Brain Diseases and Fall-Related Surgery in Older Persons.

BACKGROUND: It is known that age-related brain symptoms (gait difficulty and dementia) increase the likelihood of fall-related surgery. In contrast, it is not known which types of brain disease underlie such symptoms most. OBJECTIVE: The aim of this study was to correlate brain diseases with the types of surgeries performed at our hospital for patients who had fallen. METHODS: This was a retrospective study at a multifaculty university hospital in Japan, with a 12-month recruiting period, a follow-up period of 3.0 ± 2.5 weeks, and ≥1×/week visits. We assembled a neurogeriatric team to diagnose brain diseases with the use of brain imaging to the extent possible and correlated the diagnoses with types of fall-related surgery. RESULTS: Fall-related surgery was conducted by the orthopedics (OP) and neurosurgery (NS) faculties (total n = 124) at a ratio of about 2 to 1. The underlying brain diseases differed by faculty; for OP, surgery was most commonly performed in patients with a combination of white matter disease (WMD) and Alzheimer's disease (AD) (79%) followed by dementia with Lewy bodies. In contrast, for NS, the most common surgery was for patients with alcoholism (50%) followed by a combination of WMD and AD. CONCLUSION: Fall-related surgery was performed by the OP and NS faculties at a 2 to 1 ratio. The major underlying brain diseases were a combination of WMD and AD (79%) for OP and alcoholism (50%) for NS.

Urodynamic Assessment of Neuronal Intranuclear Inclusion Disease.

Neuronal intranuclear inclusion disease (NIID) is a disease that causes leukoencephalopathy (dementia) and peripheral neuropathy (variable manifestation including bladder dysfunction). This is the first urodynamic report to show that bladder dysfunction in NIID is a combination of detrusor overactivity, decreased bladder sensation, large post-void residual, and neurogenic changes in the sphincter electromyogram. This report will help managing bladder dysfunction in NIID.

Possible "Premotor" Multiple System Atrophy-Cerebellar Form.

We report the case of a 52-year-old Japanese man who, while he had no cerebellar ataxia or parkinsonism, was revealed to have silent cerebellar hypoperfusion/mild cerebellar atrophy and sacral autonomic disorder. His sacral autonomic disorder was urinary retention without marked prostate hyperplasia. Urodynamics-sphincter electromyography revealed detrusor hyperactivity with impaired contraction and neurogenic changes of the sphincter motor unit potentials. Although he did not have a motor disorder, these features suggested possible multiple system atrophy-cerebellar (MSA-C) form. The present case report suggests that neuroimaging helps in diagnosing "premotor" MSA-C form in situ.

Bladder Autonomic Dysfunction after a Parietal Stroke.

We describe a case of a 57-year-old man who, immediately after a right parietal ischemic stroke, showed urodynamically determined bladder sensory decrement during filling and an underactive detrusor during voiding, both of which were ameliorated during the course of his treatment. The lower urinary tract symptom (LUTS) occurs in stroke in up to 60% of patients, when it involves the frontal and insular cortices. In addition, LUTS does occur in parietal stroke as seen in our patient, presumably by sensory deafferentiation within the brain that is relevant to the central regulation of the micturition reflex.

Bladder dysfunction as the initial presentation of multiple system atrophy: a prospective cohort study.

OBJECTIVES: Multiple system atrophy (MSA) is a disease that combines autonomic (orthostatic or bladder) with motor [parkinsonian (MSA-P) or cerebellar (MSA-C)] dysfunction. While bladder dysfunction may occur earlier than motor disorders, thus far no prospective study has been available to determine how often and how early bladder autonomic dysfunction predates motor dysfunction in MSA. Therefore, we present data from detailed history-taking in patients with MSA. METHODS: This is a prospective cohort study. Detailed history-taking was performed and a questionnaire administered in 121 MSA patients (73 MSA-C, 48 MSA-P; 74 men, 47 women; age, 58 ± 8.0 years; initial recruitment period, 5 years; follow-up, 6.5 ± 4.0 years). RESULTS: Among the patients with MSA-C, 40 patients (55%) suffered motor dysfunction first, 22 (30%) suffered autonomic dysfunction first, and 11 (15%) initially suffered both simultaneously. Among the patients with MSA-P, 22 patients (46%) suffered motor dysfunction first, 22 (46%) suffered autonomic dysfunction first, and two (8%) initially suffered both simultaneously. Among the 'autonomic-first' subgroup of MSA-C patients, five suffered orthostatic dysfunction first, 13 suffered urinary dysfunction first, and four initially suffered both simultaneously. Among the 'autonomic-first' subgroup of MSA-P patients, six suffered orthostatic dysfunction first, nine suffered urinary dysfunction first, and seven initially suffered both simultaneously. Urinary symptoms were further preceded by erectile dysfunction in men. Overall, 18.2% of patients suffered only urinary symptoms initially, and the mean interval from the onset of urinary to the onset of motor symptoms was 2.8 years (range 1-7 years). CONCLUSION: In MSA patients, 18.2% presented with bladder dysfunction as the sole initial manifestation, and the mean interval from the onset of urinary to the onset of motor symptoms was 2.8 years. It is clinically important to avoid unnecessary prostatic surgery when MSA patients see urologists before neurologists.

Gastrointestinal function in dementia with Lewy bodies: a comparison with Parkinson disease.

PURPOSE: To investigate gastrointestinal function in dementia with Lewy bodies and Parkinson disease. METHODS: We examined gastric emptying and colonic transit time in 19 dementia with Lewy bodies and 46 Parkinson disease patients. RESULTS: Gastric emptying was longer in dementia with Lewy bodies than in Parkinson disease (p = 0.014). Colonic transit time tended to be longer in dementia with Lewy bodies than in Parkinson disease. There was no relationship between gastric emptying and colonic transit time, nor between gastric emptying, colonic transit time and age. CONCLUSION: Gastric emptying was prolonged in dementia with Lewy bodies compared to Parkinson disease.

Positional Vertigo After Isolated Cerebellar Nodulus Stroke: A Report of 3 Cases.

We report 3 cases (69-year-old man, 71-year-old man, and 82-year-old woman) of isolated cerebellar nodulus stroke patients, who presented with positional vertigo alone that lasted only for 2-4 days. Brain magnetic resonance imaging helped diagnosing these cases. Although rare, clinicians should be aware of isolated cerebellar nodulus stroke, when facing with patients with paroxysmal vertigo of acute onset.

Transient Ischemic Attack: Which Determines Diffusion-Weighted Image Positivity?

AIM OF THE STUDY: Diffusion-weighted image (DWI) of magnetic resonance imaging (MRI) can reveal high signal lesion in up to 50% of transient ischemic attack (TIA) patients. However, it is not well-known which factors determine developing DWI positivity. In order to answer this question, we analyzed factors relevant to DWI positivity in TIA patients. METHODS: We had 257 stroke patients at a university emergency/neurology wards. They were 140 men, 117 women, mean age 72 (45-88) years. Among them, 24 (9.3%) had TIA (14 men, 10 women, mean age 71 [58-82] years). All patients underwent a 1.5T MRI. In 24 TIA patients, we investigated the following parameters in relation with stroke maturation: ABCD2 score, smoking habits, blood profile, HbA1C, dyslipidemia, coagulation factors, carotid echography, electrocardiography, cardiac echography, chest X-ray, neurological symptom/signs, imaging, and recurrence of neurological symptom on follow-up. RESULTS: In 24 TIA patients, 13 (54%) were DWI positive and 11 (46%) were DWI negative. After an extensive analysis, all parameters were not relevant to DWI positivity except for plasma osmolarity, i.e., plasma osmolarity in DWI positive cases (305.3 mOsm/l) is significantly higher than that in DWI negative cases (301.3 mOsm/l) (P = .0064). As for recurrence, 4 of 24 TIA patients recurred. They were 1 (9.0%) of 11 DWI negative cases and 3 (23.1%) of 13 DWI positive cases. Therefore, DWI positive cases recurred more frequently than DWI negative cases did, although it did not reach statistical significance. CONCLUSIONS: TIA with DWI positivity in our institute was 54%, closely associated with initial dehydration and might predict stroke recurrence.

Urological dysfunction in synucleinopathies: epidemiology, pathophysiology and management.

OBJECTIVE: Parkinson's disease (PD) and multiple system atrophy (MSA) are major neurogenerative diseases characterized pathologically by abnormal alpha-synuclein aggregation. PD and MSA are clinically characterized by motor disorder and bladder dysfunction (mainly urinary urgency and frequency, also called overactive bladder). However, few literatures are available concerning bladder dysfunction in PD or MSA. METHOD: A systematic review. RESULTS: The bladder dysfunction in MSA is more severe than that in PD for large post-void residual or urinary retention. These bladder dysfunctions presumably reflect the different nervous system pathologies. Overactive bladder in PD reflects lesions in the brain, e.g., in the prefrontal-nigrostriatal D1 dopaminergic bladder-inhibitory pathway. Overactive bladder in MSA reflects lesions similar to PD and the cerebellum (bladder-inhibitory), and the urinary retention in MSA presumably reflects lesions in the pontine micturition center and the sacral intermediolateral nucleus of the spinal cord (bladder-facilitatory). Bladder dysfunction not only impairs an individual's quality of life, it can also cause emergency hospitalizations due to acute retention and early institutionalization. Anticholinergics are the first-line treatment for bladder dysfunction in PD and MSA patients, but care should be taken for the management of bladder dysfunction-particularly in MSA patients due to the high prevalence of difficult emptying, which needs clean, intermittent catheterization. CONCLUSIONS: This review summarizes the epidemiology, pathophysiology, and management of bladder dysfunction in individuals with PD or MSA.

Lower Urinary Tract Function in Familial Spastic Paraplegia.

In order to investigate lower urinary tract function in hereditary spastic paraplegia (HSP), we recruited 12 HSP patients: 8 men, 4 women; mean age, 64.6 years; mean disease duration, 18.9 years; walk without cane, 2, walk with cane, 6, wheelchair bound, 3. We performed urinary symptom questionnaires and a urodynamic testing in all patients. As a result, urinary symptoms were observed in all but 3, including urinary urgency/frequency (also called overactive bladder) in 9 and hesitancy/poor stream in 6. Urodynamic abnormalities included detrusor overactivity during bladder filling in 10, underactive detrusor on voiding in 8 (detrusor hyperactivity with impaired contraction [DHIC] in 5), detrusor-sphincter dyssynergia (DSD) on voiding in 3, and post-void residual in 5. Sphincter electromyography showed neurogenic motor unit potential in 4. In conclusion, we observed high frequency of urinary symptoms in HSP. Urodynamics indicated that the main mechanism is DHIC with/without DSD for their urinary symptom, and sacral cord involvement in some cases. These findings facilitate patients' care including clean, intermittent catheterization.

Bowel and bladder disorders in Parkinson's disease.

Bladder and gastrointestinal (GI) dysfunction are one of the most common in non-motor disorder of Parkinson's disease (PD). GI dysfunction consists of delayed gastric emptying and constipation, which occur in 70 percent of patients and often predate motor disorder. Delayed gastric emptying, slow colonic transit, decreased phasic rectal contraction, weak abdominal strain and paradoxical sphincter contraction on defecation are all features of GI dysfunction in PD, reflecting mostly myenteric plexus pathology. Bladder dysfunction (overactive bladder [OAB]) occurs in 70 percent of patients. This reflects central pathology, particularly in the prefrontal-nigrostriatal DI dopaminergic pathways. The dysfunction needs particular care in order to prevent delayed absorption of levodopa and emergency intestinal pseudo-obstruction.

Lower urinary tract function in dementia with Lewy bodies (DLB).

OBJECTIVES: Dementia with Lewy bodies (DLB) is the second most common degenerative cause of dementia, whereas lower urinary tract (LUT) function in DLB patients has not been fully delineated. We investigated LUT function in DLB by clinical-urodynamic observations. METHODS: We examined 32 patients with DLB (23 men, 9 women; aged 59-86 [mean, 75.9] years; disease duration, 0.2-17 [3.3] years). All patients underwent an electromyography-cystometry, and 21 patients underwent the sphincter motor unit potential analysis. RESULTS: Ninety-one percent of patients had LUT symptoms: nighttime frequency (>8 times), 84%, and urinary incontinence (>1 per week), 50%. Detrusor overactivity was revealed in 87.1%, whereas postvoid residual was minimal. Neurogenic changes were shown in 50%. CONCLUSION: LUT dysfunction is a common feature in DLB, attributable not only to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction.

Nizatidine ameliorates gastroparesis in Parkinson's disease: a pilot study.

BACKGROUND: The objective of this work was to perform an open trial of the effects of nizatidine (NZT), a selective histamine H2-receptor antagonist and a cholinomimetic, on gastroparesis in Parkinson's disease (PD) patients, using objective parameters given by a gastric emptying study using a (13) C-sodium acetate expiration breath test. METHODS: Twenty patients with PD were enrolled in the study. There were 13 men and 7 women; aged 68.0 ± 7.72 years; disease duration 5.50 ± 3.62 years. All patients underwent the breath test and a gastrointestinal questionnaire before and after 3 months of administration of NZT at 300 mg/day. Statistical analysis was performed by Student t test. RESULTS: NZT was well tolerated by all patients and none had abdominal pain or other adverse effects. NZT significantly shortened Tmax ((13) C) (the peak time of the (13) C-dose-excess curve) (P < 0.05). CONCLUSIONS: Although this is a pilot study, we found a significant shortening of gastric emptying time after administration of NZT in PD patients.

Tolterodine activates the prefrontal cortex during bladder filling in OAB patients: a real-time NIRS-urodynamics study.

AIMS: Studies of overactive bladder (OAB) have shown urothelial/suburothelial changes and increased bladder afferents, while in the brain the frontal micturition area that normally suppresses the bladder is deactivated. It has been unclear whether anticholinergic medication could reverse this suppression. To address this question, we performed a real-time NIRS (near-infrared spectroscopy)-urodynamic study in OAB patients before and after the administration of an anticholinergic agent, tolterodine. METHODS: We recruited 13 OAB patients in our outpatient clinic (9 males, 4 female; mean age 73 years). Before and after the administration of 4 mg/day tolterodine for 3 months, all patients completed the OAB-symptom scale and a NIRS-urodynamics examination. Cerebral changes in the oxy-hemoglobin concentration (oxy-Hb) were sampled. Concentration changes in oxy-Hb were calculated based on a modified Beer-Lambert approach. RESULTS: Tolterodine significantly reduced the OAB patients' nighttime frequency (P < 0.05) and increased their first-sensation volume (290-359 ml, P < 0.01). The number of patients with detrusor overactivity did not lessen significantly (11-9). The real-time NIRS-urodynamic study showed that, during slow bladder filling between start and bladder capacity, tolterodine significantly activated the right frontal micturition area of the OAB patients (P < 0.05). The activation was prominent in Brodmann's area 8, 9, 10 of the prefrontal cortex. CONCLUSIONS: Tolterodine reduced bladder sensation together with a significant activation of the frontal micturition area of OAB patients, particularly Brodmann's area 8, 9, 10 of the right prefrontal cortex. This activation seems to be a secondary phenomenon, since tolterodine does not easily penetrate the blood-brain barrier.

Dietary herb extract rikkunshi-to ameliorates gastroparesis in Parkinson's disease: a pilot study.

OBJECTIVE: To perform an open trial on the effects of the extract of the dietary herb Rikkunshi-to (RKT) on gastroparesis in Parkinson's disease (PD) patients, using objective parameters given by the (13)C-sodium acetate expiration breath test (gastric emptying study). METHODS: Twenty patients with PD were enrolled into this study. Eleven patients were male and 9 were female, with the following characteristics (mean ± SD): age, 69.4 ± 8.17 years; disease duration, 4.34 ± 4.03 years; modified Hoehn and Yahr stage, 2.37 ± 0.98, and Unified Parkinson's Disease Rating Scale Part 3 motor score, 16.6 ± 7.37. Fourteen patients came to the clinic due to constipation; 16 patients were taking 288 ± 72 mg/day levodopa/carbidopa, 2 were taking dopamine agonists, and the others were not treated yet. All patients underwent the breath test. Statistical analysis was performed using Student's t test. RESULTS: RKT was well tolerated by all patients and none experienced abdominal pain or other adverse effects, except for its bitter taste. RKT significantly reduced the peak time of the (13)C-dose-excess curve (p < 0.05). CONCLUSION: In this pilot trial, we found a significant shortening of the gastric emptying time after administration of the dietary herb extract RKT in PD patients. Further studies examining both gastric emptying and delayed-on in PD are warranted. .

Bladder function of patients with Parkinson's disease.

Bladder function of patients with Parkinson's disease alters significantly: the majority of patients have overactive bladder (urinary urgency/frequency) with little or no post-void residuals. This seems to be the result of an altered brain-bladder relationship, as in Parkinson's disease, the frontal-basal ganglia D1 dopaminergic circuit that normally suppresses the micturition reflex is altered. The pathophysiology of the bladder dysfunction in Parkinson's disease differs from that in multiple system atrophy; therefore, it might also aid in differential diagnosis. The effects of levodopa, the major drug to treat motor dysfunction, on the bladder in Parkinson's disease vary significantly; therefore, add-on therapy is often required. Anticholinergic drugs are the first-line treatment, with particular care for cognitive function in elderly patients. The second-line treatment includes serotonergics drug, desmopressin and others. Newer modalities include deep brain stimulation that improves the bladder in Parkinson's disease; and botulinum toxin is promising, particularly in difficult cases. These treatments might be beneficial in maximizing the patients' quality of life.

Is overactive bladder a brain disease? The pathophysiological role of cerebral white matter in the elderly.

Small-vessel disease of the brain affecting the deep white matter characteristically manifests with neurological syndromes, such as vascular dementia and vascular parkinsonism. There is, however, compelling evidence to suggest that white matter disease can cause overactive bladder and incontinence, and in some patients these might be the initial manifestation. As white matter disease increases significantly with age, and preferentially affects the prefrontal deep white matter, white matter disease becomes an anatomical substrate in the brain etiology of overactive bladder. Treatment entails the management of small-vessel disease risk factors and anticholinergic drugs that do not easily penetrate the blood-brain barrier, to improve bladder control. In short, when caring for elderly overactive-bladder patients, we should look at both the brain and the bladder.