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Lymphocytic pleocytosis
Lymphocytic pleocytosis is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid. It is encountered as an autoimmune response to infection in a number of neurological diseases. Increases in lymphocyte count are often accompanied by an increase in cerebrospinal protein concentrations in addition to pleocytosis of other types of white blood cells.

Symptoms
Though exact concentrations differ based on the specific disease, mild cases of lymphocytic pleocytosis are considered to begin when lymphocyte counts enter the range of 10-100 cells per mm3. In patients suffering from pseudomigraines, studies have shown concentrations ranging from 10-760 cells per mm3, with a mean concentration of 199 ± 174 cells per mm3. The rise in concentration corresponds to an inflammatory immune response typically seen during viral infections. Despite their diversity, diseases featuring lymphocytic pleocytosis share a number of symptoms, most notably headaches and neurological deficits.

Causes
Cerebral spinal fluid lymphocytic pleocytosis is generally the consequence of neurovascular inflammation and the body's immune responses. Many cases point to a viral infection as the root cause of pleocytosis, in which the immune system produces antibodies against neuronal and vascular antigens, possibly connecting it to viral meningitis and Mollaret’s disease. Certain non-viral infections, such as Lyme disease have also been considered possible causes. In some diseases, an infection precipitates an autoimmmune response, leading to increased lymphocyte levels.

Diagnosis
The presence of lymphocytic pleocytosis is generally detected through a lumbar puncture followed by clinical analysis of cerebrospinal fluid.

Diseases
Research has found the presence of lymphocytic pleocytosis in the following diseases and documented their respective mechanisms and reactions:

Herpes simplex virus-1 encephalitis
Patients that had come in with varying symptoms of fever, headache and weakness along with other symptoms for each of the cases were given a CT scan and an MRI. Lumbar punctures were performed to analyze cerebrospinal fluid levels, with 90-100% of patients found to have lymphocytic pleocytosis in varying levels. As they were treated with the Intravenous acyclovir, which worked to stop the replication process of the virus, they received another lumbar puncture and analysis of the cerebrospinal fluid. The results showed that there was persistent lymphocytic pleocytosis requiring a higher dosage of acyclovir to be taken. Patients showed signs of improvement and after treatment they were discharged and took valacyclovir. At follow up check ups afterwards, most of the patients were asymptomatic.

Pseudomigraine
Multiple studies have been performed to examine the correlation between pseudomigraines and lymphocytic pleocytosis. A pseudomigraine is characterized by a moderate or severe, throbbing headache accompanied by transient neurological symptoms and lymphocytic pleocytosis. These migraine episodes are recurrent and self-limiting. In these studies, individuals ranging from about 15-40 years of age were examined and the majority of those tested were male. After each migraine episode, the patients were all asymptomatic. When examined via EEG, CT, and MRI forms of imaging, the CT and MRI scans were all normal; however, 30 out of 42 patients had abnormal EEG scans. For 26 of these patients, there was unilateral excessive slowing while 4 of these patients experienced bilateral slowing. In another study, patients displayed an elevated level of lymphocytic pleocytosis with each pseudomigraine episode.

Susac's syndrome
In Susac's syndrome, an autoimmune response damages the blood vessels of the brain, retina and cochlea, leading to a loss of neurological functions. Patients with the syndrome suffered from hearing and vision loss and were found to have higher concentrations of lymphocytes and proteins in their cerebrospinal fluid. Treatment with immunosuppressive drugs like prednisone followed by Azathioprine were found to have significant effects and patients gradually regained lost function, in some cases after only a few weeks.

Autoimmune encephalitis
In Encephalitis, the inflammation of the brain leads to a breakdown in neurological function, causing the patient to suffer from symptoms such as fever, confusion, amnesia, personality changes, paralysis, seizures and language dysfunction. An initial viral infection is believed to start a cascade ending in autoimmunity. The most ubiquitous form, anti-NMDA receptor encephalitis, is thought to be commonly triggered by herpes infections resulting in an autoimmune response to the NR1 subunit of the NMDA receptor.

Lymphocytic pleocytosis is involved in the initial stages of the disease, lymphocytes can number in the hundreds per mm3, while later on, lymphocyte levels have a tendency to return to equilibrium. It has been proposed that this early spike in lymphocytic concentration is the result of the breaching of the blood-brain barrier during the initial viral infection, giving peripheral antibodies access to the central nervous system and leading to the development of autoimmunity.

History
Determination of lymphocytic pleocytosis became possible with the advent of the diagnostic lumbar puncture and the technology necessary to analyze the cerebrospinal fluid via microbiology, biochemistry, and immunology tests. While the first lumbar punctures were performed in the late 19th century, the tests performed on the CSF for cell counts that reveal elevated lymphocyte levels were not available until much later. Now CSF diagnostic testing is a medical procedure used commonly to diagnose or rule out certain diseases such as meningitis and for determining blood cell counts that indicate infection of the CSF.