Archive for category Pharmacological

[ARTICLE] Practice patterns for spasticity management with phenol neurolysis – Full Text HTML

Abstract

Objective: To present practice patterns for phenol neurolysis procedures conducted for spasticity management.

Design: A retrospective review of 185 persons with spasticity who underwent phenol neurolysis procedures (n = 293) at an academic rehabilitation hospital and clinic. Patient demographics, concomitant spasticity treatments, and procedure relevant information were collected.

Results: The cohort included 71.9% males and 61.6% inpatient procedures. Neurological diagnoses included stroke (41.0%), traumatic brain injury (28.6%) and spinal cord injury (24.3%). Musculoskeletal diagnoses included spastic hemiplegia or paresis (51.3%), tetraplegia (38.4) and paraplegia (9.2%). At the time of phenol neurolysis, most patients (77.5%) received concomitant pharmacological treatments for spasticity. Injection guidance modalities included electrical stimulation and ultrasound (69.3%) or ultrasound only (27.3%). A mean of 3.48 ml of phenol were injected per nerve and 10.95 ml of phenol were used per procedure. Most commonly injected nerves included the obturator nerve (35.8%) and sciatic branches to the hamstrings and adductor magnus (27.0%). Post-phenol neurolysis assessment was recorded in 54.9% of encounters, in which 84.5% reported subjective benefit. Post-procedure adverse events included pain (4.0%), swelling and inflammation (2.7%), dysaesthesia (0.7%) and hypotension (0.7%).

Conclusion: Phenol neurolysis is currently used to reduce spasticity for various functional goals, including preventing contractures and improving gait. Depending on the pattern of spasticity displayed, numerous peripheral nerves in the upper and lower extremities can be targeted for treatment with phenol neurolysis. Further research into its role in spasticity management, including studies exploring its cost-effectiveness and pharmacological and side-effects compared with other treatment options are needed.

Introduction

Characterized by hyperexcitable stretch reflexes that increase muscle tonicity and exaggerate tendon jerks, spasticity is a common motor disorder that follows a variety of central nervous system insults (1). Implicated neurological insults most often include stroke, traumatic brain injury (TBI) or spinal cord injury (SCI). Spasticity is often associated with various complications including joint contractures, muscle shortening and postural deformities (1) that lead to multiple impairments. Early goal-directed spasticity management is instrumental in helping increase the likelihood of good outcomes and limiting complications (1, 2). Unfortunately, a lack of universally standardized management and an abundance of therapeutic options make spasticity management a challenging task.

Currently, spasticity is frequently managed through a combination of therapeutic modalities, pharmaceutical options and surgical procedures (3). Pharmaceutical options include medications delivered orally, via local injections, or through intrathecal pumps. Oral medications, including baclofen and tizanidine, help decrease spasticity (3). However, systemic side-effects, such as generalized muscle weakness, sedation, confusion, and hypotension, preclude the use of higher dosages that might be warranted for control of moderate-to-severe spasticity (3, 4). Intrathecal baclofen pump (ITB) is often indicated in treating severe and/or diffuse spasticity as a means to deliver high-dosage baclofen with less concern for systemic side-effects (4). Although ITB treatment is very effective, numerous complications and the requirement for commitment to maintenance associated with this treatment makes it favourable only for some patients with severe spasticity (4, 5).

Chemoneurolysis via localized injections can help provide focal spasticity relief (1, 3, 6). In addition, the use of single-event multi-level chemoneurolysis helps treat several areas of muscle spasticity, each with varying severities (7). Medications used in chemo-neurolysis procedures include botulinum neurotoxin (BoNT), phenol, and alcohol neurolysis (3–7). Compared with phenol and the understudied alcohol neurolysis, BoNT usage in treating spasticity is documented extensively in the literature with regards to pharmacodynamics, adverse effects and clinical benefits (7–9). However, the response to chemodenervation with BoNT often requires 3–5 days to generate spasticity benefit, which generally lasts approximately 3 months. Although clinical standards permit repeating chemodenervation every 3 months, the majority of patients with spasticity prefer an increased frequency for maintaining clinical benefit (10–12). BoNT injections are associated with significant costs, and repeated injections are often further restricted by financial feasibility. In the USA, depending on the insurance being used, the approved dosage of BoNT is only 400–600 units of every 3 months. These limitations prevent the sole utility of chemodenervation for a multi-pattern treatment, e.g. elbow flexion, clenched fist, stiff knee gait, and equinovarus of the foot. Consequently, phenol neurolysis (PN) and BoNT are used in complement, with PN frequently reserved for proximal nerves and BoNT used for distal musculature.

In contrast, PN produces an almost-immediate effect that manifests within minutes of injection, which may last as long as 6 months depending on the dosage used (1, 13). In addition, PN is significantly less expensive. PN may also be re-injected before 3 months, unlike BoNT. However, the safety and efficacy of PN is less-commonly documented in the literature than BoNT chemodenervation. PN also requires a higher level of expertise to administer, and has a worse side-effect profile, which includes hypotension, prolonged pain, dysaesthesias, site inflammation, and joint fibrosis (1, 13, 14). These disadvantages for phenol usage are associated with safety concerns relative to neurotoxins, thus making BoNT a vastly more popular option for chemoneurolysis. Phenol is therefore being used increasingly less in the USA and is poorly documented in the spasticity literature. Given its advantages, PN may be superior to chemodenervation with BoNT in certain clinical scenarios. Thus, the primary purpose of the current study is to describe the utilization pattern of PN at a single site.

 

Continue —> Journal of Rehabilitation Medicine – Practice patterns for spasticity management with phenol neurolysis – HTML

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[ARTICLE] Role of Interleukin-10 in Acute Brain Injuries – Full Text

 

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation.

Introduction

Stroke and traumatic brain injury (TBI) are devastating acute neurological disorders that can result in high mortality rates or long-lasting disability. Approximately 87% of strokes are ischemic and 13% are hemorrhagic, with 10 and 3% of the latter representing intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), respectively (1). Stroke is the fourth most common cause of death in the United States, and ischemic stroke (IS) in particular is the seventh most frequent emergency department presentation (2, 3). TBI and concussions have over twice the incidence of all strokes combined (4), with more than three million people in the United States alone living with long-term disability as a result of TBI (5). Collectively, stroke and TBI have very few treatments, and despite advances in clinical management of these disorders, they are still associated with significant disability and mortality (6, 7).

Inflammation plays a central role in the pathophysiology of stroke and TBI and can have both protective and harmful effects on brain tissue (815). Although there are some distinct differences in the inflammatory cascades following the various types of acute brain injury, there are also numerous commonalities. Acute neuroinflammation is characterized by the activation of resident central nervous system (CNS) immune surveillance glial cells that release cytokines, chemokines, and other immunologic mediators, which facilitate the recruitment of peripheral cells such as monocytes, neutrophils, and lymphocytes (8, 9, 12, 15). Collectively, this initial response is helpful in the clearance of toxic entities and the restoration and repair of damaged tissue. However, during the resolution phase, with an uncontrolled and prolonged inflammatory response, secondary damage results from overactivation of this inflammatory surge and release of additional factors that led to breakdown of the blood–brain barrier (BBB), cerebral edema, cerebral hypertension, and ischemia.

Interleukin-10 is generally known as an anti-inflammatory cytokine that exerts a plethora of immunomodulatory functions during an inflammatory response and is particularly important during the resolution phase. Expression of IL-10 in the brain increases with CNS pathology, promoting neuronal and glial cell survival, and dampening of inflammatory responses via a number of signaling pathways (16). IL-10 was originally described as cytokine synthesis inhibitory factor and in addition to attenuating the synthesis of proinflammatory cytokines, IL-10 also limits inflammation by reducing cytokine receptor expression and inhibiting receptor activation (16). Furthermore, IL-10 has potent and diverse effects on essentially all hematopoetic cells that infiltrate the brain following injury. For example, IL-10 reduces the activation and effector functions of T cells, monocytes, and macrophages, ultimately ending the inflammatory response to injury (17). The structure, function, and regulation of IL-10 have been extensively reviewed elsewhere, including a review of IL-10 in the brain (1620), although not in the context of the various forms of acute brain injury. Please refer to the aforementioned reviews for additional details, including the potential cellular sources, target cells, signal transduction, and mode of action of IL-10.

Given the intriguing multifactorial role of IL-10 in the resolution of inflammatory cascades that are important for promoting neurologic recovery from acute brain injury, here we present a comprehensive literature review of preclinical and clinical studies in this area. We focus on the contribution of IL-10 in modulating various important parameters and pathophysiologic processes important for IS, SAH, ICH, and TBI outcomes, and whether IL-10 has therapeutic or biomarker potential. A better understanding of the many functions of IL-10 in the brain after injury, particularly in the resolution phase of inflammatory processes, will promote our knowledge of the pathophysiology of these debilitating disorders and guide future development of novel therapeutic approaches.[…]

Continue —> Frontiers | Role of Interleukin-10 in Acute Brain Injuries | Neurology

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[Abstract+References] Does the method of botulinum neurotoxin injection for limb spasticity affect outcomes? A systematic review 

 

To systematically review randomized controlled trials of botulinum neurotoxin for limb spasticity to determine whether different injection techniques affect spasticity outcomes.

MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials electronic databases were searched for English language human randomized controlled trials from 1990 to 13 May 2016. Studies were assessed in duplicate for data extraction and risk of bias using the Physiotherapy Evidence Database scale and graded according to Sackett’s levels of evidence.

Nine of 347 studies screened met selection criteria. Four categories of botulinum neurotoxin injection techniques were identified: (1) injection localization technique; (2) injection site selection; (3) injectate volume; (4) injection volume and site selection. There is level 1 evidence that: ultrasound, electromyography, and electrostimulation are superior to manual needle placement; endplate injections improve outcomes vs. multisite quadrant injections; motor point injections are equivalent to multisite injections; high volume injections are similar to low volume injections; and high volume injections distant from the endplate are more efficacious than low volumes closer to the endplate.

Level 1 evidence exists for differences in treatment outcomes using specific botulinum neurotoxin injection techniques. Findings are based on single studies that require independent replication and further study.

 

1. Francisco GEVaughn ABotulinum toxin in upper limb. Am J Phys Med Rehabil 2002; 81(5): 355363Google Scholar CrossRefMedline
2. Moher DLiberati ATetzlaff JAltman DGPreferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009; 6(7): e1000097Google Scholar CrossRefMedline
3. Snow BJTsui JKBhatt MHVarelas MHashimoto SACalne DBTreatment of spasticity with botulinum toxin: A double-blind study. Ann Neurol 1990; 28(4): 512515Google Scholar CrossRefMedline
4. Moher DJadad ARNichol GPenman MTugwell PWalsh SAssessing the quality of randomized controlled trials: An annotated bibliography of scales and checklists. Control Clin Trials 1995; 16(1): 6273.Google Scholar CrossRefMedline
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6. Moseley AMHerbert RDSherrington CMaher CGEvidence for physiotherapy practice: A survey of the Physiotherapy Evidence Database (PEDro). Aust J Physiother 2002; 48(1): 4349Google Scholar CrossRefMedline
7. Lui JSarai MMills PBChemodenervation for treatment of limb spasticity following spinal cord injury: A systematic review. Spinal Cord 2015; 53(4): 252264Google Scholar CrossRefMedline
8. Mills PBFung CKTravlos AKrassioukov ANonpharmacologic management of orthostatic hypotension: A systematic review. Arch Phys Med Rehabil 2015; 96(2): 366375.e6Google Scholar CrossRefMedline
9. Centre for Evidence-Based Medicine. Reflections on David Sackett’s time at the Centre for Evidence-Based Medicine. Available at: www.cebm.net/ (accessed 15 March 2015).
10. Eng JTeasell RMiller W, . Spinal cord injury rehabilitation evidence: Method of the SCIRE systematic review. Top Spinal Cord Inj Rehabil 2007; 13(1): 110Google Scholar CrossRefMedline
11. Picelli ATamburin SBonetti P, . Botulinum toxin type A injection into the gastrocnemius muscle for spastic equinus in adults with stroke: A randomized controlled trial comparing manual needle placement, electrical stimulation and ultrasonography-guided injection techniques. Am J Phys Med Rehabil 2012; 91(11): 957964Google Scholar CrossRefMedline
12. Picelli ALobba DMidiri A, . Botulinum toxin injection into the forearm muscles for wrist and fingers spastic overactivity in adults with chronic stroke: A randomized controlled trial comparing three injection techniques. Clin Rehabil 2014; 28(3): 232242Google Scholar Link
13. Ploumis AVarvarousis DKonitsiotis SBeris AEffectiveness of botulinum toxin injection with and without needle electromyographic guidance for the treatment of spasticity in hemiplegic patients: A randomized controlled trial. Disabil Rehabil 2014; 36(4): 313318Google Scholar CrossRefMedline
14. Santamato AMicello MFPanza F, . Can botulinum toxin type A injection technique influence the clinical outcome of patients with post-stroke upper limb spasticity? A randomized controlled trial comparing manual needle placement and ultrasound-guided injection techniques. J Neurol Sci 2014; 347(1–2): 3943Google Scholar CrossRefMedline
15. Gracies JMLugassy MWeisz DJVecchio MFlanagan SSimpson DMBotulinum toxin dilution and endplate targeting in spasticity: A double-blind controlled study. Arch Phys Med Rehabil 2009; 90(1): 916.e2Google Scholar CrossRefMedline
16. Childers MKPt DLHenry HComparision of two injection techniques using botulinum toxin in spastic hemiplegia. Am J Phys Med Rehabil 1996; 75(6): 462469Google Scholar CrossRefMedline
17. Im SPark JHSon SKShin J-ECho SHPark G-YDoes botulinum toxin injection site determine outcome in post-stroke plantarflexion spasticity? Comparison study of two injection sites in the gastrocnemius muscle: A randomized double-blind controlled trial. Clin Rehabil 2014; 28(6): 604613Google Scholar Link
18. Mayer NHWhyte JWannstedt GEllis CComparative impact of 2 botulinum toxin injection techniques for elbow flexor hypertonia. Arch Phys Med Rehabil 2008; 89(5): 982987Google Scholar CrossRefMedline
19. Picelli ABonetti PFontana C, . Accuracy of botulinum toxin type A injection into the gastrocnemius muscle of adults with spastic equinus: Manual needle placement and electrical stimulation guidance compared using ultrasonography. J Rehabil Med 2012; 44(5): 450452Google Scholar CrossRefMedline
20. Deshpande SGormley MECarey JRMuscle fiber orientation in muscles commonly injected with botulinum toxin: An anatomical pilot study. Neurotox Res 2006; 9(2–3): 115120Google Scholar CrossRefMedline
21. Braddom R. Physical Medicine and Rehabilitation. Philadelphia, PAElsevier Saunders2011180pp. Google Scholar
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23. World Health Organization. International Classification of Functioning, Disability and Health (ICF). World Health Organization, http://www.who.int/classifications/icf/icf_more/en/ (accessed 27 March 2014).

Source: Does the method of botulinum neurotoxin injection for limb spasticity affect outcomes? A systematic reviewClinical Rehabilitation – Aaron K Chan, Heather Finlayson, Patricia B Mills, 2017

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[ARTICLE] Practice patterns for spasticity management with phenol neurolysis – HTML

Abstract

Objective: To present practice patterns for phenol neurolysis procedures conducted for spasticity management.

Design: A retrospective review of 185 persons with spasticity who underwent phenol neurolysis procedures (n = 293) at an academic rehabilitation hospital and clinic. Patient demographics, concomitant spasticity treatments, and procedure relevant information were collected.

Results: The cohort included 71.9% males and 61.6% inpatient procedures. Neurological diagnoses included stroke (41.0%), traumatic brain injury (28.6%) and spinal cord injury (24.3%). Musculoskeletal diagnoses included spastic hemiplegia or paresis (51.3%), tetraplegia (38.4) and paraplegia (9.2%). At the time of phenol neurolysis, most patients (77.5%) received concomitant pharmacological treatments for spasticity. Injection guidance modalities included electrical stimulation and ultrasound (69.3%) or ultrasound only (27.3%). A mean of 3.48 ml of phenol were injected per nerve and 10.95 ml of phenol were used per procedure. Most commonly injected nerves included the obturator nerve (35.8%) and sciatic branches to the hamstrings and adductor magnus (27.0%). Post-phenol neurolysis assessment was recorded in 54.9% of encounters, in which 84.5% reported subjective benefit. Post-procedure adverse events included pain (4.0%), swelling and inflammation (2.7%), dysaesthesia (0.7%) and hypotension (0.7%).

Conclusion: Phenol neurolysis is currently used to reduce spasticity for various functional goals, including preventing contractures and improving gait. Depending on the pattern of spasticity displayed, numerous peripheral nerves in the upper and lower extremities can be targeted for treatment with phenol neurolysis. Further research into its role in spasticity management, including studies exploring its cost-effectiveness and pharmacological and side-effects compared with other treatment options are needed.

Introduction

Characterized by hyperexcitable stretch reflexes that increase muscle tonicity and exaggerate tendon jerks, spasticity is a common motor disorder that follows a variety of central nervous system insults (1). Implicated neurological insults most often include stroke, traumatic brain injury (TBI) or spinal cord injury (SCI). Spasticity is often associated with various complications including joint contractures, muscle shortening and postural deformities (1) that lead to multiple impairments. Early goal-directed spasticity management is instrumental in helping increase the likelihood of good outcomes and limiting complications (1, 2). Unfortunately, a lack of universally standardized management and an abundance of therapeutic options make spasticity management a challenging task.

Currently, spasticity is frequently managed through a combination of therapeutic modalities, pharmaceutical options and surgical procedures (3). Pharmaceutical options include medications delivered orally, via local injections, or through intrathecal pumps. Oral medications, including baclofen and tizanidine, help decrease spasticity (3). However, systemic side-effects, such as generalized muscle weakness, sedation, confusion, and hypotension, preclude the use of higher dosages that might be warranted for control of moderate-to-severe spasticity (3, 4). Intrathecal baclofen pump (ITB) is often indicated in treating severe and/or diffuse spasticity as a means to deliver high-dosage baclofen with less concern for systemic side-effects (4). Although ITB treatment is very effective, numerous complications and the requirement for commitment to maintenance associated with this treatment makes it favourable only for some patients with severe spasticity (4, 5).

Chemoneurolysis via localized injections can help provide focal spasticity relief (1, 3, 6). In addition, the use of single-event multi-level chemoneurolysis helps treat several areas of muscle spasticity, each with varying severities (7). Medications used in chemo-neurolysis procedures include botulinum neurotoxin (BoNT), phenol, and alcohol neurolysis (3–7). Compared with phenol and the understudied alcohol neurolysis, BoNT usage in treating spasticity is documented extensively in the literature with regards to pharmacodynamics, adverse effects and clinical benefits (7–9). However, the response to chemodenervation with BoNT often requires 3–5 days to generate spasticity benefit, which generally lasts approximately 3 months. Although clinical standards permit repeating chemodenervation every 3 months, the majority of patients with spasticity prefer an increased frequency for maintaining clinical benefit (10–12). BoNT injections are associated with significant costs, and repeated injections are often further restricted by financial feasibility. In the USA, depending on the insurance being used, the approved dosage of BoNT is only 400–600 units of every 3 months. These limitations prevent the sole utility of chemodenervation for a multi-pattern treatment, e.g. elbow flexion, clenched fist, stiff knee gait, and equinovarus of the foot. Consequently, phenol neurolysis (PN) and BoNT are used in complement, with PN frequently reserved for proximal nerves and BoNT used for distal musculature.

In contrast, PN produces an almost-immediate effect that manifests within minutes of injection, which may last as long as 6 months depending on the dosage used (1, 13). In addition, PN is significantly less expensive. PN may also be re-injected before 3 months, unlike BoNT. However, the safety and efficacy of PN is less-commonly documented in the literature than BoNT chemodenervation. PN also requires a higher level of expertise to administer, and has a worse side-effect profile, which includes hypotension, prolonged pain, dysaesthesias, site inflammation, and joint fibrosis (1, 13, 14). These disadvantages for phenol usage are associated with safety concerns relative to neurotoxins, thus making BoNT a vastly more popular option for chemoneurolysis. Phenol is therefore being used increasingly less in the USA and is poorly documented in the spasticity literature. Given its advantages, PN may be superior to chemodenervation with BoNT in certain clinical scenarios. Thus, the primary purpose of the current study is to describe the utilization pattern of PN at a single site. […]

Continue —> Journal of Rehabilitation Medicine – Practice patterns for spasticity management with phenol neurolysis – HTML

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[ARTICLE] Influence of physician empathy on the outcome of botulinum toxin treatment for upper limb spasticity in patients with chronic stroke: A cohort study – Full Text

Abstract

Objective: To examine the relationship between patient-rated physician empathy and outcome of botulinum toxin treatment for post-stroke upper limb spasticity.

Design: Cohort study.

Subjects: Twenty chronic stroke patients with upper limb spasticity.

Methods: All patients received incobotulinumtoxinA injection in at least one muscle for each of the following patterns: flexed elbow, flexed wrist and clenched fist. Each treatment was performed by 1 of 5 physiatrists with equivalent clinical experience. Patient-rated physician empathy was quantified with the Consultation and Relational Empathy Measure immediately after botulinum toxin treatment. Patients were evaluated before and at 4 weeks after botulinum toxin treatment by means of the following outcome measures: Modified Ashworth Scale; Wolf Motor Function Test; Disability Assessment Scale; Goal Attainment Scaling.

Results: Ordinal regression analysis showed a significant influence of patient-rated physician empathy (independent variable) on the outcome (dependent variables) of botulinum toxin treatment at 4 weeks after injection, as measured by Goal Attainment Scaling (p < 0.001).

Conclusion: These findings support the hypothesis that patient-rated physician empathy may influence the outcome of botulinum toxin treatment in chronic stroke patients with upper limb spasticity as measured by Goal Attainment Scaling.

Introduction

Stroke is a leading cause of adult disability (1, 2). Damage to the descending tracts and sensory-motor networks results in the positive and negative signs of the upper motor neurone syndrome (UMNS) (1–3). The upper limb is commonly involved after stroke, with up to 69% of patients having arm weakness on admission to hospital (4). Recovery of upper limb function has been found to correlate with the degree of initial paresis and its topical distribution according to the cortico-motoneuronal representation of arm movements (5–9).

Spasticity is a main feature of UMNS. It is defined as a state of increased muscle tone with exaggerated reflexes characterized by a velocity-dependent increase in resistance to passive movement (10). Upper limb spasticity has been found to be associated with reduced arm function, low levels of independence and high burden of direct care costs during the first year post-stroke (11). It affects nearly half of patients with initial impaired arm function, with a prevalence varying from 17% to 38% of all patients at one year post-stroke (11). Up to 13% of patients with stroke need some form of spasticity treatment (drug therapy, physical therapy or other rehabilitation approaches) within 6–12 months post-onset (11, 12). Botulinum toxin type A (BoNT-A) has been proven safe and effective for reducing upper limb spasticity and improving arm passive function in adult patients (13, 14). While current literature reports highly patient-specific potential gains in function after BoNT-A treatment, there is inadequate evidence to determine the efficacy of BoNT-A in improving active function associated with adult upper limb spasticity (13).

Empathy refers to the ability to understand and share the feelings, thoughts or attitudes of another person (15). It is an essential component of the physician-patient relationship and a key dimension of patient-centred care (15, 16). This is even more important in rehabilitation medicine, where persons with disabilities often report encountering attitudinal and environmental barriers when trying to obtain rehabilitative care and express the need for better communication with their healthcare providers (17).

To the best of our knowledge, no previous research has investigated the influence of physician empathy on patient outcome after spasticity treatment. The aim of this study was to examine the relationship between patient-rated physician empathy and clinical outcome of BoNT-A treatment for upper limb spasticity due to chronic stroke. […]

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[WEB SITE] Epilepsy drug therapies to be improved by new targeted approach

Published: Wednesday 17 May 2017

New research from the University of Liverpool, in collaboration with the Mario Negri Institute in Milan, published in the Journal of Clinical Investigation, has identified a protein that could help patients with epilepsy respond more positively to drug therapies.

Epilepsy continues to be a serious health problem and is the most common serious neurological disease. Despite 30 years of drug development, approximately 30% of people with epilepsy do not become free of fits (also called seizures) with currently available drugs.

New, more effective drugs are therefore required for these individuals. We do not fully understand why some people develop seizures, why some go onto develop epilepsy (continuing seizures), and most importantly, why some patients cannot be controlled with current drugs.

Inflammation

There is now increasing body of evidence suggesting that local inflammation in the brain may be important in preventing control of seizures. Inflammation refers to the process by which the body reacts to insults such as having a fit. In most cases, the inflammation settles down, but in a small number of patients, the inflammation continues.

The aim of the research, undertaken by Dr Lauren Walker while she was a Medical Research Council (MRC) Clinical Training Fellow, was to address the important question of how can inflammation be detected by using blood samples, and whether this may provide us with new ways of treating patients in the future to reduce the inflammation and therefore improve seizure control.

The research focused on a protein called high mobility group box-1 (HMGB1), which exists in different forms in tissues and bloodstream (called isoforms), as it can provide a marker to gauge the level of inflammation present.

Predicting drug response

The results showed that there was a persistent increase in these isoforms in patients with newly-diagnosed epilepsy who had continuing seizure activity, despite anti-epileptic drug therapy, but not in those where the fits were controlled.

An accompanying drug study also found that HMGB1 isoforms may predict how an epilepsy patient’s seizures will respond to anti-inflammatory drugs.

Dr Lauren Walker, said: “Our data suggest that HMGB1 isoforms represent potential new drug targets, which could also identify which patients will respond to anti-inflammatory therapies. This will require evaluation in larger-scale prospective trials.”

Innovative scheme

Professor Sir Munir Pirmohamed, Director of the MRC Centre for Drug Safety Science and Programme lead for the MRC Clinical Pharmacology scheme, said: “The MRC Clinical Pharmacology scheme is a highly successful scheme to train “high flyers” who are likely to become future leaders in academia and industry.

“Dr Walker’s research is testament to this and shows how this innovative scheme, which was jointly funded by the MRC and Industry, can tackle areas of unmet clinical need, and identify new ways of treating patients with epilepsy using a personalised medicine approach”.

Article: Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy, Lauren Elizabeth Walker et al., Journal of Clinical Investigation, doi: 10.1172/JCI92001, published 15 May 2017.

Source: Epilepsy drug therapies to be improved by new targeted approach – Medical News Today

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[WEB SITE] Can Ritalin Help Mitigate Brain Injury Symptoms?

 Question

My 54-year-old husband sustained a TBI when he fell asleep at the wheel while driving and hit a tree. The doctors say that he damaged all four parts of his brain. It’s been more than one and a half years and he’s still totally dependent on me to take care of him. Do you think Ritalin would help stimulate his brain?

Answer

Methylphenidate (Ritalin) is one of the commonly used brain stimulants in people who have suffered traumatic brain injury. It increases chemicals in the brain that have a stimulating effect (norepinephrine and dopamine).

After traumatic brain injury, doctors commonly prescribe Ritalin for low arousal or initiation, poor attention and concentration, depression, and slow processing speed. There is research that shows that Ritalin may speed recovery early after moderate to severe TBI. There is also research showing that Ritalin increases mental processing speed after TBI, which can improve memory function in some people.

All medications have side effects and the risks need to be weighed against possible benefits. One of the good things about the standard formulation of Ritalin is that it is short acting so if side effects occur they wear off in a few hours. Some potential side effects include keeping you up at night (if taken too close to bedtime), decreased appetite, headache, irritability, and paranoia.

In your husband’s case, his doctor needs to look at why he is so dependent. If arousalattention, and/or initiation are playing a significant role, a stimulant can be considered. Careful monitoring for effects and/or side effects is needed when starting this medication and it should only be done by a doctor who has experience in caring for people with traumatic brain injury. Ritalin and most stimulants are controlled substances and will require frequent visits to the doctor for prescriptions.

Source: Can Ritalin Help Mitigate Brain Injury Symptoms?

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[ARTICLE] Pharmacological interventions for traumatic brain injury – Full Text 

Psychostimulants, antidepressants, and other agents may speed the recovery of patients suffering from the functional deficits that follow an insult to the brain.

Traumatic brain injury is common in North America and has dramatic and wide-ranging effects on survivors’ quality of life. Those who survive traumatic brain injury may experience anxiety, agitation, memory impairments, and behavioral changes. When managing the immediate and long-term consequences of such injuries, clinicians have many pharmacological options, including psychostimulants, antidepressants, antiparkinsonian agents, and anticonvulsants. These and other agents can play a role in managing the neuropsychiatric, neurocognitive, and neurobehavioral sequelae of injury to the brain.

Traumatic brain injury (TBI) is commonly defined as an insult to the brain from an external force that causes temporary or permanent impairment in functional, psychosocial, or physical abilities.1 It is a significant cause of morbidity and mortality, and the leading cause of death and disability among young adults.

Common causes of TBI include motor vehicle accidents, falls, sports injuries, and violence,[1] and it is recog­nized increasingly in war zone injury.[2] In the US, approximately 2 million people will sustain a TBI each year, one-quarter of whom will require hospitalization, leading to a conservative estimate of direct and indirect costs of $50 billion to $100 billion annually.[3]

With advances in the management of head trauma, an increasing number of patients are surviving with residual neurological impairments. A National Institute of Health panel estimates that 2.5 to 6.5 million Americans currently live with TBI-related disabilities.[4]

The effective treatment of TBI requires input from multiple disciplines and professions starting at the time of injury and continuing through the rehabilitation phase.

Despite the prevalence and cost of TBI-related disabilities there is a paucity of literature reviewing modern approaches to pharmacotherapy. There is, however, growing evidence that medications may speed recovery by enhancing some neurological functions without impact­ing others.

Pharmacotherapy is in­creasingly being used in both the subacute (less than 1 month post-TBI) and chronic (more than 1 month post-TBI) phases.

Disabilities arising from TBI that have a direct impact on functioning and rehabilitative potential can be broadly classified into four main categories: decreased level of consciousness (LOC), and neuropsychiatric, neurocognitive, and neurobehavioral sequelae.5-8 Decreased level of consciousness refers to a diverse range of clinical states including coma, vegetative states, akinetic mutism, and locked-in states.

Neuropsychiatric symp­toms may present as mood disorders, posttraumatic stress disorder, and personality changes characterized by disinhibition and egocentricity. Neurocognitive injuries vary, but most frequently involve impaired attention, memory, and executive functioning.

Neurobehavioral deficits distinct from neuropsychiatric sequelae may take the form of irritability, hyperexcitability, nervousness, disinhibition, poor impulse control, restlessness, and aggression, with aggression and agitation seen in as many as 30% of brain-injured patients.[5-8]

Depending on the location of in­jury, damage can occur to a variety of neurotransmitter networks critical to cognitive processes. Investigation has focused on the loss of dopaminergic neurons that regulate executive functioning, as well as deficits in norepinephrine and acetylcholine, which limit attention—a critical function for effective rehabilitation.[9]

Fortunately, a number of pharmacological interventions show promise in helping patients cope with these losses and deficits.

Although insufficient evidence exists to establish guidelines for optimal pharmocotherapy, medications may be used to support recovery. Examples are shown in the accompanying Table, which summarizes the pharmacological approaches discussed in more detail below.

When problematic TBI symptoms are identified, clinicians can use this information to determine pharmacological options and integrate them with nonpharmacological options such as physical therapy, occupational therapy, physiatry, and the patient’s support network.

Planning a pharmacological intervention strategy
The decision to use pharmacological intervention should be the result of multidisciplinary collaboration and made with the patient or his or her substitute decision maker. Goals of therapy should be clarified, and outcomes and adverse events should be reliably tracked, particularly so medications that are ineffective or cause adverse events can be discontinued and unnecessary polypharmacy can be avoided.

Selecting the most appropriate agent requires careful analysis of the neurological disabilities present, the nature of the underlying lesion, and the time elapsed since the injury.

Psychostimulants
Psychostimulants such as methylpheni­date are most commonly used to treat attention deficit hyperactivity disorder (ADHD), a condition that involves problems with executive functioning and can be characterized as similar to brain injury both in terms of symptoms and neurotransmitter aberrations.[10]

Although the complete mechanism of action of methylphenidate remains unknown, this agent is thought to bind dopamine transporters, thereby blocking reuptake and increasing extracellular dopamine levels, particularly in the frontal cortex.[11] It is also thought to increase norepinephrine and serotonin levels.

In the majority of studies, methylphenidate has been administered  twice daily, either at a fixed dose of 10 to 15 mg or at a dose of 0.3 mg/kg.[12-15]

In the acute phase after a TBI, methylphenidate-treated patients dem­onstrated better attention, concentration, and performance on motor memory tasks at 1 month, but these benefits did not persist at 3 months. Thus, it has been suggested that while methyl­phenidate may shorten recovery time, it does not change morbidity.[12]

In the chronic phase after a TBI, patients have reported improvements in mood, work performance, and alertness, with more limited evidence suggesting an improvement of fluency and selective attention.

The impact of methylphenidate on chronic attention is more ambiguous: one study suggests improvement in long-term processing speed and attention to tasks but not increased sustained attention or decreased susceptibility to distraction.[12]

Two separate studies have suggested methylphenidate is effective in the treatment of agitation and sei­zures,[16,17] while another demonstrated no neurobehavioral benefit.[18]

Despite the accumulation of controlled clinical trials, there is no consensus on the use of stimulants in treating TBI-induced impairments in arousal and motor activity.

It should be noted that one recent review concluded “at present there is insufficient evidence to support routine use of methylphenidate or other amphetamines to promote recovery from TBI,”[19] while another review noted that at least 10 clinical trials have demonstrated a role for methylpheni­date in both adult and pediatric brain injury patients suffering from neurocognitive deficits, particularly in attention, memory, cognitive processing, and speech.[20]

Methylphenidate has a quick onset of action and relatively benign side effect profile, and we believe it to be useful in both the acute and chronic phase of TBI.

Antidepressants
Despite potentially severe consequenc­es, post-TBI psychiatric sequelae are underdiagnosed and undertreated. Fortunately, current evidence suggests that antidepressants can be used to manage both neuropsychiatric and additional neurological deficits persisting from brain injury.

Selective serotonin reuptake inhi­bitors (SSRIs) have been found useful in treating behavioral syndromes in TBI patients, particularly in the subacute stages of recovery[21] but also in chronic settings.

The majority of studies suggest that SSRIs improve neurobehavioral, neurocognitive, and neuropsychiatric deficits, specifically agitation, depression, psychomotor retardation, and recent memory loss; however, most data originates from nonrandomized trials.

Sertraline administered at an average dose of 100 mg daily for 8 weeks has been found to be beneficial for agitation, depressed mood, and deficits in psychomotor speed and recent memory; shorter treatment durations have demonstrated no benefit.[21]

Similarly, 60 mg daily of fluoxetine for 3 months was shown to be effective in the treatment of obsessive-compulsive disorder caused by brain injury.[22] Finally, paroxetine or citalopram, at a dose of 10 to 40 mg daily, was shown by another study to be equally effective in the treatment of pathological crying.[23] None of the re­viewed studies addressed neurocognitive deficits.

The highest concentration of serotonergic and adrenergic fibres is located near the frontal lobes, the most common site of traumatic contusion.[24]

Consequently, these fibres are commonly injured in TBI, suggesting that newer antidepressants with effects on both norepinephrine and serotonin, such as mirtazapine and venlafaxine, may also be effective in the treatment of TBI sequelae; however, clinical data with these agents in TBI is lacking.

Similarly, bupropion increases both dopamine and norepinephrine levels and is a weak inhibitor of serotonin reuptake. At 150 mg daily, this agent has been useful in treating restlessness.[25]

Antiparkinsonian drugs
The antiparkinsonian drugs amantadine, bromocriptine, and levodopa combined with carbidopa (e.g., Sine­met) have varied mechanisms of action, but all ultimately serve to increase dopamine levels in the brain.

Amantadine acts presynaptically to enhance dopamine release or inhibit its reuptake, and can act postsynaptically to increase the number, or alter the configuration of, dopamine re­ceptors.[26] It is also a noncompetitive NMDA receptor antagonist and may provide protection against possible glutamate-mediated excitotoxicity in the context of TBI.[27]

Bromocriptine is a dopamine receptor agonist affecting primarily D2 receptors and to a lesser extent D1 receptors.[28] The use of levodopa and carbidopa in combination directly increases dopamine levels: levodopa becomes dopamine once de­carboxylated, while carbidopa inhibits L-amino decarboxylase, allowing levodopa to reach the central nervous system.[28]

Multiple studies of amantadine at a dose of 100 to 300 mg daily have suggested its effectiveness in both the acute and chronic care phases after TBI, particularly in diffuse, frontal, or right-sided brain injury.

Currently, the evidence suggests neurocognitive or neurobehavioral deficits, particularly cognition difficulties and agitation, are primary indications for amantadine use.[26,29,30]

Amantadine-treated patients demonstrated improvements in motivation; decreased level of apathy; increased attention, concentration, and alertness; improved executive functioning; decreased processing time; reduced agitation, distractibility, fatigue, aggression, and anxiety.

In addition, patients treated with amantadine demonstrated changes in outcome LOC, specifically improved arousal and LOC as measured by the Glasgow Coma Scale. Interestingly, one study also suggested decreased mortality.[31] To date, no study has shown an improvement in memory.

Three case reports using 5 to 45 mg of bromocriptine daily,[32] and one study using a combination of 100 mg of bromocriptine with 100 mg of ephedrine,[33] showed improvement in akinetic mutism, while another study using 5 mg of bromocriptine combined with sensory stimulation led to improvements in patients with vegetative or minimal consciousness.[34]

The evidence is similarly limited for levidopa and carbidopa medications where nonrandomized studies suggest that they might be useful in the chronic phase of TBI with diffuse injury and persistent vegetative state.[35]

Combining agents has also been tried in one study that found improvements in neuropsychiatric deficits with the daily administration of 25 mg/200 mg of levodopa/carbidopa three times daily, 250 mg of amantadine, and 5 mg of bromocriptine twice daily.[36]

Anticonvulsants
Anticonvulsants have been used with varying results for treating symptoms of TBI. Valproic acid, for example, enhances inhibitory control mediated by the neurotransmitter GABA, thereby promoting general central nervous system stabilization, but findings thus far have been mixed.

Investigations utilizing 600 to 2250 mg of valproic acid daily (resulting in serum levels of 40 to 100 µg/mL), have demonstrated positive neurocognitive effects, in­cluding improved recent memory and problem-solving, as well as ameliorating neuropsychiatric and neuro­behavioral symptoms such as depression, mania, destructive and aggressive behavior, restlessness, disinhibition, impulsivity, lability, and alertness.[37-41]

Conversely, one control­led trial found valproic acid negatively impacted decision-making speed, and another suggested an increased mortality rate with valproic acid use.[37-41]

Other agents
Modafinil is a vigilance-promoting drug commonly used to treat narcolepsy and idiopathic hypersomnia, illnesses that can present with symptoms similar to those seen in TBI: excessive daytime sleepiness, inattention, and decreased ability to perform social activities.

The precise mechanism of action remains unknown, although it is believed that modafinil can inhibit GABA or increase glutamate levels in the nondopaminergic anterior hypothalamus, hippocampus, and amygdale.[42,43]

Two studies that investigated the role of modafinil in chronic TBI showed an improvement in neurocognitive deficits, specifically memory and attention, as well as improving daytime somnolence at doses between 100 and 400 mg.[44,45]

Four randomized control trials examining the use of beta-blockers, specifically propranolol and pindolol, have demonstrated beneficial effects on neurobehavioral symptoms of ag­gression and agitation in both the chronic and subacute phase. This class of drugs deserves further attention for the management of both neuropsychiatric and neurobehavioral sequelae of TBI.[46]

Neuroleptics are being used in­creasingly in the setting of delirium, and one might consider using them in an attempt to allow the brain to recalibrate neurotransmitter levels. However, it should be noted that there is some evidence that dopamine blockade may negatively affect recovery.[47,48]

There are also a number of animal studies examining drugs that have the potential to adversely affect brain recovery following TBI. These studies typically use a stroke model, so generalizing to TBI may not be possible.

Nevertheless, the evidence currently does not support the use of neuro­leptics, benzodiazepines, phen­y­toin, prazosin, trazodone, and similar agents because of their potential adverse effect on recovery, presumably through the impacts they have on neurotransmitters such as dopamine, norepinephrine, or GABA.[49-51]

Preliminary evidence suggests cho­linesterase inhibitors such as don­epezil may improve long-term cognitive outcomes, particularly in domains such as memory and attention when administered early, and further in­vestigation with these agents is also warranted.[52,53]

Finally, antiandrogenic medications, such as estrogen and medroxyprogesterone, may have a role to play in reducing inappropriate sexual be­havior in patients with TBI. In a case study and one small trial, these drugs demonstrated effectiveness.[54]

Summary
The nature of TBI sequelae, whether psychiatric, cognitive, or behavioral, is poorly understood. Likewise, the use of pharmacological interventions to improve symptoms, function, and outcome is still under development.

There are, however, a number of agents that inspire optimism. When treating neurological deficits medically, there is evidence to support the tailored use of these agents for particular TBI clinical scenarios. The timing and nature of symptoms, along with wheth­er agents are administered in the acute or chronic phase after TBI, are all relevant factors for determining proper use.

With insufficient evidence to establish guidelines for optimal treatment, care must be taken when choosing pharmacological interventions for TBI.

If the decision is made to use medications to promote TBI recovery or treat its attendant disabilities, clinicians should thoroughly document the goals of pharmacotherapy and closely monitor for side effects. Future studies will undoubtedly add to the clinician’s armamentarium for the care of TBI patients.

Competing interests
None declared.


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Source: Pharmacological interventions for traumatic brain injury | BC Medical Journal

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[WEB SITE] Cannabidiol shows promise to reduce seizures for people with difficult-to-treat epilepsy

Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study that will be presented at the American Academy of Neurology’s 69th Annual Meeting in Boston, April 22 to 28, 2017. Cannabidiol is a molecule from the cannabis plant that does not have the psychoactive properties that create a “high.”

Nearly 40 percent of people with LGS, which starts in childhood, had at least a 50 percent reduction in drop seizures when taking a liquid form of cannabidiol compared to 15 percent taking a placebo.

When someone has a drop seizure, their muscle tone changes, causing them to collapse. Children and adults with LGS have multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which involve loss of consciousness and full-body convulsions. The seizures are hard to control and usually do not respond well to medications. Intellectual development is usually impaired in people with LGS.

Although the drop seizures of LGS are often very brief, they frequently lead to injury and trips to the hospital emergency room, so any reduction in drop seizure frequency is a benefit.

“Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control,” said study author Anup Patel, MD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine in Columbus and a member of the American Academy of Neurology.

For the randomized, double-blind, placebo-controlled study, researchers followed 225 people with an average age of 16 for 14 weeks. The participants had an average of 85 drop seizures per month, had already tried an average of six epilepsy drugs that did not work for them and were taking an average of three epilepsy drugs during the study.

Participants were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol or placebo as an add-on to their current medications for 14 weeks.

Those taking the higher dose had a 42 percent reduction in drop seizures overall, and for 40 percent, their seizures were reduced by half or more.

Those taking the lower dose had a 37 percent reduction in drop seizures overall, and for 36 percent, seizures were reduced by half or more.

Those taking the placebo had a 17 percent reduction in drop seizures, and for 15 percent, seizures were reduced by half or more.

There were side effects for 94 percent of those taking the higher dose, 84 percent of those taking the lower dose and 72 percent of those taking placebo, but most side effects were reported as mild to moderate. The two most common were decreased appetite and sleepiness.

Those receiving cannabidiol were up to 2.6 times more likely to say their overall condition had improved than those receiving the placebo, with up to 66 percent reporting improvement compared to 44 percent of those receiving the placebo.

“Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures,” said Patel. “This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients.”

There is currently a plan to submit a New Drug Application to the FDA later this year.

Source: Cannabidiol shows promise to reduce seizures for people with difficult-to-treat epilepsy

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[TED Talk] David Casarett: A doctor’s case for medical marijuana

Subtitles and Transcript

0:12 I would like to tell you about the most embarrassing thing that has ever happened to me in my years of working as a palliative care physician. This happened a couple of years ago. I was asked as a consultant to see a woman in her 70s — retired English professor who had pancreatic cancer. I was asked to see her because she had pain, nausea, vomiting … When I went to see her, we talked about those symptoms and in the course of that consultation, she asked me whether I thought that medical marijuana might help her. I thought back to everything that I had learned in medical school about medical marijuana, which didn’t take very long because I had learned absolutely nothing. And so I told her that as far as I knew, medical marijuana had no benefits whatsoever. And she smiled and nodded and reached into the handbag next to the bed, and pulled out a stack of about a dozen randomized controlled trials showing that medical marijuana has benefits for symptoms like nausea and pain and anxiety. She handed me those articles and said, “Maybe you should read these before offering an opinion … doctor.”

1:29 (Laughter)

1:30 So I did. That night I read all of those articles and found a bunch more. When I came to see her the next morning, I had to admit that it looks like there is some evidence that marijuana can offer medical benefits and I suggested that if she really was interested, she should try it. You know what she said? This 73-year-old, retired English professor? She said, “I did try it about six months ago. It was amazing. I’ve been using it every day since. It’s the best drug I’ve discovered. I don’t know why it took me 73 years to discover this stuff. It’s amazing.”

2:10 (Laughter)

2:11 That was the moment at which I realized I needed to learn something about medical marijuana because what I was prepared for in medical school bore no relationship to reality.

2:22 So I started reading more articles, I started talking to researchers, I started talking to doctors, and most importantly, I started listening to patients. I ended up writing a book based on those conversations, and that book really revolved around three surprises — surprises to me, anyway. One I already alluded to — that there really are some benefits to medical marijuana. Those benefits may not be as huge or as stunning as some of the most avid proponents of medical marijuana would have us believe, but they are real. Surprise number two: medical marijuana does have some risks. Those risks may not be as huge and as scary as some of the opponents of medical marijuana would have us believe, but they are real risks, nonetheless. But it was the third surprise that was most … surprising. And that is that a lot of the patients I talked with who’ve turned to medical marijuana for help, weren’t turning to medical marijuana because of its benefits or the balance of risks and benefits, or because they thought it was a wonder drug, but because it gave them control over their illness. It let them manage their health in a way that was productive and efficient and effective and comfortable for them.

3:37 To show you what I mean, let me tell you about another patient. Robin was in her early 40s when I met her. She looked though like she was in her late 60s. She had suffered from rheumatoid arthritis for the last 20 years, her hands were gnarled by arthritis, her spine was crooked, she had to rely on a wheelchair to get around. She looked weak and frail, and I guess physically she probably was, but emotionally, cognitively, psychologically, she was among the toughest people I’ve ever met. And when I sat down next to her in a medical marijuana dispensary in Northern California to ask her about why she turned to medical marijuana, what it did for her and how it helped her, she started out by telling me things that I had heard from many patients before. It helped with her anxiety; it helped with her pain; when her pain was better, she slept better. And I’d heard all that before. But then she said something that I’d never heard before, and that is that it gave her control over her life and over her health. She could use it when she wanted, in the way that she wanted, at the dose and frequency that worked for her. And if it didn’t work for her, then she could make changes. Everything was up to her. The most important thing she said was she didn’t need anybody else’s permission — not a clinic appointment, not a doctor’s prescription, not a pharmacist’s order. It was all up to her. She was in control.

5:00 And if that seems like a little thing for somebody with chronic illness, it’s not — not at all. When we face a chronic serious illness, whether it’s rheumatoid arthritis or lupus or cancer or diabetes, or cirrhosis, we lose control. And note what I said: “when,” not “if.” All of us at some point in our lives will face a chronic serious illness that causes us to lose control. We’ll see our function decline, some of us will see our cognition decline, we’ll be no longer able to care for ourselves, to do the things that we want to do. Our bodies will betray us, and in that process, we’ll lose control. And that’s scary. Not just scary — that’s frightening, it’s terrifying. When I talk to my patients, my palliative care patients, many of whom are facing illnesses that will end their lives, they have a lot of be frightened of — pain, nausea, vomiting, constipation, fatigue, their impending mortality. But what scares them more than anything else is this possibility that at some point, tomorrow or a month from now, they’re going to lose control of their health, of their lives, of their healthcare, and they’re going to become dependent on others, and that’s terrifying.

6:17 So it’s no wonder really that patients like Robin, who I just told you about, who I met in that clinic, turn to medical marijuana to try to claw back some semblance of control. How do they do it though? How do these medical marijuana dispensaries — like the one where I met Robin — how do they give patients like Robin back the sort of control that they need? And how do they do it in a way that mainstream medical hospitals and clinics, at least for Robin, weren’t able to? What’s their secret? So I decided to find out.

6:54 I went to a seedy clinic in Venice Beach in California and got a recommendation that would allow me to be a medical marijuana patient. I got a letter of recommendation that would let me buy medical marijuana. I got that recommendation illegally, because I’m not a resident of California — I should note that. I should also note, for the record, that I never used that letter of recommendation to make a purchase, and to all of you DEA agents out there —

7:21 (Laughter)

7:22 love the work that you’re doing, keep it up.

7:25 (Laughter)

7:26 Even though it didn’t let me make a purchase though, that letter was priceless because it let me be a patient. It let me experience what patients like Robin experience when they go to a medical marijuana dispensary. And what I experienced — what they experience every day, hundreds of thousands of people like Robin — was really amazing. I walked into the clinic, and from the moment that I entered many of these clinics and dispensaries, I felt like that dispensary, that clinic, was there for me. There were questions at the outset about who I am, what kind of work I do, what my goals are in looking for a medical marijuana prescription, or product, what my goals are, what my preferences are, what my hopes are, how do I think, how do I hope this might help me, what am I afraid of. These are the sorts of questions that patients like Robin get asked all the time. These are the sorts of questions that make me confident that the person I’m talking with really has my best interests at heart and wants to get to know me.

8:33 The second thing I learned in those clinics is the availability of education. Education from the folks behind the counter, but also education from folks in the waiting room. People I met were more than happy, as I was sitting next to them — people like Robin — to tell me about who they are, why they use medical marijuana, what helps them, how it helps them, and to give me advice and suggestions. Those waiting rooms really are a hive of interaction, advice and support.

9:03 And third, the folks behind the counter. I was amazed at how willing those people were to spend sometimes an hour or more talking me through the nuances of this strain versus that strain, smoking versus vaporizing, edibles versus tinctures — all, remember, without me making any purchase whatsoever. Think about the last time you went to any hospital or clinic and the last time anybody spent an hour explaining those sorts of things to you. The fact that patients like Robin are going to these clinics, are going to these dispensaries and getting that sort of personalized attention and education and service, really should be a wake-up call to the healthcare system. People like Robin are turning away from mainstream medicine, turning to medical marijuana dispensaries because those dispensaries are giving them what they need.

9:57 If that’s a wake-up call to the medical establishment, it’s a wake-up call that many of my colleagues are either not hearing or not wanting to hear. When I talk to my colleagues, physicians in particular, about medical marijuana, they say, “Oh, we need more evidence. We need more research into benefits, we need more evidence about risks.” And you know what? They’re right. They’re absolutely right. We do need much more evidence about the benefits of medical marijuana. We also need to ask the federal government to reschedule marijuana to Schedule II, or to deschedule it entirely to make that research possible. We also need more research into medical marijuana’s risks. Medical marijuana’s risks — we know a lot about the risks of recreational use, we know next to nothing about the risks of medical marijuana. So we absolutely do need research, but to say that we need research and not that we need to make any changes now is to miss the point entirely. People like Robin aren’t seeking out medical marijuana because they think it’s a wonder drug, or because they think it’s entirely risk-free. They seek it out because the context in which it’s delivered and administered and used, gives them the sort of control they need over their lives. And that’s a wake-up call we really need to pay attention to.

11:16 The good news though is that there are lessons we can learn today from those medical marijuana dispensaries. And those are lessons we really should learn. These are often small, mom-and-pop operations run by people with no medical training. And while it’s embarrassing to think that many of these clinics and dispensaries are providing services and support and meeting patients’ needs in ways that billion-dollar healthcare systems aren’t — we should be embarrassed by that — but we can also learn from that. And there are probably three lessons at least that we can learn from those small dispensaries.

11:51 One: we need to find ways to give patients more control in small but important ways. How to interact with healthcare providers, when to interact with healthcare providers, how to use medications in ways that work for them. In my own practice, I’ve gotten much more creative and flexible in supporting my patients in using drugs safely to manage their symptoms — with the emphasis on safely. Many of the drugs I prescribe are drugs like opioids or benzodiazepines which can be dangerous if overused. But here’s the point. They can be dangerous if they’re overused, but they can also be ineffective if they’re not used in a way that’s consistent with what patients want and need. So that flexibility, if it’s delivered safely, can be extraordinarily valuable for patients and their families. That’s number one.

12:39 Number two: education. Huge opportunities to learn from some of the tricks of those medical marijuana dispensaries to provide more education that doesn’t require a lot of physician time necessarily, or any physician time, but opportunities to learn about what medications we’re using and why, prognoses, trajectories of illness, and most importantly, opportunities for patients to learn from each other. How can we replicate what goes on in those clinic and medical dispensary waiting rooms? How patients learn from each other, how people share with each other.

13:13 And last but not least, putting patients first the way those medical marijuana dispensaries do, making patients feel legitimately like what they want, what they need, is why, as healthcare providers, we’re here. Asking patients about their hopes, their fears, their goals and preferences. As a palliative care provider, I ask all my patients what they’re hoping for and what they’re afraid of. But here’s the thing. Patients shouldn’t have to wait until they’re chronically seriously ill, often near the end of life, they shouldn’t have to wait until they’re seeing a physician like me before somebody asks them, “What are you hoping for?” “What are you afraid of?” That should be baked into the way that healthcare is delivered.

13:58 We can do this — we really can. Medical marijuana dispensaries and clinics all across the country are figuring this out. They’re figuring this out in ways that larger, more mainstream health systems are years behind. But we can learn from them, and we have to learn from them. All we have to do is swallow our pride — put aside the thought for a minute that because we have lots of letters after our name, because we’re experts, because we’re chief medical officers of a large healthcare system, we know all there is to know about how to meet patients’ needs.

14:31 We need to swallow our pride. We need to go visit a few medical marijuana dispensaries. We need to figure out what they’re doing. We need to figure out why so many patients like Robin are leaving our mainstream medical clinics and going to these medical marijuana dispensaries instead. We need to figure out what their tricks are, what their tools are, and we need to learn from them. If we do, and I think we can, and I absolutely think we have to, we can guarantee all of our patients will have a much better experience.

15:00 Thank you.

15:01 (Applause)

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