Introduction
A seizure is a quick and uncontrolled brain activity that results in abnormal jerky movements, limb stiffening, and loss of consciousness. Seizures are attributed to various causes, namely, stroke, brain infections (meningitis), cancer, an overdose of certain medications, and high fever.
Repeated seizures are characteristic of epilepsy. Recently, COVID-19 has also been found to precipitate seizures. After a seizure episode, numerous changes have been reported to occur in the brain. One of them is seizure-induced pleocytosis. It is also called post-ictal pleocytosis.
What Is Seizure-Induced Pleocytosis?
Pleocytosis is the raised number of white blood cells (WBCs) in the cerebrospinal fluid (CSF). It is an uncommon finding after an epileptic attack. CSF pleocytosis is usually a result of viral or bacterial meningitis, brain cancer, or stroke. It is defined as WBCs > 10 - 12 cells/millimeter3 (mm). The white blood cells mainly raised in the CSF are polymorphonuclear leucocytes (PMNs) and lymphocytes.
What Is the Underlying Mechanism of Seizure-Induced Pleocytosis?
Seizure-induced pleocytosis is a transient phenomenon whose exact underlying mechanism is unknown. It was first described in the 1920s. The blood-brain barrier (BBB) is a network of blood vessels that prevents the entry of toxins and pathogens from reaching the brain. Theories state that a temporary break in the BBB occurs following a seizure noted in experimental animal models. As a result, the mediating immune cells, such as cytokines and chemokines, attract WBCs to the CSF.
What Are the Cases Reported of Seizure-Induced Pleocytosis?
There have been a few cases to date.
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Prokesch et al., in 1983, stated in their data review that out of 102 enlisted epileptic patients, 35 had CSF pleocytosis. Furthermore, out of the 35, 31 had pleocytosis without any cause despite the laboratory and radiology investigations. PMNs consisted of 57 % of the raised cells in the examination. They concluded that the occurrence was transient, and the CSF became normal with the patient’s rapid recovery.
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Devinsky et al. observed post-ictal pleocytosis in 7 CSF specimens in 27 epileptic patients. The patients comprised all the categories of epilepsy. They noted that seizure-induced pleocytosis was more frequent in recent samples of CSF after a seizure.
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Schmidley et al. reported seizures to be the primary cause of pleocytosis. In addition, six patients showed temporary and unexplained pleocytosis following repeated seizures. Meningitis, bacterial and viral infections, inflammation, bleeding, and cancer were excluded. The authors concluded that although seizures alone can cause pleocytosis, infectious causes also must be ruled out.
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In 2014, Johnson et al. conducted a study on children aged one month to 21 years suffering from status epilepticus (SE) without Central Nervous System (CNS) infection. SE is a state with repeated seizures with loss of consciousness within 30 minutes. Hence, it is a state of emergency. Out of the 178 children, seven had CSF pleocytosis. Further, viral studies on these patients deduced Herpes Simplex Virus (HSV) infection in six children with CSF pleocytosis. Therefore, the authors concluded that an infection causing pleocytosis in children should be considered, as seizure-induced pleocytosis is rare.
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Schachter et al. reported a case of a 68-year-old female who had epilepsy in Israel in 2017. The patient had a history of schizophrenia, diabetes mellitus type II, hypothyroidism, and high cholesterol (dyslipidemia). The patient was taking medications for the same. Computed Tomography (CT) showed no acute changes, such as evidence of bleeding, benign and malignant tumors, and inflammation. They suggested a reasonable cause for CSF pleocytosis in the patient might be a psychiatric disorder.
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Scramstad et al. conducted a similar study in 2017, revealing that seizures do not directly cause CSF pleocytosis. Alternatively, it reflects an underlying acute or chronic brain pathology. Out of the 51 patients enrolled, twelve had CSF pleocytosis. Meningitis, cocaine abuse, and alcohol withdrawal were the most probable causes.
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A recent review in 2022 suggested that the new category of SE called new-onset refractory status epilepticus (NORSE) and fever-infection-related refractory epilepsy syndrome (FIRES) must be differentiated in children. FIRES is a sub-category of NORSE in which fever occurs about 24 hours to 2 weeks before the onset of SE. CSF pleocytosis without infection can occur in this condition.
Other authors who reported a similar condition are Aminof and Simon, Edwards et al., Barry and Hauser, Peltola et al., and Tumani et al.
What Are the Investigations To Diagnose the Condition?
An elevated CSF leukocyte level hardly provides a definitive diagnosis. However, it might indicate an underlying CNS condition.
The investigations done for a diagnostic workup are
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Lumbar Puncture - It is also called the spinal tap procedure. Lumbar puncture is done for CSF analysis. Elevated WBCs, elevated glucose, and protein levels are also found.
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Electroencephalograph - Electroencephalograph or EEG is a useful and specific tool for diagnosing epilepsy. It includes spikes, sharp waves, or a combination of both.
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Magnetic Resonance Imaging - Magnetic Resonance Imaging (MRI) is superior to EEG for diagnosing seizure disorders. Also, MRI diagnoses any underlying brain disease.
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Computed Tomography - Computed Tomography, or CT, is used to diagnose space-occupying lesions (tumors, blood vessel disorders, and infections). CT Angiography is an advancement for diagnosing blood vessel disorders of the brain.
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Positron Emission Tomography - Positron Emission Tomography (PET) is an interesting imaging technique to detect any active inflammation in the brain. PET is sometimes combined with CT for better efficacy.
What Is the Management of Seizure-Induced Pleocytosis?
It is suggested that the doctors start the medication before the final diagnosis. Recurrent seizures should be managed as an emergency. Anti-epileptic drugs such as sodium valproate, carbamazepine, and oxcarbazepine are used. Adequate hydration, diet modification, surgery, and vagus nerve stimulation are advised.
Before ruling out the causative agent, the medications must be aimed at all the primary causes of pleocytosis. For bacterial meningitis, antibiotics are prescribed. Viral infection can be suspected if the CSF analysis points to lymphocytic pleocytosis. Acyclovir, an anti-viral medication, is given orally or intravenously. Advanced treatment modalities such as chemotherapy and leukapheresis are advised in specific brain tumors.
Conclusion
Seizure-induced pleocytosis is an uncommon occurrence. Only 2 % to 20 % of the previously conducted studies reveal seizure-induced CSF pleocytosis. There needs to be more supportive evidence to explain that seizures disrupt the BBB. Further, the experimental models suggest that BBB disruption leads to smaller molecules entering the brain. However, entering larger components, such as cells, is difficult. Hence, further research is required to elucidate this phenomenon.
