SEARCH

SEARCH BY CITATION

Keywords:

  • Ca channel;
  • channelopathy;
  • serotonergic input;
  • statokinesigram

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

Abstract The vestibulospinal system was evaluated using a stabilometric method in patients with migraine and episodic tension-type headache during headache-free periods. Migraine patients often complain of dizziness or vertigo during headache attacks and some exhibit these symptoms between attacks. Computerized static stabilometry is a reliable and non-invasive technique to evaluate the equilibrium function in various diseases. The subjects consisted of 21 patients with migraine, 12 patients with episodic tension-type headache and, age- and sex-matched controls. We performed two sets of static stabilometric measurements with eyes open (EO) and eyes closed (EC) for 30 s. The averages of two sessions of the following six stabilometric parameters were used for the analysis: locus length (LNG), environmental area (ENV-AREA), rectangle area (REC-AREA), locus length per second, locus length per environ area (L/E), and root mean square area. Romberg quotients (EC/EO) of these six parameters were also analyzed. The mean values of LNG, ENV-AREA and REC-AREA in the EC session in the migraine group were significantly greater than those in the controls (P < 0.05, Mann–Whitney rank sum test). Romberg quotients of all stabilometric parameters except the L/E in the migraine group were significantly greater than in the controls. Patients with episodic tension-type headache did not show any differences in the stabilometric study from the controls. The present findings suggest that patients with migraine show a significant increase of the body sway during the EC session, which indicates an underlying dysfunction in the vestibulospinal system.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

Migraine is a neurological disorder, which repeats episodic headache attacks accompanied with nausea, vomiting, photophobia and phonophobia.1 Occasionally, migraine patients complain of dizziness or vertigo.2–4 Familial hemiplegic migraine (FHM), a specific form of migraine headaches, has been revealed to be due to a mutation in the P/Q type Ca channel gene (CACNL).5 Familial hemiplegic migraine patients with CACNL mutation show cerebellar atrophy. There have been studies reporting the possible association of the FHM-gene locus to common forms of migraine (i.e. migraine with aura and without aura).6 Significant comorbidity of Ménière's disease, motion sickness, and benign paroxysmal vertigo with migraine have been reported.7–10 There have been some studies on vestibular function in migraine-related vestibulopathy,11 however, little is known about vestibular function in those with migraines without manifested vestibulopathy. A computerized static stabilometry is a reliable and non-invasive technique to evaluate equilibrium function and is useful to quantify the vestibulospinal symptoms such as dizziness, vertigo or truncal ataxia.12–14

We performed computerized static stabilometries on patients with migraine and episodic tension-type headache during headache-free periods to elucidate whether vestibulospinal dysfunction was present.

SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

Subjects

Thirty-three patients with chronic headaches participated in the present study. All participants gave their informed consent following a full explanation of the nature and aim of the study. Twenty-one patients suffered from migraine headaches, and 12 patients from episodic tension-type headache (TH). We recruited two series of age- and sex-matched volunteer healthy controls from family members of the patients and from among hospital workers. The diagnoses of the types of headaches were established in accordance with the criteria of the International Headache Society.1 Eight of the 21 patients suffered from migraine with aura and the other 13 from migraine without aura. The mean age of the migraine group was 33.9 ± 14.2 (mean ± SD) years old. The mean age of the control group for migraine (Cm) was 34.1 ± 13.3 years (n = 21). The male to female ratios were 7 : 14, both in the migraine group and in the Cm group. The mean duration of illness in the migraine group was 12.1 ± 10.7 years (range 3 months to 30 years). The mean frequency of migraine attacks was 3.9 ± 4.6/month (range 1–8/month). Seven of the 21 patients complained of dizziness during migraine attacks, however, there was no dizziness/vertigo and no clinically apparent equilibrium dysfunction during headache-free periods. No subject met the diagnostic criteria of basilar migraine including so-called migranous vertigo. The mean age of the TH group was 42.8 ± 14.4 years, and that of the control group for TH (Ct, n = 15) was 42.3 ± 13.3 years. The male to female ratios of TH and Ct were 4 : 8 and 5 : 10, respectively.

Stabilometric test procedures

All stabilometric measurements were performed during headache-free periods without preventive medication using a computerized force platform (Gravicorder GS-10 type-C; Anima Co., Tokyo, Japan) according to a standard protocol.12 The stabilometry uses vertical force transducers to determine instantaneous fluctuations in the center of pressure (COP). A statokinesigram (i.e. the sway path of the COP), was obtained from these vertical forces as the change in electric signals during a 30-s upright stance. The standard test battery included the following measurements of sway for 30 s with eyes open (EO) and eyes closed (EC). A typical chart of statokinesigrams is illustrated in Fig. 1. Each chart line indicates the path of COP during the measurement.

image

Figure 1. A typical illustration of statokinesigrams. A 17-year-old male patient suffering from migraine with aura. Left, measurement of eyes open (EO); right, eyes closed (EC). Romberg quotients of the parameters: LNG = 1.61, L/T = 1.61, L/E = 0.94, ENV-AREA = 1.71, REC-AREA = 1.70, RMS-AREA = 1.26.

Download figure to PowerPoint

The locus length (LNG) defined as the sum of the path lengths of COP were calculated using the equation:

  • image

Actual real-time calculations were carried out by the build-in program of the Gravicorder GS-10 type-C.

ENV-AREA was the size of environmental area inside the path and REC-AREA was the rectangular area of the path. The locus length per second (L/T) was calculated as LNG/t (cm/s); locus length per environ area (L/E) as LNG/ENV-AREA; root mean square area (RMS-AREA) was given as:

  • image

Where n was the total number of measure samples, i: 1, 2, 3, . . . n, Xi, Yi: locus of COP, Xm, Ym: mean value of COP (Xi, Yi).

The Romberg quotient of each parameter was calculated as EC/EO.

All subjects underwent two sets of tests both in EO and EC successively. The average of each parameter was used for the analysis. The Mann–Whitney rank sum test was employed to compare the mean value of each parameter between the groups.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

The results of the measurements with EO and EC are summarized in Table 1. There was no significant difference in any parameter in the EO test between the disease groups and age- and sex-matched controls. The mean values of LNG, ENV-AREA and REC-AREA in EC sessions of the migraine group were significantly greater than those in the controls (P < 0.05, Mann–Whitney rank sum test). The Romberg quotients of all stabilometric parameters except L/E in the migraine group were significantly greater than in the controls (Fig. 2). No stabilometric parameter in the TH group in any condition was significantly different from that in the age- and sex-matched controls.

Table 1.  Summary of statokinesigram
 CmMigraineCtTH
  • Each value represents mean ± SEM.

  • *

    P < 0.05 vs Cm (Mann–Whitney rank sum test).

  • EO, eyes-open; EC, eyes-closed. Cm, controls for migraine; Ct, controls for TH; TH, tension-type headache. LNG, locus length; L/E, locus length per environ area; ENV-AREA, environmental area; REC-AREA, rectangle area; RMS-AREA, root mean square area.

EO
LNG30.02 ± 2.2828.59 ± 2.1231.59 ± 1.9328.77 ± 2.50
LNG/TIME1.00 ± 0.080.91 ± 0.061.05 ± 0.060.95 ± 0.08
L/E31.93 ± 2.7232.34 ± 3.1131.78 ± 3.3835.42 ± 5.01
ENV-AREA1.19 ± 0.181.23 ± 0.211.21 ± 0.121.07 ± 0.16
REC-AREA4.32 ± 0.864.13 ± 0.753.78 ± 0.363.40 ± 0.49
RMS-AREA1.12 ± 0.131.14 ± 0.161.16 ± 0.131.00 ± 0.14
EC
LNG41.41 ± 3.3148.87*± 2.4148.56 ± 4.6948.46 ± 3.96
LNG/TIME1.38 ± 0.111.57 ± 0.071.61 ± 0.161.61 ± 0.13
L/E26.27 ± 2.6520.98 ± 1.9428.60 ± 3.9626.11 ± 4.02
ENV-AREA1.88 ± 0.17 2.94*± 0.312.34 ± 0.522.54 ± 0.43
REC-AREA6.06 ± 0.57 8.72*± 0.917.35 ± 1.507.63 ± 1.34
RMS-AREA1.62 ± 0.172.33 ± 0.271.83 ± 0.401.94 ± 0.31
image

Figure 2. The Romberg quotients of statokinesigram. The graphs illustrate the mean Romberg quotients (EC/EO) of LNG, L/T, L/E, ENV-AREA, REC-AREA and RMS-AREA of the sway. See text for definition of each parameter. M, migraine group; TH, tension-type headache group; Cm, age- and sex-matched control group for M, Ct: age- and sex-matched control group for TH. The Romberg quotients of the migraine group were significantly greater than in the controls (Cm), except for the L/E (Mann–Whitney test; *P < 0.001, **P = 0.003, †P = 0.022, and ††P = 0.007). The TH group shows no significant difference from the controls (Ct). The error bar indicates standard error.

Download figure to PowerPoint

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

The postural system is highly complex and regulated by feed back loops from several sensory systems, including the vestibular system, vision, proprioception from joints, tendons and muscles and superficial and deep tactile sense. A computerized static balance platform provides a quantitative test for evaluating the vestibulospinal system. Nordahl et al. performed repeated testing in a normal population and concluded that static stabilometry test are objective and reproducible.13 In addition, they reported that there was no difference in sway pattern between tall and short test subjects, between subjects with heavy and light bodyweight or between sexes. The stabilographic study has been reported to contribute to the diagnoses of cerebellar ataxia.15,16 Recent studies suggest that stabilometry are not always suitable to specify the anatomical region of the responsible focus; however, it can detect subtle vestibulospinal dysfunction.17–19 The mean values of LNG, ENV-AREA, and REC-AREA in EC sessions of the migraine group were significantly greater than in controls, however, the degree of abnormality of stabilometric parameters were smaller than the results of ataxic patients in the literature.20,21 Because we examined patients with migraine headache without any clinically apparent ataxic symptoms during the headache-free period, it is reasonable that we found only small difference in migrainous patients compared with ataxic patients. Romberg quotients of all stabilometric parameters except L/E in the migraine group were significantly greater than in the controls. The reason why only L/E in migraine showed no significant difference from the controls remained unclear, however, L/E is considered to be only slightly influenced by visual assistance. Thus, the present findings suggested small but significant vestibulospinal dysfunction in patients with migraine during headache-free periods. Importantly, this is the first report of dysfunction of vestibulospinal systems in migraine patients without clinically apparent equilibrium dysfunction.

Although it has not been fully clarified, there have been some studies that showed a possible association of migraine to dizziness, vertigo, or ataxia.7,9,11,22–24

Recent genetic studies of headaches revealed that mutations of the P/Q type Ca channel gene (CACNL) cause FHM.5 Some mutations of this gene cause episodic ataxia type-2 and expansion of the CAG repeat in the c-terminal of the CACNL gene causes spinocerebellar ataxia-6.5 Based on the discovery of mutations in the Ca channel in FHM, a hypothesis has been proposed that migraine is a channelopathic disorder. Stahl and Daroff emphasized the importance of vestibular complaints in migraine for capturing patients with a Ca channelopathy.25 Neuronal calcium channelopathies are often associated with the cerebellar dysfunction. Due to the interconnections of the cerebellum and vestibular system, these patients with calcium channelopathies often have vestibular symptoms.25

Because migraines associated vasospasm have been reported to cause sudden hearing loss,26,27 one possible explanation for the present findings is that repeated ischemic episodes during migraine attacks caused irreversible change in the central and/or peripheral vestibulospinal systems. Vasospasms might be caused from channelopathic abnormalities in the vessels feeding the brain and structures of vestibular system in migraine patients.

An alternative explanation may be a serotonergic hypothesis in connection with the Ca channel hypothesis of migraine headaches. All classes of afferent input (visual, vestibular and somatosensory) contribute to stabilization of the body during quiet stance. Among them, the static labyrinth and lateral vestibular nucleus of Deiters, which is the origin of the lateral vestibulospinal tract, are considered the main centers responsible for static equilibrium. The Romberg test is a major source of information concerning the functional status of the static labyrinth.28 The main efferent pathway of the static labyrinth is the lateral vestibulospinal tract, formed by Deiters' axons. 5-hydorxytriptamine (5-HT, serotonin) was reported to increase the firing rate of 94% of the units tested using anesthetized rat lateral vestibular nuclei.29 Based on the well-known serotonergic dysfunction in migraine,30 vestibulospinal dysfunction of migraine patients in the present study might have been caused from the serotonergic dysfunction. It remains to be elucidated how the genetic mutation in the Ca channel causes migraine headaches, however, ablation of the P/Q type Ca channel current has been reported to alter synaptic transmission.31

Using static stabilometric apparatus, we demonstrated a significant increase in body sway during the EC condition in migraine patients but not in TH patients. Regarding the existence of the subtle but significant dysfunction in vestibulospinal systems in migraine patients, the hypothesis that migraine is a channelopathy and may be associated with Ca the channel gene appears to be a promising strategy.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

This study was partly supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, Government of Japan to T.T. and K.N. Some results were presented at Japanese Headache Society, Tokyo, 20 November 1999.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES