The Use of Neuromodulation for Symptom Management
Abstract
:1. Introduction
Methodology
2. Pain
Posterior Hypothalamus as a DBS Target for Cluster Headaches
3. Blood Pressure Control
3.1. Refractory Hypertension and Deep Brain Stimulation
3.2. PAG as a DBS Target for Hypertension
3.3. PAG as a DBS Target for Orthostatic Hypotension
3.4. Subthalamic Nucleus as a DBS Target for Orthostatic Hypotension
3.5. Posterior Hypothalamus as a DBS Target to Ameliorate Orthostatic Hypotension
4. Dyspnoea in Chronic Obstructive Airway Disease
5. Micturition
5.1. STN and Micturition
5.2. Thalamus and Micturition
5.3. PAG and Micturition
5.4. PPN and Micturition
5.5. The Potential of DBS for Other Intractable Symptoms
6. Cost Effectiveness of Neuromodulation for Intractable Suffering
7. Ethical Considerations for Symptom Management
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Author | N | Patient type | Target | Results | Conclusion |
---|---|---|---|---|---|
Holmberg et al. 2005 [34] | 19 DBS; 10 controls with no stimulation (optimally medicated) | PD a | STN b | After 1 year of treatment, HRV c and BP d during tilt was reduced compared to baseline; but no difference between stimulated and non-stimulated group. | No beneficial results for orthostatic hypotension. |
Green et al. 2005 [35] | 15 | PAG Chronic pain | PAG e | In patients at rest in a seated position, stimulation using dorsally located PAG electrodes produced an elevation of approximately 16mmHg in systolic BP, whereas stimulation using ventrally located PAG electrodes caused a decrease of approximately 14mmHg in this parameter. | PAG stimulation alters BP and is dependent on whether stimulation is dorsal or ventral. |
Lipp et al. 2005 [19] | 5 | PD | STN | Electrodes inadvertently placed close to posterior hypothalamus showed BP and respiratory rate increased after stimulation. | PHA f stimulation may increase BP. |
Green et al. 2006 [36] | 11 | PAG Chronic pain | PAG | Patients experienced decreased systolic BP in ’on’ stimulation when moving from sitting to standing; in one patient with clinical orthostatic hypotension, systolic BP fell by 15% from baseline (145–148 mmHg) on changing from a sitting to standing position without stimulation, compared with a change of only 0.1% on stimulation. For those with mild orthostatic hypotension the effects were reversed. For those with orthostatic hypotension, no side effects were experienced. | Stimulation of the PAG can prevent orthostatic hypotension. |
Stemper et al. 2006 [37] | 14 | PD | STN | DBS STN, increased HR, decreased blood flow to skin, and maintained BP after 60 degrees HUTT. | Beneficial results for orthostatic hypotension. |
Green et al. 2007 [38] | 1 | chronic pain (oral cavity/soft palate pain) | PAG | Hypertensive patient with PAG stimulation for Chronic pain experienced their baseline a fall in arterial pressure. | PAG may be suitable as a HTN treatment. |
Ludwig et al. 2007 [39] | 29 (14 DBS; 15 Controls | PD | STN | BP (and HR) during rest and orthostatic conditions did not differ significantly between groups. | No beneficial results of DBS for orthostatic hypotension. |
Cortelli et al. 2007 [40] | 8 | Cluster headache | PHA | During HUTT g systolic BP maintained when ’on’ stimulus but fell by 3% when ’off’. Ratio of low:high frequency components in HRV increased during on stimulation. | PHA stimulation could aid orthostatic hypotension. CV (including diastolic BP) changes appear to be hypothalamic-mediated sympathetic activation. |
Patel et al. 2011 [41] | 1 | central pain syndrome- left hemibody pain | PAG | Despite pain returning to baseline four months after surgery, DBS continued to affect BP as indicated by blood pressure rise of 18/5 mmHg. | Despite pain returning to baseline four months after surgery, DBS continued to affect BP thus affect of DBS on BP is not just relating to pain relief. |
Sverrisdottir et al. 2014 [42] | 17 (7 PAG, 10 STN) | chronic pain/ PD | STN | Increase in orthostatic tolerance. | Beneficial results for orthostatic hypotension. |
O’Callaghan et al. 2017 [43] | 1 | chronic pain | ventral PAG | After 6 months of chronic low frequency DBS of vPAG, BP lowered from 280 to 210–230 systolic. | Possible use of PAG as therapy for intractable HTN. |
Area | Title | Status | Conditions | Interventions | Locations |
---|---|---|---|---|---|
Blood Pressure | Deep Brain Stimulation for Autonomic and Gait Symptoms in Multiple System Atrophy | Recruiting | Multiple System Atrophy|Autonomic Failure|Postural Hypotension|Bladder, Neurogenic|Gait Disorders, Neurologic | Procedure: Deep brain stimulation | John Radcliffe Hospital, Oxford, Oxfordshire, United Kingdom |
Chronic pain | Deep Brain Stimulation (DBS) for Chronic Neuropathic Pain | Recruiting | Chronic Neuropathic Pain|Post Stroke Pain|Phantom Limb Pain|Spinal Cord Injuries | Device: Active DBS|Device: Inactive DBS | University of California, San Francisco, California, United States |
Chronic pain | Safety Study of Deep Brain Stimulation to Manage Thalamic Pain Syndrome | Completed | Chronic Pain | Device: Deep Brain Stimulation for Thalamic Pain Syndrome | Cleveland Clinic Foundation, Cleveland, Ohio, United States |
Chronic pain | Combined Cingulate and Thalamic DBS for Chronic Refractory Chronic Pain | Not yet recruiting | Chronic Refractory Neuropathic Pain | Procedure: Deep brain Stimulation of cingulum anterior | Department of neurosurgery, Nice, France |
Respiratory dysfunction | The Effects Of DBS Of Subthalamic Nucleus On Functionality In Patients With Parkinson’s Disease: Short-Term Results | Recruiting | Parkinson Disease|Surgery|Respiration; Decreased|Muscle Weakness | Device: Maximum Inspiratory Pressure and Maximum Expiratory Pressure | Hatay Mustafa Kemal University, Antakya, Hatay, Turkey |
Urinary dysfunction | Effect of Deep Brain Stimulation on Lower Urinary Tract Function | Completed | Movement Disorder|Urinary Tract Disease | Procedure: deep brain stimulation ON|Procedure: Deep brain stimulation OFF | Department of Neurology, University of Bern, Bern, Switzerland|Department of Urology, University of Bern, Bern, Switzerland |
Urinary dysfunction | Deep Brain Stimulation in Patients With LUTS | Recruiting | Bladder Dysfunction|Neurogenic Bladder | Other: Cohort | Houston Methodist Research Institute, Houston, Texas, United States |
Other dysfunction | Deep Brain Stimulation and Digestive Symptomatology | Completed | Parkinson’s Disease | not specified | Rouen University Hospital, Rouen, France |
Author | N | Patient Disease | Target | Outcome Measures | Results | Conclusion |
---|---|---|---|---|---|---|
Hyam et al. 2012 [61] | 17 chronic pain; 20 movement disorder; 7 control thalamus; 10 control Gpi | Movement disorder and chronic pain | STN a and PAG b (sensory thalamus and GPi c as control) | PEFR d,FEV1 e | STN and PAG improved PEFR but not FEV1; Patient with obstructive lung function showed improved FEV1 on stimulation. | Possible to control the lungs via the brain. |
Vigneri et al. 2012 [76] | 6 PD; 5 cluster headache | PD f and cluster headaches | STN and PHA g | RR h (and HR i, BP j) | No change on vs. off stimulation for any values when supine. | Failure to find effect. |
Xie et al. 2015 [77] | 1 | PD | STN | Respiratory dyskinesia | Stimulation relieved levodopa-induced respiratory distress even in medication ’on’ phase. | Not clear how DBS controls respiratory dyskinesia. |
Author | Patient N | Patient Type- Disease And Brain Area | Target | Outcome Measure | Results | Conclusion |
---|---|---|---|---|---|---|
Finazzi-Agro, Peppe et al. 2003 [88] | 5 | PD a | STN b bilateral | Bladder compliance and capacity, first desire to void volume, bladder volume (reflex volume) and amplitude of detrusor hyperreflexic contractions, maximum flow, detrusor pressure at maximum flow and detrusor-sphincter coordination | Bladder capacity and reflex volume were increased for ’on’ stimulation. No significant differences in other parameters. | STN stimulation seems to be effective for decreasing detrusor hyperreflexia in PD. Hence a role for basal ganglia in voiding control. |
Seif et al. 2004 [90] | 16 | PD | STN | Filled bladder with isotonic saline and measured intiial desire to void, maximal bladder capcity, detursor contractions, detrusor pressure, and compliance of bladder. | Maximal bladder cacpity and volume at desire to void are both significantly higher during ’on’ stimulation. | DBS of STN normalises ’storage’ phase of micturition. |
Herzog et al. 2006 [89] | 11 | PD | STN bilateral | PET c studies measuring regional cerebral blood flow to ACC d during bladder filling. | During bladder filling, ‘off’ stimulation demonstrates increased regional blood flow to ACC and lateral frontal cortex. | Stimulation aids more effective integration of afferent bladder information. |
Winge and Nielson 2010 [78] | 107 | PD | STN | Danish Prostate Symptom Score; International prostate symptom score. | Patients with DBS had lower reporting of nocturia compared to patients with apomorphine pumps. | STN DBS results in lower levels of nocturia. |
Green, Stone et al. 2012 [91] | 6 PAG; 2 control thalamus | Chronic pain | PAG e | Sensation of filling and desire to void during saline infusion ’on’ and ’off’ stimulation. | On’ stimulation: Volume urine first escaped from penis was higher ’on’, and subjective bladder capacity was increased. This did not affect volumes at which voiding was desired. | It is possible PAG stimulation can switch off micturition. |
Aviles-Olmos, Foltynie et al. 2011 [102] | 1 | PD | PPN f rt side | NA | Detrusor overactivity/urge incontinence after DBS surgery. Voiding normal. Symptoms improved 6 months post-op with antimuscarinics. | Involvement of pontine micturition centres resulted in urge uncontinence. |
Roy et al. 2018 [108] | 6 (5 complete) | PD | PPN bilateral | Bladder volume at maximal capacity (also looked at white matter tractography). | Increase in maximal bladder capacity when ’on’ stimulation. | PPN may be a target to alleviate some LUTD symptoms. |
Kessler, Burkhard et al. 2008 [92] | 7 | Essential Tremor | Thalamus | Bladder volume at first desire to void, maximal cystometric capacity. | Stimulation decreases bladder volume at ’first’ and ’strong’ desire to void, and maximal bladder capacity. | Thalamus may have a role in micturition but is not a target for rectifying dysfunction. |
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Farrell, S.M.; Green, A.; Aziz, T. The Use of Neuromodulation for Symptom Management. Brain Sci. 2019, 9, 232. https://doi.org/10.3390/brainsci9090232
Farrell SM, Green A, Aziz T. The Use of Neuromodulation for Symptom Management. Brain Sciences. 2019; 9(9):232. https://doi.org/10.3390/brainsci9090232
Chicago/Turabian StyleFarrell, Sarah Marie, Alexander Green, and Tipu Aziz. 2019. "The Use of Neuromodulation for Symptom Management" Brain Sciences 9, no. 9: 232. https://doi.org/10.3390/brainsci9090232