MANAGEMENT OF VERTIGO

What is vertigo ?
Bedside testings for vertigo. Treatment of vertigo. Betaserc 24 in the treatment of

vertigo.

 What is vertigo ?

Bedside testings for vertigo.

Treatment of vertigo. Betaserc 24 in the treatment of

vertigo.

Maintaining balance is dependent on input from a number of sources

Eye Inner ear (vestibular system)

Skin pressure receptors Muscle and joint sensory receptors

Central Nervous system

Controls eye movements

Postural control via muscles

Balance

Goebel JA. Otolaryngol Clin North Am 2000;33:48393. Shepard NT, Solomon D. Otolaryngol Clin North Am 2000;33:45569

The vestibular system is the dominant sensory input guiding balance

Utricle Semicircular canals Otolith organs

Saccule

Vestibular nerve

Ampullae

Cochlea

Sensory hair cells within the inner ear provide information on the position and movement of the head
Goebel JA. Otolaryngol Clin North Am 2000;33:48393.

Maintaining balance is dependent on input from a number of sources

Eye Inner ear (vestibular system)

Skin pressure receptors Muscle and joint sensory receptors

Central Nervous system

Controls eye movements

Postural control via muscles

Balance Disfunction
Goebel JA. Otolaryngol Clin North Am 2000;33:48393. Shepard NT, Solomon D. Otolaryngol Clin North Am 2000;33:45569

Imbalance/ dizziness

Vertigo is one of four types of dizziness

Dizziness
Vertigo
An illusion of movement, usually rotation

Presyncope

Disequilibrium

Other subtypes

A feeling of A sense of Swimming or faintness or unsteadiness in the floating loss of lower body sensations consciousness Feelings in the head Feelings of are unaffected dissociation Relieved when Difficult to sitting down describe

Betaserc is indicated for vertigo

Drachman DA, Hart CW. Neurology 1972;22:3234. Sloane PD et al. Ann Intern Med 2001;134:82332.

DEFINITION
VERTIGO is an illusion of movement either of the person or of objects about the person. It is one of the manifestations of vestibular disorder.

Vestibular disorder

Subjective Vertigo

Objective Nystagmus Ataxia

Balance requires information of similar intensity from both vestibular systems

Head movement

Activation of cells in left vestibular system

Activation of cells in right vestibular system

Central nuclei

10

10

Normally, the input from left and right vestibular system is of similar intensity (e.g. of size 10)

HOW DOES VERTIGO DEVELOPE ?

Right vestibule damaged Left vestibule normal

abnormal firing/discharge

normal firing/discharge

Right vestibular nuclei

Left vestibular nuclei

Unequal firing/ discharge from the two sides to cerebellum & brain

VERTIGO

Vertigo can be of central or peripheral origin

Central
Involving structures in the central nervous system (e.g., cerebrum, cerebellum, brainstem)

Peripheral
Involving structures not part of the central nervous system, most frequently the inner ear

Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101. Puri V, Jones E. J Ky Med Assoc 2001;99:31621. Salvinelli F et al. Clin Ter 2003;154:3418. Strupp M, Arbusow V, Curr Opin Neurol 2001;14:1120.

Peripheral vertigo results from a dysfunction in vestibular system functioning

Central nuclei

10

In other cases, only symptomatic treatment is available In some cases, peripheral vertigo can be cured If treatment is unsuccessful, vertigo may improve slowly as compensatory mechanisms are established

Central vertigo results from a dysfunction in central processing

Central nuclei

10

10

Input from left and right vestibular system remains of similar intensity, but central processing is impaired (e.g. of size 10) Central vertigo requires central treatment

Vertigo is a common complaint in the general population

In population-based studies:
Vertigo occurs in 47% of people1, 2 Vertigo accounts for 2530% of dizziness presentations3

In people aged over 75 years:

40% of women and 30% of men report some form of postural disturbance2

1.Yardley L et al. Br J Gen Pract 1998;48:1131-35. 2.Sixt E, Landahl S Age Ageing 1984;16:3938. 3. Hanley K et al. Br J Gen Pract 2001;51:66671. 4.Toupet M et al. Rev SFORL 2004;83:5763.

VERTIGO PERIPHERAL vs CENTRAL

Symptom
Peripheral

Likely aetiology
Central

Vertigo episodes
Symptom onset

Mild/moderate
Sudden

Chronic and unremitting

Gradual

Imbalance
Nausea, vomiting Auditory symptoms Neurological symptoms

Mild/modete
Severe Common Rare

Severe
Varying Rare Common

Changes in mental status/ consciousness

Compensation/resolution

Infrequent
Rapid

Sometimes
Slow

Baloh RW. Otolaryngol Head Neck Surg 1998;119:559. Puri V, Jones E. J Ky Med Assoc 2001;99:31621.

Vertigo of Peripheral origin: causes

Condition
Benign paroxysmal positional vertigo (BPPV)

Details
Brief, position-provoked vertigo episodes caused by abnormal presence of particles in semicircular canal An excess of endolymph, causing distension of endolymphatic system
Vestibular nerve inflammation, most likely due to virus Labyrinth inflammation due to viral or bacterial infection Compromises blood flow to the labyrinthine Damage to the labyrinthine after head trauma Typically caused by labyrinth membrane damage resulting in perilymph leakage into the middle ear Inappropriate immunological response that attacks inner ear cells

Decreasing frequency

Menieres disease
Vestibular neuronitis Acute labyrinthitis Labyrinthine infarct Labyrinthine concussion Perilymph fistula Autoimmune inner ear disease

Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101. Parnes LS et al. CMAJ 2003;169:681 93. Puri V, Jones E. J Ky Med Assoc 2001;99:31621. Salvinelli F et al. Clin Ter 2003;154:3418.

Vertigo of Central origin: causes

Condition
Migraine Decreasing frequency Vascular disease Multiple sclerosis Vestibular epilepsy Cerebellopontine tumours

Details
Vertigo may precede migraines or occur concurrently Ischaemia or haemorrhage in vertebrobasilar system can affect brainstem or cerebellum function Demylination disrupts nerve impulses which can result in vertigo Vertigo resulting from focal epileptic discharges in the temporal or parietal association cortex Benign tumours in the internal auditory meatus

Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101. Salvinelli F et al. Clin Ter 2003;154: 3418. Solomon D. Otolaryngol Clin North Am 2000;33:579601. Strupp M, Arbusow V, Curr Opin Neurol 2001;14:1120.

Duration of vertigo episode can provide an indication of underlying cause

Duration of vertigo episodes

Seconds BPPV Minutes or hours Menieres disease Perilymph fistula Migraine Transient ischemic attack A day or more Vestibular neuritis Multiple sclerosis Brainstem stroke

Salvinelli F et al. Clin Ter 2003;154:3418.

 What is vertigo ?

Bedside testings for vertigo.

Treatment of vertigo. Betaserc 24 in the treatment of

vertigo.

Bedside testing for Vertigo

Balance Test
Postural Test, Eye movement test In people aged over 75 years: Romberg test, Unterberger test, Babinski-Weill test, Brny pointing test

1.Yardley L et al. Br J Gen Pract 1998;48:1131-35. 2.Sixt E, Landahl S Age Ageing 1984;16:3938. 3. Hanley K et al. Br J Gen Pract 2001;51:66671. 4.Toupet M et al. Rev SFORL 2004;83:5763.

 What is vertigo ?

Bedside testings for vertigo.

Treatment of vertigo. Betaserc 24 in the treatment of

vertigo.

CURRENT TREATMENT OPTIONS

1.Treat the underlying cause
Pharmacotherapy Particle repositioning procedure (in BPPV) Surgery

2. Symptomatic
Pharmacotherapy

3. Rehabilitative
To promote long-lasting neural reorganisation Vestibular rehabilitation exercises
Therapeutic option Depends on the type and cause of vertigo
Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101.

CURRENT TREATMENT OPTIONS

1.Treat the underlying cause 2. Symptomatic 3. Rehabilitative

Therapeutic option Depends on the type and cause of vertigo

Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101.

TREATMENT OF THE CAUSE OF VERTIGO

CAUSE TREATMENT

PERIPHERAL CAUSE
BPPV Labyrinthine concussion Menieres disease Labyrinthitis Perilymph fistula Vestibular neuritis Canalith repositioning manoeuvre (Brandt-Daroff) Vestibular rehabilitation Low-salt diet, diuretic, surgery, transtympanic gentamicin Antibiotics, removal of infected tissue, vestibular rehabilitation Bed rest, avoidance of straining Brief course of high-dose steroids, vestibular rehabilitation

CENTRAL CAUSE
Migraine Vascular disease CPA tumours Beta-blockers, calcium channel blockers, tricyclic amines Control of vascular risk factors, e.g., antiplatelet agents Surgery

Baloh RW. Lancet 1998;352:18416. Goebel JA. Otolaryngol Clin North Am 2000;33:48393.

CURRENT TREATMENT OPTIONS

1.Treat the underlying cause 2. Symptomatic 3. Rehabilitative

Therapeutic option Depends on the type and cause of vertigo

Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101.

SYMPTOMATIC TREATMENT
ANTIVERTIGO I. Vestibular Suppressant
1. Ca antagonist : Flunarizin 2. Vasodilator : Betahistine 3. Tranquilizer : diazepam, haloperidol, sulpiride 4. Antihistamin : Difenhidramine, meclizine. 5. CNS stimulant: ephedrin, amphetamin

II. Antiemetic
1. Anticholinergic : atropine, scopolamine 2. Phenotiazine : Prochlorperazine, metoclopramide. Side effects: sedation, extrapyramidal.

CURRENT TREATMENT OPTIONS

1.Treat the underlying cause 2. Symptomatic 3. Rehabilitative

Therapeutic option Depends on the type and cause of vertigo

Baloh RW. Lancet 1998;352:18416. Mukherjee A et al. JAPI 2003;51:1095-101.

VESTIBULAR REHABILITATION EXERCISE

Mechanism: neural learning and neural reorganization. Aim: to promote adaptation and compensation of the nervous system Particularly useful when:
Medical therapy is ineffective Patients have poor central integration or motor function

Baloh RW. Lancet 1998;352:18416. Goebel JA. Otolaryngol Clin North Am 2000;33:48393. Konnur MK. J Postgrad Med 2000;46:2223. Mukherjee A et al. JAPI 2003;51:1095101.

INSIGHT FOR THE REHABILITATION OF PATIENTS WITH VESTIBULAR DEFICIT

Perform vestibular rehabilitation early Favour active retraining Modify rehabilitation programs to suit individual patients Examine patients in a standardized environment Use static and dynamic test Avoid drug with sedative effect
Lacour M,Durr.Med.Research and Opinion vol 22. No.9,2006,1651-1659

 What is vertigo ?

Bedside testings for vertigo.

Treatment of vertigo. Betaserc 24 in the treatment of

vertigo.

BETASERC 24 MG
Betahistine dihydrochloride

The First H3 Receptor Antagonist

Betaserc
Mode of action: 1. Increases cochlear and cerebral blood flow. 2. Regulates firing activity of vestibular nuclei. 3. H1 agonist and H3 receptor antagonist. Dose: 24 mg b.i.d Absorption: rapid. Half-life: 3-4 hours Contraindications: Hypersensitivity Precaution: pheochromocytoma, peptic ulcer, bronchial asthma

Effect of Histamine in the Brainstem (Heteroreceptors)

H S

H3

Post-synaptic nerve H2

Betahistine on H3 Heteroreceptors (Brainstem)

H S B

H3
Serotonin has a regulatory effect on vestibular nuclei Sensation of Vertigo

Post-synaptic nerve H2

Effect of Histamine on Blood Vessels (Autoreceptors)

H

H3

Negative Feedback Control Mechanism

H1

H2
(Stomach)

Betahistine on H1 receptors and H3 Autoreceptors (Blood Vessels of the inner ear)

H B

H3

H1

H1

Relaxation of vascular smooth muscles bloodflow in CNS & inner ear

Betaserc
H3 Heteroreceptor H3 Autoreceptor

Stimulates release of Histamine

Stimulates release of serotonin Regulatory effect on Vestibular nuclei
H1 H1 Receptor Receptor

Relaxation of vascular smooth muscles Improvement of bloodflow in CNS and inner ear
Prophylactic effect (treat the cause)

Sensation of vertigo
Symptomatic effec (w/o sedation)

Betaserc: Dual Mode of Action

SYMPTOMATIC
RELIEVES CURRENT SYMPTOMS Patients can continue activities DOES NOT SEDATE Speeds up vestibular compensation Patients can continue Activities SPEEDS UP VESTIBULAR COMPENSATION Faster recovery

PROPHYLACTIC
TREATS THE CAUSE OF VERTIGO Endolympathic accumulation PREVENTS FUTURE ATTACKS Prophylactic Benefit STIMULATES NEUROPLASTICITY Improves microcirculation Stimulates reconnection of nerves

Betaserc Dosing
Linear dose response curve
The higher the dose the quicker the result

Dosing 2 x 24 mg / day In Mnires disease therapy for lifetime

BETASERC 24 MG BID: The Higher The Dose, The Greater The Efficacy

Author & Years of Study

Betahistin e dose/day (mg)

Treatmen t Duration (month)

Reduced frequency of vertigo episodes change over betahistine (%)

Canty 1981 Mira 2003

32 32

2 2

-44% -63%

Fraysse 1991
Bradoo 2004

48
48

2
1

-93%
-97%

Indications

Menieres disease Vertigo due to a primary vestibular disorder

Improvement in Patients with Menieres Disease

16 14
number of patients

Total 28 Patients

16

12 10 8 6 4 2 0 complete relief partial relief No response

Hicks, Arch Otolaryngol, 1967, 86, 610-3

11

No vertigo attacks in 75% of patients after 3 months of the treatment with Betaserc
Analysed in 59 Recurrent paroxysmal vertigo patients

25 20
No. of patients free of Vertiginous attacks

Betahistine 16 mg t.i.d. - - placebo

15 10 5 0 0 30 60 90 days

Legent F et al, Concours Med, (1988), 29

No Changes in BP & Pulse after Treatment

115.6

113

pre-treatment post-treatment

100

72.2

73.2

70.4

72

0
B.P. systolic B.P. diastolic pulse

Adapted from : Stough AR, Curr. Ther. Res., 1963, 5,10

Betaserc (betahistine dihydrochloride) vs Merislon (betahistine mesylate)

Betahistine Dihydrochloride Molecular Weight: 209 (betahistine: 136) Betahistine Mesylate Molecular Weight: 328 (betahistine: 136) Active Substance (6mg): 136/328 X 6 mg = 2.5 mg

Active Substance (8mg):

136/209 X 8mg = 5.2 mg

BETASERC

Significantly more Effective vs Flunarizine on Improving DHI

*: p<0.05 vs flunarizine
54.4 51.6

70 60
Total DHI Score

50 40 30 20 10 0
24.3 17.8 25.9 22.5

*
Betaserc 48mg/day Baseline Flunarizine 10 mg/ day 4 weeks 8 weeks

DHI: Dizziness Handicap Inventory

BETASERC Significantly More Effective vs Cinnarizine

2.5
Mean Functional Level

2 1.5 1 0.5 0 Betaserc 1.2

1.9

p<0.05

Cinnarizine Response

- In reducing duration of unsteadiness after vestibular neurectomy - In improving the efficiency of vestibular compensation

Betaserc: Advantages
Betaserc has NO antagonistic effects on H1 receptors in the brain does not sedate (no antihistamine properties) Betaserc has NO affinity for H2 receptors relatively free from gastric side effects Betaserc has NO specific interaction with non histamine receptors in the brain NO significant affinity for other neuroreceptors in the brain in contrast to cinnarizine

Betaserc: Advantages
Betaserc acts locally on the microcirculation of the inner ear via: H1 receptors rapid relief of symptoms H3 receptors long-term prophylactic effect

H3 receptors on vestibular nuclei Symptomatic effects without sedation

Betaserc does not sedate, it activates! Betaserc stimulates neuroplasticity and enhances vestibular compensation

SUMMARY
Betahistine Reduces frequency of vertigo attacks Reduces duration of vertigo attacks Reduces severity in vertigo attacks Reduces vertigo, tinnitus, and deafness in Meniere disease

CONCLUSION

Treatment of dizziness includes causal, symptomatic, and rehabilitative therapies.

Betaserc 24 is a new pharmacologic agent for symptomatic treatment as well as prophylaxis of central and peripheral vertigo.
The effect of betaserc is dose related. The higher the dose, the greater the efficacy

Betaserc has only few gastric side effect, and is unlikely to cause sedation and extrapyramidal symptoms, which commonly occur in some antivertigo drugs.