Vestibular Migraine

Outline
– 
Vestibular neuritis or
stroke: Head Impulse
Nystagmus Test for
Skew à HINTS
• 
nystagmus
• 
head impulse
• 
test of skew
– 
Vestibular migraine
– 
Treatment of
nystagmus
– 
– 
– 
Multiple sclerosis and
vertigo
Billateral
vestibulopathy and
neurological
syndromes
Wallenberg’s
syndrome
2
translates to 10 million
ar because of dizziness,3
hese visits to emergency
tients have transient or
last seconds, minutes or
prolonged dizziness that
days to weeks.4
e the term “dizziness” to
esyncope, unsteadiness,
orms of dizziness. When
tely, is accompanied by
nsteady gait, nystagmus
motion, and persists for a
al condition is known as
me.5,6 We define isolated
me (with or without hearin the absence of focal
as hemiparesis, hemialsy. Transient dizziness
osis distinct from that of
me, and the approach to
er accordingly.7 In this
ute vestibular syndrome,
cute vestibular syndrome
elf-limited condition preostviral. The condition is
ar neuritis but is somestibular neuronitis, laby hitis or acute peripheral
authors distinguish bevestibular neuritis based
ory symptoms at presenstinction is inconsistently
s are often used interle, we include labyrinthtis together as peripheral
lar syndrome — that is,
he inner ear (labyrinth) or
lar) nerve — as distinuses affecting vestibular
ral nervous system. Al-
ciation or its licensors
Correspondence to:
The evidence base for diagnosing the cause of
Dr. David E. Newman-Toker,
dizziness is limited.14 There is growing evidence
[email protected]
that the cause of acute vestibular syndrome is misCMAJ 2011. DOI:10.1503
diagnosed in many patients15–19 and that frontline
/cmaj.100174
physicians are eager for diagnostic guidelines.20,21
Regional variation in diagnostic practice is probably common,3 but little is known about factors
influencing diagnostic accuracy (e.g., access to
technology, availability of consultants, nature of
training, cultural or linguistic differences).
Narrative reviews have highlighted the importance of accurately assessing the risk of dangerous disorders, particularly ischemic stroke in
the posterior fossa, and have emphasized the utility of a focused history and physical examination
5,22–24
Alexander
Tarnutzer
Aaron
L. Berkowitz MD PhD, Karen A. Robinson PhD, Yu-Hsiang Hsieh PhD,
in these
patients.A.
However,MD,
we are
unaware
David
E.
Newman-Toker
MD
PhD
of any systematic reviews, practice parameters or
fully validated clinical decision rules applicable
Competing interests: None
izziness
is the
third
most prolonged
common mathough peripheral causes are more common,
to unselected
patients
with
acute,
declared.
jor
medical
symptom
reported
in
gendangerous
central
causes,
particularly
ischemic
dizziness
that offerA.evidence-based
guidance for
Alexander
Tarnutzer
Hsieh
PhD,
1 MD, Aaron L. Berkowitz MD PhD, Karen A. Robinson PhD, Yu-Hsiang
This article
has been
peer
eral
medical
clinics
and accounts
for
stroke in the brainstem or cerebellum, can mimic
the diagnosis
andNewman-Toker
management
of acute
vestibular
David
E.
MD
PhD
reviewed.
2
6,9–13
about
3%–5%
of
visits
across
care
settings.
In
benign
peripheral
causes
closely.
syndrome. We therefore performed a systematic
Correspondence to:
the United
States, of
thisthetranslates
10 million
The evidence base for diagnosing the cause of
review
and synthesis
medical to
literature,
Competing
interests: None
3 E. Newman-Toker,
izziness
the third
most
thoughisperipheral
causes
are moreevidence
common, Dr. David
is growing
ambulatory
visitsdiagnostic
peris year
because
of common
dizziness,ma
dizziness
limited.14 There
focusing
on bedside
predictors.
declared.
[email protected]
jor
medical
symptom
reported
in
gendangerous
central
causes,
particularly
ischemic
that the cause of acute vestibular syndrome is miswith roughly 25% of these visits to emergency
1
This2011.
article
has been peer
2
eral
medical
clinicshave
andtransient
accountsorfor diagnosed
stroke ininthe
brainstem
or15–19
cerebellum,
can mimic CMAJ
DOI:10.1503
many
patients
departments.
Many
patients
and that frontline
reviewed.
Key
points
/cmaj.100174
about
3%–5%
ofthat
visits
careminutes
settings.or2 In physicians
benign peripheral
closely.6,9–13
episodic
symptoms
lastacross
seconds,
are eager causes
for diagnostic
guidelines.20,21
Correspondence to:
the most
United
States,
this
translates
to 10 million
Thevariation
evidenceinbase
for diagnosing
cause of
but some
have
prolonged
that Regional
diagnostic
practice the
is proba•hours,
The
common
causes
of
acute dizziness
vestibular
syndrome
are vestibular
3
14
Dr. David E. Newman-Toker,
4 dizziness,
is growing
evidence
ambulatory
visits
per
year
is3 limited.
neuritis
(often
called
labyrinthitis)
andof
ischemic
strokebly
indizziness
the
brainstem
but little There
is known
about factors
persists
continuously
for
days because
to weeks.
common,
[email protected]
or
cerebellum.
that
the
cause
of
acute
vestibular
syndrome
is
miswith
roughly
25%
of
these
visits
to
emergency
influencing diagnostic accuracy (e.g., access to
In this article, we use the term “dizziness” to
2
15–19
CMAJ 2011. DOI:10.1503
•encompass
Vertebrobasilar
ischemic
stroke may
closely
mimic
peripheral
vestibular
diagnosed
in many patients
departments.
Many
patients
have
transient
and that
frontline
technology,
availability
of consultants,
nature
of
vertigo,
presyncope,
unsteadi
ness, or
/cmaj.100174
20,21
disorders,
with obvious
focal
neurologic
signs
absent
in more
than half
episodic
symptoms
that
last
seconds,
minutes
or
physicians
are
eager
for
diagnostic
guidelines.
training, cultural or linguistic differences).
and other nonspecific forms of dizziness. When
of people presenting with acute vestibular syndrome due to stroke.
hours, but
some have
prolonged
dizzinessbythat Regional
diagnostic
practicetheis im
probaNarrativevariation
reviewsinhave
highlighted
dizziness
develops
acutely,
is accompanied
• Computed
tomographyfor
hasdays
poortosensitivity
4 in acute stroke, and
3
but little
is known
about
factors
persists
continuously
weeks.
bly common,
portance
of
accurately
assessing
the
risk
of
dannausea
or
vomiting,
unsteady
gait,
nystagmus
diffusion-weighted magnetic resonance imaging (MRI) misses up to
influencing
diagnostic
accuracy
(e.g.,
access
Inin this
wethe
use
the and
term
“dizziness”
gerous
disorders,
particularly
ischemic
stroke
in to
and
intolerance
to head
motion,
persists
forfirst
a to24–48
one
five article,
strokes
in
posterior
fossa
in the
hours.
technology,
availability
of
consultants,
nature
of
encompass
vertigo,
presyncope,
unsteadi
ness,
the
posterior
fossa,
and
have
emphasized
the
utilday
or
more,
the
clinical
condition
is
known
as
• Expert opinion suggests a combination of focused history and physical
5,6
cultural
or linguistic
differences).
andvestibular
other nonspecific
dizziness.
When
ity training,
ofacute
a focused
history
and physical
examination
acute
Weofdefine
isolated
examination
as syndrome.
the initialforms
approach
to evaluating
whether
5,22–24
Narrative
have highlighted
the imdizziness
develops
isoraccompanied
vestibular
syndrome
isacutely,
due(with
to stroke.
patients.reviews
acute
vestibular
syndrome
without hear- by in these
However,
we are unaware
portance
of accurately
the risk of or
dannausea
or occurring
vomiting,
unsteady
gait,examination
nystagmus
loss)
as
in
the
absence
of focal —ofHINTS
any (horizontal
systematic
reviews,assessing
practice parameters
•ingA
three-component
bedside
oculomotor
head
impulse
test,to
nystagmus
and test
skew)
—for
identifies
stroke
with
gerous
disorders,
particularly
ischemic
stroke in
and intolerance
headasmotion,
andofpersists
neurologic
signs
such
hemiparesis,
hemi
- a fully
validated
clinical
decision rules
applicable
high
in patients is
with
acute as
vestibular
syndrome
posterior patients
fossa, andwith
haveacute,
emphasized
the utilday sensitivity
orloss
more,
the specificity
clinical
known
sensory
or and
gaze
palsy. condition
Transient
dizziness
to the
unselected
prolonged
and rules out stroke more effectively
than early diffusion-weighted MRI.
5,6
ity of athat
focused
and physical
examination
vestibulardiagnosis
syndrome.
We from
definethat
isolated
hasacute
a differential
distinct
of
dizziness
offerhistory
evidence-based
guidance
for
5,22–24
acute
vestibular
theorapproach
to theindiagnosis
and management
of acute
these patients.
acute
vestibularsyndrome,
syndromeand
(with
without hearHowever,
we vestibular
are unaware
7
diagnosis
differ accordingly.
Inofthis
We therefore
performed
systematic or
ing loss)should
as occurring
in the absence
focal syndrome.
of any systematic
reviews,
practicea parameters
review,
we focus
on such
acute as
vestibular
syndrome,
and
synthesis
of the
medical
literature,
neurologic
signs
hemiparesis,
hemi- review
fully
validated
clinical
decision
rules
applicable
CMAJ
1
whether
isolated
or gaze
not. palsy. Transient dizziness focusing
on bedside
diagnostic
predictors.
sensory
loss or
to unselected
patients
with
acute, prolonged
Most
patients withdiagnosis
acute vestibular
has
a differential
distinct syndrome
from that of dizziness that offer evidence-based guidance for
have
an acute,
benign,
self-limited
pre- to
acute
vestibular
syndrome,
and condition
the approach
the
diagnosis
and management of acute vestibular
Key
points
7
sumed
to be viral
or postviral.
The condition
diagnosis
should
differ accordingly.
In isthis syndrome. We therefore performed a systematic
•review
The most
of acute
vestibular
syndrome are vestibular
usually
called
vestibular
neuritis
but issyndrome,
somereview,
we focus
on acute
vestibular
and common
synthesiscauses
of the
medical
literature,
neuritis (often called labyrinthitis) and ischemic stroke in the brainstem
times
referred
to asorvestibular
neuronitis, laby whether
isolated
not.
focusing
on
bedside
diagnostic
predictors.
or cerebellum.
rinthitis,
orvestibular
acute peripheral
Mostneurolabyrinthitis
patients with acute
syndrome
Review
CMAJ
Does
my dizzy patient have a stroke? A systematic
review
Review
of bedside diagnosis in acute vestibular syndrome
CMAJ
Does my dizzy patient have a stroke? A systematic review
of bedside diagnosis in acute vestibular syndrome
D
D
3
HINTS to Diagnose Stroke in the Acute Vestibular Syndrome : Three-Step Bedside
Oculomotor Examination More Sensitive Than Early MRI Diffusion-Weighted Imaging
Jorge C. Kattah, Arun V. Talkad, David Z. Wang, Yu-Hsiang Hsieh and David E.
Newman-Toker
Stroke. 2009;40:3504-3510; originally published online September 17, 2009;
doi: 10.1161/STROKEAHA.109.551234
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2009 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
HINTS:
sensitivity 100%
specificity 96%
Early
MRI with DWI: sensitivity 72%
specificity 100%
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/40/11/3504
HINTS to INFARCT:Data
Impulse
(test) Normal, Fast (phase)
Supplement (unedited) at:
http://stroke.ahajournals.org/content/suppl/2009/10/01/STROKEAHA.109.551234.DC1.html
Alternating,
Refixation on Cover Test
4
Vestibular ocular motor conenctions
Activation
Inhibition Eye movement
ipsi
contra
ipsi
Lateral
MR
LR
LR
MR
→
stim.
left
←
Anterior
SR
IO
IR
SO
↑ ∩▼
↑ ▼∩
Posterior
SO
IR
IO
SR
↓ ∩▼
↓ ▼∩
L+A+P
→ ∩▼
← ▼∩
contra stim. right
5
Vestibular ocular motor connections
Normal
Left Out
Posteriors Out
right
Lateral
→
←
→
→
←
Anterior
↑ ∩▼
↑ ▼∩
↑ ∩▼
↑ ∩▼
↑ ▼∩
Posterior
↓ ∩▼
↓ ▼∩
↓ ∩▼
L+A+P
→ ∩▼
← ▼∩ → ∩ ▼
↑
↑
Right + Left
left
0
right
left
right
→ ∩▼ left
↑↑ 6
Bedside visuo-vestibular interaction
v  The
“velocity storage mechanism” merges
vestibular with visual signals (the penlight test)
– 
Peripheral nystagmus:
• 
• 
– 
Normal “velocity storage” uses visual signals to modify the
response triggered by the pathological vestibular system:
dampens the nystagmus
The peripheral nystagmus is inhibited by visual fixation
Central nystagmus :
• 
• 
Abnormal “velocity storage” is unable to use visual signals
to modify the response triggered by the pathological
vestibular system: unable to dampen the nystagmus
The central nystagmus is not inhibited by visual fixation
7
Gaze-Evoked Nystagmus
v nystagmus
in lateral and/or upward and/
or downward gaze beating toward gaze
direction
v not influenced by visual fixation
lesion: flocculus
8
(physiological) end-point nystagmus
v  in
far-lateral gaze only
v  small amplitude
v  influenced (usually reduced) by visual fixation
v  not associated to other floccular or cerebellar
signs
9
Downbeat nystagmus
1
0
Downbeat nystagmus
1
2
Downbeat nystagmus
-  Larger in lateral gaze
-  Not affected by visual
fixation
-  May be positional
-  May be increased,
decreased or inverted by
convergence
-  Site of lesion: flocculus
-  Gaze evoked nystagmus
-  Abnormal smooth pursuit
-  Abnormal VOR suppression by
visual fixation
1
3
Up-beat nystagmus
-  Larger in upgaze
-  Not affected by visual fixation
-  May be positional (and change
direction becoming DBNy)
-  May be increased, decreased or
inverted by convergence
-  Site of lesion: paramedian
medulla, pons, midbrain
1
4
Pendular nystagmus
-  No quick phase
-  May result from the
combination of horizontal,
vertical and torsional
componentes
-  May be unconjugate,
different in the two eyes
-  MS, “oculopalatal tremor”,
Whipple’s disease
1
5
Periodic alternating nystagmus
-  Horizontal ny inverting direction
every 90- 120 s
-  Not influenced by visual fixation
-  Lesion: nodulus / uvula
1
6
Internuclear Ophthalmoplegia
III
VI
Internuclear Ophthalmoplegia
v  (right
INO)
v  in lateral (left) gaze:
– 
– 
abducting (right) eye: nystagmus
adducting (left) eye: paralysis (does not move) à
paresis (slow movement)
v  normal
convergence, i.e. the paralysis or
paresis is supranuclear
Head thrust
Il soggetto mantiene il capo ruotato mentre fissa un bersaglio
postogli di fronte
Mentre il soggetto mantiene la fissazione, l’ operatore gli ruota
rapidamente la testa fino a riportarla in posizione diritta
v  Risposta normale: alla fine della rotazione il soggetto non
esegue dei movimenti saccadici di correzione
v  VOR ipoattivo: movimento saccadico di correzione nella
direzione opposta a quella di rotazione (LESIONE
VESTIBOLARE PERIFERICA)
v  VOR iperattivo: movimento saccadico nella stessa direzione
(LESIONE VESTIBOLO-CEREBELLARE)
v  Il razionale del test è basato sulla II legge di Ewald
v  Test
specifico, non molto sensibile
19
OCULAR TILT REACTION
OTR
Ocular Tilt Reaction :
a vestibular syndrome in the roll plane
22
OTR: signs
OTR – SKEW DEVIATION
Acquired vertical comitant (not paretic)
misalignment
Ocular misalignment = diplopia
Skew deviation: cover test
SINDROME DI WALLENBERG
26
Wallenberg’s Syndrome – PICA distribution infarct
involving the dorsolateral medulla
Restiform body (ICP)
Interruption of climbing fibers
facilitates Purkinje Cell inhibition of
FN leading to a functional lesion of
the FN and produces saccade
lateropulsion
Sindrome di
Wallenberg
v Lesione
v Segni ipsilaterali
–  Tratto discendente e nucleo del
–  Ipoestesia termo-dolorifica
V
emivolto
–  Fibre del IX e X
–  Disartria e disfagia
–  Peduncolo cerebellare?
–  Atassia segmentaria.
–  Vie simpatiche pupillari
–  Sd. di Horner ipsi
• 
– 
– 
– 
– 
Nuclei gracile e cuneato
Nucleo e tratto solitario
?
Tratto spino-talamico
– 
– 
– 
Ptosi + Miosi + Enoftalmo
Ipoestesia tattile discr.emisoma
Anageusia
Singhiozzo
v Segni controlaterali
–  Ipoestesia termo-dolorifica
emisoma
Sindrome di Wallenberg – segni
vestibolari ed oculomotori
v Lesione
– 
Nuclei vestibolari + vie otolitiche + fibre olivo-cerebellari
(= ipofunzione nucleo del fastigio)
v Sintomi
– 
Vertigine e lateropulsione verso il lato leso
Sindrome di Wallenberg – segni
vestibolari ed oculomotori
– 
– 
– 
– 
– 
– 
– 
Al buio occhi deviano verso il lato
leso (“lateropulsion”)
Ny spontaneo orizzonto-rotatorio
(con possibile componente
verticale)
Ocular Tilt Reaction
Saccadici orizzontali ipermetrici
verso il lato leso e ipometrici verso il
lato sano (“ipsipulsion”)
Saccadici verticaliàobliqui (hanno
una componente orizzontale verso il
lato leso)
Inseguimento lento deficitario verso
il lato sano
VOR : preponderanza direzionale
verso il lato leso
Vertigo syndromes
Benign Paroxysmal Positional Vertigo
Psychogenic Vertigo
“Central Vertigo”
Vestibular Migraine
Menière’s disease
Vestibular neuritis
Bilateral vestibulopathy
19.6%
15.9%
14.5%
07.9%
07.5%
06.7%
02.6%
31
Migraine without aura (ICHD-3)
A. At least 5 episodes fulfilling criteria B -D
B. Headache lasting 4- 72 hours (untreated or unsuccesfully treated)
C. Headache has at least 2 of the following characteristics:
1. 
unilateral location
2. 
pulsating quality
3. 
moderate or severe pain intensity
4. 
aggravation by or avoidance of routine physical activity
D. During headache at least one of the following
1. 
nausea and/or vomiting
2. 
photophobia and phonophobia
E. Not better accounted for by another ICHD-3 diagnosis
32
Migraine with aura (ICHD-3)
A. At least 5 episodes fulfilling criteria B -D
B. One or more of the following fully reversible aura symptoms
1. 
visual
2. 
sensory
3. 
speech and/or language
4. 
motor
5. 
brainstem
6. 
retinal
C. At least 2 of the following 4 characteristics:
1. 
at least one of the aura symptoms spreads gradually over ≥ 5 minutes,
and/or two or more symptoms occur in succession
2. 
each individual aura symptom last 5-60 minutes
3. 
at least one aura symptom is unilateral
4. 
the aura is accompanied, or followed within 60 minutes, by headache
D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic
attack has been excluded
33
Vestibular Migraine (VM)
A. At least 5 episodes with vestibular symptoms of moderate or severe intensity,
lasting 5 min to 72 hours
B. Current or previous history of migraine with or without aura according to the
International Classification of Headache Disorders (ICHD)
C. One or more migraine features during at least 50% of the vestibular episodes:
1. 
headache with at least two of the following characteristics: one sided
location, pulsating quality, moderate or severe pain intensity,
aggravation by routine physical activity
2. 
photophobia and phonophobia
3. 
visual aura
D. Not attributable to another disorder, in particular not to another vestibular
disorder
34
“Probable VM”
A. At least 5 episodes with vestibular symptoms of moderate
or severe intensity, lasting 5 min to 72 hours, not
explained by another vestibular disorder
B. Only one of the criteria B and C for vestibular migraine is
fulfilled (migraine history or migraine features during the
episode)
C. Not attributable to another disorder
35
Vestibular symptoms include:
Spontaneous vertigo including
• 
internal vertigo, a false sensation of self-motion
• 
external vertigo, a false sensation that the visual surround is
spinning or flowing
36
Vestibular symptoms include:
§ 
positional vertigo, occurring after a change of head position,
§ 
visually-induced vertigo, triggered by a complex or large moving
visual stimulus
§ 
head motion-induced vertigo
§ 
head motion-induced dizziness with nausea. Dizziness is
characterized by a sensation of disturbed spatial orientation.
Other forms of dizziness, e.g. spontaneous dizziness, are currently
not included in the classification of vestibular migraine
37
Vertigo is rated as:
• 
Moderate:
• 
• 
Interferes but does not prohibit daily activities
Severe:
• 
Daily activities can not be continued
38
Attack duration:
• 
Highly variable
• 
Short lasting (seconds) episodes usually triggered by head motion
or visual stimulation then consider the duration as the total
symptomatic period
• 
Full recovery may last several days / weeks
• 
chronic vs chronic transformation
39
Visual aura:
Phonophobia:
§ 
Sound induced discomfort. Usually transient and bilateral
§ 
Distinction from “recruitment”
40
but not median
In migrainous:
•  Trigeminal stimulation increases motion sickness
•  Optokinetic stimulation increases pain sensitivity
*$(2"#5 $(%'+"($()2 *4 _/%)' =0+( !0%'$% (U2"%/%'%2#*) *) 2.( #!'#0%2("%0 A300(1 5*0+$)'F %)1 2.( 5*)2"%0%2("%0
*5.0(% OP $#) 4*00*N#)7 (0(52"#5%0 '2#$+0%2#*) *4 2.( 2"#7($#)%0 7%)70#*)` P,\ %)1 \ $R Aa3 ! P,P8b , ! 8F,
V%60( 9, c+%)2#2%2#/( "('+02' *4 (0(52"#5%00& #)1+5(1 !("$(%6#0#2& 5.%)7(' #) 2.( 5*5.0(%
X+$6(" *4 %)#$%0'
I!'#0%2("%0
8
8
Q
P,G\ ! P,\P
P,9? ! P,P?
P,\Q ! P,PPQ
)', -( .%/( !"(/#*+'0& #1()2#3(1
%2#*) *4 2.( 5*5.0(%" 60**1 /(''(0'
7($#)%0 7%)70#*), 89:88 ;2#$+0%2#*)
#7)#35%)2 (44(52 *) <=> #) 6*2.
*0*7#5%0 5*)1#2#*)' A(,7, #) 2.(
*0&$!.%2#5 .&1"*!': *)( *4 2.(
E' 1#'(%'(F, 9G:8H I) J.*$(*'2%2#5K
(%" A(,7, B(C)#(D"(E' 1#'(%'(F: 2"#L
/%2#*) $%& !0%& %) #$!*"2%)2
"(7+0%2#*): 6+2 %0'* #) /%'5+0%"
#0%" %"2("& %)1 M+#1 6%0%)5( N#2.#)
#60( 2.%2 /%'5+0%" .(%1%5.( A(,7,
& .%/( % )(+"*6#*0*7#5%0 *"#7#):
( #) 2.( #)2("%52#*) 6(2N(() 2.(
' 2%"7(2 *"7%)' *4 2.( 6%'#0%" %"2("&
$+5. 2.( '%$( N%& 2.%2 0#7.2 5%)
'!(5+0%2( 2.%2 %)2#1"*$#5 %52#/%L
%)70#*) 5%) 5%+'( /%'5+0%" !("$(L
<*)2"%0%2("%0
P,QH ! P,\H
P,\@ ! P,\Q
P,\\ ! P,PH
3 /%0+(
P,PQ8
P,P\G
P,9P\
.(%"#)7, 9Q R $#'"(7+0%2(1 M+#1 6%0%)5( $%& "('+02 #)
#)5"(%'(1 #))(" (%" M+#1 !"(''+"( %)1 %) %6)*"$%0
#*) 6%0%)5( N#2. 6#*5.($#5%0 %)1 6#*$(5.%)#5%0
5*)'(S+()5(',
!"#!$%&'"#
T+" "('+02' 1($*)'2"%2( % 4+)52#*)%0 5*))(52#*)
6(2N(() 2.( 5*5.0(% %)1 /("2(6"*L6%'#0%" '&'2($ 2."*+7.
2.( 5%!'%#5#)L'()'#2#/( !"#$%"& '()'*"& )(+"*)', -(
!"*!*'( 2.%2 /("2#7*: 2#))#2+' %)1 .(%"#)7 1(35#2' %''*L
5#%2(1 N#2. $#7"%#)( %"#'( 6& (U5#2%2#*) *4 2.( 2"#7($#)%0
7%)70#*) %)1 2.%2 1&'4+)52#*) *4 2.( 5*5.0(% $%& 2"#77("
6%'#0%" %)1 50+'2(" .(%1%5.(,
)*+,'-."/0"1",(%2V.( !"('()2 N*"W N%' '+!!*"2(1 6& XIY
doi:10.1111/j.1468-2982.2006.01208.x
Serotonin-induced plasma extravasation in the murine inner ear:
possible mechanism of migraine-associated inner ear dysfunction
J-W Koo1 & CD Balaban2
1
Department of Otolaryngology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea, and 2Departments of Otolaryngology, Neurobiology, Communication Sciences & Disorders and Bioengineering, University of
Pittsburgh, Pittsburgh, PA, USA
1318
J-W Koo & CD Balaban
Koo J-W & Balaban CD. Serotonin-induced plasma extravasation in the murine
inner ear: possible mechanism of migraine-associated inner ear dysfunction.
Cephalalgia 2006; 26:1310–1319. London. ISSN 0333-1024
Sensitivity to sound and vertigo are often components of migraine. Recent
studies reflex
suggest
that plasma extravasation from intradural blood vessels may
Trigeminovasular
activation
contribute to migraine pain. This study documented plasma extravasation in the
mouse inner ear after intravenous administration of serotonin (5-HT). HorseradCGRP, substance P, neurokinin A
ish peroxidase (HRP) was injected intravenouslyStria
to trace
protein extravasation in
vascularis
mice, followed 15 min later by intravenous 5-HT
saline. Forty-five minutes
darkorcells
later,
mice
were
euthanized.
HRP
extravasation
was
visualized immunohisVasodilation (inner ear)
Extravasation (inner ear)
spiral
modiolar
artery
tochemically and quantified densitometrically. Baseline and evoked extravasaradiating
arterioles from skin,
tion in stria vascularis and tectorial membrane were
indistinguishable
dura mater and tympanic
membrane. Brain parenchyma, Scarpa’s ganglion,
Altered K+ recycling
Neurogenic inflammation
basal spiral ganglion and modiolus, and the central vestibular nerve segment
showed no significant 5-HT-induced extravasation. In contrast, 5-HT produced
extravasation in the apical spiral ganglion, modiolus, and intralabyrinthine
superior and inferior vestibular nerve. Thus, inner ear plasma extravasation is a
Dizziness, hyperacusis, hearing loss, tinnitus
potential mechanism for migraine-associated vertigo and sound sensitivity.
43
inner ear,
migraine,
neurogenic
inflammation, serotonin
Possible mechanism of the inner ear migraine!Dizziness,
model. Trigeminovascular
reflex
activation can
produce
Figure 6
vasodilation of intracranial, dural and inner ear arteries, which activates trigeminal sensory afferents. The activated
trigeminal afferents release neuropeptides [e.g. calcitonin
gene-related
peptide (CGRP),
P and of
neurokinin
A] that
Carey
D. Balaban
PhD, substance
Department
Otolaryngology,
University of Pittsburgh
produce vasodilation and local extravasation in the inner ear as well as in the meninges. Plasma extravasation induces
School
of
Medicine,
107
Eye
&
Ear
Institute,
203
Lothrop
Street, Pittsburgh, PA
local aseptic inflammation, especially in the stria vascularis, which may influence K+ recycling in the inner ear.
15213, USA. Tel. + 1 412 647 2298, fax + 1 412 647 8720, e-mail balabancd@msx.
The hypersensitive Migrainous Brain
Peripheral and Central
Sensitization in Migraine
The migrainous
“stigmata” of VM
motion sickness
v  visual vertigo
v 
v 
Vestibular symptoms
– 
– 
– 
– 
– 
v 
spontaneous vertigo
positional vertigo
visually-induced vertigo
head motion-induced
vertigo
head motion-induced
dizziness with nausea
Associated symptoms
– 
Photo- and phonophobia44
316
C.D. Balaban / Migraine, vertigo and migrainous vertigo: Links between vestibular and pain mechanisms
Fig. 1. Schematic diagram of pathways that potentially explain co-morbid migraine and balance disorders. The white boxes with black borders
show balance-related pathways and the related somatic and visceral motor response mechanisms (e.g., vestibulo-ocular and vestibulospinal
reflexes). The light gray boxes show trigeminal nociceptive sensorimotor pathways, which include afferent pathways, the periaqueductal gray
(PAG) and the trigeminovascular reflex circuit. Thalamic and sensory cortical processing pathways are indicated schematically as gray bordered
white boxes. Dark gray boxes include interoceptive, homeostatic and affective pathways that are activated by nociceptive and vestibular activity [6,
14,15,53]. The interoceptive pathways include connections between the parabrachial nucleus, central amygdaloid nucleus and insula. The
pathways for involuntary or homeostatic regulation of affect are believed to include ventral lateral prefrontal cortex, orbitofrontal cortex and the
ventral aspect of the cingulate cortex. Finally, pathways for the effortful regulation of affect include interconnections between the dorsal lateral
prefrontal cortex, dorsal medial prefrontal cortex, dorsal anterior cingulate cortex and hippocampus. The circled minus signs designate potential
sites of action of triptans at 5-HT1B , 5-HT1D and 5-HT1F receptors.
46
VM -­‐ Treatment
ü 
Preventive treatment
ž  Calcium-channel blockers
-  Cinnarizine
ü No controindications
ü Side effects: sedation, weight gain (very
long term: extrapyramidal signs, mood
depression)
ü (typical) Dosage: Stugeron 25 mg (8 drops)
bid, starting with 25 mg
VM -­‐ Treatment
ü 
Preventive treatment
ž  Tricyclic Antidepressants
-  Amitriptilyne
ü Controindications: glaucoma, prostate
hypertrophy, epilepsy, cardiac disease
ü Side effects: dry mouth, urinary retention,
glaucoma; arrythmia; agitation / sedation;
weight gain
ü (typical) Dosage: Laroxyl 20 mg (10 drops),
starting with 10 mg
VM -­‐ Treatment
ü 
Preventive treatment
ž  Beta-blockers
-  Propranolol
ü Controindications: sinus bradiycardia, AV
block, asthma, diabetes mellitus
ü Side effects: sedation; hypothension,
bradycardia
ü (typical) Dosage: Inderal R 80 mg day or
bid
VM -­‐ Treatment
ü 
Preventive treatment
ž  Antiepileptic drugs
-  Topiramate
ü Controindications:
ü Side effects: sedation, cognitive slowing,
paresthesias, renal stones (long term),
glaucoma
ü (typical) Dosage: Topamax 100 mg, starting
with 25 mg (slow increase 25 mg / wk
RECOMMENDATIONS (AAN practice guidelines 2012)
Level A. The following
Courtesy
medications are established as effective and should be
offered for migraine prevention:
§  Antiepileptic drugs (AEDs): divalproex sodium, sodium valproate, topiramate
§  beta-Blockers: metoprolol, propranolol, timolol
§  Triptans: frovatriptan for short-term MAMs prevention
§  Petasites (butterbur)
of David Zee
Level B. The following medications are probably
effective and should be considered for migraine
prevention:
• Antidepressants: amitriptyline, venlafaxine
• beta-Blockers: atenolol, nadolol
• Triptans: naratriptan, zolmitriptan for short-term MAMs prevention
• NSAIDS: fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium
• Herbal therapies, vitamins, and minerals: riboflavin, magnesium, MIG-99 (feverfew)
• Histamines: histamine SC
Level C. The following medications are possibly effective
and may be considered for migraine prevention:
• ACE inhibitors: lisinopril
• Angiotensin receptor blockers: candesartan
• alpha-Agonists: clonidine, guanfacine
• AEDs: carbamazepine
• -Blockers: nebivolol, pindolol
NSAIDs: flurbiprofen, mefenamic acid
• Herbal therapies, vitamins, and minerals: Co-Q10, estrogen
• Antihistamines: cyproheptadine
RECOMMENDATIONS
Courtesy of David Zee
Level U. Evidence is conflicting or inadequate to support
or refute the use of the following medications
for migraine prevention:
• AEDs: gabapentin
• Antidepressants
• Selective serotonin reuptake inhibitor/selective serotonin-norepinephrine reuptake inhibitors:
fluoxetine, fluvoxamine
• Tricyclics: protriptyline
• Antithrombotics: acenocoumarol, Coumadin, picotamide
• beta-Blockers: bisoprolol
• Calcium-channel blockers: nicardipine, nifedipine, nimodipine, verapamil
• Acetazolamide
• Cyclandelate
• NSAIDs: aspirin, indomethacin
• Herbal therapies, vitamins, and minerals: omega-3
• Other: HBO
VM -­‐ Treatment •  and especially patients with vestibular migraine
are at risk of developing somatoform dizziness
independently from the degree of vestibular
dysfunction (Best, 2009).
•  in dizzy patients the comorbidity of anxiety
increases health care utilization (and costs) (Wiltink,
2009)
VM -­‐ Treatment •  Migraine / vertigo / psychiatric disorders
•  Somato-psychic vs psycho-somatic
•  SSRI (triptans should not to be associated)
–  Migraine Anxiety Related Dizziness = migraine +
anxiety + balance disorders
Hints •  Recurrent vertigo? Consider VM
• 
• 
• 
• 
Personal and/or familiar history of migraine (ICHD III)
Motion sickness? Visual vertigo?
Interictal vestibular examination (quite) normal, not specific
Headache and vertigo diary
–  Diagnosis
–  Treatment
•  Plan vestibular examination during the attack
VERTIGINI E SCLEROSI MULTIPLA 56
Sintomi iniziali (%)
Età di
esordio
Neurite
ottica
Diplopia /
vertigine
Motorio
Atassia
Sensitivo
<20
23
18
10
14
46
20-29
23
12
13
11
52
30-39
13
11
21
15
44
40-49
9
17
34
13
33
>=50
6
13
51
11
32
Modificata da Weinshenker et al., 1989
Sindrome clinicamente isolata
• CIS: Clinically Isolated Syndrome
– Nell’85% dei pazienti che svilupperanno MS l’esordio è dato
dalla comparsa acuta o subacuta di sintomi neurologici dovuti ad
una singola lesione della sostanza bianca; tale presentazione è
nota come CIS.
– Dopo 14 anni il 68% delle CIS sviluppa una MS.
• Presentazione delle CIS:
• 21% NORB
• 46% sintomi e segni di sofferenza delle vie lunghe
• 10% sindrome troncoencefalica
• 23% sintomi multifocali
•  La disseminazione spaziale manca nel 77% delle CIS
•  E’ sempre assente la disseminazione temporale
Sintomi troncoencefalici / cerebellari (%)
Sintomo
All’esordio
Nel corso
della malattia
vertigine
4.3
36
diplopia
8
51
atassia
11
82
disartria
13
44
Ipoacusia
0.6
17
Disfagia
0.3
13
La causa più frequente di
vertigine nella SM? VPPB
Pseudo-neurite vestibolare ed SM
STRATEGIE TERAPEUTICHE DEL
NISTAGMO
•  Nessuna terapia
•  Terapia della “malattia”
–  VPPB
–  SM (fase acuta)
–  Conflitto neuro-vascolare / vestibular paroxysmia
–  Sindrome da deiscenza del canale superiore
–  (Neurite vestibolare)
–  (Vertigine emicranica)
–  (Atassia episodica)
•  Terapia del nistagmo
– Farmacologica
–  Strumenti ottici
–  Chirurgica
–  Tossina botulinica
6
3
Terapia del nistagmo
6
4
Terapia farmacologica del nistagmo
•  Rinforzo GABAergico
•  Baclofen, Gabapentin, Clonazepam, Isoniazide, Vigabatrin
•  Blocco canali del calcio
•  Gabapentin
•  Blocco glutamatergico
•  Memantina
•  Blocco canali del potassio
6
•  Aminopiridine: 3-4 diaminopiridina,
4 aminopiridina
5
Terapia farmacologica del nistagmo
•  Pendular nystagmus
•  In SM: gabapentin, memantine (cannabis)
•  In oculopalatal tremor:, valproate,trihexyphenidyl
•  Downbeat nystagmus
•  3,4-diaminopiridina, 4-aminopiridina, clonazepam, baclofen,
trihexyphenidyl;acetazolamide (EA2)
•  Upbeat nystagmus
•  Memantine, 3,4-diaminopiridina, 4-aminopiridina
•  Periodic alternating nystagmus
•  baclofen
6
6
Terapia farmacologica del nistagmo
• Gabapentin
–  Meccanismo d’azione? Legame Ca++ αδ2-1
–  300 - 800 mg, 3 volte al giorno
–  Dosaggi “efficaci” 1200 – 1800 mg / die
6
7
Terapia farmacologica del nistagmo
•  3-4 DAP o 4 AP
–  Blocco dei canali del potassio
–  Migliora la conduzione delle fibre demielinizzate
–  Aumenta l’attività delle cellule del Pukinije
–  5 – 10 mg, 4 volte al giorno
–  Controindicazioni
• Aritimie
• Epilessia
–  Effetti collaterali
• Parestesie
6
8
Terapia farmacologica del nistagmo
•  Baclofen
–  Agonista GABAb
–  10 mg, 3 volte al giorno
–  Effetti collaterali
• Sedazione
–  Evitare sospensione brusca
6
9
7
0
Terapia farmacologica del nistagmo
•  Memantina
– Antagonista non
competitivo NMDA
– 10 - 20 mg, 3 volte al
giorno
– Effetti collaterali
• Visione sfuocata, fatica, instabilità
7
1
•  Il nistagmo puó essere trattato farmacologicamente
•  Esiste una specificità di trattamento basata sul tipo di
nistagmo
•  Reperibilità e costo dei farmaci
•  L'obiettivo non necessariamente deve essere l'abolizione
del nistagmo
7
2
Bilateral vestibulopathy
Ann. N.Y. Acad. Sci. ISSN 0077-8923
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Issue: Basic and Clinical Ocular Motor and Vestibular Research
Cerebellar ataxia, neuropathy, vestibular areflexia
syndrome (CANVAS): a review of the clinical features
and video-oculographic diagnosis
David J. Szmulewicz,1 John A. Waterston,2 Hamish G. MacDougall,3 Stuart Mossman,4
Andrew M. Chancellor,5 Catriona A. McLean,6 Saumil Merchant,7 Peter Patrikios,8
G. Michael Halmagyi,9 and Elsdon Storey2
1
Department of Neuroscience, Alfred Hospital, Melbourne, Australia. 2 Department of Neuroscience, Monash University,
Melbourne, Australia. 3 Vestibular Research Laboratory, School of Psychology, University of Sydney, Sydney, Australia.
4
Department of Neurology, Capital Coast Health, Wellington, New Zealand. 5 Department of Medicine, Tauranga Hospital,
Wellington, New Zealand. 6 Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia. 7 Department of
Otopathology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts. 8 Department of Neurology, Royal Brisbane and
Women’s Hospital, Brisbane, Australia. 9 Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia
Address for correspondence: Dr. David J. Szmulewicz, Department of Neuroscience, Alfred Hospital, Commercial Road,
Melbourne, Victoria, 3004, Australia. [email protected]
The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a
distinct syndrome with a characteristic and measurable clinical sign—an absent visually enhanced vestibulo-ocular
reflex—in 2004. We reviewed 27 patients with this syndrome and show that a non-length-dependent sensory deficit
with absent sensory nerve action potentials is an integral component of this syndrome, which we now call “cerebellar
ataxia with neuropathy and bilateral vestibular areflexia syndrome” (CANVAS). All patients had brain MRI and 22/27
had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I. Brain and
temporal bone pathology in one patient showed marked loss of Purkinje cells and of vestibular, trigeminal, and facial
73
Tipi di nistagmo di origine centrale
Tipo
Fisiopatologia
Caratteristiche
Sede
Down -
sbilanciamento del tono
battente verso il basso; spesso
pavimento IV
beat
dei canali semicircolari
maggiore nello sguardo di lateralità
ventricolo
verticali; bias
ed in convergenza
lobo flocculo-
anteriore/posteriore sotto
nodualre
controlloo cerebellare.
Up- beat
sbilanciamento del tono
battente verso l’ alto; modulato dalla giunzione ponto-
dei canali semicircolari
posizione della testa
verticali
mesencefalica o
bulbo-pontina
Pendolare sconosciuta. Via dentato- oscillazione oculare sinusoidale con troncoencefalo
rubro-olivare? Spesso
componenti orizzontali , verticali,
associato ad amaurosi
torsionali con intensità e fase
demielinizzazione
variabili; talora dissociato
cervelletto
74
Tipi di nistagmo di origine centrale
Tipo
Fisiopatologia
Caratteristiche
Oftalmoplegia
Lesione lungo il fascicolo
Battente nella direzione di
internucleare
longitudinale mediale (FLM)
sguardo e solo nell’occhio
che connette il VI con il III nc. abdotto; adduzione incompleta o
Ricorda che il FLM convoglia lenta nei movimenti di versione,
anche segnali relativi ai
normale nei movimenti di
movimenti di inseguimento
convergenza.
lento ed al riflesso vestibolooculomotorio verticale
Il ny nell’occhio abdotto è:
Adattamento?
Aumento tono di
convergenza?
75