Impact of Nutritional Status on Antibody Titer After Booster mRNA COVID-19 Vaccine Among Elderly Adults in Japan.

BACKGROUND: Published studies on mRNA coronavirus disease 2019 (COVID-19) vaccine effects focus on younger individuals, comprising the majority of the workforce. Studies in elderly adults are sparse. METHODS: In total, 107 subjects were recruited (median age 78; interquartile range [IQR], 58.5-90.5; range, 35-105 years). Factors associated with antibody titer after the third mRNA COVID-19 vaccination were compared between 49 elderly (age ≥80; median, 94; IQR, 86-97; range, 80-105 years) and 58 younger (age ≤79; median, 61; IQR, 46-71; range, 35-79 years) adults. RESULTS: Among body mass index (BMI) categories, the group of underweight elderly adults had a lower antibody titer compared to those with normal weight (P < .01 after 1, 3, and 5 months). Elderly adults were less likely to maintain effective antibody titer (≥4160 AU/mL) compared to younger adults: 76% versus 98%, P < .001 after 1 month, and 45% versus 78%, P < .001 after 3 months. Elderly adults who maintained effective antibody titer for 5 months had a higher BMI (22.9 kg/m2 vs 20.1 kg/m2, P = .02), and were less likely to have underweight BMI (0% vs 31%, P = .02) compared to the subjects who failed to maintain effective antibody titer. CONCLUSIONS: These results highlight the impact of nutritional status and the deleterious effect of underweight BMI on antibody titer and its maintenance among elderly adults following booster mRNA COVID-19 vaccination.

Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study.

INTRODUCTION: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. METHODS: This cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients' demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. RESULTS: Ninety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. CONCLUSION: Both DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.

Comparative whole transcriptome analysis of Parkinson's disease focusing on the efficacy of zonisamide.

OBJECTIVE: Interindividual variations in responsiveness to zonisamide in patients with Parkinson's disease (PD) have been observed in clinical settings. To decipher the molecular mechanisms determining the efficacy of zonisamide, we conducted whole transcriptome sequencing analysis of patients with PD. METHODS: We selected 23 super-responders (SRs) and 25 non-responders (NRs) to zonisamide from patients with PD who had participated in a previous clinical trial for the approval of zonisamide for the treatment of 'wearing-off'. Whole transcriptome analysis of peripheral blood was conducted on samples taken before and 12 weeks after zonisamide treatment. We performed differential gene expression analysis to compare between the SRs and NRs at each time point. RESULTS: Differentially expressed genes in the pre-treatment samples were significantly enriched for glutamatergic synapses and insulin-like growth factor binding (Padj=7.8 × 10-3 and 0.029, respectively). The gene sets associated with these functions changed more dynamically by treatment in SRs than NRs (p=7.2 × 10-3 and 8.2 × 10-3, respectively). CONCLUSIONS: Our results suggest that the efficacy of zonisamide in PD patients is associated with glutamate-related synaptic modulation and p53-mediated dopaminergic neural loss. Their transcriptomic differences could be captured before treatment, which would lead to the realisation of future personalised treatment.

Long-Term Efficacy and Safety of Zonisamide for Treatment of Parkinsonism in Patients With Dementia With Lewy Bodies: An Open-Label Extension of a Phase three Randomized Controlled Trial.

OBJECTIVES: To evaluate the long-term efficacy and safety of zonisamide, an antiepileptic agent, in dementia with Lewy bodies (DLB). DESIGN: Phase three clinical trial with 12 week, randomized, placebo-controlled, double-blind, and subsequent 40 week, open-label, extension periods. SETTING: A total of 109 centers in Japan between April 2015 and November 2017. PARTICIPANTS: Outpatients diagnosed with probable DLB. INTERVENTION: Outpatients were randomly assigned to receive placebo (P) or zonisamide 25 or 50 mg/day for 12 weeks. In the subsequent open-label 40 week period, all patients initially received zonisamide 25 mg/day for at least 2 weeks followed by optional flexible dosing with zonisamide 25 or 50 mg/day for the remaining period. MEASUREMENTS: The primary outcome was efficacy on motor symptoms, assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score, over the total 52 week trial period. Effects on behavioral and psychological symptoms of dementia and cognitive function, and safety were also evaluated. RESULTS: In total, 335 patients were included in the long-term analysis: 106, 117, and 112 in the P-, 25mg-, and 50mg-Flex groups, respectively. UPDRS-III score continued to improve for an additional 12 to 16 weeks in the open-label period (mean [standard deviation] change from baseline at Week 28: -5.1 [7.3] and -6.3 [8.2] in the 25mg- and 50mg-Flex groups) and remained almost constant thereafter. No unexpected neurological or psychiatric adverse events occurred, and no adverse events increased in incidence in the open-label period. CONCLUSIONS: Long-term treatment with zonisamide was well tolerated and yielded sustained improvement in motor symptoms. TRIAL REGISTRATION: JapicCTI-152839 (Registered on 9 March 2015) https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152839.

Prefrontal network dysfunctions in rapid eye movement sleep behavior disorder.

INTRODUCTION: Resting-state functional connectivity magnetic resonance imaging (rsfcMRI) of rapid eye movement (REM) sleep behavior disorder (RBD) may provide an early biomarker of α-synucleinopathy. However, few rsfcMRI studies have examined cognitive networks. To elucidate brain network changes in RBD, we performed rsfcMRI in patients with polysomnography-confirmed RBD and healthy controls (HCs), with a sufficiently large sample size in each group. METHODS: We analyzed rsfcMRI data from 50 RBD patients and 70 age-matched HCs. Although RBD patients showed no motor signs, some exhibited autonomic and cognitive problems. Several resting-state functional networks were extracted by group independent component analysis from HCs, including the executive-control (ECN), default-mode (DMN), basal ganglia (BGN), and sensory-motor (SMN) networks. Functional connectivity (FC) was compared between groups using dual regression analysis. In the RBD group, correlation analysis was performed between FC and clinical/cognitive scales. RESULTS: Patients with RBD showed reduced striatal-prefrontal FC in ECN, consistent with executive dysfunctions. No abnormalities were found in DMN. In the motor networks, we identified reduced midbrain-pallidum FC in BGN and reduced motor and somatosensory cortex FC in SMN. CONCLUSION: We found abnormal ECN and normal DMN as a possible hallmark of cognitive dysfunctions in early α-synucleinopathies. We replicated abnormalities in BGN and SMN corresponding to subclinical movement disorder of RBD. RsfcMRI may provide an early biomarker of both cognitive and motor network dysfunctions of α-synucleinopathies.

Female, aging, difference formulations of DCI, or lower body weight increases AUC4hr of levodopa in patients with Parkinson's disease.

INTRODUCTION: There is considerable intra- and inter-individual variability in the pharmacokinetics (PK) of levodopa after oral administration. Inter-individual variability in levodopa PK has also been demonstrated in fasting single-dose studies. We examined the factors that affect levodopa PK in patients with Parkinson's disease (PD) and quantified the intensity of their respective effects. METHODS: We studied 220 patients who underwent PK assessment after administration of 1 tablet of levodopa/DOPA decarboxylase inhibitor (DCI) combination, which contained 10 mg carbidopa/100 mg levodopa or 25 mg benserazide/100 mg levodopa. PK was evaluated using non-compartmental analysis. RESULTS: In total, 220 PD patients (including 112 men) were studied. The mean age (±standard deviation) and mean disease duration was 68.1 ± 8.9 and 7.7 ± 5.8 years, respectively. The Cmax of levodopa was 9.0 ± 4.0 ng/mL, Tmax was 41.4 ± 40.2 min, and area under the blood concentration-time curve up to 4 h (AUC4hr) was 12.3 ± 3.7 ng/mL*4hr. Factors affecting AUC4hr were analyzed using multiple linear regression models. Age (1.1 ± 0.23 per +10 years, p = 3.1E-8), sex (2.2 ± 0.5 for female, p = 1.9E-5), DCI (1.4 ± 0.4 for benserazide, p = 0.0028), and body weight (-0.77 ± 0.22 per +10 kg, p = 5.4E-4) were significantly related to AUC4hr, while disease duration, dyskinesia status, and eGFR were not related to AUC4hr and Cmax. CONCLUSION: Female, aging, difference formulations of DCI, or lower body weight independently contributes to increased AUC4hr of levodopa in Japanese patients with PD in this study.

Genome-wide association study identifies zonisamide responsive gene in Parkinson's disease patients.

Long-term treatment of Parkinson's disease (PD) by levodopa leads to motor complication "wearing-off". Zonisamide is a nondopaminergic antiparkinsonian drug that can improve "wearing-off" although response to the treatment varies between individuals. To clarify the genetic basis of zonisamide responsiveness, we conducted a genome-wide association study (GWAS) on 200 PD patients from a placebo-controlled clinical trial, including 67 responders whose "off" time decreased ≥1.5 h after 12 weeks of zonisamide treatment and 133 poor responders. We genotyped and evaluated the association between 611,492 single nucleotide polymorphisms (SNPs) and "off" time reduction. We also performed whole-genome imputation, gene- and pathway-based analyses of GWAS data. For promising SNPs, we examined single-tissue expression quantitative trait loci (eQTL) data in the GTEx database. SNP rs16854023 (Mouse double minute 4, MDM4) showed genome-wide significant association with reduced "off" time (PAdjusted = 4.85 × 10-9). Carriers of responsive genotype showed >7-fold decrease in mean "off" time compared to noncarriers (1.42 h vs 0.19 h; P = 2.71 × 10-7). In silico eQTL data indicated that zonisamide sensitivity is associated with higher MDM4 expression. Among the 37 pathways significantly influencing "off" time, calcium and glutamate signaling have also been associated with anti-epileptic effect of zonisamide. MDM4 encodes a negative regulator of p53. The association between improved motor fluctuation and MDM4 upregulation implies that p53 inhibition may prevent dopaminergic neuron loss and consequent motor symptoms. This is the first genome-wide pharmacogenetics study on antiparkinsonian drug. The findings provide a basis for improved management of "wearing-off" in PD by genotype-guided zonisamide treatment.

Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: A phase 3 randomized clinical trial.

INTRODUCTION: Zonisamide is approved in Japan for treating motor dysfunction in Parkinson's disease, and might also be effective for parkinsonism in patients with dementia with Lewy bodies (DLB). Our study evaluated the safety and efficacy of zonisamide for treating parkinsonism in patients with DLB. METHODS: This multicenter, randomized, double-blind, phase 3 trial was conducted in Japan between April 2015 and November 2017. Following a 4-week run-in period, outpatients diagnosed with probable DLB who had developed parkinsonism were randomized to receive oral zonisamide (25 or 50 mg/day) or placebo for 12 weeks, followed by a 40-week open-label extension. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part III total score at Week 12. RESULTS: Of 351 patients randomized, 346 (mean age, 77.2 years; 188 males) were included in the modified intention-to-treat population. At Week 12, the group difference (least squares mean ± SEM) for changes from baseline (vs placebo) in UPDRS part III total score was -2.7 ± 0.9 (95% confidence interval [CI]: -4.4, -0.9, P = 0.005) in the zonisamide 25-mg group and -2.6 ± 0.9 (95% CI: -4.4, -0.8, P = 0.005) in the zonisamide 50-mg group. Adverse events were reported in 47.1%, 48.7%, and 54.5% of patients in the placebo and zonisamide 25- and 50-mg groups, and led to treatment discontinuation in 5.0%, 4.3%, and 9.8% of patients, respectively. CONCLUSION: Daily administration of 25- or 50-mg zonisamide significantly improved motor function compared with placebo; both doses were safe and well tolerated in patients with DLB.

[Complications and troubleshooting at the initial introduction of Levodopa-carbidopa continuous infusion gel therapy: A single-center study].

Levodopa-carbidopa intestinal gel (LCIG) therapy has been established as a device-aided treatment for advanced Parkinson's disease. We retrospectively investigated the issues related to LCIG therapy in patients with Parkinson's disease at our hospital from March 2014 to July 2018. The subjects were 18 patients including nine men and nine women. The mean duration of PD symptoms and motor fluctuation was 14.5 ± 5.9 and 7.2 ± 4.5 years, respectively. The mean age at initiation of LCIG was 60.1 ± 9.4 years and the mean treatment period was 21.1 ± 19.5 months. One hundred and sixteen LCIG-associated issues were observed, including pain at the gastrostomy site (23 cases), hypergranulation tissue (14 cases), skin redness and/or erosions (11 cases), cutaneous infections at the gastrostomy site (eight cases), percutaneous endoscopic gastrojejunostomy (PEG-J) tube occlusion in the gastrointestinal tract (19 cases), irremovable PEG-J tube (13 cases), dislocation of the PEG-J tube (six cases), and breakage of the connector (eight cases). The majority of these issues were easily diagnosed and could be managed by neurologists who are familiar with LCIG therapy.

Phenotype of a limb-girdle congenital myasthenic syndrome patient carrying a GFPT1 mutation.

We report a 38-year-old woman who presented with mild proximal dominant muscle weakness and fatigability that fluctuated during menstruation and treatment with ephedrine-containing medication. The patient had been diagnosed with "congenital myopathy with tubular aggregates" by muscle biopsy at age 19. Her revised diagnosis was congenital myasthenic syndrome (CMS) caused by a mutation in GFPT1 (2p13.3 [MIM 610542], c.722_723insG homozygote, CMS-GFPT1) based on a screening gene analysis. Muscle CT revealed diffuse atrophy of proximal and axial muscles focused on the vastus lateralis, hamstrings, medial gastrocnemius and soleus muscles. Oral administration of pyridostigmine bromide clearly ameliorated weakness and fatigability. This is the first reported case of CMS-GFPT1 in Japan. Since CMS symptoms are reactive to treatment, it is important for clinicians to make an accurate diagnosis at an early stage to improve patient QOL. Tubular aggregates in muscle biopsy and day-to-day fluctuations are important features of the disorder. Quantitative muscle strength measurement was effective for evaluating treatment efficacy.

Lidocaine injections and neck corset wearing improve dropped head syndrome in Parkinson's disease and related disorders.

BACKGROUND: Patients with Parkinson's disease and related disorders (PDRD) may exhibit dropped head syndrome (DHS), which does not yet have an effective treatment. OBJECTIVES: To evaluate the effect of combining lidocaine injection into the bilateral scalene muscles and neck corset wearing on dropped head syndrome. METHODS: We performed needle electromyography assessments of the scalene, sternocleidomastoid (SCM), levator scapulae, splenius capitis, and trapezius muscles. Patients received 2.5-5 ml injections of 1% lidocaine into both sides of the scalene muscles for 4/5 consecutive days and were instructed to wear a neck corset. We measured the neck flexion angle, which formed between the horizontal line and the straight line passing through the ear canal and orbital fossa, before (baseline) and after (Day 8 and Day 90) the intervention. RESULTS: Seven males and eight females (mean age, 68.9 years; range 56 to 85 years) who had PDRD with dropped head syndrome were enrolled in this study. Needle electromyography examination revealed abnormal discharge of the scalene muscles in all patients when the neck position was corrected; however, some patients did not show abnormal discharge of the SCM muscle. At Day 8, we observed an improvement of the neck flexion angle in 13 of the 15 patients, from an average of 27.7°â€¯±â€¯13.9° to 11.7 ±â€¯14.6°. At Day 90, the average neck flexion angle was 15.3°â€¯±â€¯17.2°. CONCLUSIONS: Combining lidocaine injection into the scalene muscles and neck corset wearing is an effective treatment regimen for DHS in patients with PDRD.

[Questionnaire survey of Scans Without Evidence of Dopaminergic Deficit (SWEDD) in Japan].

We conducted a questionnaire survey to collect epidemiological information on patients with Scans Without Evidence of Dopaminergic Deficit (SWEDD). We sent questionnaires to 4,970 neurology specialists in Japan in July 2015 and received responses from 933 of them. The total number of patients reported to have Parkinson's disease was 39,532, which included 237 cases of SWEDD in patients (111 males, 125 females, and 1 case without a gender description). The disease duration in patients with SWEDD was short; 127 cases (53.6%) had a duration less than 3 years, and 78 cases (32.9%) had a duration of 3 years or more but less than 7 years. By age, 59 cases (24.9%) occurred in individuals in their 60s, and 106 cases (44.7%) occurred in individuals in their 70s. Sixty-three neurologists stated that they performed dopamine transporter single photon emission computed tomography (DaT SPECT) on almost all patients with Parkinson's disease. They treated a total of 3,600 patients with Parkinson's disease which included 107 cases of SWEDD; therefore, approximately 3.0% of Parkinson's patients were estimated have SWEDD. The causes of SWEDD were unknown (101 cases), essential tremor (22 cases), vascular Parkinsonism (14 cases), and drug-induced Parkinsonism (14 cases). The majority of neurologists had doubts about the diagnosis of Parkinson's disease prior to confirming the diagnosis using DaT SPECT for reasons such as: normal findings on meta-iodobenzylguanidine (MIBG) myocardial scintigraphy, poor responses to anti-Parkinson drugs, lack of true akinesia, unchanged symptoms, and atypical symptoms. Two hundred and nineteen cases included reports on treatment paradigms following the SWEDD diagnosis. Of those cases, patients in 159 cases were maintained on the same treatment following diagnosis.

Phenotypic variability of Niemann-Pick disease type C including a case with clinically pure schizophrenia: a case report.

BACKGROUND: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Identifying preclinical cases is important for prevention and therapy. Here, we report three newly diagnosed NPC cases, one typical juvenile-onset case and the cases of two sisters with symptoms neurologically/psychiatrically indistinguishable from dystonia and schizophrenia, respectively. CASE PRESENTATION: In Case 1, a 25-year-old man presented with a 14-year history of intellectual disability, clumsiness, spastic ataxia, dysphagia, and frequent falls. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and filipin staining of skin fibroblasts was positive with a variant staining pattern. NPC1 gene analysis showed compound heterozygous mutations, including c.1421C > T (p.P474L), a known causative mutation, and c.3722 T > C (p.L1241S), a new mutation. In Case 2, a 28-year-old woman, the proband, who had marked splenomegaly in her childhood, survived well, contrary to the expected severe prognosis of infantile NPC. She had minor neuropsychiatric symptoms including auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of 28 years, she presented with a 1-year history of orofacial and oromandibular painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with schizophrenia. In both cases, filipin staining of skin fibroblasts was positive with variant staining patterns, as well as elevated levels of urinary bile acids. NPC1 gene analysis showed compound heterozygous mutations including c.3011C > T (p.S1004 L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new mutation. Their mother, who was under therapy with modafinil for narcolepsy, shared the latter mutation. CONCLUSIONS: Marked clinical variability was observed in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and neurological examination were quite important in the diagnostic process.

Quantitative Analysis of Surface Electromyography for Pediatric Neuromuscular Disorders.

INTRODUCTION: Needle electromyography (EMG) has been an important diagnostic tool, although discomfort may limit its use in some children. We investigated the diagnostic utility of the clustering index (CI) method, a quantitative analysis for surface EMG (SEMG), in children. METHODS: SEMG was recorded from the tibialis anterior muscle. Discriminant analysis between patients with neurogenic disorders and patients with myopathy was performed for whole epochs by using the CI and area values. RESULTS: Forty-five children (29 with myopathy, 16 with neurogenic disorders; age 9 ± 3.9 years) were enrolled. The mean discriminant function value of the neurogenic group was 0.58 ± 0.88 (-0.48-2.30), whereas that of the myopathic group was -0.55 ± 0.70 (-2.38-0.68). When the cutoff value was set at the limit of the other group, 17 of 29 children with myopathy and 7 of 16 children with neurogenic disorders were correctly classified. DISCUSSION: The CI method can be a useful noninvasive diagnostic tool in children with neuromuscular disorders. Muscle Nerve 58:824-827, 2018.

Characteristics of facial expression recognition ability in patients with Lewy body disease.

BACKGROUND: The facial expression of medical staff has been known to greatly affect the psychological state of patients, making them feel uneasy or conversely, cheering them up. By clarifying the characteristics of facial expression recognition ability in patients with Lewy body disease, the aim of this study is to examine points to facilitate smooth communication between caregivers and patients with the disease whose cognitive function has deteriorated. METHODS: During the period from March 2016 to July 2017, we examined the characteristics of recognition of the six facial expressions of "happiness," "sadness," "fear," "anger," "surprise," and "disgust" for 107 people aged 60 years or more, both outpatient and inpatient, who hospital specialists had diagnosed with Lewy body diseases of Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Based on facial expression recognition test results, we classified them by cluster analysis and clarified features of each type. RESULTS: In patients with Lewy body disease, happiness was kept unaffected by aging, age of onset, duration of the disease, cognitive function, and apathy; however, recognizing the facial expression of fear was difficult. In addition, due to aging, cognitive decline, and apathy, the facial expression recognition ability for sadness and anger decreased. In particular, cognitive decline reduced recognition of all of the facial expressions except for happiness. The test accuracy rates were classified into three types using the cluster analysis: "stable type," "mixed type," and "reduced type". In the "reduced type", the overall facial recognition ability declined except happiness, and in the mixed type, recognition ability of anger particularly declined. CONCLUSION: There were several facial expressions that the Lewy body disease patients were unable to accurately identify. Caregivers are recommended to make an effort to compensate for such situations with language or body contact, etc., as a way to convey correct feeling to the patients of each type.

A new device-aided cognitive function test, User eXperience-Trail Making Test (UX-TMT), sensitively detects neuropsychological performance in patients with dementia and Parkinson's disease.

BACKGROUND: A newer generation neuropsychological tests can take advantage of touch screen and mobile technology. We have developed a new Android application termed "User eXperience-Trail Making Test (UX-TMT)" for neurocognitive assessment and training. This study investigated the utility, including the reliability and the validity, of the UX-TMT as a screening test for cognitive decline in adults. METHODS: A total of 84 individuals aged 27-86 years were divided into three groups; healthy controls ([HC] n = 29), people with Parkinson's disease (PD; n = 28), and people with mild cognitive impairment (MCI) and dementia (MCI&D; n = 27). We examined the distributions of the scores and the time required, and the effects of age and group on these distributions. We analyzed internal consistency and convergent validity in all samples and applied receiver operator characteristic (ROC) analysis to determine a cutoff score that could differentiate the MCI & D group from the HC group. RESULTS: 97.6% of the participants completed all of the tasks, and the average total test time required for UX-TMT was 428.8 (± 109.1) s in the HC, 542.0 (± 168.7) s in the PD, and 777.5 (± 256.1) s in the MCI&D groups, respectively. The MCI&D group showed significantly lower UX-TMT scores and longer total time in completing the task than the HC group. In an ROC analysis, a score of 21 showed high sensitivity (.83) and specificity (.92), and the UX-TMT score plus age improved sensitivity to .96. Additionally, the UX-TMT scores showed significant correlation with the Mini-Mental State Examination (Japanese version) scores (r = .77, p = .001), and Cronbach's alpha (.71-.83) indicated acceptable internal consistency. CONCLUSION: The UX-TMT demonstrated high reliability and validity to detect cognitive decline in Japanese adults, highlighting its utility as a screening tool for epidemiological and clinical research.

Consensus for the measurement of the camptocormia angle in the standing patient.

INTRODUCTION: Camptocormia is characterized by a pathological forward flexion of the trunk, which is reversible when lying and worsened by standing and walking. So far there is no consensus on how to measure the angle of flexion, and studies therefore give differing results. Harmonization is needed for both research and clinical practice. Orthopedic measures are not useful for this purpose. METHODS: Two expert raters independently analyzed the photographs of 39 Parkinson patients with camptocormia while standing. They used four different methods to determine the camptocormia angle. The results were compared statistically. An international Consensus Group reviewed the results and drafted recommendations. RESULTS: The four methods yielded camptocormia angles that differed by up to 50% in the same patient. Inter-rater reliability and test-retest reliability also differed, but were satisfactory to excellent. CONCLUSION: This Consensus Group concluded that two of the methods qualified as reliable measures of the trunk angles in standing patients based on their clinimetric properties. They propose that the 'total camptocomia angle' be the angle between the line from the lateral malleolus to the L5 spinous process and the line between the L5 spinous process and the spinous process of C7. They also propose that the 'upper camptocormia angle' be the angle of the lines between the vertebral fulcrum to the spinous processes of L5 and C7, respectively. An app is provided on the web for these measurements (http://www.neurologie.uni-kiel.de/de/axial-posturale-stoerungen/camptoapp).

Supplemental Treatment for Huntington's Disease with miR-132 that Is Deficient in Huntington's Disease Brain.

Huntington's disease (HD) is an intractable neurodegenerative disorder caused by mutant Huntingtin (HTT) proteins that adversely affect various biomolecules and genes. MicroRNAs (miRNAs), which are functional small non-coding RNAs, are also affected by mutant HTT proteins. Here, we show amelioration in motor function and lifespan of HD-model mice, R6/2 mice, by supplying miR-132 to HD brains using a recombinant adeno-associated virus (rAAV) miRNA expression system. miR-132 is an miRNA related to neuronal maturation and function, but the level of miR-132 in the brain of R6/2 mice was significantly lower than that of wild-type mice. Our miR-132 supplemental treatment, i.e., supplying miR-132 to the brain, produced symptomatic improvement or retarded disease progression in R6/2 mice; interestingly, it had little effect on disease-causing mutant HTT mRNA expression and its products. Therefore, the findings suggest that there may be a therapeutic way to treat HD without inhibiting and/or repairing disease-causing HTT genes and gene products. Although miR-132 supplement may not be a definitive treatment for HD, it may become a therapeutic method for relieving HD symptoms and delaying HD progression.

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease.

OBJECTIVE: The causes of "delayed-on" and "no-on" phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. CASE DESCRIPTION: A 69-year-old man with PD presented with "delayed-on" and "no-on" phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an "off" state. Videofluoroscopic examination of swallowing in an "off" state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of "delayed-on" and "no-on" phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of "no-on" phenomena decreased. CONCLUSION: In PD patients, the "no-on" phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.