G325R GBA mutation in Parkinson's disease: Disease course and long-term DBS outcome

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Speech impairment in Parkinson’s disease: acoustic analysis of unvoiced consonants in Italian native speakers

The study of the influence of Parkinson’s Disease (PD) on vocal signals has received much attention over the last decades. Increasing interest has been devoted to articulation and acoustic characterization of different phonemes. Method: In this study we propose the analysis of the Transition Regions (TR) of specific phonetic groups to model the loss of motor control and the difficulty to start/stop movements, typical of PD patients. For this purpose, we extracted 60 features from pre-processed vocal signals and used them as input to several machine learning models. We employed two data sets, containing samples from Italian native speakers, for training and testing. The first dataset - 28 PD patients and 22 Healthy Control (HC) - included recordings in optimal conditions, while in the second one - 26 PD patients and 18 HC- signals were collected at home, using non-professional microphones. Results: We optimized two support vector machine models for the application in controlled noise conditions and home environments, achieving 98% ± 1.1 and 88% ± 2.8 accuracy in 10-fold cross-validation, respectively. Conclusion: This study confirms the high capability of the TRs to discriminate between PD patients and healthy controls, and the feasibility of automatic PD assessment using voice recordings. Moreover, the promising performance of the implemented model discloses the option of voice processing using low-cost devices and domestic recordings, possibly self-managed by the patients themselves

A new index to assess turning quality and postural stability in patients with Parkinson's disease

Parkinson's disease is a neuro-degenerative disorder characterized by the progressive death of dopamine neurons. This leads to delayed and uncoordinated movements, and impacts on the patients’ motor performance with reduced movement intensity, increased axial rigidity and impaired cadence regulation. Turning provides privileged insights in postural instability and fall prediction, as it is regularly performed during daily activities, requires multi-limb coordination. The objective of this work was to define a Quality of Movement (QoM) index, inferred from inertial data related to turns, and strictly correlated with the patient's motor conditions, postural stability, and stage of the disease. Such a concise representation finds its main application in the remote monitoring of patients during daily activities at home. We have recorded and analyzed 180° turns in 72 patients, using inertial sensors embedded in the smartphone. We have set up an algorithm for binary classification of patients: mild vs. moderate/severe conditions, according to the Hoehn and Yahr scale of disease progression and disability degree. Our QoM index is defined as the a posteriori probability output by this binary classifier. It exhibits high correlation (r = 0.73) with the clinical score of postural stability, as well as with the average of four clinical scores related to movement impairment (r = 0.75). These results, together with the widespread smartphone use, provide a step in the direction of a practical, objective and reliable tool for PD patients remote monitoring in domestic environment

Pregnancy, fertile life factors, and associated clinical course in PRKN early-onset Parkinson’s disease

introduction: as the most common cause of autosomal recessive early onset parkinson’s disease (EOPD), parkin type parkinson’s disease (PRKN-PD) may affect female patients in childbearing age. accordingly, issues related to fertility must be adequately addressed. here, we landscaped fertile life factors and pregnancy course of a PRKN-PD cohort, including both novel cases directly observed at our center and published ones. methods: six patients with confirmed PRKN-PD were examined by a structured interview on reproductive factors and associated modifications of PD disturbances, including one case followed up throughout pregnancy which was described in greater detail. six studies reporting fertile life factors of nine PRKN-PD patients were reviewed collecting homogeneous data on fertile life and pregnancy course. results: PRKN-PD female patients experienced motor fluctuations with the menstrual cycle, pregnancy, and puerperium, which suggests a role for sex hormones in PD clinical burden. In some cases, abortion and miscarriages occurred during the organogenesis phase in patients receiving oral antiparkinsonian therapy; however, levodopa/benserazide monotherapy resulted to be the safest choice in pregnancy. conclusion: collectively these data disclose the importance of pre-conception counseling in childbearing age PRKN-PD patients and EOPD in general

How resistant are levodopa-resistant axial symptoms? Response of freezing, posture, and voice to increasing levodopa intestinal infusion rates in Parkinson disease

Background and purpose: Treatment of freezing of gait (FoG) and other Parkinson disease (PD) axial symptoms is challenging. Systematic assessments of axial symptoms at progressively increasing levodopa doses are lacking. We sought to analyze the resistance to high levodopa doses of FoG, posture, speech, and altered gait features presenting in daily-ON therapeutic condition. Methods: We performed a pre-/postinterventional study including patients treated with levodopa/carbidopa intestinal gel infusion (LCIG) with disabling FoG in daily-ON condition. Patients were evaluated at their usual LCIG infusion rate (T1), and 1 h after 1.5× (T2) and 2× (T3) increase of the LCIG infusion rate by quantitative outcome measures. The number of FoG episodes (primary outcome), posture, speech, and gait features were objectively quantified during a standardized test by a blinded rater. Changes in motor symptoms, dyskinesia, and plasma levodopa concentrations were also analyzed. Results: We evaluated 16 patients with a mean age of 69 ± 9.4 years and treated with LCIG for a mean of 2.2 ± 2.1 years. FoG improved in 83.3% of patients by increasing the levodopa doses. The number of FoG episodes significantly decreased (mean = 2.3 at T1, 1.7 at T2, 1.2 at T3; p = 0.013). Posture and speech features did not show significant changes, whereas stride length (p = 0.049), turn duration (p = 0.001), and turn velocity (p = 0.024) significantly improved on doubling the levodopa infusion rate. Conclusions: In a short-term evaluation, the increase of LCIG dose can improve "dopa-resistant" FoG and gait issues in most advanced PD patients with overall good control of motor symptoms in the absence of clinically significant dyskinesia

Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.This work was supported by EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS grant No. 115565