Correlation with sympathetic skin response, 123I-MIBG scintigraphy, and 123I-FP-CIT SPECT in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD), and other parkinsonian syndromes are known to cause striatonigral dopaminergic system dysfunction and autonomic disturbances, including the vasomotor and sudomotor nervous systems. The detection of 123I-FP-CIT SPECT (DaT scan) imaging and autonomic dysfunction helps differentiate PD from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The sympathetic skin response (SSR) is a simple, non-invasive electrophysiological test that assesses the sympathetic sudomotor nervous system. It is reported that the SSR is impaired in patients with PD, MSA, and PSP. OBJECTIVE: To study the relationship between SSR, 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy and DaT scan imaging parameters in patients with PD, MSA, and PSP. METHODS: The study included 62, 25, and 19 patients with PD, MSA, and PSP, respectively. The SSR, MIBG cardiac scintigraphy, and DaT scan imaging were examined. The amplitude and latency of the SSR were measured in all limbs and were compared with the results of MIBG cardiac scintigraphy and DAT scan imaging. RESULTS: The SSR amplitudes were lower than reported normal subjects' reference values in PD, MSA, and PSP. The SSR amplitude only correlated with MIBG cardiac scintigraphy and DaT scan imaging parameters in PD. Multiple regression analyses also showed a significant relationship between the amplitudes of SSR and DaT scan imaging in PD. CONCLUSION: Unlike MSA, and PSP, the sudomotor nervous system is parallelly involved with cardiac sympathetic and central dopaminergic dysfunction from the early stage of PD.

High doses of opioids usage for amyotrophic lateral sclerosis patients with non-invasive ventilation.

INTRODUCTION: While opioids have been found to be useful in relieving suffering in amyotrophic lateral sclerosis (ALS), there is a lack of evidence concerning how and how much to use them in practice. This study was conducted to clarify how opioids were used for patients with ALS. METHODS: We performed a retrospective case-based analysis at a single tertiary neurology center in Tokyo from 2010 to 2018. We enrolled patients with ALS who had died before the end of 2018. We examined the opioid dosage equivalent of morphine hydrochloride and patients' clinical backgrounds, focusing on ventilatory support. RESULTS: Morphine was administered in 110 patients with ALS, and 84 were followed up until their death. Of these 84 patients, 57 (69.9%) did not use mechanical ventilation until death (no-MV group), and 21 (22.9%) utilized only non-invasive ventilation (NIV group). Final morphine dosage in the NIV group was significantly higher (mean 65.7 mg [SD 54.6], range 10-200 mg) than in the no-MV group (mean 31.7 mg [SD 26.9], range 0-120 mg; p = 0.015, Welch's t-test). The NIV group needed psychotropic drugs more frequently than the no-MV group (62% [n = 13] vs. 35% [n = 20]). CONCLUSION: Patients in the NIV group used opioids for a statistically significantly longer time and at a higher dose than those in the no-MV group. Symptom control with opioids alone may be difficult, and the development of multifaceted evaluation and care is desirable.

Long-Term Trends and Sociodemographic Inequalities of Emotional/Behavioral Problems and Poor Help-Seeking in Adolescents During the COVID-19 Pandemic.

PURPOSE: During the first 3 years of the coronavirus disease (COVID-19) pandemic, we investigated the long-term trends of emotional/behavioral problems and poor help-seeking behavior in adolescents and examined the sociodemographic inequalities in these trends. METHODS: A multiwave cross-sectional survey was conducted in Japan from October-November 2020, June-July 2021, and June-July 2022 using an anonymous questionnaire. Trends of emotional/behavioral problems (e.g., emotional symptoms, hyperactivity/inattention, and total difficulties) and poor help-seeking were tested using a chi-squared test with Bonferroni correction. The effects of sociodemographic factors (grade, gender, country of origin, and number of parents) on emotional/behavioral problems and poor help-seeking were examined by two mixed-effect logistic regression models: (1) with fixed effects for years and sociodemographic factors and (2) stratified by years if the interaction terms between years and each sociodemographic factor were significant. RESULTS: The prevalence of total difficulties and emotional symptoms was the highest in 2021. The number of adolescents reporting hyperactivity/inattention and poor help-seeking increased between 2020 and 2021 and remained high in 2022. Inequalities in emotional/behavioral problems and poor help-seeking behavior were found with respect to all sociodemographic factors. DISCUSSION: Despite the persistent emotional/behavioral problems, the results suggested that the number of adolescents who were unable to seek help increased during the COVID-19 pandemic. Additionally, heterogeneities in the trends with respect to grade, gender, country of origin, and number of parents were detected. Prioritized supports targeting those with sociodemographic disadvantages may be needed to mitigate these inequalities in response to the pandemic.

[MR neurography reveals fascicular constriction of the median nerve in a patient with neuralgic amyotrophy].

Diagnosing neuralgic amyotrophy can be challenging in clinical practice. Here, we report the case of a 37-years old Japanese woman who suddenly developed neuropathic pain in the right upper limb after influenza vaccination. The pain, especially at night, was severe and unrelenting, which disturbed her sleep. However, X-ray and MRI did not reveal any fractures or muscle injuries, and brain MRI did not reveal any abnormalities. During neurological consultation, she was in a posture of flexion at the elbow and adduction at the shoulder. Manual muscle testing suggested weakness of the flexor pollicis longus, pronator quadratus, flexor carpi radialis (FCR), and pronator teres (PT), while the flexor digitorum profundus was intact. Medical history and neurological examination suggested neuralgic amyotrophy, particularly anterior interosseous nerve syndrome (AINS) with PT/FCR involvement. Innervation patterns on muscle MRI were compatible with the clinical findings. Conservative treatment with pain medication and oral corticosteroids relieved the pain to minimum discomfort, whereas weakness remained for approximately 3 months. For surgical exploration, lesions above the elbow and fascicles of the median nerve before branching to the PT/FCR were indicated on neurological examinations; thus, we performed high-resolution imaging to detect possible pathognomonic fascicular constrictions. While fascicular constrictions were not evident on ultrasonography, MR neurography indicated fascicular constriction proximal to the elbow joint line, of which the medial topographical regions of the median nerve were abnormally enlarged and showed marked hyperintensity on short-tau inversion recovery. In patients with AINS, when spontaneous regeneration cannot be expected, timely surgical exploration should be considered for a good outcome. In our case, MR neurography was a useful modality for assessing fascicular constrictions when the imaging protocols were appropriately optimized based on clinical assessment.

Educational challenges for 22q11.2 deletion syndrome in Japan: Findings from a mixed methods survey.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is characterised by a changing pattern of overlapping intellectual, physical, and mental disabilities along the course of one's life. However, the impact of overlapping disorders (multimorbidity) on educational challenges remains unclear. METHOD: A survey was conducted with 88 caregivers of individuals with 22q11DS. A quantitative analysis of educational challenges and support needs divided into age groups (7-12, 13-15, 16-18, and 19 years and over) and a qualitative analysis of the free-text items in the questionnaire was conducted. RESULTS: Caregivers were more interested in comprehensive developmental support when their children were younger, and the emphasis shifted to concerns regarding environments that matched individual characteristics at older ages. Furthermore, when there are multiple disabilities or disorders, support is concentrated on the more obvious disabilities, and the lack of support for the less superficially obvious disabilities associated with multiple difficulties, including mental health problems, can be a challenge for people with 22q11DS and their families. CONCLUSIONS: This study suggests a need for increased focus on multimorbidity and associated disabilities in school education that are difficult to observe because of their mildness or borderline levels if present alone.

Comparison of Bitterness Intensity between Prednisolone and Quinine in a Human Sensory Test Indicated Individual Differences in Bitter-Taste Perception.

Prednisolone is a frequently prescribed steroid with a bitter, unpalatable taste that can result in treatment refusal. Oral suspensions or powder dosage forms are often prescribed, particularly to pediatric patients, as they improve swallowability and ease of dose adjustment. Consequently, the bitterness of prednisolone is more apparent in these dosage forms. Few studies have investigated prednisolone's bitterness. Thus, in this study, 50 adults evaluated the bitterness of prednisolone using the generalized Labeled Magnitude Scale (gLMS), in comparison with quinine, a standard bitter substance. Overall, prednisolone-saturated solution demonstrated the same extent (mean gLMS score: 46.8) of bitterness as 1 mM quinine solution (mean gLMS score: 40.1). Additionally, large individual differences were observed in the perception of the bitterness of prednisolone and quinine. Perceived flavors of some drugs are reportedly associated with bitter-taste receptor (TAS2Rs) polymorphisms. Therefore, we investigated the relationship between subjects' genetic polymorphisms of TAS2R19, 38, and 46, and their sensitivity to bitterness. Although a relationship between TAS2R19 polymorphisms and the perception of quinine bitterness was observed, no significant relationship was found between the perceived bitterness of prednisolone and the investigated genes. Ultimately, the results show that despite individual differences among subjects, the cause of prednisolone's strong bitterness is yet to be elucidated.

The difference in the diaphragmatic physiological measures between inspiratory and expiratory phases in ALS.

INTRODUCTION: We aimed to clarify the differences in static and dynamic diaphragm parameters between the expiratory and inspiratory phases in amyotrophic lateral sclerosis (ALS). METHODS: Twenty patients with early-stage ALS and 16 healthy controls were enrolled in the study. We measured the amplitudes of compound muscle action potential (phCMAP) by electrical stimulation of the phrenic nerve and the zone of apposition wall thickness of the diaphragm (DT) using ultrasonography. We analyzed the differences in phCMAP (∆phCMAP) and DT (∆DT) between the end-inspiratory and end-expiratory phases and their correlation with forced vital capacity (FVC). RESULTS: The ΔphCMAP (mean 129.7 ± SD 204.7 µV) and ∆DT (0.80 ± 0.88 cm) in patients were significantly smaller than those in controls (348.6 ± 247.7 µV, p = 0.0003 and 1.89 ± 1.10 cm, p = 0.0002, respectively). Although ∆DT was significantly correlated with FVC, we found no correlation between ∆phCMAP and FVC. The phCMAP was paradoxically smaller during inspiration than during expiration in 35% of patients but in none of the controls. CONCLUSION: Dynamic parameters of the diaphragm were abnormal in early-stage ALS. The paradoxical reduction in phCMAP during inspiration may reflect early respiratory dysfunction. Assessment of dynamic abnormalities of the diaphragm may provide helpful information for respiratory management in patients with ALS.

Sex-based differences in the longitudinal association between autistic traits and positive psychotic experiences in adolescents: A population-based cohort study.

Previous reports have suggested a cross-sectional association between autistic traits and psychotic experiences (PEs) in adolescents. However, while both autistic traits and PEs show sex-related differences, no studies have directly assessed whether such differences exist in the longitudinal association between autistic traits and PEs. Using a population-based adolescent cohort sample (n = 3007), we tested whether the longitudinal association between autistic traits and positive PEs was affected by sex-based differences using regression analyses. Autistic traits were assessed at 12 years old (timepoint 1 [T1]), and PEs were assessed at 12 and 14 years old (T1 and T2). Subsequently, we tested whether subdomains of autistic traits (difficulties in social interaction, communication, imagination, attention to detail, and attention switching) were associated with subtypes of PEs (auditory hallucinations, visual hallucinations, and delusions) using structural equation modeling, after controlling for PEs at T1, socio-economic status, school performance and parents' psychiatric disorders. After controlling for PEs at T1, we did not find any associations between autistic traits at T1 and PEs at T2 in both sexes. There was no significant positive or negative association between all subdomains of autistic traits and subtypes of PEs in both sexes. Autistic traits do not seem to predict future PEs in general adolescents regardless of sex.

Trajectory and course of problematic alcohol use after the Great East Japan Earthquake: Eight-year follow-up of the Higashi-Matsushima cohort study.

BACKGROUND: Problematic alcohol use (PAU) after natural disasters is an unignorable public health issue. However, the long-term trajectory and course of PAU after an earthquake disaster remain unknown. METHODS: The Higashi-Matsushima cohort study was conducted between 2012 (time 1) and 2019 (time 8) in areas affected by the Great East Japan Earthquake in 2011. In the annual health checks, participants responded to self-report questionnaires on PAU, traumatic experiences (e.g., house damage), resources (e.g., social support), and other covariates (e.g., gender, psychological distress). The trajectory and course of PAU were estimated by latent growth model and latent class analyses. Risk factors for the long-term course of PAU were calculated by multinomial logistic regression analysis with multiple imputation. The analytical sample comprised 8929 residents who participated in at least one survey across the eight time points. RESULTS: The trajectory of PAU showed a sustained trend (slope <0.001). Three potential courses of PAU (No PAU course: 84.3%, Subthreshold PAU course: 12.4%, and Persistent PAU course: 3.4%) were estimated. The long-term course of PAU, especially the persistent PAU course, was predicted by house damage (OR = 1.43, 95% CI 1.06 to 1.92), less social support (OR = 0.71, 95% CI 0.53 to 0.96), gender (male) (OR = 16.86, 95% CI 9.42 to 30.20), and psychological distress (OR = 1.15, 95% CI 1.09 to 1.20). CONCLUSIONS: Long-term support is needed after an earthquake disaster, especially for residents who in early phases of the disaster suffer from PAU, males, and those in vulnerable situations resulting from conditions such as severe house damage, low social support, or high psychological distress.

Medical, welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross-sectional survey in Japan.

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (ß = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (ß = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (ß = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.

Trigeminal Neuralgia Caused by Dural Arteriovenous Fistula of the Transverse-Sigmoid Sinus without Vessel Compression at Root Entry Zone.

Objective: The vessel compression at the root entry zone (REZ) of trigeminal nerve is a common cause of trigeminal neuralgia (TN). We report a rare case of TN caused by dural arteriovenous fistula (DAVF) of the transverse-sigmoid sinus without vessel compression at REZ. Case Presentation: A 45-year-old woman presented with right side tinnitus and was diagnosed as a DAVF of the right transverse-sigmoid sinus (Borden Type I). After that, the facial pain in the right maxillary nerve area appeared and was getting worse. DSA revealed an enlargement of the artery of foramen rotundum (AFR) as one of the feeding arteries. MRI revealed no evidence of vascular compression at REZ. The patient was treated with transarterial embolization (TAE) with Onyx via the branches of the middle meningeal artery (MMA) and occipital artery (OA). The AFR decreased in size and the facial pain was improved. However, the DAVF and the facial pain were recurred. Finally, the DAVF was completely embolized with transvenous embolization (TVE). During 1-year follow-up period, the patient remained free of pain without recurrence. Conclusion: The compression of the maxillary nerve by the AFR might result in TN, because the pain diminished after shrinkage of the AFR by the endovascular treatment.

Implementation of online classes during national school closure due to COVID-19 and mental health symptoms of adolescents: A cross-sectional survey of 5000 students.

Aim: Online classes were implemented in numerous schools during the school closure due to COVID-19. The present study examined the relationship between online classes during national school closure and mental health symptoms after the reopening of schools. Methods: We conducted a cross-sectional survey from October 1 to November 7, 2020 using an anonymous self-reported questionnaire to evaluate 21 junior and senior high schools in the Saitama prefecture of Japan. Out of the 5538 students who were recruited, 5000 agreed to participate. The relationship between the implementation of online classes and mental health symptoms (emotional symptoms, psychotic experience [PE], and smartphone addiction) was evaluated using mixed-effect logistic regression models, while controlling for individual and class-level covariates (e.g., gender, grades). Results: Implementation of online classes was reported by 78.2% of classroom teachers, and it was associated with lower rates of emotional symptoms (OR = 0.79, 95% CI = 0.63-0.99, p = 0.040) and smartphone addiction (OR = 0.79, 95% CI = 0.65-0.96, p = 0.020), but not related to PE (OR = 0.91, 95% CI = 0.61-1.36, p = 0.637). Conclusions: Implementing online classes during the national school closure might have had a potential protective effect for adolescents' mental health symptoms (especially emotional symptoms and smartphone addiction) after the reopening of schools during the ongoing COVID-19 pandemic.

Bidirectional relationship of problematic Internet use with hyperactivity/inattention and depressive symptoms in adolescents: a population-based cohort study.

Problematic Internet use (PIU), hyperactivity/inattention, and depressive symptoms are comorbid problems in adolescence, but the causal relationships among these issues are unclear. To assess the relationships among PIU, hyperactivity/inattention, and depressive symptoms in adolescents in the general population. This longitudinal cohort study used data from the Tokyo Teen Cohort study in Tokyo, Japan, for two years between October 2012 and January 2015. Of the 3171 pairs of children and parents, 3007 pairs continued to participate in the second wave of the Tokyo Teen Cohort study. A total of 3007 children were included in the analysis (mean [standard deviation] age, 9.7 [0.4] years; 1418 women [47.2%]. Cross-lagged panel analysis revealed that PIU at timepoint 1 was significantly associated with hyperactivity/inattention at timepoint 2 (ß = 0.03; 95% confidence interval (CI) 0.01-0.06), and hyperactivity/inattention at timepoint 1 was also significantly associated with PIU at timepoint 2 (ß = 0.07; 95% CI 0.04-0.10), even after adjustments were made for depressive symptoms. Furthermore, PIU at timepoint 1 was significantly associated with depressive symptoms at timepoint 2 (ß = 0.05; 95% CI 0.01-0.12), and depressive symptoms at timepoint 1 were also significantly associated with PIU at timepoint 2 (ß = 0.05; 95% CI 0.02-0.07), even after adjustments were made for hyperactivity/inattention. These results support the bidirectional relationships among PIU, hyperactivity/inattention, and depressive symptoms. PIU may be a target to improve hyperactivity/inattention and depressive symptoms in adolescents.

Validation of the General Medicine in-Training Examination Using the Professional and Linguistic Assessments Board Examination Among Postgraduate Residents in Japan.

PURPOSE: In Japan, the General Medicine In-training Examination (GM-ITE) was developed by a non-profit organization in 2012. The GM-ITE aimed to assess the general clinical knowledge among residents and to improve the training programs; however, it has not been sufficiently validated and is not used for high-stake decision-making. This study examined the association between GM-ITE and another test measure, the Professional and Linguistic Assessments Board (PLAB) 1 examination. METHODS: Ninety-seven residents who completed the GM-ITE in fiscal year 2019 were recruited and took the PLAB 1 examination in Japanese. The association between two tests was assessed using the Pearson product-moment statistics. The discrimination indexes were also assessed for each question. RESULTS: A total of 91 residents at 17 teaching hospitals were finally included in the analysis, of whom 69 (75.8%) were women and 59 (64.8%) were postgraduate second year residents. All the participants were affiliated with community hospitals. Positive correlations were demonstrated between the GM-ITE and the PLAB scores (r = 0.58, p < 0.001). The correlations between the PLAB score and the scores in GM-ITE categories were as follows: symptomatology/clinical reasoning (r = 0.54, p < 0.001), physical examination/procedure (r = 0.38, p < 0.001), medical interview/professionalism (r = 0.25, p < 0.001), and disease knowledge (r = 0.36, p < 0.001). The mean discrimination index of each question of the GM-ITE (mean ± SD; 0.23 ± 0.15) was higher than that of the PLAB (0.16 ± 0.16; p = 0.004). CONCLUSION: This study demonstrates incremental validity evidence of the GM-ITE to assess the clinical knowledge acquisition. The results indicate that GM-ITE can be widely used to improve resident education in Japan.

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis.

OBJECTIVE: A large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS. METHODS: A total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis. RESULTS: Patients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively). CONCLUSIONS: The HFO amplitude in ALS is increased, but does not predict survival. SIGNIFICANCE: The enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.

[A proposal of a novel palliative care scale and analysis of suffering in amyotrophic lateral sclerosis].

OBJECTIVE: We proposed a novel palliative care scale (Amyotrophic Lateral Sclerosis Palliative Care Scale: ALSPCS) for patients with ALS, and analyzed the suffering reported by patients. METHODS: Thirty-one patients participated in the study. The ALSPCS has 15 items to evaluate physical and psychological suffering; patients scored their subjective suffering on a scale of 0-5 for each item. This study analyzed 13 of 15 items. RESULTS: The mean scores obtained from the patients were as follows: 'dyspnea', 2.5; 'pain', 2.4; 'restlessness', 2.4; 'thirst', 3.0; 'burning sensation', 2.0; 'choking', 2.0; 'nausea', 0.4; 'constipation', 1.5; 'insomnia', 2.5; 'anxiety', 3.5; 'loneliness', 2.4; 'irritation', 2.1; and 'communication difficulty', 2.3. Multiple correlation analysis using Spearman's rank correlation coefficient showed significant correlations of dyspnea with restlessness, thirst, burning sensation and anxiety; of restlessness with dyspnea, thirst, loneliness and irritation; and of anxiety with dyspnea, thirst and loneliness (P < 0.0038 after Bonferroni's correction). In the principal component analysis, every item showed a positive loading value in the first principal component. Dyspnea, restlessness, thirst, anxiety, loneliness and irritation had loading values >0.7; thus, these symptoms might be the main features in ALS patients. The total scores or each ALSPCS score showed no significant association with post-assessment survival period. CONCLUSION: This study, using ALSPCS, showed that the subjective suffering of ALS patients was variable and strongly correlated with each other. Appropriate and comprehensive assessment of physical and psychological affliction with ALSPCS could be potentially useful in verifying the effectiveness of palliative care for end-of-life stage ALS patients in the future.