Renal sympathetic nervous system and the effects of denervation on renal arteries

Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal-as well as systemic-level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements.Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

Early changes of graft function,cytokines and superoxide dismutase serum levels after donor liver denervation and Kupffer cell depletion in a rat-to-rat liver transplantation model

BACKGROUND: Hepatic reperfusion injury may cause acute inflammatory damage, producing significant organ dysfunction, and is an important problem in liver transplantation. This experiment aimed to study early changes of hepatic function after donor liver denervation and Kupffer cell depletion in rat-to-rat liver transplantation and to evaluate the effect of pre-treatment on liver reperfusion injury. METHODS: Donor rats were divided into four groups: control group; group G was pre-treated with gadolinium chloride (G), an inhibitor of Kupffer cells; group H with hexamethonium (H), a sympathetic ganglionic blocking agent; and group HG, with combined H and G pre-treatment. Under the same conditions, serum alanine aminotransferase (ALT), arterial ketone body ratio (AKBR), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) of recipient rats were assessed at 4, 8, 16 and 24 hours after liver transplantation. Histological studies of the grafts were compared. RESULTS: HG pre-treatment significantly decreased ALT, TNF-alpha, and IL-6 levels, increased AKBR and SOD levels, and demonstrated less pathological damage at 8, 16 and 24 hours compared with the control group. Similar trends were also found in the other groups (G and H). However, the differences among them were not significant at 4 postoperative hours. CONCLUSIONS: Donor denervation and Kupffer cell depletion had preventive effect on liver reperfusion injury. HG pre-treatment is a feasible and reproducible method to protect grafts from reperfusion injury.

Renal sympathetic denervation in resistant hypertension

Resistant hypertension remains a major clinical problem despite the available multidrug therapy.Over the next decades,its incidence will likely increase given that it is strongly associated with older age and obesity.Resistant hypertension patients have an increased cardiovascular risk,thus effective antihypertensive treatment will provide substantial health benefits.The crosstalk between sympathetic nervous system and kidneys plays a crucial role in hypertension.It influences several pathophysiological mechanisms such as the central sympathetic tone,the sodium balance and the systemic neurohumoral activation.In fact,studies using several animal models demonstrated that the renal denervation prevented and attenuated hypertension in multiple species.Large reductions in blood pressure were also observed in malignant hypertension patients submitted to sympathectomy surgeries.However,these approaches had an unacceptably high rates of periprocedural complications and disabling adverse events.Recently,an innovative non-pharmacological therapy that modulates sympathetic activation has been successfully developed.Renal sympathetic percutaneous denervation is an endovascular procedure that uses radiofrequency energy to destroy the autonomic renal nerves running inside the adventitia of renal arteries.This method represents a promising new approach to the strategy of inhibiting the sympathetic nervous system.The aim of this review is to examine the background knowledge that resulted in the development of this hypertension treatment and to critically appraise the available clinical evidence.

Renal sympathetic denervation in therapy resistant hypertension-pathophysiological aspects and predictors for treatment success

Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheterinterventional renal sympathetic denervation(RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success.

Effects of renal sympathetic denervation on cardiac systolic function after myocardial infarction in rats

This study investigated the therapeutic effects of renal denervation on cardiac systolic function after myocardial infarction （MI） in rats and the mechanism involved. Fifty male SD rats were randomly assigned to the sham group （n = 15）, the MI group （n = 20）, and the MI plus renal denervation group （n = 15）. MI was established through thoracotomic ligation of the anterior descending artery. Renal denervation was achieved by laparotomic stripping of the renal arterial adventitial sympathetic nerve, approximately 3 mm from the abdominal aorta. Left ventricular function and hemodynamics were measured several weeks following MI. The left ventricular systolic function of the MI group was significantly reduced and the systolic blood pressure （SBP） remarkably declined. In rats with MI treated with renal denervation, the left ventricular ejection fraction （EF）, fractional shortening （FS） and SBP markedly improved compared with the MI group. However, heart rate and fibrosis decreased significantly. These findings suggest that renal denervation has therapeutic effects on post-MI cardiac dysfunction. These effects are associated with increased left ventricular ejection fraction （LVEF） and SBP, as well as reduced heart rate and fibrosis. This may represent a new approach to the treatment of post-MI remodeling and subsequent heart failure.

Renal artery denervation suppresses intractable ventricular arrhythmia in patients with left heart thrombosis

Transcutaneous renal artery denervation （RND） has beeninitially developed for destruction of efferent nerve fireswith luminal delivery of radiofrequency or ultrasonic energyaiming blood pressure reduction in patients with refractoryhypertension. However, other positive results of RNDwere described afterwards, and they include suppression ofatrial fibrillation and ventricular tachycardia （VT） storm.

Renal denervation as an option for the management of hypertension

Hypertension is a multifactorial condition which makes the development of treatment approaches difficult. The vast majority of patients are treated with lifestyle measures either alone or in combination with antihypertensive drugs, and this approach is largely successful in controlling blood pressure. However, for a subgroup of patients, control of blood pressure remains resistant to this approach and therefore the development of new strategies is im- perative. The sympathetic nervous system has been known to be implicated in hypertension for many decades, and evidence from studies in the past has revealed the benefit of reducing sympathetic nerve activity in the control of blood pressure albeit with severe side effects. Recent technological advances have allowed for specific targeting of the renal sympathetic nerves by catheter ablation. The Symplicity HTN-1 and HTN-2 trials have provided strong evidence for renal denervation giving rise to considerable blood pressure reductions in treatment-resistant hyper- tensives and, due to the high incidence of hypertension worldwide, this carries the promise of further reducing the global burden of hypertension and its attendant complications. Here we review the evidence for renal denervation in the management of hypertension.

Endovascular denervation(EDN):From Hypertension to Non-Hypertension Diseases

Recently,the use of endovascular denervation(EDN)to treat resistant hypertension has gained significant attention.In addition to reducing sympathetic activity,EDN might also have beneficial effects on pulmonary arterial hypertension,insulin resistance,chronic kidney disease,atrial fibrillation,heart failure,obstructive sleep apnea syndrome,loin pain hematuria syndrome,cancer pain and so on.In this article we will summarize the progress of EDN in clinical research.

Chemical renal artery denervation with appropriate phenol in spontaneously hypertensive rats

Objective To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). Methods RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. Results A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. Conclusion Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.

Changes following denervation to the masseter muscle

BACKGROUND： Masseter muscle nerve is often injured in mandible osteotomy. What changes in food intake and masseter muscle will be brought after masseter muscle nerve injury？ OBJECTIVE： This study was designed to selectively establish animal models of denervated masseter muscle and investigate the effects of severing masseter muscular nerve on masseter muscle and animal＇s food intake. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Laboratory Animal Center, Nanfang Hospital, Southern Medical University from September to November 2005. MATERIALS： A total of 50 healthy, adult, SPF-grade, New Zealand rabbits, of both genders, were used to develop an animal model of selectively denervated masseter muscle. METHODS： Five rabbits were randomly selected as normal controls. According to various mutilation methods, the remaining animals were randomly divided into 3 experimental groups, with 15 rabbits in each group： masseter muscular neural stem denervated, masseter muscular neural superior branch-denervated, and masseter muscular neural inferior brancb-denervated groups. Self-control comparison was performed on each animal. The right masseter muscle served as the experimental side, and the left masseter muscle served as the control side. In each group, 3 time points （2, 8, and 24 weeks post-surgery） were allotted for observation. MAIN OUTCOME MEASURES： At the pre-set time points, masseter muscular thickness was measured with a Logic 500 color Doppler ultrasonic diagnostic apparatus. Masseter muscle tissue was resected for hematoxylin eosin staining. Masseter muscular fiber diameter and area were measured with an optical microscope. Masseter muscle tissue was sectioned and nicotinamide adenine dinucleotide tetrazolium oxidoreductase （NADH-TR） and adenosine triphosphatase staining were performed. Following staining, the sections were quantitatively analyzed using an IBAS200 image analyzer. RESULTS： Post-surgery food intake： No abnormal food intake was found after surgery among the three groups. Intragroup comparison： In each experimental group, following denervation, masseter muscular thickness was decreased （P 〈 0.05） and masseter muscular fiber cross-section area was reduced in the experimental side compared to the control side （P 〈 0.05）. Inter-group comparison： There was a significant difference in masseter muscular thickness and masseter fiber cross-section area among the three experimental groups （P 〈 0.05）. There was no significant difference in masseter fiber type between the control side of the three experimental groups and the normal control group （P 〉 0.05）. CONCLUSION： Following various methods of masseter muscle denervation, masseter muscle thickness and masseter fiber cross-section area was reduced by varying degrees. Denervated masseter muscle did not influence food intake of experimental animals or alter masseter muscle fiber ratio.

Respiratory neuroplasticity following carotid body denervation Central and peripheral adaptations

Historically, the role of the carotid bodies in ventilatory control has been understated, but the current view suggests that the carotid bodies （1） provide a tonic, facilitory input to the respiratory network, （2） serve as the major site of peripheral 02 chemoreception and minor contributor to CO2/H＋ chemoreception, and （3） are required for ventilatory adaptation to high altitude. Each of these roles has been demonstrated in studies of ventilation in mammals after carotid body denervation. Following carotid body denervation, many of the compromised ventilatory ＂functions＂ show a time-dependent recovery plasticity that varies in the degree of recovery and time required for recovery. Respiratory plasticity following carotid body denervation is also dependent on species, with contributions from peripheral and central sites/mechanisms driving the respiratory plasticity. The purpose of this review is to provide a summary of the data pointing to peripheral and central mechanisms of plasticity following carotid body denervation. We speculate that after carotid body denervation there are altered excitatory and/or inhibitory neuromodulator mechanisms that contribute to the initial respiratory depression and the subsequent respiratory plasticity, and further suggest that the continued exploration of central effects of carotid body denervation might provide useful information regarding the capacity of the respiratory network for plasticity following neurologic injury in humans.

Renal Denervation:Past,Present,and Future

Over the past decade,percutaneous renal denervation has been vigorously investigated as a treatment for resistant hypertension.The SYMPLICITY radiofrequency catheter system(Medtronic CardioVascular Inc.,Santa Rosa,CA,USA)is the most tested device in clinical trials.After the positive results of small phase I and II clinical trials,SYMPLICITY HTN-3(a phase III,multi-center,blinded,sham-controlled randomized clinical trial)was completed in 2014,but did not show signifi cant blood pressure lowering effect with renal denervation compared to medical therapy and caused the investigators and industry to revisit both the basic science elements of renal denervation as well as the design of related clinical trials.This review summarizes the SYMPLICITY trials,analyzes the SYMPLICITY HTN-3 data,and provides insights gained from this trial in the design of the most recent clinical trial,the SPYRAL HTN Global clinical trial.Other than hypertension,the role of renal denervation in the management of other disease processes such as systolic and diastolic heart failure,metabolic syndrome,arrhythmia,and obstructive sleep apnea with the common pathophysiologic pathway of sympathetic overactivity is also discussed.

Comparison of a 5 F Microtube-Irrigated Ablation Catheter and a General Ablation Catheter in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To assess the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter.Methods:Sixty patients with resistant hypertension were divided into two groups:a microtube-irrigated ablation catheter group and a general ablation catheter group.We conducted 12-month follow-up of all patients and recorded clinical blood pressure,ambulatory blood pressure,medication use,and biochemistry test results in both groups at the baseline and at the 12-month follow-up.Results:All patients underwent renal denervation.At the 6-month follow-up,ambulatory blood pressure in the mi-crotube-irrigated ablation catheter group was signifi cantly lower than in the general ablation catheter group(systolic blood pressure 142.0±14.4 mmHg vs.150.8±17.9 mmHg,P=0.04;diastolic blood pressure 81.2±7.0 mmHg vs.87.6±8.0 mmHg,P=0.002).At the 12-month follow-up,the between-group difference in ambulatory blood pressure was not statistically signifi cant.At the 12-month follow-up,the number of antihypertensive drugs and diuretics used in the microtube-irrigated ablation catheter group was less than in the general ablation catheter group(P=0.043).There was no statistical difference between the two groups in the results of biochemistry tests and echocardiography.Conclusion:The microtube-irrigated ablation catheter is more effective in treating hypertension than the general ablation catheter at the 6-month follow up and thus fewer antihypertensive drugs were used in the microtube-irrigated ablation catheter group than in the general ablation catheter group.

Main Renal Artery Plus Branch Ablation in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To study the safety and effi cacy of denervation of renal artery branches in the treatment of resistant hy-pertension.Methods:Sixty patients with resistant hypertension were enrolled.The patients were randomly assigned to the main renal artery plus branch ablation group or the main renal artery ablation group.The clinical data and operation-related parameters,including number of ablation points,temperature,and average energy,were recorded.Ambulatory blood pressure was taken for all patients at the baseline and at 6 months after treatment.Offi ce blood pressure was recorded before treatment and after treatment every 3 months for 2 years.Results:Sixty patients with resistant hypertension were enrolled in this study.There were 30 patients in each group.Angiography was performed after ablation.No renal artery complications,such as stenosis and dissection,occurred in the two groups.There was no signifi cant difference in age,sex,BMI,comorbid disease,and medication between the two groups(P>0.05).The number of ablation points for the main renal artery plus branch ablation group was greater than that for the main renal artery ablation group.The offi ce blood pressure and 24-hour blood pressure were signifi cantly lower 6 months after treatment than before treatment in both groups(P<0.05).Offi ce blood pressure in the main renal artery plus branch ablation group was lower than that in the main renal artery ablation group during the 3-12-month follow-up period,with a statistical difference.However,as the follow-up time increased,the difference disappeared.Conclusion:The results of this study show that main renal artery plus branch ablation is a safe interventional method,but there was no obvious advantage on long-term follow-up compared with only main renal artery ablation.

Catheter-based renal sympathetic nerve denervation on hypertension management outcomes

BACKGROUND Renal sympathetic denervation(RSD)provides a minimally invasive interventional treatment modality for patients with resistant hypertension.However,the post-operative outcomes remain a key area of investigation since its earliest clinical trials.AIM To evaluate patient outcomes after RSD intervention among peer-reviewed patient cases.METHODS A systematic review of literature on MEDLINE,Google Scholar,and the Cochrane Database of Systematic Reviews for RSD case studies to assess post-operative hypertension readings and medical management.RESULTS Among 51 RSD cases,the post-operative RSD patients report an apparent reduction with a mean number of 3.1 antihypertensive medications.The mean systolic arterial blood pressure 1 year following RSD was 136.0 mmHg(95%CI:118.7-153.3).CONCLUSION The apparent improvements in office systolic blood pressure after 12 month postoperative RSD can support the therapeutic potential of this intervention for blood pressure reduction.Additional studies which utilized a uniform methodology for blood pressure measurement can further support the findings of this systematic review.

Fracture Healing in a Denervation and/or Nerve Ending Interpositioning Model in the Rat

Background: In this experimental study, we aimed to determine the possible changes in fracture healing due to denervation and/or nerve ending interpositioning. Methods: 50 Wistar Albino type male rats were divided into three study groups. A standard transverse diaphysial fracture in the femurs of the same side of all subjects under anesthesia was created and the fracture were fixed intramedullarily. While preserving the structural integrity of the sciatic nerve in the first group, neurectomy to the nerve in the second group was performed. In the third group, following the sciatic nerve cut, the proximal end of the nerve were interposed the fracture line. After a 28-day observational period, the callus formation in the subjects was examined radiologically, biomechanically and histopathologically. Results: Among all groups, the third group subjects showed significant increase in radiological area measurements when they are compared to the second group rats. There was no significant difference in biomechanical measurements of fractured femurs of the three groups. In histopathological evaluations, it was observed that denervation had increased the thickness of the cartilage and the number of the chondrocytes and osteoclasts significantly but decreased the number of fibroblasts compared to the control group. In addition to the denervation nerve ending interpositioning increased the bone thickness and the number of the osteoblasts but decreased the number of the osteoclasts significantly. Conclusions: While radiological observations exhibit that nerve ending interpositioning has resulted more hypertrophic callus formation, histopathological evaluations led us to that denervation created partial (immature) callus formation and nerve ending interpositioning demonstrated larger but immature callus formation.

The Effect of Renal Sympathetic Denervation (RSD) in Atrial Fibrillation (AF) Inducibility

Objective: The purpose of this study is to investigate the effects of renal sympathetic nerve stimulation (RSN-S) and ablation (RSN-A) on atrial effective refractory period (ERP) and AF in normal canine heart. Atrial Fibrillation (AF) is a complex disease and one of the most frequent arrhythmias, especially in elderly patients. Multiple mechanisms are involved including interaction between the autonomic nervous system (ANS), electrophysiological properties of the atria, and vulnerability for AF. Cardiac overload increases the incidence of AF. In lone AF the triggers are in the pulmonary veins. AF caused by underlying disease has different mechanism. Atrial fibrillation (AF) is associated with activity of renin-angiotensin-aldosterone system (RAAS). Reduction in renal nor-adrenaline spillover could be achieved after renal sympathetic denervation (RSD). Methods: 1) Establish of atrial fibrillation model;2) Ventricular rate analysis of AF;3) Statistical analysis. Results: 1) The establishment of atrial fibrillation model;2) Inducibility and duration of AF;3) The changes of AERP dispersion. Conclusion: Left RSN-S shortened left atrial ERP, increased ERP dispersion, but did not change right atrial ERP. Bilateral RSN-A produced significant prolongation in both atrial ERP, but did not affect ERP dispersion. The on time of RD effect is at 4 hrs after RD procedure and the RD effect on AF will last for 20 hrs after RD procedure.

Effects of Scopolamine on Blood Vessels in Rabbit Ear after Sympathetic and Sensory Denervation

Objectives To investigatethe effects and involved mechanisms of scopolamine(Scop) on rabbit ear blood vessels. Methods Rabbitear blood vessels were desympathetic and desensoryinnervation with surgical operation. Diameters of dor-sal auricular arterial trunks in vivo were measuredwith a pair of compasses and the ruler in a dissectingmicroscope, and effluents from isolated ear underconstant perfusion pressure were recorded with a digi-tal drop-recorder. Results Intramuscular injectionof Scop 0.1 mg/kg made the diameter of denerveddorsal auricular arterial trunks, as well as that of in-nerved ones, significantly increased. Scop by itself,atthe maximal concentration (Cmax) of 3μM, 30μMand 300μM, did not alter the effluent flow from theisolated denervated rabbit ear, but chlorpromazine(CPZ), at Cmax of 1μM, acetylcholine (ACh), 0.25μM, all significantly increased the effluent flow, andnorepinephrine (NE), 0.1μM, significantly decreasedthe effluent. Scop, 3μM, did not affect ACh (0.25μM)-induced the increase of effluent flow, but Scop,30μM, alleviated the increase. Scop, 3μM, did notaffect NE (0.1μM)-induced the decrease of effluentflow, but Scop, 10, 30 and 100μM, significantly alle-viated the decrease. Conclusions The study sug-gests that Scop has no direct vasodilator effect. Thevasodilator effect of Scop is not due to the blockade ofmuscarinic receptor. However, Scop can dilate bloodvessels contracted by α_1-adrenoceptor activation.

Effects of Denervation on the Mid-term Results of Knee Joint Functions after Non-resurfaced Total Knee Arthroplasty

Objective:Total knee arthroplasty(TKA)has become an effective treatment modality for end-stage osteoarthritis and rheumatoid arthritis.Postoperative problems such as anterior knee pain affect postoperative patient satisfaction.Patellar denervation has been proposed as a technique to relieve pain,but its efficacy remains controversial.This study evaluated the mid-and long-term effects of patellar denervation on postoperative knee joint functions,hoping to provide better guidance for clinical practice.Methods:This study is a prospective randomized controlled double-blind study.58 patients undergoing bilateral non-resurfaced total knee arthroplasty were included and randomized into two groups.Both groups underwent total knee arthroplasty while patellar denervation was performed only on the experimental group.Information regarding whether if patellar denervation was performed were withheld from all patients and outcome assessors.All surgeries were performed by the same high-level professional physician,and the post-stable knee prosthesis system(PS Scorpio NRG PS,Stryker)was used during the surgeries.The knee joint functions were evaluated by professional assessors before and after surgery.The evaluation indicators mainly include KSS scoring,Western Ontario and McMaster Universities(WOMAC)scoring and Visual Analogue Scale(VAS),FJS scoring,etc.The follow-up period was 3 years and 5 years after surgery.Results:The experimental group had better KSS and FJS scores than the control group,the difference was statistically significant.There was no significant inter-group difference in WOMAC and VAS scores.Conclusion:The patellar denervation in TKA patients has positive effects on the mid-and long-term recovery of knee joint functions,and the postoperative satisfaction is better.

Neurosurgical and pharmacological management of dystonia

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal posturing.Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention.For most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic alleviation.Pharmacological agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of patients.In more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of life.Deep brain stimulation(DBS)targets these anatomical locations to minimize dystonia symptoms.Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS.These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile.This review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.