Inotersen to Treat Polyneuropathy Associated with Hereditary Transthyretin (hATTR) Amyloidosis.

Background: Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients. Results: Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver - where protein production takes place. Conclusion: hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of < 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level.

A Comprehensive Update of the Superior Hypogastric Block for the Management of Chronic Pelvic Pain.

PURPOSE OF REVIEW: This is a comprehensive review of the superior hypogastric block for the management of chronic pelvic pain. It reviews the background, including etiology, epidemiology, and current treatment available for chronic pelvic pain. It then presents the superior hypogastric block and reviews the seminal and most recent evidence about its use in chronic pelvic pain. RECENT FINDINGS: Several definitions exist for chronic pelvic pain (CPP), making the diagnosis more challenging for the clinician; however, they commonly describe continuous pain lasting 6 months in the pelvis, with an overwhelming majority of patients being reproductive-aged women. This pain is often one of mechanical, inflammatory, or neuropathic. It is generally underdiagnosed and affects anywhere between 5 and 26% of women. The diagnosis of chronic pelvic pain is clinical, consisting of mainly of a thorough history and physical and ruling out other causes. The pathophysiology is often endometriosis (70%) and also includes PID, adhesions, adenomyosis, uterine fibroids, chronic processes of the GI and urinary tracts, as well as pelvic-intrinsic musculoskeletal causes. Treatment includes physical therapy, cognitive behavioral therapy, and oral and parenteral opioids. Interventional techniques provide an added tier of treatment and may help to reduce the requirement for chronic opioid use. Superior hypogastric plexus block is one of the available interventional techniques; first described in 1990, it has been shown to provide long-lasting relief in 50-70% of patients who underwent the procedure. Two approaches described so far, both under fluoroscopy, have seen similar results. More recently, ultrasound and CT-guided procedures have also been described with similar success. The injectate includes local anesthetic, steroids, and neurolytic agents such as phenol or ethanol. CPP is a common debilitating condition. It is diagnosed clinically and is underdiagnosed globally. Current treatments can be helpful at times but may fall short of satisfactory pain relief. Interventional techniques provide an added layer of treatment as well as reduce the requirement for opioids. Superior hypogastric plexus block provides long-lasting relief in many patients, regardless of approach. Evidence level is limited, and further RCTs could help provide better tools for evaluation and patient selection.

Treatment and Management of Loin Pain Hematuria Syndrome.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Pharmacological options for the treatment of chronic migraine pain.

Migraine is a debilitating neurological condition with symptoms typically consisting of unilateral and pulsating headache, sensitivity to sensory stimuli, nausea, and vomiting. The World Health Organization (WHO) reports that migraine is the third most prevalent medical disorder and second most disabling neurological condition in the world. There are several options for preventive migraine treatments that include, but are not limited to, anticonvulsants, antidepressants, beta blockers, calcium channel blockers, botulinum toxins, NSAIDs, riboflavin, and magnesium. Patients may also benefit from adjunct nonpharmacological options in the comprehensive prevention of migraines, such as cognitive behavior therapy, relaxation therapies, biofeedback, lifestyle guidance, and education. Preventative therapies are an essential component of the overall approach to the pharmacological treatment of migraine. Comparative studies of newer therapies are needed to help patients receive the best treatment option for chronic migraine pain.