Extrapyramidal Symptoms


Background

  1. Many meds may cause mvmt disorders that mimic Extrapyramidal Syndromes (EPS)
  2. Mvmt disorders are divided into
  3. Standardized method for assessing mvmt
Hyperkinetic Diseases:

Dystonias/Dyskinesias

Background

  • Syndrome of abnormal muscle contraction
  • Produces repetitive involuntary twisting mvmts, abnormal posturing of neck, trunk, face, extremities

Pathophysiology

  • Sequelae from dopamine receptor blockade
    • Usually develop w/in 1st several Tx doses OR
    • After large incr of dosage of antipsychotic meds
    • Basal ganglia abnormalities
  • Induced by neuroleptics, butyrophenones, phenothiazines, benzamides
    • Neuroleptics: less w/ metoclopramide, prochlorperazine, haloperidol
    • Parkinson's Tx (levodopa; may alternate w/ akinesia-"on-off phenomenon")

Epidemiology

  • Early presentation
  • 2-12% incidence

History/Symptoms

  • Rigidity, spasms
  • Hx of antipsychotic meds

Physical Exam

  • Rigidity, spasmodic body mvmts; sustained muscular contractions
    • Tongue, mouth, neck, back, limbs, trismus, grimacing
  • Bizarre gait, writhing, tonic contractions, lordosis
  • Torticollis: abnormal involuntary neck mvmts, abnormal neck postures
  • Opisthotonos: back muscle spasm causing head & lower limbs to bend backwards, body arch forward
  • Oculogyric crisis: continuous rotatory eye mvmts
  • Laryngeal dystonia: (rare) life-threatening form of dystonia that manifests as stridor, difficulty breathing, choking

Labs/Tests

  • Drug screen/levels, chemistry to r/o other causes/illness

Imaging

  • CT/MRI to r/o tumors, abscesses, ischemia

Treatment

  • Discontinue/reduce inciting med
  • Anticholinergic (control neuroleptic induced dystonia)
    • Benztropine: 1-2 mg IM then 2 mg PO qD x3 d  (if on haldoperidol at home)
    • Diphenhydramine (Benadryl): 50 mg IM/IV then 50 mg PO qD
  • Benzodiazepines
    • Diazepam
    • Lorazepam: 1 mg PO q8hrs for muscle relax & anxiolysis
  • Botulinum toxin
    • Most appropriate Tx for focal dystonia not resolved by d/c inciting drug OR w/ trial of anticholinergic Tx

 

Akathisia

Background

  • Subjective feeling of restlessness assoc w/ objective motor restlessness

Pathophysiology

  • Adverse effects caused by blockade of dopamine receptors
    • Phenothiazines > butyrophenones, antidepressants, levodopa
    • Early presentation
  • Often mistaken for worsening agitation, leading incorrectly to an incr in antipsychotic dose
  • Usually develops w/in first few days of Tx w/ inducing agent
    • Ie, 40% of pts given 10 mg of IV prochlorperazine develop akathisia w/in 1 hour

Epidemiology

  • 20% incidence

History/Symptoms

  • Motor restlessness
  • "Random heebie-jeebies"
  • Inability to stand still

Physical Exam

  • General: anxious, fidgety
  • Pts may appear normal on physical exam findings

Labs/Tests

  • Drug screen/levels, chemistry to r/o other causes/illness

Imaging

  • CT/MRI to r/o tumors, abscesses, ischemia

Treatment

  • Stops days-wks after d/c med
    • may be permanent
    • Occasional persistent lifelong adverse drug rxn
  • Anticholinergics (1st line)
    • Diphenhydramine: 50 mg IV (severe); 50 mg PO q8hrs (mild); 50 mg PO QD (prophylaxis)
    • Benztropine: 1-2 mg IM; then 2 mg PO QD
  • Benzodiazepines
    • Lorazepam: 1-2 mg PO q8hrs
  • Beta-Blockers
    • Propranolol 20-80 mg PO q8hrs

Tardive Dyskinesia

Background

  • Abnormal involuntary mvmts secondary to use of drugs that block dopamine receptor activity
  • Most typical mvmts induced by dopamine receptor blockers
    • Choreiform mvmts/gait

Pathophysiology

  • Prolonged dopamine receptor blockade causing hypersensitivity
    • Neuroleptics, any dopaminergic antagonist drug
    • Prolonged presentation (12 mos)
    • May be permanent
  • Also is assoc w/ dystonic effects to rest of body (tardive dystonia)
  • Risk Factors
    • Age: 5 times higher risk if >45 yo

Epidemiology

  • More common & severe in elderly
  • Incidence 30-50% w/ neuroleptic Tx
    • Annual incidence of 5% per year for 1st several yrs of neuroleptic drug

History/Symptoms

  • Involuntary lip smacking, sucking, jaw movements, tongue writhing, grimacing
  • Speech, swallowing difficulties
  • Hx of exposure to anti-dopaminergic drugs
    • Ie, metoclopramide

Physical Exam

  • General: dystonic body mvmts
  • Pts may appear normal on physical exam findings

Labs/Tests

  • Drug screen/levels, chemistry to r/o other causes/illness

Imaging

  • CT/MRI to r/o tumor, abscesses, ischemia

Treatment

  • No adequate therapy
  • Prevention desirable
    • Prudent use of drugs implicated in TD
    • Limiting use of dopamine antagonists to appropriate pts
    • Limiting length of exposure to dopamine antagonists
    • Withdrawal of offending drug or toxin if choreoathetoid mvmts emerge
  • Initial Tx: reduce, gradually eliminate drug responsible if medically/psychiatrically possible
  • Mild-moderate choreoathetosis: agents that deplete central dopamine may help
    • Tetrabenazine, reserpine
    • Benzodiazepines, botulinum toxin, anticholinergics (specific mvmt disorders)

 

Essential Tremor

Background

  • Repetitive, often regular, oscillatory mvmts
  • Caused by alternating, or synchronous, irregular contraction of opposing muscle groups
  • Usually involuntary

Pathophysiology

  • Induced by certain med & toxins
    • Precise anatomic lesion unclear
  • Tremor affects upper extremities, head (titubation), voice
  • Rarely affects lower extremities

Epidemiology

  • Most common mvmt disorder in adults

History/Symptoms

  • Exposure to lithium, terbutaline, valproate, TCAs, antihistamines, etc
  • Tremors of head, voice, arms
  • Involuntary

Physical Exam

  • General: tremors, shaky voice
  • Pts may appear normal on physical exam findings

Labs/Tests

  • Drug screen/levels, chemistry to r/o causes/illness

Imaging

  • CT/MRI r/o tumors, abscesses, ischemia

Treatment

  • Initial Tx: d/c offending drug(s)
  • Beta-blockers
    • Propranolol: 10 mg TID, titrate to affect
  • Anticonvulsants
    • Primidone: start at low doses; 25 mg QHS, titrate to affect (NMT 100 mg QD)
    • Topiramate: titrate slowly to 400 mg QD
      • Monitor for sedation & cognitive impairment
  • Benzodiazepines
    • Clonazepam: 0.5 mg PO TID, titrate to affect (NMT 20 mg QD)

 

 

Hypokinetic Diseases:

Parkinsonism

Background

  • Hypokinetic mvmt disorders: paucity of spontaneous mvmt
    • Bradykinesia or lack of spontaneous mvmt akinesia
    • Often accompanied by rigidity
  • Parkinsonism: common mvmt disorder that displays akinesia & rigidity
  • Most often a manifestation of Parkinson dz
  • May also be drug induced

Pathophysiology

  • Any drug that depletes brain dopamine or blocks brain dopamine receptors
    • Dopamine receptor blockade results in decr dopamine activity
    • Leads to disinhibition of globus pallidum, suppression of thalamic nuclei, reduced excitation of motor cortex
    • Neuroleptics (esp prochlorperazine), TCA's, CCB's, metoclopramide, methyldopa, lithium
  • Develops subacutely w/in 1st wks of drug introduction or incr in dosage
  • May resolve over several wks or be permanent

History/Symptoms

  • Exposure to inciting drugs
    • Ie, Metoclopramide (widely used as gastric motility agent): potent dopamine receptor blocking agent; readily induces parkinsonism
  • Development of signs/Sx over months rather than years
    • Parkinson’s dz takes years
  • Symmetrical onset of Parkinsonism’s motor signs
    • Parkinson’s dz is usually unilateral in onset
  • Presence of other mvmt disorders in addition to Parkinsonism
    • Tardive dyskinesia, dystonia

Physical Exam

  • General: resting AND action tremor, mask-like facies, abnormal gait
  • Bradykinesia, cogwheel rigidity, postural instability
  • Pts may appear normal on physical exam findings

Labs/Tests

  • Drug screen/levels, chemistry to r/o other causes/illness

Imaging

  • CT/MRI to r/o tumors, abscesses, ischemia

Treatment

  • Aimed at controlling Sx
    • Removal of Parkinsonism inducing agent
  • Use of meds for pts w/ drug or toxin induced Parkinsonism considered only after withdrawal of offending agent
  • Dopaminergic drugs alleviate major motor Sx
    • Levodopa: start at lowest available dose; titrate to effect
  • MAOIs & catechol O-methyltransferase inhibitors
    • MAOI: Selegeline, Rasagaline
    • COMT: Entacapone, Tolcapone
  • Dopamine agonists
    • Pramipexole
  • Amantadine 100 mg PO BID, titrate to effect (NMT 300 mg QD)
  • Anticholinergic agents rebalance cholinergic dopaminergic mechanisms w/in CNS
    • Benztropine 1-8 mg PO
    • Trihexyphenidyl 1-15 mg PO