The Impact of Polypharmacy on Management of Lower Urinary Tract Symptoms in Parkinson's Disease.

Lower urinary tract (LUT) symptoms are a common presentation of autonomic dysfunction in Parkinson's disease (PD). Symptoms significantly impact quality of life and are associated with worsening of motor symptoms and increased risk for falls. Different medical co-morbidities can often contribute to LUT symptoms, and a thorough evaluation therefore becomes essential. The effects of medications used for Parkinson's disease and other co-existing medical co-morbidities on LUT symptoms is often underestimated. Treatment options include behavioural therapy, oral agents such as antimuscarinic and beta-3 receptor agonist agents, botulinum toxin and neuromodulation. The first-line oral agents cause adverse effects that may exacerbate pre-existing Parkinson's disease-related symptoms. Furthermore, these oral agents can interact with other medications used in Parkinson's disease, and the challenges posed by interactions on pharmacological effects and metabolism are discussed. Knowledge about drug interactions can help in effective management of such patients and mitigate the risks for developing adverse effects.

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.

Testing sensation of gently squeezing the testes has diagnostic value in spinal cord injury men.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Determine the diagnostic value of testing the sensation of squeezing the testes. SETTING: Research group run by the University of Antwerp. METHODS: During the clinical examination, it was evaluated if male spinal cord injury (SCI) patients felt gentle squeezing of the testes. The outcome was related to the type of SCI, to the sensations of the light touch of the dermatomes of the perineum, of bladder filling, of overactive detrusor (DOA) contractions during urodynamics, and of electrosensation elicited in different parts of the lower urinary tract. The neurological pathways elicited by these tests were compared. RESULTS: Seventy-four patients were included, mean age 46 ± 17 years, a number of weeks post SCI 318 ± 586. Sensation in the testes was present in 72.2%. In patients with AIS A, the sensation was found positive in 41%, while all with AIS B-D felt the sensation. Testes sensation was strongly correlated with the sensation of touch of the perineum and with the filling sensation during cystometry, proving a dorsal column pathway. The sensation of DOA contractions and electrosensation in the bladder, bladder neck/proximal, and distal urethra were not significantly related to the outcome of the testicular examination, showing that anterior and lateral spinothalamic pathways were not involved CONCLUSIONS: Our data show that sensation from gently squeezing the testes informs about the dorsal column from spinal cord level T10-L2 upwards. The test can help refine the neurologic diagnosis after SCI. We advocate to include this easy-to-do test in the neuro-urologic clinical examination.

Diabetic Cystopathy Occurs Independently from Other Atherosclerotic Risks.

It has not yet been clarified whether atherosclerotic risks other than diabetes are related to bladder small fiber neuropathy (cystopathy) in type 2 diabetes. The aim of this study was to answer this question by urodynamics. This was a retrospective study. The subjects were 44 patients: 27 male, 17 female; mean age 67.0 ± 12.7 years; mean duration of diabetes 16.8 ± 13.1 years; mean HbA1c 7.8 ± 1.2%. We analyzed the relationship between diabetic cystopathy (at least one of the following abnormalities in urodynamics: decreased bladder sensation, post-void residual, detrusor overactivity, low-compliance detrusor) and clinical items, i.e., severity and duration of diabetes, nerve conduction, body mass index, blood pressure, cardio-ankle vascular stiffness index, and ultrasound Doppler echography (plaque score, intima-media thickness) in these patients. As a result, urodynamic diabetic cystopathy was not correlated with any of the above systemic items. In conclusion, the above findings suggest that bladder small fiber neuropathy can occur independently from systemic atherosclerotic risks.

The relationship between lower urinary tract function and 123ioflupane scintigraphy in drug-naïve Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is the most common degenerative cause of movement disorder, and autonomic dysfunction has been recognized in this disorder. PD patients' lower urinary tract (LUT) function is not established. We investigated LUT function in PD by single-photon emission computerized tomography (SPECT) imaging of the dopamine transporter with 123I-ioflupane and clinical-urodynamic observations. PATIENTS AND METHODS: We retrospectively analyzed the cases of 30 patients diagnosed with PD based on published criteria who completed a systematized lower urinary tract symptoms (LUTS) questionnaire and a urodynamics examination irrespective of the presence of LUTS. None of the patients were taking anti-parkinsonian medication during the study. RESULTS: The questionnaire revealed that all 30 patients had LUTS: night-time urinary frequency (in 70%), urinary incontinence (40%), and daytime urinary frequency (80%). A urodynamic study revealed a mean volume at the first sensation at 92.3 ml, bladder capacity at 200.9 ml, and detrusor overactivity in 50%. Sphincter electromyography revealed neurogenic change in 13.6% of those for whom the test was performed. The average SBR showed a significant correlation with bladder capacity (Spearman's correlation coefficient p = 0.0076) and Hoehn Yahr motor stage (Spearman's correlation coefficient p = 0.012). CONCLUSION: Our findings demonstrate that the striatum is relevant to the higher control of storage in micturition function in PD.

Gastrointestinal dysfunction in neuroinflammatory diseases: Multiple sclerosis, neuromyelitis optica, acute autonomic ganglionopathy and related conditions.

Disorders of the nervous system can produce a variety of gastrointestinal (GI) dysfunctions. Among these, lesions in various brain structures can cause appetite loss (hypothalamus), decreased peristalsis (presumably the basal ganglia, pontine defecation center/Barrington's nucleus), decreased abdominal strain (presumably parabrachial nucleus/Kolliker-Fuse nucleus) and hiccupping and vomiting (area postrema/dorsal vagal complex). In addition, decreased peristalsis with/without loss of bowel sensation can be caused by lesions of the spinal long tracts and the intermediolateral nucleus or of the peripheral nerves and myenteric plexus. Recently, neural diseases of inflammatory etiology, particularly those affecting the PNS, are being recognized to contribute to GI dysfunction. Here, we review neuroinflammatory diseases that potentially cause GI dysfunction. Among such CNS diseases are multiple sclerosis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein associated disorder, and autoimmune encephalitis. Peripheral nervous system diseases impacting the gut include Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, acute sensory-autonomic neuropathy/acute motor-sensory-autonomic neuropathy, acute autonomic ganglionopathy, myasthenia gravis and acute autonomic neuropathy with paraneoplastic syndrome. Finally, collagen diseases, such as Sjogren syndrome and systemic sclerosis, and celiac disease affect both CNS and PNS. These neuro-associated GI dysfunctions may predate or present concurrently with brain, spinal cord or peripheral nerve dysfunction. Such patients may visit gastroenterologists or physicians first, before the neurological diagnosis is made. Therefore, awareness of these phenomena among general practitioners and collaboration between gastroenterologists and neurologists are highly recommended in order for their early diagnosis and optimal management, as well as for systematic documentation of their presentations and treatment.

Female detrusor underactivity: Two uterine leiomyoma cases.

INTRODUCTION: Female urinary retention is rare. CASE PRESENTATION: Case 1, a 35-year-old nulliparous woman, and case 2, a 47-year-old nulliparous woman, had transient urinary retention. A urodynamics revealed increased bladder sensation in case 1 and detrusor underactivity with a large post-void residual in cases 1 and 2. Both women had a uterine leiomyoma of >10 cm in diameter. Soon after extraction of the tumor, retention episodes disappeared completely in case 1. CONCLUSION: Although rare, uterine leiomyoma should be listed as a cause of female detrusor underactivity.

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.

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.

Bladder recovery relates with increased mid-cingulate perfusion after shunt surgery in idiopathic normal-pressure hydrocephalus: a single-photon emission tomography study.

AIMS OF STUDY: It is reported that severe bladder disorder in idiopathic normal-pressure hydrocephalus (iNPH) is predicted by right frontal hypoperfusion. However, it is not known whether bladder recovery is predicted by brain perfusion change after shunt surgery. To address this issue, we compared bladder and brain function before and after shunt surgery in iNPH. METHODS: We enrolled 75 patients in the study. Before and 12 months after shunt surgery, we analyzed brain perfusion by SPECT and bladder disorder by a specialized grading scale. The scale consisted of grade 0, none; grade 1, urinary urgency and frequency; grade 2, urinary incontinence 1-3 times a week; grade 3, urinary incontinence >daily; and grade 4, loss of bladder control. More than one grade improvement is defined as improvement, and more than one grade decrement as worsening; otherwise no changes. RESULTS: Comparing before and after surgery, in the bladder-no-change group (32 cases) there was an increase in blood flow which is regarded as reversal of enlargement in the Sylvian fissure and lateral ventricles (served as control). In contrast, in the bladder-improved group (32 cases) there was an increase in bilateral mid-cingulate, parietal, and left frontal blood flow (p < 0.05). In the bladder-worsened group (11 cases) no significant blood flow change was observed. CONCLUSION: The present study showed that after shunt surgery, bladder recovery is related with mid-cingulate perfusion increase in patients with iNPH. The underlying mechanism might be functional restoration of the mid-cingulate that normally inhibits the micturition reflex.

Lower urinary tract dysfunction in patients with brain lesions.

Stroke and brain tumor are well-known brain diseases. The incidence of lower urinary tract dysfunction (LUTD) in these patients ranges from 14% to 53%, mostly overactive bladder (OAB), and is higher when the frontal cortex is involved. This presumably reflects damage at the prefrontal cortex, cingulate cortex, and other areas that regulate (mainly inhibit) the micturition reflex. White-matter disease (WMD) is a chronic, bilateral form of cerebrovascular disease, leading to a high prevalence of OAB (up to 90%). Since WMD is particularly common in the elderly, WMD may be one of the anatomic substrates for elderly OAB. Traumatic brain injury and normal-pressure hydrocephalus are rather diffuse brain diseases, which cause OAB with a prevalence rate of 60-95%. Recent neuroimaging studies have shown a relationship between LUTD and the frontal cortex in these diseases. Data on other brain diseases, particularly affecting deep brain structures, are limited. Small infarctions, tumors, or inflammatory diseases affecting the basal ganglia, hypothalamus, and cerebellum lead to mainly OAB. In contrast, similar diseases affecting the brainstem lead to either OAB or urinary retention. The latter reflects damage at the periaqueductal gray and the pontine micturition center that directly relay and modulate the micturition reflex. Urinary incontinence (UI) in brain disease can be divided into two types: neurogenic UI (due to OAB) and functional UI (immobility and loss of initiative/cognition). These two types of UI may occur together, but management differs significantly. Management of neurogenic UI includes anticholinergic drugs that do not penetrate the blood-brain barrier easily. Management of functional UI includes behavioral therapy (timed/prompted voiding with physical assistance and bladder/pelvic floor training) and drugs to treat gait as well as cognition that facilitate continence. These treatments will maximize the quality of life in patients with brain diseases.

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.

Predictors of the disappearance of triad symptoms in patients with idiopathic normal pressure hydrocephalus after shunt surgery.

We identified factors that predict the disappearance of the triad of symptoms (gait disturbance, cognitive impairment and urinary incontinence) of idiopathic normal pressure hydrocephalus (iNPH) following shunt surgery in this study. We classified 71 patients with iNPH into those whose objective symptoms disappeared (disappearance group) or remained (residual group), for each of the triad symptoms 12 months after shunt surgery. Logistic regression analyses were used to identify the predictors of the disappearance of symptoms among 10 variables before shunt surgery (e.g., age, sex, severity of symptoms, Evans index, cerebrospinal fluid (CSF) pressure, CSF stasis on computerized tomographic cisternography, regional cerebral blood flow on single photon emission computed tomography, three kinds of prior diseases). For each of the triad symptoms, mild symptoms before shunt surgery were predictors of the disappearance of the symptom. Young age was also a predictor of the disappearance of gait disturbance. When the analysis was conducted using subscores of the Mini Mental State Examination, a successful visuoconstruction subtest and an absence of hypertension were predictors of the disappearance of cognitive impairment. None of the neuroimaging examinations predicted the disappearance of symptoms after shunt surgery in this study.

Pathologic thoracic spine fracture in presence of Parkinson's disease and diffuse ankylosis: successful management of a challenging condition.

BACKGROUND: Patients with Parkinson's disease have higher risk of complications and revision surgery following spine surgery. Spinal fracture in an ankylosed spine is also difficult to treat. We recently treated a case of thoracic spine fracture in a patient with Parkinson's disease complicating a severely ankylosed spine. There is no report describing surgical treatment of spine fracture in such a difficult condition, thus, we firstly report the case and discuss the reasons for a successful result. CASE PRESENTATIONS: A 68-year-old man with Parkinson's disease had a pathologic thoracic spine fracture at T11. Four days after onset, he was referred to a local hospital because of gradually increasing back pain, but no spinal fracture was pointed out at that time. Because he developed lower extremity bilateral numbness and weakness, he was transported to our hospital, eight days after onset. When referred to our hospital, he exhibited severe back pain and paralysis of the lower extremities due to spinal cord involvement. Emergency surgery was performed. Decompression of T10-11 was performed followed by instrumented spinal fusion from T8 to L2. A dramatic neurological improvement was observed following surgery, and complete bony fusion was achieved. At the final two-year postoperative follow-up, the patient had no pathological symptoms related to spinal fracture and no instrument failure was observed. CONCLUSION: This patient had Parkinson's disease and a severely ankylosed spine, both of which may lead to unsatisfactory surgical results from spinal surgery. Generally, patients with Parkinson's disease have an increased risk for adjacent segment disease and instrument failure. In this patient, fusion surgery did not change the number of fused segments because operated segments were already ankylosed. Because no stress force exists between adjacent vertebral bodies, a severely ankylosed spine may help prevent screw pullout. Thus, treatment of a spinal fracture in an ankylosed spinal segment is a less adverse condition for patients with Parkinson's disease. Our experience led us to think that a combination of Parkinson's disease with severely ankylosed spine does not necessarily suggest unsatisfactory outcomes after surgical treatment of spinal fracture.