Cerebrospinal fluid leaks secondary to dural tears: a review of etiology, clinical evaluation, and management.

OBJECTIVE: Damage to the dura mater often occurs in trauma cases of the head and spine, surgical procedures, lumbar punctures, and meningeal diseases. The resulting damage from dural tears, or durotomy, causes cerebrospinal fluid (CSF) to leak out into the surrounding space. The CSF leak induces intracranial hypotension, which can clinically present with a range of symptoms not limited to positional headaches which can confound accurate diagnosis. Current methods of evaluation and management of dural tears are discussed herewith, as well as the present understanding of its etiology, which may be classified as related to surgery, procedure, trauma, or connective tissue disorder. METHODS: We piloted a MEDLINE® database search of literature, with emphasis on the previous five years, combining keywords such as "cerebrospinal fluid leak," "surgery," "procedure," and "trauma" to yield original research articles and case reports for building a clinical profile. RESULTS: Patients with suspected dural tears should be evaluated based on criteria set by the International Headache Society, radiological findings, and a differential diagnosis to accurately identify the tear and its potential secondary complications. Afflicted patients may be treated promptly with epidural blood patches, epidural infusions, epidural fibrin glue, or surgical repair. At this time, epidural blood patches are the first line of treatment. Dural tears can be prevented to an extent by utilizing minimally invasive techniques and certain positions for lumbar puncture. Surgical, trauma, lumbar puncture, and epidural injection patients should be observed very carefully for dural tears and CSF leaks as the presenting clinical manifestations can be highly individualized and misguiding. CONCLUSION: Because studies have demonstrated a high frequency of dural tears, particularly in spinal surgery patients, there is a need for prospective studies so that clinicians can develop an elaborate prevention strategy and response to avoid serious, unseen complications.

Revisiting the pineal gland: a review of calcification, masses, precocious puberty, and melatonin functions.

Introduction: The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement and curiosity. Methods: We review present an up-to-date review including the anatomy, embryology, and physiology of the pineal gland and its ability to secrete hormones including melatonin, pathophysiology of pineal gland tumors, cysts, and calcifications, their clinical presentation including their association with parkinsonism and precocious puberty, and various treatment approaches. Results: Exploring the biochemistry of melatonin, various calcification morphologies, and pineal tumors may uncover a wider role and the exhaustive case study consolidation allows clinicians to carefully review the literature and aid their treatment approaches. Conclusion: It is imperative that clinicians and diagnosticians are able to distinguish manifestations of an overlooked gland.

Using lectures to identify student misconceptions: a study on the paradoxical effects of hyperkalemia on vascular smooth muscle.

Medical students have difficulty understanding the mechanisms underlying hyperkalemia-mediated local control of blood flow. Such control mechanisms are crucial in the brain, kidney, and skeletal muscle vasculature. We aimed to identify medical students' misconceptions via assessment of students' in-class knowledge and, subsequently, improve future teaching of this concept. In-class polling was performed with the TurningPoint clicker response system (n = 860) to gauge students' understanding of three physiological concepts related to hyperkalemia: membrane potential (Vm), conductance, and smooth muscle response. Vm includes the concepts of equilibrium potential (Veq) for specific ions, as well as driving force (DF = Vm - Veq). Students understood the concept of DF (~70% answered correctly), suggesting their understanding of Vm. However, students misunderstood that hyperkalemia results in depolarization (~52% answered correctly) and leads to an increase in potassium conductance (~31% answered correctly). Clarification of the type of smooth muscle as vascular increased the percentage of correct responses (~51 to 73%). The data indicate that students lacked knowledge of specific potassium conductance in various muscle types, resulting in divergent responses, such as the canonical depolarization in skeletal muscle versus hyperpolarization in smooth muscle cells during hyperkalemia. Misunderstanding of this crucial concept of conductance is directly related to the students' performance. Furthermore, we connected the paradoxical effect of hyperkalemia to pathological acute and chronic hyperkalemia clinical scenarios.

Current understanding of tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncologic emergency from the intracellular release of material in lysing malignant cells. The earlier it is treated, the less likely it is to be harmful to an individual and spread through the body. Common complications of TLS include arrhythmias, which are caused by hypocalcemia or hyperkalemia, renal failures due to hyperuricemia or hyperphosphatemia, and seizures. Furthermore, the risk to develop TLS varies widely based on several factors including factors that are related to disease, the patient, and the treatment of the patient. Laboratory data can be used to gauge the severity of TLS based on patient serum levels for specific markers. On the contrary, evidence of TLS via radiological imaging and electrocardiogram findings has been a limited way to evaluate TLS, indicating the need for further research in this area. Common trends of treatment have also been seen in the past several years, evident by case studies seen in the following literature review.

Neurological and neuropsychiatric manifestations of porphyria.

Porphyrias are inherited disorders of the heme biosynthetic pathway, usually characterized by dermatological changes due to the accumulation of byproducts in the pathway. Select porphyrias also affect the nervous system, namely hereditary coproporphyria, acute intermittent porphyria and variegate porphyria. Complications include paralysis, hyponatremia which can risk central pontine myelinolysis, seizures and coma. Neurological complications usually result from severe episodes of acute attacks. Acute attacks may also elicit neuropsychiatric symptoms such as confusion, hallucinations, anxiety and psychosis. However, these manifestations are generally self-limiting. Due to the generally low incidence of porphyria and full knowledge the associated neurological and psychiatric manifestations, we review the relevant porphyrias along with their clinical manifestations, evaluation, and management to raise its awareness in the clinical picture and to prevent misdiagnosis. Porphyria should be considered within the differential diagnosis for unexplained neurological symptoms.

Neuro-urological sequelae of lumbar spinal stenosis.

PURPOSE: Lumbar spinal stenosis is characterized by the narrowing of the spinal canal, which subsequently induces impingement of neural elements in the lumbar spine. Thus, symptoms of lumbar spinal stenosis are typically associated with damage to those neural elements. Herewith, we target the genitourinary symptoms of lumbar spinal stenosis and the importance of differentiating these symptoms from other genitourinary pathologies, namely benign prostatic hyperplasia. MATERIALS AND METHODS: MeSH and keywords relevant to lumbar spinal stenosis and the organs of the urinary tract were used to a guide a literature search on MEDLINE. RESULTS: Bladder dysfunction, lower urinary tract symptoms (e.g. urinary incontinence, detrusor overactivity and underactivity, as well as frequent urinary tract infections), renal osteodystrophy and sexual dysfunction (e.g. erectile dysfunction and priapism) are implicated in lumbar spinal stenosis. CONCLUSIONS: It is imperative for urologists to conduct a thorough history and physical examination so that they will not misdiagnose secondary genitourinary manifestations of lumbar spinal stenosis as primary problems or misunderstand secondary problems. Urological consultations are also integral to prioritizing patients with the highest risk of bladder damage for corrective spinal surgery.

Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning.

Lead poisoning is a stealthy threat to human physiological systems as chronic exposure can remain asymptomatic for long periods of time before symptoms manifest. We presently review the biophysical mechanisms of lead poisoning that contribute to male infertility. Environmental and occupational exposure of lead may adversely affect the hypothalamic-pituitary-testicular axis, impairing the induction of spermatogenesis. Dysfunction at the reproductive axis, namely testosterone suppression, is most susceptible and irreversible during pubertal development. Lead poisoning also appears to directly impair the process of spermatogenesis itself as well as sperm function. Spermatogenesis issues may manifest as low sperm count and stem from reproductive axis dysfunction or testicular degeneration. Generation of excessive reactive oxygen species due to lead-associated oxidative stress can potentially affect sperm viability, motility, DNA fragmentation, membrane lipid peroxidation, capacitation, hyperactivation, acrosome reaction, and chemotaxis for sperm-oocyte fusion, all of which can contribute to deter fertilization. Reproductive toxicity has been tested through cross-sectional analysis studies in humans as well as in vivo and in vitro studies in animals.

Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management.

Genitourinary syndrome of menopause, a new term for a condition more renowned as atrophic vaginitis, is a hypoestrogenic condition with external genital, urological, and sexual implications that affects >50% of postmenopausal women. Due to sexual embarrassment and the sensitive nature of discussing symptoms, genitourinary syndrome of menopause is greatly underdiagnosed. The most up-to-date literature pertaining to clinical manifestations, pathophysiology, etiology, evaluation, and management of genitourinary syndrome of menopause is comprehensively reviewed. Early detection and individually tailored pharmacologic (eg, estrogen therapy, selective estrogen receptor modulator, synthetic steroid, oxytocin, and dehydroepiandrosterone) and/or nonpharmacologic (eg, laser therapies, moisturizers and lubricants, homeopathic remedies, and lifestyle modifications) treatment is paramount for not only improving quality of life but also for preventing exacerbation of symptoms in women with this condition.

Neuro-urological manifestations of Parkinson's disease.

This article highlights the urological manifestations of Parkinson's disease, the neurological pathways shared by Parkinson's and its urological diseases.

Functional characterization of an AQP0 missense mutation, R33C, that causes dominant congenital lens cataract, reveals impaired cell-to-cell adhesion.

Aquaporin 0 (AQP0) performs dual functions in the lens fiber cells, as a water pore and as a cell-to-cell adhesion molecule. Mutations in AQP0 cause severe lens cataract in both humans and mice. An arginine to cysteine missense mutation at amino acid 33 (R33C) produced congenital autosomal dominant cataract in a Chinese family for five generations. We re-created this mutation in wild type human AQP0 (WT-AQP0) cDNA by site-directed mutagenesis, and cloned and expressed the mutant AQP0 (AQP0-R33C) in heterologous expression systems. Mutant AQP0-R33C showed proper trafficking and membrane localization like WT-AQP0. Functional studies conducted in Xenopus oocytes showed no significant difference (P > 0.05) in water permeability between AQP0-R33C and WT-AQP0. However, the cell-to-cell adhesion property of AQP0-R33C was significantly reduced (P < 0.001) compared to that of WT-AQP0, indicated by cell aggregation and cell-to-cell adhesion assays. Scrape-loading assay using Lucifer Yellow dye showed reduction in cell-to-cell adhesion affecting gap junction coupling (P < 0.001). The data provided suggest that this mutation might not have caused significant alterations in protein folding since there was no obstruction in protein trafficking or water permeation. Reduction in cell-to-cell adhesion and development of cataract suggest that the conserved positive charge of Extracellular Loop A may play an important role in bringing fiber cells closer. The proposed schematic models illustrate that cell-to-cell adhesion elicited by AQP0 is vital for lens transparency and homeostasis.

Clinical utility of ozone therapy and hyperbaric oxygen therapy in degenerative disc disease.

Ozone can be medically useful concerning healing wounds and relieving pain in various conditions, such as disc disease. The aspects of human blood ozonation have been reviewed, as well as potential complications that may arise. The mechanisms of ozone therapy are discussed in detail. It is imperative to recognize ozone as a useful proxy in oxidative-stress related diseases, consolidating other medical gases recognized for their therapeutic importance. The utility of hyperbaric oxygen therapy is also discussed. Disc herniation is very common, as more than 3 million cases are treated per year. Herein we review the medical, surgical, and gene-based therapies that ozone therapy can provide regarding disc disease.

Surfer's myelopathy: A review of etiology, pathogenesis, evaluation, and management.

Context: Surfer's myelopathy (SM) is an acute syndrome identified by nontraumatic paraparesis or paraplegia. Though traditionally tied to first-time surfers, the condition encompasses any activity involving hyperextension of the back such as gymnastics, yoga, and Pilates.Methods: MEDLINE® and Google Scholar literature searches were gathered to identify relevant case reports for determining the etiology, pathogenesis, evaluation, and management of SM.Results: While the rare nature of SM limits its full understanding, studies have pinpointed that hyperextension in the back leads to vasculature insufficiency secondary to dynamic compression of the artery of Adamkiewicz. In surfing, this hyperextension combined with the execution of the Valsalva maneuver while trying to stand up on the surfboard likely increases intraspinal pressure. Due to its nontraumatic origin, the presence of SM is not immediately clear. Moreover, its similarity in clinical and radiological presentations with other entities can further complicate diagnosis. Seemingly, idiopathic urological symptoms can be explained by the physician if they conduct a thorough history.Conclusion: In an effort to raise awareness for the practicing physician, we presently review the etiology, diagnosis, treatment, and prolonged effects of SM. With the surging popularity of surfing as well as the advent of children participating in precarious sports and activities at an earlier age, we can expect a rising incidence of traumatic and nontraumatic spinal cord injuries. Neurologists, urologists, emergency medicine and sports medicine physicians alike can utilize this review to build a high index of suspicion for SM. The risk factors for SM should be conveyed to those participating in novices in surfing, yoga, gymnastics, ballet, and any activity enabling sustained or repeated spinal extension. Increased general awareness will facilitate increased symptom recognition in order to arrest aggravation of injury.

Psychosocial and Sexual Implications of Repaired Cleft Lip in an Adult Male.

We describe the case of a 32-year-old man with repaired cleft lip complaining of sexual difficulties, which were determined to be multifactorial in origin. A negative body impression, anatomical difficulty in engaging in sexual acts, the indirect impact of secondary complications of cleft lip, and the negative perception of his dysmorphia from potential sexual partners led to his current state. Cleft lip and palate (CLP) are the most common malformations of the craniofacial region. The malformations of anatomical structures involved in CLP can manifest through several variations of clinical features and phenotypes, typically affecting hearing, social integration, speech, and feeding. From birth to the end of growth, a multidisciplinary approach involving orthodontists, speech therapists, psychologists, and social workers is essential for adequate management, even after surgical repair. This case report illustrates the critical importance of the functionality of normal lips essential for sexual function and psychosocial issues encountered in a patient with repaired cleft lip, as this issue likely has a higher prevalence than the literature actually suggests. Adding a psychiatrist on the panel for pediatric reconstructive surgery teams and post-repair rehabilitation would be essential to managing potential sexual and psychological issues into adulthood.

The Role of Diabetes Mellitus in Diseases of the Gallbladder and Biliary Tract.

BACKGROUND: The increasing prevalence of diabetes mellitus worldwide continues to pose a heavy burden. Though its gastrointestinal impact is appropriately recognized, the lesser known associations may be overlooked. OBJECTIVE: We aim to review the negative implications of diabetes on the gallbladder and the biliary tract. METHODS: A MEDLINE® database search of literature was conducted with emphasis on the previous five years, combining keywords such as "diabetes," "gallbladder," and "biliary". RESULTS: The association of diabetes to the formation of gallstones, gallbladder cancer, and cancer of the biliary tract are discussed along with diagnosis and treatment. CONCLUSION: Though we uncover the role of diabetic neuropathy in gallbladder and biliary complications, the specific individual diabetic risk factors behind these developments is unclear. Also, in addition to diabetes control and surgical gallbladder management, the treatment approach also requires further focus.

Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment.

BACKGROUND: Advances in treatment and increased awareness have improved the prognosis for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of 3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and secondary comorbidities. Previous research has provided evidence that increased renal sympathetic nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation (RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However, recent clinical trials have called into question RDN's efficacy. Numerous limitations must be addressed to discern the true effectiveness of RDN as a therapeutic option for RH. OBJECTIVE: We aimed to review the current understanding of RH, the anatomy of renal arteries, physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN as a treatment option, and all relevant clinical trials treating RH with RDN. METHODS: We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with emphasis on the previous five years, combining keywords such as "resistant hypertension" and "renal denervation." CONCLUSION: A plethora of information is available regarding heightened RSNA leading to RH. RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical understanding per individual basis, stricter guidelines regarding study design, increased operator experience, and integrating the use of a multielectrode catheter.

Juxtaglomerular Cell Tumor: Reviewing a Cryptic Cause of Surgically Correctable Hypertension.

Juxtaglomerular cell tumor (JGCT), or reninoma, is a typically benign neoplasm generally affecting adolescents and young adults due to modified smooth muscle cells from the afferent arteriole of the juxtaglomerular apparatus. Patients experience symptoms related to hypertension and hypoka-lemia due to renin-secretion by the tumor. MRI, PET, CT, and renal vein catheterizations can be used to capture JGCTs, with laparoscopic ultrasonography being most cost-efective. Surgical removal is the best option for management; electrolyte imbalances are a potential complication which may be assuaged via pre-surgical administration of aliskiren, a renin inhibitor. Considering the vast etiology for hypertension and rarity of JGCT, the diagnosing physician must have a high index of suspicion for JGCT. Early recognition and management can help prevent cardiovascular or pregnancy complications and fatalities, vascular invasion and metastasis, improve quality of life, and limit socioeconomic liabilities. Herein we review the epidemiology, genetics, histopathol-ogy, clinical presentation, and management of this rare condition. The impact of genetics on prognosis warrant further research.

The anticancer potential of metformin on prostate cancer.

BACKGROUND: Prostate cancer (PCa) is characterized as the most frequent type of cancer in males. Recent research has suggested patients who have diabetes mellitus taking metformin (MF) have a lower risk of PCa. MF has antineoplastic effects such as adenosine monophosphate-activated protein kinase (AMPK)-dependent and independent mechanisms, suppression of androgen signaling pathway, and alterations of insulin-like growth factor-1 (IGF-1) signaling pathways that cause the growth and proliferation of PCa. Based on epidemiological factors, patients with diabetes mellitus may have a protective effect on PCa. METHODS: A literature search on MEDLINE® was conducted using a combined query of "prostate cancer" and "metformin" to yield publications unveiling the mechanisms of action, biological effects, epidemiological evidence, and research advances of MF with respect to PCa. RESULTS: Evidence has shown that MF has multiple antineoplastic effects through AMPK-dependent and independent mechanisms, the alteration of IGF-1 signaling pathways, suppression of the androgen receptor pathway, inhibition of the mTOR pathway, and lipogenesis. Conduction of meta-analysis suggests mortality benefit to patients who exhibit PCa when taking MF. Clinical trials have shown evidence, demonstrating MF to improving significantly. CONCLUSIONS: Herewith we review the literature regarding the numerous mechanisms of action of MF on PCa in order to decrease or repress the growth, proliferation, and differentiation of PCa cells. We analyze the molecular impacts of MF as well as adjunct therapies such as androgen deprivation therapy, aspirin, statin, or chemotherapy, proposing that MF may have a future role in the treatment protocol of PCa whether as a monotherapy or in combination with other drugs.

Etiology, Diagnosis, and Management of Seminal Vesicle Stones.

BACKGROUND/AIMS: Seminal vesicle (SV) stones are a rare, and thus readily misdiagnosed condition in practice. Understanding the etiology, diagnosis, and management are crucial to guide a urologist's care, and are provided in this literature review. METHODS: The inclusion criteria for the literature search, using the search engines MEDLINE® and PubMed was conducted using a combined query of "seminal vesicle stone" and the following keywords: calculi, hematospermia, calcification, and transrectal ultrasound (TRUS). RESULTS: The etiology of SV stones is currently unknown where majority of the patients present with having painful ejaculation and hematospermia. However, clinicians have reported potential etiologies by categorization as an inflammatory or non-in-flammatory. A majority of the previous cases had shown multiple stones being present in the SV duct system that are typically diagnosed through radiological examination such as TRUS, MRI, or plain radiographs. Amongst the many imaging approaches, TRUS remains the primary imaging diagnoses of SV calculi. Transurethral seminal vesiculoscopy has shown to be used in an abundant of the case reports to be an ideal surgical approach for managing small SV stones. In regard to larger stones, a transperitoneal laparoscopic protocol is proper. CONCLUSION: The current imaging techniques have increased the case reports and diagnosis of SV calculi; however, more research is warranted for understanding the pathogenesis of the formation of SV stones. An optimal management of the extraction of SV stones depends on a number of factors such as size and location.