Diagnosis and Management of Vertigo

Todays Talk
Dizziness and Vertigo Vertigo Diagnosis Treatment Options Focus of Betahistine in Vertigo Management

Todays Talk
Dizziness and Vertigo Vertigo Diagnosis Treatment Options Focus of Betahistine in Vertigo Management

Dizziness
Third most common complaint among all outpatients1 Single most common complaint among patients older than 75 years1 Generic term used to describe a variety of experiences including giddiness, lightheadedness, faintness, vertigo, fogginess, imbalance, unsteadiness and ataxia2

1. 2.

Chawla N, Olshaker J. Med Clin N Am 2006; 90: 291-304 Nettina S. Topics in Adv Nurs, [ejournal] assessed online Oct 09

Dizziness
Dizziness refers to various abnormal sensations relating to perception of the bodys relationship to space1 Dizziness can be caused by many different medical conditions2 It is estimated that as many as half of cases are due to vestibular disorders2

1.

Sloane P et al, Ann Intern Med 2001; 134: 823-32

2. Hall C and Cox C. Otolaryngol Clin N Am 2009: 42: 161169

Types of Dizziness
Vertigo Presyncopal lightheadedness Disequilibrium Other dizziness

Sloane P et al, Ann Intern Med 2001; 134: 823-32

Vertigo
It is a false sensation that the body or the environment is moving (usually spinning) and suggests a disturbance of the vestibular system1 Accounts for 54% of cases of dizziness2 Vestibular vertigo affects more than 5% of adults in 1 year in the Unites States3 Incidence increases with age4

1. 2. 3. 4.

Sloane P et al, Ann Intern Med 2001; 134: 823-32 Lauuguen R. Am Fam Physician 2006; 73: 244-54 Neurology 2005;65:898-904 Samy H et al. www.emedicine.medscape .com as accessed on October 2009

Types of Vertigo
Peripheral Central Other types

Chawla N and Olshaker J. Med Clin N Am 2006; 90: 261-304

Peripheral Vertigo
Arise from abnormalities in the vestibular end organs (semicircular canals and utricle), the vestibular nerve, and the vestibular nuclei. Most of these causes are benign and readily treatable

Chawla N and Olshaker J. Med Clin N Am 2006; 90: 261-304

Types of Peripheral Vertigo

BPPV Acute suppurative labyrinthitis Vestibular neuritis

Peripheral Vertigo Menieres Disease Acoustic neuroma

Chawla N and Olshaker J. Med Clin N Am 2006; 90: 261-304 BPPV= Benign parosxymal positional vertigo

Trauma

Central Vertigo
There is an involvement of the brain especially the cerebellum Exhibits more serious consequences and aggressive treatment is recommended

Chawla N and Olshaker J. Med Clin N Am 2006; 90: 261-304

Types of Central Vertigo

Cerebellar hemorrhage Central Vertigo Brainstem ischemia Vertebrobasilar Insufficiency

Chawla N and Olshaker J. Med Clin N Am 2006; 90: 261-304

Clues to Distinguish
Characteristics
Severity Onset Duration Positional Fatigable Postural instability Hearing loss or tinnitus Other neurologic symptoms Associated Nystagmus

Peripheral
Severe Sudden Seconds to Minutes Yes Yes Able to walk; unidirectional instability Can be present Absent Horizontal

Central
Mild Gradual Weeks to Months No No Falls while walking; severe Usually absent Usually present Vertical

Chawla N and Olshaker J. Med Clin N Am 2006; 90: 261-304. Swartz R. Am Fam Physician 2005; 71: 1129-30

Most common causes of Vertigo

Benign Paroxysmal positional vertigo (BPPV) Menieres disease Vestibular Neuritis

Brandt T, Zwergal A, Strupp M. Expert Opin Pharmacother 2009; 10: 1537-48

Todays Talk
Dizziness and Vertigo Vertigo Diagnosis Treatment Options Focus of Betahistine in Vertigo Management

Diagnosis

Patient complains of dizziness

Does the patient have true vertigo? Comment An illusion of movement, often horizontal and rotatory. Associated nausea and vomiting indicate a peripheral rather than central cause. May result from peripheral neuropathy, eye disease, musculoskeletal weakness or peripheral vestibular disorders. Caused by cardiovascular disorders reducing cerebral perfusion It may result from panic attacks with hyperventilation

Ask: Possible cause Q. Does the room spin Vertigo around? A. Yes Q. Do you feel unsteady? A. Yes Dysequilibrium

Q. Do you feel like you may Presyncope faint? A. Yes Q. Do you feel lightheaded? Lightheadedness A. Yes is non-specific and hard to diagnose

Kanagalingam J et al. BMJ 2005; 330: 523

Patient complains of dizziness YES

Does the patient have true vertigo? NO

Is the patient taking any Drug that can cause vertigo?

Continue evaluation appropriate for Lightheadedness, presyncope, or disequilibrium

Medications and substances that can cause dizziness or vertigo Aminoglycosides Anticonvulsants, Furosemide Antidepressants, Ethacrynic acid, Anxiolytics. Acetylsalicyclic acid, Alcohol Amiodarone Nicotine Quinine, Caffeine Cisplatinum, Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Anti-Alzheimers medications Labuguen RH. Am Fam Physician 2006; 73: 244-51

Patient complains of dizziness YES

Does the patient have true vertigo? NO

Is the patient taking any Drug that can cause vertigo? YES Consider stopping medication If possible NO

Continue evaluation appropriate for Lightheadedness, presyncope, or disequilibrium

Obtain general History

Obtaining History
Ask for family history including hereditary conditions such as migraine and risk factors for cerebrovascular disease Sexual history should also be noted. Certain sexually transmitted diseases such as syphilis have otologic symptoms Consider age, as it is associated with some underlying conditions (diabetes or hypertension) and these conditions are associated with higher risk of cerebrovascular causes of vertigo
Labuguen RH. Am Fam Physician 2006; 73: 244-51 Kanagalingam J et al. BMJ 2005; 330: 523

Patient complains of dizziness

Does the patient have true vertigo? YES NO Continue evaluation appropriate for Lightheadedness, presyncope, or disequilibrium

Is the patient taking any Drug that can cause vertigo?

YES
Consider stopping medication If possible

NO

No history of other possible causes of vertigo

Obtain general History

Obtain history on the duration of vertigo

Vertigo lasting for few seconds

Features Possible Diagnosis Spontaneous episodes (i.e. no Unilateral loss of vestibular function consistent provoking factors) Spontaneous episodes (i.e. no Late stages of Menieres disease consistent provoking factors) Nausea and/or vomiting Moderate imbalance Nausea and vomiting Late stages of acute vestibular neuronitis

Goebel J. Otolayngol Clin N Am 2000; 33:483-93 Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Vertigo lasting for several seconds to few minutes

Features Possible Diagnosis Induced by position change Benign paroxysmal positional vertigo History of cervical spine trauma Nausea and/or vomiting Induced by changes in head Perilymphatic fistula* or position Superior semicircular canal dehiscence Changes in ear pressure, head trauma, excessive straining, loud noises Hearing loss
* vertigo with perilymphatic fistula can also last from several minutes to hours

Goebel J. Otolayngol Clin N Am 2000; 33:483-93 Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Vertigo lasting for several minutes to hours

Features Possible Diagnosis Cardiovascular risk factors Transient ischemic attack or stroke Neurological symptoms Hearing loss (In case of involvement of the inferior cerebellar artery involvement)

Goebel J. Otolayngol Clin N Am 2000; 33:483-93 Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Vertigo lasting for hours

Features Fluctuating hearing loss Tinnitus, aural fullness History of migraine Headache# Visual aura# Phonophobia, photophobia
# Typical headache and aura is absent

Possible Diagnosis Menieres disease Migrainous vertigo

Goebel J. Otolayngol Clin N Am 2000; 33:483-93 Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Vertigo lasting for days

Features Severe nausea and vomiting Recent upper respiratory illness or middle ear illness Moderate imbalance Nausea and vomiting Imbalance Focal neurological findings Possible Diagnosis Early acute vestibular neuritis viral Labyrinthits (if hearing loss is present)

Cerebellopontine angle tumour; cerebrovascular disease; multiple sclerosis

Goebel J. Otolayngol Clin N Am 2000; 33:483-93 Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Vertigo lasting for weeks

Features Possible Diagnosis History of anxiety, panic disorder or Psychogenic vertigo depression

Goebel J. Otolayngol Clin N Am 2000; 33:483-93 Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Patient complains of dizziness

Does the patient have true vertigo? YES NO Continue evaluation appropriate for Lightheadedness, presyncope, or disequilibrium

Is the patient taking any Drug that can cause vertigo?

YES
Consider stopping medication If possible

NO

No history of other possible causes of vertigo

Obtain general History

Obtain history on the duration of vertigo

Perform head and neck and cardiovascular examination

Head and Neck Examination

Findings Vesicles on the tympanic membrane Henneberts sign (i.e., vertigo or nystagmus caused by pushing on the tragus and external auditory meatus of the affected side) Valsalva maneuver (i.e., forced exhalation with nose plugged and mouth closed to increase pressure against the eustachian tube and inner ear) causes vertigo Other otoscopic findings Inference Herpes zoster oticus Perilymphatic fistula

Perilymphatic fistula or Superior semicircular canal dehiscence

Cerumen impaction or any foreign object in the ear canal Fluid behind the ear drum, perforation or extensive Middle ear disease (ototis media, scarring chronic otitis, cholesteatoma etc)
Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Cardiovascular Examination
Findings Orthostatic changes in systolic blood pressure (e.g., a drop of 20 mm Hg or more) and pulse (e.g., increase of 10 beats per minute) upon standing Carotid bruit, heart murmur or irregular rhythm Inference Orthostatic hypotension, dehydration etc Cardiac arrhythmia

Chawla N and Olshaker JS. Med Clin N Am 2006; 90: 291-304 Labuguen RH. Am Fam Physician 2006; 73: 244-51 Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Patient complains of dizziness

Does the patient have true vertigo? YES NO Continue evaluation appropriate for Lightheadedness, presyncope, or disequilibrium

Is the patient taking any Drug that can cause vertigo?

YES
Consider stopping medication If possible

NO

No history of other possible causes of vertigo Obtain history on the duration of vertigo Perform head and neck and cardiovascular examination
Negative

Obtain general History

Perform neurologic examination

Neurological Examination
Fixation suppression test Head Thrust Test (Head Impulse Test) Posthead shake nystagmus Dix-Hallpike Maneuver Positional Tests

Goebel J. Semin Neurol 2001: 21: 391-8

Warning clinical features warranting neuroimaging

Very sudden onset (seconds) of vertigo that persists and not provoked by position Association with new onset of (occipital) headache Association with deafness but no typical Menieres history Acute vertigo with normal head impulse test Associated with central neurological signs such as severe gait and truncal ataxia

Hung Kuo C. Aus Fam Physician 2008; 37: 341-47

Todays Talk
Dizziness and Vertigo Vertigo Diagnosis Treatment Options Focus of Betahistine in Vertigo Management

Treatment
Vestibular Rehabilitation Therapy (VRT) Pharmacotherapy

Vestibular Rehabilitation Therapy

Involves series of maneuvers involving head, eye and body movements These stimulate the in-build adaptive mechanism Helps patients with peripheral vestibular hypofunction to return to normal activities of daily living and a high quality of life

Kirtane M. Ind J Otolaryngol HNS 1999; 51: 27-36 Hall C, Cox C. Otolaryngol Clin N Am 2009;42: 161169

VRT- Goals
Improve balance Minimize falls Decrease subjective sensations of dizziness Improve stability during locomotion Reduce overdependency on visual and somatosensory inputs Improve neuromuscular coordination Decrease anxiety and somatization due to vestibular disorientation
Zapanta P . http://emedicine.medscape.com/article/883878-print as accessed on December 2009

EXERCISES IN BED : EYE AND HEAD MOVEMENTS

Convergence Exercises

Bending alternately forward and backward

Looking up and down

Looking alternately left and right

Turning alternatively to the left and then right

EXERCISES IN STANDING POSITION

Throwing a small ball from hand to hand under the knee

Changing from sitting to standing, initially with eyes open and then with the eyes closed

Throwing a small (ping pong) ball in, an arc from hand to hand and following it with the eyes

EXERCISES WHILE WALKING

Throwing and catching the ball while walking

Walking around in the room with eyes open and closed

Walking up and down a flight of stairs

Playing any game involving bending, stretching and aiming with the ball

EXERCISES IN SITTING POSITION

Shrugging and rotating shoulders

Bending forward and picking up objects from the floor

Turning head and trunk alternately to the left and the right

Pharmacotherapy
Can be symptomatic or specific Specific treatments are very few (lack of proper data) Most common approach is symptomatic management

Rascol O et al, Drugs 1995; 50: 777-91

Aims of Symptomatic treatment

Eliminate vertigo Enhance or at least non compromise- of the process of vestibular compensation Reduction of neuro-vegetative and pyschoaffective signsnausea, vomiting, anxiety, that often accompany vertigo

Rascol O et al, Drugs 1995; 50: 777-91

Vestibular compensation (VC)

VC is a natural process by which the brain helps the body overcome the feeling of vertigo Takes place mainly at vestibular nuclei (a structure present in the brain stem) The vestibular nuclei receives inputs from the two ears from each side
Lacour M. Curr Med Res Opion 2006; 22: 1651-9

Vestibular Deficit in Vertigo

NOSE

INTACT EAR Vestibular Nuclei

INTACT

INTACT

DAMAGED

Vestibular Nuclei

Normal individual

Imbalance of activity at vestibular nuclei causes vertigo

Lacour M. Curr Med Res Opion 2006; 22: 1651

Reasons for reduced activity at VN of the damaged side

(2) Inhibition by the intact VN (1) Reduced input from the ear

INTACT Vestibular Nuclei

DAMAGED

Imbalance of activity at vestibular nuclei causes vertigo

Vestibular Compensation
There is an increase in histamine levels at VN by the brain Histamine helps achieve VC However, it takes about 3 months for by our body to achieve VC and overcome the symptom of vertigo Hence, treatment should be focused towards hastening VC
Lacour M. Curr Med Res Opion 2006; 22: 1651-9 Lacour M. J Clin Pharmacol (In press)

INTACT Vestibular Nuclei

DAMAGED

Classification of Pharmacotherapy for management of Vertigo

Vestibular Suppressants Drugs that facilitate compensation process

Vestibular Suppressants

Reduction in the symptom of vertigo comes at a price of reduction in vestibular function

Rascol O et al, Drugs 1995; 50: 777-91 Lacour M. Curr Med Res Opion 2006; 22: 1651-9

Treatment with Vestibular Suppressants

Suppressants reduce activity at intact side and thus hamper recovery by VC Hence, they are not recommended for long term use They should be discontinued as soon as possible
Lacour M. Curr Med Res Opion 2006; 22: 1651-9

INTACT Vestibular Nuclei

DAMAGED

Commonly used vestibular suppressants in practice

Drug
Meclizine Cinnarizine Prochlorperazine

Dosage
12.5-50 mg TID 30 mg TID 5 to 10 mg BID or TID

Adverse Reactions
Sedating, precaution in prostatic enlargement Sedation, CNS depression Extrapyramidal side effects

Vestibular Suppressants
Useful for prevention of nausea and reduce vomiting (generally to be used for not more that 1-3 days) post an event Should be discontinued as soon as possible after event subsides They are not to be used chronically or for prophylaxis against subsequent attacks

Lacour M. Curr Med Res Opion 2006; 22: 1651-9 Goebel J. Otolaryngol Clin N Am 2000; 33: 483-93 Brandt T, Vertigo. Its Multisensory Syndromes, 2nd Ed: Pg 49-61

Todays Talk
Dizziness and Vertigo Vertigo Diagnosis Treatment Options Focus of Betahistine in Vertigo Management

Role in Vestibular Compensation

Ideally medication in addition to controlling vertigo should facilitate the healing process and to restore the vestibular function at the damaged VN. Drugs facilitating the histaminergic system have been found effective in the treatment of vertigo and facilitating VC.

Effect of betahistine on locomotor balance recovery in cats

Betahistine treated cats showed a time benefit of 2 weeks in maximum performance

This time benefit was due to early achievement of compensation

Tighilet B, Leonard J, Lacour M. J Vest Res 1995;5:53-66

Role of betahistine in VC
(3) Reducing inhibition by intact by H3 hetro antagonistic action (1) Increasing the levels of histamine in the VN by H3 auto antagonistic action

(2) Increases the activity of the damaged VN by H1 agonistic action

INTACT Vestibular Nuclei

DAMAGED

Betahistine helps achieve the activity of the damaged side within 1 month Giving a time benefit of 2 months !! As compared to the natural course of VC
Lacour M. Curr Med Res Opion 2006; 22: 1651-9; Lacour M. J Clin Pharmacol (In press)

Clinical Studies

Superior to placebo in reducing frequency of vertigo

18 ENT practices in the Netherlands 82 patients suffering from vertigo of various origins

Oosterweld et al, JDR J Drug TherRes 1989; 14:122-6

Effective in both Menieres and BPPV

144 patients suffering from recurrent vertigo related to Menieres disease or PPV

Mira et al, Eur Arch Otorhinolaryngol 2003; 260: 73-7

Effective in acute vertigo

N=29 outpatients with acute vertigo Bradoo et al, Indian JOHNS 2000; 52: 151-8

Week 0

Week 1

Week 2

Week 3

Comparable Efficacy: 24 mg BID vs. 16 mg TID

24 mg BID is as effective as 16 TID in terms of reduction in vertigo spells There was no difference between groups in terms of incidence of adverse events 24 mg BID would be of particular importance in patients non-adherent or partially adherent to treatment

N= 120 ptns with well established Meniers Disease

Gananca M et al, Acta Oto-Laryngologia 2008; 1-6

High Dose, Long Duration Studies

Long term Study- 1 year Higher the dose better the effect

N=112 patients with Menire's disease

Strupp M et al, Acta Oto-Laryngologia 2008; 128: 520-4

Effect on cerebral blood flow

SPECT- Indian Study

(A) Reference Image
SPECT MRI

Pre-Betahistine Therapy (15.06.1999) No. 2540

Post-Betahistine Therapy (12.07.1999) No.

2922 R L R L

11 patients with no peripheral vertigo and with probable diagnosis of ischemia (lack of blood supply) of the Vertebro-basilar artery were included

Left temporal lobe

Krisha BA, Kirtane MV et al Neurology India 2000; 48: 255-9

SPECT- Indian Study

(B) Reference Image
SPECT MRI

Pre-Betahistine Therapy (27.02.1998)

No.791

Post-Betahistine Therapy (10.03.1998) No.

1950

11 patients with no peripheral vertigo and with probable diagnosis of ischemia (lack of blood supply) of the Vertebro-basilar artery were included

Right inferior cerebellar region

Krisha BA, Kirtane MV et al Neurology India 2000; 48: 255-9

(C)

SPECT- Indian Study

Reference Image
Pre-Betahistine Therapy (17.03.1999)
No.1086 MRI

SPECT

Post-Betahistine Therapy (08.04.1999)

No.1599 R L R L

11 patients with no peripheral vertigo and with probable diagnosis of ischemia (lack of blood supply) of the Vertebro-basilar artery were included

Right parieto-occipital region

Krisha BA, Kirtane MV et al Neurology India 2000; 48: 255-9

Betahistine Versus Other Agents

Superior to Cinnarizine

88 patients with peripheral vertigo Deering RB et, Curr med Opion 1986; 10: 209-14

Betahistine associated superior responder rate

Gananca et al, Rev Bras Otorrinolaringol 2007;73(1):12-8.

100 90 80 70 60 50 40 30 20 10 0

88.7 75 70.5 65.8 63.4

91.6

82.4 79.4 86.2 81.5 51.6

Patient (%)

28.9

Meniere's Disease

Other vestibular disorders

N=1,100 outpatients with established Mnires disease or other peripheral vestibulopathies

Betahistine Flunarizine Cinnarizine Gingko Biloba extract Clonazepam No medication

Betahistine associated low incidence of adverse effects compared to others

N=1,100 outpatients with established Mnires disease or other peripheral vestibulopathies

35 30
Patient (%)

25 20 15 10 5 0
0

29.9 26.2 23.8 17.1 13.4 9.1 7.4 0 0 Sleepiness

Betahistine Flunarizine

14.7

2.1

2.8

3 2.3

4.5 2.3

Depression
Cinnarizine Gingko Biloba extract

Axiety
Clonazepam No medication

Gananca et al, Rev Bras Otorrinolaringol 2007;73(1):12-8.

Superior to Flunarizine
4.5

Mean severity of vertigo

4 3.5 3 2.5 2 1.5 1 0.5 0

3.8

3.9

0.6

Day 0
55 patients with recurrent vertigo

Day 60 Flunarizine
Fraysse B et al, Acta- Otolaryngologica 1991; Suppl 490: 3-10

Betahistine

Superior to prochlorperazine

N=30 patients with Menieres disease

Aantaa E et al; Ann Clin 1976; 8: 284-7

Jeck-Thole et al, Drug Saf 2006; 29: 1049-59

Dosage

VERTIN, Prescribing Information

Summary
Betahistine has demonstrated robust efficacy in treatment of vertigo and Menieres disease Betahistine reduces intensity, frequency and duration of vertigo episodes The effect of betahistine is dose dependent Betahistine facilitates the process of compensation Betahistine has well documented safety data