Hypophosphatemia in generalized tonic-clonic seizures: a cohort analysis

Transient loss of consciousness (LOC) is very common issue. Syncopes and generalized tonicclonic (GTC) seizures are common causes mostly differentiated by history. Several laboratories serum markers (mostly creatine kinase and lactate) can be helpful especially when history is unreliable. We explore the potential supporting role of electrolytes plasma level in that setting. We retrospectively collected 178 consecutive episodes of loss of consciousness in adults from the EEG database of our hospital (CHUV, Lausanne) seen over 3 years in our emergency department. Plasma level of the different electrolytes (sodium, potassium, phosphate, calcium, magnesium) were recorded as well as basic demographics, diagnosis, blood sample delay and history of alcohol abuse. We analysed 128 episodes with sufficient documentations (7 had uncertain diagnosis): we compared electrolytes values between GTC seizures (75 episodes) and other LOC, (46 episodes). Phosphate and calcium levels were associated with GTC seizures; median=0.79 (range 0.34-1.37) vs 0.93 mmol/l (range 0.52-1.56) p=0.001 for phosphate and median= 2.32 (range 1.92-2.53) vs 2.27 mmol/l (range 2.0-2.53) p=0.03 for calcium. Considering abnormal values, only hypophosphatemia (94% of abnormal phosphate level) was associated with GTC seizures with 37 (51 %) abnormal phosphate in GTC seizures and 15 (33%) in other LOC (p=0.02, Chi squared), independently from blood sampling delay, alcohol abuse and other electrolytes level. Hypophosphatemia below 0.6 mmol/L was 93% sensitive and 85% specific of GTC seizure. Hypophosphatemia was self-limited. Our data suggest that transient hypophosphatemia is common after GTC seizures. This hypophosphatemia is unlikely to be causing the seizure, but is rather a consequent intracellular shift. Phosphate level could be another biological marker helping differentiate GTC seizures from other LOC, especially when history is unclear. Timing of the blood sample should be taking into account in its interpretation. A prospective study is needed to confirm these findings.