Clinical characteristics of patients with Parkinson's disease with reduced 123I-metaiodobenzylguanidine uptake in the major salivary glands and heart.

BACKGROUND: Parkinson's disease (PD) shows cardiac sympathetic denervation (SD) in 123I-metaiodobezylguanidine (MIBG) scintigraphy. Recently, SD in the major salivary glands (MSG-SD) was introduced as a possible radiological feature of PD. OBJECTIVE: To identify the clinical characteristics of patients with PD with reduced MSG and cardiac MIBG uptake (dual-SD) compared with those with reduced MSG or cardiac MIBG uptake only (single-SD). METHODS: We recruited 90 patients with PD and 30 controls and evaluated their non-motor (e.g., hyposmia, autonomic dysfunction) and motor (e.g., Movement Disorder Society-Unified Parkinson's Disease Rating Scale) features. We also assessed MIBG uptake in the MSG and heart using a quantitative semi-automatic method, and compared MIBG uptakes between PD and controls. We set cut-off values for optimal sensitivity and specificity, and compared the clinical characteristics of patients with PD between dual- and single-SD groups. RESULTS: MSG and cardiac MIBG uptakes were significantly reduced in PD. Sixty-one patients had dual-SD, 25 had single-SD, and four had non-SD. In patients with PD with normal cardiac SD, 76.5% (13/17) of whom showed abnormalities only in MSG-SD. When clinical characteristics were compared between the dual-SD and single-/non-SD groups, patients in the dual-SD group were older and had more severe hyposmia and autonomic dysfunction, except motor features. Multiple logistic regression analysis identified age as an important confounder. CONCLUSIONS: Patients with PD with dual-SD have more severe non-motor features than other patients. Autonomic dysfunction might progress independently from dopaminergic degeneration. Furthermore, our findings indicate that aging is a crucial factor in PD progression.

Reduced 123I-MIBG uptake in the parotid and submandibular glands in patients with Parkinson's disease identified using a quantitative semi-automatic method.

OBJECTIVES: To analyze 123I-metaiodobenzylguanidine (MIBG) uptake in the parotid and submandibular glands in patients with Parkinson's disease (PD) in comparison with controls, and to compare MIBG uptake between those glands and the myocardium. Furthermore, we aimed to identify the relationships between clinical features and MIBG uptake. METHODS: We recruited 77 patients with PD and 21 age-matched controls. We assessed MIBG scintigraphy in the major salivary glands and myocardium. We calculated the MIBG uptake ratio in the parotid glands/mediastinum (P/M), submandibular glands/mediastinum (S/M), and heart/mediastinum (H/M) using a quantitative semi-automatic method. We investigated the correlations between MIBG uptake and clinical features. RESULTS: The P/M and H/M ratios in the early and delayed phases were significantly reduced in PD patients compared to controls, while the delayed phase S/M ratio was reduced in PD patients compared to controls. The P/M ratio correlated with the S/M ratio, while neither the P/M nor S/M ratio correlated with the H/M ratio. Between PD patients and controls, sensitivity and specificity were 54.8% and 59.1% for the delayed phase P/M ratio, while sensitivity and specificity were 59.5% and 61.0% for the delayed phase S/M ratio, respectively. Furthermore, sensitivity and specificity for the delayed phase H/M ratio were 85.7% and 79.2, respectively. CONCLUSION: MIBG uptake in the parotid and submandibular glands was reduced in patients with PD. Furthermore, sympathetic denervation in the major salivary glands and myocardium might progress independently. Our findings suggest a new aspect of the pathological distribution of PD.

Effects of Long-term Hybrid Assistive Limb Use on Gait in Patients with Amyotrophic Lateral Sclerosis.

Objective To assess the long-term effects of hybrid assistive limb (HAL) treatment on gait in patients with amyotrophic lateral sclerosis (ALS). Methods Three courses of treatment with HAL were administered to three women with ALS. Each course had a four- to five-week duration, during which the treatment was performed nine times, with a rest period of at least two months between each course. Gait ability (2-minutes-walk and 10-m-walk tests), ALS Functional Rating Scale-Revised, and respiratory function tests were performed before and after each treatment course. Patients Patients diagnosed with ALS, according to the updated Awaji criteria, by board-certified neurologists in the Department of Neurology and Department of Rehabilitation Medicine, Toho University Omori Faculty of Medicine between January and December 2019 were recruited. Results The average time from the start to the end of the 3 courses was 319.7±33.7 days. A multiple regression analysis was performed for the 2-minutes-walk and 10-m-walk tests, using the baseline value, each participant's ID, and time point as covariates. Changes after each course were considered outcomes. Following the 3 treatment courses, the 2-minutes walk distance improved by 16.61 m (95% confidence interval, -9.33-42.54) compared with the baseline value, but this improvement was not statistically significant (p=0.21). However, cadence significantly improved by 1.30 steps (95% confidence interval, 0.17-2.42; p=0.02). Conclusion Long-term, repetitive HAL treatments may help patients with ALS maintain their gait.

Similarities, differences and overlaps between frailty and Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder clinically characterized by bradykinesia, rest tremor, rigidity, and postural and gait disturbances, which are frequently observed in older people. It also shows non-motor symptoms, such as depression, anxiety, cognitive impairment and dementia. The number of patients is gradually increasing worldwide. Aging is a risk factor for the onset of Parkinson's disease, and various physiological effects of aging influence its progression. Frailty is a geriatric syndrome in which the reversible and vulnerable status between robustness and disability is affected by various physiological stressors with aging. Frailty consists of physical, psychological and social aspects. Furthermore, sarcopenia, a syndrome characterized by the loss of muscle mass, strength and function, is also significantly associated with frailty. To maintain the quality of life of older people, frailty, including sarcopenia, should be quickly and appropriately managed. Polypharmacy is an important factor causing the progression of frailty in geriatric syndrome. Although Parkinson's disease and frailty have similar symptoms, and are considered to affect each other, the clinical features and mechanisms of both largely remain unclear. Nevertheless, little literature on the relationship between frailty and Parkinson's disease is currently available. This narrative review aims to clarify the relationships between Parkinson's disease and frailty, not only on the physical, but also on the mental, cognitive, and social aspects and issues regarding polypharmacy in Parkinson's disease explored by previous studies. Geriatr Gerontol Int 2022; 22: 259-270.

Robot-assisted training using hybrid assistive limb ameliorates gait ability in patients with amyotrophic lateral sclerosis.

OBJECTIVE: The Hybrid Assistive Limb (HAL; CYBERDYNE, Inc., Japan) is a wearable robot device that provides effective gait assistance according to voluntary intention by detecting weak bioelectrical signals of neuromuscular activity on the surface of the skin. We used HAL for patients with amyotrophic lateral sclerosis (ALS) to determine whether HAL training had an effect on their gait ability. METHODS: We conducted a single-center, single-arm, observational study. Patients with ALS underwent HAL training once per day (20-40 min per session) for 9-10 days for at least 4 weeks. Gait ability was evaluated using the 2-minute walk test, the 10-meter walk test without the assistance of HAL, and activities of daily living (ADL) using the Barthel Index and Functional Independence Measures before and after a full course of HAL training. RESULTS: There were no dropouts or adverse events during the observation period. Gait function improved after HAL training. The 2-minute walk test revealed a mean gait distance of 73.87 m (36.65) at baseline and 89.9m (36.70) after HAL training (p = 0.004). The 10-meter walk test showed significantly improved cadence, although gait speed, step length on the 10-m walk, or ADL measurements did not change significantly. CONCLUSIONS: Although HAL is not a curative treatment for ALS, our data suggest that HAL may be effective in ameliorating and preserving gait ability in patients with ALS.

Individual voxel-based morphometry adjusting covariates in multiple system atrophy.

INTRODUCTION: This study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD). METHODS: We included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI. RESULTS: On iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD. CONCLUSION: iVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.

Contradictory Responses to the COVID-19 Pandemic in Amyotrophic Lateral Sclerosis Patients and Their Families and Caregivers in Japan.

Objective The coronavirus disease 2019 (COVID-19) pandemic has resulted in a shortage of medical resources, including ventilators, personal protective equipment, medical staff, and hospital beds. We investigated the impact of COVID-19 in amyotrophic lateral sclerosis (ALS) patients, their families, caregivers, and medical experts. Methods We conducted a nationwide ALS webinar about COVID-19 in May 2020 and sent a questionnaire to those enrolled. Results A total of 135 participants (31 ALS patients; 23 families and caregivers of ALS patients; 81 medical experts) responded to this cross-sectional self-report questionnaire. The results showed that tracheostomy and invasive ventilation (TIV) was used in 22.6% of ALS patients, whereas 77.4% of ALS patients were not under TIV. Among non-TIV patients (n=24), 79.2% did not want TIV in the future. However, 47.4% of non-TIV patients not wanting a tracheostomy in advanced stages replied that they would want an emergency tracheostomy if they developed COVID-19-related pneumonia. These results suggest that ALS patients may be receptive to emergency treatments for reasons other than ALS. In addition, approximately half of the ALS patients agreed with the policy of not ventilating the elderly or ALS patients in case of a ventilator shortage. Furthermore, compared with medical experts, few ALS patients reported that the chance for ALS patients to obtain work was higher due to the increasing availability of remote work. Conclusions This survey indicates that the COVID-19 pandemic might be associated with increased distress about access to care and work, inducing contradictory responses and potential hopelessness among ALS patients.

Dopamine Transporter Imaging in Parkinson Disease: Progressive Changes and Therapeutic Modification after Anti-parkinsonian Medications.

Parkinson disease (PD) is a slowly progressive neurodegenerative disease characterized by the loss of dopaminergic neurons and terminals in the nigrostriatal system. Dopamine transporter (DAT) imaging is widely performed for the differential diagnosis of PD and other degenerative parkinsonism from essential tremor, vascular parkinsonism, and drug-induced parkinsonism. DAT is the plasma membrane carrier specific to dopamine neurons that are responsible for re-uptaking dopamine from the synaptic cleft back into the nerve ending. DAT binding might reflect striatal presynaptic dysfunction or DAT expression in PD patients. Longitudinal studies of DAT imaging have reported progressive changes from early PD patients. This imaging may be used as a progressive biomarker. Follow-up DAT imaging for therapeutic interventions has been applied for several anti-parkinsonian drugs. We herein review the progressive changes and therapeutic modification of DAT binding by anti-PD medications in early PD patients.

Utility of thermographic measurements of laterality of body surface temperature to prevent misdiagnosis of acute Wallenberg's syndrome.

INTRODUCTION: Acute Wallenberg's syndrome (WS) is sometimes misdiagnosed as a nonstroke disease including auditory vertigo, and careful neurological examination is required for a precise diagnosis. Lateral difference of body surface temperature (BST) had been reported as a symptom of WS, although further details of this symptom are currently lacking. Our aim was to investigate the laterality of BST of patients with acute WS using thermography and the usefulness of thermography to detect acute WS. METHODS: Nine consecutive patients with new-onset acute WS and nine patients with acute pontine infarction, intended for a comparison, were enrolled. Using thermography, the BST of patients was measured and initially evaluated visually. Detailed BSTs were measured using dedicated software. We examined the relationship between BST and other clinical factors, including first diagnosis, clinical symptoms, and MRI findings. RESULTS: Four patients with WS (44.44%) were misdiagnosed with nonstroke disease and did not receive a thermography assessment at their first visit; in contrast, all acute pontine infarction patients were diagnosed with brain infarction. Eight patients with WS (89%) showed a laterality of BST at multiple sites, and three of eight patients showed a whole-body laterality of BST; in contrast, only two pontine infarction patients showed laterality of BST at one or two sites. These lateral BST differences were easily observed visually using thermography within two minutes. The BST laterality gradually decreased over time in almost all patients with WS. The infarction size in the WS patients with whole-body laterality of BST was craniocaudally larger than in the other patients, and the size was smallest in the patient showing no BST laterality. CONCLUSIONS: In contrast to acute pontine infarction patients, almost all patients with acute WS showed lateral BST differences, which was easily detected with thermography. Thermography may thus be a useful tool to prevent misdiagnosis of acute WS.

Preventive Treatment with Lomerizine Increases Cerebral Blood Flows during the Interictal Phase of Migraine.

BACKGROUND: Changes in regional cerebral blood flow (rCBF) were reported in migraineurs. However, little is known how preventive medications of migraine can influence rCBF. Lomerizine, a calcium channel blocker, has been used for migraine prophylaxis in Japan. We examined rCBF after lomerizine treatment. SUBJECTS AND METHODS: Migraine was diagnosed according to the criteria of the International Classification of Headache Disorders, Third Edition beta. Migraine subtype was classified into migraine with aura (MA) and migraine without aura (MO). Lomerizine (10 mg/day, per oral) was administered for 3 months. Headache Impact Test-6 (HIT-6) and blood pressure (BP) were compared at baseline and end point. Brain single photon emission computed tomography using 99mTc-ethyl cysteinate dimer was performed at the interictal period. Brain SPECT data were analyzed according to revised version of 3-dimensional stereotaxic region of interest template. Clinic-radiological variables were analyzed by paired Student's t test. RESULTS: Ten migraineurs (4 men and 6 women) participated in the present study. Mean age was 54.1 (standard deviation [SD] 10.1) years. Mean duration of migraine was 25.3 (SD 9.8) years. Migraine subtype showed 4 MA and 6 MO patients. Mean score of HIT-6 was 66.3 (SD 11.7). Lomerizine treatment decreased HIT-6 scores significantly (P < .01). BP did not differ significantly after lomerizine treatment. Lomerizine treatment increased rCBF 20% approximately in the frontal, the parietal, the temporal, and the occipital region. CONCLUSIONS: The present study indicated a significant increase in interictal rCBF after lomerizine treatment in migraineurs. The upregulation of rCBF could contribute to the antimigraine mechanism of lomerizine.

Treatment with telmisartan, a long-acting angiotensin II receptor blocker, prevents migraine attacks in Japanese non-responders to lomerizine.

Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50-75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.

Clinical Profile and Changes of Serum Lipid Levels in Epileptic Patients after Cerebral Infarction.

BACKGROUND: Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). SUBJECTS AND METHODS: Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients. Serum lipid levels were measured before and at 3 months after AED treatment. RESULTS: The prevalence of PSE was 7.0% in CI patients. The TOAST etiology disclosed large-artery atherosclerosis in 68 patients (45%), cardioembolism in 63 patients (42%), and undetermined cause in 19 patients (13%). CVD risk profile showed obesity of 18 patients (12%), current smoker of 30 patients (20%), hypertension of 75 patients (50%), diabetes mellitus of 32 patients (21%), dyslipidemia of 15 patients (10%), and atrial fibrillation of 63 patients (42%). CBZ or PHT administration increased serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels significantly compared to baseline and AED-untreated controls. Those levels were not increased significantly in other AED and control groups. Serum high-density lipoprotein-cholesterol and triglyceride levels did not differ statistically in all groups. CONCLUSIONS: The prevalence of post-CI epilepsy was 7.0%. The pathogenesis contributed to atherothrombosis and cardioembolism. CBZ or PHT administration increased serum TC and LDL-C significantly. Thus, we should pay more attention to serum lipid levels in patients receiving cytochrome P450 (CYP)-induced AEDs, and might considerer switching to non-CYP-induced AEDs in patients with unfavorable serum lipid changes.