dr.

Ki ki Mohammad I qbal , SpS
1
Keseimbangan Tubuh Dikontrol oleh 3 Sistem Sensoris
Vestibular, Visual, Proprioseptif
Balance
dyfunction
Imbalance / Dizziness
Central Nervous System
Skin, Muscle and J oint
(Proprioceptive)
Postural control
via muscles
Goebel JA. Otolaryngol Clin North Am 2000;33:483–93.
Shepard NT, Solomon D. Otolaryngol Clin North Am 2000;33:455–69
Controls eye
movements
Eye
(Visual)
Inner Ear
(Vestibular system)
2
Somatosensory
system
Psycho-affective
symptom
Neurovegetative
symptom
Failure of
Central
Compensation
VERTI GO
Patofisiologi Keseimbangan
Visual
system
Vestibular
system
 Perasaan berputar baik seseorang terhadap
sekelilingnya ataupun sekelilingnya
terhadap seseorang
 Vertigo bukan suatu diagnosa penyakit, tapi
hanya merupakan simptom
 Dokter harus menentukan apa penyebabnya
4
VERT I GO
Pada studi berbasis populasi :
 Vertigo terjadi pada sekitar 4–7%
1, 2

Pada populasi dengan usia di atas 75 tahun :
 Prevalensi vertigo 13% - 38%
 40% perempuan dan 30% laki-laki
mengeluhkan beberapa bentuk gangguan
postural
2

1.Yardley L et al. Br J Gen Pract 1998;48:1131-35
2.Sixt E, Landahl S Age Ageing 1984;16:393–8

5
Pr eval ensi Ver t i go
Vest i bul ar Non Vest i bul ar
Sensasi Spinning Swimming, floating,
swaying, rocking
Lama serangan Episodik Konstan
Pencetus Pergerakan kepala
atau badan
Stress, hiperventilasi,
lingkungan ramai
Gejala penyerta Mual, muntah, tinitus,
ketulian, oscillopsia
Pucat, takikardia,
sinkope
6
Kl asi f i kasi Ver t i go
7
7
S E N T R A L P E R I F E R
Ver t i go Vest i bul ar
5
10
8
Disfungsi apparatus vestibular & nervus vestibularis
Vertigo Vestibular Perifer
10
10
Kelainan di nukleus vestibularis dan connecting central pathway
9
Vertigo Vestibular Sentral
Disfungsi proses sentral
S Y M P T O M V E R T I G O
PERIPHERAL CENTRAL
Episodes Acute and
remitting
Chronic and
unremitting
Onset Sudden Gradual
Intensity Severe Mild / mod
Nausea, vomiting Severe Varying
Auditory symptoms Common Rare
Neurological symptoms Rare Common
Changes in consciousness Infrequent Sometimes
Compensation / resolution Rapid Slow
Baloh RW. Otolaryngol Head Neck Surg 1998;119:55–9. Puri V, Jones E. J Ky Med Assoc 2001;99:316–21.
10
Vertigo Perifer vs Sentral
Condi ti on Detai l s
Benign paroxysmal
positional vertigo
(BPPV)
Brief, position-provoked vertigo episodes caused by
abnormal presence of particles in semicircular canal
Meniere’s disease An excess of endolymph, causing distension of
endolymphatic system
Vestibular neuronitis Vestibular nerve inflammation, most likely due to virus
Acute labyrinthitis Labyrinth inflammation due to viral or bacterial infection
Labyrinthine infarct Compromises blood flow to the labyrinthine
Labyrinthine
concussion
Damage to the labyrinthine after head trauma
Perilymph fistula Typically caused by labyrinth membrane damage
resulting in perilymph leakage into the middle ear
Autoimmune inner ear
disease
Inappropriate immunological response that attacks inner
ear cells
D
e
c
r
e
a
s
i
n
g

f
r
e
q
u
e
n
c
y

Baloh RW. Lancet 1998;352:1841–6. 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;99:316–21. Salvinelli F et al. Clin Ter 2003;154:341–8.
11
Penyebab Vertigo Perifer
Condi ti on Detai l s
Migraine Vertigo may precede migraines or occur concurrently
Vascular disease Ischaemia or haemorrhage in vertebrobasilar system
can affect brainstem or cerebellum function
Multiple sclerosis Demylination disrupts nerve impulses which can
result in vertigo
Vestibular
epilepsy
Vertigo resulting from focal epileptic discharges in the
temporal or parietal association cortex
Cerebellopontine
tumours
Benign tumours in the internal auditory meatus
Baloh RW. Lancet 1998;352:1841–6. Mukherjee A et al. JAPI 2003;51:1095-101. Salvinelli F et al. Clin Ter 2003;154:
341–8. Solomon D. Otolaryngol Clin North Am 2000;33:579–601. Strupp M, Arbusow V, Curr Opin Neurol 2001;14:11–20.
12
Penyebab Vertigo Sentral
D
e
c
r
e
a
s
i
n
g

f
r
e
q
u
e
n
c
y

 Tidak dijumpai perasaan berputar
 Pasien mengeluhkan merasa melayang,
mengambang, bergoyang, mengayun
 Biasanya pada saat berdiri
 Merasa enak kalau duduk
 Mual dan muntah biasanya tidak ada
 Ggn organ penglihatan atau somatosensorik
13
Ver t i go Non Vest i bul ar
14

Neur oki mi a Ver t i go

NEUROTRANSMITTER PERI FER SENTRAL
Glutamat Eksitatori Synap Afferen Eksitatori
Acethylcholine (ACH) Eksitatori Synap Efferen Eksitatori
GABA Inhibitori Inhibitori
Glycine Belum Jelas Inhibitori
Dopamine Belum Jelas Eksitatori
Norepinephrine Belum Jelas Modulator
5-Hydroxytryptamine Belum Jelas Eksitatori
Histamine Belum Jelas Inhibitori ?
 Glutamat → neurotransmitter eksitatori utama
 Acethylcholine (ACH) → agonis perifer dan
sentral → reseptor muskarinik
 Di perifer → ACH terlibat pada eferent
brainstem – sinaps sel rambut
 Di sentral → 5 subtipe reseptor ACH →
di pons dan medulla → berhubungan
dgn dizziness (subtipe M2)
15
Neur oki mi a Ver t i go
 GABA dan glycine → neurotransmitter
inhibitori → pada koneksi antara second
order neuron vestibular dan neuron
okulomotorius
 Pengaruh reseptor glycine → << diketahui
16
Neur oki mi a Ver t i go
 Norepinefrin → terlibat secara sentral dalam
memodulasi intensitas reaksi stimulasi
vestibular dan memfasilitasi kompensasi
 Dopamin → memfasilitasi kompensasi
vestibular
 Agen selektif utk subtipe reseptor serotonin
→ memodulasi nausea
17
Neur oki mi a Ver t i go
 Histamin → dijumpai pada struktur vestibular
sentral secara difus
Terdapat 3 subtipe reseptor histamin
(H1, H2, H3) → respons vestibular
 Agonis H3 → menginhibisi pelepasan
histamin, dopamin dan ACH
Pada vertigo → meningkatnya Histamin reseptor
18
Neur oki mi a Ver t i go
 Anamnesis
 Pemeriksaan Fisik & Neurootologi
 Pemeriksaan Penunjang
19
Di agnosa Ver t i go
20
 Effective management requires identification of
vertigo type and cause.
 Aim of treatment :
1. Treat the underlying cause :
● Pharmacotherapy
● Particle repositioning procedure
● Surgery
2. Manage symptoms :
● Pharmacotherapy
3. Promote long-lasting neural reorganisation :
● Vestibular rehabilitation exercises
Penat al aksanaan
21
TI PE VERTI GO PENGOBATAN
PERI FER :
BPPV Canalith repositioning manoeuvre
Labyrinthine concussion Vestibular rehabilitation
Meniere’s disease Low-salt diet, diuretic, surgery, transtympanic gentamicin
Labyrinthitis Antibiotics, removal of infected tissue, vestibular rehabilitation
Perilymph fistula Bed rest, avoidance of straining
Vestibular neuritis Brief course of high-dose steroids, vestibular rehabilitation
SENTRAL :
Migraine Beta-blockers, calcium channel blockers, tricyclic amines
Vascular disease Control of vascular risk factors, e.g., antiplatelet agents
Cerebellopontine tumours Surgery
Penat al aksanaan
22
TERAPI SIMPTOMATIK VERTIGO :

SUPRESAN
VESTI BULAR
ANTI EMETI KUM
Penat al aksanaan
23
TERAPI SIMPTOMATIK VERTIGO :
1) Supresan vestibular :
a) Antihistamin
antikholinergik :
● Dimenhydrinate
50 mg/4-6 jam
● Diphenhydramine
● Meclizine
12,5-50 mg/4-6 jam
b) Benzodiazepine :
● Lorazepam
0,5 mg 2x sehari
● Diazepam
2 mg 2x sehari
● Clonazepam
0,5 mg 2x sehari
Hain TC and Yacovino D. Pharmacologic Treatment for Persons with Dizziness. Neurol Clin 2005;23:831-853
Penat al aksanaan
24
TERAPI SIMPTOMATIK VERTIGO :
1) Supresan vestibular :
c) Calcium channel
blocker :
● Flunarizine
10 mg 1x sehari
● Cinnarizine
25 mg 3x sehari
d) Obat lainnya :
● Betahistine
● Ginkgo biloba
● Baclofen
● Amantadine
Hain TC and Yacovino D. Pharmacologic Treatment for Persons with Dizziness. Neurol Clin 2005;23:831-853
Penat al aksanaan
25
TERAPI SIMPTOMATIK VERTIGO :
2) Anti emetikum :
a) Phenothiazine :
● Prochlorperazine (5-10 mg tiap 6-8 jam)
● Promethazine (25 mg tiap 6-8 jam)
b) Metoclopramide (10 mg 3x sehari)
c) Domperidone
d) Sulpiride
e) Ondansetron (4-8 mg 3x sehari)
Hain TC and Yacovino D. Pharmacologic Treatment for Persons with Dizziness. Neurol Clin 2005;23:831-853
Penat al aksanaan
26

 Agonis reseptor H1 yg lemah dan antagonis
reseptor H3 moderat → negative feedback
dalam mengkontrol pelepasan histamin →
fasilitasi neurotransmisi histaminergik di otak
 Pemberian betahistine → reduksi peningkatan
refleks vestibulo okular → me↑ aliran darah
pada telinga bagian dalam
Bet ahi st i ne
27

 Bekerja pd neuron histaminergik
tuberomamilaria dan nukleus vestibularis
 Betahistine memainkan peranan penting dalam
memperbaiki aliran darah telinga tengah
 Meningkatnya oksigenasi telinga tengah ,
mencegah kerusakan reseptor sensorik dan
memperbaiki fungsi normal sel rambut yang
sensitif gerakan
Bet ahi st i ne
28

 Diroleransi dgn baik dan efek samping minimal
 Dosis tinggi (36-48 mg/hr) lebih efektif dari pada
dosis rendah (18-24 mg/hr)
 Efektif untuk vertigo vestibuler perifer terutama
yg rekuren
Bet ahi st i ne
0
2
4
6
8
10
12
6 mg 12 mg 6 mg 12 mg
BPPV MV

N
u
m
b
e
r

o
f

c
a
s
e
s

o
n

H
i
g
h

S
t
i
m
u
l
a
t
i
n
g

R
a
t
e

A
B
R

ABR: Auditory Brainstem Response, BPPV: Benign Positional Paroxysmal Vertigo, MV: Migrainous Vertigo
administered for 1 month, n: 37
Merislon 12mg t.i.d is more effective
than Merislon 6mg t.i.d
1

pre
post
1. Graph adapted from Zi-ming W, et al. The effect of betahistine mesylate as a treatment to vertigo induced by inner ear ischemia. Chinese Scientific Journal of Hearing and Speech Rehabilitation 2007; 5: 26-29.
2. Japanese Package Insert, July 2009; 8th version
p<0.01 p<0.01
I
N
-
M
R

F
I
-
1
4
C
-
0
1

0
20
40
60
80
100
120
6 mg 12 mg 6 mg 12 mg
BPPV PCI
D
H
I

S
c
o
r
e

DHI: Dizziness Handicap Inventory, DHI Score: 0-30 is mild, 31-60 is medium, 61-100 is severe, BPPV:
Benign Positional Paroxysmal Vertigo, PCI: Posterior Circulation Ischemia,
administered 1 month, n:60
Improves Quality of Life
Vertigo patient
1

pre
post
1. Graph adapted from Zi-ming W, et al. The effect of betahistine mesylate as a treatment to vertigo induced by inner ear ischemia. Chinese Scientific Journal of Hearing and Speech Rehabilitation 2007; 5: 26-29.
2. Japanese Package Insert, July 2009; 8th version
I
N
-
M
R

F
I
-
1
4
C
-
0
2

0
20
40
60
80
100
3 7 14 30 60 90
I
m
p
r
o
v
e
m
e
n
t

r
a
t
e

(
%
)

Days

LM: Liberatory Manoeuvre, BE: Betahistine mesylate, BPPV: Benign Positional Paroxysmal Vertigo.
32mg/day administered until complete recovery, n=52
Addition of Merislon provides
faster recovery of BPPV patients
1

LM
LM-BE
*
*
1. Cavaliere M, et al. Benign Paroxysmal Positional Vertigo: a study of two manoeuvres with and without betahistine. Acta Otorhinolaryngol Ital 25, 107-112, 2005.
2. Japanese Package Insert, July 2009; 8th version



*p<0.05
I
N
-
M
R

F
I
-
1
4
C
-
0
3

⎹⎹
1. Cavaliere M, et al. Benign Paroxysmal Positional Vertigo: a study of two manoeuvres with and without betahistine. Acta Otorhinolaryngol Ital 25, 107-112, 2005.
2. Japanese Package Insert, July 2009; 8th version



0
20
40
60
80
100
3 7 14 30 60 90
I
m
p
r
o
v
e
m
e
n
t

r
a
t
e

(
%
)

Days

BD: Brandt Daroff Exercises, BE: Betahistine mesylate, BPPV: Benign Positional Paroxysmal Vertigo,
32mg/day administered until complete recovery, n=51
Addition of provides
faster recovery of BPPV patient
1

BD
BD-BE
*
*
*p<0.05
I
N
-
M
R

F
I
-
1
4
C
-
0
4

⎹⎹
0
0.5
1
1.5
2
2.5
Before therapy 1 3 6 12
M
e
a
n

s
c
o
r
e

o
f

v
e
r
t
i
g
o

s
y
m
p
t
o
m
s

Week
No Statistically significant difference between the therapy group
t.i.d has similar efficacy with
combination of two Anti vertigo drugs
1

Dimenhydrinate + Cinnarizine (n=40) Betahistine (n=40)
1. Adopted from Novotny, et al., Fixed combination of cinnarizine and dimenhydrinate versus betahistine dimesylate in the treatment of Meniere’s disease, International Tinnitus Journal, Vol.8, No.2: 115-123 (2002)
2. Japanese Package Insert, July 2009; 8th version
I
N
-
M
R

F
I
-
1
4
C
-
0
5

99%
Total Adverse
Reaction :
26 patients
1%
Merislon is well tolerated
2

No Adverse Reaction Adverse Reaction
Total Patient:
2.254
1. Graph adapted from Zi-ming W, et al. The effect of betahistine mesylate as a treatment to vertigo induced by inner ear ischemia. Chinese Scientific Journal of Hearing and Speech Rehabilitation 2007; 5: 26-29.
2. Japanese Package Insert, July 2009; 8th version
Doses: 18mg – 36mg /day
Common Adverse Reaction:
Nausea (0.44%), Skin Eruption (0.13%)
I
N
-
M
R

F
I
-
1
4
C
-
0
6

Mesylate salt 5x more soluble, and 2.6x more
bioavailable than the hydrochloride salt
Mean plasma concentrations in male beagle
Engel GL, et al. Salt form selection and characterization of LY333531 mesylate monohydrate. International Journal of Pharmaceutics 198 (2000): 239-247
I
N
-
M
R

F
I
-
1
4
C
-
0
7

1. Konfirmasi Vertigo ?
2. Tentukan Jenis
3. Tentukan Letak Lesi
4. Cari Kausa
5. Pilih Terapi :
 Kausal
 Simtomatik
 Rehabilitasi
Vertigo Vestibular Vertigo Non Vestibular
Perifer Sentral Visual Somatosensorik
(Proprioseptif)
Al gor i t ma Ver t i go
36
TERIMA KASIH
37
37