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

C. Comorbidity
Migraine is often associated with other episodic
brain disorders; in addition, comorbidity is often
bidirectional. Together, this suggests common
underlying pathology and genetic origin.
Migraineurs have significantly increased risk
(several-fold higher than non-migraineurs) for
epilepsy, depression and anxiety disorders,
patent foramen ovale and stroke. The incidence
of comorbidity can depend on age and cofactors
including smoking and the use of oral contraceptives.
Moreover, high-frequency migraineurs have a 16-fold
increase in white matter and cerebellar lesions.
II. THE MIGRAINE ATTACK: CLINICAL
PHASES AND PATHOPHYSIOLOGY
Migraine attacks consist of up to four distinct phases,
described briefly below. It is important to note that
not every patient will experience every phase:
1. Premonitory phase. Up to one third of patients
may occasionally experience premonitory symptoms
prior to the onset of the aura and/or headache
phase. These warning signs may include
changes in mood (e.g., depression or irritation),
hyperactivity or fatigue, neck pain, smell anomalies,
food cravings, and water retention.
2. Aura phase. As many as one third of patients
may experience transient visual, sensory, motor,
brainstem, or cognitive aura symptoms in at least
some of their attacks. These focal neurological
symptoms typically last up to an hour, but may
last from several hours to several days. In addition,
the aura phase typically precedes the headache
phase by 5 min to 1 h, but can also occur
simultaneously with, or following, the headache
phase.
3. Headache phase. The headache phase itself is
highly debilitating, with severe throbbing pain
and associated symptoms including nausea,
vomiting, and sensitivity to light and sound as
well as to head movement and touch. In most
cases, this phase lasts for about a day, but can
last 3 days.
4. Recovery and interictal phase. Recovery from a
migraine attack can take from several hours to
Natuurkundige voordrachten I Nieuwe reeks 89
Migraine: de ontrafeling van een complexe ziekte
several days, during which the patient is often
fatigued. Following recovery, the patient enters
an interictal period in which clinical symptoms
are absent.
III. THE MIGRAINE AURA AND CORTICAL
SPREADING DEPRESSION
A. Cortical spreading depression in
experimental animals
It is now generally accepted that the aura preceding
a migraine headache is not the result of vascular
constriction, as was previously believed, but rather
is most likely caused by the human equivalent of a
phenomenon called cortical spreading depression
(CSD). First reported by Leão in the 1940s, CSD can
be best described as a wave of transient (ca. 1–2 min)
depolarization that sweeps in all directions across
the cerebral cortex. This depolarization is believed
to involve both neurons and glial cells, and spreads
through contiguous areas of brain cortex at a rate
of 2–5 mm/min without regard to functional cortical
divisions or arterial territories. In experimental
animals, the electrophysiological changes are associated
with changes in cerebral blood flow (CBF):
there is a small, brief reduction in CBF followed by
a large increase in CBF lasting several minutes, after
which blood flow is reduced for up to an hour and
is accompanied by a loss of the cerebrovascular
response to hypercapnia. CSD is currently believed
to serve to protect the brain from strong stimuli, as
it can be readily triggered by direct electrical stimulation
of the cerebral cortex, cerebrocortical trauma
or ischemia, or by cortical application of strongly
depolarizing concentrations of K + or excitatory
amino acids such as glutamate.
B. CSD and the migraine aura
A wealth of clinical evidence supports the notion
that CSD is the underlying basis of the migraine
aura. For example, when mapped to the visual
cortex, visual aura symptoms typically travel from
the center of the visual field to the periphery at a
speed of approximately 3 mm/min, on par with the
propagation rate of CSD in experimental animals. In
addition, the positive (e.g., scintillations, paresthe-
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