Prolactin Levels in Sudden Unexpected Death in Epilepsy

Abstract

- Summary:Purpose: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure.Methods: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy.The majority of sudden unexpected deaths in epilepsy (SUDEP) are unwitnessed, and in the absence of a better explanation, death is believed to be the result of a seizure. Clinical evidence for terminal seizure is found in up to about a third of cases (1-5), but whether seizures (either witnessed or unwitnessed) always precede SU-DEP is unknown.Serum prolactin has been observed to increase after generalized tonicklonic seizures (6-10) and complex partial seizures (8,ll-16), and the mechanism by which seizures are proposed to cause prolactin elevation involves propagation of the electrical discharge to the hypothalamus, thereby influencing prolactin release (16). Generally serum prolactin does not rise after simple partial or pseudoseizures (8,9,15,17,18 Results: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects.Conclusions: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15-20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure. Key Words: Prolactin-Epilepsy-Sudden unexpected death.The purpose of this study was to examine prolactin levels in SUDEP and control groups. If prolactin was consistently increased in SUDEP cases, but not in controls, then we would infer that terminal seizui-es had occurred in the SUDEP group.

Sudden unexpected death in epilepsy patients: Risk factors

“…1. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][16][17][18][19][20][21][22][23][24][25][26]45,46 A number of strong risk factors for SUDEP were identified: young age, early onset of seizures, the presence of generalized tonic clonic seizures, male sex and being in bed. Weak risk factors were prone position, one or more subtherapeutic bloodlevels, being in the bedroom, a structural brain lesion and sleeping.…”

“…Weak risk factors were prone position, one or more subtherapeutic bloodlevels, being in the bedroom, a strucural brain lesion and sleeping. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][16][17][18][19][20][21][22][23][24][25][26]45,46 In another evidence-based analysis, the main risk factors were a seizure preceding death, subtherapeutic AED levels, youth (age 15-30 years), high seizure frequency (more than 15 seizures per month), high number of AED (more than two) and long duration of epilepsy (more than 15 years). 40 The different results may be explained by different definitions of the factors and by a different methodology.…”

Postmortem biochemistry: Current applications

“…Factors may be non-adherence with anticonvulsant therapy (antiepileptic drugs, AEDs) or co-prescription of drugs such as tricyclic antidepressants and clozapine that may lower the seizure threshold. It has been suggested that plasma prolactin could indicate recent seizure activity/status epilepticus, but it has been found that this is not a reliable diagnostic marker [122]. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT…”

Clinical Pharmacology: Drugs as a Benefit and/or Risk in Sudden Unexpected Death in Epilepsy?

“…Arrhythmias, which may have morbid potential, can occur commonly in association with seizures. 61,85,86 Why the vast majority of patients survive such occurrences unscathed is a mystery. Physicians must always consider the fact that in some patients, subconvulsant, interictal, or seizure activity may masquerade as cardiac arrhythmias, while in other patients, cardiac arrhythmias may masquerade as seizures.…”