Non-motor Features Research Articles

Synbiotic supplementation may globally improve non-motor symptoms in patients with stable Parkinson’s disease: results from an open label single-arm study

Gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in people with Parkinson’s Disease (PD). Probiotics and prebiotics are emerging as a potential therapeutic approach for PD patients. The aim of this paper was to assess the neurological and gastroenterological effects in PD patients with constipation after the administration of a synbiotic product, with a focus on behavioral and cognitive symptoms. We enrolled patients with stable PD who met diagnostic criteria for functional constipation and/or irritable bowel syndrome with constipation according to Rome IV Criteria. Patients received a synbiotic treatment (Enterolactis Duo, containing the probiotic strain Lacticaseibacillus paracasei DG and the prebiotic fiber inulin) for 12 weeks. A neurological and a gastroenterological evaluation were collected before and after the treatment. In addition, 16S rRNA gene profiling and short chain fatty acid quantification were performed to characterize the microbial ecosystem of fecal samples collected before (n = 22) and after (n = 9) the synbiotic administration. 30 patients were consecutively enrolled. After treatment, patients performed better in MDS-UPDRS part 1 (p = 0.000), SCOPA-AUT (p = 0.001), TAS-20 (p = 0.014), HAM-D (p = 0.026), DIFt (p = 0.003), PAS-A (p = 0.048). Gastroenterological evaluations showed improvements in PAC-SYM score (p < 0.001), number of complete bowel movement (p < 0.001) and BSFS (p < 0.001). After the synbiotic administration, we observed a significant increase in the abundance of the order Oscillospirales, as well as the Oscillospiraceae family and the species Faecalibacterium prausnitzii within this order in fecal samples. Synbiotic treatment demonstrates potential efficacy in ameliorating non-motor features in PD patients.

Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.

Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalisation. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the last two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease.

Shared and distinct cortical morphometric alterations in five neuropsychiatric symptoms of Parkinson’s disease

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse–compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson’s disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson’s disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson’s disease and 167 age- and sex-matched healthy participants from Parkinson’s Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse–compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse–compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson’s disease and psychosocial causes.

Pain in Multiple System Atrophy: A Community-Based Survey.

Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals. This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA. A community-based, online survey was conducted from February to May 2023. Invitations were extended to MSA individuals and informal MSA caregivers through patient advocacies and social media. We included 190 persons with MSA and 114 caregivers. Eighty-seven percent of MSA individuals reported pain, which was more prevalent among women (odds ratio [OR]: 6.38 [95% confidence interval, CI: 1.27-32.08], P = 0.025) and low-income groups (OR: 5.02 [95% CI: 1.32-19.08], P = 0.018). Neck and shoulders (58%), back (45%), and legs (45%) were mostly affected. In the neck and shoulders, pain was associated with MSA core features, like orthostatic intolerance (OR: 4.80 [95% CI: 1.92-12.02], P = 0.001) and antecollis (OR: 3.24 [95% CI: 1.54-6.82], P = 0.002). Seventy-six percent of individuals experiencing pain received treatment, mostly nonsteroidal anti-inflammatory drugs (47%), acetaminophen (39%), and opioids (28%). Only 53% of respondents reported at least partial satisfaction with their current pain management. Pain mostly impacted work, household activities, and hobbies of MSA individuals, and caregivers' social activities. Pain is more prevalent than previously reported in MSA and particularly affects women and low-income groups. Despite its frequency, pain management remains suboptimal, highlighting an urgent therapeutic need, likely entailing an optimized management of MSA core motor and non-motor features. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Resting-State Network Analysis Reveals Altered Functional Brain Connectivity in Essential Tremor.

Introduction: Essential tremor (ET) comprises motor and non-motor-related features, whereas the current neuro-pathogenetic basis is still insufficient to explain the etiologies of ET. Although cerebellum-associated circuits have been discovered, the large-scale cerebral network connectivity in ET remains unclear. This study aimed to characterize the ET in terms of functional connectivity as well as network. We hypothesized that the resting-state network (RSN) within cerebrum could be altered in patients with ET. Methods: Resting-state functional magnetic resonance imaging (fMRI) was used to evaluate the inter- and intra-network connectivity as well as the functional activity in ET and normal control. Correlation analysis was performed to explore the relationship between RSN metrics and tremor features. Results: Comparison of inter-network connectivity indicated a decreased connectivity between default mode network and ventral attention network in the ET group (p < 0.05). Differences in functional activity (assessed by amplitude of low-frequency fluctuation, ALFF) were found in several brain regions participating in various RSNs (p < 0.05). The ET group generally has higher degree centrality over normal control. Correlation analysis has revealed that tremor features are associated with inter-network connectivity (|r| = 0.135-0.506), ALFF (|r| = 0.313-0.766), and degree centrality (|r| = 0.523-0.710). Conclusion: Alterations in the cerebral network of ET were detected by using resting-state fMRI, demonstrating a potentially useful approach to explore the cerebral alterations in ET.

"Exercise… to Me, It's Freedom": Motivation, Support, and Self-Management to Keep Physically Active with Parkinson's Disease: A Qualitative Study.

The benefits of exercise have been widely explored among people with Parkinson's (PwP). Exercise can improve non-motor (fatigue, pain, sleep, etc.) and motor features (balance, muscle strength, gait speed, etc.), maintain function, as well as prevent disease progression. Although the benefits are well known, PwP continue to show difficulty adhering to physical activity and exercise. This study aims to explore motivation to exercise, support, and self-management needs among people with Parkinson's, their family members, and physiotherapists. Purposeful and maximum-variation sampling methods (age, sex, geographical setting, and disease severity) were employed. PwP and family members were recruited through physiotherapy services and local support groups. Twelve semi-structured interviews with PwP and two group interviews, one with family members (n = 4) and one with physiotherapists (n = 5), were conducted. Interview guides were informed by patient-public input and a recent systematic review. Interviews were recorded, transcribed, and analysed using thematic analysis informed by the Grounded Theory methodology. Four common themes emerged: (1) The value of an intrinsic connection with exercise, for which there are challenges. A greater connection to exercise led to long-term adherence. (2) Adapting exercise to the needs and preferences of a person is essential. Preferred exercises and environments were mixed, with differences emerging between sexes. (3) Physiotherapists' aim to only maintain physical function led to frustration. Limited self-management opportunities, stigma, and dehumanisation were discussed. (4) Non-motor symptoms, stigma, fear, and determination as well as apathy, pain, and low mood were discussed. Exercise provided physical, emotional, and social rewards. Supports are necessary; however, challenges arise when PwP's motivations are mismatched to family members' and physiotherapists' goals. Co-created goals, tailored to their preferences, and exercise plans with supported self-management are recommended.

Baseline Depressive Symptoms as a Predictor of Incident Dementia in a Prospectively Followed Cohort of Elders with Essential Tremor

Introduction: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. Methods: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants’ baseline depression scores. Results: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02–1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02–1.25, p = 0.02). Conclusion: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population.

Tango classes in people with Multiple Sclerosis (PwMS): Impact on motor and non-motor functions

BackgroundWhile music-based therapy (MBT) has been shown to improve motor and non-motor features in multiple sclerosis (MS), benefits of tango have never been assessed. ObjectiveTo evaluate the benefits of tango classes on quality of life (QoL), mood, fatigue, gait, balance, perception of cognitive disorder and sexuality in people with MS. Methods7 participants (age 41.14 ± 14.27 years, disease duration 14.14 ± 7.6 years) and respective partners undertook one-hour weekly classes for 20 weeks. Participants had early-stage MS (EDSS<3.5). They were assessed for mood (ZUNG rating scale; Beck Depression Inventory -II); balance (Berg Balance Test; Tinetti scale), cognition (MS Neuropsychological Screening Questionnaire), SD (Multiple Sclerosis Intimacy and Sexuality Questionnaire), fatigue (Fatigue Severity Scale) and QoL (36-Item Short Form Survey). ResultsGroup comparison of pre-post change scores showed a general improvement in all the outcome measures, which was significant in mood, SD, cognition and QoL. Discussions and conclusionTango classes provides benefits to pwMS, especially on non-motor symptoms. Follow-up assessment is required to confirm the durability of these effects.

Non-motor symptoms in PD evaluated during pharmacological ON state by a new tool: The NoMoS-ON scale. Is always the "ON" state beneficial?

ObjectivesTo evaluate non-motor symptoms (NMS) occurring during ON pharmacological state and validate a new questionnaire, the Non-motor symptoms-ON scale (NoMoS-ON), exploring ON NMS in Parkinson's disease (PD). Material and methodsPatients with PD were evaluated by a new questionnaire, the NoMoS-ON scale, evaluating 17 items related to the main symptoms experienced during the ON state. PD patients who experienced at least one symptom in ON were defined ON-NMS+. Internal consistency and test-retest reliability of NoMoS-ON scale were also assessed. ResultsOne-hundred and thirty-seven PD patients were consecutively enrolled (79 men and 58 women, age 69.4 ± 9.5 years (mean ± SD)). Seventy-seven patients were ON-NMS+ (56.6 %). PD patients with short disease duration (<7 years) showed the presence of unpleasant NMS: “sleepiness”, “light-headedness”, “nausea/vomiting”. PD patients with longer disease duration experienced pleasant non-motor features including “feel lot of energy”, “feel physical well-being”. ON-NMS+ were also associated with female gender (OR 2.81, 95%CI 1.37–5.77, p-value 0.005) and with motor fluctuations (OR 2.41, 95%CI 1.20–4.83, p-value 0.013). Cronbach's alpha was 0.61 and 5 items had adequate item-to-total correlations (r ≥ 0.40). Test–retest reliability was acceptable (intraclass correlation coefficient, ICC = 0.77). ConclusionsThe NoMoS-ON scale is a valid, reproducible and reliable questionnaire capturing the ON NMS in PD. PD patients with disease duration shorter than 7 years showed the presence of unpleasant NMS whereas those with longer disease duration experienced pleasant non-motor features. This could help the physician in the therapy management of PD patients in different phases of their disease.

Digital outcome measures from smartwatch data relate to non-motor features of Parkinson’s disease

Monitoring of Parkinson’s disease (PD) has seen substantial improvement over recent years as digital sensors enable a passive and continuous collection of information in the home environment. However, the primary focus of this work has been motor symptoms, with little focus on the non-motor aspects of the disease. To address this, we combined longitudinal clinical non-motor assessment data and digital multi-sensor data from the Verily Study Watch for 149 participants from the Parkinson’s Progression Monitoring Initiative (PPMI) cohort with a diagnosis of PD. We show that digitally collected physical activity and sleep measures significantly relate to clinical non-motor assessments of cognitive, autonomic, and daily living impairment. However, the poor predictive performance we observed, highlights the need for better targeted digital outcome measures to enable monitoring of non-motor symptoms.

Effect of motor, non-motor clinical features including sleep quality, and prescription pattern on adherence to antiparkinsonian medications in Parkinson’s disease

Objectives: Adherence to antiparkinsonian medications (APMs) may significantly influence Parkinson’s disease (PD) outcome. The present study assesses the role of motor and non-motor features, and prescription patterns on adherence. Materials and Methods: This observational and cross-sectional study included 50 PD patients taking APMs for ≥24 months. Demographic data, PD characteristics, treatment, and follow-up history were collected. Patients following up at least once in six months were considered as regular, else were labeled irregular. Montreal cognitive assessment, patient health questionnaire-4, Pittsburgh sleep quality (SQ) index, Epworth sleepiness scale, global quality of life (GQOL) scale, and Morisky Green Levine medication adherence scale (MGL-MAS) were used to evaluate cognition, depressive and anxiety features, SQ, excessive daytime sleepiness (EDS), quality of life (QOL), and APMs adherence, respectively. Results: Nearly half (46%) of the PD patients reported high adherence (MGL-MAS = 0). Most of the clinical characteristics were comparable between those with medium/low and high adherence, except for a larger proportion of patients in the medium/low adherence group belonging to Hoehn–Yahr stage &gt;2 (P = 0.02). A comparable proportion of patients in both groups reported poor SQ (P = 0.52) and EDS (P = 0.32). In comparison to the high adherence group, a significantly lower median GQOL score was observed in the medium/low adherence group (median [interquartile range] = 65 [50–70] vs. 80 [70–85]; P &lt; 0.001). The APMs prescription and follow-up patterns were comparable between both groups. Conclusion: More than half the PD patients reported medium-to-low adherence. While motor severity and depressive symptoms were associated with medium-to-low adherence, poor SQ was comparable in both groups. Those with medium-to-low adherence reported poor QOL.

Language impairment in sporadic and familial (type 8) amyotrophic lateral sclerosis: A comparative study.

Language is frequently affected in patients with sporadic amyotrophic lateral sclerosis (sALS), with reduced performance in naming, syntactic comprehension, grammatical expression, and orthographic processing. However, the language profile of patients with familial type 8 ALS (ALS8), linked to p.P56S VAPB mutation, remains unclear. We investigated language in patients with ALS8 by examining their auditory comprehension and verbal production. We included three groups of participants: (1) patients with sALS (n = 20), (2) patients with familial ALS8 (n = 22), and (3) healthy controls (n = 21). The groups were matched for age, sex, and education level. All participants underwent a comprehensive language battery, including the Boston Diagnostic Aphasia Examination, the reduced Token test, letter fluency, categorical fluency (animals), word definition from the Cambridge Semantic Memory Research Battery, and a narrative discourse analysis. Participants also were evaluated using Addenbrooke's Cognitive Exam-Revised Version, the Hospital Anxiety and Depression Scale, and the ALS Functional Rating Scale-Revised. Compared to controls, sALS and ALS8 patients had impaired performance on oral (syntactic and phonological processing) comprehension and inappropriate discourse cohesion. sALS and ALS8 did not differ in any language measure. There was no correlation between language scores and functional and psychiatric scales. ALS8 patients exhibit language deficits that are independent of motor features. These findings are consistent with the current evidence suggesting that ALS8 has prominent non-motor features.

Investigation of the nonmotor symptoms in patients with STN-DBS therapy in comparison with those without STN-DBS.

The impact of STN-DBS on NMS remains rather as an underestimated topic. Besides, the significance of NMSs in QOL indexes of PD subjects with STN-DBS is unknown. We primarily aimed to evaluate the NMSs and their significance in QOL indexes in PD subjects comparatively with and without STN-DBS therapy. We enrolled all consecutive PD subjects with and without STN-DBS who applied to our movement disorders outpatient clinics between January/2023 and September/2023. We performed comprehensive assessments of the motor and nonmotor features including the clinical scales of Movement Disorder Society-sponsored revisionof the MDS-UPDRS, NMSS, HAM-A, HAM-D, and the PDQ-39. Overall, 48 PD subjects with STN-DBS and 161 without STN-DBS treatment were included. The comparative analyses revealed that the sub-scores of the MDS-UPDRS-2, -3 and -4 were higher in the STN-DBS group. However, the MDS-UDPRS-1 and the total scores of the NMSS were similar between groups. Among eight subitems of the NMSS, only, the sub scores of the mood/cognition and the gastrointestinal tract differed. Remarkably, the significant correlations between the scores of the QOL and the NMSS scores in the STN-DBS (-) group, did not persist within the STN-DBS group. Remarkably, the correlations between the NMSS and PQQ-39 disappeared for most of the sub scores within the STN-DBS group. We found indirect evidence regarding the benefit of STN-DBS therapy on NMSs in our cross-sectional study. Besides, we found weaker impact of NMSs in QOL indexes in PD subjects with STN-DBS therapy.

Daidzein ameliorates nonmotor symptoms of manganese-induced Parkinsonism in zebrafish model: Behavioural and biochemical approach.

Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder characterized by motor dysfunction. Environmental factors, especially manganese (Mn), contribute significantly to PD. Existing therapies are focused on motor coordination, whereas nonmotor features such as neuropsychiatric symptoms are often neglected. Daidzein (DZ), a phytoestrogen, has piqued interest due to its antioxidant, anti-inflammatory, and anxiolytic properties. Therefore, we anticipate that DZ might be an effective drug to alleviate the nonmotor symptoms of Mn-induced Parkinsonism. Naïve zebrafish were exposed to 2mM of Mn for 21 days and intervened with DZ. Nonmotor symptoms such as anxiety, social behaviour, and olfactory function were assessed. Acetylcholinesterase (AChE) activity and antioxidant enzyme status were measured from brain tissue through biochemical assays. Dopamine levels and histology were performed to elucidate neuroprotective mechanism of DZ. DZ exhibited anxiolytic effects in a novel environment and also improved intra and inter fish social behaviour. DZ improved the olfactory function and response to amino acid stimuli in Mn-induced Parkinsonism. DZ reduced brain oxidative stress and AChE activity and prevented neuronal damage. DZ increased DA level in the brain, collectively contributing to neuroprotection. DZ demonstrated a promising effect on alleviating nonmotor symptoms such as anxiety and olfactory dysfunction, through the mitigation of cellular damage. These findings underscore the therapeutic potential of DZ in addressing nonmotor neurotoxicity induced by heavy metals, particularly in the context of Mn-induced Parkinsonism.

Relationship of Hearing Loss to Parkinson's Disease, Dementia, and APOE Genotype in Adults.

Background: Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients. Methods: A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability. Dementia was assessed by filling out the Clinical Dementia Rating and Mini-Mental State Examination questionnaires. The severity of PD was assessed using the Modified Hoehn and Yahr scale. Blood samples were tested for the gene expression of APOE. Results: Out of the 72 cases, there were 44 males and 28 females, with an average age of 64.4 ± 9.1 years. A total of 41 out of 72 cases had dementia and had a worse hearing threshold than those without dementia (47.1 ± 24.4 vs. 31.7 ± 22.1 dB, p = 0.006). A total of 58 patients were diagnosed with PD, with 14 of them classified as having severe symptoms (Modified Hoehn and Yahr scale > 2). Patients with severe PD were found to have a worse hearing threshold (49.6 ± 28.3 vs. 30.3 ± 17.8 dB, p = 0.028) and higher prevalence of dementia (12/14 vs. 18/44, p = 0.006). Among 10 individuals with the APOE ε4 gene, the prevalence of dementia was higher than those without the ε4 allele (9/10 vs. 32/62, p = 0.036). Conclusions: Hearing loss is common in severe PD and in dementia patients. Severe PD has a negative impact on the hearing threshold and cognitive dysfunction. Patients with APOE ε4 have a higher prevalence of dementia.

Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson's disease.

Neurogenic orthostatic hypotension (nOH) is a frequent nonmotor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-h ambulatory blood pressure monitoring (ABPM) showed good accuracy in diagnosing nOH. This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to the well-defined prognostic role of bedside nOH. Patients with PD who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, and mortality, during an up-to-10-year follow-up. Significant ABPM-hypotensive episodes were identified when greater than or equal to two episodes of systolic BP drop ≥ 15mmHg (compared with the average 24h) were recorded during the awakening-to-lunch period. A total of 99 patients (74% male, age 64.0 ± 10.1years, and PD duration 6.4 ± 4.0years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. On Kaplan-Meier analysis, patients with ABPM-hypotensive episodes showed earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and shorter survival (8.0 versus 9.5years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and Hoehn and Yahr stage) a significant association was confirmed between ABPM-hypotensive episodes and falls [odds ratio (OR) 3.626; p = 0.001), hospitalizations (OR 2.016; p = 0.038), and dementia (OR 2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR 1.908; p = 0.048). The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.

Spectral Domain and Angiography Optical Coherence Tomography in Parkinson’s Disease: Structural And Vascular Changes in the Retina Correlate with Disease Severity and Progression

Background. Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. Visual disturbances have been also described among non-motor features. Objective. We aimed to investigate the structural and vascular changes in the retinal and choroidal vascular networks, and to assess any relationship with motor and non-motor symptoms (NMS) in PD patients. Methods. Ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), and subfoveal choroidal thickness (SFCT) were examined using spectral domain-optical coherence tomography (SD-OCT). The vessel density (VD) of retinal and choriocapillary vascular networks in macular area and the foveal avascular zone (FAZ) area were evaluated by OCT angiography (OCTA). All patients underwent clinical evaluation using motor section of the Unified PD Rating Scale (UPDRS-III) and the Hoehn and Yahr (HY) scale. Results. A total of 48 eyes from 24 PD patients and 50 eyes from 25 controls were assessed. At SD-OCT, GCC and RNFL were more significantly thin in patients compared to controls. At OCTA exam, PD subjects showed lower values in VD of superficial capillary plexus (SCP) and radial peripapillary capillary plexus in comparison to controls, whereas FAZ area resulted in a significant increase in the patient group. We found a negative correlation between the age at onset and VD of SCP, and between HY score and RNFL thickness and FAZ. UPDRS-III score was negatively correlated with VD of deep capillary plexus. Discussion. The impairment of retinal structure and microvasculature seems to correlate with disease severity and progression in PD. Retinal anomalies can be considered as non-motor manifestations that could occur already in the early stage of the disease.

Dopa Responsive Dystonia with Marked Diurnal Fluctuation (Sagawa Disease) Forty-Five Years of Follow–Up

Objective: To describe the clinical course and very long personal follow-up of a patient with Segawa Disease Methods: The medical records of the patient since the diagnosis at the age of 9 years until her last follow-up at the age of 55 years were obtained and summarized Results: The long-term follow-up showed an excellent long-lasting response to L-DOPA therapy and also revealed that non-motor psychiatric features are an integral part of the disease rather than an emotional side effect of chronic motor disability. Conclusion: Long term follow-up of Segawa syndrome can provide additional information on prognosis and quality of life in old age, which are not known yet.

Effect of Dl-3-n-Butylphthalide on olfaction in rotenone-induced Parkinson's rats.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Olfactory dysfunction (OD) is an important nonmotor feature of PD. Dl-3-n-Butylphthalide (NBP) is a synthetic compound isolated from Apium graveolens seeds. The present study was conducted to investigate the effect of NBP on olfaction in rotenone-induced Parkinson's rats to explore the mechanism and pathway of OD in PD. The PD model was established using rotenone-induced SD rats, divided into blank control, model, and treatment groups. A sham group was also established, with 10 rats in each group. The treatment group was given NBP (1 mg/kg, 10 mg/kg, and 100 mg/kg, dissolved in soybean oil) intragastrically for 28 days. Meanwhile, the control group rats were given intra-gastrically soybean oil. After behavioral testing, all rats were executed, and brain tissue was obtained. Proteomics and Proteomic quantification techniques (prm) quantification were used to detect proteomic changes in rat brain tissues. Compared with the control group, the model group showed significant differences in behavioral tests, and this difference was reduced after treatment. Proteomics results showed that after treatment with high-dose NBP, there were 42 differentially expressed proteins compared with the model group. Additionally, the olfactory marker (P08523) showed a significant upregulation difference. We then selected 22 target proteins for PRM quantification and quantified 17 of them. Among them, the olfactory marker protein was at least twofold upregulated in the RTH group compared to the model group.

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients: a rare occurrence?

Amyotrophic lateral sclerosis (ALS) is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. While the typical clinical phenotype of ALS involves both upper and lower motor neurons, human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions, expanding the phenotype of ALS. Although superoxide dismutase 1 (SOD1) mutations represent a minority of ALS cases, the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies. Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1 (SOD1-ALS), no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation. In this narrative review, we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS. The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms, pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.