The effects of intensive neurorehabilitation on sequence effect in Parkinson's disease patients with and without freezing of gait

Background: The sequence effect (SE), defined as a reduction in amplitude of repetitive movements, is a common clinical feature of Parkinson's disease (PD) and is supposed to be a major contributor to freezing of gait (FOG). During walking, SE manifests as a step-by-step reduction in step length when approaching a turning point or gait destination, resulting in the so-called destination sequence effect (dSE). Previous studies explored the therapeutic effects of several strategies on SE, but none of them evaluated the role of an intensive rehabilitative program. Objectives: Here we aim to study the effects of a 4-week rehabilitative program on dSE in patients with PD with and without FOG. Methods: Forty-three patients (30 males, 70.6 \ub1 7.5 years old) with idiopathic PD were enrolled. The subjects were divided into two groups: patients with (PD + FOG, n = 23) and without FOG (PD - FOG, n = 20). All patients underwent a standardized 4-week intensive rehabilitation in-hospital program. At hospital admission (T0) and discharge (T1), all subjects were evaluated with an inertial gait analysis for dSE recording. Results: At T0, the dSE was more negative in the PD + FOG group (-0.80 \ub1 0.6) when compared to the PD - FOG group (-0.39 \ub1 0.3) (p = 0.007), even when controlling for several clinical and demographic features. At T1, the dSE was reduced in the overall study population (p = 0.001), with a more pronounced improvement in the PD + FOG group (T0: -0.80 \ub1 0.6; T1: -0.23 \ub1 0.4) when compared to the PD - FOG group (T0: -0.39 \ub1 0.3; T1: -0.22 \ub1 0.5) (p = 0.012). At T1, we described in the overall study population an improvement in speed, cadence, stride duration, and stride length (p = 0.001 for all variables). Conclusions: dSE is a core feature of PD gait dysfunction, specifically in patients with FOG. A 4-week intensive rehabilitative program improved dSE in PD patients, exerting a more notable beneficial effect in the PD + FOG group

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.[Background] As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited.[Objective] The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.[Methods] We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.[Results] We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.[Conclusions] Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.This project was funded by The Michael J. Fox Foundation (ID 15015.02)Peer reviewe

Harmonic ratio is the most responsive trunk-acceleration derived gait index to rehabilitation in people with Parkinson's disease at moderate disease stages

Harmonic ratios (HRs), recurrence quantification analysis in the antero-posterior direction (RQAdetAP), and stride length coefficient of variation (CV) have recently been shown to characterize gait abnormalities and fall risk in people with Parkinson's disease (pwPD) at moderate disease stages

Outcome of long-term complications after permanent metallic left bronchial stenting in children

OBJECTIVES: We describe the way we treated 7 children with critical long-term complications after metallic balloon-expandable stenting in the left mainstem bronchus. METHODS: Endoscopic follow-up included a first bronchoscopy 3 weeks after stenting, then monthly for 3 months, every 4-6 months up to 1 year and at scheduled times to calibrate stent diameter up to final calibration. When major complications occurred, patients underwent chest computed tomographic angiography. RESULTS: In 1 of the 7 children (median age 2.8 years), metallic left bronchial stenting served as a bridge to surgery. After a median 4-year follow-up, all 7 children experienced recurrent stent ovalizations with stent breakage in 3 and erosion in 1. In 4 children, computed tomographic angiography showed abundant peribronchial fibrous tissue, in 2 left mediastinal rotation and in 1 displacement along the left bronchus after pulmonary re-expansion as the cause of stent-related complication. Of the 7 children, 6 underwent surgery (5 posterior aortopexy and 1 section of the ligamentum arteriosus) and 3 required nitinol stents placement within the metallic ones. One patient completed the follow-up, and 1 patient was lost to follow-up. All 5 remaining children still have permanent bronchial stents in place, patent and re-epithelialized after a median 10.5-year follow-up. There were no deaths. CONCLUSIONS: Satisfactory anatomical relationships when children have stents placed in the left mainstem bronchus alone do not guarantee the final success. Several mechanisms intervene to cause critical stent-related complications in children during growth. Permanent metallic stents should be used carefully, and only in selected patients

Un bambino con tachipnea - A child with tachypnea

Il surfactante polmonare, un complesso di proteine proteiche, è sintetizzato, aggregato e secreto dalle cellule alveolari di tipo II ed ha la funzione di ridurre la tensione superficiale, ponendosi all’interfaccia aria-acqua a livello alveolare. La porzione lipidica rappresenta la quasi totalità del complesso, mentre la porzione proteica è associata alle proteine tipo A, B, C e D. Un importante componente del metabolismo del surfactante è il trasportatore proteico (ABCA3) dei fosfolipidi all’interno dei corpi lamellari (1). Mutazioni dei geni delle proteine del surfactante sono state associate allo sviluppo di pneumopatie interstiziali. La malattia polmonare causata da mutazioni del gene ABCA3 è un disturbo ereditario autosomico recessivo. Una percentuale significativa di casi segnalati è rappresentata da eterozigoti composti con espressione variabile della malattia nel periodo neonatale o nell’infanzia . Lo spettro clinico e la gravità della malattia polmonare causata dalla carenza di ABCA3 è infatti estremamente variabile e fortemente dipendente dalle mutazioni causanti e dal modello morfologico-patologico indotto . Uno studio di coorte del 2017 ha mostrato come la presentazione più frequente delle mutazioni del gene ABCA3 sia un quadro di RDS neonatale severo, clinicamente non distinguibile dalla PAP e con rischio di esito infausto elevato entro il primo anno di età (5). Sebbene una piccola parte dei disordini del surfattante sia dovuta a mutazioni causanti una sua alterata o mancata produzione, la gran parte delle patologie del surfattante che esitano in un quadro di PAP sono causate dalla distruzione del GM-CSF da parte di autoanticorpi, determinando così la perdita della cruciale funzione di clearence alveolareed un conseguente accumulo di residui cellulari depositati in tale sede. Attualmente la PAP può essere classificata come primaria, a sua volta suddivisa in autoimmune quando è causata da autoanticorpi anti-GM-CSF (questa forma rappresenta circa il 90% dei casi) ed in ereditaria quando dovuta a mutazioni del gene per il recettore del GM-CSF (6), o secondaria. Quest’ultima forma, più frequentemente riscontrabile in età adulta, è associata principalmente a patologie sottostanti, quali malattie ematologiche (sindromi mielodisplastiche, leucemia mieloide acuta, leucemia linfoblastica acuta, leucemia cronica mielocitica, leucemia linfatica cronica, anemia aplastica, mieloma multiplo, linfoma e macroglobulinemia di Waldenstrom), neoplasie non ematologiche (adenocarcinoma polmonare, glioblastoma e melanoma), malattie infettive (citomegalovirus, Mycobacterium tuberculosis, Nocardia, Pneumocystis jirovecii), sindromi da immunodeficienza/disgregazione (AIDS, amiloidosi, sindrome di Fanconi, agammaglobulinemia, malattia di Bechet, dermatomiosite giovanile, acidosi tubulare renale e SCID) ed infine esposizioni tossiche per inalazione di polveri inorganiche (alluminio, cemento, silice, titanio ed indio), di polveri organiche (sostanze agricole, farina da forno, fertilizzanti e segatura) o di fumi (cloro, prodotti per la pulizia, benzina, petrolio, biossido di azoto, vernice e fumi di plastica sintetica). Infine, esiste una forma di PAP (in letteratura anche definita come PAP-Like) causata da mutazioni dei geni del surfattante (SFTPB, SFTPC, ABCA3 e TTF1 (NKX2.1)). La forma associata a mutazioni del surfattante (come nel nostro caso) può esordire con un quadro di insufficienza respiratoria grave sin dalla nascita, mentre la presentazione clinica delle altre forme include dispnea ingravescente, tachipnea, tosse e perdita di peso in un quadro di pneumopatia interstiziale ad esordio adolescenziale o in età adulta. La diagnosi può essere sospettata sulla base della storia clinica, di reperti radiologici tipici, della citologia al BAL, dei risultati della biopsia polmonare e/o di biomarker compatibili. Indubbiamente, nel sospetto clinico di PAP, deve essere effettuata la ricerca degli anticorpi anti-GM-CSF al fine di escludere la forma autoimmune, che rimane la più comune. Da un punto di vista radiologico, si possono spesso evidenziare opacità bilaterali e simmetriche alla radiografia del torace (non sempre presenti, soprattutto nelle fasi iniziali di malattia), mentre la TC del torace mostra un quadro di ground glass diffuso in tutte le forme di PAP. Infine, a livello endoscopico il BAL può apparire denso e lattescente dal punto di vista macroscopico (soprattutto nelle condizioni più gravi), mentre l’esame citologico rivela tipicamente la colorazione PAS positiva e la presenza di macrofagi schiumosi associati a sedimenti epiteliali. Per quanto concerne il trattamento della PAP, l’unica evidenza di efficacia è a favore del lavaggio polmonare totale, che viene eseguito in anestesia generale usando un tubo con doppio lume endotracheale per ventilare un polmone mentre l’altro viene riempito e svuotato ripetutamente con soluzione fisiologica, allo scopo di rimuovere fisicamente il surfattante dal polmone. Questa terapia non è stata ancora standardizzata e non esistono linee guida per un approccio univoco in termini di volume di soluzione fisiologica necessario, tipo di ventilazione post-intervento e successiva eventuale fisioterapia posizionale. Per la forma autoimmunitaria esistono diversi studi sull’utilizzo di GM-CSF esogeno per via sia sottocutanea sia aereosolica, ma tale pratica ancora non ha presentato risultati incoraggianti (7, 8). Infine, l’efficacia delle strategie terapeutiche finora considerate sembra non essere soddisfacente nei pazienti con mutazioni del gene ABCA3. Diversi studi mostrano una lieve risposta al surfattante esogeno dal punto di vista degli scambi gassosi, mentre l’utilizzo di steroide e idrossiclorochina ha presentato effetti esclusivamente transitori (5). Un report ha descritto un miglioramento significativo in pazienti con mutazione del gene ABCA3 trattati con metilprednisolone ad alte dosi, idrossiclorochina e azitromicina in combinazione, ma ulteriori dati serviranno per confermare questi risultati (9). La ricerca scientifica dovrebbe focalizzare la propria attenzione su nuove terapie, allo scopo di identificare molecole che abbiano come bersaglio diretto le mutazioni e i meccanismi sottostanti a queste patologie