management of tremor
DESCRIPTION
This presentation was made from Vinken and Bruyn's Handbook of Clinical Neurology, Marsden's Book of Movement Disorder, Movement Disorder SocietyTRANSCRIPT
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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