs of neuropathy, including 48 participants naive to l-dopa treatment. All patients underwent clinical, functional, and morphologic assessment of sensory and autonomic nerves through dedicated questionnaires, quantitative sensory testing, sympathetic skin response, dynamic sweat test, and punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation was visualized with specific antibodies and analyzed by confocal microscopy. Data were compared with those obtained from sex- and age-comparable healthy controls. In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side differences. RESULTS: Intraepidermal nerve fiber density was lower in patients compared to controls in all the examined sites (p < 0.001). The loss was higher in the more affected side (p < 0.01). A loss of autonomic nerves to vessels, sweat glands, and arrector pili muscles and of Meissner corpuscles and their myelinated endings in glabrous skin was found (p < 0.001). Patients showed increased tactile and thermal thresholds, impairment of mechanical pain perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated groups differed only for Meissner corpuscle density (p < 0.001). CONCLUSIONS: Both large and small fiber pathology occurs in the early stages of PD and may account for the sensory and autonomic impairment. l-Dopa affects the 2 populations of fibers differently.

Management of intrathecal baclofen therapy for severe acquired brain injury: consensus and recommendations for good clinical practice.

Although widespread in the treatment of generalised spasticity due to severe acquired brain injury, clinical use of intrathecal baclofen administered through an implanted catheter is not yet supported by full scientific evidence. The aim of the study is to provide recommendations for good clinical practice regarding intrathecal baclofen therapy. We used a modified RAND Delphi method to develop consensus-based medical guidelines, involving clinicians who use intrathecal baclofen therapy throughout Italy. The clinicians were asked 38 questions grouped in six areas (patient selection, contraindications for implant, tests prior to implant, method of implant and management of therapy, efficacy evaluation and goal setting, and management of complications). To establish consensus, 75% agreement was required in answers to every question. Consensus was reached on the second round of the Delphi process on 27/38 questions (71%), specifically those regarding identification of objectives, efficacy evaluation, and method of implant and management of therapy, whereas management of complications and contraindications for implant remained critical areas. Despite the limits of our method, a set of recommendations was drawn up for clinical practice in this sector. The study also revealed residual critical areas and indicated future lines of research necessary to reach evidence-based consensus.

Validity and reliability of textile system Sensoria for posturographic measurements.

OBJECTIVES: Smart fabrics and interactive textiles are a relatively new area of research, with many potential applications in the field of biomedical engineering. The ability of smart textiles to interact with the body provides a novel means to sense the wearer's physiology and respond to the needs of the wearer. Physiological signals, such as heart rate, breathing rates, and activity levels, are useful indicators of health status. These signals can be measured by means of textile-based sensors integrated into smart clothing which has the ability to keep a digital record of the patient's physiological responses since his or her last clinical visit, allowing doctors to make a more accurate diagnosis. Similarly, in rehabilitation, it is difficult for therapists to ensure that patients are complying with prescribed exercises. Smart garments sensing body movements have the potential to guide wearers through their exercises, while also recording their individual movements and adherence to their prescribed programme. METHODS: In this paper, we present the new wireless textile system Sensoria, with pressure sensing capability for static posturography. The gold standard for static posturography is currently the use of a pressure or force plate but, due to their very complexity and expensiveness, the applicability outside laboratories is extremely limited. RESULTS: This paper focuses on the agreement between the static computed posturography assessed by means of a traditional stabilometric platform and the Sensoria system, in twenty subjects with Parkinson's Disease (PD). CONCLUSIONS: Preliminary results showed a significant agreement between the two methods, suggesting a clinical use of Sensoria for low cost home care based balance impairment assessments.

Exercise training effects on elderly and middle-age patients with chronic heart failure after acute decompensation: A randomized, controlled trial.

BACKGROUND: The aim of this study was to evaluate the effect of exercise training on cardiac function in heart failure (HF) patients recently suffering from acute decompensation. Radionuclide ambulatory ventricular function monitoring (VEST) was used to detect variations in cardiac hemodynamics during training period. METHODS: This was a monocentric, randomized, controlled trial. We enrolled 72 HF patients [left ventricle ejection fraction (LVEF) <40%] within two weeks after acute cardiogenic pulmonary edema: 40 in the elderly group, 32 in the middle-aged group. Trained patients underwent a specific four-weeks exercise program (closed-chain resistive activities and abdominal exercises) which was supervised by a therapist in agreement with patients' characteristics. Catecholamines at rest, echocardiography, right-heart catheterization, and bicycle ergometer were performed. VEST was performed at the end of the 4weeks-training in all patients in order to assess patients' cardiac hemodynamics [LVEF, cardiac output (CO), stroke volume]. RESULTS: Exercise training significantly improved exercise duration, peak oxygen consumption, and ventilatory threshold both in elderly and middle-aged patients (p<0.0001) after the 4-week controlled training. Despite age (F=35.086, p<0.0001; F=16.967, p<0.0001; F=42.574, p=0.03, respectively), training reliably influence previous cardiopulmonary parameters (F=29.402, F=16.421, F=26.80, p<0.0001, respectively). Norepinephrine and epinephrine were significantly reduced in both trained groups. Peak LVEF (37.3±4.7% vs 34±6.2%, p=0.002), peak stroke volume (43.3±3.9% vs 37.5±4.3%, p=0.001), and peak CO (63.4±6.1% vs 48.2±4.7%, p<0.0001) increased in middle-aged patients after 4-week training. CONCLUSIONS: Exercise training improves cardiac performance indexes and pulmonary function in both middle-aged and elderly HF patients early after an acute episode of cardiac decompensation.

Analysis of reaching movements of upper arm in robot assisted exercises. Kinematic assessment of robot assisted upper arm reaching single-joint movements.

Robot-mediated therapy (RMT) has been a very dynamic area of research in recent years. Robotics devices are in fact capable to quantify the performances of a rehabilitation task in treatments of several disorders of the arm and the shoulder of various central and peripheral etiology. Different systems for robot-aided neuro-rehabilitation are available for upper limb rehabilitation but the biomechanical parameters proposed until today, to evaluate the quality of the movement, are related to the specific robot used and to the type of exercise performed. Besides, none study indicated a standardized quantitative evaluation of robot assisted upper arm reaching movements, so the RMT is still far to be considered a standardised tool. In this paper a quantitative kinematic assessment of robot assisted upper arm reaching movements, considering also the effect of gravity on the quality of the movements, is proposed. We studied a group of 10 healthy subjects and results indicate that our advised protocol can be useful for characterising normal pattern in reaching movements.

Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis.

BACKGROUND AND OBJECTIVES: The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. METHODS: Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. RESULTS: The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m(2). The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. CONCLUSIONS: Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

Does pain relief influence recovery of consciousness? A case report of a patient treated with ziconotide.

For people with cervical spinal cord injury (SCI), access to computers can be difficult, thus several devices have been developed to facilitate their Disorders of consciousness (DOC) are difficult to classify. The degree of consciousness varies from coma to vegetative state or unresponsive wakefulness syndrome (UWS) and minimally conscious state. Correct diagnosis has important ethical and legal implications, and pain may be cause of misdiagnosis. We describe here a patient with traumatic brain injury, classified as UWS. His clinical picture was dominated by spasticity, and pain. He underwent intrathecal treatment of spasticity with baclofen. Improvement was not that expected. However, there was a dramatic improvement when ziconotide was added to relieve pain; the patient began to eat by mouth, talk, and his tracheal tube could be removed and he is currently classified as having severe disability. The suspension of ziconotide caused a clear re-worsening of clinical condition, reverted by his reintroduction. Pain is an important factor in patients with DOC. Anecdotal reports of improved consciousness with intrathecal baclofen therapy may be due to pain relief. Reduction of pain in DOC is important and drugs should not interfere with cognition, and must be effective and manageable. Ziconotide may be one of the possible candidate due to its synergistic antispastic action in combination with baclofen when an intratecal pump has been implanted.

Postganglionic sudomotor denervation in patients with multiple system atrophy.

OBJECTIVE: To evaluate postganglionic autonomic involvement in multiple system atrophy (MSA). METHODS: We quantified sudomotor innervation in skin biopsy of 29 patients with MSA (19 male and 10 female; age 60.0 ± 7.7 years) and 29 age- and sex-matched healthy subjects. Samples were obtained from thigh and leg and, in 20 out of the 29 cases, also from fingertip. Dysautonomic complaints were evaluated by SCOPA-AUT, a self-administered questionnaire. Sudomotor function was evaluated in a subgroup of patients by the silastic imprint test. Skin samples were processed by indirect immunofluorescence using pan-neuronal and selective cholinergic markers. Total length of sudomotor nerves was measured on digital confocal images using a semiautomated morphometric approach. RESULTS: Measurements of sudomotor nerve density (total length of nerve per volume of glandular tissue) favorably correlated to values obtained using a stereologic unbiased method. Sudomotor nerve density was lower in patients compared to controls in all the examined sites (0.9 ± 0.2 vs 1.9 ± 0.4 nm/µm(3), p < 0.001, in fingertip; 0.7 ± 0.2 vs 1.9 ± 0.5 nm/µm(3), p < 0.001, in thigh; 0.6 ± 0.2 vs 1.8 ± 0.4 nm/µm(3), p < 0.001, in leg). CONCLUSIONS: Our data support the hypothesis that postganglionic impairment occurs in MSA and may contribute with the coexisting degeneration of central structures to the development of dysautonomic disorders in this condition.

Predictors of recovery of responsiveness in prolonged anoxic vegetative state.

OBJECTIVE: The number of patients in prolonged postanoxic vegetative state (VS) is increasing. However, little information is available about prognostic markers of long-term outcome in patients who remain in VS more than 1 month postonset. The present 2-year prospective clinical study aimed to identify prognostic markers, recorded in the chronic phase, that might be useful for predicting recovery of responsiveness in a cohort of postanoxic VS patients. METHODS: We enrolled 43 inpatients with prolonged anoxic VS (23 female; age range 12-83 years). We collected data about medical history, clinical findings, and neurophysiological assessments at study entry (1-6 months postonset), and assessed their relationships with outcome at 24 months postonset; for defining outcome, patients were classified as responsive or unresponsive on the basis of clinical criteria and on Coma Recovery Scale-Revised (CRS-R). RESULTS: Nine patients had recovered responsiveness (but 2 of them died after awakening), whereas 12 patients remained in VS and 22 had died in VS. Functional abilities were severely affected in all responsive survivors. Responsive patients were significantly younger and showed higher CRS-R total score and lower Disability Rating Scale score at study entry than patients who did not recover. All responsive survivors had spared pupillary light reflex and nociceptive response, and paroxysmal sympathetic hyperactivity. Logistic regression analysis showed that the presence of median nerve somatosensory evoked potentials and CRS-R total score ≥ 6 were significant predictors of recovery of responsiveness. CONCLUSIONS: Clinical features and evoked potentials are useful predictors of long-term recovery of responsiveness in patients with prolonged postanoxic VS.