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Cerebrospinal fluid pleocytosis following simple complex partial and generalized tonic-clonic seizures.

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Cerebrospinal Fluid
Pleocytosis Following
Simple, Complex Partial,
and -Generalized
Tonic-Clonic Seizures
Orrin Devinsky, MD, N. Swan Nadi, PhD,
William H. Theodore, MD, and Roger J. Porter, MD
We observed postictal pleocytosis in 7 of 62 cerebrospinal fluid specimens obtained from 27 patients with
epilepsy. Each patient had a known seizure disorder;
none had any other cause for the pleocytosis. The maximum number of leukocytes was 12/mm3;the maximum
number of erythrocytes was 130/mm3.Postictal pleocytosis was more common in samples obtained within 12
hours of the last seizure. Although previous studies have
emphasized that pleocytosis is more common after repetitive generalized tonic-clonic seizures, we found increased leukocyte counts in cerebrospinal fluid after single simple, complex partial, or generalized tonic-clonic
Devinsky 0, Nadi NS, Theodore WH, Porter RJ.
Cerebrospinal fluid pleocytosis following simple,
complex partial, and generalized tonic-clonic
seizures. Ann Neurol 1988;23:402-403
Pleocytosis following generalized tonic-clonic seizures
and focal motor seizures has been reported as a transient phenomenon in patients with n o other cause to
account for the changes in the cerebrospinal fluid
(CSF) 11-41. These previous studies examined CSF
specimens from patients admitted to city hospitals in
whom repetitive generalized tonic-clonic seizures had
often occurred and fever was frequently present. The
majority of the patients’ seizures were caused by alcoho1 withdrawal and head trauma. Because most patients were seen in the emergency room, the precise
characterization of ictal phenomena and the patient’s
activities during the preceding days were not known.
The study reported here, in contrast, reviewed results
of analysis of CSF samples from 27 patients with epi-
From The Medical Neurology Branch, National Institutes of Health,
Bethesda, MD.
Received Sep 4, 1987, and in revised form Oct 7. Accepted for
publication Oct 7, 1987.
Address correspondence to Dr Devinsky, Medical Neurology
Branch, NIH, Building 10, Room 5N248, 9000 Rockville Pike,
Bethesda. MD 20892.
lepsy in whom lumbar puncture (LP) was performed in
a controlled setting. We observed 7 cases of postictal
pleocytosis in 6 patients; the pleocytosis followed a
simple partial seizure in 1 case, complex partial seizures in 5 cases, and a generalized tonic-clonic seizure
in 1 case.
We performed 62 LPs on 27 hospitalized patients with
epilepsy and a single LP on each of 11 normal volunteers.
The patients ranged in age from 14 to 44 years; control
subjects’ ages ranged from 19 to 49 years. The study was
conducted at the Clinical Epilepsy Section of the National
Institutes of Health between July 5, 1986, and June 30,
1987. The LPs were obtained primarily to study biochemical
changes in the CSF after seizures. All patients or legal guardians signed informed consent for the protocol, which was
approved by the human studies subcommittee of the National Institute for Neurological and Communicative Disorders and Stroke. N o LP was performed during the first 48
hours after admission. Sixty of the 62 LPs in patients with
seizures were performed within 72 hours of the last seizure
(mean, 17.6 hours); the 2 other LPs were done 7 and 9 days,
respectively, after the last seizure. There was no evidence of
recent central nervous system infection, inflammatory disorder, infarction, trauma, or subarachnoid hemorrhage in any
patient. CSF was analyzed at the hematology and chemistry
laboratories of the National Institutes of Health for cell
count and differential, and glucose and protein levels. In all
cases, information concerning the clinical features and duration of the seizures was recorded during hospitalization (using video-electroencephalographic telemetry in 8 cases,
nurses’ or doctors’ reports in 49 cases, and patients’ reports
in 5 cases).
CSF was clear and colorless in all cases. CSF analysis of
the 11 specimens obtained from control subjects was
entirely normal. The CSF white blood cell (WBC)
count did not exceed 2 cellslmm3 in any of the
Table 1 lists the causes of epilepsy in the 27 patients
studied. Table 2 describes the relationship between
seizure type and presence of postictal pleocytosis (i.e.,
more than 5 WBCs/mm3) in aLl patients. Among the
specimens demonstrating postictal pleocytosis, not one
had more than 2% polymorphonuclear leukocytes or a
red blood cell count exceeding 190/mm3. Pleocytosis
was not more common following generalized tonicclonic seizures (1 of 9 cases; 11%)than simple (1 of 7;
15%) or complex (5 of 43; 12%) partial seizures.
Neither of the 2 CSF samples obtained after atonic
seizures nor the specimen obtained after a myoclonic
seizure revealed pleocytosis. There was no apparent
relationship between the duration or number of sei-
Table 1 . Causes of Seizures and Number
of Lumbar Punctures Pe$omed
No. of Patients
No. of LPs"
Idiopathic, history of
febrile seizures
Encephalitis (childhood)
Meningitis (childhood)
Head trauma (childhood)
Stroke (childhood)
Birth trauma
Tuberous sclerosis
"Numbersin parentheses are patients in whom postictal pleocytosis
was observed.
LP = lumbarpuncture.
Table 2. Seizure Type and Postictal Pleqtosis
Seizure Type
Single seizure
Simple partial
Single seizure
Single seizure
Complex partial
Single seizure
Single seizure
2 seizures in 4 hr 1
2 seizures in 4 hr 1
Generalized tonicclonic
Single seizure
Single seizure
2 seizures in 4 hr 2
1 2 hr
3-10 hr
15 min-7 hr
1 hr
10 min-9 days
15 min-7 hr
45 min
2 0 min
20 min-48 hr
30 min
20 min-12 hr
"Interval between last seizure and lumbar puncture.
= lumbarpuncture.
zures and postictal pleocytosis. However, among the 7
CSF specimens tested after simple partial seizures,
pleocytosis followed only the longest simple partial seizures (330 seconds). In all of the patients in whom
postictal pleocytosis was observed, other CSF specimens examined after seizures were normal. Postictal
pleocytosis usually occurred within 90 minutes of the
seizure (5 of 7 cases; 71%); in 2 cases, pleocytosis
occurred 17 and 20 hours, respectively, after the seizure. The average interval between the last seizure and
the time of LP in the 7 cases in which postictal pleocy-
tosis was found was 5.8 hours ( + 0.78 SD, based on
log-transformed data), and in the 55 cases without
postictal pleocytosis the average interval was 25.0
hours ( k 0.87 SD) (p = 0.10, power = 0.57; MannWhitney test performed on log-transformed data).
There was an elevation in the CSF protein level
(range, 48 to 77 mg/dl) in 16 CSF specimens from 10
In the present study, mild CSF pleocytosis occurred
after seizures in 11% (7 of 62) of the specimens examined. Although previous reports have documented
pleocytosis following some focal motor or generalized
tonic-clonic seizures [1-41, we also found pleocytosis
following simple and complex partial seizures. In our
patients, the maximum concentration of CSF WBCs
was 12/mm3;none of the CSF samples with pleocytosis
had more than 2% polymorphonuclear leukocytes.
Others have found that after generalized tonic-clonic
status epilepticus, the concentration of CSF WBCs
may reach 80/mm3 and the percentage of polymorphonuclear leukocytes may be as high as 92% C41.
The CSF pleocytosis in our patients was most likely
a direct result of the seizures. None had any recent
disorder associated with CSF pleocytosis other than
seizures. In 92% of cases the last seizure before the LP
was witnessed by telemetry or by a nurse or physician
on the epilepsy ward. The CSF specimens were clear
and colorless. There was no evidence of central nervous system trauma resulting from seizures in these
patients. The mechanism responsible for postictal
pleocytosis is uncertain but may involve breakdown of
the blood-brain barrier or release of chemotactic substances into the CSF [21.
It is important to emphasize that both seizures and
CSF pleocytosis may accompany disorders such as
herpes simplex encephalitis and meningitis, which are
treatable but potentially fatal if not promptly recognized. Therefore, in all cases of CSF pleocytosis following partial or generalized seizures, other causes
must be carefully considered.
1. Aminoff MJ, Simon RP. Status epilepticus: causes, clinical features, and consequences in 98 patients. Am J Med 1980;
2. Edwards R, Schmidley JW,
Simon RP. How often does a CSF
pleocytosis follow generalized convulsions? Ann Neurol 1983;
3. Prokesch RC, Rimland D, Petrini JL, Fein AB. Cerebrospinal
fluid pleocytosis after seizures. South Med J 1983;76:322-327
4. Schrnidley JW,
Simon RP. Postictal pleocytosis. Ann Neurol
1981 3 81-84
Brief Communication: Devinsky et al: CSF Pleocytosis 403
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simple, generalized, complex, following, pleocytosis, clonic, seizure, partial, toni, fluid, cerebrospinal
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