Management of Tremor

TREMOR
Compiled by
Dr PS Deb MD, DM (Neurology)
Director Neurology GNRC Hospitals
Guwahati, Assam, India

TREMOR
 Rhythmical, involuntary oscillatory movement of a
body part, produced by either synchronous or
alternating contractions of antagonist muscles (1-
3).
 Type:
 Rest
 Action
 Postural
 Kinetic

TREMOR EVALUATION
 History
 Age of onset, progression
 Family history
 Systemic symptoms : diaphoresis, palpitations,
and bowel irregularities
 Association: other neurological disease, Drug use
 Examination
 Rate : Frequency
 Amplitude
 Location: Part of the body affected
 Modification:
 Rest (repose)
 Actional
 Postural (static)
 Movement
 Task specific
 Other factors: Anxiety, exertion, sleep, drugs
 Special tests:
 Handwriting
 Drawing Archimedes spirals
 Ability to transfer water between 2 cups or drink
from a cup
 Investigation
 EMG: Antagonist muscle shows, burst
synchronous / asynchronous
 Recording: Acceterometer, Goniometer, Computer

PATHOPHYSIOLOGY
 Due to burst of α motor neuron, synchrony in antagonistic
muscle, presumably inadequately in the strength and timing of
contraction of opposite muscle group.
 Rhythmic burst of discharge of unitary cellular activity in VIM of
thalamus synchronous with tremor on contralateral side with
stopping of tremor by voluntary or passive movement due to
disappearance of burst
 The neurons are arranged somatotopically and respond to
kinesthetic impulse from the muscle and joint involved
 In monkey VIM contains large sized neuron receive dense
projection from the cerebellar nuclei and spinocerebellar tract
 Tremor can be abolished by lesion of VIM
 VIM is key nucleus which is sensory in character as well as
interfering motor activity

PATHOPHYSIOLOGY
 Synchronous burst also occur in sensory-motor cortex,
important for tremor generations.
 Passive stretching of muscle →
 >1Hz Non Parkinsonian
 < 1Hz Parkinsonian
 Suggest tremor rhythm is strongly influenced by spinal reflex
mechanism
 Pathway not clear pyramidal / extrapyramidal
 Probably tremor is produced in the reticular formation
the brain stem or thalamus and is modified and
regulated in its rhythm setting by spinal reflex
mechanism most prominently by the kinesthetic sence.

PATHOPHYSIOLOGY
Frequency Site System involved Human form
8-12Hz None Olivocerebellum Physiological
6-8 Hz Dentate N. Olivocerebellum Essential
3-6 Hz Midbrain
tegmentum
Thalamo-cortical Parkinsonism
Lamore 1984 in monkey Hornalive (GABA antagonist) injection

Oscillation in
Inf- Olive
Activation of
Purkenji Cells
Reticulospinal,
vestibulospinal,
cerebellothalamic
system
Tremor
Tremor abolished by inf. Olive lesion
But, no such lesion found in human except palatal myoclonus

PATHOGENESIS OF TREMOR
Red-
nucleus
OliveCerebellum
Cortex
Basal
Ganglion
Thalamus
Ant.
Horn
Cells
Muscle
External
Protuberance

REST TREMOR
 Parkinsonian syndrome
 Multiple Systems Atrophy,
 Progressive Supranuclear Palsy (PSP),
 Corticobasal Syndrome,
 Parkinsonism-Dementia-ALS of Guam,
 Progressive Pallidal Atrophy,
 Diffuse Lewy Body disease
 Heredodegenerative disorders
 Huntington's disease,
 Neuroacanthocytosis,
 Neurodegeneration with Brain Iron Accumulation,
 Gerstmann-Strausler-Scheinker disease,
 Neuronal Ceroid Lipofuscinosis

CAUSES OF REST TREMOR
 Secondary parkinsonism
 Toxins
 carbon monoxide,
 MPTP,
 manganese,
 methanol,
 cyanide poisoning)
 Drugs
 neuroleptics,
 dopamine depleting drugs,
 Antiemetics
 Infections
 Creutzfeldt-Jakob disease,
 Subacute Sclerosing Panencephalitis,
 fungal
 post-encephalitic
 Metabolic disorders
 hypothyroidism,
 chronic hepatic degeneration,
 mitochondrial cytopathies
 Other:
 vascular events,
 head trauma,
 neoplastic or
 paraneoplastic conditions
 Severe essential tremor
 Midbrain (rubral) tremor
 Psychogenic tremor

PARKINSONIAN TREMOR
 Incidence: 60-70% at the onset(8).
 Rate : 3-7Hz variable
 Amplitude: moderate
 Location: One of both hand→ feet → jaw → tongue
 Type:
 Flexion extension of hand , adduction abduction of
finger, pronation supination of forearm
 Flexion extension of finger + adduction abduction
of thumb – pin rolling tremor
 Foot flexion extension
 Lips and jaw opening and clossing
 Tongue in and out
 Eyes flutter when closed
 Other type: 15-30%
 Fast frequency postural or action tremor
 Paralysis agitance: gentle distal tremor
 Post encephalatic: proximal slow tremor
 Elderly my have tremor for long time without other
features of parkinsonism which may develop later
 Progression:
 Modification:
 Increased
 At the time of repose
 Emotional stress
 Walking
 Reduced
 when hand is supported
 by willed movement
 During deep sleep, relaxation
 Rigidity
 Functional interference
 Does not interfere with voluntary movement
 Association: other neurological disease
 EMG: Antagonist muscle shows, burst synchronous
/ asynchronous
 Recording: Acceterometer, Goniometer, Computer

PAHTOPHYSIOLOGY
 Not due to nigrostriatal dopaminergic deficit
 Animal lesion of SN, striatopallidal → no tremor
 All patients with SN lesion do not have tremor
 Central oscillator in thalamus, cerebellum, globus pallidus, or
subthalamic nucleus,
 Monkey: lesion between SN and RN in midbrain tegmentum
→ parkinsonian like tremor (Ward)
 Severity may correlates with loss of subgroup of
mesencephalic neurons
 A midbrain lesion near the red nucleus can involve the
nigrostriatal pathway in addition to cerebellar outflow tracts
and cause a tremor at rest as well as an action tremor, known
as a Holmes, or rubral, tremor. (5)

RX PD TREMOR
 Dopamineric agent : 50% reduction with levodopa ,
Amantadine, clozapine, propranolol,and mirtazapine,
 Botulinum toxin has been found to effective for some
patients with PD hand tremor (19,20) and jaw tremor
(21).
 The subthalamic nucleus is the most common surgical
target for medically refractory PD-related tremor (8)
 but lesioning or deep brain stimulation of the thalamic
nucleus ventralis intermedius can also be performed.
 A lack of major benefit has been observed with gamma
knife thalamotomy (22).

OTHER REST TREMORS
 Cerebellar rest tremor: also due to striatonigral lesion
 Hereditary chin tremor
 Paroxysmal tremor
 Dystonic disorder with tremor – spasmodic torticollis – 1-6.5 Hz
 Shuttering attack of children
 Whole body tremor + sympathetic changes
 ± Essential tremor or FH of ET
 Jittering of new born infent
 With other signs of CNS hyperactivity
 Hypermobility
 Hypertonicity
 Easy to startle
 Due to pre or post natal insult

POSTURAL TREMOR
 Physiologic
 Essential

PHYSIOLOGICAL TREMOR
 Asymptomatic oscillation of body
 Present even during sleep
 Cannot be seen by eyes
 Frequency 8-13 Hz
 Due to (Marsden)
 Mechanical resonance frequency of related joints
 Irregularity of muscle contraction in an un-fused tetanus of
slow firing motor unit
 Reflexion of balistocardiogram
 Oscillation in the spinal monosynaptic reflex

ENHANCED PHYSIOLOGIC TREMOR
 Frequency :8-13Hz (altered by mechanical
loading, alpha/beta stimulation)
 Due to increased operation of segmental stretch
reflex consequent to mechanical changes produced
in the muscles by its beta adgrenergic stimulation

PHYSIOLOGIC TREMOR
 Physiologic tremor enhanced by
 Emotion – anxiety stress
 Exercise, fatigue
 beta-agonists,
 dopaminergic drugs,
 stimulants,
 valproic acid,
 carbamazepine,
 verapamil,
 epinephrine,
 psychiatric drugs,
 methylxanthines (coffee,
tea),
 cyclosporine,
 interferon, and flunarizine.(5-
7)
 stress,
 Endocrine: hypoglycemia,
thyrotoxicosis,
pheochromocytoma,
adrenocorticosteroids
 Toxin: mercury, lead, alcohol
withdrawal

OTHER CAUSES OF POSTURAL TREMOR
 Dystonia,
 Parkinsonism,
 Myoclonus,
 Kennedy syndrome,
 Roussy-Levy syndrome.
 Parkinson syndromes may have a postural component,
known as a re-emergent tremor,
 Midbrain lesion or cerebellar dysfunction (titubation)
(5).
 Psychogenic.

ESSENTIAL TREMOR
 Inherited, constitutional malady characterized by kinetic tremor in
the absence of other neurological signs
 Prevalence – 0.9% increases with age >95years >20%
 Onset: childhood or late life
 Progression : Unilateral to bilateral and from arm to head after
several year, voice, tongue, leg and trunk can be involved rarely,
slowly progressive with increased severity
 It can be hereditary (30%) with variable penetrance or sporadic
and has a bimodal age at onset.
 Etiology : Unknown (Genetic, toxic)
 Pattern: Kinetic tremor, postural and during action (writing,
drinking,), >50% have intention component, rarely rest tremor
also

ESSENTIAL TREMOR
 Frequency : 4-12 Hz inversely related to amplitude
 Amplitude more than physiological, increases gradually and large
proportion are disabled
 Type: Postural action tremor, sometime intentional, rarely rest (frequency
4-12Hz)
 Site: Aadduction-abduction movement of the fingers (individual finger can
be affected) and flexion-extension movement of the hands-> Head no-no
(F>M)-> voice and jaw, lower limbs are rarely affected.
 Modification: Forment’s sign: Tremor and cog-wheeling increased
voluntary activity even in opposite limbs and reduced by relaxation
 Increased by cold, exercise, emotion, sympathetic stimulation
 Associated cerebellar features (mild ataxia of gait ), Mild cognitive
difference

PATHOPHYSIOLOGY
 Cerebellum (Purkinje cells) and inferior olive have
been implicated by fMRI, PET, diffusion tensor
imaging and Pathological studies

ASSOCIATED NEUROLOGIC DISEASE
 Parkinson’s disease
 Higher incidence of PD in
ET 24times
 In familial PD ET common
 Spasmodic torticollis
 Torsion dystonia
 Essential myoclonus
 Peripheral neuropathy
 Fredrick's ataxia
 Physiological tremor
 Other condition
 Essential hypertension
 CVD
 CHD
 Alcoholism
 Intelligent professional

ESSENTIAL TREMOR TYPE (MARSDEN)
 Type I – Benign exaggerated essential tremor (8-12Hz)
 Type II – Benign pathological essential tremor (5-7Hz)
 Type III – Severe pathological essential tremor (4-6Hz)
frequently spasmodic, not responsive to therapy
 Type IV – Symptomatic essential tremor, associated with other
neurological conditions

ESSENTIAL TREMOR - RX
 Standard Rx: Propranolol, Primidone
 Other Rx: Other beta blockers, Topiramate
, Gabapentin , benzodiazepine
 Deep brain stimulation: in resistance cases
 Ventralis intermedius (Vim)
 Thalamotomy not recommended

KINETIC TREMOR
 Kinetic tremor refers to oscillation
during a visually-guided voluntary
movement (5).
 Cerebellar outflow tract disorder
 Stroke
 Demyelination
 Infection or post-infection
 Viral, bacterial, fungal, parasitic, prion
 Trauma
 Neoplastic or paraneoplastic
 Endocrinopathies
 Hereditary disease
 Spinocerebellar ataxias,
 Wilson's disease
 Medications
 Phenytoin, valproate, amiodarone, lithi
um
 Heavy metals & toxins
 Organic mercury, alcohol, toluene
 Midbrain (rubral) tremor
 Severe essential tremor
 Psychogenic tremor

CEREBELLAR TREMOR MILD
 Mild (simple) rapid 10Hz distal (unresponsive to INH)
 Severe (Rubral – Gorden Holmes 1904) – not rubral but upper
brain stem lesion involving dentato-thalaminc and dentato-olivary
system
 Proximal can be distal Arm > Leg, head and trunk can be
involved
 Irregular low frequency (3-5Hz)
 High amplitude, increased amplitude with prolonged posture
 Intention tremor, increased with goal directed movement of
difficult pathway
 Perpendicular to the direction of movement
 Associated rest tremor due to involvement of different pathway.

CAUSES OF INTENTION TREMOR
 Multiple sclerosis
 Brainstem tumor
 Benedict’s syndrome

PATHOPHYSIOLOGY
 Dysfunction of cerebellar-based motor control
 mechanical oscillation of joints and their muscles,
 stretch reflex oscillations through afferent muscle
spindle pathways to the brain, and centrally-located
oscillatory neuronal groups (5).
 Cerebellar tremor tends to occur ipsilateral to a lesion of
the deep cerebellar nuclei or outflow tracts through the
superior cerebellar peduncle (5).
 It is likely injury to these outflow tracts through the
midbrain that cause the kinetic component of a Holmes,
or rubral, tremor.

TREATMENT OF KINETIC TREMOR
 Difficult:
 CBZ in small trial
 Glutethimide in MS
 Bnezodiazepine
 Baclofen
 Botox no use
 Tetrahydrocanabinol
 5 Hydroxytryptophan
 INH 900-1200mg/d with Pyridoxin
 Removal of cause
 Behavioral modification: wrist weight while eating
 Surgical
 Thalamotomy or
 Deep brain stimulation of the nucleus ventralis intermedius (Vim)

CEREBELLAR INTENTION TREMOR
 Rhythmic oscillation on reaching the target perpendicular to
the direction of movement
 Once the target is reached tremor will cease after 1 sec
(postural tremor will continue once the target is reached)
 Frequency 3-5 Hz
 Sometime associated with titubation of head and trunk
 Interferes with voluntary act
 Drugs ineffective
 Stereotaxis improve tremor but not function
 Adding wt to the limb
 Vigorous friction of the joints

PERIPHERAL NEUROPATHY WITH TREMOR
 Hereditary motor sensory neuropathy with ET
 Chronic relapsing neuropathy after 2-3rd relapse 6-8Hz
tremor improve with neuropathy
 Paraprotenemia with neuropathy (IgM benign)
 Muscles are not weak, motor conduction reduced,
proprioception normal
 Recovery phase of GBS
 Rarely Diabetic neuropathy
 Uremic neuropathy
 Porphyria

PATHOGENESIS OF TREMOR IN PN
 Enhanced physiologica tremor by weakness and
impairment of stretch reflex (Shid et al)
 Loss of large fiber sensory function -> imbalance in
the sensory input to the motor neuron pool
(Shahani and Yong)
 Primary CNS disorder
 Spinocerbellar pathway involved -> impaired central
function

WILSON DISEASE
 Postural and intension tremor
 3-5Hz severe poximally
 Can increase amplitude with time
 Wing beating tremor at shoulder when abducted at
90 degree and elbow flexed

POST TRAUMATIC
 Proximal postural and intentional
 Following sever head trauma
 Stereotactic VIM lesion
 Propranolol

ALCOHOLIC TREMOR
 Exaggerated physiological
 Essential tremor – inherited as different tract
 3Hz leg tremor - by standing and closing eyes –
ant cerebellar lesion

TASK SPECIFIC TREMOR
1. Primary writing tremor
 Related to essential tremor, writer’s cramp, dystonia
 Alcohol, Propranolol, Anticholinergic improve in some
2. Vocal tremor
1. Related to ET, family history
1. Respond to alcohol, propranolol
2. Not related to ET, no family
1. Does not respond to beta blocker

ORTHOSTATIC TREMOR
 On standing
 Reduced by walking
 Clonazepam 4-6mg effective

HYSTERICAL TREMOR
 Commonly action tremor
 May persist in repose
 Irregular frequency
 Unilateral
 Disappear when attention diverted and restart
tremor shift to other parts of body

ASTERIXIS
 Arrhythmic lapses of sustained posture
 Sudden interruption of muscular contraction allow
gravity or inherent elasticity of muscle to produce a
movement when the patient corrects with overshoot
 Metabolic encephalopathy
 Anticonvulsant
 Anticonvulsant
 Unilateral Asterixis
 Ant. Cerebral occlusion
 Thalamotomy
 Mid brain lesion

Management of Tremor

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