The low dopamine hypothesis: A plausible mechanism underpinning residual urine, overactive bladder and nocturia (RON) syndrome in older patients.

INTRODUCTION: Aging is associated with a combination of several lower urinary tract (LUT) signs and symptoms, including residual urine, overactive bladder and nocturia. One of the mechanisms of this LUT dysfunction that has not been discussed in dept so far is the role of dopamine (DA). METHODS: In this narrative review, we explore the dopaminergic hypothesis in the development of this combination of LUT signs and symptoms in older adults. RESULTS: DA is one of the neurotransmitters whose regulation and production is disrupted in aging. In synucleinopathies, altered DAergic activity is associated with the occurrence of LUTS and sleep disorders. Projections of DAergic neurons are involved in the regulation of sleep, diuresis, and bladder activity. The low dopamine hypothesis could explain the genesis of a set of LUT signs and symptoms commonly seen in this population, including elevated residual urine, Overactive bladder syndrome and Nocturia (discussed as the RON syndrome). This presentation is however also common in older patients without synucleinopathies or neurological disorders and therefore we hypothesise that altered DAergic activity because of pathological aging, and selective destruction of DAergic neurons, could underpin the presentation of this triad of LUT dysfunction in the older population. CONCLUSION: The concept of RON syndrome helps to better understand this common phenotypic presentation in clinical practice, and therefore serves as a useful platform to diagnose and treat LUTS in older adults. Besides recognizing the synucleinopathy "red flag" symptoms, this set of multi-causal LUT signs and symptoms highlights the inevitable need for combination therapy, a challenge in older people with their comorbidities and concomitant medications.

Psychological symptoms among healthcare workers handling COVID-19 patients.

INTRODUCTION: Healthcare workers serve as the frontliners against the coronavirus 2019 disease (COVID-19) and this puts them most at risk of infection as they attend to numerous patients with unknown status. This study aimed to examine stress, anxiety, and depression among healthcare workers caring for COVID-19 patients in Sarawak General Hospital (SGH), Malaysia. MATERIALS AND METHODS: This cross-sectional observational study conducted in SGH during the pandemic with an online self-administered questionnaire composed of two parts, the socio-demographic characteristics, and the Depression Anxiety Stress Scale (DASS). RESULTS: A total of 105 healthcare workers responded to this study. A questionnaire in both Bahasa Melayu and English was used. The findings showed that all healthcare workers had mild anxiety, with the majority experiencing mild stress (57.1%), and almost half of the respondents experiencing mild depression (41%). Female subjects had a significant higher mean score in anxiety level and stress level compared to male subjects (10.0±3.20 vs. 8.6±2.93, p<0.05; 14.1±4.76 vs. 10.7±3.70, p<0.05, respectively). Staff who were transferred from other units to handle COVID-19 cases experienced more psychological symptoms. There were significant correlations between the depression, anxiety and stress levels among the healthcare workers and the number of children they had (r=0.739, p=0.001; r=0.642, p=0.001; r=1, p =0.001 respectively). However, the stress level among the healthcare workers was reversely correlated with their years of working experience (r=-0.199, p=0.042). CONCLUSION: This study identified some socio-demographic factors associated with increased levels of stress, anxiety and depression among the healthcare workers during pandemic, which may lay ground for future interventions.

Urodynamics in patients with multiple sclerosis: A consensus statement from a urodynamic experts working group.

AIMS: Urodynamics (UDS) is often indicated for multiple sclerosis (MS) patients either at presentation to specialized medical centers or after failure of conservative management of lower urinary tract dysfunction (LUTD). However, the ideal moment and context to indicate this exam in this group of patients remain controversial. We aimed to establish a consensus panel to address the role of UDS in MS patients. METHODS: A panel representing urology, rehabilitation medicine, and neurology skilled in neuro-urology participated in a consensus-forming project using a Delphi method to reach consensus on the role of UDS in MS patients. RESULTS: In total, five experts participated. All panelists participated in the four phases of the consensus process. Consensus was reached if ≥70% of the experts agreed on recommendations. To facilitate a common understanding among all experts, a face-to-face consensus meeting was held in Florence in September 2017 and then with a follow-up teleconference in March 2018. By the end of the Delphi process, formal consensus was achieved for 100% of the items and an algorithm was then developed in a face-to-face meeting in Philadelphia in August 2018. The final expert opinion recommendations were approved by the unanimous consensus of the panel. CONCLUSIONS: UDS represents an important diagnostic tool for MS patients and is particularly useful to evaluate the pattern of LUT dysfunction in high-risk patients. There is a lack of high-evidence level studies to support an optimal urodynamic long-term follow-up protocol.

Urogenital symptoms in mitochondrial disease: overlooked and undertreated.

BACKGROUND AND PURPOSE: Bowel symptoms are well documented in mitochondrial disease. However, data concerning other pelvic organs is limited. A large case-control study has therefore been undertaken to determine the presence of lower urinary tract symptoms (LUTS) and sexual dysfunction in adults with genetically confirmed mitochondrial disease. METHODS: Adults with genetically confirmed mitochondrial disease and control subjects were recruited from a specialist mitochondrial clinic. The presence and severity of LUTS and their impact on quality of life, in addition to sexual dysfunction and bowel symptoms, were captured using four validated questionnaires. Subgroup analysis was undertaken in patients harbouring the m.3243A>G MT-TL1 mitochondrial DNA mutation. A subset of patients underwent urodynamic studies to further characterize their LUTS. RESULTS: Data from 58 patients and 19 controls (gender and age matched) were collected. Adults with mitochondrial disease had significantly more overactive bladder (81.5% vs. 56.3%, P = 0.039) and low stream (34.5% vs. 5.3%, P = 0.013) urinary symptoms than controls. Urodynamic studies in 10 patients confirmed that bladder storage symptoms predominate. Despite high rates of LUTS, none of the patient group was receiving treatment. Female patients and those harbouring the m.3243A>G MT-TL1 mutation experienced significantly more sexual dysfunction than controls (53.1% vs. 11.1%, P = 0.026, and 66.7% vs. 26.3%, P = 0.011, respectively). CONCLUSIONS: Lower urinary tract symptoms are common but undertreated in adult mitochondrial disease, and female patients and those harbouring the m.3243A>G MT-TL1 mutation experience sexual dysfunction. Given their impact on quality of life, screening for and treating LUTS and sexual dysfunction in adults with mitochondrial disease are strongly recommended.

Testing for urinary tract colonization before high-dose corticosteroid treatment in acute multiple sclerosis relapses: prospective algorithm validation.

BACKGROUND AND PURPOSE: To evaluate a dipstick algorithm for urinary tract colonization, prior to high-dose corticosteroid treatment in acute relapses of multiple sclerosis (MS). METHODS: Prospective cohort study of 267 consecutive patients with MS relapses requiring corticosteroid treatment in a hospital-based, ambulatory, acute MS relapse clinic. A total of 18 participants met the exclusion criteria, leaving 249 for analysis. Main outcome measures were urinary dipstick sensitivity, specificity, positive predictive value, negative predictive value and safety of antibiotic co-treatment with high-dose corticosteroids. RESULTS: Significant bacteriuria (≥10(5) colonies ml) rate in this population was 11% (95% CI, 7.1-14.9). Specificity and sensitivity of positive leucocyte esterase or nitrite were 78% and 65%. Negative predictive value of urine dipstick was 96%. No clinical adverse events occurred in the 3% (95% CI, 0.9-5.1) of patients with a false-negative dipstick. Eighteen per cent of patients were unnecessarily treated with antibiotics for 48 h. CONCLUSION: Urinary dipstick testing allows for rapid and safe management of patients suffering from an acute MS relapse. The algorithm is conservative, and future work is needed to reduce the false-positive rate.

Descriptive study of acute disseminated encephalomyelitis and evaluation of functional outcome predictors.

BACKGROUND: Outcome following Acute Disseminated Encephalomyelitis (ADEM) is variable and there are only limited studies from India. AIM: The study aims to evaluate the predictors of functional outcome in a cohort of patients with ADEM. SETTING: Tertiary-care teaching hospital. MATERIALS AND METHODS: Patients admitted with the diagnosis of ADEM from 1999 to 2004 have been included. Clinical features and radiological findings were evaluated. Functional outcome at discharge was scored using modified Rankin Scale and patients were followed up regularly. STATISTICAL ANALYSIS: Chi-Square test or Fisher's exact test, and Student's t test for comparison of categorical and continuous variables, respectively, and logistic regression for multivariate analysis. RESULTS: Sixty-one patients were evaluated (mean age 22+/-15.9 years, 1-65). Fifty-two patients had preceding febrile illness or vaccination with mean 9.1+/-12.5 days interval to first neurological symptom. Non-specific febrile illnesses were the commonest trigger. Commonest findings were motor signs (n=41), impaired consciousness (n=33), bladder symptoms (n=21), ataxia (n=15), and seizures (n=14). Between adult (mean age 30.1+/-13.1 years, 13-65, n=38), and pediatric (mean age 6.2+/-2.8 years, 1-12, n=23) patients, language disturbances were more common in the latter (P=0.047). MR imaging (n=35) demonstrated lesions mostly in frontoparietal white matter (n=23) and thalamus (n=15). Nine patients expired. Patients with poor functional outcome at discharge more often had impaired consciousness (P=0.038) and seizures (P=0.06). At follow-up (n=25), deficits included motor signs (n=15) and bladder symptoms (n=5). CONCLUSIONS: ADEM has a wide range of neurological presentations and language disturbances are more common in pediatric patients. The presence of impaired consciousness, and possibly seizures, predict poor functional outcome at hospital discharge.

A UK consensus on the management of the bladder in multiple sclerosis.

Bladder symptoms in multiple sclerosis (MS) are common and distressing but also highly amenable to treatment. A meeting of stakeholders involved in patients' continence care, including neurologists, urologists, primary care, MS nurses and nursing groups was recently convened to formulate a UK consensus for management. National Institute for Health and Clinical Excellence (NICE) criteria were used for producing recommendations based on a review of the literature and expert opinion. It was agreed that in the majority of cases, successful management could be based on a simple algorithm which includes using reagent sticks to test for urine infection and measurement of the post micturition residual urine volume. This is in contrast with published guidelines from other countries which recommend cystometry. Throughout the course of their disease, patients should be offered appropriate management options for treatment of incontinence, the mainstay of which is antimuscarinic medications, in combination, if necessary, with clean intermittent self-catheterisation. The evidence for other measures, including physiotherapy, alternative strategies aimed at improving bladder emptying, other medications and detrusor injections of botulinum toxin A was reviewed. The management of urinary tract infections as well as the bladder problems as part of severe disability were discussed and recommendations agreed.

A UK consensus on the management of the bladder in multiple sclerosis.

Bladder symptoms in multiple sclerosis (MS) are common and distressing but also highly amenable to treatment. A meeting of stakeholders involved in patients' continence care, including neurologists, urologists, primary care, MS nurses and nursing groups was recently convened to formulate a UK consensus for management. National Institute for Health and Clinical Excellence (NICE) criteria were used for producing recommendations based on a review of the literature and expert opinion. It was agreed that in the majority of cases, successful management could be based on a simple algorithm which includes using reagent sticks to test for urine infection and measurement of the post micturition residual urine volume. This is in contrast with published guidelines from other countries which recommend cystometry. Throughout the course of their disease, patients should be offered appropriate management options for treatment of incontinence, the mainstay of which is antimuscarinic medications, in combination, if necessary, with clean intermittent self-catheterisation. The evidence for other measures, including physiotherapy, alternative strategies aimed at improving bladder emptying, other medications and detrusor injections of botulinum toxin A was reviewed. The management of urinary tract infections as well as the bladder problems as part of severe disability were discussed and recommendations agreed.

Identifying barriers to help-seeking for sexual dysfunction in multiple sclerosis.

BACKGROUND: Sexual dysfunction (SD) is common in multiple sclerosis (MS), however, under-reported. OBJECTIVE: The aim of this study was to identify barriers faced by patients with MS and healthcare professionals (HCPs) in discussing SD. METHODS: This was a two-part prospective study carried out at a tertiary care centre. Patients with MS were surveyed using a 29-item questionnaire and SD was assessed using the MSISQ and ASEX questionnaires; depression screened with PHQ-2. HCPs were surveyed using a 23-item questionnaire. RESULTS: Seventy four patients (mean age 42.4 ± 10.7, 54 females) and 98 HCPs (mean age 45.8 ± 8.9, 90 females) participated. SD was significant, with primary (36.4%), secondary (27%) and tertiary (29.8%) contributory factors. Commonest barriers reported by patients were dominance of neurological symptoms (N = 30, 40.5%), presence of family or friends (N = 28, 37.8%), and not being asked (N = 25, 33.8%), while HCPs reported presence of family or friends (N = 34, 34.7%), lack of knowledge about SD (N = 30, 30.6%), and inadequate time during the consultation (N = 27, 27.6%). CONCLUSIONS: Barriers to discussing SD are similar between patients and HCPs. The most common barriers are addressable through modifications in the clinic environment, raising awareness and providing training opportunities.

Juvenile Behçet's disease: highlighting neuropsychiatric manifestations and putative genetic mechanisms.

Behçet's disease is a multisystem inflammatory disorder of unknown etiology. We report a 12-year-old boy who presented with features of raised intracranial tension and seizures and was found to have cerebral venous sinus thrombosis on evaluation. Behçet's disease was diagnosed based on occurrence of recurrent oral and genital ulcers in the past and characteristic skin lesions subsequently. He also showed significant personality changes including multiple attempts of deliberate self-harm. Pedigree analysis revealed that six family members spanning three generations had recurrent oral ulcers and three members satisfied the criteria for Behçet's disease. Clinical features varied amongst the family members and there was suggestion of genetic anticipation. The index case was carrying HLA-B37/B7 and the mother was carrying B37/B40. Our report sheds light on the genetics of Behçet's disease. Unusual features were early age of onset, cerebral venous sinus thrombosis, significant personality changes and strong family history with phenotypic heterogeneity.

Dysmyelinating neuropathy in benign form of megalencephalic leukoencephalopathy with subcortical cysts: a novel observation from south India.

A 37-year-old gentleman presented with macrocephaly since early childhood and progressive impairment of motor and cognitive functions. Magnetic resonance imaging revealed extensive white matter involvement and frontotemporal subcortical cysts. Absent ankle jerk and abnormal nerve conduction study raised a possibility of associated peripheral neuropathy. Sural nerve biopsy was suggestive of dysmyelinating neuropathy. This report serves to expand the clinical spectrum of this rare leukodystrophy.

Hepatic myelopathy: a rare complication following extrahepatic portal vein occlusion and lienorenal shunt.

A 19-year-old gentleman presented with slowly progressive spastic paraparesis, 2 years after the therapeutic lienorenal shunt for portal hypertension secondary to cirrhosis and portal vein occlusion. After 2 years of initial evaluation, the motor functions had not worsened further. He did not have any obvious clinical or EEG features of hepatic encephalopathy. Other causes for myelopathy were ruled out. Contribution of portal vein occlusion to portosystemic shunting has not been reported previously in patients with 'hepatic myelopathy.' This uncommon complication needs to be considered in patients with shunt surgery for relieving portal hypertension.

Urologic symptoms and functional neurologic disorders.

The term functional urologic disorders covers a wide range of conditions related broadly to altered function rather than structure of the lower urinary tract, mainly of impaired urine voiding or storage. Confusingly, for a neurologic readership, these disorders of function may often be due to a urologic, gynecologic, or neurologic cause. However, there is a subset of functional urologic disorders where the cause remains uncertain and, in this chapter, we describe the clinical features of these disorders in turn: psychogenic urinary retention; Fowler's syndrome; paruresis (shy-bladder syndrome); dysfunctional voiding; idiopathic overactive bladder, and interstitial cystitis/bladder pain syndrome. Some of these overlap in terms of symptoms, but have become historically separated. Psychogenic urinary retention in particular has now largely been abandoned as a concept, in part because of the finding of specific urethral electromyogram findings in patients with this symptom now described as having Fowler's syndrome, and their successful treatment with sacral neurostimulation. In this chapter we review the poorly researched interface between these "idiopathic" functional urologic disorders and other functional disorders (e.g., irritable-bowel syndrome, fibromyalgia) as well as specifically functional neurologic disorders. We conclude that there may be a relationship and overlap between them and that this requires further research, especially in those idiopathic functional urologic disorders which involve disorders of the urethral sphincter (i.e., voluntary muscle).

A cytological study of hepatitis B surface antigen localization using orcein staining in hepatocellular carcinoma.

Twenty patients of suspected hepatocellular carcinoma (HCC) were studied to test the hypothesis that orcein staining of cytological specimens from HCC can detect hepatitis B surface antigen (HBsAg). HBsAg status, cytological examination of fine needle aspiration cytology (FNAC) material for diagnosis by Papanicolaou and modified orcein staining for HBsAg were carried out. Observer variability and agreement on orcein positivity was assessed and analyzed using kappa statistics. HCC was diagnosed in 13 patients and 8 were HBsAg positive; 8 had orcein positivity as judged by observer 2 and 7 by observer 1. A significant kappa value of 0.837 suggested a high degree of observer agreement in the interpretation of orcein positivity. This technique is safe and quick and can supplement the histopathological diagnosis of hepatitis B virus associated HCC.

A rare case of porphyria.

INTRODUCTION: Congenital erythropoietic porphyria is one of the rare forms of an intriguing group of metabolic disorders known as porphyrias. Less than 200 cases have been reported in the literature. CLINICAL PRESENTATION: We report the case of a 27-year-old gentleman who had the clinical profile suggestive of porphyria, now presenting with anaemia. The type of porphyria was found to be congenital erythropoietic porphyria by biochemical assay and cause for anaemia was haemolysis, a well-known association with the erythropoietic porphyrias. TREATMENT: The management of porphyrias is essentially symptomatic. He was treated with blood transfusions and haematinics. CONCLUSION: The patient improved symptomatically and he is on regular followup. With the development of gene therapy, a specific cure for this rare type of porphyria is expected in the near future.