DEFINITION (Brandt 2002)

■ - Vertigo is an unpleasant distortion of static

gravitational orientation, or an erroneous
perception of motion of either the sufferer or the
environment. It is not a disease entity, but rather
the outcome of many pathological or physiological
processes (Brandt 2002).
- Hallucination of movement (Troost 2004).

♦ Syndromal manifestation of vertigo consists of :

• Vertigo (spatial orientation & motion perception)
• Nystagmus (vestibulo-ocular reflex)
• Ataxia (postural)
• Nausea & vomiting (vegetative effects)
 INCIDENCE OF VERTIGO
(Brandt 2002)

• 5-10% of all patients seen by general

practitioners
• 10-20% seen by neurologists &
otolaryngologist
The Ear
 The Inner Ear

(horizontal)
 SUPERIOR

Endolymphatic sac

Semicircular
canals
Anterior
vertical
Posterior
vertical
Horizontal

ANTERIOR POSTERIOR

LOCATION OF VESTIBULAR & COCHLEAR DIVISIONS OF THE INNER EAR

 endolymph Crus commune

Semicicular
canals

Anterior
vertical
perilymph

Horizontal

Posterior
vertical

BONY & MEMBRANOUS LABYRINTH

Bony labyrinth is bounded by petrous portion of the temporal bone. Membranous labyrinth contains
organ of hearing (cochlea) & equilibrium (utricle, saccule, & semicircular ducts).
Bone & membranous labyrinth filled with perilymph, membranous labyrinth filled with endolymph)
 Ampullary
crista

Semicircular
canal
Angular
acceleration

A. The ampullary crista contains the hair

cells. The hair bundles of the hair cells
extend into the cupula, which stretches
from the crista to the roof of the ampulla
Endolymph
B. The cupula is displaced when the head moves, flow
& the hair cells are also displaced
HAIR CELLS IN THE VESTIBULAR LABYRINTH TRANSDUCE MECHANICAL
STIMULI INTO NEURAL SIGNALS
 Axis of
hair cells

Ampulla

(Move clockwise
because of inertia) Horizontal
canals

Depolarization Hyperpolarization
(excitation) (inhibition)
Because of inertia, rotation of the head in a counterclockwise direction causes endolymph
to move clockwise. This reflects the stereocilia in the left canal in the excitatory direction
& excites the afferent fibers on this side. In the right canal the hair cells are hyperpolarized
& afferent firing there decreases.
 CLASSIFICATION OF VERTIGO
(Brandt 2002)
Physiological stimulation
■ Height vertigo
■ Motion sickness

Pathological dysfunction
♦ Labyrinthine & vestibular nerve disorders 
(peripheral)
♦ Central vestibular disorders  (central)
 Syndromal manifestations of
vertigo (Brandt 2002)
-----------------------------------------------------------------
Syndrome Manifestation
------------------------------------------------------------------
• Spatial orientation &
motion perception Vertigo
• Vestibulo-Ocular reflex Nystagmus
• Posture Ataxia
• Autonomic Nausea, vomiting,
anxiety
------------------------------------------------------------------
CLASSIFICATION OF PHYSIOLOGICAL VERTIGO & VESTIBULAR DISORDERS WITH THEIR
ORIGIN AT DIFFERENT SITES WITHIN PERIPHERAL OR CENTRAL VESTIBULAR
STRUCTURES (Brand & Daroff, 2002)
 Visual input

equilibrium

Proprioceptiual Vestibular input

input labyrinths.
 RE-AFFERENCES EXPECTED
AFFERENCES

----------------
CENTRAL
STORE
----------------

NEURAL MISMATCH CONCEPT OF VERTIGO AND MOTION SICKNESS

(Brandt 2002)
 HIGHER
CENTERS
OCULOMOTOR
SYSTEM CEREBELLUM

END VESTIBULAR
END
ORGAN NUCLEI ORGAN

RETICULAR
FORMATION

inhibition AUTONOMIC
SYSTEM

MOTOR
SYSTEM

Communication between the vestibular system & other system of centers in the CNS
(Durrant 1982)
 CN VIII
(Vestibular
Labyrinth portion)

Cerebellum
Vertigo

Brainstem
Vestibular
nuclei

CAUSES OF VERTIGO
 FREQUENCY OF DIFFERENT VERTIGO
SYNDROMES (Brandt 1989-1999)
--------------------------------------------------------------------------------------------------------------------
Diagnosis Frequency
n %
--------------------------------------------------------------------------------------------------------------------
■ Benign paroxysmal positional vertigo (BPPV) 533 17.6
■ Somatoform phobic postural vertigo 434 14.3
■ Central vestibular syndromes with vertigo 364 12.0
■ Peripheral vestibulopathy (vestibular neuritis) 263 8.7
■ Basilar migraine, vestibular migraine 241 7.9
■ Meniere’s disease 200 6.6
■ Bilateral vestibular failure 89 2.9
■ Psychogenic vertigo (without 2) 89 2.9
■ Vestibular paroxysmia (neurovascular cross compression) 63 2.1
■ Perilymph fistula 7 0.3
■ Various rare vertigo syndrome 112 3.7
■ Unknown etiology 132 4.3
■ Central vestibular syndromes (without vertigo) 396 13.0
■ Other disorders 115 3.8
-------------------------------------------------------------------------------------------------------------------
 DD PERIPHERAL VS CENTRAL
VERTIGO (Finestone 1982)
--------------------------------------------------------------------------------------------------------------
Symptome Peripheral Central
--------------------------------------------------------------------------------------------------------------
♦ Hallucination of movement Definite Less definite
♦ Onset Usually paroxysmal Seldom paroxysmal
♦ Intensity Usually severe Seldom severe
♦ Duration Usually short Longer
♦ Influence of head position Frequent Seldom
♦ Nystagmus Present Present or absent
♦ Autonomoc nervous system Definite Less intense or absent
♦ Tinnitus Frequently present Seldom present
♦ Deafness Frequently present Seldom present
♦ Disturb’s of consciousness Seldom present More frequently present
♦ Other neurologic signs Usually absent Frequently absent
--------------------------------------------------------------------------------------------------------------
 SPINNED
PERIPHERAL CENTRAL
Sudden (Onset) Yes Slow, gradual
Positional Yes No
Intensity Severe Ill defined
Nausea/Diaphoresis Frequent Infrequent
Nystagmus Torsional/horizontal Vertical
Ear (hearing loss) Can be present Absent
Duration Paroxysmal (< 1 min) Constant
CNS signs Absent Usually present

Carvalho et al. CTU , Oct, 2004

CAUSES OF PERIPHERAL VERTIGO CAUSES OF CENTRAL VERTIGO
(Finestone 1982) (Finestone 1982)
----------------------------------------------------- ---------------------------------------------------
■ Ear ♦Vertebrobasilar insufficiency
Acute otitis media ♦ Stroke (cerebellar)
Chronic otitis media ♦ Tumors, cerebellar or brainstem,
Mastoid infection, acute & chronic primary or
Cholesteatoma metastatic
Local trauma ♦ Degenerative disease of CNS (eg M.S.)
Foreign body or impacted cerumen ♦ Head trauma
■ Meniere’s syndrome ♦ Psychogenic
■ Benign paroxysmal positional ♦ Epilepsy
vertigo (BPPV) ♦ Migraine equivalent
■ Vestibular neuronitis
■ Ototoxic drugs
■ Otoslerosis
■ Motion sickness
■ Psychogenic
 MENIERE’S DISEASE (MD)
TRIAD: (Colletti 2000)
- Vertigo spells + nausea vomiting
- Fluctuating but progressive hearing loss
- Tinnitus

INCIDENCE: 7.5 – 160 per 100.000 persons.

PATHOPHYSIOLOGY: (Strupp 2006)

• Too high production or too low absorption of endolymph
(endolymph hydrops).
• ↑ endolymph pressure causes periodic rupturing or
leakage  opening of nonselective stretch-activited ion
channels of the membrane separating endolymph from
perilymph space.
 Pathophysiology of Meniere’s
Disease
• Pathophysiology: Newer theories
– Multifactorial inheritance
– Immune-mediated phenomena
– Association of allergies
• Study by Gottschlich et al.
– 50% meeting criteria have antibodies to 70-kD
heat-shock protein
– 70-kD HSP implicated in AI-SNHL
 2 VARIANTS OF MENIERE’S
DISEASE (MD) (Colletti 2000)
■ Cochlear MD :
♦ Fluctuating aural fullness
♦ Sensorineural hearing loss
♦ Tinnitus
♦ No vertigo
■ Vestibular MD:
● Meniere’s episodes of vertigo without
cochlear symptoms
 “BPPV”
“B” = Benign “V” = Vertigo
♦ Not a brain tumor ♥ An illusion of motion
♦ Can be severe and disabling “The room is spinning”
Other descriptions
“P” = Paroxysmal ♥ Rocking
♥ Tilting
■ Episodic, not persistent
♥ Somersaulting
■ Helpful feature in the
♥ Descending in an elevator
differential diagnosis

“P” = Positional
● Occurs with position of head
● Turning over in bed
● Looking up
● Bending over
 BPPV

CHARACTERISTIC HISTORY
- If you turn the head
- After a few seconds delay, vertigo occurs
- Resolves within 1 minute if you don’t move
- If you turn your head back, vertigo recurs in
the opposite direction
- Incidence : 60-70 yrs (F:M = 2:1)
 2 CAUSES OF BPPV
• Most common cause
• Dysfunction of posterior SCC (semicircular ch.)
• Cupulolithiasis vs. Canalithiasis
• Cupulolithiasis
– Calcium deposits embedded on cupula in ampulla
– PSCC becomes dependent on gravity
• Canalithiasis
– Calcium debris (otoconia) displaced into PSCC
– Does not adhere to cupula in ampulla
 Canalolithiasis Theory
• Canalolithiasis theory is the most widely accepted theory
of the pathophysiology of BPPV
• Otoliths (calcium carbonate particles) are normally
attached to a membrane inside the utricle and saccule
• The utricle is connected to the semicircular ducts
• These otoliths may become displaced from the utricle to
enter the posterior semicircular duct since this is the
most dependent of the 3 ducts
• Changing head position relative to gravity causes the
free otoliths to gravitate longitudinally through the canal.
• The concurrent flow of endolymph stimulates the hair
cells of the affected semicircular canal, causing vertigo.
 Canalolithiasis Theory
BPPV is generally thought
to be due to otoconia
(crystals of ca-carbonate)
in the utricle displaced to
semicircular canals.
The utricle is damaged by
head injury, infection, dege-
neration in old age.
Otoconia is dissolved natural-
ly or reabsorbed by “dark
cells” of the labyrinth.
(Timothy C.Hain 2007)

Otoconia =
(small crystals of
calcium carbonate)
ATYPICAL BPPV (Timothy C. Hain 2007)
Horizontal canal BPPV
Anterior canal BPPPV
Cupulolithiasis
Vestibulolithiasis
Multicanal patterns
 Causes
• Idiopathic
• Infection (viral neuronitis)
• Head trauma
• Degeneration of the peripheral end organ
• Surgical damage to the labyrinth
 Symptoms
• Starts suddenly
• First noticed in bed, when waking from sleep.
• Any turn of the head bring on dizziness.
• Patients often describe the occurrence of
vertigo with
– tilting of the head,
– looking up or down (top-shelf vertigo)
– rolling over in bed.
• nausea and vomiting.
• There is no new hearing loss or tinnitus.
 Diagnosis
• Lab Studies:
– No pathognomonic laboratory test for BPPV exists.
Laboratory tests may be ordered to rule out other
pathology.
• Imaging Studies:
– Head CT scan or MRI.
• Procedures:
– The Dix-Hallpike test, along with the patient's history,
aids in the diagnosis of BPPV.
 Vestibular Neuritis
• Sudden onset of peripheral vertigo
• Usually without hearing loss
• Period of several hours - severe
• Lasts a few days, resolves over weeks
• Inflammation of vestibular nerve -
presumably of viral origin
• Spontaneous, complete symptomatic
recovery with supportive treatment
• Treatment aimed at stopping inflammation
 Vestibular Neuritis
• Ariyasu et al.
– 20 patients: double-blinded, crossover
– Methylprednisolone vs. placebo
– 90% decrease in vertigo within 24 hours vs.
30% of placebo group
– Placebo switched to steroid after 24 hours
with decrease in vertigo over next 24 hours
– 16 patients receiving steroid with resolution
had normal ENG within one month
DIX-HALLPIKE MANEUVER

The patient is brought from sitting

to a supine position, with the head
turn 450 to one side & extended
200 backward  burst of nystagmus
(Timothy C. Hain 2007)
 on ENG

Horizontal eye position

Vertical eye position

Horizontal (top) & vertical (bottom) eye position during Dix-Hallpike test.
Bottom trace shows the upbeating nystagmus.
Torsional nystagmus cannot be recorded on ENG.
(Timothy C.Hain 2007)
PROVOCATIVE MANEUVRES FOR POSITIONAL VERTIGO & NYSTAGMUS
Patient abruptly moved from sitting to head hanging 450 below horizontal plane &
rotated 450 to one side and vice versa (Todd 2004).
 BENIGN PAROXYSMAL
POSITIONAL VERTIGO
(Todd 2004)
A A. The nystagmus fast phase is
horizontal-rotary directed
toward the lower ear

B. The nystagmus fast phase is

upward toward the forehead
when gaze is directed to the
B upper ear

C. With the eyes in the central

orbital position, the nystagmus
fast phase is vertical upward
C and rotary toward the lower ear
 MANAGEMENT OF VERTIGO
(Brandt 2002)

----------------------------------------------------
• Pharmacologic therapies
• Physical therapies
• Surgical interventions
----------------------------------------------------
 PHARMACOLOGIC THERAPIES
FOR VERTIGO (Brandt 2002)
--------------------------------------------------------------------------------------------------------------------
Therapy Vertigo
--------------------------------------------------------------------------------------------------------------------
♦Vestibular suppressant Acute peripheral & vestibular nuclei lesions,
Prevention of motion sickness
♦ Antiepileptics Vestibular epilepsy, vestibular paroxysmia
(disabling positional vertigo), paroxysmal dysarthria &
ataxia in MS), other central vestibular paroxysms,
superior oblique myokymia
♦ Beta-blockers Basilar migraine (vestibular migraine; benign recurrent
vertigo)
♦ Betahistine Meniere’s disease
♦ Antibiotics Infection of the ear & temporal bone
♦ Ototoxic antibiotics Meniere’s disease (meniere drop attacks)
♦ Corticosteroids Vestibular neuritis, autoimmune inner ear disease
♦ Baclofen Downbeat or upbeat nystagmus or vertigo
♦ Acetazolamide Familial periodic ataxia or vertigo
--------------------------------------------------------------------------------------------------------------------
Symptomatic Pharmacotherapy
• Predominant targeted vestibular
neurotransmitters:
– Cholinergic
– Histaminergic
– GABA neurotransmitters - negative inhibition
• Vomiting center transmitters:
– Dopaminergic (D2)
– Histaminergic (H1)
– Serotonergic
• Multiple classes of drugs effective
Symptomatic Pharmacotherapy

• Anticholinergics - scopolamine, meclizine

• Antihistaminergic - dimenhydrinate
• Gamma-aminobutyric acid enhancing
(GABA-ergic) agents - lorazepam, valium
• Anti-dopaminergic - droperidol
 Symptomatic Pharmacotherapy
• Some drugs of the antihistamine class are
useful for symptomatic control of vertigo
• Have anti-motion sickness properties in large
part due to inhibition of vestibular system H1
histaminergic neurotransmitters
• Examples include dimenhydrinate (Dramamine)
and promethazine (Phenergan)
• Also suppress the vomiting center
 PHYSICAL THERAPIES FOR
VERTIGO (Brandt 2002)
---------------------------------------------------------------------------------
Deliberate manoeuvres Benign paroxysmal positioning
vertigo (BPPV)

Vestibular exercises Vestibular rehabilitation, central

compensation of acute vestibular
loss, habituation for prevention
of motion sickness, improvement
of balance skills (eg in the elderly)

Neck collar Cervical vertigo (fiction or reality?)

---------------------------------------------------------------------------------
 SURGICAL INTERVENTIONS
FOR VERTIGO (Brandt 2002)

-------------------------------------------------------------------------------------------------------------
■Decompression of VIIIth nerve Acoustic tumor or cyst
■ Decompression of vertebral artery Rotational vertebral artery occlusion
■ Ampullary nerve section Benign paroxysmal postioning vertigo
(BPPPV) canal plugging
■ Endolymphatic shunt Meniere’s disease
■ Vestibular nerve section or Intractable Meniere’s disease
labyrinthectomy
■ Surgical patching Perilymph fistula
------------------------------------------------------------------------------------------------------------
COMMONLY USED ANTIVERGINOUS
& ANTIEMETIC DRUGS (1) (Brandt 2002)
--------------------------------------------------------------------------------------------------------
Drug Dosage Action
--------------------------------------------------------------------------------------------------------
■Anticholinergics Muscarinic Antagonist
- Scopolamine 4-6 x 0.6mg po or
(transderm) Transderm 1 q 3 days

■Antihistamines
- Dimenhydrinate 4-6 x 50 mg po/4-6x im Histamine (H1) Antagonist
(dramamine) 100 mg supp q8-10h Muscarine Antagonist
- Meclizine 4-6 x 25mg po Histamine (H1) Antagonist
(antivert,bonine) Muscarine Antagonist
- Promethazine 4-6 x 15-50 mg po/ im Histamine (H1) Antagonist
(phenergan) 4-6 x supp Muscarine Antagonist
Dopamine (D2) Antagonist
---------------------------------------------------------------------------------------------------------
COMMONLY USED ANTIVERGINOUS
& ANTIEMETIC DRUGS (2) (Brandt 2002)
-------------------------------------------------------------------------------------------------------
Drug Dosage Action
-------------------------------------------------------------------------------------------------------
♦Phenothiazine
-Prochlorperazine 4-6x5-10 mg po/4xim Muscarine Antagonist
2 x 25 mg supp Dopamine (D2) Antagonist
♦Butyrophenone
-Droperidol 2 x 2.5 – 5 mg im Muscarine A.
(inapsine) Dopamine (D2) Antagonist
♦Benzodiazepines
-Diazepam 5-10 mg po, 2-4 x im GABAA agonist
(valium) 4-6 x 1V
-Clonazepam 3 x 0.5 mg GABAA agonist
--------------------------------------------------------------------------------------------------------
 Treatment
• Medications
• The Canalith Repositioning Procedure
(CRP)
• Surgery
 Medications
• Antiemetic
• Antihistaminic
• Anticholinergic
 Canalith Repositioning
Procedure ( CRP )
• The treatment of choice for BPPV, known as the Epley
maneuver.
• The patient is positioned in a series of steps so as to slowly
move the otoconia particles from the posterior semicircular
canal back into the utricle.
• Takes approximately 5 minutes.
• The patient is instructed to wear a neck brace for 24 hours and
to not bend down or lay flat for 24 hours after the procedure.
• One week after the CRP, the Dix-Hallpike test is repeated.
• If the patient does experience vertigo and nystagmus, then the
CRP is repeated with a vibrator placed on the skull in order to
better dislodge the otoconia.
 The Epley Maneuver If vertigo affects the R. ear,
turn head to the right

Debris deposited
In utricle. Patient
experiences relief

Debris
in PSCC

Inner ear (right side)

Hold for 30 seconds Anterior )
Posterior ) SCC
Lateral )
Utricle
Crista ampullaris
Anterior
Lateral

Posterior
PSCC
Inverted

Debris

Hold for Settling debris

30 seconds causes nystagmus
 The Epley Maneuver
• Contraindications
– Unstable heart disease
– High grade carotid stenosis
– Severe neck disease
– Ongoing CNS disease (TIA/stroke)
– Pregnancy beyond 24th week gestation
(relative)

Furman JM, Cass SP. N Engl J Med 1999;341:1590-96

 Brandt-Daroff Exercises
Timothy C. Hain 2007)

• Method of treating BPPV, usually used when

the office treatment fails.
• These exercises should be performed
– for two weeks, three times per day
– for three weeks, twice per day.
• In each time, one performs the maneuver as
shown five times.
• 1 repetition = maneuver done to each side in
turn (takes 2 minutes)
 Brandt-Daroff Exercises
(Timothy C.Hain 2007)

Time Exercise Duration

---------------------------------------------
Morning 5X 10 min
Noon 5X 10 min
Evening 5X 10 min
---------------------------------------------
 EXERCISE THERAPY (Todd 2004)
Patient begins in sitting position & then rapidly to the side, placing the head on the
bed or table  remains there until vertigo subsides & then returns to sit, remaining
there until vertigo subsides. The maneuvre is repeated toward the opposite side.
10-20 repetitions 3 X daily.
 Surgery

• Singular neurectomy
• Vestibular Nerve Section
• Posterior Canal Plugging Procedure
POSTERIOR CANAL PLUGGING PROCEDURE
(Timothy C. Hain 2007)
 TREATMENT OF MENIERE’S
DISEASE (MD)
USA : low-salt diet, diuretic, intratympanic injection of
gentamycin and corticosteroid (Strupp 2006), systemic
streptomycin (Colletti 2000).
Europe: betahistine (Strupp 2006)
Longterm medical treatment (Colletti 2000)
Na restriction 2 g/day (the endolymph sac is rich in K &
expands at the expense of Na-rich perilymphatic system);
Bananas & orange juice to ↑ K intake; Acetazolamide
(diuretic) is based on the localization of carbonic
anhydrase in the dark cells & stria vascularis. Supressant
drugs: cinnarizine, promethazine, diazepam.
Betahistine 3 X 16 mg for 3 months.
Surgical treatment for disabling MD (Colletti 2000)
Endolymphatic sac decompression, endolymphatic shunt,
labyrinthectomy, selective vestibular neurectomy +
betahistine after operation for adaptive compensation.
Vestibular neurectomy is to date the surgical treatment of
choice.
 Newer Treatment of Meniere’s
Disease
• Immunosuppressive agents gaining favor
– Systemic and intra-tympanic glucocorticoids
– Cyclophosphamide
– Methotrexate
• Shea study - intractable Meniere’s
– 48 patients intra-tympanic dexamethasone
– 66.7% elimination of vertigo
– 35.4% improvement in hearing (>10dB and/or
15% change in word recognition score)
VESTIBULAR MIGRAINE (Strupp 2006)
• Recurrent attacks of vertigo, ataxia of stance &
gait, visual disorders, other brainstem symptoms,
occipitally located head pressure, pain, nausea,
vomiting.

Treatment:
• Prophylactic as for mIgraine with aura:
betablockers (metroprolol, propanolol), valproic
acid for 3-6 months.
• Tricyclic antidepressants; zolmitriptan; topiramate
migraine vertigo with auditory symptoms;
lamotrigine 1 X 100 mg more marked effect on
vertigo.
 MODE OF ACTION OF BETAHISTINE
(Solvay pharm 2006)
------------------------------------------------------------------------------------
■ A weak partial H1 receptor agonist  lower affinity than histamine
■ Negligible H2 receptor affinity
■ Potent antagonistic H3 receptor  ↑ histamine release 
↑ microcirculation of inner ear & ↓ endolymphatic pressure 
symptomatic relief of vertigo.
■ Inhibits basal spike generation of the vestibular afferent neurons
in lateral & medial vestibular nuclei  control posture
■ ↑ histamine synthesis & release within tuberomammilary nuclei 
improves vestibular compensation.
■ ↑ the messenger RNA (mRNA) for histidine decarboxylase 
blocking the presynaptic H3 receptors & induces H3 downregulation
■ Betahiststine + its metabolite aminoethylpyridine  ↓ ampullar
receptor resting discharge  ↓ vertigo
■ ↑ levels of 5-HT in brain stem  inhibits activity of vestibular nuclei.
-----------------------------------------------------------------------------------------------------
 ↑ release of
neurotransmitter
inhibits release
of neurotransmitter

PROPOSED EFFECT OF BETAHISTINE ON H3 RECEPTORS IN THE BRAIN

BETAHISTINE INCREASES BLOOD FLOW TO THE INNER EAR (Suga 1969)

BETAHISTINE INHIBITS FIRING RATE OF POLYSYNAPTIC NEURONES IN THE LATERAL

VESTIBULAR NUCLEUS OF CATS (Unemoto 1982)
EFFECT OF BETAHISTINE & PLACEBO ON THE FREQUENCY OF VERTIGO (Oosterveld 1989)

EFFECT OF BETAHISTINE & PLACEBO ON THE SEVERITY OF VERTIGO (Oosterveld 1989)

 EFFECT OF BETAHISTINE ON THE DURATION OF VERTIGO
ATTACKS (Legent 1988)

EFFECT OF BETAHISTINE VS CINNARIZINE ON THE NUMBER OF VERTIGO ATTACKS

(Deering 1986)
 UVN = unilateral vestibular
neurectomy

EFFECT OF BETAHISTINE ON UNILATERAL VESTIBULAR NEURECTOMIZED RATS

The functional recovery is strongly facilitated in the groups of cats under beta-
histine treatment  the time required for full recovery is half that of the control &
placebo groups (Lacour 2006).
 Dose-and duration-dependent effects of betahistine
dihydrochloride treatment on histamine turnover in the rat.
Tighilet et al. Eur J Pharm 8 September 2005.

Betahistine dihydrocloride per os in the normal

cat interferes with histamine turnover by ↑ the
basal expression level of histidine decaroxylase
mRNA of neurons located in the tubero-
mammilary nuclei of the posterior hypothalamus
 blocking the presynaptic H3 receptors &
induces H3 downregulation  ↑ histamine
release  ↑ micro-circulation of inner ear & ↓
endo-lymphatic pressure  symptomatic relief
of vertigo.
Management of acute vertigo with betahistine
Bradoo et al. Indian Journal of Otolaryngology and Head and
Neck Surgery 2000; 52: 152-158.

Open prospective study of 29 outpatients with vertigo

Dose: 3 X 16 mg betahistine/day, for a maximum of 6

weeks

Results: betahistine showed a significant improvement in

the frequency, duration & severity of vertigo attacks.
Associated symptoms eg tinnitus, nausea, vomiting,
headache, faintness showed a significant improvement.

Side effects: none. No sedation.

Optimizing the pharmacologic component of
integrated balance therapy
Gananca et al. Brazilian J Otolar 2007; 70: 1-8

1.100 outpatients with Meniere’s disease or peripheral

vestibulopathies treated with no medication or betahistine,
cinnarizine, clonazepam, flunarizine, or Ginkgo biloba.

Results:
♦ In Meniere’s disease betahistine was significant more
effective than all other drugs at 60-120 days.
♦ For non-Meniere’s disorders: betahistine was as effective
as cinnarizine & clonazepam, but more effective than
flunarizine & Ginkgo biloba.
SIDE EFFECTS OF BETAHISTINE
(Jeck-Thole & Wagner, Solvay Pharm 2006)

• Of > 130 million patients since approved in Canada

1968 (> 35 years) until 31/12/005: 554 adverse drug
reaction (ADR):
• CNS (18.1% n=180): Paresthesia 16 pts; tremor 18 pts;
headache 30 pts; dizziness & vertigo 51 pts
• SKIN (17.3% n=172); rashes 47 pts; pruritis 35 pts;
urticaria 29 pts; edema 35 pts
• GI (12.9% n -128): nausea 30 pts; vomiting 14 pts;
abdominal pain 17 pts.
• RESPIRATION (3.5% n = 35): asthma, bronchospasm &
wheezing 9 pts; dyspneu 15 pts, cough 5 pts.
• TUMOR (0.3% n =3) : suspected phaeochromocytoma
1 pt; 2 pts dubious.
• DEATH (4 deaths dubious)