The impact of patients' pre-treatment expectations on immunosuppressive treatment outcomes in myasthenia gravis: A pilot correlational study.

INTRODUCTION/AIMS: The impact of treatment expectations on active treatment outcomes has not been specifically investigated in neuromuscular disorders. We thus explored in myasthenia gravis (MG) the contribution of patients' pre-treatment expectations combined with an immunosuppressant drug on treatment outcomes. METHODS: This pilot correlational study involved 17 patients with generalized MG, scheduled to start immunosuppressant azathioprine. At baseline, a healthcare professional administered: (i) the Stanford Expectations of Treatment Scale; (ii) a structured checklist paper form asking patients which side-effects they expected to develop after starting azathioprine, coupled with a standardized framing of statements. Quantitative Myasthenia Gravis (QMG) score and daily dose of concomitant drugs were assessed by neurologists as clinical outcomes. Clinical outcomes and side-effects were re-assessed at 3 and 6 months, and clinical outcomes were monitored at 18 months. RESULTS: Clinically significant improvement in the QMG scores was achieved at 3 or 6 months. The level of state anxiety appeared to act as moderator of pre-treatment negative expectations (strong, positive, indicative correlation, rs = .733, p = .001). The latter were, in turn, associated with the fulfillment of side-effects that patients expected to develop with the new treatment (moderate, positive, indicative correlation, rs = .699, p = .002). No significant correlation emerged between positive and negative expectations. DISCUSSION: Our findings show a very quick clinical response and also suggest that patients' expectations and anxiety contributed to treatment outcomes, highlighting the importance of promoting safety messages and education strategies around newly introduced treatments. Future goals include evaluating a larger cohort that includes a matched control group.

Efficacy of rituximab in anti-myelin-associated glycoprotein demyelinating polyneuropathy: Clinical, hematological and neurophysiological correlations during 2 years of follow-up.

BACKGROUND AND PURPOSE: We evaluated the clinical and neurophysiological efficacy of rituximab (RTX) in a neurophysiologically homogeneous group of patients with monoclonal gammopathy and immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody (anti-MAG) demyelinating polyneuropathy. METHODS: Twenty three anti-MAG-positive polyneuropathic patients were prospectively evaluated before and for 2 years after treatment with RTX 375 mg/m2 . The Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (INCAT-ds), modified INCAT sensory score (mISS), Medical Research Council sum score, Patients' Global Impression of Change scale were used, IgM levels were assessed and extensive electrophysiological examinations were performed before (T0) and 1 year (T1) and 2 years (T2) after RTX treatment. RESULTS: At T1 and T2 there was a significant reduction from T0 both in mISS and in INCAT-ds, with a p value < 0.001 in the inferential Friedman's test overall analysis. Ulnar nerve Terminal Latency Index and distal motor latency significantly changed from T0 to T1 and in the overall analysis (p = 0.001 and p = 0.002), and ulnar nerve sensory nerve action potential (SNAP) amplitude was significantly increased at T2 from T1, with a p value < 0.001 in the overall analysis. Analysis of the receiver-operating characteristic curves showed that a 41.8% increase in SNAP amplitude in the ulnar nerve at T2 from T0 was a fair predictor of a mISS reduction of ≥2 points (area under the curve 0.85; p = 0.005; sensitivity: 90.9%, specificity: 83.3%). CONCLUSIONS: This study suggests that RTX is effective in patients with clinically active demyelinating anti-MAG neuropathy over 2 years of follow-up, and that some neurophysiological variables might be useful for monitoring this efficacy.

Perfusion-computed tomography for simultaneous bilateral middle cerebral artery occlusion.

Bilateral simultaneous middle cerebral artery occlusion is a rare condition that may lead to severe neurological disability or death, thus requiring rapid intervention in order to restore vessels patency and brain perfusion. Perfusion-computed tomography is demonstrated to be a fundamental tool for selecting stroke patients candidate to mechanical thrombectomy, but its role for guiding the optimal strategy of endovascular treatment in concomitant multivessel cerebral occlusion has never been reported. We describe a case of bilateral middle cerebral artery occlusion in which perfusion-computed tomography was crucial both for addressing to endovascular procedure and planning the sequence treatment of mechanical thrombectomies.

Carotid artery stenting during endovascular thrombectomy for acute ischemic stroke with tandem occlusion: the Italian Registry of Endovascular Treatment in Acute Stroke.

PURPOSE: The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT. METHODS: We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3 months' mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage. RESULTS: Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3 months' mortality (OR 0.407, 95% CI 0.171-0.969, p = 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3 months' mortality (aOR 0.430, 95% CI 0.187-0.989, p = 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121-3.518, p = 0.019), successful recanalization (aOR 2.433, 95% CI 1.263-4.686, p = 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173-7.050, p = 0.021). CAS was associated with lower 3 months mortality (OR 0.373, 95% CI 0.141-0.982, p = 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099-3.942, p = 0.024) after adjustment for variables associated with 3 months' mortality and successful recanalization, respectively. CONCLUSIONS: Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3 months' mortality.

COVID-19 pandemic-related anxiety, distress and burnout: prevalence and associated factors in healthcare workers of North-West Italy.

BACKGROUND: The COVID-19 pandemic caused drastic changes in healthcare and severe social restrictions. Healthcare workers (HCWs) are on the front line against the virus and have been highly exposed to pandemic-related stressors, but there are limited data on their psychological involvement for a large sample in Italy. AIMS: To investigate the prevalence of anxiety, distress and burnout in HCWs of North-West Italy during the COVID-19 pandemic, and to detect potential psychosocial factors associated with their emotional response. METHOD: This cross-sectional, survey-based study enrolled 797 HCWs. Participants completed the Impact of Event Scale - Revised, the State-Trait Anxiety Inventory - Form Y and the Maslach Burnout Inventory; demographic, family and work characteristics were also collected. Global psychological outcome, differences among professions and independent factors associated with worst psychological outcome were assessed. RESULTS: Almost a third of the sample had severe state anxiety and distress, high emotional exhaustion and depersonalisation, and low personal accomplishment. Distress was higher in women and nurses, whereas depersonalisation was higher in men. Family division, increased workload, job changes and frequent contact with COVID-19 were associated with worst psychological outcome. Trait anxiety was associated with significantly higher risk for developing state anxiety, distress and burnout. CONCLUSIONS: An elevated psychological burden related to the COVID-19 pandemic was observed in HCWs of North-West Italy. The identification of family and work characteristics and a psychological pre-existing condition as factors associated with worst psychological outcome may help provide a tailored, preventive, organisational and psychological approach in counteracting the psychological effects of future pandemics.

Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis.

INTRODUCTION: Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because of the risk of progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV). Areas covered: This review analyzes all the safety aspects related to the use and safety of natalizumab in MS patients. Other than PML, post-marketing, safety red-flags have been reported, as liver or haematological serious adverse events. Pregnancy evidences will be pointed out. The risk of PML depends on: concomitant or previous immunosuppression, exposure duration, anti-JCV antibody level. In natalizumab-related PML the average survival is 77%; prognostic features and information for the earliest identification of PML have been identified to maximally reduce its incidence, mortality and morbidity. Expert opinion: Natalizumab is a highly effective drug for MS patients but its safety issues represent a relevant limitation and impose strict clinical surveillance of treated patients. Some post-marketing safety red-flags have been pointed out, with higher attention to severe liver failures and limphoma cases. If PML and its consequences are considered the most relevant issues, a continuous surveillance must be maintained also regarding other possible SAEs like liver diseases and malignancies.

Pro-inflammatory cytokine and chemokine mRNA blood level in multiple sclerosis is related to treatment response and interferon-beta dose.

Of 37 multiple sclerosis patients, 19 suboptimal responders were randomized to 375 (n=12) or 250µg (n=7) interferon (IFN)-ß-1b. mRNA levels of 23 cytokines, chemokines, and chemokine receptors were quantified by TaqMan low-density array (TLDA) real-time polymerase chain reaction. Better treatment responses or increased IFN-ß doses were associated with elevated IL-10 and TGF-ß and decreased CXCL10, IL-18, IFN-γ, and TNF-α transcript levels. Adjusting for dose, poor treatment responses resulted in a 4-fold increase in CXCL10 and IFN-γ expression (Mantel-Haenszel RR=3.74, p<0.0001). CXCL10 and IFN-γ mRNA levels were reliable indicators of treatment response. TLDA can be used to tailor IFN-ß-1b therapy.