Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review.

Objectives: The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population. Materials and Methods: We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options. Results: Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion. Conclusion: This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.

Vitamin D and Lupus: Are we doing enough?

The aim of this study is to identify rheumatology practice care gaps in evaluating for vitamin D deficiency in systemic lupus erythematosus (SLE), as well as adherence to vitamin D replacement in SLE patients currently on corticosteroid therapy. Data for this study were collected from the Southern California Lupus Registry in addition to data extraction from medical health records. Evaluation of serum vitamin D level within 6 months of patient encounter, current or prior use of systemic corticosteroids, and vitamin D replacement in patients receiving corticosteroid therapy were noted. Vitamin D deficiency was defined as serum 25(OH)D3 less than 30 ng/ml. Of 182 patients in the cohort, data were available for 176. Evaluation of vitamin D deficiency was noted in 49 patients (28%), 27 (55%) of whom had abnormal values. Current corticosteroid use was noted in 56 (32%) patients and prior use in 73 (41%). Vitamin D replacement was prescribed to 30 (54%) patients with current corticosteroid use. In an academic rheumatology clinic, we have identified underevaluation for vitamin D deficiency in SLE patients despite increasing awareness of its contribution to disease activity. Further, routine supplementation of vitamin D is particularly lacking in individuals receiving systemic corticosteroids. This presents a practical opportunity for improvement in SLE clinical care.

Movement Disorders in Chronic Kidney Disease - A Descriptive Review.

OBJECTIVES: The objective of this study is to describe the mechanism of damage to subcortical structures in chronic kidney disease (CKD) and to describe the range of movement disorders associated with CKD. MATERIALS AND METHODS: We have reviewed the Medline literature up to January of 2020 using key words movement disorders and chronic kidney disease. The reviewed articles were studied for mechanisms of subcortical damage in CKD as well as type of the reported movements, their frequency and updated treatment. RESULTS: The search revealed 183 articles most of them dealing with restless legs syndrome. The damage to basal ganglia in CKD resulted from several mechanisms including accumulation of nitro tyrosine caused by reactive oxygen species and action of uremic toxins leading to endothelial damage and dysfunction of blood-brain barrier. Involuntary movements in CKD include restless legs syndrome (RLS), myoclonus, asterixis, dystonia, chorea, tremor, and Parkinsonism. CONCLUSIONS: Chronic kidney disease can cause several abnormal involuntary movements via damaging basal ganglia and subcortical structures. The most common movement disorders in CKD are RLS, myoclonus and asterixis. Restless legs syndrome and myoclonus when severe, need and respond to treatment. Movement disorders in CKD improve with improvement of kidney function.

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms.

Downregulation of P-glycoprotein (P-gp) is implicated in the pathophysiology of inflammatory bowel disease (IBD). Berberine, a principal isoquinoline alkaloid extracted from Berberis species, has been reported to exhibit therapeutic potential in IBD. In this study, we used a dextran sulfate sodium (DSS)-induced colitis rat model to evaluate the effect of berberine on P-gp and explore its mechanism of action. Berberine treatment improved DSS-induced colitis symptoms, attenuated inflammatory markers (myeloperoxidase, tumor necrosis factor-α, and interleukin-1ß and -6), and enhanced P-gp expression in a dose-dependent manner. Although colonic expression of the P-gp-related nuclear receptor pregnane X receptor and transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) were downregulated in the colitis model, gene and protein expression analysis revealed that berberine treatment reversed only the downregulation of Nrf2. In vitro studies using Caco-2 cells showed that the multidrug resistance 1 (MDR1) gene and P-gp protein were upregulated by berberine in a dose- and time-dependent manner. Significant upregulation of the MDR1 gene by berberine was abrogated by Nrf2 silencing, indicating that the Nrf2-mediated pathway was responsible for this activation. Luciferase assays showed a dose-dependent increase in Nrf2 reporter gene activity after berberine treatment in Caco-2 cells, with a significant 2-fold elevation at 2.5 µM berberine, suggesting that berberine is a strong Nrf2 activator. These results indicate the possible involvement of Nrf2-mediated upregulation of P-gp in the therapeutic effect of berberine on colitis and highlight the potential of P-gp and/or Nrf2 as new therapeutic targets for IBD.

An investigation into symptoms, diagnosis, treatment, and treatment complications in patients with retrosternal goiter.

INTRODUCTION: Retrosternal goiter refers to any thyroid enlargement in which over 50% of the thyroid permanently located under the thoracic inlet or the lower pole of thyroid is not palpable with the neck in hyperextended position. Due to the increasing number of surgical procedures of retrosternal goiter, the present study was carried out to examine the symptoms, diagnosis, treatment, and treatment complications in retrosternal goiter patients. MATERIALS AND METHODS: Data related to demographic data (age and gender), clinical symptoms (dyspnea, dysphagia, dysphonia, lumps in neck, and hoarseness), methods of diagnosis (computed tomography [CT], chest X-ray [CXR], ultrasonography, and magnetic resonance imaging), and postoperative complications (bleeding, early and late dysphonia, early and late dyspnea, transient and permanent hypocalcemia, transient, and permanent recurrent laryngeal nerve paralysis) were collected. RESULTS: According to the results 71.4% of patients were women and most of the participants (67.1%) aged 45-60 years. Mass in the neck was the most frequent symptoms before surgery (88.6%). The most common incision for thyroidectomy (95/7%) was neck Collar incision. Diagnosis method in 82.9% and 17.1% of cases was, respectively, based on CT scans with CXR and CT scans with CXR and ultrasound. According to the postoperative pathologic findings, 58.5% of the cases were multinodular goiter, 22.9% were papillary cell carcinoma, 7.1% were medullary carcinoma, 5.7% were anaplastic carcinoma, 5.7% were thyroid lymphoma, and only 1.4% were thyroid adenoma. Postoperative complications occurred in 47.14% of patients. Most common complication was early transient dysphonia. CONCLUSION: This study recommends that retrosternal goiter should be operated early under suitable conditions, and the best diagnosis tool and best surgery methods are CT scan and surgery with collar incision, respectively.

Botulinum Toxin Treatment of Movement Disorders.

Botulinum neurotoxins (BoNTs) are now among the most widely used therapeutic agents in clinical medicine with indications applied to the fields of movement disorders, pain disorders, and autonomic dysfunction. In this literature review, the efficacy and utility of BoNTs in the field of movement disorders are assessed using the criteria of the Guideline Development Subcommittee of the American Academy of Neurology. The literature supports a level A efficacy (established) for BoNT therapy in cervical dystonia and a level B efficacy (probably effective) for blepharospasm, hemifacial spasm, laryngeal dystonia (spasmodic dysphonia), task-specific dystonias, essential tremor, and Parkinson rest tremor. It is the view of movement disorder experts, however, that despite the level B efficacy, BoNTs should be considered treatment of first choice for blepharospasm, hemifacial spasm, laryngeal, and task-specific dystonias. The emerging data on motor and vocal tics of Tourette syndrome and oromandibular dystonias are encouraging but the current level of efficacy is U (undetermined) due to lack of published high-quality studies.

Botulinum toxin treatment of pain syndromes -an evidence based review.

This review evaluates the existing level of evidence for efficacy of BoNTs in different pain syndromes using the recommended efficacy criteria from the Assessment and Therapeutic Subcommittee of the American Academy of Neurology. There is a level A evidence (effective) for BoNT therapy in post-herpetic neuralgia, trigeminal neuralgia, and posttraumatic neuralgia. There is a level B evidence (probably effective) for diabetic neuropathy, plantar fasciitis, piriformis syndrome, pain associated with total knee arthroplasty, male pelvic pain syndrome, chronic low back pain, male pelvic pain, and neuropathic pain secondary to traumatic spinal cord injury. BoNTs are possibly effective (Level C -one class II study) for female pelvic pain, painful knee osteoarthritis, post-operative pain in children with cerebral palsy after adductor release surgery, anterior knee pain with vastus lateralis imbalance. There is a level B evidence (one class I study) that BoNT treatment is probably ineffective in carpal tunnel syndrome. For myofascial pain syndrome, the level of evidence is U (undetermined) due to contradicting results. More high quality (Class I) studies and studies with different types of BoNTs are needed for better understanding of the role of BoNTs in pain syndromes.

Botulinum Toxin Treatment in Multiple Sclerosis-a Review.

Purpose of review The purpose of this review is to provide updated information on the role of botulinum neurotoxin (BoNT) therapy in multiple sclerosis (MS). This review aims to answer which symptoms of multiple sclerosis may be amenable to BoNT therapy. Recent findings We searched the literature on the efficacy of BoNTs for treatment of MS symptoms up to April 1st 2017 via the Yale University Library's search engine including but not limited to Pub Med and Ovis SP. The level of efficacy was defined according to the assessment's criteria set forth by the Subcommittee on Guideline Development of the American Academy of Neurology. Significant efficacy was found for two indications based on the available blinded studies (class I and II) and has been suggested for several others through open-label clinical trials. Summary There is level A evidence (effective- two or more class I) that injection of BoNT-A into the bladder's detrusor muscle improves MS-related neurogenic detrusor overactivity (NDO) and MS-related overactive (OA) bladder. There is level B evidence (probably effective- two class II studies) for utility of intramuscular BoNT-A injections for spasticity of multiple sclerosis. Emerging data based on retrospective class IV studies demonstrates that intramuscular injection of BoNTs may help other symptoms of MS such as focal tonic spasms, focal myokymia, spastic dysphagia, and double vision in internuclear ophthalmoplegia. There is no data on MS-related trigeminal neuralgia and sialorrhea, two conditions which have been shown to respond to BoNT therapy in non-MS population.