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.

PATHOPHYSIOLOGYFrequency 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 lesionBut, no such lesion found in human except palatal myoclonus

PATHOGENESIS OF TREMOR

Red-nucleus

OliveCerebellum

Cortex

Basal GanglionThalamus

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, lithium 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 tremor1. 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

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