Prolactin changes after seizures classified by EEG monitoring

We examined the postictal hyperprolactinemia after seizures classified by EEG and video telemetry. Prolactin did rise after complex partial seizures that involved motor behaviors and was not further increased by secondary generalization. Nontemporal partial seizures or pseudoseizures did not demonstrate this increase. There was no difference in prolactin elevation after generalized tonic-clonic seizures, whether secondarily generalized or generalized from onset. A discriminant function accurately classified 94% of patients with pseudoseizures and 66% of patients with true cerebral seizures for an overall classification accuracy of 72%.     

Capillary prolactin measurement for diagnosis of seizures

Measurement of serum prolactin levels can be useful in the diagnosis of epilepsy, since prolactin levels often rise after seizures, but not after most imitators of epilepsy. Utility of the test is limited by the need to obtain blood 10 to 20 minutes after the episode. The present study documents the validity of prolactin measurements using capillary blood, which was obtained by the finger-stick method after a possible seizure and then applied to filter paper. Venous and capillary prolactin levels were determined 10 to 20 minutes after seizure-like episodes in 20 patients who were studied in an epilepsy monitoring unit. Venous and capillary prolactin values correlated, with a Pearson coefficient of 0.90. Using a criteria of any elevation above the laboratory upper limit of normal, capillary prolactin values correctly identified seizure versus pseudoseizure in 9 (100%) of 9 patients with generalized tonic-clonic seizures, in 5 (71%) of 7 patients with complex partial seizures, and 4 (100%) of 4 patients with pseudoseizures. Prolactin values were unaffected by leaving filter paper samples at room temperature for up to 1 week. This study suggests the utility of diagnostic capillary blood collection kits to assist in the diagnosis of epilepsy in outpatients.     

Nocturnal prolactin and growth hormone levels in children with complex partial and generalized tonic-clonic seizures

This study measures whether there is a rise in the secretion of nocturnal prolactin and growth hormone (GH), during the delta phase of the first sleep cycle in children who are suffering from either complex partial or generalized tonic-clonic seizures. The findings are compared with those obtained in the control group of patients which is made up who suffer from pseudoseizures. There is a moderate but significant rise in the nocturnal prolactin plasma level in both types of infantile seizures. No significant difference was found in the GH.     

Induction of Pseudoseizures with Intravenous Saline Placebo

Summary: For a 2-year period, all patients admitted to the inpatient adult EEG videotelemetry unit of the University of Miami School of Medicine underwent attempted event induction with intravenous normal saline placebo. Of 175 patients monitored during that period, 101 underwent attempted placebo saline induction, whereas 58 patients were either in the pediatric age group, were undergoing a repeat hospitalization (i.e., depth electrode monitoring), or refused induction. The final diagnosis in each patient was established after re-view of the history; physical, interictal, and ictal EEG findings; brain imaging studies; interictal and postictal brain single photon emission computed tomography (SPECT) and serum prolactin levels; psychiatric and psychological evaluations; and detailed neuropsychological testing. Final diagnoses were separated into epilepsy alone, pseudoseizures, epilepsy and pseudoseizures, and other (neither epilepsy nor pseudoseizures). No patient with an eventual diagnosis of epilepsy alone was inducible. Forty-one patients with a diagnosis of epilepsy were not inducible. Of 32 patients with an eventual diagnosis of pseudoseizures, 29 were inducible. One of these 29 was also diagnosed with epilepsy. Three patients with aneventual diagnosis of pseudoseizures were not inducible; 90.6% of patients with an eventual diagnosis of pseudoseizures were inducible, i.e., had events identical to those reported by history, after injection of saline placebo. Placebo saline injection is a safe and effective means of distinguishing epilepsy from pseudoseizures.     

Plasma prolactin concentrations following epileptic and pseudoseizures.

Serial plasma prolactin levels were measured following eighteen generalised seizures, ten partial seizures and eight pseudoseizures. Prolactin levels were elevated following generalised seizures, but were normal following the other seizure types. Plasma prolactin levels may, therefore, be helpful in differentiating between generalised and pseudoseizures. The optimal time for estimating the prolactin level was 15-20 minutes following the seizure.     

Patients with pseudoseizures: intellectual and cognitive performance

We compared cognitive and intellectual performance of patients with pseudoseizures (pseudoseizure-only group), pseudoseizures and epilepsy (mixed seizure group), and generalized epileptic seizures (generalized seizure group). The pseudoseizure-only group performed significantly better on all measures except those of simple motor function. There were no significant differences between those with mixed and generalized seizures. Therefore, cognitive and intellectual performances of patients with pseudoseizures are influenced by the presence or absence of concomitant epilepsy, and suggest that it is necessary to distinguish patients with and without epilepsy in studies of pseudoseizures.     

Tuesday July 4, 200615:00–17:00Hall 3ADiscussion Group SessionPsychogenic pseudoepileptic seizures; a critical review of etiological factors, diagnostic procedures, and treatment outcomes

¹ B. Schmitz (   ¹ Department of Neurology, Campus Virchow-Klinikum, Charité, Berlin, Germany )
The diagnosis of dissociative seizures is not difficult in the majority of cases. The prognosis is however much poorer than the prognosis of epileptic seizures and treatment strategies have not been systematically evaluated. Surprisingly little research has focused on psychological mechanisms underlying the development of pseudoseizures.
The lecture will summarise the existing literature on psychological etiological factors including traumatic events and childhood abuse as well as gender aspects in patients with exclusive pseudoseizures and in patients with epilepsy plus pseudoseizures.     

Predictivity of Plasma Prolactin Levels in Differentiating Epilepsy from Pseudoseizures: A Prospective Study

The predictivity of raised plasma prolactin (PRL) concentrations in differentiating seizure from syncopal attack was prospectively assessed in all patients consecutively admitted to the Clinica Neurologica of Brescia, Italy in a 12-month period who fulfilled the criteria for either a seizure or syncopal attack. Postictal plasma prolactin concentration (P1) was assessed as soon as possible after the event. Three further assessments were performed: P2 was sampled 1 h after P1, P3, and P4 were sampled in the morning for the next 2 days. Patients who had had a seizure showed significantly increased P1 concentrations, when P1 was sampled within 60 min of the attack. In seizure patients assessed >1 h after the event, P1 was not significantly different from either P2, P3, or P4. In patients who had had a syncopal attack, PRL concentration never increased. In patients assessed ≤60 min after the seizure, cutoff criterion of P1 exceeding by + 3 SD the mean calculated on P2, P3, and P4 yielded a positive predictive value of 89% and a negative predictive value of 61%. These findings confirm that plasma prolactin concentration is highly predictive of true epilepsy but barely predictive of pseudoseizures.     

Serum prolactin and cortisol concentrations after grand mal seizures

Serial serum prolactin and cortisol levels were measured in five patients after a grand mal seizure and in four volunteers with simulated seizures. Single levels were measured after a witnessed seizure in 26 patients and in a matched control group. Significant increase in both prolactin and cortisol levels occurred after seizures. The change in cortisol level may reflect a non-specific stress response, but the increase in prolactin levels could not be accounted for on this basis, and probably indicates an alteration in hypothalamic neurotransmitter activity during the seizure. These findings may have clinical value in the diagnosis of epilepsy.     

Serum prolactin and cortisol levels in evaluation of pseudoepileptic seizures

In 6 patients with epilepsy, a twofold increase in serum prolactin levels followed true epileptic seizures, but no significant change followed pseudoepileptic attacks in 6 other patients. Serum prolactin concentration is a useful biochemical marker to distinguish between epileptic and pseudoepileptic seizures. Serum cortisol levels also increased after epileptic seizures, but diurnal and individual variations render the cortisol level a less reliable indicator of such attacks.     

Epilepsy and pseudoseizures derived from their dissociation]

Many epileptic patients have pseudoseizures (psychogenic nonepileptic seizures mimicking epileptic seizures) derived from their dissociation (conversion) or other psychiatric symptoms. The pseudoseizure cast many problems on medical support for their management. In this article I reported the result of investigation of pseudoseizures in an epilepsy unit in department of psychiatry, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry. And I reffered to treatment and prognosis of pseudoseizures. The key points for psychiatrists in treating epileptic patients having pseudoseizures were; 1) not to hesitate to consult with specialists about diagnosis, 2) to distinguish a pseudoseizure from an epileptic seizure and to treat them separately, 3) not to treat seizure phenomena but patients by keeping reliable relationship with them.     

Endocrine function following complex partial seizures

Previous studies have demonstrated hyperprolactinemia following generalized tonic-clonic seizures and after electroconvulsive therapy. We found transient hyperprolactinemia following complex partial seizures but little change in serum gonadotropins, thyroid-stimulating hormone, growth hormone, or cortisol. Serum prolactin was invariably normal interictally. Postictal elevation of serum prolactin may represent a biochemical marker of complex partial seizures, and it offers a potential pathogenic mechanism for the sexual dysfunction that often complicates temporal lobe epilepsy.     

The clinical value of serum prolactin measurement in the differential diagnosis of complex partial seizures

The time course of changes in serum prolactin after complex partial seizures has been determined and compared to similar changes after other types of seizure and non-epileptic attacks. Seizures in 33 subjects were recorded on video EEG telemetry. Peak serum prolactin concentrations occurred 15-20 min after tonic-clonic seizures, 10 min after complex partial seizures, and were highest after generalised tonic-clonic seizures. Serum prolactin concentrations remained less than 1000 mU/l after absences and non-epileptic attacks. Application of Bayes' theorem showed that where serum prolactin was greater than 1000 mU/l 5-10 min post event this would identify genuine tonic-clonic or complex partial seizures. The false negative rate of this test was 9% for tonic-clonic seizures and 38% for complex partial seizures. Failure of serum prolactin to rise after an attack is of little value in distinguishing complex partial seizures from non-epileptic attacks.     

Prolactin in partial epilepsy: an indicator of limbic seizures

A study was performed to evaluate changes in serum prolactin levels after simple and complex partial seizures, and to identify which specific anatomical structures must be involved in seizures for postictal elevation of prolactin levels to occur. Seventy-eight seizures were studied in patients with electrodes implanted bilaterally into amygdala, hippocampus, hippocampal gyrus, and frontal sites. All 38 complex partial seizures had bilateral limbic ictal discharges, and each was followed by a significant increase in prolactin concentration (mean peak, 50.8 ng/ml; range, 16.0 to 150.0 ng/ml). Eight of 10 simple partial seizures with unilateral high-frequency regional limbic discharges were followed by prolactin elevation (mean peak, 28.2 ng/ml; range, 13.4 to 44 ng/ml). Thirty simple partial seizures with other ictal limbic discharges or without limbic discharges were not followed by an elevated prolactin level. The data indicate that serum prolactin levels always rise after complex partial seizures involving the temporal lobes, and rise after certain simple partial seizures involving limbic structures. Thus, measurement of the prolactin level can help identify which simple partial seizures involve mesial temporal lobe structures. Limbic structures serve to trigger prolactin release, which may depend upon spread of the seizure to subcortical structures.     

Hormones and epilepsy

The complex interactions of neurosecretions with the developing brain suggest that it has multiple site and time-specific vulnerabilities that may contribute to the pathogenesis of several forms of epilepsy, yet, on the other hand, may provide several new forms of therapy. Catamenial seizures can be clearly related to hormonal changes, although other factors are important, such as altered drug metabolism during menses. Progesterone appears to be especially effective in treating seizures. Optimal forms of treatment for catamenial epilepsy have not been established; however, several forms of progesterone are available and may be helpful, including those in oral contraceptives. Special care in the selection of oral contraceptives may be an important adjunct in caring for women with epilepsy. Altered secretion of neurohormones suggests important clues to the sexual dysfunction and psychopathology associated with temporal lobe epilepsy. New approaches to these patients include the clinical evaluation for sexual dysfunction along with the measurement of prolactin, testosterone, LH, and FSH levels, and treatment of sexual dysfunction by the effective use of anticonvulsants. Elevated plasma hormones (especially prolactin) following seizures can help to distinguish true seizures from pseudoseizures. Effects of anticonvulsant drugs on endocrine function are important, particularly with respect to their ability to lower the efficacy of oral contraceptives by competitive binding. A number of hormonal changes have been described with several drugs, which suggest that their complex central and peripheral effects might help to explain some aspects of normal hormone activity as well as some common side effects of the drugs.     

Comparison of the effects of frontal and temporal lobe partial seizures on prolactin levels.

The acute effects of partial (focal) epileptic seizures on serum prolactin levels were studied in two groups of patients: (1) 10 with temporal lobe seizures and (2) 11 with seizures that arose from the frontal lobes, recorded on cable video-electroencephalographic telemetry. Six of the eight complex partial seizures of temporal lobe origin were associated with a marked rise in prolactin levels at 10 minutes after onset (rise in levels, from a mean of 279 to 534 mU/L), compared with a rise in only one of the eight frontal lobe complex partial seizures. None of the five simple partial seizures (two of temporal and three of frontal lobe origin) was associated with a marked rise in prolactin levels. This difference in prolactin response following complex partial seizures of frontal and temporal lobe origin may help in the clinical differentiation of these seizures. A failure of prolactin levels to rise does not, however, exclude a diagnosis of complex partial seizures; thus, this measurement will not help in the clinical differentiation of frontal lobe complex partial seizures from psychogenic attacks.     

Pseudoseizures — risk factors and prognosis

Risk factors and prognosis for pseudoseizures were studied in a matched pairs case-control investigation of Epilepsy Clinic out-patients. The case group comprised 28 patients with pseudoseizures, 4 of whom were without a prior diagnosis of epilepsy. The control group consisted of 28 age- and sex-matched epileptic patients. There was a marked female preponderance, 86%, in the group with pseudoseizures. The frequency of previous psychiatric problems was significantly higher in the case- than in the control group, while the factors major cerebral damage and idiopathic generalized epilepsy were significantly less prevalent. At follow-up, median 5.8 years after diagnosis of pseudoseizures, 45% of the patients in the case group were free from all types of seizures. A significantly higher proportion of cases, 55%, were living on public disablement pension, compared to 23% of control patients.     

Prolactin levels in sudden unexpected death in epilepsy

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. 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.     

Epileptic seizures induced by sexual abuse. Pathogenic and pathoplastic factors

Previous sexual abuse is now thought to be a common cause of non-epileptic seizures (pseudoseizures). However, since sexual abuse is common, a previous history of sexual abuse may also occur in people with actual epilepsy. We present six patients in all of whom sexual abuse may, by acting as a stressor in the already predisposed, have precipitated epilepsy and in some of whom the abuse may have affected the actual experiences of the epilepsy itself: all but one of the patients had partial seizures.     

Serum neuron-specific enolase in children with febrile seizures: time profile and prognostic implications

Compared to publications of elevated levels of neuron-specific enolase (NSE) in adult patients with single seizures or epilepsy, data in children are rare. We studied serial NSE serum concentrations in children after febrile convulsions (FC). In addition, the predictive value of NSE levels in serum for recurrence of FC or further development of epilepsy was determined. Serum NSE levels were determined at (1) 0-2 h, (2) 6-8 h and (3) 20-24 h after a first or second FC in children aged 4 months to 6 years. Eighty-two patients (35 female, 47 male) aged four months to 5.7 years were included. Seventy-one children had generalized, and seven focal FC. The seizures in the remaining four patients could not be properly classified. During the follow-up of 14-28 months 13 patients had at least one more FC and in five epilepsy due to recurrent afebrile seizures was diagnosed. There was no statistically significant elevation of NSE concentration in the group of children with FC or the group with recurrent FC or epilepsy. The comparison of the NSE values at different times after FC did not show any significant differences either. It seems from our results that NSE activity cannot be used as a predictor for possible brain damage caused by FC and that it is not of predictive value considering further FC or development of epilepsy. We cannot confirm the published results of the elevation of NSE serum levels in adults with single seizures or status epilepticus.