Effects of Social Distancing on Quality of Life and Emotional-Affective Sphere of Caregivers and Older Patients Hospitalized in Rehabilitation Departments during COVID-19 Quarantine: An Observational Study.

During the COVID-19 emergency, institutional social distancing conditions were established, preventing family and caregivers' access to rehabilitation departments. Our study goal was to assess inpatients' and caregivers' anxiety, depression, and Quality of Life (QoL) during the Italian lockdown due to the pandemic. We investigated anxiety, depression, and QoL in 53 patients and 51 caregivers, using the Beck Anxiety Inventory (BAI), the Beck Depression Inventory-II (BDI-II), and the Short Form 36 Health Survey (SF36). These questionnaires were given to patients after one (T0) and two months (T1) since the hospitalization. The BAI showed that anxiety was moderate for 7.5% of patients and 23.5% of caregivers, and severe for 35.8% of patients and 17.6% of caregivers. The BDI found moderate depression in 11.3% of patients and 15.7% of caregivers, and severe depression in 34.0% of patients and 9.8% of caregivers. Depression was higher in patients than caregivers, while no differences were detected in anxiety. Compared to normative data, patients' QoL declined in all eight SF36 dimensions, while caregivers' QoL declined only in social, emotional, and mental components. Unexpectedly, patients still hospitalized at T1 showed significant improvements in both anxiety and three QoL subscores. These findings emphasize the importance of psychological support for patients and their families.

Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study.

OBJECTIVE: Patients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment. METHODS: Patients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients. RESULTS: We enrolled 25 MuSK-MG patients (20 females), aged 16-79 years at the study time, with disease duration ranging 0.6-48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005). CONCLUSIONS: Cholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease. SIGNIFICANCE: R-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is.

Serotonin Levels and Cognitive Recovery in Patients with Subacute Stroke after Rehabilitation Treatment.

Post-stroke depression and cognitive impairment are common conditions affecting patients after stroke. Serotonin is a neurotransmitter involved in modulating, among others, mood, cognition, learning, and memory. Sub-optimal serotonin activity may be in part responsible for cognitive deficits seen in depression. In this pilot study serotonin levels were evaluated in 29 patients with sub-acute stroke before and after a rehabilitation treatment (consisting of a program of upper limb robotic rehabilitation in addition to conventional physical therapy treatment). We employed the Back Depression Inventory scale to evaluate symptoms of depression, and specific tools to evaluate cognitive functions. We found a significant reduction of the serotonin levels after rehabilitation in the whole group (T0: 85.9 ± 92.4 ng/mL; T1: 61.9 ± 58.4 ng/mL; p = 0.0018), as well as in the subgroup of patients untreated with Selective Serotonin Reuptake Inhibitors (SRRI), (mean serotonin at T0: 154.0 ± 102.3 ng/mL; mean serotonin at T1: 92.9. ± 68.7 ng/mL at T1; p = 0.005). We also found a correlation with cognitive assessment: in particular, the change from baseline of the serotonin (ΔSerotonin) was correlated with the changes from baseline of the Rey's Figure (ΔROCF) (r = 0.535; p < 0.05), the Tower of London (ΔToL) (subscore point: r = 0.621; p < 0.005; subscore time: r = -0.619; p < 0.005) meaning that a serotonin levels decrease is associated with a worsening of cognitive functions. Considering patients treated and untreated with SSRIs separately, in patients treated with SSRIs (n = 16) we found only a positive correlation between ∆Serotonin and ∆ToL (subscore point: r= 0.587; p = 0.045), whereas in patients untreated with SSRIs (n = 13) we found a positive correlations between ΔSerotonin and ΔROCF (r = 0.700; p = 0.036), ∆Stroop (subscore time: r = 0.750; p = 0.020) and ∆Tol (subscore point: r = 0.740; p = 0.023) and a negative correlation between ΔSerotonin and ∆Tol (subscore time: r= -0.833; p = 0.005). These results suggest that variation of serotonin levels should be monitored in patients during a rehabilitation program, not only for their relationship with depression symptoms, but also for the correlation with cognitive performance.

Association Study of SLC6A4 (5-HTTLPR) Polymorphism and Its Promoter Methylation with Rehabilitation Outcome in Patients with Subacute Stroke.

Recently it has been suggested that serotonin transporter (SLC6A4) and its 5HTTLPR polymorphism could be involved in post stroke recovery. Here, we characterized the methylation profile of two different CpG islands within the SLC6A4 promoter region in the whole blood of 50 patients with subacute stroke before and after a six-week rehabilitation treatment. These patients were genotyped for 5HTTLPR polymorphism identifying patients on the basis of short (S) and L (L) alleles: 17 patients LL, 22 patients LS and 11 patients SS. At baseline, all CpG sites for both CpG islands displayed a heterogeneous methylation percentage that were not influenced by the different genotypes. After rehabilitation, we found a significant variation in the methylation levels (increase/decrease) in the specific CpG sites of both CpG islands. The statistical analysis showed a significant relationship between the LL, LS and SS alleles and the outcome of the rehabilitation intervention (χ2 (2,50) = 6.395, p = 0.041). Specifically, we found a significant difference between patients with or without a favorable outcome in the LL (11.1% with a favorable outcome) and in the SS (54.4% with a favorable outcome) groups. Our data suggest that 5-HTTLPR polymorphisms and SLC6A4 promoter methylation may be employed as a non-invasive biological marker of recovery in patients with stroke undergoing rehabilitation.

Robotic Rehabilitation: An Opportunity to Improve Cognitive Functions in Subjects With Stroke. An Explorative Study.

Background: After a stroke, up to three-quarters of acute and subacute stroke survivors exhibit cognitive impairment, with a significant impact on functional recovery, quality of life, and social engagement. Robotic therapy has shown its effectiveness on motor recovery, but its effectiveness on cognitive recovery has not fully investigated. Objective: This study aims to assess the impact of a technological rehabilitation intervention on cognitive functions in patients with stroke, using a set of three robots and one sensor-based device for upper limb rehabilitation. Methods: This is a pilot study in which 51 patients were enrolled. An upper limb rehabilitation program was performed using three robots and one sensor-based device. The intervention comprised motor/cognitive exercises, especially selected among the available ones to train also cognitive functions. Patients underwent 30 rehabilitation sessions, each session lasting 45 minutes, 5 days a week. Patients were assessed before and after the treatment with several cognitive tests (Oxford Cognitive Scale, Symbol Digit Modalities Test, Digit Span, Rey-Osterrieth Complex Figure, Tower of London, and Stroop test). In addition, motor (Fugl-Meyer Assessment and Motricity Index) and disability (modified Barthel Index) scales were used. Results: According to the Oxford Cognitive Scale domains, a significant percentage of patients exhibited cognitive deficits. Excluding perception (with only one patient impaired), the domain with the lowest percentage of patients showing a pathological score was praxis (about 25%), while the highest percentage of impaired patients was found in calculation (about 70%). After the treatment, patients improved in all the investigated cognitive domains, as measured by the selected cognitive assessment scales. Moreover, motor and disability scales confirmed the efficacy of robotics on upper limb rehabilitation in patients with stroke. Conclusions: This explorative study suggests that robotic technology can be used to combine motor and cognitive exercises in a unique treatment session. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04164381.

BDNF rs6265 Polymorphism and Its Methylation in Patients with Stroke Undergoing Rehabilitation.

Brain-Derived Neurotrophic Factor (BDNF) and its rs6265 single nucleotide polymorphism (SNP) play an important role in post-stroke recovery. We investigated the correlation between BDNF rs6265 SNP and recovery outcome, measured by the modified Barthel index, in 49 patients with stroke hospitalized in our rehabilitation center at baseline (T0) and after 30 sessions of rehabilitation treatment (T1); moreover, we analyzed the methylation level of the CpG site created or abolished into BDNF rs6265 SNP. In total, 11 patients (22.4%) were heterozygous GA, and 32 (65.3%) and 6 (12.2%) patients were homozygous GG and AA, respectively. The univariate analysis showed a significant relationship between the BDNF rs6265 SNP and the modified Barthel index cut-off (χ2(1, N = 48) = 3.86, p = 0.049), considering patients divided for carrying (A+) or not carrying (A-) the A allele. A higher percentage of A- patients obtained a favorable outcome, as showed by the logistic regression model corrected by age and time since the stroke onset, compared with the A+ patients (OR: 5.59). At baseline (T0), the percentage of BDNF methylation was significantly different between GG (44.6 ± 1.1%), GA (39.5 ± 2.8%) and AA (28.5 ± 1.7%) alleles (p < 0.001). After rehabilitation (T1), only patients A- showed a significant increase in methylation percentages (mean change = 1.3, CI: 0.4-2.2, p = 0.007). This preliminary study deserves more investigation to confirm if BDNF rs6265 SNP and its methylation could be used as a biological marker of recovery in patients with stroke undergoing rehabilitation treatment.

Management challenges in muscle-specific tyrosine kinase myasthenia gravis.

Myasthenia gravis with antibodies to muscle-specific tyrosine kinase (MuSK-MG) is generally considered a severe disease because of the associated weakness distribution with prevalent involvement of bulbar muscles and a rapidly progressive course and early respiratory crises. Its treatment can be unrewarding, owing to poor response to acetylcholinesterase inhibitors in most patients, disease relapses in spite of high-dose immunosuppression, and development of permanent bulbar weakness. High-dose prednisone plus plasma exchange is the recommended approach for treating rapidly progressive bulbar weakness. In the disease management, oral steroids proved effective, plasma exchange produced marked, albeit short-term, improvement, while conventional immunosuppressants were comparatively less effective. Rituximab is a promising treatment for refractory MuSK-MG; in uncontrolled studies, nearly all treated patients achieved significant improvement with substantial decrease of medication. It is yet to be clarified whether the early use of rituximab could prevent the permanent bulbar weakness, which constitutes a relevant disability in these patients.