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Objective To test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1). Methods In a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects. Results The facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS. Conclusions The results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations. Significance These observations can be used to optimize iTBS investigational and therapeutic applications.

Introduction Isolated head tremor, a pathological condition characterized by head tremor without dystonic postures or tremor in other body parts, has recently been suggested to be a form of dystonia. It is however still unclear whether isolated head tremor precedes dystonia or remains unmodified overtime. Methods We enrolled 20 patients with isolated head tremor. For each patient, we assessed videos recorded at enrollment and after 5 years. The videotapes were reviewed by two independent experienced movement disorder specialists who evaluated and scored tremor and CD severity using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor and the revised Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), respectively. Results Upon enrollment, all 20 patients showed isolated head tremor. Mean tremor severity was 2.7 ± 0.9 as measured using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor total score. At the 5-year follow-up examination, 15 (75%) of the 20 patients with isolated head tremor showed dystonic postures in the neck, while the remaining 5 patients (25%) had only isolated head tremor. Mean severity of dystonia as measured using the TWSTRS-2 total score was 11.8 ± 3.6. Head tremor severity was unchanged between baseline and the 5-year follow-up examination (p > 0.05). At the follow-up examination, no patients had tremor or dystonia in a body part other than the neck, nor did they develop bradykinesia or other parkinsonian signs. Conclusions Our longitudinal study demonstrated that patients with isolated head tremor may develop cervical dystonia over time.

We aimed to investigate salivary caffeine content, caffeine absorption and metabolism in Parkinson’s disease (PD) and verify whether salivary caffeine can be used as a biomarker of PD. We enrolled 98 PD patients and 92 healthy subjects. Caffeine and its major metabolite, paraxanthine, were measured in saliva samples collected before and 4 h after the oral intake of caffeine (100 mg). We measured caffeine absorption as the normalized increase in caffeine levels, and caffeine metabolism as the paraxanthine/caffeine ratio. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the Hoehn & Yahr, the presence of motor complications, and levodopa equivalent dose (LED) were assessed and correlated with caffeine levels, absorption, and metabolism. The effects of demographic and environmental features possibly influencing caffeine levels were also investigated. Caffeine levels were decreased in patients with moderate/advanced PD, while caffeine levels were normal in patients with early and de-novo PD, unrelated to caffeine intake. Caffeine absorption and metabolism were normal in PD. Decreased salivary caffeine levels in PD were associated with higher disease severity, longer duration, and the presence of motor complications, no significant association was found with LED. Salivary caffeine decrease correlates with PD progression.

OBJECTIVE: To review studies assessing the efficacy of occupational therapy interventions on quality of life in patients with Parkinson's disease. METHOD: We followed the international guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses checklist. Databases (PubMed, Physiotherapy Evidence Database, OTsekeer, Scopus, Cinhal, and Web of Science) were searched to identify randomized controlled trials of occupational therapy interventions in patients with Parkinson's disease up to 2019 and with no restriction on language. The primary outcome of the meta‐analysis was the evaluation of quality of life following occupational therapy interventions. Because of the heterogeneity of the studies, we examined the data by using a random effect model. RESULTS: We identified 15 randomized controlled trials that met the inclusion criteria, and 4 of these were included in the meta‐analysis. Studies with a follow‐up of 2 to 3 months showed that occupational therapy interventions significantly improved the quality of life in patients with Parkinson's disease, with a mean difference of −2.08 (95% confidence interval, −2.52 to −1.64; P

Background Parkinson's disease patients may show a tremor that appears after a variable delay while the arms are kept outstretched (re-emergent tremor). The objectives of this study were to investigate re-emergent tremor pathophysiology by studying the role of the primary motor cortex in this tremor and making a comparison with rest tremor. Methods We enrolled 10 Parkinson's disease patients with both re-emergent and rest tremor. Tremor was assessed by spectral analysis, corticomuscular coherence and tremor-resetting produced by transcranial magnetic stimulation over the primary motor cortex. We also recorded transcranial magnetic stimulation-evoked potentials generated by motor cortex stimulation during rest tremor, tremor suppression during wrist extension, and re-emergent tremor. Spectral analysis, corticomuscular coherence, and tremor resetting were compared between re-emergent tremor and rest tremor. Results Re-emergent tremor showed significant corticomuscular coherence, causal relation between motor cortex activity and tremor muscle and tremor resetting. The P60 component of transcranial magnetic stimulation-evoked potentials reduced in amplitude during tremor suppression, recovered before re-emergent tremor, was facilitated at re-emergent tremor onset, and returned to values similar to those of rest tremor during re-emergent tremor. Compared with rest tremor, re-emergent tremor showed similar corticomuscular coherence and tremor resetting, but slightly higher frequency. Conclusions Re-emergent tremor is causally related with the activity of the primary motor cortex, which is likely a convergence node in the network that generates re-emergent tremor. Re-emergent tremor and rest tremor share common pathophysiological mechanisms in which the motor cortex plays a crucial role. © 2020 International Parkinson and Movement Disorder Society.

Introduction Transcranial magnetic stimulation-evoked electroencephalography potentials (TEPs) have been used to study motor cortical excitability in healthy subjects and several neurological conditions. However, optimal recording parameters for TEPs are still debated. Stimulation rates could affect TEP amplitude due to plasticity effects, thus confounding the assessment of cortical excitability. We tested whether short interpulse intervals (IPIs) affect TEP amplitude. Methods We investigated possible changes in TEP amplitude and global mean field amplitude (GMFA) obtained with stimulation of the primary motor cortex at IPIs of 1.1–1.4 s in a group of healthy subjects. Results We found no differences in TEP amplitude or GMFA between the first, second and last third of trials. Discussion Short IPIs do not affect TEP size and can be used without the risk of confounding effects due to short-term plasticity.

We evaluated levels of serum neurofilament light chains (NfL), a known biomarker of neuroaxonal damage, in patients with cervical dystonia (CD) and healthy controls (HCs). CD patients had normal NfL levels supporting the hypothesis that CD may be considered as a functional network disorder rather than as a neurodegenerative disease.

Introduction Suicidal ideation is increased in Parkinson's disease (PD) patients. The possible relationship between parkinsonian motor and non-motor symptoms and suicidal ideation in PD is unknown. The aim of the study was to evaluate suicidal ideation in patients with PD in a controlled study specifically designed to identify the clinical correlates of PD suicidal ideation. Methods We consecutively enrolled 100 patients with PD, 76 patients with psoriasis and 80 healthy subjects. Motor symptoms and complications were evaluated by using the International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale. Non-motor symptoms were evaluated by means of the Non-Motor Symptoms assessment scale for PD. All patients also underwent a psychiatric evaluation that included the administration of the Columbia-Suicide Severity Rating Scale. Results Suicidal ideation was present in 31% of PD patients, 16% of patients with psoriasis and 2% of healthy controls. PD patients showing suicidal ideation have more frequent motor complications, more severe non-motor symptoms and a higher perceived disability than patients without suicidal ideation. Suicidal ideation correlated with the presence of motor complications as well as with non-motor symptom severity, perceived disability severity and the presence of psychiatric disorders. Conclusions Our findings showed that suicidal ideation is increased in PD patients compared with healthy controls and patients with psoriasis and that several clinical PD features, including motor complications and non-motor symptoms, are associated with suicidal ideation in PD. The results suggest a multi-factorial origin of PD suicidal ideation.

Introduction Alpha-synuclein (α-syn) aggregation is the pathological hallmark of Parkinson's Disease (PD). In this study, we measured α-syn total (α-syntotal), oligomeric α-syn (α-synolig) and α-synolig/α-syntotal ratio in the saliva of patients affected by PD and in age and sex-matched healthy subjects. We also compared salivary α-syntotal measured in PD with those detected in Progressive Supranuclear Palsy (PSP), in order to assess whether salivary α-syn can be used as a biomarker for PD and for the differential diagnosis between PD and PSP. Methods We studied 100 PD patients, 20 patients affected by PSP and 80 age- and sex-matched healthy subjects. ELISA analysis was performed using two commercial ELISA platforms and a specific ELISA assay for α-syn aggregates. Results We detected lower α-syntotal and higher α-synolig in PD than in healthy subjects. Conversely in PSP salivary α-syntotal concentration was comparable to that measured in healthy subjects. Receiver Operating Characteristic analyses revealed specific cut-off values able to differentiate PD patients from healthy subjects and PSP patients with high sensitivity and specificity. However, there was no significant correlation between clinical and molecular data. Conclusion Salivary α-syn detection could be a promising and easily accessible biomarker for PD and for the differential diagnosis between PD and PSP.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD).We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 FI ≤ 0.21), or frail (FI 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations.Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered.The present findings indicate that the FI is associated with both motor and non-motor features of PD.

Patients with COVID-19 pneumonia can develop hypoxemic acute respiratory failure (hARF) with the need for positive end-expiratory pressure (PEEP). The administration of a continuous positive airway pressure (CPAP) through a helmet improves oxygenation and avoids intubation [1, 2]. A European consensus document suggests that helmet CPAP should be the first therapeutic choice for hARF caused by COVID-19 pneumonia, mainly for minimising aerosol generation [3–5]. However, recommendations are based on experts' opinion and consider only evidence obtained in critically ill COVID-19 patients [3]. The Surviving Sepsis Campaign does not recommend the administration of CPAP for the initial management of severe COVID-19 [6]., Helmet CPAP treatment fails in up to 44% of patients with moderate-to-severe hypoxemic acute respiratory failure due to COVID-19 pneumonia

Background Possible pathophysiological mechanisms underlying Parkinson's disease (PD) clinical subtypes are unknown. The objective of this study was to identify pathophysiological substrate of PD subtypes using neurophysiological techniques. Methods One hundred de novo PD patients participated. We collected patient demographic and clinical data, which were used to perform a hierarchical cluster analysis. The neurophysiological assessment tested primary motor cortex excitability and plasticity using transcranial magnetic stimulation. To evaluate motor performance, we performed a kinematic analysis of fast index finger abduction. To investigate sensory function and sensorimotor mechanisms, we measured the somatosensory temporal discrimination threshold at rest and during movement, respectively. Results Hierarchical cluster analysis identified 2 clinical clusters. Cluster I ("mild motor-predominant") included patients who had milder motor and nonmotor symptoms severity than cluster II patients, who had a combination of severe motor and nonmotor manifestations (diffuse malignant). We observed that the diffuse malignant subtype had increased cortical excitability and reduced plasticity compared with the mild motor-predominant subtype. Kinematic analysis of motor performance demonstrated that the diffuse malignant subtype was significantly slower than the mild motor-predominant subtype. Conversely, we did not observe any significant differences in sensory function or sensorimotor integration between the two PD subtypes. Conclusions De novo PD subtypes showed different patterns of motor system dysfunction, whereas sensory function and sensorimotor integration mechanisms did not differ between subtypes. Our findings suggest that the subtyping of PD patients is not a mere clinical classification but reflects different pathophysiological mechanisms. Neurophysiological parameters may represent promising biomarkers to evaluate PD subtypes and their progression. © 2020 International Parkinson and Movement Disorder Society.

Introduction Re-emergent tremor (RET) is a postural tremor that appears after a variable delay in patients with Parkinson's disease (PD). The aim of the present study was to evaluate the occurrence and the clinical characteristics of RET in a population of patients with PD. Methods We consecutively assessed 210 patients with PD. We collected the patients' demographic and clinical data. RET was clinically characterized in terms of latency, severity and body side affected. We also investigated a possible relationship with motor and non-motor symptoms and differences in the clinical features in patients with and without RET. Results RET was present in 42/210 patients. The mean latency of RET was 9.20 ± 6.8 seconds. Mean severity was 2.4 ± 1.9. RET was unilateral in 21 patients. Patients with RET had less severe speech, posture and gait disorders and upper limb and global bradykinesia than patients without RET. Similar findings were observed when we compared patients with RET with patients with tremor at rest associated with action tremor, patients with isolated action tremor and patients with no tremor. By contrast, patients with RET tremor did not clinically differ from those with isolated tremor at rest. Conclusion Our results suggest that patients with RET and patients with isolated tremor at rest represent the same clinical subtype, whereas patients with action tremor (whether isolated or associated with tremor at rest) might belong to a distinct subtype that is clinically worse. Patients with RET represents a benign subtype of PD, even within the tremor-dominant phenotype.

The fabrication and characterization of an infrared photodetector based on GaAs droplet epitaxy quantum dots embedded in Al0.3Ga0.7As barrier is reported. The high control over dot electronic properties and the high achievable number density allowed by droplet epitaxy technique permitted us to realize a device using a single dot layer in the active region. Moreover, thanks to the independent control over dot height and width, we were able to obtain a very sharp absorption peak in the thermal infrared region (3-8 μm). Low temperature photocurrent spectrum was measured by Fourier spectroscopy, showing a narrow peak at 198 meV (∼6.3 μm) with a full width at half maximum of 25 meV. The observed absorption is in agreement with theoretical prediction based on effective mass approximation of the dot electronic transition.

ObjectiveTo perform a simultaneous evaluation of potential risk/protective factors of Parkinson disease (PD) to identify independent risk/protective factors, to assess interaction among factors, and to determine whether identified risk factors predict etiologic subtypes of PD.MethodsWe designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbid conditions, and drugs. The study enrolled 694 patients with PD and 640 healthy controls from 6 neurologic centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis.ResultsThe simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.4–0.9), smoking (OR 0.7, 95% CI 0.6–0.9), physical activity (OR 0.8, 95% CI 0.7–0.9), family history of PD (OR 3.2, 95% CI 2.2–4.8), dyspepsia (OR 1.8, 95% CI 1.3–2.4), and exposure to pesticides (OR 2.3, 95% CI1.3–4.2), oils (OR 5.6, 95% CI 2.3–13.7), metals (OR 2.8, 95% CI 1.5–5.4), and general anesthesia (OR 6.1, 95% CI 2.9–12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified 4 subtypes with different risk factor profiles. In group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents was present in 30% of patients. In groups 2 and 3, a family history of PD was lacking, while exposure to toxic agents (group 2) and dyspepsia (group 3) played major roles. Group 4 consisted of patients with no risk factors.ConclusionsThis study demonstrated that 9 factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same participant.

Background Previous studies investigating the risk of suicide in patients with Parkinson's disease (PD) have reported conflicting results. This study evaluated suicide risk in PD and investigated the relationship between suicide risk and perceived disability, hopelessness and affective temperaments in PD. Methods One-hundred and twenty PD patients were consecutively enrolled. The diagnosis of PD was based on clinical criteria. All patients underwent a psychiatric evaluation that included the administration of the Columbia-Suicide Severity Rating Scale, the Italian Perceived Disability Scale, the Beck Hopelessness Inventory and the TEMPS-A questionnaire. The results were compared with those of a control group of 91 patients affected by another chronic disease, ie, open angle glaucoma. Results Parkinson's disease patients had higher suicidal ideation, higher perceived disability and lower hyperthymia than the control group. In PD, higher perceived disability was associated with higher current and lifetime suicidal ideation, lower hyperthymia, older age and higher scores on negative temperaments. Suicidal ideation, negative temperaments and hopelessness were risk factors for perceived disability, while hyperthymia was a protective factor for perceived disability. Discussion Patients with PD have an increased risk of suicidal ideation. Increased suicidal ideation in PD is associated with the increased perceived disability. A psychiatric assessment that includes the investigation of suicide risk and perceived disability is recommended in patients with PD.

Background and purpose Patients with Parkinson's disease (PD) with resting tremor may be affected by a tremor that appears after a varying latency while a posture is maintained, a phenomenon referred to as re-emergent tremor (RET). The aim of the study was to evaluate the occurrence and clinical features of RET in patients with PD tested off and on treatment, and to compare the effect of dopaminergic treatment on RET with the effect on resting and action tremor. Methods We consecutively enrolled 100 patients with PD. Patients were clinically evaluated 24 h after withdrawal of therapy (off-treatment phase) and 60 min after therapy administration (on-treatment phase). We collected the demographic and clinical data of patients with PD. The severity of the disease was assessed by means of the Hoehn and Yahr scale and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. We evaluated the latency, severity and body side affected both off and on treatment in patients with RET. Results Re-emergent tremor was present in 24% of the patients with PD off treatment and in 19% of the patients on treatment. Dopaminergic treatment reduced the clinical severity of RET. Dopaminergic treatment increased the number of patients with unilateral RET and reduced the number of those who had bilateral RET. RET and resting tremor responded similarly to dopaminergic treatment, whereas action tremor was less responsive. Patients with RET had milder motor symptoms than patients without RET both off and on treatment. Conclusions Dopaminergic treatment modified RET occurrence, severity and body distribution. Dopaminergic depletion plays a role in the pathophysiology of RET.