Cerebrospinal Fluid Sodium Increases in Migraine

Abstract

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 + , Ca 2+ , 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 Ca 2+ , 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 Ca 2+ , 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.

Characterization of the Ionic Profile of the Extracellular Space of the Injured and Ischemic Brain: A Microdialysis Study

“…This upper limit was similar to the upper reference levels of 3.6 -4.1 mmol/L in the CSF of controls described by others. 2,3 Is the ionic profile normal in the apparently non-damaged brain?…”

“…Under steady state, the intracellular concentration of potassium ([K + ] i ) in the CNS is typically around 145 mmol/L, and the extracellular potassium concentration ([K + ] o ) is ~3 mmol/L. [1][2][3] Transmembrane sodium gradients have the opposite orientation, and the extracellular concentration of sodium ([Na + ] o ) is much higher that its intracellular concentration ([Na + ] i ). The ATP-dependent Na + /K + -pump of intact brain cells maintains a concentration gradient between the intracellular and extracellular compartments of approximately 1:10.…”

Capillary Endothelial Na+, K+, ATPase Transporter Homeostasis and a New Theory for Migraine Pathophysiology

“…29 We suggest that, during increased NKAT activity, the decrease in [K + ]e/csf has been minimized by the strong glial regulation system for [K + ]. 45 The magnitude of the NKAT role in the brain 42,43 suggests that its increased activity is the most likely cause of the increased [Na + ]csf and [Na + ]e in migraine, though further studies of [Na + ]e and [Na + ]csf are required.…”

“…29 [Na + ]csf rose significantly during the peak of migraine compared with the non-headache state of migraineurs and controls. This increase is found only in the cerebrospinal fluid (CSF) and not the plasma samples of migraineurs, which argues for a brain source and against a systemic origin.…”

Trace Elemental Analysis and Some Mathematical Tools used to Study Migraine with the Help of Flame Atomic Absorption Spectroscopic Technique

“…et.al. [79] have studied cerebrospinal fluid sodium increate in migraine and found that modestly elevated extracellular Na(+) in MH(+) may cause the neural changes that underline clinical features of migraine.…”