Prion and prion-like protein strains: Deciphering the molecular basis of heterogeneity in neurodegeneration

Increasing evidence suggests that neurodegenerative disorders share a common pathogenic feature: The presence of deposits of misfolded proteins with altered physicochemical properties in the Central Nervous System. Despite a lack of infectivity, experimental data show that the replication and propagation of neurodegenerative disease-related proteins including amyloid-\u3b2 (A\u3b2), tau, \u3b1-synuclein and the transactive response DNA-binding protein of 43 kDa (TDP-43) share a similar pathological mechanism with prions. These observations have led to the terminology of "prion-like" to distinguish between conditions with noninfectious characteristics but similarities with the prion replication and propagation process. Prions are considered to adapt their conformation to changes in the context of the environment of replication. This process is known as either prion selection or adaptation, where a distinct conformer present in the initial prion population with higher propensity to propagate in the new environment is able to prevail over the others during the replication process. In the last years, many studies have shown that prion-like proteins share not only the prion replication paradigm but also the specific ability to aggregate in different conformations, i.e., strains, with relevant clinical, diagnostic and therapeutic implications. This review focuses on the molecular basis of the strain phenomenon in prion and prion-like proteins

The use ultrasound guided for refilling intrathecal baclofene pump in complicated clinical cases: A practical approach

Muscular spasticity due to neurological disorders is a heavy cause of severe pain and disability for many patients, compromising the independence and quality life. Baclofene is a good tool to guarantee patients independence and pain control. Anyway in chronic therapy oral treatment become unsatisfactory. In all these cases, intrathecal baclofen therapy (ITB), after sub fascial implantation of intrathecal pumps is used as an important long term treatment to reduce spasticity. After pump implantation the drug reservoir must be refilled periodically in order to maintain the reduction of spasticity and avoid the symptoms and signs of withdrawal. ITB refilling, which involves the insertion of a needle through the skin until the access port of the pump, is often hard, mainly due to the layer of abdominal fat, spasticity, suboptimal pump positioning, pump rotation or inversion, and scar formation over the implantation site. To avoid the difficulties of ITB refilling radiography or other invasive supportive examinations are sometimes needed. We reported here our experience and we suggest a simple method to use the ultrasound in refilling with particular attention to some cases with complications after implantation with a difficult approach in refilling. We used the ultrasound examination to identify the access port of her pump so as to avoid multiple needle punctures and infections and radiation exposition. Ultrasound-guided technique may facilitate ITB refill in technically challenging cases. With ultrasound ITB was easily detectable and was quite simple to identify the exact point of needle injection. In the last years different new applications for ultrasounds are emerging. In our opinion the use of Doppler ultrasounds in the study of muscles and nerves represent an emerging tool for the physician's neurological rehabilitation

Return to school in the COVID-19 era: considerations for temperature measurement

COVID-19 pandemics required a reorganisation of social spaces to prevent the spread of the virus. Due to the common presence of fever in the symptomatic patients, temperature measurement is one of the most common screening protocols. Indeed, regulations in many countries require temperature measurements before entering shops, workplaces, and public buildings. Due to the necessity of providing rapid non-contact and non-invasive protocols to measure body temperature, infra-red thermometry is mostly used. Many countries are now facing the need to organise the return to school and universities in the COVID-19 era, which require solutions to prevent the risk of contagion between students and/or teachers and technical/administrative staff. This paper highlights and discusses some of the strengths and limitations of infra-red cameras, including the site of measurements and the influence of the environment, and recommends to be careful to consider such measurements as a single \u201csafety rule\u201d for a good return to normality

Skin wetness sensitivity across body sites commonly affected by pain in people with migraine

Objective: The objective of this study was to evaluate skin wetness perception and thermal sensitivity in people with migraine and similar healthy controls.Background: Environmental triggers, such as cold and humidity, are known triggers for pain in people with migraine. Sensory inputs might be implicated in such heightened responses to cold-humid environments, such that a migraine-induced hypersensitivity to cold wetness could be present in people with migraine. However, we lack empirical evidence on skin thermal and wetness sensitivity across skin sites commonly associated with reported pain in migraine, such as the forehead.Methods: This prospective cross-sectional observational study, conducted in a university hospital setting, evaluated skin wetness perceptions and thermal sensations to wet non-noxious warm-wet, neutral-wet, and cold-wet stimuli applied to the forehead, the posterior neck, and the index finger pad of 12 patients with migraine (mean and standard deviation for age 44.5 +/- 13.2 years, 7/12 [58%] women) and 36 healthy controls (mean and standard deviation for age 39.4 +/- 14.6 years, 18/36 [50%] women).Results: On the forehead, people with migraine reported a significantly higher wetness perception than healthy controls across all thermal stimulus (15.1 mm, 95% confidence interval [CI]: 1.8 to 28.5, p = 0.027, corresponding to similar to 15% difference), whereas no significant differences were found on the posterior neck nor on the index finger pad. We found no differences among groups in overall thermal sensations (-8.3 mm, 95% CI: -24.0 to 7.3, p = 0.291; -7.8 mm, 95% CI: -25.3 to 9.7, p = 0.375; and 12.4 mm, 95% CI: -4.0 to 28.9, p = 0.133; forehead, posterior neck, and index finger, respectively).Conclusion: These findings indicate that people with migraine have a heightened sensitivity to skin wetness on the forehead area only, which is where pain attacks occur. Future studies should further explore the underlying mechanisms (e.g., TRPM8-mediated cold-wet allodynia) that lead to greater perception of wetness in people with migraine to better understand the role of environmental triggers in migraine

Rapidly evolving Creutzfeldt-Jakob disease in COVID-19: from early status epilepticus to fatal outcome

We report the case of a 70-year-old man coming to our attention for new onset refractory status epilepticus (NORSE) in a rapidly evolving CJD during SARS-CoV-2 co-infection. Our case report describes a fulminant CJD evolution associated with SARS-CoV-2 infection, which led to patient death after 15 days from admission. First EEG presented continuous diffuse spikes, sharp waves and sharp-and-slow wave complexes, pattern consistent with a non-convulsive status epilepticus (NORSE). Our case supports how CJD with SARS-CoV-2 co-infection could be characterized by an accelerated evolution, as already hypothesize for others microorganism infections, and how the diagnosis might be more challenging due to its uncommon presentations, such as NORSE

e-Health solution for home patient telemonitoring in early post-acute TIA/Minor stroke during COVID-19 pandemic

Background: When it comes to critical early post-acute TIA/stroke phase, there is a lack of a comprehensive multi-parametric telemonitoring system. The COVID-19 emergency, its related global mobility restrictions and fear of hospitalization further highlighted the need of a comprehensive solution. Objective: We aimed to design and test a pragmatic e-Health system based on multiparametric telemonitoring to support of TIA/stroke patients in sub-acute phase during the COVID-19 pandemic. Methods: We proposed a telemonitoring system and protocol for TIA/minor stroke patients during COVID-19 pandemic for patients at risk of stroke recurrence. This system involves the use of portable devices for BP/HR/SpO2/temperature sensing, panic-button, gateway, and a dedicated ICT platform. The protocol is a 14-day multiparametric telemonitoring, therapy, and emergency intervention based on vital sign alteration notifications. We conducted a proof-of-concept validation test on 8 TIA/minor stroke patients in the early post-acute phase (< 14 days from ischemic event). Results: The proposed solution allowed to promptly and remotely identify vital sign alterations at home during the early post-acute phase, allowing therapy and behavioral intervention adjustments. Also, we observed a significant improvement of quality of life, as well as a significant reduction of anxiety and depression status. TUQ showed ease of use, good interface quality and high user satisfaction of the proposed solution. The 3-month follow-up showed total adherence of prescribed therapy and no stroke/TIA recurrence or other emergency department admissions. Conclusion: The proposed e-Health solution and telemonitoring protocol may be highly useful for early post-acute remote patient management, thus supporting constant monitoring and patient adherence to the treatment pathway, especially during the COVID-19 emergency

Wake-up Stroke Outcome Prediction by Interpretable Decision Tree Model

Outcome prediction in wake-up ischemic stroke (WUS) is important for guiding treatment strategies, in order to improve recovery and minimize disability. We aimed at producing an interpretable model to predict a good outcome (NIHSS 7-day<5) in thrombolysis treated WUS patients by using Classification and Regression Tree (CART) method. The study encompassed 104 WUS patients and we used a dataset consisting of demographic, clinical and neuroimaging features. The model was produced by CART with Gini split criterion and evaluated by using 5-fold cross-validation. The produced decision tree model was based on NIHSS at admission, ischemic core volume and age features. The predictive accuracy of model was 86.5% and the AUC-ROC was 0.88. In conclusion, in this preliminary study we identified interpretable model based on clinical and neuroimaging features to predict clinical outcome in thrombolysis treated wake-up stroke patients

Bortezomib-induced muscle toxicity in multiple myeloma

Multiple myeloma (MM) accounts for ~13% of all hematologic malignancies. Bortezomib treatment is effective in MM, but can be complicated with neurological side effects. We describe a patient with symptomaticMM who had a reversible metabolic myopathy associated with bortezomib administration and pathologically characterized by excessive storage of lipid droplets together with mitochondrial abnormalities. In a single-center prospective study, 14 out of 24 patients with symptomatic MM were treated with bortezomib and, among these, 7 developed muscular signs and/or symptoms. The myopathy was characterized by a proximal muscle weakness involving lower limbs and was an early complication. Complete resolution of muscle weakness occurred after treatment discontinuation. Conversely, none of the patients who received a treatment without bortezomib developed muscular symptoms. Experimental studies demonstrate that in primary human myoblasts bortezomib at low concentrations leads to excessive storage of lipid droplets together with structural mitochondrial abnormalities, recapitulating the pathologic findings observed in patient's muscle. Our data suggest that patients treated with bortezomib should be monitored for muscular signs and/or symptoms and muscle weakness should alert the clinician to the possibility of myopathy. Bortezomib-induced metabolic myopathy is a potentially reversible entity with important implications for management and treatment of patients with MM

Four-week trunk-specific exercise program decreases forward trunk flexion in Parkinson's disease: A single-blinded, randomized controlled trial

INTRODUCTION: Pathological forward trunk flexion is a disabling and drug-refractory motor complication of Parkinson's disease (PD) leading to imbalance, pain, and fall-related injuries. Since it might be reversible, early and multidisciplinary management is emphasised. The primary aim was to compare the effects of a four-week trunk-specific rehabilitation program on the severity of the forward trunk flexion. The secondary aim was to compare the training effects on the motor impairments, dynamic and static balance, pain, falls, and quality of life. METHODS: 37 patients with PD (H&Y\u202f 64\u202f4) and forward trunk flexion were randomized in the experimental (n\u202f=\u202f19) or control group (n\u202f=\u202f18). The former consisted of active self-correction exercises with visual and proprioceptive feedback, passive and active trunk stabilization exercises and functional tasks. The latter consisted of joint mobilization, muscle strengthening and stretching, gait and balance exercises. Protocols lasted 4 weeks (60\u202fmin/day, 5 days/week). Before, after, and at 1-month follow-up, a blinded examiner evaluated patients using primary and secondary outcomes. The primary outcome was the forward trunk flexion severity (degree). Secondary outcomes were the UPDRS III, dynamic and static balance, pain falls, and quality of life assessment. RESULTS: The experimental group reported a significantly greater reduction in forward trunk flexion than the control group from T0 to both T1 (p\u202f=\u202f0.003) and T2 (p\u202f=\u202f0.004). The improvements in dynamic and static balance were significantly greater for the experimental group than the control group from T0 to T2 (p\u202f=\u202f0.017 and 0.004, respectively). Comparable effects were reported on the other outcomes. Pre-treatment forward trunk flexion values were highly correlated to post-treatment trunk deviation changes. CONCLUSION: The four-week trunk-specific rehabilitation training decreased the forward trunk flexion severity and increased postural control in patients with PD. NCT03741959

Neurophysiological and BOLD signal uncoupling of giant somatosensory evoked potentials in progressive myoclonic epilepsy: a case-series study

In progressive myoclonic epilepsy (PME), a rare epileptic syndrome caused by a variety of genetic disorders, the combination of peripheral stimulation and functional magnetic resonance imaging (fMRI) can shed light on the mechanisms underlying cortical dysfunction. The aim of the study is to investigate sensorimotor network modifications in PME by assessing the relationship between neurophysiological findings and blood oxygen level dependent (BOLD) activation. Somatosensory-evoked potential (SSEP) obtained briefly before fMRI and BOLD activation during median-nerve electrical stimulation were recorded in four subjects with typical PME phenotype and compared with normative data. Giant scalp SSEPs with enlarger N20-P25 complex compared to normal data (mean amplitude of 26.2\u2009\ub1\u20098.2\u2009\u3bcV after right stimulation and 27.9\u2009\ub1\u20093.7\u2009\u3bcV after left stimulation) were detected. Statistical group analysis showed a reduced BOLD activation in response to median nerve stimulation in PMEs compared to controls over the sensorimotor (SM) areas and an increased response over subcortical regions (p\u2009\u20092.3, corrected). PMEs show dissociation between neurophysiological and BOLD findings of SSEPs (giant SSEP with reduced BOLD activation over SM). A direct pathway connecting a highly restricted area of the somatosensory cortex with the thalamus can be hypothesized to support the higher excitability of these areas