Spasticity, Rigidity, and Other Motor Symptoms in Neurodegenerative Disorders Zoltan Mari, MD
Ruvo Family Chair & Director, Parkinson’s & Movement Disorders Program
Clinical Professor of Neurology, University of Nevada
Adjunct Associate Professor of Neurology, Johns Hopkins University
Hypertonias
OUTLINE
Definitions and classifications of increased muscle tone (hypertonias)
Evaluation and management of hypertonias: Properly identify and diagnose the etiology/nature of hypertonia – a vignette Physical therapy Pharmacotherapy Chemodenervation: Phenol/ethanol Botulinum toxins Surgery DISCLOSURES
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Institutionally awarded research support from: NIH, PF, MJFF, Eli Lilly, Cerevel, Amneal, NeuroDerm
Consulting fees from: GB Sciences, Biogen, GKC, Acadia, Elsevier
Hypertonias
1 Definitions • Spasticity: Caused by lesions in the pyramidal tract (i.e. upper motor neurons) such the corticospinal tract MS MSA (MSA may cause cerebellar pathology [MSA-C] leading to hypo-, not hypertonia, but it may well cause pathology affecting long tracts [corticospinal included] leading to spasticity Stroke Spinal cord compression Motor neuron disease Weakness usually present More resistance in one direction the other direction More tone in initial part of movement – “Clasp knife spasticity” It is velocity dependent (i.e. more noticeable with fast movements) • Rigidity: Seen in extrapyramidal disorders (i.e. Parkinson’s), often implicating the rubrospinal or vestibulospinal tracts Subtypes include: Cog wheel rigidity (Parkinson’s) – Tremor superimposed on this hypertonia that results in intermittent increase in tone during the movement. Lead pipe rigidity (neuroleptic malignant syndrome, Parkinsonism-hyperpyrexia syndrome or less commonly stiff man syndrome) – Uniform increase in tone Same resistance in all directions Not velocity dependent – does not vary with speed of movement of muscle groups involved • Dystonia: Sustained or repetitive involuntary muscle contractions resulting in twisting and repetitive movements or abnormal fixed postures – common in PD • Paratonia (Gegenhalten): Inability to relax muscles during muscle tone assessment Oppositional paratonia ("gegenhalten"): subjects involuntarily resist to passive movements – usually seen in cases of dementing disorders and/or frontal pathology Facilitatory paratonia ("mitgehen"): subjects involuntary assist passive movements (does not represent hypertonia – only mentioned here for completeness)
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Vignette
• 70 years old gentleman • History significant for advanced PD (diagnosed in 2013, DaTscan in 2018 showed profound ioflupane uptake loss, taking 250 mg levodopa 7x/day), severe spinal stenosis (multiple surgeries, significant spinal cord impingement with signal changes) • In addition, his PD presentation included what was believed to be dystonias • Currently c/o of episodic, extremely severe stiffening of muscles in both LEs, as well as lumbar paraspinal musculature These contractions are reported to be “extremely painful” No clear relationship between C/L dosing and the timing of these episodes The episodes are getting worse over the years
Hypertonias
2 Personal kinetograph (PKG) analysis performed, to identify C/L response
While there is C/L response, the patient remains under-medicated Increased PTI signals significant immobility Lack of dyskinesias rules out the possibility of ON-dystonias as a possible source of hypertonia, but OFF-dystonia remains possible While the patient seems under- treated, a pure OFF-rigidity or dystonia cause is unlikely
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Vignette Summary
• Multiple contributors to hypertonia simultaneously possible • Timing to C/L dosing can inform about dopaminergic mechanisms – OFF dystonia is often painful, whereas rigidity usually isn’t • Spasticity is probably a contributor, however, unlikely to be prominently episodic • PKG analysis confirmed some C/L related variation in motor speed • Further effort may include: Additional C/L could confirm a primarily dopaminergic source – if episodes improve – a deterrent is the already very high daily C/L dose + the lack of a clear result from previous similar attempts to increase C/L A (diagnostically) even better alternative is the use of “rescue” (rapid acting parenteral) dopamine options BoNT injections – a limitation being the overall size of affected muscles PT may be limited due to the prominently episodic nature of the hypertonia SPS may be considered (anti-GAD65 testing) Hypertonias
3 Negative Clinical Aspects of Hypertonia
• Interferes with mobility, exercise, and joint range of motion • Interferes with activities of daily living • Causes pain (see Vignette) • Makes patient care more difficult, including ADLs, transfers, basic care • Causes sleep disturbance • As demonstrated in the vignette, the exact source/etiology of hypertonia may be confusing, ambiguous, and/or multi-factorial • Interference with ambulatory abilities
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Positive Clinical Aspects of Hypertonia
• Maintains muscle tone • May counter (flaccid) weakness • Helps support circulatory function • May prevent formation of deep vein thrombosis • May assist in activities of daily living • May assist in maintaining erect posture • May assist in gait Hypertonias
4 Mechanical Contracture vs Hypertonia
Mechanical (not active muscle) Hypertonia (active muscle) • Fixed • Dynamic • Tendon and/or ligament • Slow stretch • Charcot joint • Palpable antagonistic • Heterotopic ossification muscle action • Increased reflexes
Most often, both mechanical and muscle factors
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Assessing Hypertonia
• History • Neurological examination • Measurement tools
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5 Key Questions in History
• Location?
• Time of day, aggravating/alleviating factors? (diary)
• Painful spasms?
• Functional limitations?
• Need for extensor tone in legs for standing?
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Neurological Examination
• Standard musculoskeletal examination including range of motion (may be measured with a goniometer) • Detailed neurologic examination • Clonus • Tone measures (eg, Ashworth scale)
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6 Modified Ashworth Scale (MAS)
• 0 = Normal tone • 1 = Slight “catch” • 1+ = Significant “catch” • 2 = Mild, limb moves easily • 3 = Moderate, passive range of movement difficult • 4 = Severe, rigid limb
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Quantitative Evaluation
• Gait lab with surface electromyography (mostly research use)
• Fugl-Meyer test for upper-limb dexterity
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For educational purposes only.
7 What Is Meaningful Function?
Passive Function Active Function • Increased ROM • Improved upper limb use: • Improved positioning Reaching, grasping, releasing • Increased ease of hygiene • Improved mobility • Improved cosmesis • Improved gait • Decreased spasm frequency • Decreased energy • Improved orthotic fit expenditure • Decreased pain
ROM = range of motion. Brin M. Muscle Nerve. 1997;20:s208. Hypertonias
Goal Attainment Scales (GAS)
• Select 2 SMART (specific, measurable, achievable, realistic, time-frame) goals with patient -2 did not achieve by a lot -1 did not achieve by a little 0 achieved +1 exceeded by a little +2 exceeded by a lot
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8 Spectrum of Care for Management of Hypertonias
Intrathecal Prevent Baclofen Nociception Therapy
Rehabilitation Oral Therapy Drugs Patient
Orthopedic Injection Treatment Therapy
Neurosurgery
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Treatment Paradigms
“Old School” “New School” • Stepwise approach • Generalized vs localized • • Modalities Acute vs chronic • Patient-specific analysis of • Medications side effects • Injections • Mix and match therapies • Tendon surgery early • Nerve ablation • Consider multiple simultaneous etiologies and localizations
Hypertonias
9 Simplified Treatment Algorithm for Hypertonias
Treat Underlying Disease/Specific Etiology
PT/OT Medical Treatments Surgical Treatments
Stretch/Splint Oral Medications Myelotomy Dorsal Rhizotomy Positioning Chemodenervation: -BoNT Injections Other Surgeries Other Modalities -Phenol/Ethanol (Tendon Transposition, etc) Intrathecal Baclofen
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Oral Medications (1)
• Baclofen Binds GABA-b receptors Side effects—weakness, lethargy, rebound seizures—if stopped abruptly
GABA = gamma-aminobutyric acid. Hypertonias
10 Oral Medications (2)
• Dantrolene Blocks Ca++ channels in muscle No CNS effects, but causes significant weakness Hepatic dysfunction rare
CNS = central nervous system. Hypertonias
Oral Medications (3)
• Tizanidine (TIZ) Alpha-2 agonist Side effects: Lethargy, orthostasis, dry mouth Inferior to BoNT in head-to-head placebo- controlled trial (Simpson)
BoNT = botulinum toxin. Simpson et al. J Neurol Neurosurg Psych. 2009;80:380-385. Hypertonias
11 Oral Medications (4)
• Diazepam Enhances GABA through benzodiazepine receptors in brain Rapid development of tolerance Side effects: Drowsiness, delirium, abuse potential, withdrawal seizures
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Cannabinoids
• THC and CBD • Cochrane analysis reviewed 38 papers—only 6 were RCTs. • Nonsignificant improvements in 6-minute walk and MAS scores, but significant subject improvement. • Med legalization
CBD = cannabidiol; THC = tetrahydrocannabinol; RCT = randomized controlled trial. Lakhand S, et al. BMC Neurol. 2009;9:1-6. Hypertonias
12 Intrathecal Baclofen
• Generalized spasticity • Not controlled or side effects from oral medications • Delivers approximately 1/50 dose baclofen direct to cerebrospinal fluid • Infinitely programmable • Refill every 3 to 12 months • Mechanical complications
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Phenol and Alcohol
. Causes degeneration of both motor sensory fibers . Can do nerve blocks in pure motor nerves but avoid mixed or sensory nerves . Motor point blocks . Lasts 4 to 9 months . Inexpensive
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13 Reported Clinical Use of BoNT Is Diverse and Expanding Sensory Neuromuscular Autonomic
Chronic Adult Spasticity Migraine* Strabismus* Cerebral Palsy Blepharospasm* Achalasia
Bladder
Cervical Dystonia* Hyperhidrosis* Painful *US approved indications for botulinum toxin. Wrinkles* Neuropathy
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Botulinum Toxins
. Can be injected using anatomic landmarks or as motor point block . Four formulations in United States: onabotulinumtoxinA (Botox®*) abobotulinumtoxinA (Dysport®†) incobotulinumtoxinA (Xeomin®‡) rimabotulinumtoxinB (Myobloc®§) . Lasts 2 to 4 months . Variable FDA-approvals for upper- and lower- limb spasticity in children and adults
FDA = US Food and Drug Administration. *Dublin, Ireland: Allergan, Inc; †Basking Ridge, NJ: Ipsen Biopharmaceuticals Limited; ‡Greensboro, NC: Merz Pharma GmbH & Co KGaA; §Louisville, KY: Solstice Neurosciences, LLC.
Hypertonias
14 Hypertonias Simpson DM, et al. Neurology. 2016.
Botulinum Toxin Dosing
• Toxin dosing among formulations is NOT equivalent • Dosing mostly art, not science, based on size of the muscle (and patient) and degree of spasticity • Dosing table available in Sheean et al1 • Dosing peak effects for various muscles in Yablon et al2
Hypertonias
1. Sheean G, et al. Eur J Neurol. 2010;17:74-93; 2. Yablon SA, et al. Mov Disord. 2010;26:209-215.
15 Injection Techniques
• Guidance produces significantly better results than using anatomic landmarks alone • Ultrasound and electrical stimulation were equally effective in a study of stroke- related upper-limb spasticity.
Hypertonias
Picelli et al. Clin Rehab. Aug 14, 2013. Epub ahead of print.
Using Ultrasound for BoNT Guidance
• Avoid high-risk structures (eg, vessels, nerves, untargeted muscles)
• Isolate deep or overlapping muscles
• Visually confirm electrical stimulation guidance
• More rapid and comfortable
1. Alter et al. In: Alter KE et al. Ultrasound-Guided Chemodenervation Procedures: Text and Atlas. 2013; procedure (research 2. Alter and Munin. In: Alter KE et al. Ultrasound-Guided Chemodenervation Procedures: Text and Atlas. 2013; 3. Alter and Munin. In: Alter KE et al. Ultrasound-Guided Chemodenervation Procedures: Text and underway) Atlas. 2013. 4. Image: Jost W. Pictorial Atlas of Botulinum Toxin Injection. 2nd ed. Surrey, United Kingdom: Quintessence Publishing Co, Ltd; 2012.
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16 Elbow
• Flexion/pronation muscles? Biceps (2-joint rule) Brachialis Brachioradialis Pronator teres Pronator quadratus
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Hand
• Flexed wrist, MCPs, PIPs, DIPs Flexor carpi radialis and ulnaris, flexor digitorum superficialis, flexor digitorum profundus, lumbricals
DIP = distal interphalangeal; MCP = metacarpophalangeal; PIP = proximal interphalangeal.
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17 Hand
• Thumb in palm Flexor pollicis longus Flexor pollicis brevis Adductor pollicis Opponens pollicis
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Lower Limb
• Hip flexion/adduction Iliopsoas, rectus femoris, adductor magnus/longus/brevis • Knee flexion Biceps femoris Semimembranosus Semitendinosus • Equinovarus Gastrocnemius/soleus Posterior tibialis
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18 Case
. 40-year-old man with long-standing MS. Has a scissoring gait with bilateral equinovarus, hamstring, and hip flexion/adduction spasticity with minimal mechanical contracture. He has not responded to oral medications.
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Question 3
How would you treat this patient? A. Intrathecal baclofen trial B. Phenol injections into bilateral adductors, rectus femoris, medial hamstrings, gastrocnemius and posterior tibialis C. Botulinum toxin injections into bilateral adductors, rectus femoris, medial hamstrings, gastrocnemius, and post tibialis D. Options A and B are both reasonable.
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19 Answer
D. Options A, B, or C are reasonable depending on patient preference and social and financial issues. Aggressive splinting or serial casting is probably needed as well. Note that ceiling dose limitations may restrict the number of muscles that can be treated with BoNT, necessitating combination Rx.
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Ankle and Foot
• Inversion/supination Tibialis posterior • Great toe, D2-5 toe flexion Flexor digitorum longus Flexor digitorum brevis Flexor hallucis longus • Great toe extension Extensor hallucis longus
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20 BoNT Therapy: Open Questions
• Injection technique Surface anatomy; EMG; electrical stimulation • Optimal dose; volume; dilution • Number and location of injection sites • Serotype/brand differences • Immunogenicity and clinical relevance • Patient access (cost; regulatory approval)
EMG = electromyography. Hypertonias
Summary: Evaluation & Management of Hypertonias
• Establish the definition of “meaningful function” • Future studies: Populations (homogenous vs heterogenous) Outcome measures (passive vs active; 1˚ vs 2˚) BoNT injection paradigms Fixed vs flexible Muscle targeting (anatomy; EMG/electrical stimulation, sonography-guided; endplates) • Early, acute, or “hyperacute” BoNT treatment Prophylaxis for development of spasticity? Cortical plasticity improve active function
CNS = central nervous system. Hypertonias
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