1. Robert Altman November 17th 2010
Approach to Tremors
Robert Altman
November 17th 2010

2. Questions you should be able to answer after this session
What is the most common movement disorder?
Name 2 drugs that can enhance a physiologic tremor and 2 that can turn someone akinetic and rigid?
What is a first line therapy for early tremor in PD for a 45 yr old?
What are the 2 P’s for essential tremor treatment?
Which tremor is so stirkingly unilateral and disabling that the patient’s limb is deemed non-functional?
Tensor or levator in essential palatal tremor?

3. References AAN Movement Disorders Syllabus, 2010 Toronto
AAN Continuum 2007, 2010 Movement Disorders
Videos courtesy of YouTube and AAN Continuum CD
As usual; good review articles
Tremor : Clinical Features, Pathophysiology, and Treatment: Neurol Clin 27 (2009) 679–695
Grimes DA. Tremor--easily seen but difficult to describe and treat. Can J Neurol Sci Mar;30 Suppl 1:S59-63.
Gupta A, Lang AE. Psychogenic movement disorders. Curr Opin Neurol Aug;22(4):430-6.

4. Contemplate... Definition of tremor
Rational and logical categorization
Examples of each
Therapies for each
Focus in essential tremor
Definition
Genetics
Clinical
Pharmacological and non-pharma treatments
Surgical therapies (refractory cases)
What / where to lesion or stimulate?
Psychogenic Movement Disorders*

5. Definition: Tremor Movement of a body part Involuntary (even PMD)
Rhythmical
Regularly recurrent
Oscillatory
Around central plane

6. Categorization
Previously described in terms of activation condition (rest vs. movement), brain region affected (rubral), presence or absence of medical condition(hypothyroid), existence of neurological conditions (dystonia), topography (limb, head, voice), frequency.....
Complicated and contradictory
Generally not necessary to diagnose and properly treat
Phenomenology and a syndromic classification of tremor consensus statement Movement Disorder Society (MDS) [1998]

7. Does this help your understanding...?

8. Treat the correct cause
Central generator
Peripheral generator

9. Action Rest TREMOR Kinetic Postural Parkinsonian Drug induced
Arise during voluntary contraction of skeletal muscle
Action
Kinetic
-intention
Postural
Rest
Parkinsonian
Drug induced
Limb fully relaxed

10. Continuum 2010 Movement Disorders

11. 3 golden rules in tremor assessment
Action vs. Rest
History & Physical
Pattern recognition

12. Action Most Common: Less Common: Essential tremor
Enhanced physiological tremor
Drug-Induced action tremor
Dystonic
Less Common:
Orthostatic
Cerebellar
Psychogenic
Wilsonian
FXTAS
Peripheral neuropathy-related
Midbrain or rubral

13. On history Tremor causing Rx? Caffeine, nicotene?
Diarrhea, weight loss, heat intolerenace?
Sudden onset?
Temporal course? Static or progressive?
What body regions?

14. On exam Postural / sustension: Kinetic part: What joints?
Thumb posturing? Other abnormal postures?
Distractibility, entrainment, suggestibility?
Kinetic part:
Pouring, drinking, using a spoon, FNF, Archimedes spiral test
Intentional component (worsen as draw near target)
Re-emergent?
Dystonic postures accompanying? (thumb)

15. Essential Tremor Most common adult-onset movement disorder
5% general population
Genetics: AD, variable penetrance, no gene found (polygenic)
Central generator: thought to represent cerebellar-thalamo-cortical outflow pathology
Kinetic and postural, mainly arms; 4-12Hz
Progressive
Armshead (“yes-yes” vs. “no-no”)
Voice / vocal cord, chin, tongue
Unilateral  bilateral
Rare in LE’s
No parkinsonian or dystonic features.

16. Disability Interferes with ADL’s
Feeding
Spoon, drinking from a cup
Writing
Typing
Personal hygiene
Interferes w/ occupational motor tasks

17. Diagnostic Criteria Core Secondary / Supportive
Bilateral action tremor of the hand and forearms
Absence of other neurologic signs
Caveat: cogwheeling*
May have isolated head tremor with no signs of dystonia
Secondary / Supportive
Long duration (3 yrs)
+ family Hx
Beneficial response to ETOH
50-90% of cases, but careful for rebound phenomenon
* See next slide

18. Non-motor ET symptoms Non-motor (tremor) symptoms being recognized
Cognitive decline
Anxiety
Gait disturbances
Hearing loss
Implications for screening, treatment plans
Tandem gait difficulties
Anxiety  Tan et al 2005
cognition,Benito-Leon et al 2006, neurology 2009
GaitSinger et al 1994
Hearing lossbenito-leon 2007

19. Archimedes Spiral Test
Diagnostic and for follow-up
Exam pearl: wing-beating position elicits it best; out of phase (destructive interference)

20. Treatment of ET DBS (not lesional) General principals
Treat only if bothersome
The longer the tremor has been there the more difficult Tx will be
Limb tremor responds much better than head/neck to oral Rx
Non-pharmacologic
Biofeedback
Weighted objects (e.g., utensils)
Only dampens it temporarily, not viable long term treatment option
Pharmacologic
2 P’s ; alone or in combo. Is there concurrent HTN?
Primidone, propranolol (Inderal)
Others: benzodiazepenes, gapapentin anecdotal use but not class A evidence (see table in appendix)
Botox
Voice, head
DBS (not lesional)
ViM of VL of thalamus in refractory cases
90% improvement with ventralis intermedius stimulation
a/e to surgery <1% in expert centers

21. 2 P’s * Caution for hypotension, bradycardia in elderly  falls
A/E  impotence, drowsiness, confusion, h/a. Exercise intolerence
= be careful in COPD / ASTHMA and DB on oral hypoglycemics  BB can mask hypoglycemic episodes!
patients don’t develop tolerence to BB
Primidone patient’s eventually habituate to the s/e

23. Enhanced Physiologic Tremor (EPT)
Appears to be peripherally generated (not central like ET)
Based on inertial loading electrophysiological analysis
Faster postural and kinetic tremor than ET (7-12Hz); very low amplitude.
Very easily visible
15-35 yo
Anxious phenotype
Mainly voice and limb
No head
May have some cogwheeling, no frank rigidity
Endogenous & exogenous (see next slide) causes Tx
Reversible
Reassurance
Low dose beta-blockers, bzdp
Endogenous = hyperT4, hypoglycemia

24. Drug Induced Action Tremor (EPT)
Based on history
Temporal onset
Sympathomimetics++ (ß-adrenergic bronchodilators)
caffeine, nicotene
SSRI, Li, valproate, roids!
Withdrawal relieves symptoms
Limb, never head
Treatment
Remove causative agent
Bb or bzdp can dampen tremor if causative Rx absolutely necessary
 neuroleptics, lithium, corticosteroids, calcium channel blockers, ethanol, beta adrenergic agonists, valproic acid, theophylline, thyroid hormones, cardiac antiarrhythmics, nicotine, and tricyclic antidepressants

25. Dystonic Tremor Commonly misdiagnosed as ET
Tremulous muscle activity in patients with dystonia
Pulling or pain sensation in region affected (e.g., neck)
Limbs (UE>LE), head (neck) or both (limb precedes neck)
Voice: strangled speech, voice break
Postural or kinetic
Not rythmic, nor oscillatory, not around 1 axis
Exam may reveal tonic muscle activity in tremoulous or conta-tremulous limb
Tremulousness is directional
Spooning of hands, fatiguing, thumb flexion or other dystonic postures
May have scarf hiding hypertrophied muscle (eg neck with toriticollis)
Dystonic tremor may be reduced by antagonistic gestures geste antagonistique
Commonly misdiagnosed as ET
Pharma treatment: anti-dystonic agents (baclofen, artane), bzdp, bb, botox (torticollis, voice)
Surgical (refractory): selective denervation, DBS
Dystonic tremor may be reduced by antagonistic gestures geste antagonistique),

26. Orthostatic Tremor Rare ‘Unsteadiness’ when standing o/e
Avoid situations when have to stand still (at movies)
o/e
Rapid 13-18hz, low amplitude tremor/rippling in calves only on standing
Visible and palpable
pseudodystonic
Confirmed with EMG
Rx:
Nothing evidence based
Most common =Clonazepam, sinemet
Tried inderal, primidone, gabapentin, phenytoin, cbz, ethosux, baclofen, diamox
Subtype of ET actually by some catagorization schemes

27. Cerebellar Tremor Central cerebellar disorders (e.g.,SCA)
Kinetic with terminal worsening = intentional
May have postural component, but rest absent
In multiple planes
Slow, 3-5 hz
Presence of overshooting
Other cerebellar signs (hypermetric saccades, dysarthria, scanning speech, ataxic gait, head titubation, dyssynergia)
Treatment
DBS
thalamic

28. Wilson’s Disease associated Tremor
Can be action (rest, combination)
Postural (possibly wing-beating)
Kinetic (like ET)
Young (<40 yo)
Exam reveals multifocal and multisystemic disorder (long-tract, cognitive, neuro-psychiatric)
Trivia: what are the genetics? Mode of transmission? On what layer of the cornea would you look to find KF rings? Tx
Chelation
Penicillamine controversial
Trientene
Tetrathiomolybate
Zinc once levels normalize
Bb for action tremor AR
Gene = ATP7B gene on chromosome 13q
Layer of cornea = Descemet..
Striatal and generalized neuronal loss. Diffuse gliosis with Alzheimer’s types I and II astrocytes and Opalski’s cells (of microglial origin)
Tx:
Penicillamine-D; can cause drug induced lupus, myasthenic-like picture, subacute worsening prompting cessation...
Zinc
Less toxic = Trientin, ammonium tetrathiomolybdate
Liver translplant

29. FXTAS (fragile X tremor ataxia syndrome)
Multiple complaints in addition to tremor
Cerebellar or parkinsonian
Cognition, dysexectuive function
Male family members (grandchildren) have MR
MR brain
Classic picture
Tx: bb for action tremor
 intention tremor and/or ataxia, with peripheral neuropathy, autonomic dysfunction, and gradual cognitive decline beginning with memory and executive function deficits. Psychiatric features are often present, and may include anxiety, dysinhibition, depression, and apathy. MRI features of FXTAS include global brain atrophy, white matter disease in the subcortical, middle cerebellar peduncles (MCP) and periventricular regions

30. Peripheral neuropathy-related tremor
PN by history of same limb with tremor
Intertial loading leads to suppression of tremor proving peripheral generator
More common with demyelinating PN’s, also seen in HMSN1 (Levy-Roussy) and IgM dysgammaglobulinemic neuropathies
Temporal linkage
o/e
Peripheral neuropathy readily apparent on tremulous limb
Sensory impairment, weakness 4/5 MRC, altered DTR
Tremor present when muscle strength allows limb to maintain certain postures
Vanishes if weakness too severe or if limb power returns to normal
Tx:
Underlying neuropathy
BB for AT
What do you think about DBS?
 By and large, they are relatively uncommon and generally consist of irregular postural or kinetic tremors of variable frequency from 4 to 11 Hz. Not all peripheral neuropathies have been identified with tremor, and most of them have been demyelinating and specifically dysgammaglobulinemic neuropathies (especially IgM disorders). Tremors have also been reported in type 1 hereditary motor and sensory neuropathies (Roussy-Levy syndrome). Tremors have also been reported with chronic inflammatory demyelinating polyneuropathies in the recovering phase of Guillain-Barré syndrome (Said et al 1982; Elbe 1983; Smith et al 1984; 1995).

31. Midbrain / Rubral / Holmes
Lesion based, central generator
Sudden onset focal neurological insult
Progressive forms can occur (tumor or expanding vascular lesion)..some say this is typical even for stroke.
Strikingly unilat, HB or monomelic
Non-rythmic, <4.5 Hz, high amplitude
Rest, action (postural and kinetic)
Severity: kinetic > postural > rest
Severe and disabling, limb entirely handicapped
Imaging confirms pontine-midbrain lesion affecting cerebellar outflow tracts and dopaminergic nigrostriatal fibers
Rx:
AT primidone, bb
Rest Levodopa, DA, Anti-chol
DBS (refratory)
YouTube:
rubral tremor.wmv
Aka thalamic tremor, myorhythmia
A delay of up to 2 years between the lesion and tremor onset is typical

32. Palatal “myoclonus” – actually tremor
Essential vs. symptomatic
See Chenjie’s presentation, great comparative table
 Although it resembles a tremor, the movement is repetitive rather than oscillatory and involves contraction of agonist muscles only. The cause of the auditory ear click is unknown, but it occurs more commonly in essential palatal myoclonus, which is idiopathic, than in symptomatic palatal myoclonus that is secondary to a structural lesion in the brain stem.

33. Rest Tremor(s) Most Common: Less Common: Parkinsonian
Drug-induced rest tremor
ET (with rest component; rare…15-20%)
Less Common:
Wilsonian
Midbrain

34. Critical Elements from Hx & Exam
History
Rx?
Change in arm swing, gait, facial expression?
Previous CVA, dementia?
Exam
Arms at rest (whole interview and dynamic exam)
‘pill-rolling’ quality
Symmetry
Limb or hemi-body
Arm extension test
Not true postural, rather emergent (with crescendo after several seconds)

35. Parkinsonian Tremor Classically @ rest; 3-5 Hz Often HB If arm
Pron-sup rather than flx-ext
Check for limb “posturing” flexion/fist formation hand, thumb flexion
Re-emergent tremor during arm extension or during tasks (pouring water) causes considerable misdiagnosis with ET
May be more disabling than rest tremor
Other hallmark-cardinal features
Motor: asymmetric rigidity, bradykinesia, postural instability, fatiguing
Non-motor: RBD, hyposmia, constipation, mood, sebborhea, ANS dysfunction (orthostasis, ED, etc.), excessive daytime sleepiness, RLS, body pain
Aversion to caffeine...?

36. PD tremor DA 1st line Levodopa Anticholinergics (rare) Consider bzdp
Cogentin, artane, amantadine
Consider bzdp
Refractory DBS

37. Drug Induced Temporal link with Rx
Antipsychotics (typical>atypical), Li
Can look practically identical to Parkinsonian tremor
Removal of medication should result in complete resolution
Tx:
Remove or diminish offending agent
Levodopa (even if on Da blocking agents) or anticholinergics can be tried

38. Psychogenic Tremor (PMD)
History
Exam
Sudden, abrupt onset
Link with psychological stressor
Maximal tremor at onset, rather than slowly progressive
Static course
Spontaneous remissions/cures
Psychiatric comorbidities
Somatisation
Entrainment, co-activation, distractibility and suggestibility (I will trigger your tremor..., or use magic tuning fork)
Give-way weakness
Non-physiological or unusual features
Variable frequency or direction
Unusual combined rest, postural, kinetic
Changes speeds throughout exam
Fatigues with prolonged exam
Little response to pharmacotherapy
Intertial loading leads to tremor worsening
“la belle indifference”
Perceived disability out of proportion to exam findings
Coactivation sign. This is observed when testing a trembling limb for rigidity and there is resistance to the passive movement. Two additional features should be present: 1) the tremor is dependent on there being an increase in tone (i.e. the examiner feels the patient “fighting” against him or her); and 2) the tremor disappears when the voluntary increase in tone disappears.

39. Psychogenic Movement Disorders (PMD)
Gupta A, Lang AE. Psychogenic movement disorders. Curr Opin Neurol Aug;22(4):430-6.

40. PMD Not a diagnosis of exclusion
Enough qualifiers to be included on Ddx early on
Should be recognized and treated rapidly to avoid stigmatization, ‘crazy’ label
CBT, neurologist (a movement disorder induced by internal stress), psychiatrist (somatization)

41. Frequency of PMD in clinical practice%

42. Questions you should be able to answer after this session
What is the most common movement disorder?
Name 2 drugs that can enhance a physiologic tremor and 2 that can turn someone akinetic and rigid?
What is a first line therapy for early tremor in PD for a 45 yr old?
What are the 2 P’s for essential tremor treatment?
Which tremor is so strikingly unilateral and disabling that the patient’s limb is deemed non-functional?
Tensor or levator in essential palatal tremor?

43. Thanks!

45. Palatal Myoclonus saga...
Essential Palatal Myoclonus
Symptomatic Palatal Myoclonus
25% of cases
Most cases
No lesions
Lesion in Mollaret triangle
Presence of ocular abnormalities, facial asymmetry, hemiparesis, etc
Abnormality on neuroimaging (e.g. olivary nucleus hypertrophy)
Audible click: tensor veli palatini inserts in Eustachian tube (entire soft palate)
No audible click: levator veli palatini (edges only)
Myoclonus and click disappears in sleep
Myoclonus persist during sleep
Can be transiently aborted by patient, certain neck postures, mouth opening
Cannot be aborted
From Chenxie!

46. Palatal Myoclonus: involvement of central tegmental tracts
Olivary Hypertrophy instead of degeneration depending on location of lesion
Parvocellular (palatal) portion of the red nucleus
Multiple causes: neurodegenerative, infectious, inflammatory, demyelination, traumatic, ischemic,