Transcript Halim Fadil, MD - Kane Hall Barry Neurology

Movement Disorder Program
Kane Hall Barry Neurology
Bedford/Keller
Halim Fadil, MD: Movement Disorder Neurologist
Susan Imke, FNP: Gerontological Nurse
Practitioner
In partenership with:
Abdolreza Siadati, MD, Neurosurgeon
Fort Worth Brain and Spine Institute
Dr. Linda Csiza, PT, DSc, NCS
Riata Therapy Specialists
• Neurology Residency: LSU Shreveport, LA
• Neurophysiology Fellowship: UC Davis
• Movement Disorders Fellowship: Cedars-Sinai
Medical Center, Los Angeles, CA
With Dr. Michele Tagliati
What Is Essential Tremor?
• ET is a neurologic disorder characterized by
uncontrollable shaking or tremor
• Essential means
− There is no other cause for tremor
− There are no other neurologic signs
What causes ET?
• The true cause of ET is still not understood
• Also known as “familial tremor”
• Genetics is responsible in 50% of the people
with the condition
How common is ET?
• The most common movement disorder
• Affects as many as 7.6 million people in the
US
• About 2.2 % of the US population
• 5% of people age > 65 y have ET
Louis ED and Ottman R. How many people in the USA have Essential Tremor?
Deriving a Population Estimate based on Epidemiological Data. Tremor Other Hyperkinet
Mov 2014
Celebrities with ET
• Late senator Robert Byrd
• John Adams: 2nd US President
• John Q. Adams: 6th US President
• Actress Katharine Hepburn
Who gets ET?
• Can occur at any age, however there is a
bimodal distribution with peaks in the second
and sixth decades (1, 2)
Bain et al. A study of heredity of essential tremor. Brain 1994 (1)
Lou and Jankovitch. Essential tremor: Clinical correlates in 350 patients.
Neurology 1991 (2)
Manifestations of ET
• Bilateral tremor of the hands and forearms
• May also involve the head, voice ,and sometimes
legs and trunk
• Postural and kinetic (associated with action)
tremor
• Tremor usually worsens with emotional stress
and may improve with alcohol
Bain P, et al. Criteria for the diagnosis of essential tremor. Neurology 200
Manifestations of ET
•Functional disabilities in basic and instrumental
activities of daily living
• Balance problems with risk of fall in some cases
• Non-motor features:
– Mild cognitive impairment
– Mood disorders: Anxiety, depression (1)
– Sleep disturbance, ?Rapid eye movement sleep behavior disorder
– ?Reduction of sense of smell
(1) Sinoff and Badarny. Tremor other Hyperkinet Mov 2014.
Manifestations of ET
• Tremor starts insidiously and progresses slowly
• ET is not dangerous but can be disabling
Diagnosis
• Clinical: Based on symptoms
• There is no lab test or radiological scan
• Rule-out other conditions and medications that
may cause a tremor
Other Causes of Tremor
• Drug induced: Caffeine, Amphetamines, Prozac,
Lithium, Lipitor, Depakote, Amiodarone,
Verapamil
• Electrolyte imbalance: Low Ca, Low Na
• Thyroid dysfunction
• Parkinson’s Disease
• Post traumatic tremor
• Multiple Sclerosis
• Physiologic tremor
Misdiagnosis of ET and PD is Common
•Clinical studies have found a high level of
misdiagnosis of ET and PD
• A previous diagnosis of PD was rejected in 15% of
patients using standardized criteria and > 1 year
follow-upa
• ~26% of patients receiving antiparkinsonian medication
did not have a parkinsonian syndromeb
• A previous diagnosis of ET was rejected in 37% of
patients using standardized criteriac
a. Schrag A, et al; b. Meara J, et al; c. Jain S, et al
Is ET Related to PD?
• NO, NO, NO
• ET tremor differs from PD
• ET patients do not feel slow or stiff
• ET patients do not have difficulty walking
• ET does not progress into PD
• Some patients can have both diagnoses
Areas of Uncertainty
Definite PDa
Asymmetric tremor
Areas of Clinical
Uncertaintyb-f
Mixed tremor types
Resting tremor
Questionable bradykinesia
Bradykinesia
(Slowness)
Questionable response to
dopaminergic therapy
Rigidity (Stiffness)
Definite ETg
Symmetric tremor
Postural and kinetic
(action) tremor
Voice or head tremor
Family history of tremor
Ambiguous/Overlapping Symptoms
PD symptoms
ET symptoms
+ postural and kinetic tremors
+ symmetric tremor
+ symmetric tremor
+ rest tremor
+ no bradykinesia (slowness)
+ cogwheeling present
+ no rigidity (stiffness)
DaT Scan: SPECT Images
Normal
Early Parkinson’s D
Reduction of the dopamine transporter correlates with the loss of presynaptic
Dopamine seen in parkinsonian syndromes
Case Presentation
• Woman age 60 y presents for evaluation of a longstanding tremor
• -7year history of bilateral symmetric hand tremor that
occurs with activity and is especially bothersome
when she writes or holds a cup
• Tremor improves with wine. Her father had a similar
tremor
• Not bothersome but has increased in past several
months
• Recently noticed occasional right-arm tremor at rest
Case Presentation (cont)
• Neurologic examination
• Bilateral action tremor when she holds a cup
• Slight rest tremor component in the right arm
• Trace of increased tone in the right wrist
• Normal balance and gait
• No other medical history
Case Conclusion
• The patient had a history of long-standing ET supported by a positive
family history (present in 50% of patients) and response to alcohol
• In addition to the bilateral action tremor typical of ET, the examination
demonstrates subtle features of asymmetric rest tremor, suggestive of
early PD
• The clinical diagnosis is ET but you are concerned that she may have
early PD in addition
• Two possible approaches
− Clinical follow-up to see if she develops clearer features of parkinsonism
− Obtain a dopamine transporter SPECT scan
• Patient elects to have the SPECT scan
− SPECT demonstrates normal dopamine uptake
− ET is confirmed
Summary
• ET and PD are clinical diagnoses, but
symptoms can sometimes overlap, causing
misdiagnosis
• Timely and accurate diagnosis of PD and ET
will advance appropriate treatment and improve
the patient’s quality of life
• Patients with atypical symptoms may benefit
from dopamine transporter SPECT to
differentiate between a parkinsonian syndrome
and ET
Treatment of Essential Tremor
• There is no cure
• Treatment is symptomatic.
Approaches to treatment
• Physical and psychological measures
• Lifestyle modifications
• Pharmacologic treatments
• Botulinum toxin injection
• Deep Brain Stimulation surgery
Approaches to treatment
• The selection of treatment options must be
based on individual needs, taking into account
patient history, tremor severity, coexistent
diseases, current medications, response to
previous therapy, and other factors.
Approaches to treatment: No treatment
• Because no therapies are known to prevent or
slow the natural progression of ET
• Treatment is recommended only when tremor
begins to interfere with a patient's ability to
perform ADLs or leads to social embarrassment
• No treatment may be the best option if functional
disability is minimal
Approaches to treatment:
• Physical measures: Weighted wrist cuffs,
weighted utensils
• Psychological measures: Relaxation therapy
• Lifestyle changes:
– Restricting caffeine intake and other stimulants.
– Alcohol may improve the tremor, so BEWARE of alcohol
abuse
Antihypertensive Medications
• These include beta blockers and calcium channel
blockers and are used to treat hypertension and
other cardiovascular conditions.
• Two clinical studies suggest that propranolol
(Inderal) reduces tremor in patients with ET.
• Others include atenolol (Tenormin) and sotalol
(Sotacor).
Antihypertensive agents
• Propanolol (Inderal) is a first line agent for ET
• Dose: 60 mg to 320 mg daily
• Response rate: 50% to 70%
• Tremor improvement: 50%
• Dropout rate: 20%
• Side effects: Drop of blood pressure, bradycardia,
fatigue, erectile dysfunction, drowsiness, dyspnea
seen in 60%
Antiepileptics
• Primidone (Mysoline) is a first line agent for ET
• Dose: 250 mg to 750 mg daily
• Response rate: 30% to 50%
• Tremor improvement: 50% to 70%
• Dropout rate: 20% to 30%
• Side effects: Sedation, fatigue, dizziness,
confusion, nausea, flu-like symptoms seen in
22% to 72%
Antiepileptics
• Topiramate (Topamax) is a second line agent for
ET
• Dose: 150 mg to 300 mg daily
• Response rate: 30% to 40%
• Tremor improvement: 20% to 37%
• Dropout rate: 30%
• Side effects: Paresthesias, sedation, fatigue, weight
loss, dizziness, confusion, nausea, seen in 50%
Antiepileptics
• Gabapentin (Neurontin) is a second line agent for
ET
• Dose: 1200 mg to 3600 mg daily
• Response rate: 30%
• Tremor improvement: 30% to 40%
• Dropout rate: 10%
• Side effects: Sedation, weight gain, dizziness,
nausea seen in 30% to 40%
Antiepileptics
• Pregabalin (Lyrica) is a second line agent for ET
• Dose: 150 mg to 600 mg daily
• Response rate: 30% to 50%
• Tremor improvement: 30% to 40%
• Dropout rate: 10%
• Side effects: Sedation, weight gain, dizziness,
nausea seen in 30% to 40%
Benzodiazepines
• Clonazepam (Klonopin) is a second line agent for
ET
• Dose: 0.5 mg to 4 mg daily
• Response rate: 50% to 70%
• Tremor improvement: 30% to 50%
• Dropout rate: 10%
• Side effects: Sedation, cognitive impairment,
Tolerance, dependance, abuse seen in 50%
Antipsychotics
• Clozapine (Clozaril) ) is an atypical neuroleptic
with minimal extrapyramidal side effects that
has been shown to reduce tremor by 45-50% in
two controlled studies. Third line agent
• However, clozapine use has a 1% risk of
agranulocytosis, a serious side effect, and its
use should be reserved for refractory cases.
Botulinum Toxin
• Chemodenervation using botulinum toxin A
(Botox) has been demonstrated to reduce hand
and head tremor in patients with ET.
• Its use is hampered by side effects including hand
weakness.
• Two controlled studies and 4 uncontrolled studies
demonstrated improvement in limb tremor with
BTX.
Treatment of Essential Tremor
• About 30 % to 50 % of ET patients will not
respond to medical therapy
Surgical Treatment
• Thalamotomy is a stereotactic procedure that
creates a lesion in the ventral intermediate
nucleus (VIM) of the thalamus.
• Studies have typically reported an 80–90%
improvement in tremor symptoms compared to
baseline.
Surgical Treatment
• Deep brain stimulation (DBS) uses
high frequency electrical stimulation
from an implanted electrode to modify
activity in the target area, usually the
VIM thalamus.
• The electrode is connected to a pulse
generator which is implanted in the
chest wall.
• DBS is usually reserved for patients
who are refractory to
pharmacotherapy.
Deep Brain Stimulation
Indications of surgery?
• Certainty of diagnosis
• Severe symptoms with related disability
• Proper trial of pharmacological treatment
DBS anatomical Target
• Ventral Intermediate nucleus of the thalamus
Deep Brain Stimulation
Advantages
• Does not involve destructive brain lesions
• Bilateral procedures associated with minimal risk
• Stimulation settings can be adjusted to maximize
benefit and minimize adverse effects
• Does not preclude future therapies that depend on the
integrity of the basal ganglia
Olanow et al. Neurology. 2001;56(suppl 5):S1-S88.
Deep Brain Stimulation
Disadvantages
• Mechanical and infectious adverse effects associated
with implanted device
• Need to periodically replace battery
• High cost
Olanow et al. Neurology. 2001;56(suppl 5):S1-S88.
Coping tips for daily living
• Learn to use your tremor-free hand
• Hold your chin toward your chest or turn your
head to the side to control the tremor
• Use travel mugs with lids
• Carry straws with you
• Avoid caffeine, ephedra, and any OTC meds that
may increase the heart rate
• Keep your elbows close to your body when
performing tasks
Coping tips for daily living
• Stress control: Massage therapy,..
• In restaurants, request that your meat be cut in
the kitchen, avoid buffets..
• Use heavier glasses and mugs, dishes with
vertical sides
• Use an electric toothbrush
• Print rather than write script, write in small letters
Be who you are and say what you feel
because those who matter don’t mind
and those that mind don’t matter
-Dr. Seuss
Thank you