4th Journal Reading

Wednesday, December 10th 2014

Subclinical cerebellar dysfunction in

patients with migraine: Evidence from
eyeblink conditioning

Presenter
Moderator

: dr. Steviyani
: dr. Iskandar Nasution Sp.S FINS

INTRODUCTION
There is some evidence for a cerebellar dysfunction,
commonly of mild degree, in patients with migraine
In more recent years balance abnormalities and
paroxysmal vertigo have been shown to occur frequently
in the most common subtype of familial hemiplegic
migraine (FHM) (6). Cerebellar symptoms have been
found in FHM-1, which is caused by mutations in the
CACNA1A gene
To date, only a few studies have investigated cerebellar
function in common forms of migraine

 A behaviourally neutral conditioned stimulus (CS), such

as a tone, is presented and followed by the
unconditioned stimulus (US), such as a corneal air-puff
This is delivered to the eye, eliciting a reflexive blink, the
unconditioned response (UR), which consists of closure
of the eyelid in human
Studies in patients with cerebellar degeneration and
focal cerebellar lesions have shown that both acquisition
and timing of CRs is dependent on the cerebellum in
humans

 Eyeblink conditioning has proved helpful to search for

cerebellar dysfunction in various neurological diseases
The aim of the present study was to determine whether
eyeblink conditioning is impaired in patients with
common forms of migrain
Impaired eyeblink conditioning would provide evidence
for a cerebellar involvement in migraine
In addition, we were interested whether possible findings
in eyeblink conditioning were more pronounced in
migraine with aura than without aura

METHODS
32

24 Migraine
without aura

Mean age 26.88.8, age

range 1849 years

8 Migraine with
aura

Patients were interviewed about

visual aura symptoms, paresthesias,
limb numbness and possible speech
disorders preceding headache
symptom
between February 2009 and November 2010

Inclusion criteria
Duration of illness was at
least one year
regular menstrual cycle or
taking oral contraceptive
were included
They were allowed to use
acute headache medication
None of the control subjects
had a history of neurological
diseases

Exclusion criteria
Patients fulfilling criteria
for medication overuse
headache with
accompanying tensiontype headache
Patients with chronic
migraine or more than 10
attacks per month

 Eyeblink conditioning was at least seven days before or after

a migraine attack or acute migraine treatment
To determine cerebellar signs or ataxia symptoms the
neurological examination included the International ICARS
& SARA The clinical examination was conducted either by
D.T. or M.G
At the beginning of the experiment hearing thresholds were
determined in each subject using 1 KHz, the frequency of the
CS

ANALYSIS
In paired trials analyses of variance for repeated measures
(ANOVAs) were calculated with percentage CR incidence as
dependent variable, block as within-subject factor and group
as between-subject factor
Results of timing parameters of conditioned eyeblink CRs,
spontaneous blink rate, alpha blinks and eyeblink URs were
compared between groups (all controls vs. all migraine
patients) using unpaired t tests.

RESULTS

DISCUSSION
In the present study the acquisition of eyeblink
CRs was significantly reduced in patients with
migraine
Findings in MwoA patients were less marked
than in MwA patients
Impaired acquisition of eyeblink CRs suggests
that cerebellar function is affected in patients
with migraine.

 Findings of several human lesion and brain imaging

studies provide good evidence that the human
cerebellum is essentially involved in simple delay
eyeblink conditioning Thus, the present findings
suggest a cerebellar dysfunction in patients with
migraine
Impaired eyeblink conditioning has also been shown in
essential tremor and has been interpreted in favour of
disturbed cerebello-cortical pathways in this condition
Eye movement and balance are controlled by the medial
cerebellum. Mild balance disorders in tandem stance in a
few patients in the present study are in line with mild
dysfunction of the medial cerebellum in migraine

 Disordered cerebellar function has been suggested

following findings of mild hypermetria of reaching
movements in MwoA, and, more pronounced, in MwA
hypermetria has been discussed as related to a
disturbed function of the lateral cerebellum
Finally, there is some evidence for circulatory changes in
patients with migraine
adaptive timing of eyeblink CRs is known to be
cerebellar dependent, the cortex of the anterior
cerebellar lobe seems to be of particular importance
Reduced CR acquisition is not always accompanied by
disordered CR timing

LIMITATIONS
Relatively small groups and different
number of patients
high oestrogen levels have been shown to
enhance procedural memory function, all
female patients were investigated in the
menstrual cycle phase of high oestrogen
For that reason findings cannot be
generalised

CONCLUSIONS
Findings of the present eyeblink conditioning study
strengthen previous clinical data and suggest that the
cerebellum is affected in common forms of migraine,
possibly because of ion channel or neurotransmitter
abnormalities, SD or circulatory changes
Whether this is predominant in MwA needs to be
confirmed in further studies with larger groups of
patients.

REFERENSI 2

REFERENSI 8