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Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAThirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity.Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected.Eight weeks of treatment with PEA-LUT restore GABAThis study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Objective A high proportion of patients experience fatigue and impairment of cognitive functions after coronavirus disease 2019 (COVID-19). Here we applied transcranial magnetic stimulation (TMS) to explore the activity of the main inhibitory intracortical circuits within the primary motor cortex (M1) in a sample of patients complaining of fatigue and presenting executive dysfunction after resolution of COVID-19 with neurological manifestations. Methods Twelve patients who recovered from typical COVID-19 pneumonia with neurological complications and complained of profound physical and mental fatigue underwent, 9 to 13 weeks from disease onset, a psychometric evaluation including a self-reported fatigue numeric-rating scale (FRS, Fatigue Rating Scale) and the Frontal Assessment Battery (FAB). Intracortical activity was evaluated by means of well-established TMS protocols including short-interval intracortical inhibition (SICI), reflecting GABAA-mediated inhibition, long-interval intracortical inhibition (LICI), a marker of GABAB receptor activity, and short-latency afferent inhibition (SAI) that indexes central cholinergic transmission. TMS data were compared to those obtained in a control group of ten healthy subjects (HS) matched by age, sex and education level. Results Post-COVID-19 patients reported marked fatigue according to FRS score (8.1 ± 1.7) and presented pathological scores at the FAB based on Italian normative data (12.2 ± 0.7). TMS revealed marked reduction of SICI, and disruption of LICI as compared to HS. SAI was also slightly diminished. Conclusions The present study documents for the first time reduced GABAergic inhibition in the M1 in patients who recovered from COVID-19 with neurological complications and manifested fatigue and dysexecutive syndrome. Significance TMS may serve as diagnostic tool in cognitive disturbances and fatigue in post-COVID-19 patients.

Movement disorders encompass a variety of conditions affecting the nervous system at multiple levels. The pathologic processes underlying movement disorders alter the normal neural functions and could lead to aberrant neuroplastic changes and to clinical phenomenology that is not expressed only through mere motor symptoms. Given this complexity, the responsiveness to pharmacologic and surgical therapies is often disappointing. Growing evidence supports the efficacy of neurorehabilitation for the treatment of movement disorders. Specific form of training involving both goal-based practice and aerobic training could drive and modulate neuroplasticity in order to restore the circuitries dysfunctions and to achieve behavioral gains. This chapter provides an overview of the alterations expressed in some movement disorders in terms of clinical signs and symptoms and plasticity, and suggests which ones and why tailored rehabilitation strategies should be adopted for the management of the different movement disorders.

Fatigue and cognitive difficulties are reported as the most frequently persistent symptoms in patients after mild SARS-CoV-2 infection. An extensive neurophysiological and neuropsychological assessment of such patients was performed focusing on motor cortex physiology and executive cognitive functions.Sixty-seven patients complaining of fatigue and/or cognitive difficulties after resolution of mild SARS-CoV-2 infection were enrolled together with 22 healthy controls (HCs). Persistent clinical symptoms were investigated by means of a 16-item questionnaire. Fatigue, exertion, cognitive difficulties, mood and 'well-being' were evaluated through self-administered tools. Utilizing transcranial magnetic stimulation of the primary motor cortex (M1) resting motor threshold, motor evoked potential amplitude, cortical silent period duration, short-interval intracortical inhibition, intracortical facilitation, long-interval intracortical inhibition and short-latency afferent inhibition were evaluated. Global cognition and executive functions were assessed with screening tests. Attention was measured with computerized tasks.Post COVID-19 patients reported a mean of 4.9 persistent symptoms, high levels of fatigue, exertion, cognitive difficulties, low levels of well-being and reduced mental well-being. Compared to HCs, patients presented higher resting motor thresholds, lower motor evoked potential amplitudes and longer cortical silent periods, concurring with reduced M1 excitability. Long-interval intracortical inhibition and short-latency afferent inhibition were also impaired, indicating altered GABAPatients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.

Background. Hand functionality and finger dexterity are impaired in patients with Parkinson’s disease (PD). These disturbances lead to a dependency in activities of daily living (ADL) and poor quality of life (QoL). Objective. We aimed to evaluate whether a specific occupational therapy (OT) program is effective in improving finger and hand dexterity and its impact on ADL in PD patients. Methods. We retrospectively studied PD patients, hospitalized for a 4-week multidisciplinary intensive rehabilitation treatment (MIRT) between January 2015 and June 2018. All patients underwent 1 h/day OT treatment, 5 days a week. The primary outcome measure was the O’Connor finger dexterity test; secondary outcome measures were the Minnesota dexterity test, UPDRS II, and Self-Assessment Parkinson’s Disease Disability Scale (SPDDS). These measures were assessed at admission (T0) and discharge (T1). Results. Based on the Hoehn and Yahr scale (H&Y), patients were divided into two groups: 262 subjects in H&Y stage Conclusions. We showed that PD patients who underwent a rehabilitation protocol including OT experienced improvements in finger dexterity and hand functionality. Our results underline the relevance of OT in improving autonomy and QoL in PD patients.

ObjectiveWe evaluated the efficacy of muscle-targeted nutritional support on the functional outcomes of multidisciplinary intensive rehabilitation treatment (MIRT) in patients with Parkinson disease (PD) or parkinsonism.MethodsWe conducted a pragmatic, bicentric, randomized (1:1), assessor-blind controlled trial (Protein, Leucine and Vitamin D Enhancing Rehabilitation [PRO-LEADER]; April 2017 to January 2018) in cognitively intact patients with PD or parkinsonism and undergoing a 30-day MIRT. Patients (n = 150) received a standard hospital diet with or without a whey protein–based nutritional supplement enriched with leucine and vitamin D twice daily. The primary efficacy endpoint was the increase in the distance walked during a 6-minute walking test (6MWT). Secondary endpoints were changes in 4-meter walking speed, Timed Up and Go test (TUG), Berg balance scale, handgrip strength, Self-assessment Parkinson's Disease Disability Scale, body weight, and skeletal muscle mass (SMM).ResultsNutritional support resulted in greater increase in the distance walked during 6MWT (mean 69.6 meters [95% confidence interval (CI) 60.7–78.6]) than no support (51.8 meters [95% CI 37.0–66.7]): center-adjusted mean difference, 18.1 meters (95% CI 0.9–35.3) (p = 0.039). Further adjustment for changes in dopaminergic therapy and SMM yielded consistent results: mean difference, 18.0 meters (95% CI 0.7–35.2) (p = 0.043). A meaningful effect was also found for the following secondary endpoints: 4-meter walking speed (p = 0.032), TUG (p = 0.046), SMM, and SMM index (p = 0.029). Six patients discontinued the nutritional therapy due to mild side effects.ConclusionThe consumption of a whey protein–based nutritional formula enriched with leucine and vitamin D with MIRT improved lower extremity function and preserved muscle mass in patients with PD or parkinsonism.Clinicaltrials.gov identifierNCT03124277.Classification of evidenceThis study provides Class I evidence that for patients with parkinsonism undergoing intensive rehabilitation, a whey protein–based nutritional formula enriched with leucine and vitamin D increased distance walked on the 6MWT.

The knowledge about the effects of cannabis on human cortical brain processes is increasing. In this regard, transcranial magnetic stimulation (TMS) enables the evaluation of central nervous system function, including drug effects. Moreover, repetitive TMS (rTMS) has been used therapeutically in several substance use disorders. In this scoping review, we summarize and discuss studies that have employed TMS and rTMS techniques in users of cannabis for recreational purposes. In subjects with a history of persistent cannabis use, TMS studies showed reduced short-interval cortical inhibition (SICI). This observation points more at neurobiological changes of chronic cannabis use than to a direct effect of cannabis on gamma-aminobutyric acid (GABA) A receptors. Moreover, individuals vulnerable to becoming long-term users of cannabis may also have underlying pre-existing abnormalities in SICI. Of note, the use of cannabis is associated with an increased risk of schizophrenia, and the down-regulation of GABAergic function may play a role. Less frequent cannabis use and spontaneous craving were observed following rTMS applied to the dorsolateral prefrontal cortex (DLPFC). There is emerging evidence that the posterior cingulate cortex and the precuneus are potential targets for rTMS intervention in cannabis use disorder. However, larger and randomized trials should corroborate these encouraging findings.

Transcranial magnetic stimulation (TMS) can be a useful tool for the assessment of the brain functional reorganization in subjects with hemiplegic cerebral palsy (HCP). In this review, we performed a systematic search of all studies using TMS in order to explore the neuroplastic changes that occur in HCP patients. We aimed at investigating the usefulness of TMS to explore cortical excitability, plasticity and connectivity changes in HCP. Children with HCP due to unilateral lesions of the corticospinal system had ipsilateral motor evoked potentials (MEPs) similar to those recorded contralaterally. TMS studies demonstrated that occupational and constraint-induced movement therapy were associated with significant improvements in contralateral and ipsilateral corticomotor projection patterns. In addition, after intensive bimanual therapy, children with HCP showed increased activation and size of the motor areas controlling the affected hand. A TMS mapping study revealed a mediolateral location of the upper and lower extremity map motor cortical representations. Deficits in intracortical and interhemispheric inhibitory mechanisms were observed in HCP. Early hand function impairment correlated with the extension of brain damage, number of involved areas, and radiological signs of corticospinal tract (CST) degeneration. Clinical mirror movements (MMs) correlated with disability and CST organization in subjects with HCP and a positive relationship was found between MMs and MEPs strength. Therefore, TMS studies have shed light on important pathophysiological aspects of motor cortex and CST reorganization in HCP patients. Furthermore, repetitive TMS (rTMS) might have therapeutic effects on CST activities, functional connectivity and clinical status in children with HCP.

Background: Movement disorders encompass various conditions affecting the nervous system. The pathological processes underlying movement disorders lead to aberrant synaptic plastic changes, which in turn alter the functioning of large-scale brain networks. Therefore, clinical phenomenology does not only entail motor symptoms but also cognitive and motivational disturbances. The result is the disruption of motor learning and motor behavior. Due to this complexity, the responsiveness to standard therapies could be disappointing. Specific forms of rehabilitation entailing goal-based practice, aerobic training, and the use of noninvasive brain stimulation techniques could "restore" neuroplasticity at motor-cognitive circuitries, leading to clinical gains. This is probably associated with modulations occurring at both molecular (synaptic) and circuitry levels (networks). Several gaps remain in our understanding of the relationships among plasticity and neural networks and how neurorehabilitation could promote clinical gains is still unclear. Purposes: In this review, we outline first the networks involved in motor learning and behavior and analyze which mechanisms link the pathological synaptic plastic changes with these networks' disruption in movement disorders. Therefore, we provide theoretical and practical bases to be applied for treatment in rehabilitation.

Introduction: COVID-19-associated muscular complications may comprise myalgia, weakness, wasting, and rhabdomyolysis. Skeletal muscle damage in COVID-19 may be due to direct infection by the virus SARS-CoV-2 through interaction with the ACE2 receptor, systemic hyper-inflammatory state with cytokine release and homeostatic perturbation, an autoimmune process, or myotoxic drugs. Disclosing the cause of weakness in an individual patient is therefore difficult.Case Description: We report two patients, who survived typical COVID-19 pneumonia requiring intensive care treatment and who developed early on myalgia and severe proximal weakness in all four limbs. Laboratory exams revealed elevated serum creatine kinase and markedly increased C-reactive protein and interleukin 6, concurring with a systemic inflammatory response. On admission in neurorehabilitation (4 and 7 weeks after COVID-19 onset, respectively), the patients presented with proximal flaccid tetraparesis and limb-girdle muscle atrophy. Motor nerve conduction studies showed decreased amplitude and prolonged duration of compound muscle action potentials (CMAPs) with normal distal motor latencies and normal conduction velocities in median and ulnar nerves. Needle electromyography in proximal muscles revealed spontaneous activity in one and myopathic changes in both patients.Discussion: Clinical, laboratory, and electrodiagnostic findings in these patients were unequivocally consistent with myopathy. Interestingly, increased distal CMAP duration has been described in patients with critical illness myopathy (CIM) and reflects slow muscle fiber conduction velocity due to membrane hypo-excitability, possibly induced by inflammatory cytokines. By analogy with CIM, the pathogenesis of COVID-19-related myopathy might also depend on hyperinflammation and metabolic pathways that may affect muscles in a pathophysiological continuum from hypo-excitability to necrosis.

We focus attention on problems that are affecting the informal caregivers of patients with neurodegenerative disorders in the time of COVID‐19. The pandemic is increasing difficulties in the management of the frailest people and their isolation is actually even more tangible than it was in the past. The social restrictions and the lockdown of many activities are putting the system of care provided by informal caregivers on the edge of collapse. We incite the scientific community to face these concerns and provide clinicians clear indications for assisting and supporting caregivers in the care of their relatives during this period. We suggest that e‐health programs could become the ideal “environment” to favor the continuity of care for patients with neurodegenerative conditions and guarantee the required support to their caregivers, both directly in terms of psychological management and indirectly for helping them in disease management.

More than half of patients who recover from COVID-19 experience fatigue. We studied fatigue using neuropsychological and neurophysiological investigations in post-COVID-19 patients and healthy subjects. Neuropsychological assessment included: Fatigue Severity Scale (FSS), Fatigue Rating Scale, Beck Depression Inventory, Apathy Evaluation Scale, cognitive tests, and computerized tasks. Neurophysiological examination was assessed before (PRE) and 2 min after (POST) a 1-min fatiguing isometric pinching task and included: maximum compound muscle action potential (CMAP) amplitude in first dorsal interosseous muscle (FDI) following ulnar nerve stimulation, resting motor threshold, motor evoked potential (MEP) amplitude and silent period (SP) duration in right FDI following transcranial magnetic stimulation of the left motor cortex. Maximum pinch strength was measured. Perceived exertion was assessed with the Borg-Category-Ratio scale. Patients manifested fatigue, apathy, executive deficits, impaired cognitive control, and reduction in global cognition. Perceived exertion was higher in patients. CMAP and MEP were smaller in patients both PRE and POST. CMAP did not change in either group from PRE to POST, while MEP amplitudes declined in controls POST. SP duration did not differ between groups PRE, increased in controls but decreased in patients POST. Patients' change of SP duration from PRE to POST was negatively correlated to FSS. Abnormal SP shortening and lack of MEP depression concur with a reduction in post-exhaustion corticomotor inhibition, suggesting a possible GABAB-ergic dysfunction. This impairment might be related to the neuropsychological alterations. COVID-19-associated inflammation might lead to GABAergic impairment, possibly representing the basis of fatigue and explaining apathy and executive deficits., Highlights • Neuropsychological and neurophysiological features of fatigue were studied in post-COVID-19 patients. • Apathy, deficits in executive functions and reduction in global cognition were found. • Abnormal shortening of cortical silent period and lack of MEP depression were demonstrated after a fatiguing task. • Disruption of post-exhaustion corticomotor inhibition suggests GABA-ergic dysfunction. • GABA-ergic impairment might subtend fatigue and executive deficits in COVID-19.

The clock drawing test (CDT) is widely used in clinical neuropsychological practice. However, its neuroanatomical correlates have not been well established. This study investigated the effects of theta burst stimulation (TBS) applied over different brain regions on CDT scores in patients with Alzheimer’s disease (AD). The 10–20 positions F3, F4, T3, T4, TP3, TP4, P3, P4, as determined by a 10–20 positioning cap, were targeted. Excitatory intermittent TBS (iTBS) was given over the above-mentioned eight regions to ten AD patients and ten control subjects on separate days. CDT was administered at baseline (T0), during the 5 min following the TBS (T1) and 60 min after TBS (T2), with an inter-session interval of at least 4 days. iTBS over TP4 and P4 transiently increased Rouleau CDT score in AD patients. When targeting TP4 and P4, mainly the area of the supramarginal/angular gyrus and the inferior parietal lobe, corresponding respectively to the Brodmann areas 40/39 and 7/40, are reached. iTBS thus seems able to modulate activity of the right posterior parietal cortex in AD patients performing the CDT. Our results provide physiological evidence that those parietal regions are functionally important for the execution of the Rouleau CDT. This finding suggests that CDT has reliable neuroanatomical correlates, and support the notion that this test can be used as a good marker of right parietal brain dysfunction. The present study also highlights the therapeutic potential of the induction of neuromodulatory effects using non-invasive brain stimulation techniques.

Parkinson's disease (PD) results in a complex deterioration of motor behavior. Effective pharmacological or surgical treatments addressing the whole spectrum of both motor and cognitive symptoms are lacking. The cumulative functional impairment may have devastating socio-economic consequences on both patients and caregivers. Comprehensive models of care based on multidisciplinary approaches may succeed in better addressing the overall complexity of PD. Neurorehabilitation is a highly promising non-pharmacological intervention for managing PD. The scientific rationale beyond rehabilitation and its practical applicability remain to be established. In the present perspective, we aim to discuss the current evidence supporting integrated motor-cognitive and aerobic rehabilitation approaches for patients with PD while suggesting a practical framework to optimize this intervention in the next future.

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD.

BACKGROUND Parkinsonian patients in advanced stages of disease suffer from many motor and non-motor symptoms, whose responsiveness to dopamine replacement therapy and deep brain stimulation is poor. It is necessary to find complementary strategies in order to improve the clinical conditions of patients in advanced Parkinson's disease (PD) stages. OBJECTIVE We aimed to understand whether an inpatient, motor-cognitive, multidisciplinary, aerobic, intensive and goal-based rehabilitation treatment (MIRT), specifically designed for PD, is effective for patients in advanced stages of disease. METHODS 638 Parkinsonian patients, hospitalized to undergo a 4-week MIRT, were retrospectively identified. According to the Hoehn & Yahr (H&Y) scale, 496 were in H&Y stage 3 and 142 in H&Y stage 4-5. Outcome measures included: Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), Six Minute Walk Test (6MWT), and Parkinson's Disease Disability Scale (PDDS). RESULTS At baseline all measures, except UPDRS IV, significantly worsened passing from H&Y stage 3 to H&Y stage 4-5 (p≤0.002 all). After rehabilitation all outcome measures significantly improved in both groups of patients (p

Background Dopamine Replacement Therapy (DRT) represents the most effective treatment for Parkinson’s disease (PD). Nevertheless, several symptoms are unresponsive to treatment and its long-term use leads to serious side effects. To optimize the pharmacological management of PD, dopamine-agonists are often prescribed to “de-novo” patients. Moreover, several studies have shown the effectiveness and the synergic effect of rehabilitation in treating PD. Objective To evaluate the synergism between DRT and rehabilitation in treating PD, by investigating the short and the long-term effectiveness of a multidisciplinary, intensive and goal-based rehabilitation treatment (MIRT) in a group of patients treated with Rotigotine. Materials and methods In this multicenter, single blinded, parallel-group, 1:1 allocation ratio, randomized, non-inferiority trial, 36 “de-novo” PD patients were evaluated along 18 months: 17 were treated with Rotigotine plus MIRT; 19 were treated with Rotigotine alone (R). The primary outcome measure was the total score of Unified Parkinson’s Disease Rating Scale (UPDRS). The secondary outcomes included the UPDRS sub-sections II and III (UPDRS II-III), the 6-Minute Walk Test (6MWT), the Timed Up and Go Test (TUG) and the amount of Rotigotine. Patients were evaluated at baseline (T0), 6 months (T1), 1 year (T2), and at 18 months (T3). Results No differences in UPDRS scores in the two groups (total score, III part and II part, p = 0.48, p = 0.90 and p = 0.40, respectively) were found in the time course. Conversely, a greater improvement in Rotigotine + MIRT group was observed for 6MWT (p

ObjectiveTo evaluate whether a 4-week multidisciplinary, aerobic, motor-cognitive and intensive rehabilitation treatment (MIRT) improves the quality of life (QoL) of patients with Parkinson’s disease (PD), in the short-term and long-term period.MethodsThis is a prospective, parallel-group, single-centre, single-blind, randomised clinical trial (ClinicalTrials.gov NCT02756676). 186 patients with PD, assigned to experimental group, underwent MIRT; conversely, 48 patients, assigned to control group, did not receive rehabilitation. Parkinson’s Disease Questionnaire-39 was assessed 2 (T0), 10 (T1) and 18 (T2, only experimental group) weeks after the enrolment. We compared T1 versus T0 scores within subjects and delta scores (T1–T0) between subjects. To investigate the long-term effects, we compared T2 and T0 scores in the experimental group.ResultsAt T0, no between-group differences in the Global Index Score (GBI) were observed (experimental group: 43.6±21.4, controls: 41.6±22.9, P=0.50). At T1, we did not find significant changes in controls (delta score: 1.2±9.9, P=0.23), and we found an improvement in GBI in the experimental group (delta score: −8.3±18.0, PConclusionsA rehabilitation treatment such as MIRT could improve QoL in patients with PD in the short-term and long-term period. Even though the single-blind design and the possible role of the placebo effect on the conclusive results must be considered as limitations of this study, the improvement in outcome measure, also maintained after a 3-month follow-up period, suggests the effectiveness of MIRT on the QoL.Clinical trial registrationNCT02756676: Pre-results.

Objectives To assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. Design Randomized controlled study with 6-month follow-up. Setting A PD and brain injury rehabilitation department in a general hospital. Participants Patients (N=34) with moderate-stage PD. Intervention Seventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). Main Outcome Measures The primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. Results BBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. Conclusions Aquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor and nonmotor symptoms. Both of them imply a negative impact on Health-Related Quality of Life. A significant one is the stigma experienced by the parkinsonian patients and their caregivers. Moreover, stigma may affect everyday life and patient’s subjective and relational perception and it may lead to frustration and isolation. Aim of the present work is to qualitatively describe the stigma of PD patients stemming from literature review, in order to catch the subjective experience and the meaning of the stigma construct. Literature review was performed on PubMed database and Google Scholar (keywords: Parkinson Disease, qualitative, stigma, social problem, isolation, discrimination) and was restricted to qualitative data: 14 articles were identified to be suitable to the aim of the present overview. Results are divided into four core constructs: stigma arising from symptoms, stigma linked to relational and communication problems, social stigma arising from sharing perceptions, and caregiver’s stigma. The principal relations to these constructs are deeply analyzed and described subjectively through patients’ and caregiver’s point of view. The qualitative research may allow a better understanding of a subjective symptom such as stigma in parkinsonian patients from an intercultural and a social point of view.

Background: Attention is crucial to voluntary perform actions in Parkinson’s disease (PD), allowing patients to bypass the impaired habitual motor control. The asymmetrical degeneration of the dopaminergic system could affect the attentional functions. Objective: To investigate the relationship between the asymmetric dopaminergic degeneration and the attentional resources in Parkinsonian patients with right-side (RPD) and left-side (LPD) motor symptoms predominance. Methods: 50 RPD, 50 LPD, and 34 healthy controls underwent visual (V), auditory (A), and multiple choices (MC) reaction time (RTs) tasks. For PD patients, these tasks were performed before and after a 4-week intensive, motor-cognitive rehabilitation treatment (MIRT). The effectiveness of treatment was evaluated assessing Unified Parkinson’s disease Rating Scale (UPDRS) III and Timed-up and Go Test (TUG). Results: RTs did not differ between PD patients and healthy controls. Before MIRT, no differences between LPD and RPD patients were observed in RTs (p = 0.20), UPDRS III (p = 0.60), and TUG (p = 0.38). No differences in dopaminergic medication were found between groups (p = 0.44 and p = 0.66 before and after MIRT, respectively). After MIRT, LPD patients showed a significant reduction in MC RTs (p = 0.05), V RTs (p = 0.02), and MC-V RTs. A significant association between changes in RTs and improvements in UPDRS III and TUG was observed in LPD patients. Conclusion: attention does not differ among RPD patients, LPD patients and healthy controls. Only LPD patients improved their performances on attentional tasks after MIRT. We argue that the increased early susceptibility of the left nigrostriatal system to degeneration affects differently the cognitive modifiability and the neuroplastic potential. Our results could provide insight into new therapeutic approaches, highlighting the importance to design different treatments for RPD patients and LPD patients.

An established method to assess effective brain connectivity is the combined use of transcranial magnetic stimulation with simultaneous electroencephalography (TMS–EEG) because TMS-induced cortical responses propagate to distant anatomically connected brain areas. Alzheimer’s disease (AD) and other dementias are associated with changes in brain networks and connectivity, but the underlying pathophysiology of these processes is poorly defined. We performed here a systematic review of the studies employing TMS–EEG co-registration in patients with dementias. TMS–EEG studies targeting the motor cortex have revealed a significantly reduced TMS-evoked P30 in AD patients in the temporo-parietal cortex ipsilateral to stimulation side as well as in the contralateral fronto-central area, and we have demonstrated a deep rearrangement of the sensorimotor system even in mild AD patients. TMS–EEG studies targeting other cortical areas showed alterations of effective dorsolateral prefrontal cortex connectivity as well as an inverse correlation between prefrontal-to-parietal connectivity and cognitive impairment. Moreover, TMS–EEG analysis showed a selective increase in precuneus neural activity. TMS–EEG co-registrations can also been used to investigate whether different drugs may affect cognitive functions in patients with dementias.

Background Freezing of gait (FOG) is one of the most disabling symptoms of Parkinson disease (PD). Different land-based rehabilitation approaches based on motor and cognitive strategies can be effective in treating FOG. Although there are data about the efficacy of aquatic therapy in ameliorating this phenomenon, no study has explored the combined effect of land-based therapies plus aquatic therapy in patients with PD who have FOG. Objective The objective was to investigate the effectiveness of a multidisciplinary, intensive, motor-cognitive rehabilitation treatment (MIRT) in improving FOG and whether implementation with aquatic therapy (MIRT-AT) adds further benefits. Design The design consisted of a single-blind, parallel-group, 1:1 allocation ratio, randomized trial. Setting The Department of Parkinson Disease, Movement Disorders and Brain Injury Rehabilitation at “Moriggia-Pelascini” Hospital (Gravedona ed Uniti, Como, Italy) was used as the setting. Participants Sixty hospitalized patients with PD who had FOG in Hoehn and Yahr stage 2 or 5-3 were included. Intervention Sixty patients with PD + FOG were randomly assigned to 2 groups: 30 underwent a 4-week MIRT and 30 underwent a 4-week MIRT-AT. Measurements The primary outcome measure was the Freezing of Gait Questionnaire; secondary outcome measures were total Unified Parkinson Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, Berg Balance Scale, Timed Up and Go Test, and 6-Minute Walk Test. These measures were assessed both at admission and discharge. Results Participants in the 2 groups had similar age, sex distribution, Hoehn and Yahr stage, and most-affected side. At baseline, no difference in outcome measures was observed between the 2 groups. After treatment, a significant time effect was observed for all variables in both groups. No significant time × group interaction was observed. A between-group analysis showed nonsignificant differences between values at T1 and values at T0 for all variables. Limitations The limitations were the lack of a control group and follow-up. Conclusions We showed that a multidisciplinary, intensive, and goal-based rehabilitation treatment, such as MIRT, improves FOG in patients with PD. Although aquatic therapy could be considered a useful approach for treating FOG, it does not add further benefits to this kind of motor-cognitive rehabilitation.

Dopaminergic medication can induce severe addictive behaviours (e.g., pathological gambling) in susceptible Parkinson's disease (PD) patients. It is still unknown which particular neurocognitive processes become exacerbated or dysfunctional in PD patients with addictive behaviours. We sought to systematically review the relevant literature to identity potential neurocognitive correlates of medication-induced addictive behaviours in PD. We framed our review around neurocognitive processes central to four dominant accounts of substance addiction: 'aberrant learning', 'incentive sensitization', 'impulsivity to compulsivity' and 'impaired response inhibition and salience attribution'. Searches of the PubMed and Scopus databases were completed on June 23, 2017. To be included, studies were required to involve: (a) medicated PD patients, without a history of deep brain stimulation, with and without addictive behaviours; (b) a reward-related or decision-making task; and (c) statistical comparison of addictive and non-addictive groups' 'on' medication performance on the task(s). Studies were summarised qualitatively with statistically significant (p

Background Gait disturbances in Parkinson's disease (PD) are highly disabling and poorly responsive to drugs, especially in advanced stages. While the efficacy of a treadmill training based on external feedback and cues (treadmill-plus) on gait disturbances in early PD stages is demonstrated, no definitive evidence exists about advanced stages. Objective We aimed to evaluate the feasibility and the effects of a treadmill-plus training on gait disturbances in advanced PD. Methods Two hundred and six PD patients from medium to more advanced Hoehn & Yahr stage (stage 2, n = 79, stage 3 n = 74, and stage 4 = 53) who underwent a 4-week treadmill-plus training, were retrospectively identified. All patients were able to walk on a treadmill for one minute at 1.5 km/h, without support. Feasibility was evaluated by measuring safety, adverse events, and attrition rate. The effects of treatment were evaluated by assessing, both at enrolment and at the end of treatment, the on-land, self-paced 6-minute Walking Test (6MWT) and the gait parameters obtained from the treadmill during a 1.5 km/h trial. Results All patients completed the treadmill-plus training and no adverse events were recorded, even among more disabled patients. After training, we observed a significant improvement in the 6MWT, an increase in step length and a reduction of cadence and step variability in the whole sample. After stratifying patients according to disease stage, we found that patients in more advanced stages experienced the same improvements in all gait parameters as patients in less advanced stages. Conclusions Treadmill-plus training is well tolerated and may have a positive impact on many aspects of gait in more advanced PD stages.