Jaarboek no. 89. 2010/2011 - Koninklijke Maatschappij voor ...

Migraine: de ontrafeling van een complexe ziekte
Familial Hemiplegic Migraine
Prof. dr. M.D. Ferrari
Afdeling Neurobiologie, Leids Universitair Medisch Centrum, Leiden
Abstract
Migraine is a severely debilitating episodic disor-
der affecting up to 12% of the general population.
Migraine arises from both genetic and environmental
factors, complicating our understanding of what
makes the migraine brain susceptible to attacks. In
recent years, powerful genetic screening tools have
revealed several single genes linked to migraine.
One example of a monogenic subtype of migraine
is familial hemiplegic migraine (FHM), a rare form of
migraine with aura.
The fact that FHM and common multifactorial
migraine have many overlapping clinical features
indicates that they likely share underlying pathophysiological
pathways. In addition, the identification
of monogenic subtypes has made it possible
to generate suitable animal models for migraine.
The purpose of this review is to present an overview
of the clinical features of migraine and discuss the
continuing highway of migraine gene discovery.
The genes associated with FHM will be discussed,
including what we have learned from studying the
functional consequences of FHM mutations in cellular
and animal models.
I. INTRODUCTION
A. Migraine is a disabling episodic
disorder
Migraine is one of the most common neurological
disorders, affecting at least 12% of the general population.
A primary headache disorder, migraine is
typically characterized by disabling episodic attacks
of severe throbbing unilateral headache, often
accompanied by any or all of the following: nausea.
hypersensitivity to sound and/or light, and head
movement. A typical episode can last about a day,
Natuurkundige voordrachten I Nieuwe reeks 89
and the frequency of attacks varies widely among
migraineurs (see below).
In approximately one third of migraineurs, the
headache is preceded by an aura that typically lasts
20–60 min. This aura usually consists of unilateral
homonymous visual symptoms, such as flashing lights
in a jagged pattern and vision loss (hemianopsia),
which begin paracentrally and slowly expand over
minutes as a hemifield defect. Migraine auras may also
include other transient focal neurological symptoms.
Because of the wide range of symptoms exhibited by
migraineurs, the International Headache Society has
designated diagnostic criteria for defining migraine, as
shown in Table 1 (Headache Classification Committee
of The International Headache Society, 2004).
Migraine can be classified into two general categories:
(1) migraine with aura (MA; previously
called classic(al) migraine), in which at least some
of the attacks temporally coincide with distinct
transient focal neurological aura symptoms; and (2)
migraine without aura (MO; previously called common
migraine), in which there are no identifiable
associated neurological symptoms of a focal nature.
In both groups, migraine attacks are often precipitated
by triggers specific to the individual, and can
include hormonal changes, certain odors, flashing
lights, sound, dehydration, alcohol consumption,
and altered sleep and eating patterns. However,
the trigger can also vary within individuals and can
change during their lifetime.
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voor Natuurkunde ‘Diligentia’ te ’s-Gravenhage
op 4 april 2011
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