Cerebrospinal Fluid Sodium Increases in Migraine


  • Michael G. Harrington MD,

  • Alfred N. Fonteh PhD,

  • Robert P. Cowan MD,

  • Kathy Perrine BS, MT, ASCP,

  • Janice M. Pogoda PhD,

  • Roger G. Biringer PhD,

  • Andreas F.R. Hühmer PhD

  • From Huntington Medical Research Institutes, Molecular Neurology, Pasadena, CA (Drs. Harrington, Fonteh, and Cowan); Huntington Hospital, Clinical Laboratory, Pasadena, CA (Ms. Perrine); Statology, Ventura, CA (Dr. Pogoda); and Thermo Electron, San Jose, CA (Drs. Biringer, Hühmer).

Address all correspondence to Dr. Michael G. Harrington, Molecular Neurology, HMRI, 99 North El Molino Avenue, Pasadena, CA 91101.


Background.—Pharmaceuticals with calcium- or sodium-channel-blocking activity have proven useful for migraine prophylaxis, and calcium channel, sodium transporter, and sodium channel gene mutations have been found in familial hemiplegic migraine. However, it is not known whether calcium or sodium homeostasis is altered in migraine.

Objective.—To compare levels of sodium, calcium, potassium, and magnesium in cerebrospinal fluid (CSF) and blood plasma between migraineurs and controls.

Methods.—We recruited 20 migraineurs without aura and 11 controls prospectively, and studied migraineurs in sick (MH+) and well (MH) states. We collected lumbar CSF and venous blood plasma, quantified elements with ion-selective electrodes or colorimetry, and determined osmolality by depression of freezing point. We compared levels of Na+, Ca2+, K+, and Mg among and also within subjects who were studied in both MH+ and MH states.

Results.—Mean CSF Na+ levels were increased by 3 mmol/L in MH+ compared with MH and by 4 mmol/L compared to controls (P < 0.005). In 4 subjects who were sampled in both MH+ and MH states, mean CSF Na+ concentration increased by 2 mmol/L in the MH+ state compared with the MH state (P < 0.05). Simultaneous plasma Na+ levels did not differ among the 3 clinical groups, nor did osmolality, total Ca and Ca2+, K+, and total Mg levels in CSF.

Conclusions.—Compared to both controls and the MH state, CSF Na+ concentration increased in MH+ independently from other clinical or pharmacological fluctuations, CSF concentrations of Ca2+, Mg, and K+, and blood plasma Na+ levels. These results implicate a deviation of Na+ homeostasis in migraine. The modestly elevated extracellular Na+ in MH+ may cause the neural changes that underlie clinical features of migraine.