Time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy.

AIMS: Because time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy (MSA) are yet unknown, we aimed to determine these parameters through a combination of urodynamic examination and the results of a questionnaire on urinary symptoms. METHODS: We retrospectively reviewed 66 patients with MSA who responded to a urinary symptoms questionnaire and underwent urodynamic examination more than twice. The participants' mean age was 62 years and mean disease duration at the first urodynamic examination was 3.2 years. Mean duration between the first and second urodynamic examination was 441 days. RESULTS: With regard to overall (both genders) time-dependent change, none of the urinary symptoms showed significant differences. In the urodynamic examination there were significant differences in reduced urine flow, increased post-void residuals, and decreased detrusor contractility at the second examination. With regard to gender differences, at the first examination, night-time urinary frequency, and voiding symptoms were significantly more severe in male than in female patients; however, at the second examination, except for urinary urgency, gender differences were not observed for any other symptoms. In urodynamic examination, the degree of detrusor contraction was significantly less in male patients at the first examination. However, no significant differences were found in urodynamic examination at the second examination. CONCLUSIONS: The present study indicates that voiding dysfunction progressed without significant worsening of voiding symptoms. In addition, gender differences are important in evaluating urinary dysfunction being basically less severe in female than in male patients, at least during the early stage. Neurourol. Urodynam. 33:516-523, 2014. © 2013 Wiley Periodicals, Inc.

[Bladder Dysfunction and Neurology: How to Assess Neurogenic Bladder Dysfunction?]

Here we reviewed bladder dysfunction in neurological diseases. Diseases of the brain cause overactive bladder (OAB); peripheral neuropathy including lumbar spondylosis results in postvoid residual; and spinal cord diseases cause a combination of OAB and postvoid residual. Multiple system atrophy mimics bladder dysfunction related to spinal cord disease. Conversely, in cases of bladder dysfunction of unknown etiologies, the underlying disease can be identified by the bladder dysfunction pattern. Aging also causes nocturnal polyuria. The collaboration between neurologists and urologists is highly recommended to maximize the quality of life of neurological patients.

Receiver operating characteristic analysis of sphincter electromyography for parkinsonian syndrome.

AIMS: We performed receiver operating characteristic (ROC) analysis to determine the ability of sphincter electromyography (EMG) to distinguish multiple system atrophy (MSA) from other parkinsonisms. The following was determined: (1) the appropriate motor unit potential (MUP) parameter among duration, phase, and amplitude; (2) the desirable parameter of our duration criteria; that is, more than 20% MUPs having >10 ms duration (criteria a) or mean duration >10 ms (criteria b). METHODS: We retrospectively reviewed 441 case records where sphincter EMG were performed in patients with parkinsonian syndromes: MSA, n = 263; Parkinson's disease, n = 129; dementia with Lewy bodies, n = 25; and progressive supranuclear palsy, n = 24. We performed ROC analysis of the data sets. RESULTS: The area under the curve used to differentiate MSA from other parkinsonian syndromes was 0.68 in duration, 0.57 in phase, and 0.51 in amplitude, respectively; these values were statistically significant. With regard to our duration criteria, area under the curve was 0.69 for the average duration of MUPs (criteria b) and 0.67 for percentage of MUPs of duration >10 ms (criteria a); these values were also statistically significant. CONCLUSIONS: This study suggests that duration is appropriate parameter for the differentiation of MSA. However, the area under the curve of the mean duration was insufficient to confirm the diagnosis; sphincter EMG should be used as a supportive diagnostic tool for the diagnosis of MSA.

Urinary dysfunction in early and untreated Parkinson's disease.

BACKGROUND: Urinary dysfunction is common in Parkinson's disease (PD); however, little is known about urinary dysfunction in early and untreated PD patients. METHODS: Fifty consecutive untreated PD patients (mean age, 66.7; mean disease duration, 23.6 months; and mean Hoehn & Yahr scale, 1.9) were recruited; those with other conditions that might have influenced urinary function were excluded. Patients were evaluated using a urinary questionnaire and urodynamic studies. RESULTS: Sixty-four per cent complained of urinary symptoms (storage, 64.0%; voiding, 28.0%). Urodynamic studies showed abnormal findings in the storage phase in 84%, with detrusor overactivity (DO) and increased bladder sensation without DO in 58.0% and 12.0% of patients, respectively. In the voiding phase, detrusor underactivity, impaired urethral relaxation such as detrusor sphincter dyssynergia, and bladder outlet obstruction were present in 50.0%, 8.0% and 16% of patients, respectively. In patients with both storage and voiding phase abnormalities, DO+detrusor underactivity was the most common finding. Few patients experienced urge incontinence and/or quality-of-life impairment owing to urinary dysfunction; none had low-compliance bladder or abnormal anal-sphincter motor unit potential. These urinary symptoms and urodynamic findings were not correlated with gender, disease severity or motor symptom type. CONCLUSION: Urinary dysfunction, manifested primarily as storage disorders with subclinical voiding disorders and normal anal-sphincter electromyography, occurs in early and untreated PD patients. In cases with severe voiding disorder and/or abnormal anal-sphincter electromyography, other diagnoses should be considered.

Gastric myoelectrical differences between Parkinson's disease and multiple system atrophy.

The electrogastrogram (EGG) was recorded for 24 hours in 17 Parkinson's disease (PD) patients, 17 multiple system atrophy (MSA) patients, and 8 healthy control subjects to elucidate the differences in the EGG findings between the two diseases. Eight EGG segments (3 preprandial, 3 postprandial, and 2 sleep segments) were selected from the total recording for spectral analysis, from which we obtained the dominant frequency (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. PD patients showed irregular slow waves, high HFR%, and high ICDF, whereas MSA patients showed regular slow waves and low ICDF. Although DF and NFR% increased after meal in controls, postprandial increases in DF and NFR% were less significant in both patient groups compared to the controls. The PD patients presented gastric dysrhythmias indicating gastric pacemaker disturbances. The MSA patients showed regular slow waves with low variability of the slow wave rhythm (low ICDF), which might have resulted from the involvement of gastric autonomic nerve function.

Questionnaire-based assessment of pelvic organ dysfunction in multiple system atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized clinically by any combination of autonomic, cerebellar, and extrapyramidal symptoms. Autonomic symptoms are usually severe, and urinary symptoms are one of the cardinal features of MSA. Bowel dysfunction and sexual dysfunction are also common in MSA. Quality of life (QOL) in patients with MSA is severely impaired by the presence of pelvic organ dysfunction. Therefore, we aimed to examine the prevalence of pelvic organ dysfunction in patients with MSA. We recruited 256 patients with MSA seen at our neurology clinic. The mean age was 62 years. The control group comprised 158 individuals, and the mean age was 52 years. We administered a questionnaire on pelvic organ dysfunction to the MSA and control groups. The questionnaire had sections focusing on the bladder, bowel, and sexual function. Dysfunction, as described in the responses, was evaluated as normal, mild (>once a month), moderate (>once a week), or severe (>once a day). The Mann-Whitney's U-test was used for statistical analysis. When compared with the control group, the prevalence of pelvic organ dysfunction in the MSA group was significantly higher for urinary storage and voiding dysfunction, bowel dysfunction, and sexual dysfunction. QOL in the MSA group was therefore significantly impaired because of urinary dysfunction (70%, 76%), bowel dysfunction (40% of the men), and sexual dysfunction (26%, 45%). Pelvic organ dysfunction is common in MSA, and QOL is severely impaired in patients with MSA.

Comparing bromocriptine effects with levodopa effects on bladder function in Parkinson's disease.

To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and 1 hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, after the L-dopa administration, urinary urgency aggravated. UDS revealed an aggravated DO (P < 0.05), a decreased FSV and bladder capacity (P < 0.01, 0.05), an increased WFmax (P < 0.05), an increased AG number, and a decreased PVR (P < 0.01). A single dose of bromocriptine proved to exacerbate urinary urgency and DO in the storage phase, and improve bladder emptying through increased detrusor contractility and decreased bladder outlet obstruction, within hours. With the exception of bladder outlet obstruction, these effects of bromocriptine are similar to the effects of L-dopa, albeit slightly less pronounced.

Altered heart rate control in response to postural change in patients with Machado-Joseph disease (SCA3).

To assess heart rate (HR) regulation in Machado-Joseph disease (MJD), we evaluated HR variability at rest and the initial HR response to standing suddenly in 13 MJD patients and 26 normal control subjects. A head-up tilt (HUT) test involving the monitoring of blood pressure, HR, and cerebral oxy/deoxyhemoglobin concentration was also performed in each participant. There was no significant difference in HR variability at rest between the two groups, but the transient HR rise just after standing suddenly in the MJD group was significantly less than that in the control group (p < 0.01). The HUT test, where each participant was gradually tilted upward, induced a significantly greater HR increase in the MJD group compared with the controls (p < 0.01), while there were no significant differences in the blood pressure and cerebral oxygenation changes between the two groups. In our MJD study, the transient HR rise just after standing suddenly was diminished, and HR markedly increased during sustained orthostatic stress.

Effects of electrical stimulation of the striatum on bladder activity in cats.

AIMS: Parkinson's disease (PD) affects the nigrostriatal projections leading to micturition disturbance in most cases. Overactive bladder (OAB) symptoms such as urinary urgency or urgent urinary incontinence are common amongst PD patients. Several urodynamic studies have revealed that detrusor overactivity causes OAB symptoms in PD patients. We assert that striatal dysfunction might contribute to the pathogenesis of detrusor overactivity in PD patients. However, the role of the striatum in bladder contraction remains unclear. METHODS: We generated spontaneous isovolumetric bladder contractions in 12 ketamine-anesthetized adult male cats and subsequently performed electrical stimulation and extracellular single-unit recording in the striatum. RESULTS: Electrical stimulation applied to the posterior ventral caudate nucleus and the adjacent putamen reduced inhibition of the spontaneous bladder contraction. None of the responses were facilitatory. Electrical stimulation was most effective at an amplitude of 70-400 microA. Forty-six neurons that exhibited correlation to spontaneous bladder contraction were recorded in the striatum. Thirty-five neurons were found to be tonically active throughout the bladder relaxation phase, and the remaining 11 neurons were active during the bladder contraction phase. These particular neurons were located within the area in which spontaneous bladder contraction was inhibited by electrical stimulation. CONCLUSIONS: Electrical stimulation was found to inhibit bladder contraction, and a correlation was observed between spontaneous bladder relaxation/contraction and neuronal firing in the posterior ventral striatum.

Bickerstaff's brainstem encephalitis after an outbreak of Campylobacter jejuni enteritis.

Twenty-eight patients suffered Campylobacter jejuni enteritis after eating raw chicken. Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies. In contrast, none of the others did the autoantibodies. C. jejuni was cultured from all stool samples from five patients with enteritis alone. All the isolates had the same genotype, cst-II (Asn51), which are characteristic of strains isolated from Bickerstaff's brainstem encephalitis. These findings suggest that host susceptibility may play a role in inducing the production of anti-ganglioside antibodies and the development of Bickerstaff's brainstem encephalitis.

Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay.

NMO-IgG, a disease-specific autoantibody for neuromyelitis optica, recognizes aquaporin-4 (AQP4) and has been examined by indirect immunofluorescence assay. We developed an enzyme-linked immunosorbent assay (ELISA) to detect anti-AQP4 antibodies by establishing methods for expression in a baculovirus system and purification of recombinant AQP4 as antigen. Elevated anti-AQP4 antibody titers in serum were found in 15 (71%) of 21 patients with neuromyelitis optica, 4.3% of 46 patients with multiple sclerosis, none of 51 normal controls, and 2.6% of 115 patients with other neurological diseases. The ELISA system can be substituted for the conventional NMO-IgG assay.

PET study of brain acetylcholinesterase in cerebellar degenerative disorders.

To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.

Genetically confirmed Huntington's disease masquerading as motor neuron disease.

We describe a patient with Huntington's disease (HD) who showed asymmetrical upper limb amyotrophy as a main manifestation. Chorea and psychiatric symptoms were not prominent. Electromyography revealed generalized active and chronic denervation and fasciculations. A genetic test showed 46 CAG repeats in the huntingtin gene. Asymmetrical amyotrophy restricted to the upper limb has been reported in some patients with progressive chorea and amyotrophy without acanthocytosis, but genetically proven cases of HD have rarely been reported. It is not known why only a few HD patients show the motor neuronal loss; however, certain as-yet-unidentified genetic factors combined with some environment factors and the underlying cellular dysfunctions by polyglutamine aggregation could be responsible for the motor neuronal loss similar to that in amyotrophic lateral sclerosis.

Peripheral nerve demyelination in multiple sclerosis.

OBJECTIVE: To elucidate the frequency of peripheral nerve demyelination in multiple sclerosis (MS). There are a number of case reports describing MS patients associated with demyelinating neuropathy, but its frequency in a whole MS population is unknown. METHODS: Extensive nerve conduction studies were prospectively performed in 60 consecutive patients with relapsing-remitting MS. Multiple excitability measurements using threshold tracking were also performed in median motor axons and superficial radial sensory axons. RESULTS: Nerve conduction abnormalities suggestive of demyelination were found for 3 (5%) of the patients. Two of them developed clinically evident neuropathy, whereas the remaining one had only generalized areflexia in addition to MS symptoms/signs. In all the three, MS preceded demyelinating neuropathy by several years. Excitability testing showed that supernormality and threshold electrotonus at the tested sites (median motor axons at the wrist, and radial sensory axons at the mid-forearm) were similar in the normal and MS groups. CONCLUSIONS: MS patients do not generally have peripheral nerve demyelination, but approximately 5% of patients develop demyelinating neuropathy. The association could result from a common pathogenesis possibly due to epitope spreading during the long course of MS. SIGNIFICANCE: Association of chronic inflammatory demyelinating polyneuropathy with MS is not frequent, but needs to be recognized as a treatable condition.

Changes in excitability properties associated with axonal regeneration in human neuropathy and mouse Wallerian degeneration.

OBJECTIVE: The aim of this study was to investigate changes in excitability properties associated with axonal regeneration in human neuropathy and a mouse Wallerian degeneration model. METHODS: Threshold tracking was used to measure axonal excitability indices such as strength-duration time constant (SDTC), threshold electrotonus, supernormality in median motor axons at the wrist of 13 patients with vasculitic neuropathy in their recovery phase, and in tibial motor axons at the ankle of mice with sciatic nerve crush. In the mouse model, excitability testing was performed 4, 8, 12, and 20weeks after the nerve crush. RESULTS: In patients, there were longer SDTC, greater threshold changes at 0.2ms in latent addition, and greater threshold changes in depolarizing and hyperpolarizing threshold electrotonus, compared with controls. The pattern of changes in excitability indices was similar to those in experimental nerve crush, in which the indices remained abnormal for 20weeks after the crush. These changes suggest an increase in nodal persistent sodium currents, whereas multiple factors may also contribute to changes in excitability properties, such as axonal hyperpolarization, increased internodal resistance, and altered potassium currents. CONCLUSIONS: Excitability properties in regenerating axons are characterized by increased nodal persistent currents with variable combination of changes in passive properties, membrane potential, and potassium currents. SIGNIFICANCE: Increased persistent sodium currents are potential reasons for positive symptoms in patients with axonal neuropathy. Sodium channel blockers could be considered a treatment option.

Potassium channel antibody-associated encephalitis with hypothalamic lesions and intestinal pseudo-obstruction.

A subgroup of limbic encephalitis is associated with antibodies against voltage-gated potassium channels (VGKC), and responds well to immuno-modulating therapies. Anti-VGKC antibodies are also found in Isaacs' syndrome and Morvan's syndrome, both of which are sometimes complicated by thymoma. We describe a 52-years-old man with limbic encephalitis, thymoma, and anti-VGKC antibodies, who presented with autonomic dysfunctions such as severe intestinal pseudo-obstruction, hyperhidrosis and hypertension. Thymectomy and corticosteroid therapy remarkably improved his symptoms. Brain magnetic resonance imaging showed hypothalamic lesions, in addition to the bilateral involvement of the medial temporal lobes. This patient had severe autonomic dysfunctions resembling those of Morvan's syndrome. This case may represent a subgroup of VGKC-antibody associated syndromes with a wide spectrum of symptoms, including Isaacs' syndrome, Morvan's syndrome, and limbic encephalitis.

Development of Isaacs' syndrome following complete recovery of voltage-gated potassium channel antibody-associated limbic encephalitis.

Autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with acquired neuromyotonia (Isaacs' syndrome) and related disorders such as Morvan's syndrome and some cases of limbic encephalitis. The mechanisms underlying the various phenotypes induced by VGKC-Abs are not fully understood. Recently, we reported a case of LE with VGKC-Abs accompanied by severe intestinal pseudo-obstruction and thymoma. Thymectomy and immunosuppressive therapy induced dramatic clinical improvement of LE symptoms, and VGKC-Abs titers decreased from 1254 pM to 549 pM (normal>100 pM). Seventeen months later, the patient developed progressive generalized muscle cramping, paresthesias in his lower extremities, excessive sweating, and severe constipation. There was no recurrence of the LE. Electromyography showed fasciculation potentials and myokymic discharges, and the plasma VGKC-Abs titer was again elevated to 879 pM. Here we report a case of Isaacs' syndrome after complete remission of LE with VGKC-Abs that may provide an insight into a possible link among VGKC-Abs associated syndromes.

Mechanism of bladder dysfunction in idiopathic normal pressure hydrocephalus.

AIM: To elucidate the mechanism of bladder dysfunction in idiopathic normal pressure hydrocephalus (iNPH) by a urodynamic study. METHODS: Forty-two patients with possible iNPH, who were diagnosed by clinical symptoms/signs (gait, cognitive, and urinary disorders) with typical imaging features (ventricular enlargement) and normal cerebrospinal fluid pressure, were enrolled. The subjects included 36 men and 6 women; mean age, 72 years (62-83 years). All patients underwent a urodynamic test according to the definitions and methods proposed by the International Continence Society. RESULTS: Lower urinary tract symptoms were seen in 93% of the patients, with storage symptoms (93%) being more common than voiding symptoms (71%); and urinary urgency (overactive bladder) (64%)/frequency (64%) being more common than urinary incontinence (57%). The mean values for the maximum flow rate and post-void residual (PVR) volume were 11.7 ml/sec and 42.1 ml, respectively. PVR >100 ml was noted in six patients (three men, three women; range, 100-228 ml). Although the majority of patients had normal bladder volume at the first sensation (mean 134 ml), bladder capacity was small (mean 200 ml) and detrusor overactivity was seen in 95% of patients. CONCLUSIONS: While incontinence can result secondarily from gait disturbance or dementia, detrusor overactivity mostly underlies urinary urgency/frequency and incontinence in iNPH.

Diffusion tensor analysis of corpus callosum in progressive supranuclear palsy.

INTRODUCTION: Progressive supranuclear palsy (PSP) is a neurodegenerative disease featuring parkinsonism, supranuclear ophthalmoplegia, dysphagia, and frontal lobe dysfunction. The corpus callosum which consists of many commissure fibers probably reflects cerebral cortical function. Several previous reports showed atrophy or diffusion abnormalities of anterior corpus callosum in PSP patients, but partitioning method used in these studies was based on data obtained in nonhuman primates. In this study, we performed a diffusion tensor analysis using a new partitioning method for the human corpus callosum. METHODS: Seven consecutive patients with PSP were compared with 29 age-matched patients with Parkinson's Disease (PD) and 19 age-matched healthy control subjects. All subjects underwent diffusion tensor magnetic resonance imaging, and the corpus callosum was partitioned into five areas on the mid-sagittal plane according to a recently established topography of human corpus callosum (CC1-prefrontal area, CC2-premotor and supplementary motor area, CC3-motor area, CC4-sensory area, CC5-parietal, temporal, and occipital area). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in each area and differences between groups were analyzed. RESULTS: In the PSP group, FA values were significantly decreased in CC1 and CC2, and ADC values were significantly increased in CC1 and CC2. Receiver operating characteristic analysis showed excellent reliability of FA and ADC analyses of CC1 for differentiating PSP from PD. CONCLUSION: The anterior corpus callosum corresponding to the prefrontal, premotor, and supplementary motor cortices is affected in PSP patients. This analysis can be an additional test for further confirmation of the diagnosis of PSP.

Sympathetic sweat responses and skin vasomotor reflexes in carpal tunnel syndrome.

OBJECTIVE: To investigate cutaneous sympathetic functions in carpal tunnel syndrome (CTS) using sympathetic sweat responses (SSwRs) and skin vasomotor reflexes (SVmRs). METHODS: In 29 hands (20 patients) with idiopathic CTS, SSwRs were recorded with a sudorometer from the thenar eminence, and SVmRs were used to measure cutaneous blood flow using a Doppler flowmeter placed on the index finger tip. Normal data were obtained from 15 volunteers of similar age. RESULTS: SSwRs or SVmRs were abnormal in 23 (80%) hands; SSwRs were absent in 38%, whereas SVmRs were abnormally decreased in 59%. Autonomic symptoms were present in 18 (62%) hands; finger edema (38%) and dry hand (35%) were frequent symptoms. Autonomic symptoms, and abnormal SSwRs and SVmRs did not correlate with results of nerve conduction studies. CONCLUSIONS: Skin sudomotor or vasomotor sympathetic function is frequently impaired in CTS. Susceptibility to compression ischemia may be different in sympathetic unmyelinated and large myelinated fibers.