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

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

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

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

rTMS in the treatment of drug addiction: An update about human studies.

Drug addiction can be a devastating and chronic relapsing disorder with social, psychological and physical consequences, and more effective treatment options are needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has been assessed in a growing number of studies for its therapeutic potential in treating addiction. This review paper offers an overview on the current state of clinical research in treating drug addiction with rTMS. Because of the limited research in this area, all studies (including case reports) that evaluated the therapeutic use of rTMS in nicotine, alcohol or illicit drug addiction were included in this review. Papers published prior to December 2012 were found through an NCBI PubMed search (http://www.ncbi.nlm.nih.gov). A total of eleven studies were identified that met review criteria. There is nascent evidence that rTMS could be effective in reducing cocaine craving, and nicotine and alcohol craving and consumption, and might represent a potential therapeutic tool for treating addiction. Further studies are needed to identify the optimal parameters of stimulation for the most effective treatment of drug addiction, to improve our comprehension of the treatment neurophysiological effects, and to conduct rigorous, controlled efficacy studies with adequate power