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International Journal of Medicine and

Pharmaceutical Sciences (IJMPS)


ISSN(P): 2250-0049; ISSN(E): 2321-0095
Vol. 6, Issue 2, Apr 2016, 7-12
TJPRC Pvt. Ltd.

SERUM PROLACTIN LEVELS AS A DISTINGUISHING BIOLOGICAL


MARKER BETWEEN TRUE AND PSEUDOSEIZURES:
A PROSPECTIVE LONGITUDINAL STUDY
PANKAJ AWASTHI1 & ANKITA BAJPAI2
1
2

Lecturer, Department of Medicine, GSVM Medical College, Kanpur, Uttar Pradesh, India

Resident, Department of Community Medicine, GSVM Medical College, Kanpur, Uttar Pradesh, India

ABSTRACT
Background
Epilepsy is a major neurological disorder which affects about 50 million people around the globe. It is considered
as a public health problem by World Health Organization (WHO). Pseudo seizure is also an area of concern in todays
stressful lives and its difficult to distinguish between the two. Thus the current study was undertaken.
Objectives

seizures.
Methods
All patients of seizures admitted in the inpatient ward of department of medicine and who fulfilled the inclusion
criterias were studied in the study period of six months from July 2015 to December 2015. We thus carried out our study
in a total 90 patients.

Original Article

To assess the role of serum prolactin levels as a biological marker to distinguish between true and pseudo

Results
The mean of the baseline prolactin levels of the subjects with epileptic seizures and pseudo seizures were 338.26
and 316.41 respectively and there was no significant difference between the two mean levels, whereas the mean of the
postictal prolactin levels measured after 15 minutes of the seizure was 1795.49 in case of epileptic seizures and 387.12 in
case of pseudo seizures and there was a statistically significant difference between the two means. On comparison of means
of the baseline and postictal prolactin levels a highly significant difference was found in case of epileptic seizure (p < 0.01),
whereas there was no significant difference in case of pseudo seizures (p > 0.05).
Conclusions
Serum prolactin levels following true epileptic seizures rise to a statistically significant level compared to that in
case of pseudo seizures. Thus the level of elevation in the serum prolactin level can be used as a distinguishing marker
between true epileptic seizure and pseudo seizure.
KEYWORDS: Serum Prolactin Level, True Epileptic Seizure, Pseudo Seizure, Biological Marker

Received: Feb 11, 2016; Accepted: Feb 19, 2016; Published: Feb 25, 2016; Paper Id.: IJMPSAPR20162

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Pankaj Awasth & Ankita Bajpai

INTRODUCTION
Epilepsy is a chronic non-communicable disorder of the nervous system that affects people of all age groups
around the world. Epilepsy is one of the worlds oldest recognized disease conditions, with written records which date back
to 4000 BC. [1]
Epilepsy is defined by International League against Epilepsy (ILAE; 1993) as a condition characterized by
recurrent (two or more) epileptic seizures, unprovoked by any immediate identified cause. [2]
Epilepsy, a condition affecting the people worldwide is a chronic disorder of the brain. It is usually characterized
by recurrent seizures, which include brief episodes of involuntary movement involving a part of the body (partial) or the
entire body (generalized), and is sometimes accompanied by loss of consciousness and also loss of control of bowel or
bladder function.
Seizure episodes occur due to excessive electrical discharges in a group of cells located within the brain. Different
parts of the brain can be affected by such discharges. Seizures can range from the briefest lapses of attention or muscle
jerks (absence seizures) to severe and prolonged convulsions (generalised tonic colonic seizures). Seizures can also vary in
frequency, they may account for less than 1 per year to several per day.
One seizure does not means a person is suffering from epilepsy (up to 10% of people worldwide have one seizure
during their lifetime). Epilepsy is defined as having two or more unprovoked seizures. [1] Approximately 50 million people
worldwide have epilepsy, making it one of the most common neurological diseases globally. [1]
According to the World Health Organization (WHO), of the 50 million people with epilepsy worldwide, 80%
reside in developing countries. Epilepsy was estimated to account for 0.5% of the global burden of disease, accounting for
7,307,975 disability adjusted life years (DALYs) in 2005. [3]
It is estimated that there are more than 10 million persons with epilepsy (PWE) in India. Its prevalence is about
1% in our population. [4]
Another condition resembling epilepsy and which is often misdiagnosed as epilepsy is pseudo seizures
Peudoseizures are also known by another term i.e. Psychogenic Non-Epilepic Seizures (PNES) . Often, the misdiagnosis of
epilepsy is very common. Even the most experienced epileptologists mistake non-epileptic seizures for epileptic seizures
and vice versa.
Such misdiagnosis occurs as the seizures are quite real, and people who have them do not have conscious,
voluntary control over them. They are false only in that they have no physical cause or any focal discharge in brain;
rather, they are psychological or physical reactions to stressful situations. Although their causes are different, pseudoseizures definitely resemble epileptic seizures and often its difficult to tell the difference.
This problem of misdiagnosis can be solved by measurement of serum prolactin levels in the post-ictal phase of
epileptic patients.
The American Academy of Neurology (AAN) has also released evidence-based recommendations for the use of
serum prolactin tests in differentiating between epileptic and non-epileptic seizures.[5]

Impact Factor (JCC): 5.4638

NAAS Rating: 3.54

Serum Prolactin Levels as a Distinguishing Biological Marker between


True and Pseudo seizures: A Prospective Longitudinal Study

The normal range of serum prolactin levels in males and females are different. In males the normal range is 53360 mIU/L and in females it is 40-530 mIU/L. [6]
The AAN developed the following practice recommendations for physicians considering a laboratory blood test to
diagnose epileptic seizures:

When measured in appropriate clinical settings at 10 to 20 minutes after a suspected event, elevated serum
prolactin levels are useful in distinguishing generalized tonic-clonic seizures or complex partial seizures from
psychogenic no epileptic seizures in adults and older children.

Serum prolactin levels should be representative of the baseline prolactin level when measured more than six hours
after a suspected episode.[5]
Thus the present study was carried out to assess the role of serum prolactin levels as a marker to distinguish

between true and pseudo seizures.

MATERIALS AND METHODS


A prospective longitudinal study was carried out among the patients admitted in the inpatient ward of Department
of Medicine, LLRM Hospital, and Kanpur. The study duration was of six months from July 2015 to December 2015.
Patients admitted in the ward with the complain of seizures were included in the study according to the following
inclusion and exclusion criteriasInclusion Criteria: All the male and female patients suffering from seizure attacks and willing to participate in
the study
Exclusion Criteria: Excluding conditions like physiological hyper secretion, hypothalamic pituitary stalk
damage, pituitary hyper secretion, systemic disorders and drug induced hyper secretion of prolactin, which lead to an
increased serum level of prolactin. And patients not willing to participate in the study
Thus a total 90 patients were studied.
Approval for the study was taken from the Institutes ethical committee. All the study subjects were explained the
purpose of study and their consent was taken for the same.
Diagnosis of true and pseudo seizures was made on the basis of clinical signs and symptoms and the EEG
findings. Baseline serum prolactin levels and serum prolactin levels 15 minutes after the attack of seizure were recorded.
The information gathered from the study subjects was tabulated according to pre-designed classified tables. Data was
analysed on the basis of defined aims and objectives. Quantitative analysis of data was done using percentages and Chisquare tests. Means were compared by Paired-Sample T test and Independent-Sample T test using SPSS 20 version.

RESULTS
In our study out of the 90 subjects studied 34 were males and 56 were females. Among the 90 study subjects 73
were suffering from true epileptic seizures and 17 were cases of pseudo seizures. The mean of the baseline prolactin levels
of the subjects with epileptic seizures and pseudo seizures were 338.26 and 316.41 respectively and there was no
significant difference between the two mean levels (p > 0.05). Table 1
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Pankaj Awasth & Ankita Bajpai

Table 1: Baseline Mean Prolactin Levels in Patients of


Epileptic Seizures and Pseudo Seizures
Type of Seizures Mean Standard Deviation
Epileptic seizure
338.26 109.94
Pseudo seizure
316.41 79.25
t = -0.945, p =0 .352
The mean of the postictal prolactin levels measured after 15 minutes of the seizure was 1795.49 in case of
epileptic seizures and 387.12 in case of pseudo seizures. On applying Independent-sample T test a highly significant
difference was found between the two means, (p < 0.01). Table 2
Table 2: Postictal Mean Prolactin Levels in Patients of
Epileptic Seizures and Pseudo Seizures
Type of Seizures Mean Standard Deviation
Epileptic seizure
1795.49 734.16
Pseudo seizure
387.12 283.16
t = -12.805, p < .0001
Out of the 73 study subjects having true epileptic seizures serum prolactin level was found to be elevated more
than two folds of the baseline level in 66 subjects. And there was a highly significant association between the type of
seizure and the level of elevation of Serum prolactin (p < 0.01). Table 3
Table 3: Relation between Type of Seizure and Level of
Elevation of Prolactin
More than Two Folds Increase
in Prolactin Level
No.
Percentage
Epileptic seizure
73
66
90.41
Pseudo seizure
17
2
11.76
2 = 46.178, C.I. = 95%, d. f.= 1, p <0.0001
Type of Seizure

Total

On comparison of means of the baseline and postictal prolactin levels using Paired-Sample T test, a highly
significant difference was found in case of epileptic seizure (p < 0.01), whereas there was no significant difference in case
of pseudo seizures (p > 0.05). Table 4
Table 4: Relationship between Baseline and Postictal mean
Prolactin level and Type of Seizure

Baseline prolactin levels


Postictal prolactin levels

Mean Prolactin Levels with Standard Deviation


Epileptic Seizure
Pseudo Seizure
338.26 109.94
316.41 79.25
1795.49 734.16
387.12 283.16
t = 16.562
t = 1.033
p<0.0001
p=0.317

DISCUSSIONS
Differentiating between pseuduseizure presenting in an epileptiform manner and epilepsy presents major
diagnostic difficulties. Distinction between the two conditions is very important, however, since management of the two
disorders differs a lot.

Impact Factor (JCC): 5.4638

NAAS Rating: 3.54

Serum Prolactin Levels as a Distinguishing Biological Marker between


True and Pseudo seizures: A Prospective Longitudinal Study

11

Increased level of serum prolactin level has emerged as a possible tool in the differentiation of true epileptic
seizures from pseudo seizures.
The findings of our study are parallel to the findings of the studies done by Trimble MR et al
[8]

, Collins WCJ et al

[9]

and Singh UK et al

[10]

[7]

, Abbott RJ et al

, who also found the levels of serum prolactin to rise drastically in case of

true epileptic seizures as compared to those of pseudo seizure.


The timing of the peak level, around 15 minutes after a seizure attack in our study, is also in agreement with the
studies of by Trimble MR et al

[7]

and Abbott RJ et al

[8]

. Our study showed a significant increase in levels of serum

prolactin at 15 minutes following seizure and insignificant change with pseudo seizure compared to basal levels, similar
results were found in the study of Beg M et al [11] in their study.
The magnitude of the peak level was found to be two - three times above the normal range which is again
corroborated in the studies of Trimble MR et al [7], Abbott RJ et al [8], Collins WCJ et al [9] and Singh UK et al [10]. Also as
stated in the study of Chen DK et al

[12]

most studies used a serum prolactin of at least twice baseline value as abnormal

and diagnostic of true seizure, similar results are found in our study.
Our findings confirmed that plasma prolactin levels are unchanged following pseudo seizures. This and other studies by
Trimble MR et al [7] and Abbott RJ et al [8] therefore, suggest that estimation of plasma prolactin is useful in differentiating
between true and pseudo seizures. The optimal time for this estimation is 15-20 minutes following a seizure?
In our study all interracial prolactin concentrations were within the normal range as corroborated in the study of
Torbjorn T et al [13].
However the results of our study are contrary to the findings of Alving J et al

[14]

who found a statistically

significant rise in serum prolactin level after an attack of pseudo seizure.


The mechanism, by which true epileptic seizures induce a short lived elevation of plasma prolactin following
seizures, is not known. Stress causes an elevation of plasma prolactin. However, this is unlikely to be the cause following
seizures as it has been shown by Abbott RJ et al [8] that, while serum cortical rises following simulated seizures, prolactin is
not significantly elevated.
Prolactin secretion is predominantly under inhibitory control from the hypothalamus.
Dopamine appears to be the major inhibitory transmitter involved. It is possible that a rise in plasma prolactin will
occur only when the abnormal electrical discharge in an epileptic seizure passes through the hypothalamic region.

CONCLUSIONS
Our study revealed that about 15-20 minutes following a true epileptic seizure there is an elevation in the serum
prolactin levels up to two to three times its baseline level. And this elevation is not marked in case of pseudo seizures. Thus
the level of rise in serum prolactin level can be used as a biological marker for distinguishing true and pseudo seizures.
REFERENCES
1.

Epilepsy-Fact sheet N999, May 2015. Available from: http://www.who.int/mediacentre/factsheets/fs999/en/

2.

Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia. 1975; 16:1
66. [Pub Med]

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editor@tjprc.org

12

Pankaj Awasth & Ankita Bajpai


3.

Geneva: World Health Organization; 2006. WHO. Neurological Disorders: Public Health Challenges.

4.

Sridharan R, Murthy BN. Prevalence and pattern of epilepsy in India. Epilepsia. 1999; 40:6316. [Pub Med]

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Lisa Graham Aan Releases Guidelines for the Use of Serum Prolactin Assays in Diagnosing Epileptic Seizures, Am Fam
Physician. 2006 Apr 1;73(7):1284

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Harrisons- Principles of internal medicine: Longo, Fauci, Kasper, Hauser, Jameson, Loscalzo; 18th edition, Mc Graw Hill
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Trimble MR. Serum prolactin in epilepsy and hysteria.Br Med J 1978; 2:1682.

8.

Abbott RJ, Browning MCK, Davidson DLW. Serum prolactin and cortisol concentrations after grand mal seizures. J Neurol
Neurosurg Psychiatry 1980;43: 163-7

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Collins WCJ, Lanigan 0, Callaghan N. Plasma prolactin concentrations following epileptic and pseudo seizures. Journal of
Neurology, Neurosurgery, and Psychiatry 1983; 46:505-8

10. Singh UK, Jana UK. Plasma Prolactin in Epilepsy and Pseudo seizures. Indian Paediatrics 1994; 31: 667-69
11. Beg M, Afzaal S, Ahmad S, Gaur RK, Ahmad J, Khan HS. Serum prolactin and luteinising hormone- Biological markers of
Seizure disorders. Indian journal of Behavioural Sciences, 1999; 9(2):54-8
12. Chen DK, So YT, Fisher RS .Use of Serum Prolactin in Diagnosing Epileptic Seizures: Report of the Therapeutics and
Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005;65(5):66875
13. Tom son T, Lindbom U, Nilsson BY, Svanborg T Eva, T Dan E H Anderson. Serum prolactin during status epilepticus. Journal
of Neurology, Neurosurgery, and Psychiatry 1989;52: 1435-37
14. Alving J. Serum prolactin levels are elevated also after pseudo-epileptic seizures. Seizure 1998;7:85-9

Impact Factor (JCC): 5.4638

NAAS Rating: 3.54