Icing after skeletal muscle injury decreases M1 macrophage accumulation and TNF-α expression during the early phase of muscle regeneration in rats.

Following skeletal muscle injury, both myogenic and immune cells interact closely during the regenerative process. Although icing is still a common acute treatment for sports-related skeletal muscle injuries, icing after muscle injury has been shown to disrupt macrophage accumulation and impair muscle regeneration in animal models. However, it remains unknown whether icing shortly after injury affects macrophage-related phenomena during the early stages of muscle regeneration. Therefore, we focused on the distribution of M1/M2 macrophages and cytokines expressed predominantly by macrophages during the early stages of muscle regeneration after muscle crush injury. Icing resulted in a decrease, not retardation, in the accumulation of M1 macrophages, but not M2 macrophages, in injured muscles. Consistent with the decrease in M1 macrophage accumulation, icing led to a reduction, instead of delay, in the level of tumor necrosis factor-α (TNF-α) expression. Additionally, at subsequent timepoints, icing decreased the number of myogenic precursor cells in the regenerating area and the size of centrally nucleated regenerating myofibers. Together, our findings suggest that icing after acute muscle damage by crushing disturbs muscle regeneration through hindering tM1 macrophage-related phenomena.

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.

Unloading during skeletal muscle regeneration retards iNOS-expressing macrophage recruitment and perturbs satellite cell accumulation.

After skeletal muscle injury, unloading disturbs the regenerative process of injured myofibers, in a manner highly attributed to impairment of macrophage functions. However, the effect of unloading on the spatiotemporal context of proinflammatory macrophage recruitment and satellite cell accumulation within the damaged area remains unclear. This study focused on macrophages expressing inducible nitric oxide synthase (iNOS) that synthesize nitric oxide, a key regulator of muscle regeneration, and compared the continuous hindlimb unloading (HU) by tail suspension versus weight-bearing (WB) after skeletal muscle crush injury in rats. We found that in the WB group, the recruitment of iNOS+ proinflammatory macrophages into the injured site gradually increased until their peak number at 48 h post-injury. In the HU group, the accumulation of iNOS+ macrophages until 48 h after injury was significantly less than that in the WB group and continued to increase at 72 h. In accordance with attenuated and/or delayed iNOS+ macrophage recruitment, whole iNOS expression at 24 and 48 h after injury was weakened by unloading. Additionally, in the HU group, satellite cell content of dystrophin-positive non-injured areas diminished at 48 h after injury, and the numbers of activated satellite cells within the regenerating area at 72 and 96 h post-injury were significantly smaller than those in the WB group. These findings suggest that muscle regeneration under unloading conditions results in attenuated and/or delayed recruitment of iNOS+ macrophages and lower iNOS expression in the early phase after muscle injury, leading to perturbed satellite cell accumulation and muscle regeneration.

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.

Inhibition of the migration of MCP-1 positive cells by icing applied soon after crush injury to rat skeletal muscle.

Migration of the macrophages to the injured site soon after the skeletal muscle injury is crucial for subsequent regeneration of the muscle fibers. The Monocyte chemoattractant protein-1 (MCP-1) is important chemokine for regulating migration of the monocytes/macrophages. Earlier reports have discussed that icing applied soon after muscle crush injury retards muscle regeneration through retardation of macrophage migration. The MCP-1+ cells and neutrophils might promote the migration of the macrophages. To test the hypothesis that icing soon after the skeletal muscle injury affects MCP-1+ cells and neutrophils, we examined the effect of icing on MCP-1+ cells and neutrophils after crush injury to skeletal muscle in rats. Owing to the icing application for 20 min soon after the injury, accumulation of the macrophages was inhibited until 12 h after injury. Numbers of the neutrophils at 3 h after the injury and the MCP-1+ cells at 6 h and later after the injury in the icing group were significantly lower than those in the non-icing group, suggesting that these phenomena contribute to the retardation of macrophage migration.

Urodynamic findings in patients with Creutzfeldt-Jakob disease: a case report.

AIM OF STUDY: Urinary dysfunction in Creutzfeldt-Jakob disease (CJD) patients is attributed to functional incontinence, since they often have immobility and loss of motivation. In contrast, previously no urodynamic findings are available in CJD patients. CASE REPORT: We had 2 CJD patients who had urinary frequency and urinary retention. We performed urodynamics with the spouse's informed consent in order to explore the mechanism of urinary dysfunction in those cases. Case 1 had typical acute cognitive deterioration with incontinence and urinary retention, while case 2 had subacute cognitive deterioration (that started after admission) and nocturia. The urodynamic findings were diverse. One feature was detrusor overactivity during bladder filling in case 1. Another feature of urodynamic finding includes neurogenic change of sphincter EMG in case 1 and decreased bladder sensation in case 2. CONCLUSION: Urodynamics in our two CJD patients revealed detrusor overactivity and neurogenic sphincter electromyogram, presumably reflecting pathological lesions in the prefrontal cortex/basal ganglia as well as the sacral spinal cord in CJD.

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.

Voiding Dysfunction in Spinocerebellar Ataxia Type 31.

OBJECTIVE: To describe a case of SCA31 who presented with possible neurogenic voiding dysfunction. METHODS: A case report. RESULTS: A 73-year-old man with a 5-year history of cerebellar ataxia developed partial urinary retention. His father and a sister had cerebellar ataxia. Brain magnetic resonance imaging revealed cerebellar atrophy, and gene analysis revealed TGGAA repeat prolongation, and he was diagnosed with spinocerebellar ataxia 31. Urodynamics revealed normal bladder filling but a slightly weak detrusor and a post-void residual urine volume of 130 mL, whereas his prostate volume was normal (26 mL). External sphincter electromyography revealed neurogenic change in the motor unit potentials. In order to lessen the post-void residual, hewas started on 15mg/day pilocarpine with benefit. The weak detrusor and sphincter electromyography abnormality indicated involvement of the sacral spinal cord in this disorder. CONCLUSION: Neurogenic urinary retention in SCA31 can be listed in the clinical differential diagnosis of cerebellar ataxia. However, possible outflow obstruction in men should always be explored.

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.

Imidafenacin on bladder and cognitive function in neurologic OAB patients.

OBJECTIVE: To explore imidafenacin's effects on bladder and cognitive function in neurologic overactive bladder (OAB) patients. METHODS: Sixty-two subjects (25 men, 37 women; mean age 70 years (25-86) with OAB due to neurologic diseases) were enrolled in the study. We conducted a urinary symptom survey and cognitive tests (MMSE, FAB, ADAS-cog) in all patients. We performed urodynamics in 35 patients and measured real-time near-infrared spectroscopy (NIRS)-urodynamics in eight patients before and after the administration of imidafenacin, an anticholinergic agent, for 3 months at 0.2 mg/day. RESULTS: Imidafenacin significantly ameliorated urinary urgency, nighttime urinary frequency, and quality of life index (p < 0.05). Three cognitive measures did not change significantly. Urodynamics showed increased bladder capacity (p < 0.05) but detrusor overactivity did not change significantly. NIRS showed that the subtraction of oxyhemoglobin between the start of filling and the first sensation increased in the bilateral prefrontal area but without statistical significance. CONCLUSIONS: Imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Regarding cognitive function, imidafenacin is safely used in OAB patients due to neurologic diseases. SYNOPSIS: In order to explore imidafenacin (anticholinergic agent)'s effects on bladder and brain function, we performed urinary questionnaire, cognitive tests, urodynamics and near-infrared spectroscopy (selected cases) in 62 overactive bladder (OAB) patients due to various neurologic diseases. As a result, imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Imidafenacin seems safe in treating OAB patients due to neurologic diseases.

How the Bladder Senses? A Five-Grade Measure.

OBJECTIVES: During bladder filling, the bladder starts to sense it and the sensation steadily increases. However, little is known concerning volume-sensory correlation in normal bladder and pressure-sensory correlation during detrusor overactivity (DO). We aimed to real-time assess bladder sensation in normal bladder and DO using a five-grade measure. METHODS: We enrolled 74 normal individuals and 87 patients with DO (51 terminal, 36 phasic). During slow bladder filling, we instructed individuals to indicate sensation in five grades: 1, first sensation; 2, obviously greater than 1 but less than 3; 3, first desire to void when he or she usually goes to toilet; 4, obviously greater than 3 but less than 5; and 5, strong desire to void. We also instructed individuals to report other sensations, such as pain. RESULTS: The five-grade measure is feasible in all participants, showing a volume and pressure- sensory correlation. Among the five grades, grade 0 to 1 was the longest, followed by grade 4 to 5, in all participants. Grade 0 to 1 in phasic DO and grade 4 to 5 in terminal and phasic DO were shorter than those in normal bladder (P < 0.05). Eighty-six percent of patients with DO reported that the rapidly increased sensory grade is akin to urinary urgency in daily life. CONCLUSION: The five-grade measure is feasible to assess a volume and pressure-sensory correlation. Using this measure the sensory grade rapidly increased during DO compared with normal bladder, and 86% of the patients with DO reported that it is akin to urinary urgency in daily life.

Weak detrusor contractility correlates with motor disorders in Parkinson's disease.

Limited attention has been paid to the relationship between urinary symptoms or urodynamic findings and motor disorders in Parkinson's disease (PD). We aimed to correlate pressure-flow urodynamic parameters with video-gait analysis parameters in PD. We recruited 41 patients with PD (25 men and 16 women; age, 70.6 ± 8.5 years; H & Y motor grading: 2 [range, 1-3]; disease duration: 4 years [range, 1-7]; taking levodopa 300 mg/day [range, 100-400]). All patients underwent pressure-flow urodynamics (parameters: first sensation, bladder capacity, detrusor overactivity [noted in 24 patients], and Watts factor [WF]) and video-gait analysis (parameters: time and number of strides for 5-m gait [simple task] and time for timed up and go [complex task]). Statistical analysis was made by Mann-Whitney's U-test for analyzing the relation between detrusor overactivity and gait as well as Spearman's rank-correlation coefficient test for analyzing the relation between the remaining parameters and gait. We found no relation between filling-phase urodynamics (detrusor overactivity, first sensation, and bladder capacity) and video-gait analysis parameters. By contrast, we found a significant relation between voiding-phase urodynamics (WF, reflecting detrusor power) and all three video-gait analysis parameters (reflecting lower-half bradykinesia and loss of postural reflex) in our PD patients (P < 0.01). The close relation between the WF and motor disorders in the present study suggests that, though clinically mild, a weak detrusor in PD might have a central origin. We should follow postvoid residual volume carefully in PD patients with advanced gait disorder, because postvoid residual volume might increase in such patients.

Lower Urinary Tract Function in Spinocerebellar Ataxia 6.

OBJECTIVE: To investigate lower urinary tract function in spinocerebellar ataxia type 6 (SCA6). METHODS: We recruited, without bias, nine SCA6 patients with a mean cytosine-adenine-guanine repeat length of 24.3 (21-26, normal <18). They were four men, five women; mean age 58.6 years; mean disease duration 8.2 years. We performed a urinary symptom questionnaire and a urodynamics. RESULTS: Urinary symptoms were observed in five of nine patients (56%) and urinary frequency in three of nine patients (33%), and none had urinary retention. Urodynamic abnormalities included detrusor overactivity in one (11%) and weak detrusor on voiding in two, but none had postvoid residual urine. Sphincter electromyography revealed, while mild in degree, neurogenic change in five of the eight patients (63%) on whom the test was performed. CONCLUSION: We observed urinary frequency in 33%; detrusor overactivity in only 11%; and neurogenic change in the sphincter electromyography in 63% of our nine SCA6 patients. These findings might be relevant to the cerebellar and spinal cord pathologies of this disease.

Do Sacral/Peripheral Lesions Contribute to Detrusor-Sphincter Dyssynergia?

OBJECTIVES: While detrusor-sphincter dyssynergia (DSD) occurs in conjunction with lesions between the brainstem and the sacral cord, it is not well known whether sacral/peripheral lesions contribute to DSD. We studied the relationship between DSD and sacral/peripheral lesions. METHODS: One hundred and forty-four patients with diverse neurologic etiologies underwent urodynamic study and analysis of motor unit potentials in the external sphincter muscles, 117 of whom were able to void during a urodynamic test. Sacral/peripheral lesion (SPL) is defined as neurogenic change in motor unit potentials. Detrusor overactivity (DO) is defined as involuntary detrusor contractions during the filling phase, which commonly occurs in lesions above the sacral cord. We considered DO as a putative indicator of supra-sacral lesion. RESULTS: DSD was found in 44 (30.6%), SPL in 71 (49.3%), and DO in 83 (57.6%) of 144 patients, respectively. The incidence of DSD was the same in the SPL positive group (31%) and the SPL negative group (30.1%). By contrast, within the subgroup of patients without DO, the incidence of DSD was significantly more common in the SPL positive group (41.4%) than in the SPL negative group (25.0%) (P < 0.05). In 53 of the SPL positive group who were able to void, postvoid residual >100 mL was more common in patients with DSD (not statistically significant). CONCLUSION: The results of the present study suggest that not only suprasacral pathology, but also sacral/peripheral lesions can produce DSD. In light of the previous reports, DSD might also result from partial lesions in peripheral branches of the sphincter circuit.

Meningitis-retention syndrome: first case of urodynamic follow-up.

The combination of acute urinary retention and aseptic meningitis has not been well recognized. This combination can be referred to as meningitis-retention syndrome (MRS), when accompanied by no other abnormalities. However, the responsible site of lesions for urinary retention in MRS remains obscure, despite the areflexic detrusor at the time of urinary retention. We recently encountered a man with MRS in whom a urodynamic study was performed twice. In that case, an initially areflexic detrusor became overactive after a 4-month period, suggesting an upper motor neuron bladder dysfunction.

Pathogenesis of reduced or increased bladder sensation.

OBJECTIVE: Pathogenesis of reduced or increased bladder sensation is not well known. Hence, we systematically investigated the frequency of reduced or increased bladder sensation in neurologic/mental diseases. METHODS: We analyzed 911 patients who were referred from within our hospital. Data registries included a diagnosis, a lower urinary tract symptom questionnaire, a urodynamic study, and neurological examinations. Reduced bladder sensation is defined as bladder volume at the first sensation >300 ml. Increased bladder sensation is defined as bladder volume at the first sensation <100 ml. These patients were stratified into those with and without DO. RESULTS: Neuropathies are the most common cause of reduced bladder sensation (33.3-43.8% in diabetic neuropathy, etc.). Myelopathies are the second most common cause (17.4-25.0% in multiple sclerosis, etc.). Less common is brain diseases (9.6% in multiple system atrophy, etc.). In contrast, myelopathies are the most common cause of increased bladder sensation without DO (25.0-40.0% in spinal forms of systemic lupus erythematosus, Sjogren's syndrome, etc.). Neuropathies are the second most common (17.3-22.2% in post-pelvic organ surgery, diabetic neuropathy, etc.). Less common is brain/mental diseases (20.0% in psychogenic bladder dysfunction, 8.1% in Parkinson's disease, etc.). CONCLUSION: The present study revealed that neuropathies are the most common cause of reduced bladder sensation in neurologic/mental diseases. Increased bladder sensation without DO occurs mainly in peripheral and central sensory pathway lesions, as well as in basal ganglia lesions and psychogenic bladder dysfunction. Reduced and increased bladder sensation should be a major treatment target for maximizing patients' quality of life.

Progressive supranuclear palsy presenting with urinary retention and sleep apnea.

We report a case of a 62-year-old Japanese-Australian woman with progressive supranuclear palsy (PSP) who presented with prominent urinary retention, neurogenic changes in sphincter electromyography, and obstructive sleep apnea syndrome. Urodynamic study revealed a combination of detrusor overactivity during filling and underactivity during voiding. All these non-motor symptoms in PSP mimicked those of multiple system atrophy.

Herbal medicine-induced meningitis-retention syndrome.

A 73-year-old woman developed subacute meningitis-retention syndrome (MRS), dermatitis, and latent pneumonitis likely due to the herbal medicines Shinbu-Tou and Rikkunshi-Tou. The responsible site of lesions for urinary retention seemed to be the spinal micturition pathways and, to a lesser extent, the sacral spinal cord. All of her clinical manifestations were successfully ameliorated within three weeks of discontinuation of the herbal remedies.