Pathophysiology of Migraine-Related Dizziness

1
Pathophysiology of Migraine-Related Dizziness
Joseph Furman1,3,4, Dawn Marcus2, Patrick
Sparto3,1,4, Mark Redfern4,1,3, and J. Richard
Jennings5 Departments of 1Otolaryngology,
2Anesthesiology, 3Physical Therapy,
4Bioengineering, and 5Psychiatry, University of
Pittsburgh, Pittsburgh, PA  
Abstract The pathophysiological basis for
migraine-related dizziness is unknown but may
relate to both central and peripheral vestibular
abnormalities. The present study was undertaken
to explore several potential abnormalities in
migraine-related dizziness by assessing
vestibulo-spinal function, visual-postural
responses, spatial orientation, and
attention-balance interference in well-defined
patients. Subjects included headache-free
controls (C), subjects who met the International
Headache Society (IHS) criteria for migraine but
who had no symptoms suggestive of a vestibular
system abnormality (M-V), and subjects who
met both IHS criteria for migraine and the
Neuhauser criteria for migraine-related
vestibulopathy (MV), referred to in study as
migraine-related dizziness (MRD). Subjects with
recognized neurotologic syndromes such as
Menieres disease were excluded from all groups.
For each experimental paradigm, five subjects
from each group were tested. Abnormalities in
MRD subjects included decreased VOR gain,
increased sway on Equitest platform posturography
and optic flow in an immersive virtual
environment slowed reaction time on dual tasks of
interference between attentional processes and
the VOR, and excessive visual dependence on
subjective visual vertical testing. Taken
together, these results suggest that patients
with migraine-related dizziness manifest
abnormalities in vestibular function and are more
visually dependent than persons with migraine
without vertigo or headache-free controls. The
basis for these group differences is uncertain
but may relate to serotonergic mechanisms in the
central vestibular system.
Discussion

• Methods
• Subjects Three groups of (n5 each)
  Migraine-related dizziness
• Migraine without dizziness Headache-free
  controls
• Procedures Each subject was tested with
  Earth-vertical axis rotation (EVAR), off-vertical
  axis rotation (OVAR) (See Figure 2.),
  visual-vestibular interaction, computerized
  dynamic platform posturography (CDP), optic flow
  in a virtual environment (See Figure 3.),
  subjective visual vertical (SVV) using rod and
  disk (See Figure 4.), and reaction time (RT)
  during rotation (See Figure 2.)
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Results

Responses of patients with MRD suggest that these
patients have central vestibular dysfunction
between episodes of dizziness. This patient
group manifests evidence for both visual and
somatosensory dependence and for increased
interference between vestibular stimulation and
cognitive processing. Figure 9 provides a
schematic overview of how migraine and vestibular
function may interact.
Table 1. Results from Rotational Testing. Note
that EVAR gain is decreased and OVAR modulation
is increased in the MRD group.
Figure 6. Optic flow testing. Note that patients
with MRD sway more than the other subjects.
Figure 2. Off-vertical axis rotation device
Introduction Migraine headache is highly
prevalent, with population-based studies
reporting migraine in 15 of women and 6 of men
in both the United States and Europe. Migraine
is often associated with dizziness, vertigo, and
imbalance and migraine-related dizziness may be
the most common cause of dizziness that presents
to neurotologists. The purpose of this study was
to obtain pilot data for a larger study of the
pathophysiology of migraine-related dizziness
(MRD). The selection of subjects was
accomplished using diagnostic criteria for
migraine headache established by the
International Headache Society and diagnostic
criteria for migraine-related dizziness recently
published by Neuhauser et al 1 (See Figure 1).
Figure 9. Schematic diagram of neurological
linkages between migraine-related pathways
(unshaded boxes, thin lines, and small
arrowheads) and vestibular pathways (shaded
boxes, thick lines, and bold arrowheads). Solid
lines indicate classical synaptic processing
dashed lines indicate local or distant effects
via neuropeptide release. The vestibular nuclei
may influence noradrenergic and serotonergic
pathways (Ve1) that contribute to triggering
migraine attacks and modulating pain pathways,
information processing in the spinal trigeminal
nucleus caudalis (Ve2) and thalamocortical
mechanisms (Ve3). In addition, there is a
hypothetical contribution (indicated by 'Ve4?')
from peptide release from primary
vestibulo-cochlear sensory terminals into inner
ear fluids during normal activation, which may
act synergistically with trigeminal-associated
peptide release at blood vessels. Conversely,
migraine mechanisms may affect vestibular
processing via monoaminergic pathways (M1),
trigemino-vestibular connections (M2) and
cortical mechanisms (M3). Abbreviations
CGRP-calcitonin gene-related peptide, DRN-dorsal
raphe nucleus, LC-locus coeruleus, LTeg-lateral
tegmental noradrenergic neurons, NKA-Neurokinin
A, PAG-periaqueductal gray, RMag-nucleus raphe
magnus, SP-substance P. This figure appeared in
Furman et al. (2003) 2 .
Figure 7. Results from SVV. Note that patients
with migraine are influenced more than normal
subjects by a moving disk. Note that data were
available from too few migraine patients to
subdivide the data according to the presence of
MRD.
Figure 3. Optic Flow Testing

• References
• Neuhauser, H., M. Leopold, M. von Brevern, G.
  Arnold and T. Lempert (2001). "The interrelations
  of migraine, vertigo, and migrainous vertigo."
  Neurology 56(4) 436-41. Current opinion paper
• Furman, J. M., D. A. Marcus and C. D. Balaban
  (2003). "Migrainous vertigo development of a
  pathogenetic model and structured diagnostic
  interview." Curr Opin Neurol 16(1) 5-13.

Figure 4. Subjective Visual Vertical Testing
Acknowledgement Supported by the National
Headache Foundation, Merck Company, the Eye and
Ear Foundation, and the Raymond Elizabeth Bloch
Charitable and Educational Foundation.
Figure 1. Flowchart for Diagnosis of MRD
Figure 8. Results from RT. Note that there is
greater interference in the MRD group.
Figure 5. Results from CDP. Note that the MRD
group shows a vestibular deficit/surface
dependent type pattern of increased sway.