Balance the imbalance DIAGNOSIS & MANAGEMENT OF VERTIGO - PRESENT SENARIO

Dizziness
3 4 varients of dizziness

-A definite rotational sensation or vertigo -A sensation of faintness or impending loss of consiousness -Desequilibrium or sense of imbalance -An illdefined sense of dizziness or light headedness

VERTIGO
-A subjective sensation of movement -May feel either that him involving in space or that objects in the environment are moving around him. -It also include feeling of swaying movement of body
3

OTHER TYPE OF DIZZINESS

Faintness- generally indicates hemodynamic factors causing brain ischemia . 3 Disequilibrium- refers to a sense of unsteadiness or imbalance & occure during ambulation ,especially when stressed like rapid turning, in the dark & suggests cerebellar incordination, muscle weakness & peripheral sensory impairment . 3 Light headedness- is a frequently a neurologoic complaints & may have no stereotyped condition for its prepitation or aggravation other than emotional stress .
3
4

ANATOMY AND PHYSIOLOGY*

*RELATED TO VERTIGO
5

Utricular nerve e

ry

ve
10

Central projection of peripheral vestibular system

11

12

CAUSES OF VERTIGO

13

What causes vertigo?

3 Contradictory information from

The vestibular system (ears) 2The visual system (eyes) The Proprioceptive system (muscles, joints)

14

Causes of Vertigo
PERIPHERAL Menieres disease

Labyrinthitis Vestibular neuropathy BPPV Trauma CENTRAL- referred to mnemonic VERTIGO V vascular causes like Stroke , Vertebrobasilar insufficiency , migraine , vasculitis & vascular elements like decreased cardiac output , orthostatic hypotension,anemia,hypoxia,hypoglycemia

15

CAUSES OF CENTRAL VERTIGO

E Epilepsy(vertiginous) R Rx or drug related like ANTIBIOTICS- aminoglycosides, ANTIHYPERTENSIVES HYPNOTIC-SEDATIVE DRUGS- phenytoin, barbiturates, & alcohol. TRANQUILLIZERS Phenothiazine,Benzodiazepines & Tricyclic antidepressants ASPIRIN QUININE
16

CAUSES OF CENTRAL VERTIGO

T TUMOUR Primary like Acoustic neuroma, Glioma, intraventricular tumours and secondary metastatic tumours of brain. - TRAUMA - THYROID- Hypothyroidism I INFECTIONS viral, syphilis, vestibular neuronitis. G GLIAL DISEASE Multiple sclerosis O OULAR PATHOLOGY- weakness of extra ocular muscles .

17

Vertigo: Traditional Classification

Peripheral

(arises in vestibule) Intermediate

Vestibular

(arises in vestibular nerve) Central (arises in vestibular nuclei)

Vertigo

Non-vestibular (arises outside the vestibular system)

18

19

Sites of Vertigo

Physiology of Peripheral Vertigo

Vestibular apparatus consist of semicircular canal - utricle - saccule All these have sensory hair cells having stereocilia arranged in ascending fashion. The longest steriocilia is k/a Kinocilia. Movement of steriocilia towards kinocilia- Stimulation Movement of steriocilia opposite to kinocilia- Inhibition
3

20

Conditions resulting in stimulation of only one labyrinth results in unequal impulses reaching to brain leading to state of dysequilibrium & manifest as vertigo or dizziness.
21

Causes of Peripheral Vertigo

3 Benign Paroxysmal Positional Vertigo 3 Menieres Disease 3 Labyrinthitis 3 Head Injuries & Surgical Trauma 3 Pressure Vertigo
22

Causes of Intermediate Vertigo

3 Vestibular neuronitis 3 Acoustic neuroma 3 Drugs alcohal, aminoglycosides,

anticonvulsants, antidepressanta, antihypertensive, barbiturates, cocaine .

23

Causes of Central Vertigo

3 3 3 3 3
24

VBI (Vertebrobasilar Insufficiency) Arteriosclerosis Cervical Spondylosis Whiplash injuries of Neck Brain Tumors

Non-Vestibular Causes of Vertigo

3 3 3

Ocular vertigo Anemia Cardiovascular (orthostatic hypotension) Cerebrovascular disorders Psychogenic Brain tumors

3 3 3 3 3

Head injuries Epilepsy Multiple sclerosis Hypoglycemia Migraine

3 3
25

Another classification of vertigo

3

Paroxysmal Vertigo - sudden attack comes on quickly, lasts for a short time The single attack - sudden intense attack fading away slowly Chronic vertigo - not severe Positional vertigo - occurs following sudden movements of head in certain positions Dizzy spells - lasting a few seconds occurring irregularly

3 3

3
26

27

DIAGNOSIS OF VERTIGO

28

29

Medical History
3 3

Description of symptoms by patient Classification of vertigo attacks (Which type, how debilitating, frequency, duration, vegetative symptoms)

Influencing circumstances (Injuries, drugs taken, stress, eating pattern, Illnesses) Secondary symptoms Tinnitus, Hearing loss, Headache, nausea/ vomiting

30

Biswas A., Neurotological History Taking IN An Introduction to Neurotology, 1998, 8-11

Vestibular Function Tests

3 Vestibulo spinal reflex

Romberg test Unterberger test Modified Sikatani test Babinski-weill test Barany Pointing test

31

Adapted from Biswas A.,Clinical tests in Neurotology IN An Introduction to Neurotology, 1998, 13-25

Vestibulo ocular reflex

Cold caloric test (Kobrak test) Bithermal test ( Fitzgerald-Hallpike test) Air caloric test Dundas Grant air caloric test Fistula test ENG Optokinetic test Rotation test

32

33

Patient closes eyes and stretches arms out in front Walks on spot for a minute The knees raised as high as possible Patients with vertigo will start to turn his axis in particular direction
34

BARANYS

Deviation to one side in pointing occurs in patients with vertigo

35

Babinsky- Weill Test

Patient closes his eyes and takes 5 steps forward and 5 steps back for 30 seconds

36

Patient with vertigo starts to walk in a star shape

FITZGERALD- HALLPIKE / BITHERMAL CALORIC TEST

3 3 3

Patient in supine position with head flexed at 30 with horizontal. Ear is irrigated with water at 44 C & 30 C separately for periode of 40 Sec each with the gap of 5 minute between both irrigations. Duration & character of nystagmus is observed . Normal duration of nystagmus is 90-120 Sec with direction for cold water towards opposite ear & for warm water for same side. (mnemonic COWS) If time,duration & severity decreases on one side CANAL PARESIS If no reaction is observed on one side DEAD LABYRINTH

3 3

37

OTHER CALORIC TESTS

3

KOBRAKS/ COLD CALORIC TEST- Position similar to bithermal test with irrigation with 10-15cc of ice cold water. AIR CALORIC TEST- Air at different temperature like 17.5 C,45.5 C is passed into ear & nustafmus is noted. DUNDAS GRANT AIR CALORIC TEST Ethyle chloride is sprayed on a copper tube & then air from the tube is passed into the ear . Ntstagmus is noted .

38

39

FISTULA TEST
3

Pressure is increased in EAC with Siegles speculum or by applying pressure over tragus & occurance of any nystagmus or vertigo is noted.

POSITIVE FISTULA TEST- indicates fistula in labyrinth especially in LSC . 3 NEGATIVE FISTULA TEST-Normal labyrinth or dead labyrinth . 3 FALSE POSITIVE TEST- Also K/a Hanneberts Sign is seen in Menieres disease and Congenital syphilis. 3 FALSE NEGATIVE TEST- Seen in cases of dead labyrinth
3
40

3 ENG measures the function of the vestibular system,

ELECTRONYSTAGMOGRAPHY

through the occulormotor pathways rather than the auditory pathways. 3 In ENG we compare slow; phase velocity and fast phase velocity of the nystagmus , of which slow phase velocity is more important . 3 Standerd Deviation (SD) between two ear should not be more than 30 % for a normal person .
3 Practically

41

without ENG we use a costless procedure to count fast componant in 10 Sec. Of maximum nystagmus periode which is known as a cumulative velocity .

ELECTRONYSTAGMOGRAPHY

A battery of 6 tests are performed.

Saccade Test: Patient looks back and forth at a visual target on a screen. Gaze Test: Patient gazes right, left, up, down and center. Tracking Test: Patient follows a visual target on an horizontal plane. Optokinetic Test: Patient follows a series of moving lights on a horizontal plane. Position Test: Patient moves in various position focusing on one target. Caloric Test: Patients ears are stimulated 2x each with warm and cool air or water

42

ROTATION TEST
There are two kinds of computerized rotation tests: auto head rotation and rotary chair. 3 In auto head rotation tests, the person being tested is asked to look at a fixed target and move his/her head back and forth or up and down for short periods of time. 3 During rotary-chair tests, the computerized chair moves for the person being tested. 3 Less usfull than caloric test because it stimulates both the ear simultaneously.
3

43

OPTOKINETIC TEST
3

The person sits in front of a rotating drum with alternate white and black vertical strips . Nowdays a computerised horizontal bar with traking light has replaced a rotatory drum stimulation optokinetic test . The nystagmus induced is recorded

44

INVESTIGATIONS
HEMATOLOGIC INVESTIGATIONS - CBC - CHEMICAL SCREENING LIKE BUN,ALBUMIN & GLOBULIN - T3 & TSH - FTA ABS URINE ANALYSIS RADIOLOGICAL STUDIES - MASTOID & INTERNAL ACOUSTIC CANAL VIEWS - CT SCAN - SKULL & CERVICAL SPINE RADIOLOGY

45

INVESTIGATIONS
OPTIONAL TESTS-five hour glucose tolerance test - polycyclic tomograms of the petrous bone - ECG - EEG - Psychometric testing

46

Nystagmus
Spontaneous
When Looking straight ahead When When focusing looking on fixed sideways spot When following moving object When head is in particular position

Induced
When When changing turning position the head of head

47

Induced nystagmus
3

Positional nystagmus Any nystagmus that occurs when the head is in position other than normal upright Positioning nystagmus occurs when change of head position and used to diagnose BPPV

48

Differentiation of Peripheral and Central Vertigo

Sign / Symptoms
Latency Duration Fatiguability Adaptation

Pheripheral
2- 10 second Stopes in 30 Sec or less present disappears in 50 Sec

Central
none Continuous for more than 1 minute absent Persist

49

(Contd.)

Differentiation of Peripheral and Central Vertigo

Sign / Symptom Vertigo Direction of spin Direction of fall Duration of symptoms Tinnitus and /or deafness Associated central abnormalities Common causes Peripheral (Labyrinth) Central (Brainstem or Cerebellum) Always present, Severe May be mild or Absent Toward fast phase Varied Toward slow phase Variable Finite (minutes, days, May be chronic weeks) but recurrent Often present Usually absent None Infection (labyrinthitis), Meniere's, neuronitis, ischemia, trauma, toxin Extremely common Vascular, demyelinating, neoplasm

50

Daroff R. B., Faintness Syncope, Dizziness and vertigo IN Harrisons Principles of Internal Medicine, 14th Edition, 105

MANEGMENT OF PERIPHERAL VERTIGO

51

MANEGMENT OF MENIRES DISEASE

If Mnire is due to a secondary cause (ie, Mnire syndrome), primary first-line management is the diagnosis and treatment of the primary disease (eg, thyroid disease). MEDICAL MANEGMENT3 Vestibulosuppressants (eg, meclizine) 3 Diuretics or diuretic-like medications (eg, hydrochlorothiazide). 3 Steroids
52

MANEGMENT OF MENIRES DISEASE

3

In an acutely vertiginous patient, management is directed toward vertigo control.

Intravenous (IV) or intramuscular (IM) diazepam provides excellent vestibular suppression and antinausea effects. Steroids can be given for anti-inflammatory effects in the inner ear. IV fluid support can help prevent dehydration and replaces electrolytes.

53

SURGICAL MANEGMENTCONSERVATIVE SURGERY- If serviceable hearing

MANEGMENT OF MENIRES DISEASE

present. I. ENDOLYMPHATIC SAC DECOPMRESSION II. SHUNT PROCEDURE Between sac & mastoid cavity or subarachnoid space.

DESTRUCTIVE SURGERY-If hearing is not serviceable.

LABYRINTHECTOMY II. VESTIBULAR NEURECTOMY
I.
54

MANEGMENT OF BPPV
3

The Dix-Hallpike test, along with the patient's history, aids in the diagnosis of BPV.

55

MANEGMENT OF BPPV
3

TREATMENTMedications-Antiemetic - Antihistaminic -Anticholinergic The Canalith Repositioning Procedure (CRP) Surgery

56

Canalith Repositioning Procedure

3 3 3

( CRP )

3 3

The treatment of choice for BPPV. Also 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.

57

Canalith Repositioning Procedure

( CRP )

58

THE T/T OF BPPV IS CRP MANEUVERS AS DESCRIBED BY SEMONT AND EPILEY FOR POSTERIOR CANAL AND HAMID AND LEMPERT FOR HORIZONTAL CANAL . SEMONT MANEUVER IS EFFECTIVE IN TREATING PC CUPOLITHIASIS, EPILEY FOR PC CANALITHIASIS, LEMPERT FOR HC CANALITHIASIS & HAMID FOR HC CUPULOLITHIASIS. LEMPERT AND HAMID MANEUVERS 59

60

61

62

DEHISCENCE OF SUPERIOR SEMICIRCULAR CANAL SYNDROME

SYNDROME CHARACTERIZED BY SOUND OR PRESSURE INDUCED VERTIGO 3 DEFINITIVE TREATMENT ISRESURFACING OR PLUGGING THE BONY DEFECT VIA MIDDLE FOSSA OR TRANSMASTOID APPROACH 3 PRESSURE EQUALIZING (PE) TUBE ,DIAMOX AND TOPAMAX TO CONTROL SYMPTOMS
3
63

LARGE VESTIBULAR AQUEDUCT SYNDROME

DEVELOPMENTAL ANOMALY OF INNER EAR PRESENT WITH SUDDEN SENORINEURAL OR FLUCTUATING HEARING LOSS IN CHILDHOOD 3 DEFINITIVE T/T IS COCHLEAR IMPLANTS 3 SYMPTOMS STABILZED WITH LOW SALT DIET, HYDROCHLOROTHIAZIDE AND VESTIBULAR SUPPRESSANTS
3
64

LARGE COCHLEAR AQUEDUCT SYNDROMES

CLINICAL,AUDIOLOGIC AND VESTIBULAR FINDING IN PATIENTS CONSISTENT WITH HYDROPS, ON THE SIDE IDENTIFIED BY CT 3 RESPOND TO T/T WITH DIAMOX AND/OR TOPAMAX
3

65

66

Brandt-Daroff Exercises
method of treating BPPV, usually used when the office treatment fails. 3 These exercises should be performed for two weeks, three times per day for three weeks, twice per day. 3 In each time, one performs the maneuver as shown five times. 3 1 repetition = maneuver done to each side in turn (takes 2 minutes)
3
67

Brandt-Daroff Exercises

68

SURGICAL MANEGMENT OF BPPV

3

Singular neurectomy Vestibular Neurectomy Posterior Canal Plugging Procedure

69

Posterior Canal Plugging Procedure

Recently developed procedure 3 Replaced the singular neurectomy. 3 A mastoidectomy is performed through an incision made behind the ear. 3 The balance center is then uncovered . 3 The posterior semicircular canal is opened, exposing the delicate membranous channel in which the crystalline debris is floating. 3 The canal is then gently, but firmly packed off with tissue so the debris can no longer move within the canal and strike against the nerve endings. 3 The canal is then sealed and the incision closed.
70

MANEGMENT OF LABYRINTHITIS
Bed rest & maintanance of hydration 3 Antiemetic & antivertigo. 3 Benzodiazepenes in case of sever vomiting & vertigo. 3 Steroids 3 Antibiotics in case of bacterial labyrinthitis 3 Antiviral drugs- role is not well documented. 3 Surgical- if it is secondary to middle ear disease requiring surgical treatment. 3 Antioxidents 3 Vestibular rehabilitation exercises.
3
71

MANEGMENT OF VESTIBULAR NEUROPATHY

3 Symptomatic 3 Steroids 3 Antibiotics in case of active middle ear disease. 3 Vestibular rehabilitation exercises
72

EXERCISES IN
VESTIBULAR HABITUATION THERAPY

73

EXERCISES IN BED : EYE MOVEMENTS

Looking up and then down

74

Looking alternately left and right

75

Convergence exercise
76

EXERCISES IN BED : HEAD MOVEMENTS

Bending alternately forward and backward

77

EXERCISES IN BED : HEAD MOVEMENTS

Turning alternatively to the left and then right

78

EXERCISES IN SITTING POSITION

Shrugging and rotating shoulders

79

EXERCISES IN SITTING POSITION

80

Bending forward and picking up objects from the floor

EXERCISES IN SITTING POSITION

Turning head and trunk alternately to the left and the right
81

EXERCISES IN STANDING POSITION

Changing from sitting to standing, initially with eyes open and then with the eyes closed
82

EXERCISES IN STANDING POSITION

Throwing a small (ping pong) ball in, an arc from hand to hand and following it with the eyes
83

EXERCISES IN STANDING POSITION

Throwing a small ball from hand to hand under the knee

84

EXERCISES WHILE WALKING

Throwing and catching the ball while walking

85

EXERCISES WHILE WALKING

Walking around in the room with eyes open and closed

86

EXERCISES WHILE WALKING

Walking up and down a flight of stairs

87

EXERCISES WHILE WALKING

Playing any game involving bending, stretching and aiming with the ball
88

Pharmacotherapy (Antivertigo drugs)

3 3 3 3 3

Vasodilators Antiemetics Labyrinthine sedatives Anxiolytics Diuretics

89

Anti- emetics
Antihistamines Anti Phenothiazines Miscellaneous Cholinergics

Large overlap between the effects produced by antihistamines, anticholinergics and phenothiazines.
90

Phenothiazines (Prochlorperazine, Thiethylperazine)

3

Prochlorperazine is less sedating than some other phenothiazines but drowsiness still occurs Also causes hypotension, Parkinsonian side effects
--Betts T et al, Brit. J. Clin. Pharmac, 1991, 32, 455-8, --Curley JWA, E N T Journal, 1984, 65, 555-560

The drug which most commonly causes parkinsonism in general practice is Prochlorperazine
--Chaplin S, Geriatric Medicine, 1989, Feb, 13-14

91

Anxiolytics (Tranquilizers)
(Benzodiazepines such as diazepam, Lorazepam)
3 3 3

No effect on the underlying vertigo Helps patient endure the symptoms by allaying anxiety Many side effects drowsiness and sedation, dependence and addiction abuse potential, psychomotor impairment, memory loss, interactions with alcohol

92

Harris T, Ear Nose Throat J, 1984, 65, 551-5

Diuretics
(e.g. Furosemide, Hydrochlorthiazide)
3 3

Used in vertigo and menieres disease Reduce the volume of endolymph by promoting urine flow and reducing fluid retention. Use mainly associated with electrolyte imbalance

Ludman H, Brit. Med. J., 1981, 282, 454-457, Harris T, Ear Nose Throat J, 1984, 65, 551-5
93

Cinnarizine, Flunarizine, Cyclizine

3

Labyrinthine Sedative With Antihistaminic action

Drowsiness and blurred vision (Difficult for patients who drive or operate machinery) 3 Delay normal vestibular compensation process 3 Cinnarizine and Flunarizine act via calcium antagonism, unspecific action may cause side effects Weight gain & depression (serotonergic effects) Extrapyramidal symptoms (dopaminergic effects) G.I. upset
Cinnarizine, Collin Dollery Therapeutic Drugs, C240-3, Godfraind T et al, Drugs of Today, 1982, XVIII(1), 27-42, Venkataraman S, Neurosciences Today, 1997, Vol. I, 3&4, 205-6, Norre M E, Crit Rev. Phy. Rehab. Med., 1990, 2,2,101-20

94

Betahistine
Trusted therapy for more than 41 million Vertigo patients worldwide

95

Data on file

Betahistine - Chemistry
Histamine
N CH2CH2NH2 CH2CH2NHCH3

Betahistine

N H

Histamine analogue, can be given orally with no histamine like side effects
Van Cauwenberge P B, et al, Acta Otolaryngol, 1997, suppl. 526, 43-6, Venkataraman S, Neurosciences Today, 1998, II, 1 & 2, 56-8

96

Betahistine : Pharmacokinetics
3 3 3 3 3 3

Oral administration Rapid and complete absorption Mean plasma half life :- 3-4 Hrs. Complete excretion via urine in 24 hours Very low plasma protein binding One metabolite (2-aminoethyl pyridine) is found to be active

97

Betahistine : Mode of Action

Vascular Effects (in inner ear & brain) Neurological Effects (in brain)

98

H3-AUTORECEPTORS CONTROLLING THE RELEASE OF HISTAMINE

Histaminergic Neuron

H3 autoreceptor

H1
99

H2

Adapted Van Cauweneberge PB, Acta Otolaryngol, 1997, suppl. 526, 43-6, Venkataraman S, Neurosciences Today, 1998, II, 1 & 2, 56-8

EFFECTS OF BETAHISTINE

100

Venkataraman S, Neurosciences Today, 1998, II (1 & 2), 56-8

Betahistine - Vascular Effects

H3 autoreceptors antagonist Inhibits autoregulation of histamine release H1 agonist

Improves cochlear microcirculation Improves cerebral / vertebrobasilar blood flow

101

Venkataraman S, Neurosciences Today, 1998, II (1 & 2), 56-8

Betahistine - Neurological Effects

Blocks H3 heteroreceptors Increases release of other neurotransmitters e.g. serotonin Regulates firing activity of vestibular nuclei
102

Venkataraman S, Neurosciences Today, 1998, II (1 & 2), 56-8, Biswas A, Ind. J. Otolaryngol H N S, 1997, 49(2), 179-81

Betahistine : Mode of action

Blocks H3 heteroreceptors stimulates release of other neurotransmitter e.g. serotonin Regulatory effect on vestibular nuclei H3 autoreceptors Stimulates release of histamine direct stimulatory effect H1 receptor improvement of cochlear & cerebral blood flow Symptomatic relief of vertigo Prophylactic effect of vertigo

103

BETAHISTINE
Therapeutic Indications
3 3

Vertigo Menieres Syndrome

Dosage Recommendations
3

24-48 mg /day

104

Betahistine -Tolerance
3 No sedation 3 No gastric side effects 3 No anticholinergic effects 3 No extrapyramidal side effects
Bradoo RA et al, Ind. J. Otolaryngol HNS, 2000, 52(2), 151-8, Biswas A, Ind. J. Otolaryngol H N S, 1997, 49(2), 179-81
105

Betahistine: No affinity for H2 receptors

3

H2 receptors predominate in stomach and control gastric secretion Betahistine has no effect on H2 receptors. Betahistine is generally free of gastric side effects

3 3

106

Betahistine, Collin Dollery Therapeutic Drugs, B 62-5 Van Cauwenberge PB, Acta Otolaryngol, 1997, Suppl. 526, 43-6

Betahistine
3 Contraindications - Not known 3 Precaution / Caution for use

Betahistine, being a histamine analogue, should be used with caution in patients with pheochromocytoma, peptic ulcer, bronchial asthma, concurrent use of antihistamines
Bradoo RA et al, Ind. J. Otolaryngol HNS, 2000, 52(2), 151-8

107

Betahistine
3 Contraindications - Not known 3 Precaution / Caution for use

Betahistine, being a histamine analogue, should be used with caution in patients with pheochromocytoma, peptic ulcer, bronchial asthma, concurrent use of antihistamines
Bradoo RA et al, Ind. J. Otolaryngol HNS, 2000, 52(2), 151-8

108

Betahistine No antagonistic effect on H1 receptors

3

Antihistamines block H1 receptors in brain, causing sedation or drowsiness Betahistine, stimulates H1 receptors Betahistine, does not slow down vestibular compensation, unlike antihistamines. Hence is suitable for use with vestibular habituation therapy.
Kirtane MV, Ind. J. Otolaryngol HNS, 1999, 51(2),27-36

3 3

109

Betahistine - Summary
3

Pharmacokinetics: Rapid and complete absorption after oral route Pharmacology: It is a H1 agonist and H3 receptor antagonist. It increases cochlear and cerebral blood flow and regulates firing activity of vestibular nuclei. Dose: 24-48 mg /day Indication: vertigo, menieres syndrome Contraindications: not known Precaution for use: pheochromocytoma, peptic ulcer, bronchial asthma

3 3 3 3

110

111