Disease Rating Scale Scores Research Articles

Association of Cervical Vestibular-Evoked Myogenic Potentials (VEMP) and Postural Instability in Patients with Parkinson's Disease: A Cross-Sectional Study.

Postural instability is a common problem in patients with Parkinson's disease (PD). The appropriate cooperation of vestibular, visual, and proprioceptive signals along with apt anticipatory and adaptive postural responses is essential for postural stability. Abnormalities in this sensorimotor admixture lead to postural instability in PD. The function of vestibular otolith function and its central connections in postural instability of PD is still obscure. Cervical vestibular-evoked myogenic potentials (VEMP) can be used to assess the function of the saccular part of otolith and its connections. We aimed to study the role of dysfunction of the saccule and its connections at the brainstem by comparing the VEMP with normal controls and correlating it with the postural instability in patients with PD. Thirty patients with PD and 30 healthy volunteers were included in the study, after obtaining the institutional ethical committee approval. Patient's demographic data, stage and duration of illness, treatment history, history of fall, postural instability, Unified Parkinson's Disease Rating Scale (UPDRS) score, and Non-Motor Symptoms Scales (NMSs) were noted. Cervical VEMP analysis was done for both patients and controls. Patients with absent VEMP had significant postural instability, a history of falls, and a high UPDRS score. Mean P13 and N23 latencies were prolonged, and the amplitude was significantly low in patients with PD. Absent cVEMP was significantly associated with postural instability, non-motor symptoms, especially gastrointestinal, miscellaneous symptoms, and mood/cognition. VEMP can be considered an early electrophysiological marker for dysfunction of otolith and its central connections.

Assessing initial MRI reports for suspected CJD patients

BackgroundMRI is invaluable for the pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), demonstrating characteristic diffusion abnormalities. Previous work showed these changes were often not reported (low sensitivity), leading to eventual diagnosis at a more advanced state. Here, we reviewed the situation a decade later, on the presumption of improved access and awareness over time.MethodsWe reviewed initial MRI scans of 102 consecutive suspected sCJD patients recruited to the National Prion Monitoring Cohort study between 2015 and 2019, assessing for characteristic signal changes in the striatum, thalamus and cortical ribbon. We compared our findings to formal reports from referring centres. Requesting indications were studied to assess if they were suggestive of CJD. Patients were examined and their MRC Prion Disease Rating Scale scores recorded.ResultsWe identified characteristic MRI abnormalities in 101 cases (99% sensitivity), whilst referring centres reported changes in 70 cases (69% sensitivity), which was a significant improvement in reporting sensitivity from 2012. Reporting sensitivity was associated with signal change in the cerebral cortex, and with the number of regions involved, but not significantly affected by clinical information on request forms, or referring centres being regional neuroscience/non-neuroscience centres. Similar to a previous study, patients with missed abnormalities on initial reporting possessed lower MRC Scale scores when referred to the NPC than those correctly identified.ConclusionsWhilst local MRI reporting of sCJD has improved with time, characteristic abnormalities remain significantly under detected on initial scans. Sensitivity is better when the cerebral cortex and multiple regions are involved. We re-emphasize the utility of MRI and encourage further efforts to improve awareness and sensitivity in the assessment of patients with rapidly progressive dementia.

Predictive Indicators of Kinematic Writing Ability in Patients with Parkinson’s Disease: Focusing on Cognition, Depression, and Motor Abilities

Objectives: Parkinson’s disease (PD) can affect not only motor abilities but also cognition and depression. The purpose of this study was to investigate the predictive indicators of kinematic writing ability in patients with Parkinson’s disease.Methods: Seventy-two subjects (47 patients with PD, 25 normal adults [NA]) performed tasks; including sentence writing along visual cues using software that could measure pen pressure, letter size, and writing speed.Results: Firstly, discriminant analysis showed that the writing speeds were good discriminators for the PD group. Secondly, the PD group showed positive correlation between the Korean version of the Montreal Cognitive Assessment (MoCA-K) score and pen pressure in the ‘writing within square blanks task’. They also showed a positive correlation between the Unified Parkinson’s Disease Rating Scale (UPDRS) score and letter size in the ‘free writing task’. The PD group showed a negative correlation between UPDRS score and writing speed in the ‘writing within square blank task’. Thirdly, the MoCA-K score showed significant explanatory power for pen pressure, and the UPDRS score showed significant explanatory power for the writing speed in the PD group.Conclusion: This study is significant in that it confirms the importance of considering various factors such as cognitive ability when examining the writing characteristics of patients with PD, which have been focused only on motor skills so far.

Utilizing 7-Tesla Subthalamic Nucleus Connectivity in Deep Brain Stimulation for Parkinson Disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective surgical treatment for patients with advanced Parkinson disease (PD). Combining 7.0-Tesla (7T) T2- and diffusion-weighted imaging (DWI) sequences allows for selective segmenting of the motor part of the STN and, thus, for possible optimization of DBS. Materials and Methods7T T2 and DWI sequences were obtained, and probabilistic segmentation of motor, associative, and limbic STN segments was performed. Left- and right-sided motor outcome (Movement Disorders Society Unified Parkinson’s Disease Rating Scale) scores were used for evaluating the correspondence between the active electrode contacts in selectively segmented STN and the clinical DBS effect. The Bejjani line was reviewed for crossing of segments. ResultsA total of 50 STNs were segmented in 25 patients and proved highly feasible. Although the highest density of motor connections was situated in the dorsolateral STN for all patients, the exact partitioning of segments differed considerably. For all the active electrode contacts situated within the predominantly motor-connected segment of the STN, the average hemi-body Unified Parkinson’s Disease Rating Scale motor improvement was 80%; outside this segment, it was 52% (p < 0.01). The Bejjani line was situated in the motor segment for 32 STNs. ConclusionThe implementation of 7T T2 and DWI segmentation of the STN in DBS for PD is feasible and offers insight into the location of the motor segment. Segmentation-guided electrode placement is likely to further improve motor response in DBS for PD. However, commercially available DBS software for postprocessing imaging would greatly facilitate widespread implementation.

White matter damage in patients with mild cognitive impairment in Parkinson's disease.

This study investigates the correlation between white matter structural damage and cognitive impairment in patients with Parkinson's disease (PD) and mild cognitive impairment (MCI). A total of 40 patients with PD were divided into two groups, i.e., a mild cognitive impairment (PD-MCI) and a normal cognitive (PDN) group, and 20 healthy patients were enrolled as the control group. Changes in the white matter structure of patients with PD were evaluated using diffusion tensor imaging (DTI), and cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) scale and Mini-Mental State Examination (MMSE). Finally, the correlations between the two groups were analyzed. The Unified Parkinson's Disease Rating Scale score was significantly higher in the PD-MCI than in the PDN group (P=0.008). The total MoCA and MMSE scores in the PD-MCI group were significantly lower than in the PDN and control groups (P<0.01). Patients in PDMCI group were tested by MMSE scale, and the abnormal score rate was 60.0%. Among them, 8 PD patients with normal MMSE total score were found to have mild cognitive impairment by MoCA evaluation. When compared with the PDN and control groups, the MoCA scores for visual space, which is assessed as part of the MoCA scale and generally represents bilateral parietal function; naming; memory; and attention were significantly lower in the PD-MCI group (P<0.001). When compared with the PDN group, the fractional anisotropy (FA) values for the right parietal and left occipital lobes were significantly lower in the PD-MCI group (P=0.005; P=0.018). The relationship between MoCA value and right parietal white matter and left occipital white matter was 0.555, 0.474, respectively. A Pearson's correlation test was conducted to compare the FA values and MoCA scores of the various brain areas in the PD-MCI group and revealed a significant positive correlation between the MoCA score and the white matter of the right parietal and left occipital lobes (P<0.01). Patients with PD experience early cognitive impairment, and the MoCA scale can be used for early screening. In addition, the DTI of white matter can highlight early white matter damage. In the current study, the damaged brain areas displayed by DTI were consistent with areas showing decreased MoCA scores and were positively correlated with the severity of PD.

Traditional East Asian Herbal Medicine Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer’s disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to evaluate the efficacy and safety of herbal medicine for AD treatment. The PubMed, CENTRAL, EMBASE, CNKI, OASIS, KTKP, and CiNii databases were searched until June 2020 for randomized controlled trials (RCTs) on herbal medicine for AD, and a meta-analysis of 57 RCTs was conducted. For cognitive function, herbal medicine significantly improved the Mini-Mental State Examination (MMSE) and AD Assessment Scale-Cognitive Subscale (ADAS-cog) scores compared with conventional medicine. The MMSE scores showed no significant difference between the groups treated with herbal medicine and donepezil; however, herbal medicine significantly lowered the ADAS-cog score. Acori Graminei Rhizoma-containing and Cnidii Rhizoma-containing herbal medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine showed a positive, but not statistically significant, tendency toward improving the MMSE score compared with conventional medicine. Herbal medicine with conventional medicine significantly improved the MMSE, ADAS-cog, and Montreal Cognitive Assessment (MoCA) scores compared with conventional medicine, and herbal medicine with donepezil also significantly improved these scores compared with donepezil. Acori Graminei Rhizoma or Cnidii Rhizoma-containing herbal medicine with conventional medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine + conventional medicine significantly improved the MMSE score, but not the ADAS-cog score, compared with conventional medicine. For behavioral and psychological symptoms of dementia, the Neuropsychiatry Inventory (NPI) score was not significantly different between herbal and conventional medicines. Herbal medicine with conventional medicine significantly improved the NPI and Behavioral Pathology in Alzheimer’s Disease Rating Scale scores compared with conventional medicine. The NPI score showed no significant difference between the groups treated with herbal medicine and placebo. Furthermore, herbal medicine with conventional medicine significantly lowered plasma amyloid beta levels compared with conventional medicine alone. Herbal medicine, whether used alone or as an adjuvant, may have beneficial effects on AD treatment. However, owing to the methodological limitations and high heterogeneity of the included studies, concrete conclusions cannot be made.

Psychometric Properties of Clinical Indicators for Identification and Management of Advanced Parkinson's Disease: Real-World Evidence From G7 Countries.

IntroductionStandardized and validated criteria to define advanced Parkinson’s disease (PD) or identify patient eligibility for device-aided therapy are needed. This study assessed the psychometric properties of clinical indicators of advanced PD and eligibility for device-aided therapy in a large population.MethodsThis retrospective analysis of the Adelphi Parkinson’s Disease Specific Programme collected data from device-aided therapy-naïve people with PD in G7 countries. We assessed the presence of 15 clinical indicators of advancing PD and seven indicators of eligibility for device-aided therapy in patients classified with advanced PD or as eligible for device-aided therapy by the treating physician. Accuracy was assessed using area under the curve (AUC) and multivariable logistic regression models. Construct validity was examined via known-group comparisons of disease severity and burden among patients with and without each clinical indicator.ResultsOf 4714 PD patients, 14.9% were classified with advanced PD and 17.5% as eligible for device-aided therapy by physician judgment. The presence of each clinical indicator was 1.9- to 7.3-fold more likely in patients classified with advanced PD. Similarly, the presence of device-aided therapy eligibility indicators was 1.8- to 5.5-fold more likely in patients considered eligible for device-aided therapy. All indicators demonstrated high clinical screening accuracy for identifying advanced PD (AUC range 0.84–0.89) and patients eligible for device-aided therapy (AUC range 0.73–0.80). The Unified Parkinson’s Disease Rating Scale (UPDRS) score, cognitive function, quality of life, and caregiver burden were significantly worse in indicator-positive patients.ConclusionSpecific clinical indicators of advanced PD and eligibility for device-aided therapy demonstrated excellent psychometric properties in a large sample, and thus may provide an objective and reliable approach for patient identification and treatment optimization.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00313-9.

Association of serum uric acid and non-motor symptoms in Parkinson's disease: A cross-sectional study from a movement disorders clinic in Lagos, Nigeria

Background and Objective: The role of serum uric acid (SUA) as a biomarker in Parkinson's disease (PD) remains exploratory and has not been described in our population. The objective of this study was to explore the profile of SUA and its relationship to nonmotor symptoms (NMS) burden in PD. Methods: This cross-sectional study recruited 70 persons with PD and 140 matched healthy controls in Lagos, Nigeria. PD was diagnosed using the United Kingdom PD Society Brain Bank criteria. NMS were assessed with the NMS Questionnaire (NMS-Quest). SUA was measured using standard methods. Results: The mean ages of PD and controls were 63 ± 9.4 years and 62.9 ± 8.8 years, respectively (P = 0.65), with no difference when compared by sex. The median PD duration (interquartile range [IQR]) was 4 (4.25) years. Median Hoehn and Yahr stage (IQR) was 2.5 (1.0). The mean total unified Parkinson's disease rating scale score was 70.7 ± 23.7. The mean NMS-Quest score was 8.5 ± 3.8. Mean SUA level was significantly lower in PD compared to controls (2.42 ± 0.75 mg/dL vs. 3.73 ± 1.09 mg/dL [P = 0.000]). There was a nonsignificant inverse linear trend of association (r = −0.184; P = 0.126) between the total NMS-Quest score and SUA level in PD. Logistic regression analysis revealed hyposmia and memory impairment were significantly related to lower SUA levels (P = 0.02 and P = 0.04, respectively). Conclusion: Our study corroborates the potential of SUA as a serum biomarker in PD and a possible role in defining non-motor symptom burden. Further exploration to clarify the association and interrogate the impact of interventions is warranted.

The power of instruction on retropulsion: A pilot randomized controlled trial of therapeutic exercise focused on ankle joint movement in Parkinson’s disease

IntroductionAlthough retropulsion is a serious complication of Parkinson’s disease (PD), it is unknown whether ankle joint movement patterns can be targeted to treat retropulsion. The primary aim of this study was to investigate the effectiveness of therapeutic exercise focused on instructions regarding ankle joint movement on retropulsion in PD. MethodsTwenty patients with moderate PD were randomly allocated to the experimental intervention (INSTR) or control groups. The INSTR group received a 2-week therapeutic exercise program (40 min/day, five times/week) that involved repeated backward pulls on the shoulders with instructions to land on the toes as a response, and the control group received the same intervention without the instructions. The primary outcome was the difference in changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS part III) score between the study groups at weeks 1 and 2. ResultsThe improvement in the MDS-UPDRS part III scores was significantly greater for the INSTR group in the week 1 (p = 0.033, pη2 = 0.241) and week 2 (p = 0.004, pη2 = 0.401) assessments. However, the provision of instructions to land on the toes as a backward response induced improvement in the only scores related to the backward response, and no significant between-group differences were observed in the other outcomes. ConclusionThe 2-week therapeutic exercise program with instructions to treat retropulsion improved the backward response. Trial registrationUMIN-CTR, UMIN000042722.

2021 marks a new era for Alzheimer's therapeutics

2021 marks a new era for Alzheimer's therapeutics

Plasma neurofilament light chain as a biomarker in Wilson's disease

IntroductionNeurofilament light chain (NfL) was recently proposed as a promising blood biomarker for nervous system diseases, including Wilson's disease (WD). In this study, we investigated plasma NfL concentrations in patients with different types of WD and their correlations with clinical manifestations and brain atrophy. MethodsSeventy-five WD cases (54 neurological type, 21 hepatic type) and 27 age-matched healthy controls were included in this study. We compared plasma NfL concentrations between the different types and correlated them with Unified Wilson's Disease Rating Scale (UWDRS) scores. Patients were allocated to stable and unstable groups according to changes in UWDRS scores and clinical assessment. We compared the differences in plasma NfL concentrations between groups. Voxel-based morphometry (VBM) and FreeSurfer software were used to analyze MRI images. We investigated the correlation between plasma NfL concentrations and volume of gray matter, white matter, and several areas of interest in the brain MRI of 24 patients. ResultsPlasma NfL concentrations were significantly higher in neurological type WD than in hepatic type WD (8.16 vs. 3.19 pg/mL, p < 0.001). Plasma NfL concentrations were positively correlated with UWDRS scores (r = 0.291, p = 0.035) in patients with neurological type WD. Plasma NfL was significantly higher in unstable patients than in stable patients (10.74 vs. 7.23 pg/mL, p = 0.004). Significant negative associations were found between plasma NfL level and the volumes of total gray matter, bilateral caudate nucleus, putamen, and nucleus accumbens. ConclusionPlasma NfL is valuable as a biomarker for neurological damage in patients with WD.

Automated and accurate assessment for postural abnormalities in patients with Parkinson\u2019s disease based on Kinect and machine learning

BackgroundAutomated and accurate assessment for postural abnormalities is necessary to monitor the clinical progress of Parkinson’s disease (PD). The combination of depth camera and machine learning makes this purpose possible.MethodsKinect was used to collect the postural images from 70 PD patients. The collected images were processed to extract three-dimensional body joints, which were then converted to two-dimensional body joints to obtain eight quantified coronal and sagittal features (F1-F8) of the trunk. The decision tree classifier was carried out over a data set established by the collected features and the corresponding doctors’ MDS-UPDRS-III 3.13 (the 13th item of the third part of Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale) scores. An objective function was implanted to further improve the human–machine consistency.ResultsThe automated grading of postural abnormalities for PD patients was realized with only six selected features. The intraclass correlation coefficient (ICC) between the machine’s and doctors’ score was 0.940 (95%CI, 0.905–0.962), meaning the machine was highly consistent with the doctors’ judgement. Besides, the decision tree classifier performed outstandingly, reaching 90.0% of accuracy, 95.7% of specificity and 89.1% of sensitivity in rating postural severity.ConclusionsWe developed an intelligent evaluation system to provide accurate and automated assessment of trunk postural abnormalities in PD patients. This study demonstrates the practicability of our proposed method in the clinical scenario to help making the medical decision about PD.

Basal ganglia atrophy-associated causal structural network degeneration in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by both motor and non‐motor symptoms. A convergent pathophysiological hallmark of PD is an early selective vulnerability within the basal ganglia circuit. However, the causal interactions between basal ganglia atrophy and progressive structural network alterations in PD remain unaddressed. Here, we adopted voxel‐based morphometry method to measure gray matter (GM) volume for each participant (n = 84 PD patients and n = 70 matched healthy controls). Patients were first divided into three stages according to the Hoehn and Yahr (H&Y) and the Part III of Unified Parkinson's Disease Rating Scale scores respectively to analyze the stage‐specific GM atrophy patterns. Then, the modulation of early caudate atrophy over other brain structures was evaluated using the whole‐brain voxel‐wise and region‐of‐interest‐wise causal structural covariance network approaches. We found that GM atrophy progressively expands from the basal ganglia to the angular gyrus, temporal areas, and eventually spreads through the subcortical–cortical networks as PD progresses. Notably, we identified a shared caudate‐associated degeneration network including the basal ganglia, thalamus, cerebellum, sensorimotor cortex, and cortical association areas with the PD progressive factors. These findings suggest that the early structural vulnerability of basal ganglia in PD may play a pivotal role in the modulation of motor and non‐motor circuits at the structural level. Our work provides evidence for a novel mechanism of network degeneration that underlies the pathology of PD and may have potential clinical applications in the development of early predictors of PD onset and progress.

Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis.

Background:Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice.Methods:Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events.Results:Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD −1.31, 95% CI −1.57 to −1.04, P < .00001) for motor UPDRS score, (16 trials; SMD −1.26, 95% CI −1.49 to −1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD −1.02, 95% CI −1.27 to −0.77, P < .00001) for mental UPDRS score, (10 trials; SMD −1.54, 95% CI −1.93 to −1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD −1.56, 95% CI −1.90 to −1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001).Conclusions:P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.

Dance Intervention Using the Feldenkrais Method Improves Motor, and Non-Motor Symptoms and Gait in Parkinson's Disease: A 12-Month Study.

ObjectiveThe aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period.MethodsThis was a single-arm study in which 12 subjects with Parkinson’s disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months.ResultsDance intervention decreased motor scale (Unified Parkinson’s Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL.ConclusionOur findings suggest that dance intervention can be a complementary management method for PD patients.

A Case Report of Non-Motor Symptoms Evaluated Using the Non-Motor Symptom Scale in a Patient with Secondary Parkinsonism Presumed to be Probable Lewy Body Dementia and Improved with Combined Treatment with Herbal Medicine and Acupuncture

Parkinson's syndrome is a degenerative brain disease that presents characteristic motor symptoms of tremor, rigidity, and gait disturbance. In addition to these motor symptoms, Parkinson's syndrome also presents non-motor symptoms (NMSs) such as sleep disturbance and cognitive decline. NMSs reduce patient's quality of life and psychosocial functioning and cause economic burden on the patient, so appropriate evaluation and treatment are required. Lewy body dementia is one of the several diseases belonging to Parkinson's syndrome. Its symptoms such as cognitive function, memory impairment, and hallucinations occur with Parkinsonism. Although drug therapy is being used with drug treatment to treat non-motor symptoms, it has limitations such as side effects, which stimulated interest in other complementary treatment methods such as oriental medicine treatment, dance, and yoga.&lt;br/&gt;The patient in this case complained of tremor in the right upper extremity, muscle hypertension and pain, and persistent vision, memory, and cognitive decline. The patient was diagnosed with probable Lewy body dementia. The patient was hospitalized for 4 months and received acupuncture and herbal medicines. After treatment, the patient's NMS scale scores decreased from 90 to 63, and the Unified Parkinson's Disease Rating Scale scores (summed I, II, and III) decreased from 17 points to 8 points. The Beck Depression Inventory score decreased from 22 points to 13 points. In addition, the patient's subjective evaluation revealed improvement.&lt;br/&gt;In this case, a patient diagnosed with probable Lewy body dementia who did not respond to the standard treatment and did not want to take medications showed improvement in not only motor symptoms but also NMSs after integrative Korean medicine treatment.

The Efficacy of High- or Low-Frequency Transcranial Magnetic Stimulation in Alzheimer's Disease Patients with Behavioral and Psychological Symptoms of Dementia.

Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown. A total of 32 AD patients with psychobehavioral symptoms were selected as the study subjects. Among them, 16 patients were included in the high-frequency TMS group with an average disease duration of 6.22 ± 2.55years. The low-frequency TMS group was gender and age matched with a disease course of 7.02 ± 3.33-year average duration. The high-frequency TMS group received TMS treatment twice per day for 4weeks under 80% MT stimulation intensity, 10-Hz frequency for 0.5h each time, and the low-frequency TMS group received TMS treatment of 2-Hz frequency for 0.5h each time. Neuropsychological status was assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The behavioral ability was assessed by the Abilities of Daily Living (ADL) scale; cognitive function was evaluated by Mini-Mental State Examination (MMSE). The levels of β amyloid 40 and 42 (Aβ40 and Aβ42) in plasma were detected using a double-antibody sandwich enzyme-linked immunosorbent assay. All patients underwent brain magnetic resonance imaging (MRI) before and after the experiment. After 2weeks of treatment, the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those before the treatment, and they continued to decrease after 4weeks of treatment. The BEHAVE-AD and ADL scores of the low-frequency TMS group were also significantly lower than before treatment. The comparison between groups at different time points showed that the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those of the patients in the low-frequency TMS group. The MMSE of high-frequency TMS-treated patients increased from 14.22 ± 3.55 before treatment to 14.67 ± 2.22 at 2week's treatment and 17.33 ± 3.11 at 4week's treatment (p < 0.01) in contrast to 14.19 ± 3.47, 14.28 ± 3.41, and 14.49 ± 2.79, respectively, found in the low-frequency TMS group. At week 4, the high-frequency TMS-treated group's plasma Aβ40 did not change compared to that before treatment. No effects on plasma Aβ42 were observed between the high- vs. low-frequency TMS groups. The incidence of adverse reactions during treatment was comparable between groups. These results indicate that high-frequency TMS has the advantages of fast results, good efficacy, and high safety for the treatment of psychobehavioral abnormalities in AD patients. In addition, our study suggests that high-frequency TMS intervention can further improve the cognitive function of AD patients.

The amplitude of low-frequency fluctuation predicts levodopa treatment response in patients with Parkinson's disease

IntroductionLevodopa has become the main therapy for motor symptoms of Parkinson's disease (PD). This study aimed to test whether the amplitude of low-frequency fluctuation (ALFF) computed by fMRI could predict individual patient's response to levodopa treatment. MethodsWe included 40 patients. Treatment efficacy was defined based on motor symptoms improvement from the state of medication off to medication on, as assessed by the Unified Parkinson's Disease Rating Scale score III. Two machine learning models were constructed to test the prediction ability of ALFF. First, the ensemble method was implemented to predict individual treatment responses. Second, the categorical boosting (CatBoost) classification was used to predict individual levodopa responses in patients classified as moderate and superior responders, according to the 50% threshold of improvement. The age, disease duration and treatment dose were controlled as covariates. ResultsNo significant difference in clinical data were observed between moderate and superior responders. Using the ensemble method, the regression model showed a significant correlation between the predicted and the observed motor symptoms improvement (r = 0.61, p < 0.01, mean absolute error = 0.11 ± 0.02), measured as a continuous variable. The use of the Catboost algorithm revealed that ALFF was able to differentiate between moderate and superior responders (area under the curve = 0.90). The mainly contributed regions for both models included the bilateral primary motor cortex, the occipital cortex, the cerebellum, and the basal ganglia. ConclusionBoth continuous and binary ALFF values have the potential to serve as promising predictive markers of dopaminergic therapy response in patients with PD.

Measurement of the facial nerve thickness and its correlation with freezing phenomenon and hypomimia in Parkinson’s disease

ObjectiveHypomimia is one of the diagnostic features in Parkinson's disease, and freezing blocks may also occur with the degenerative process. We investigated that the thickness of the cranial facial nerve that innervates facial expressions, and the relationship between bradymimia and freezing phenomena in these patients. MethodsWe included 70 patients and healthy participants in this cross-sectional study. Clinical characteristics, modified Hoehn and Yahr (mHY) stages, Unified Parkinson's Disease Rating Scale (UPDRS) scores and Freezing of Gait Questionnaire (FOG-Q) scores of Parkinson's patients were recorded. FOG-Q was scored between 1 and 4 points. The thickness of the facial nerve and its neighborhoods of numerically equal groups were measured radiologically in the internal acoustic channel (IAC) with magnetic resonance imaging of temporal lobe. Right and left facial nerve thicknesses were compared. ResultsThe right facial nerve thicknesses of the patient and control groups were measured as 0.97 ± 0.12 mm and 1.20 ± 0.10 mm at the proximal level and 0.71 (0.69–0.81) mm and 1.21 (1.13–1.24) mm at the distal level, respectively (P < 0.001). Notably, the facial nerve was more atrophied on the right than on the left (P < 0.001). Facial nerve to IAC ratio (%) was significantly lower and cerebrospinal fluid thickness distance (%) measurement was significantly higher (P < 0.001). Also, the FOG-Q and facial nerve to IAC ratio were negatively correlated (P = 0.049, rho = −0.335). ConclusionsOur study provides new information about the facial nerve and its neighborhoods and clinical relationships in individuals with PD. In studies investigating hypomimia and FOG in Parkinson's, neuroimaging of the facial nerve can also be used. These results need to be proven with more comprehensive studies.

Using Machine Learning for Predicting the Best Outcomes With Electrical Muscle Stimulation for Tremors in Parkinson's Disease.

Recent studies have identified that peripheral stimulation in Parkinson’s disease (PD) is effective in tremor reduction, indicating that a peripheral feedback loop plays an important role in the tremor reset mechanism. This was an open-label, quasi-experimental, pre- and post-test design, single-blind, single-group study involving 20 tremor-dominant PD patients. The objective of this study is to explore the effect of electrical muscle stimulation (EMS) as an adjunctive treatment for resting tremor during “on” period and to identify the best machine learning model to predict the suitable stimulation level that will yield the longest period of tremor reduction or tremor reset time. In this study, we used a Parkinson’s glove to evaluate, stimulate, and quantify the tremors of PD patients. This adjustable glove incorporates a 3-axis gyroscope to measure tremor signals and an EMS to provide an on-demand muscle stimulation to suppress tremors. Machine learning models were applied to identify the suitable pulse amplitude (stimulation level) in five classes that led to the longest tremor reset time. The study was registered at the www.clinicaltrials.gov under the name “The Study of Rest Tremor Suppression by Using Electrical Muscle Stimulation” (NCT02370108). Twenty tremor-dominant PD patients were recruited. After applying an average pulse amplitude of 6.25 (SD 2.84) mA and stimulation period of 440.7 (SD 560.82) seconds, the total time of tremor reduction, or tremor reset time, was 329.90 (SD 340.91) seconds. A significant reduction in tremor parameters during stimulation was demonstrated by a reduction of Unified Parkinson’s Disease Rating Scale (UPDRS) scores, and objectively, with a reduction of gyroscopic data (p < 0.05, each). None of the subjects reported any serious adverse events. We also compared gyroscopic data with five machine learning techniques: Logistic Regression, Random Forest, Support Vector Machine (SVM), Neural Network (NN), and Long-Short-Term-Memory (LSTM). The machine learning model that gave the highest accuracy was LSTM, which obtained: accuracy = 0.865 and macro-F1 = 0.736. This study confirms the efficacy of EMS in the reduction of resting tremors in PD. LSTM was identified as the most effective model for predicting pulse amplitude that would elicit the longest tremor reset time. Our study provides further insight on the tremor reset mechanism in PD.