Yosuke Aiba

Nizatidine Ameliorates Slow Transit Constipation in Parkinson's Disease

To the Editor: Constipation (slow transit and anorectal types) is one of the most common nonmotor disorders in Parkinson’s disease (PD). Neuronal degeneration with alpha-synuclein-positive Lewy bodies appears in the myenteric plexus. Constipation leads to emergency intestinal pseudoobstruction, interferes with levodopa absorption, triggers malignant syndrome, and can appear earlier than motor disorder. Because slow-transit constipation is not responsive to levodopa, add-on therapies have been tried, with variable benefits. The results of a colonic transit time (CTT) test before and after administration of nizatidine, which acts on histamine H2 receptors, is presented. Inclusion criteria were PD and gastrointestinal tract (GIT) symptoms (upper: nausea, postprandial bloating; lower: bowel movement <3 times a week, difficult defecation) (12 participants complained of constipation). Individ-

Levodopa Does Not Worsen Gastric Emptying in Parkinson's Disease.

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Genetic Screening for Spinocerebellar Ataxia Genes in a Japanese Single-Hospital Cohort

Objective Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, multiple system atrophy of cerebellar type (MSA-C), and sporadic late cortical cerebellar atrophy. Recently, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was identified in a cohort of patients with non-MSA-C sporadic cerebellar ataxia. The aim of this study is to genetically screen genes involved in SCA in a Japanese single-hospital cohort. Methods Over an 8-year period, 140 patients with cerebellar ataxia were observed. There were 109 patients with sporadic cerebellar ataxia (no family history for at least four generations, 73 patients with MSA-C, and 36 patients with non-MSA-C sporadic cerebellar ataxia) and 31 patients with familial cerebellar ataxia. We performed gene analysis comprising SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA) in 28 of 31 non-MSA-C sporadic patients who requested the test. Familial patients served as a control. Results Gene abnormalities were found in 57% of non-MSA-C sporadic cerebellar ataxia cases. Among patients with sporadic cerebellar ataxia, abnormalities in SCA6 were the most common (36%), followed by abnormalities in SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). In contrast, gene abnormalities were found in 75% of familial cerebellar ataxia cases, with abnormalities in SCA6 being the most common (29%). For sporadic versus familial cases for those with SCA6 abnormalities, the age of onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) in the former than in the latter (not statistically significant). Conclusion Autosomal-dominant mutations in SCA genes, particularly in SCA6, are not rare in sporadic cerebellar ataxia. The reason for the frequency of mutations in SCA6 remains unclear; however, the reason may reflect a higher age at onset and variable penetrance of SCA6 mutations.

Myasthenia Gravis Manifesting As Head Drop in an Elderly Adult with Parkinson's Disease.

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Transdermal Dopamine Agonist Ameliorates Gastric Emptying in Parkinson's Disease.

This research is supported by Grant T15LM007442 from the National Library of Medicine. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Chaudhuri: study design, recruitment, data collection, preparation of manuscript. Oudejans: data analysis and interpretation. Thompson, Demiris: study design, assisting primary author throughout the study, data interpretation, preparation of final manuscript. Sponsor’s Role: None.

Amyotrophic Lateral Sclerosis Presenting Respiratory Failure as the Sole Initial Manifestation

It is rare that amyotrophic lateral sclerosis (ALS) presents with respiratory failure as the sole initial manifestation. A 72-year-old man with mild chronic obstructive pulmonary disease developed exertional dyspnea for 13 months. He then progressed to limb weakness that led to the diagnosis of ALS. Although rare, ALS can present with respiratory failure as the sole initial manifestation more than 1 year prior to limb weakness.

Frontal executive function and the bladder: A study of dementia with Lewy bodies

Pathophysiology of bladder dysfunction in dementia with Lewy bodies (DLB, a disease that shares pathology with Parkinsons disease [PD]) is disturbed prefrontal‐basal ganglia pathway. Similarly, DLB/PD patients have frontal executive dysfunction by the same mechanism.

Tafamidis improves bladder function in hereditary ATTR amyloidosis

A 71‐year‐old man with a family history of hereditary ATTR (ATTRm) amyloidosis, began to have sensory disturbance in his extremities at age 65. Although he had no cardiac or gastrointestinal symptoms, a head‐up tilt test, ultrasound echography, myocardial scintigraphy, and upper gastric biopsy showed abnormality. This, together with the findings of nerve conduction study and gene analysis, confirmed a diagnosis of ATTRm. He was started on 20 mg/day tafamidis meglumine, a transthyretin tetramer stabilizer, and 0.5 mg/day clonazepam, a GABAergic drug. Somatic nerve functions were unchanged or slightly worsened. However, his bladder autonomic nerve function, as assessed by a urodynamic test, showed mild improvements characterized by recovery of bladder sensation and contractility.

MIBG myocardial scintigraphy identifies premotor PD/DLB during a negative DAT scan period: Second report: MIBG test identifies premotor PD/DLB

Neuroimaging markers for Parkinsons disease (PD)/dementia with Lewy bodies (DLB) include dopamine transporter (DAT) scanning and metaiodobenzylguanidine (MIBG) myocardial scintigraphy. It is unknown which marker is useful to identify the premotor phase PD/DLB. We reported four patients who, during a negative DAT scan period, had a positive MIBG result that suggested premotor PD/DLB. Here we report 18 additional patients.

Parkinson's disease and prostate enlargement: Both contribute to overactive bladder in the elderly

DOI: 10.1111/iju.13792 Both PD and BPE, known to cause OAB, are common in the elderly. However, it is not known which contributes more to OAB in the elderly. To answer this question, we studied urodynamic differences between patients with BPE alone, BPE and PD, and PD alone. We had 89 male patients; comprising 12 BPE alone, 31 BPE and PD, and 46 PD alone, and the details are shown in Table S1. We defined BPE as 3-D ultrasound prostate volume >20 mL. Prostatic tumor, urethral stricture and other LUT disorders were carefully excluded. We had a total of 43 BPEs (prostate volume 28–68 mL), irrespective of LUT symptom, with alpha-adrenergic antagonists, 5-alpha reductase inhibitors and so on (no anticholinergics). We diagnosed PD using the published criteria. We had a total of 77 men with PD; the mean HY was grade 2; the mean duration of disease was 2.0 years; and all were taking 200 mg/day levodopa or other medication (no anticholinergics). All patients underwent urodynamics with informed consent, and all patients completed the International Prostate Symptom Score questionnaire (data not shown). We divided DO into phasic DO (Fig. 1a) and terminal DO (Fig. 1b). Statistics was analyzed by Student’s t-test and Spearman’s rank correlation coefficient test. This study was approved by the IRB (No. 2011-059). Regarding the frequency of DO, phasic DO in the total PD patients seemed more common than that in BPE patients (no statistical significance), and terminal DO in the total BPE patients seemed more common than that in PD patients (no statistical significance; Table S2). Obstruction in the total BPE patients seemed more common than that in PD patients (no statistical significance). NDV volume in the total PD patients was significantly smaller than BPE patients (P < 0.01). Also, SDV volume in the total PD patients was smaller than BPE (P < 0.01, P = 0.05). If we examined the total PD sample, age did not significantly relate with LUT functions. In contrast, disease duration and HY motor grade were significantly related with SDV (P = 0.05 and P < 0.01, respectively; Table S3). This is the first study to show that smaller NDV and MDV volume were more significantly related with PD than BPE. The pattern of DO might also differ; for example, phasic DO is common in PD, whereas terminal DO is common in BPE, although without statistical significance. Smaller NDV and MDV in PD might indicate increased bladder sensation. Cerebral areas involved in the sensory processing of bladder afferents are different from those involved in somatic afferents (Tables S1,S2). Bladder afferent inputs reach the midbrain periaqueductal gray, projecting to the cingulate and insular cortices. The basal ganglia play a role in sensory gating. Deep brain stimulation of the subthalamic nucleus reverses abnormally reduced first sensation and bladder capacity in PD, together with activation of the insular cortex. The mechanism to determine either phasic or terminal DO remains to be answered, and future studies are warranted. There are management issues. In BPE alpha-blockers are used, whereas they might worsen hypotension in PD. Conversely, alpha stimulants for postural hypotension in PD might worsen urination in BPE. Prostatic surgery is not contraindicated in BPE with PD, after excluding multiple system atrophy (mimicking PD). We still do not know the effectiveness of drugs on phasic DO (in PD) versus terminal DO (in BPE), whereas phasic DO might be difficult to treat because of its neurogenic nature. However, urodynamics can become an option to suspect BPE + PD if we see phasic DO. In such an event, the collaboration of urologists and neurologists is recommended for further treatment of PD. Anticholinergic drugs and/or selective beta-3 receptor antagonist, together with alpha-1 blockers and 5-alpha reductase inhibitors, are used in the treatment of OAB in BPE, and in PD men aged >50 years. In men with PD aged <50 years and in women with PD, anticholinergics and/or beta-3 antagonist can be used alone. Limitations included a small sample size. Negative results might be not negative, whereas positive results might be a chance co-occurrence. Therefore, confirmatory studies with a larger sample size are required. As BPE and PD can occur together in the elderly, when we see phasic DO or subtle neurological symptoms (gait and cognitive disorders), it is recommended to refer patients to neurologists and collaborate together, in order to maximize patients’ quality of life.