Urinary Disturbances Research Articles

Urinary metabolic disturbance in the olfactory bulbectomized rats and the modulatory effects of fluoxetine

AimsThe present study aims to investigate the impacts of olfactory bulbectomy (OBX) on urinary metabolic profile and tryptophan metabolites in prefrontal cortex (PFC) of rats, and to explore the regulation effects of fluoxetine. Main methodsOBX model was developed by aspiration of olfactory bulbs. After fluoxetine treatment (10 mg/kg) for 14 days, urine samples were collected and behavior tests were applied. Tryptophan (TRP) metabolites and neurotransmitters in PFC were determined by prominence ultrafast liquid chromatography-QTRAP-mass spectrometry, and tryptophan hydroxylase 2 (TPH2) and indoleamine-2,3-dioxygenase 1 (IDO1) were evaluated by western blot. Urinary metabolites were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabonomics strategy. Key findingOBX rats showed hyperlocomotion in open field, hyperactivity in open arm and despair status, and fluoxetine reserved these behavioral abnormalities. The levels of TRP, 5-HIAA, 5-HIAA/5-HT ratio and DA increased, while kynurenine and 5-HT decreased in PFC of OBX rats. The activities of TPH2 and IDO1were inhibited after OBX. Twenty-six altered metabolites were identified as potential biomarkers in OBX rats involved in tryptophan metabolism, gut microbiota metabolism, energy metabolism, purine metabolism, ascorbate and aldarate metabolism, and tyrosine metabolism. Among them, 15 abnormal metabolites were corrected by fluoxetine to some extent. SignificanceOur results revealed that urinary metabolic profile changed greatly in OBX rats, and identified biomarkers might be helpful for the diagnosis of agitated depression. The regulation effects of fluoxetine on urinary metabolic profile and tryptophan metabolites in PFC might contribute to its antidepressant action in OBX rats.

Pathophysiological Mechanisms of Nocturia and Nocturnal Polyuria: The Contribution of Cellular Function, the Urinary Bladder Urothelium, and Circadian Rhythm

Alterations to arginine vasopressin (AVP) secretion, the urinary bladder urothelium (UT) and other components of the bladder, and the water homeostasis biosystem may be relevant to the pathophysiology of nocturia and nocturnal polyuria (NP). AVP is the primary hormone involved in water homeostasis. Disruption to the physiological release of AVP or its target effects may relate to several urinary disturbances. Circadian dysregulation and the effects of aging, for example, the development of oxidative stress and mitochondrial dysfunction, may play a role in nocturia voiding symptoms. The urinary bladder UT not only acts as a highly efficient barrier that is maintained during the filling and voiding of the urinary bladder, but is also capable of sensory and transducer function through a network of functional receptors and ion channels that enable reciprocal communication between UT cells and neighboring elements of the bladder mucosa and wall. Functional components of the UT (eg, claudins and receptors or ion channels) play important roles in AVP-mediated water homeostasis. These components and functions involved in water homeostasis, as well as kidney function, may be affected by the aging process, including age-related mitochondrial dysfunction. The characteristics of NP are discussed and the association between NP and circadian rhythm is examined in light of reports that suggest that nocturia should be considered as a type of circadian dysfunction. Many possible pathologic mechanisms that underlie nocturia and NP have been identified. Future studies may provide further insight into pathophysiology with the hope of identifying new treatment modalities.

093 How to diagnose lewy body dementia? Prevalence and underlying relationship between clinical and neuropsychological features of DLB

IntroductionDespite its importance for management, prognostication and selection of patients for clinical trials, the diagnosis of Dementia with Lewy Bodies (DLB) remains challenging. Complicating this is a recent change in the diagnostic criteria which has arguably shifted the expected phenotype of DLB patients. In this study we aimed to characterize and examine the relationship between cognitive and clinical diagnostic variables in DLB patients to uncover latent symptom clusters that may streamline future diagnostic approaches in the clinic.MethodsThe clinical and neuropsychological profile of 27 prospectively recruited participants diagnosed with probable DLB and 25 age-matched controls was characterized according to the most recent consensus criteria.Symptoms were scored using a novel combination of established clinical and research instruments.ResultsWe demonstrate comparable sensitivity of formal neuropsychological testing and bedside screening tools (MOCA/MMSE) for identifying domain-specific differences between controls and patients(p<0.001). Optimal sensitivity thresholds for diagnosis of Parkinsonism (88.9%) were explored yielding a prevalence range of 50%-90% within our cohort.Factor analysis using all core and supportive features of the diagnostic criteria identified 6 independent factors accounting for 81% of the total variance. Unique relationships identified included between hallucinations and fluctuations and excessive daytime somnolence; between REM sleep behavior disorder and orthostatic hypotension; and Parkinsonism and urinary disturbance. ‘Prodromal’ symptoms including autonomic and early neuropsychiatric features are represented in the remaining factors.ConclusionParsimonious delineation of clinical variables using identified symptom clusters can aid DLB diagnosis.Clusters are also used to highlight latent pathological relationships. Appropriate instruments and thresholds for detecting dementia and core and suggestive features are presented.

Normal Pressure Hydrocephalus with Primary Presentation of Psychiatric Disturbance: Case Report.

Progressive impairment of cognitive function is a common feature seen in patients with normal pressure hydrocephalus (NPH). Along with cognitive decline, many of the other classic symptoms of NPH are chronic and rarely present with overwhelming anxiety. We report the case of a 63-year-old man who presented with recent primary psychiatric manifestation of severe disabling anxiety and otherwise a minimal change in gait and no urinary disturbance. The patient's work-up consisted of magnetic resonance imaging that showed moderate ventriculomegaly but no findings concerning for acute obstructive hydrocephalus. A single-photon emission computed tomography scan was markedly abnormal with severe hypoperfusion consistent with hydrocephalus. Initially shunting was not advised but was eventually performed after a dramatic response to a large-volume lumbar puncture. After considerable discussion, he underwent elective ventriculoperitoneal shunt placement and had dramatic and sustained improvement in his anxiety. We believe this case report is a unique description of NPH symptomology and might guide future research or clinical decision making.

Clinical features of long segmental myelopathy caused by nitrous oxide

To analyze the clinical and imaging characteristics of the neurological damage caused by nitrous oxide (N2O). In the study, 10 patients in the Department of Neurology of China-Japan Friendship Hospital from October 2015 to February 2018 were retrospectively analyzed for the demographic data, the history of inhaled N2O, clinical features, blood examination, electrophysiological examination, spinal magnetic resonance imaging and therapeutic efficacy profiles. The male-to-female ratio was 4:6 and it presented with an age-of-onset 17-26 years [the average age: (20.80±3.12) years]. The time from inhaled N2O to onset was 1 month to 1 year [the average time: (6.95±4.19) months]. Paralysis in all the patients and numbness in 9 patients were the main clinical features, while positive Lhermitte's sign in 3 patients, urinary and defecation disturbance in 4 patients were also found. Blood examination indicated anemia in 2 patients, giant cell anemia in 1 case and small cell hypochromic anemia in 1 case. 3 cases had been treated with vitamin B12 in an external hospital, and the other 7 cases had abnormal increase in homocysteine levels. Electrophysiological examinations showed sensory and motor nerve involvement in 9 patients, and motor nerve involvement in 1 patient. The severity of lower extremity lesion was significantly heavier than that of upper extremity. Spinal magnetic resonance imagings showed that long segmental lesions were present in the cervical spinal cord of all the patients, 3 cases with long segmental lesions of the thoracic cord and 2 cases with spinal cord swelling. In 6 cases, the horizontal axis had an "inverted V-type" T2 high signal, 1 case was classified as "crescent", and 3 cases were "eight-shaped". The symptoms in these 10 cases were alleviated in varying degrees after stopping the inhalation of nitrous oxide, actively supplementing high doses of vitamin B12 and doing early rehabilitation exercises. Myelopathy with nitrous oxide presents as paralysis and numbness in limb extremities. In imaging, cervical spinal cord damage is common, accompanied by thoracic spinal cord damage. The horizontal axis is more common in the "inverted V-type". Treatment with high doses of vitamin B12 is effective.

Spinal Dural Arteriovenous Fistulas: Clinical Outcome After Surgery Versus Embolization: A Retrospective Study

Spinal dural arteriovenous fistulas (SDAVFs) are rare vascular spinal malformations. According to the reported data, surgery seems to result in better occlusion rates than endovascular treatment. However, the post-treatment evolution of neurological symptoms stratified by the treatment remains unknown. The main objective of the present study was to compare the clinical outcomes for patients according to the treatment method. The data from 63 patients with SDAVFs from 2000 to 2017 at 4 academic neurosurgical departments were retrospectively analyzed. Preoperative and postoperative examination neurological status was assessed using the Aminoff-Logue scale (ALS), which evaluates gait and micturition disturbances. Initial occlusion, late recurrence, and complications of the 2 techniques were also reviewed. Patients who had undergone surgery and embolization improved clinically on the ALS (P= 0.0009), and no significant differences were found between the 2 techniques. Subgroup analysis using the ALS showed that patients who had undergone surgery and embolization without late recurrence improved (P < 0.0001 and P=0.0334, respectively) and that patients who had undergone surgery or embolization with late recurrence did not improve. The initial occlusion rate was in favor of surgery, with 91.3% versus 70% for endovascular treatment (P= 0.050). The late recurrence rate was higher for embolization (21.4% vs. 9.1% for surgery; P= 0.28). Surgery can be proposed as first-line treatment of SDAVFs after multidisciplinary discussion between neurosurgeons and neuroradiologists. The development of late recurrence negatively affects the neurological outcome of patients.

SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal phenotypes

Although genetic testing is increasingly used in clinical nephrology, a large number of patients with congenital abnormalities of the kidney and urinary tract (CAKUT) remain undiagnosed with current gene panels. Therefore, careful curation of novel genetic findings is key to improving diagnostic yields. We recently described a novel intellectual disability syndrome caused by de novo heterozygous loss-of-function mutations in the gene encoding the splicing factor SON. Here, we show that many of these patients, including two previously unreported, exhibit a wide array of kidney abnormalities. Detailed phenotyping of 14 patients with SON haploinsufficiency identified kidney anomalies in 8 patients, including horseshoe kidney, unilateral renal hypoplasia, and renal cysts. Recurrent urinary tract infections, electrolyte disturbances, and hypertension were also observed in some patients. SON knockdown in kidney cell lines leads to abnormal pre-mRNA splicing, resulting in decreased expression of several established CAKUT genes. Furthermore, these molecular events were observed in patient-derived cells with SON haploinsufficiency. Taken together, our data suggest that the wide spectrum of phenotypes in patients with a pathogenic SON mutation is a consequence of impaired pre-mRNA splicing of several CAKUT genes. We propose that genetic testing panels designed to diagnose children with a kidney phenotype should include the SON gene.

Evaluation of the potentiating effects of antidepressants on the contractile response to noradrenaline in guinea pig urethra smooth muscles.

We investigated the potential augmenting effects of 19 clinically available antidepressants on noradrenaline (NA)-induced contractions in guinea pig urethra smooth muscle (USM). Concentration-response curves for NA-induced contractions in guinea pig USM strips were obtained in the absence or presence of selected antidepressants. Desipramine, an active metabolite of imipramine, produced a contraction and potentiated NA-induced contraction at the distal urethra without affecting the proximal urethra. Further, nortriptyline and amoxapine, tricyclic antidepressants, produced a contraction and potentiated NA-induced contraction at the distal urethra. NA-induced contraction was unaffected or reduced by imipramine, clomipramine, trimipramine, and amitriptyline at the proximal and distal urethra. Maprotiline, a tetracyclic antidepressant, potentiated NA-induced contraction at the distal urethra. NA-induced contraction was unaffected by mianserin at the proximal and distal urethra. Paroxetine, a selective serotonin reuptake inhibitor (SSRI), potentiated NA-induced contraction at the distal urethra, while NA-induced contraction was unaffected by fluvoxamine, sertraline, and escitalopram at the proximal and distal urethra. Milnacipran, a serotonin-noradrenaline reuptake inhibitor (SNRI), potentiated NA-induced contraction at the proximal and distal urethra, whereas duloxetine potentiated it at the distal urethra. Mirtazapine slightly inhibited NA-induced contraction at the distal urethra. Aripiprazole and sulpiride did not affect NA-induced contractions at the proximal nor distal urethra. Trazodone inhibited NA-induced contraction at both urethras. Desipramine, nortriptyline, amoxapine, maprotiline, paroxetine, milnacipran, and duloxetine likely induce urinary disturbance by increasing urethral resistance and augmenting NA-induced contraction, which should be carefully considered when delivering guidance for drug administration to patients.

Recent Advances in Pharmacological and Phytochemistry Studies on Phyllanthus amarus

The use of medicinal plants for the treatment of various diseases has been increased due to minimum side effect compared to synthetic drug. Further the herbal products are considered as safe drugs. Phyllanthus amarus claimed tribal people for remedy of different diseases namely diarrhoea, dysentery, dropsy, jaundice, intermittent fevers, kidney problems, urinary bladder disturbances, pain, gonorrhea, diabetes, urogenital disorders, chronic dysentery, skin ulcers, sores, swelling, itchiness, tubercular ulcers, ringworm, scabies and wounds. Phyllanthus amarus contains isobubbialine, epibubbialine, securinine, nor-securinine, dihydrosecurinine, geraniin, corilagin, 1,6-digalloylglucopyranoside rutin , quercetin3-O-glucopyranoside, amarulone, niranthin, nirtetralin, phyltetralin, hypophyllanthin, phyllanthin, hypo-phyllanthin, demethylenedioxy-niranthin, kaempferol, astragalin, etc chemical constituents in its different parts. The extract of Phyllanthus amarus retains multiple pharmacological activities such as Anticarcinogenic, Antiproliferative, Gastroprotective, Cardioprotective, Antileptospiral, Antibacterial, Antidiabetic, Antiviral, Antivenom, Antiinflammatory etc. We planned to illustrate the recent studies appeared in Phytochemisty and Pharmacological activities of Phyllanthus amarus in order to highlight its multi-activity properties.

A Series of Biopsy-proven Patients with Immunoglobulin G4-related Neurological Disease.

Aim:To study the clinical presentation, radiological findings, and therapy responsiveness of patients with biopsy-proven immunoglobulin G4 (IgG4)-related neurological disease.Methods:The study was conducted between January 2016 and March 2018 from the Department of Neurology and Pathology of Nizam's Institute of Medical Sciences. Patients with neurological symptoms and biopsy suggestive of IgG4-related disease (IgG4-RD) were included. These patients were studied for their demographic pattern and clinical presentation. The presence of serological markers such as vasculitic profile and IgG4 levels was analyzed. Radiological findings were studied in detail. Therapeutic agents used and the response to therapy were assessed.Results:There were six cases with IgG4-related neurological disease which were all hypertrophic pachymeningitis. The age ranged from 35 to 64 (mean = 46) years. The clinical presentation was acute in one, subacute in two, and chronic in three patients. The most common presenting symptom was headache (4), followed by gait and/or urinary disturbances (2), paraparesis (1), and diplopia (1). IgG4 levels were elevated in 50% of them. Pseudotumor-like mass and sinovenous thrombosis, not described previously, were seen in one patient. All the patients were treated with oral or intravenous steroid. Rituximab was given in three patients; azathioprine was the steroid-sparing agent in one patient. Those with acute/subacute onset of presentation had an excellent response to steroids. All the patients with a chronic duration of their symptoms received empirical anti-tuberculous therapy before a definitive diagnosis of Ig G4-RD was made.Conclusions:The characterization of patients with IgG4-related neurological disease based on the understanding of the clinical spectrum increases the confidence in the clinician to resort to early immunosuppression, thereby having prognostic implications.

Имидафенацин в лечении гиперактивного мочевого пузыря и ургентного недержания мочи: результаты открытого многоцентрового рандомизированного контролируемого клинического исследования

The analysis of the results of a multicenter, open, randomized comparative phase III clinical trial on the use of imidafenacin for treating patients with OAB was carried out. A clinical study was conducted according to GCP standards in 12 urological centers of the Russian Federation with the support of company AO "R-Pharm". A total of 296 patients (men and women) aged from 18 to 65 years with OAB and urgent urinary incontinence were included in the study. All patients were randomized into two groups. In Group 1 (n=148) patients received -cholinoblocker imidafenacin 1 tablet (0,1 mg) twice a day. Group 2 patients (n=148) were prescribed a comparison drug tolterodine 1 tablet (2 mg) twice a day, as well. The duration of treatment was 12 weeks. The analysis of results showed a significant decrease in the OAB symptoms in both groups. In Group 1 a decrease of episodes of urge urinary incontinence was more pronounce compared to Group 2, as well as amount of day-time and night-time of episodes of urge urinary incontinence by the 2nd, 4th, 8th and 12th weeks of treatment in comparison with baseline scores. There were no differences between two groups in the severity of reducing average urinary frequency per day. Reducing the severity of urinary disturbances in patients of both groups was accompanied by an improvement in the quality of life. There was a significant and similar decrease in the average total score of both OAB Awareness Tool and EQ-5D questionnaires. Tolerability of treatment was satisfactory in both groups and there were no differences in the adverse events in Group 1 and 2. Imidafenacin showed high clinical efficacy for treating patients with OAB, which is not inferior, and in some values, is superior in comparison to tolterodine. Both drugs had a similar safety and tolerability profile.

Эффективность применения фосфомицина трометамола при остром неосложненном цистите

Acute cystitis is the most common type of uncomplicated urinary tract infection. A choice of antibiotics for the treatment depends not only on the spectrum of antimicrobial activity against pathogens, but also on the pharmacokinetic properties, due to high urine concentration after single or double use is needed. In addition, high safety profile and acceptable cost are important. Fosfomycin is one of the drugs whose efficiency in treating of patients with lower urinary tract infection is proved. It has been on the pharmaceutical market for a long time and is widely used in urologic practice. There is a risk of a decreasing of efficiency of fosfomycin, considering sustained downward trend in the sensitivity of uropathogens. This causes a need to monitor the resistance of main uropathogens to fosfomycin. In this article our experience of using of fosfomycin for the treatment of women with acute uncomplicated cystitis is presented. to evaluate an efficiency of fosfomycin trometamol for treatment of women with acute uncomplicated cystitis. During the period from September to November 2018, we performed an examination and treatment of 57 women with acute uncomplicated cystitis aged from 19 to 40 years. All patients were prescribed 1 sachet of Fosfomycin Esparma (fosfomycin trometamol) after urination. The examinations were carried out on the 1st, 3rd and 7th day, including an evaluation of urination frequency, urgency, nocturia and pain intensity. In addition, urinalysis and urine culture using solid media with determination of the type of pathogens, sensitivity to antibiotics and the level of bacteriuria were also performed. Baseline, all patients had complaints of pain in the bladder, urethral discomfort and frequent urination, but passing only small amount of urine. All women had leucocyturia and bacteriuria. By the 3rd day after receiving fosfomycin, urinary disturbances persisted in 22.8% patients and 17.5% of women still described pain. Mild leucocyturia was determined in 42% cases. Urine culture was negative. By the 7th day after the start of therapy, all clinical and laboratory data were returned to the normal values in all patients. Based on the results of our study, we recommend the fosfomycin as the first-line treatment of uncomplicated lower urinary tract infection due to broad spectrum, low resistance of uropathogens, high safety profile and good compliancy.

Thoracic myelopathy secondary to ossified ligamentum flavum and dural ossification – A series of 19 cases and review of literature

Objective: Thoracic myelopathy has gradually risen to be a prominent diagnosis in patients with persistent upper back pain, bladder symptoms and spastic paraparesis. Often encountered, these conditions pose a serious dilemma to neurosurgeons with respect to surgical planning, timing of surgery, prognosis and possible complications and outcome assessment. In view of these queries and to clarify the indications of when to intervene the following study has been undertaken. To analyze the clinical presentation, radiological features, clinical implications and surgical nuances and outcomes in patients with single and multiple level dorsal canal ossified ligamentum flavum (D-OLF) and associated dural ossification (DO). Patients and methods: Nineteen patients with the diagnosis of thoracic myelopathy (TM) were identified between January 2012 and March 2017. All patients were treated surgically, with decompressive laminectomies, in a single tertiary care center in Southern India. mJOA was calculated preoperatively and assessed postoperatively and a mean mJOA was calculated to assess the significance in neurological improvement. The data was collected from the medical records department and various factors were analyzed, using SPSS software, for correlation.Results: Mean age of our group was 50.84 years with a range of 29 to 71 years. It comprised of 11 males and 8 females. All patients had features of myelopathy. Surgery did have a positive effect on neurological improvement (p = 0.001) in all patients except one. Dural ossification had correlation with pre op and post op urinary disturbances with p value of 0.02. (Mann Whitney Test for 2 independent variables used). A total of ten patients had urinary symptoms pre operatively, out of which six patients showed postoperative improvement at the end of one year. Four of these patients continued to have symptoms, two patients were on Clean Intermittent Catheterisation (CIC), and one patient had features of hesitancy and frequency. Preoperative bladder dysfunction was a strong predictor for continued bladder dysfunction at the end of 1 year (p < 0.004). Conclusions: All patients with D-OLF and or DO presented with myelopathic features. MRI with concurrent CT spine helps to delineate dural ossification from D-OLF and helped to rule out other differentials. The classical “tram track” and “comma sign” is well noted in CT spine and helps to plan surgical approach and anticipate probable complications. Patients with concurrent D-OLF and DO and long segment pathology had increased risk of intraoperative dural tears and postoperative CSF leaks. These subset of patients had a peaked incidence of bladder involvement or non-improvement of existing bladder dysfunction, postoperatively. Patients with D-OLF and DO seemed to do better after surgical decompression. Surgery should be offered once diagnosis is confirmed on imaging, as all patients in out study, except one, showed postoperative neurological improvement.Our study concluded that patients with prolonged preoperative symptoms persisted to have them even after surgery. Patients with concurrent D-OLF and DO showed more significant improvement, postoperatively, in terms of mJOA – postop with a p = 0.002 as compared to patients with D-OLF alone.We recommend that each case be treated individually and treatment should be planned appropriately, based on the radiology and levels involved, keeping in mind the preoperative symptoms and their duration.

Non‐motor symptoms in early Parkinson's disease with different motor subtypes and their associations with quality of life

The aim of this study was to examine non-motor symptoms in different Parkinson's disease (PD) motor subtypes and their associations with quality of life (QoL). A total of 132 patients with early PD with comprehensive motor examinations and non-motor symptom assessments were included. Motor subtypes were classified based on Stebbins' method. Non-motor symptoms were assessed by the Non-Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson's Disease Questionnaire-8. We identified 66 patients (50%) with tremor-dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non-motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non-motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD. Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non-motor symptoms may improve patients' QoL.

Two cases of sporadic adult-onset neuronal intranuclear inclusion disease preceded by urinary disturbance for many years

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease defined by the presence of eosinophilic hyaline intranuclear inclusions. The initial and main clinical feature of adult-onset NIID is predominantly dementia. We present herein 2 cases of sporadic adult-onset NIID with longstanding urinary disturbance prior to development of other neurological symptoms. Case 1: A 71-year-old woman was admitted after she lost consciousness while bathing. She presented slowly progressive bladder dysfunction starting at the age of 40. Recently, she complained of recurrent light-headedness on standing. Her neurological findings showed miosis, muscle weakness, rigidity, hyporeflexia, sensory disturbance, cerebellar ataxia, and orthostatic hypotension. Case 2: A 68-year-old man was admitted because of episodes of transient loss of consciousness. Ten years earlier, he had developed urinary dysfunction. His neurological findings revealed cognitive dysfunction, cerebellar ataxia, and hyporeflexia. Both patients had leukoencephalopathy and motor-sensory neuropathy. In both cases, diffusion-weighted imaging showed high-intensity signals in the corticomedurally junction; and skin biopsy samples revealed ubiquitin-positive intranuclear inclusions. Therefore, we made a diagnosis of adult-onset NIID. Although numerous cases of this disorder have been reported in the past, there were only a few cases showing the development of other neurological symptoms after longstanding urinary disturbance. Our cases suggest that it is worthwhile considering the possibility of NIID in cases with a long-term history of neurogenic bladder dysfunction.

Urinary dysfunction in traumatic brain injury survivors – A retrospective study

Survivors of a traumatic brain injury (TBI) frequently suffer from urinary dysfunction. Possible causes are midbrain dysfunction and primary lesions, but cognitive and behavior factors may also play a role. Overactive bladder (OAB) is a frequent urinary disturbance as opposed to urinary retention. In this study, we aim to investigate altered findings in urodynamic tests and possible relations to other TBI outcomes. A retrospective study was conducted with 24 post-TBI patients (21 male, 3 female) admitted to our unit during a 3 year period. Exclusion criteria included stroke, spinal cord injury, previous history of urological pathology or surgery and absence of urodynamic evaluation. Information was gathered relative to results of urodynamics, TBI imaging, initial GCS scale, urinary symptoms, vesical regime, neuropsychological and ultrasound results. Of the 24 patients studied, all had severe TBI with a mean age of 40.1 years and a predominance of motor vehicle related accidents (66.7%) and axonal diffuse injury (62.5%). Median time from TBI was 7.5 months and only 2 patients had a normal urodynamic study. Urinary symptoms were present in 17 (70.8%) patients and the majority (58.3%) had filling symptoms. There was previous history of urinary tract infection in 32% patients. Neuropsychological evaluation was altered in all but one of the assessed patients. The majority had OAB (62.4%) and altered bladder sensation (70.8%). Mean total vesical capacity was 343.6 mL. Elevated postvoid residual volume (37.5%) and detrusor sphincter dyssynergia (37.5%) was observed. Most patients had urinary symptoms and an overactive bladder. A subset of patients showed detrusor sphincter dyssynergia, a finding not frequently described. Cognitive impairment can play a role in urologic dysfunction and pseudodyssynergia might be present during the urodynamic test. Further studies are needed to assess urologic dysfunction in severe TBI survivors.

Spinal Intramedullary Abscess Secondary to Dermal Sinus in Children.

Congenital dermal sinuses (CDS) are uncommon lesions. They are most often noted in lumbosacral region and may lead to meningitis or spinal abscess. Intramedullary spinal cord abscess (IMSCA) due to CDS is rare and often co-exists with an inclusion tumor such as dermoid/epidermoid cyst. Literature review was done to analyze all cases of pediatric IMSCA secondary to CDS by searching online databases starting from the oldest case reported. Only 50 cases have been reported and were analyzed. Mean age was 22.6 months (range 1 month-15 years). Fever, acute flaccid lower limb weakness, and urinary disturbances were the most common presenting features. Dermal sinus was commonest in lumbosacral region. Inclusion cysts were observed in 50% of cases. Staphylococcus aureus was the most the common organism. Mean follow-up duration was 18.2 months (range 1 week-156 months). Majority of the cases underwent multilevel laminectomy with myelotomy and drainage of abscess. Outcome was good-to-excellent in around 60% cases with four deaths. Presence of fever and limb weakness was significantly associated with poor outcomes. Intramedullary abscess secondary to CDS is very rare. Complete sinus tract excision, myelotomy and drainage of abscess, and decompression of co-existent inclusion cysts with prolonged antibiotic therapy remain the standard treatment. Approximately 60% cases achieve good outcomes. Fever and limb weakness portend poorer outcomes than those without.

Prodromal symptoms of multiple sclerosis in primary care

Early diagnosis and treatment initiation significantly influence long-term disability outcome in multiple sclerosis (MS). We aimed at identifying prodromal symptoms of MS in primary care settings. This was a nested case-control study comparing the occurrence of various symptoms in MS patients versus controls at 0 to 2, 2 to 5, and 5 to 10 years before index date (first MS record). A total of 10,204 incident MS cases were identified within the United Kingdom Clinical Practice Research Datalink between January 1, 1987 and February 28, 2016 (median age = 47 years, interquartile range [IQR] = 39-57, females = 7,308 [71.6%]). Patients were matched to 39,448 controls with no MS record by sex, year of birth, general practitioner, and year of registration (age = 47 years, IQR = 39-56, females = 28,248 [71.6%]). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using conditional logistic regression. MS patients had significantly higher risk of presenting up to 10 years prior to index date with gastric, intestinal, urinary, and anorectal disturbances, anxiety, depression, insomnia, fatigue, headache, and various types of pain. MS risk progressively increased with each additional symptom presented (0-2 years: OR = 1.51, 95% CI = 1.47-1.55, p < 0.001; 2-5 years: OR = 1.29, 95% CI = 1.25-1.33, p < 0.001; 5-10 years: OR = 1.20, 95% CI = 1.15-1.26, p < 0.001). Sensitivity analyses in patients with age at index < 40 years and no neurological disturbances prior to symptoms of interest showed consistent results. Various clinical disturbances precede MS diagnosis by several years, supporting a prodromal phase to the disease and improving our clinical knowledge of early MS. Integrating these symptoms in the diagnostic procedure may help earlier disease identification. Ann Neurol 2018.

Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis.

To evaluate the efficacy, safety, and tolerability of repetitive Transcranial Magnetic Stimulation (rTMS) associated with standard drug therapies for neuropathic pain that does not respond to pharmacological treatment alone in patients with Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC). Secondary goals were to assess the effects of rTMS on Lower Urinary Tract Symptoms (LUTS) and Quality of Life (QOL). Fifteen patients with BPS/IC were enrolled in this randomized, double-blind, sham stimulation-controlled, crossover study. Patients were treated for 2 weeks with either real-rTMS (for five consecutive days in 20-min sessions) or sham-rTMS (for five consecutive days in 20-min sessions). After a 6-week washout period, the patients who had previously undergone real-rTMS underwent sham-rTMS, and vice versa. Patients were rated at each visit by means of questionnaires on pain, urinary disturbances, depression, and QOL. The statistical analysis revealed significant effects of real-rTMS, when compared with sham-rTMS, on pain (in the VAS, Functional Neuropathic Pelvic Pain, Neuropathic Pain Symptom Inventory, McGill questionnaire, and Central Sensitization Inventory), urinary LUTS (in the Overactive Bladder Questionnaire score, bladder emptying, and daily urinary frequency), and QOL (in the subscores of the SF-36 related to physical pain and to emotional status). No serious adverse events were reported during the study. The results of this study show that rTMS applied with an H-coil over the M1 in the area corresponding to the pelvic region in patients with BPS/IC appears to improve chronic pelvic pain (CPP) and associated urinary disorders.

A clinicopathological study of carcinoma penis in a rural population in Southern India

Background: Carcinoma penis is not an uncommon malignancy in rural population. The various epidemiological, clinical and pathological factors were analysed and compared with the global standards. To analyse the epidemiological, clinical, and pathological characteristics of carcinoma penis and their influence on the outcome of management strategies adopted.Methods: This prospective study was conducted in government Villupuram medical college hospital Villupuram between July 2015 and July 2017 over 42 new carcinoma penis cases that were treated in the department of general surgery. Particularly about the site of origin of the lesion whether prepuce, glans, corona, or shaft.Results: The most common presenting symptom in our study was the growth. It constitutes about 71% of the cases. Ulcer and discharge are seen in 24 and 3 percent of cases respectively. Most of the cases present with multiple symptoms. Apart from these symptoms urinary disturbance and weight loss are the most common associated symptom. Pain is absent in most of the cases unless there is a superadded infection. Nodal disease as a presenting symptom is not seen in our study. But 3 patients present recurrence as nodal disease after treatment of primary.Conclusions: Screening of the high-risk age group will decrease in unnecessary delay in presentation of the disease. Educating about the personal hygiene will decrease the possible etiology of the disease. Improving the self-discipline by cessation of smoking and avoiding extramarital contact will significantly decrease the disease frequency.