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The mystery of lymphocytosis: How does this phenomenon occur in the brain?
Lymphocytosis, or lymphocytic hyperplasia, refers to an abnormal increase in lymphocytes in the cerebrospinal fluid. This phenomenon is often considered a sign of central nervous system infection or inflammation and is seen in a variety of neurological diseases, such as pseudomigraine, Susac syndrome, and encephalitis. Although lymphocytes account for about a quarter of the body's white blood cells, they are relatively rare in cerebrospinal fluid. Under normal circumstances, the number of white blood cells in cerebrospinal fluid is usually less than 5 per microliter, but in cases of lymphocytosis, the number of lymphocytes can jump to more than 1,000 per microliter. The increase in lymphocyte counts is accompanied by an increase in protein concentration in the cerebrospinal fluid and an increase in other types of white blood cells.
While the exact concentration varies by disease, mild cases of lymphocytosis are generally considered to begin when the lymphocyte count enters the range of 10 to 100 cells per mm3.
In healthy individuals, the white blood cell count in the cerebrospinal fluid is usually between 0 and 5. Studies of patients with pseudomigraine have shown lymphocyte concentrations ranging from 10 to 760 per mm3, with a mean of 199 ± 174. An increase in the white blood cell count to more than 500 per mm3 may cause turbidity in the cerebrospinal fluid during diagnostic testing. This increase usually corresponds to an inflammatory immune response during viral infection. Despite the diversity of the disease, lymphocytic disorders generally share several symptoms, most notably headache and neurologic deficits.
Causes of lymphocytosis
Lymphocytosis in the cerebrospinal fluid is generally caused by an immune response to neurovascular inflammation. Many cases suggest that viral infection is the underlying cause of the myeloma, with the immune system producing antibodies against neural and vascular antigens. This provides a possible link between viral meningitis and Mollaret's disease. Some non-viral infections, such as Lyme disease, have also been suggested as possible causes. In some diseases, infection triggers an autoimmune response that leads to an increase in lymphocyte counts.
DiagnosisThe presence of lymphocytosis is usually detected by lumbar puncture followed by clinical analysis of the cerebrospinal fluid.
Diagnosis
Cerebral spinal fluid obtained by lumbar puncture is analyzed for appearance and pressure, and its glucose and protein content and white blood cell count are used to detect or diagnose a variety of conditions, including subarachnoid hemorrhage, multiple sclerosis, and various Types of meningitis. Although a lumbar puncture may return a normal white blood cell count of 0 to 5 cells per microliter, this does not rule out the possibility of disease.
Diseases
Studies have found lymphocytosis in the following diseases and have documented their respective mechanisms and responses:
Viral encephalitis
In encephalitis, inflammation of the brain causes damage to nerve function. People may experience fever, confusion, memory loss, personality changes, paralysis, seizures, and speech problems. Viral infection can directly cause encephalitis or trigger a series of reactions that ultimately lead to autoimmunity, both of which ultimately lead to an increase in the concentration of lymphocytes in the cerebrospinal fluid. Studies have found that more than 90% of patients infected with herpes simplex virus have varying degrees of lymphocytosis. Intravenous aciclovir can be used to prevent viral replication; higher doses may be used if lymphocytosis persists.
Pseudo-migraine
Several studies have investigated the association between pseudomigraine and lymphocytosis. Pseudomigraine is characterized by moderate or severe, usually bilateral, throbbing headaches with transient neurologic symptoms and lymphocytosis. These migraine attacks are recurrent and self-limiting. In these studies, the ages were mostly between 15 and 40 years old, and males accounted for the majority. After each headache attack, the patient remained symptom-free. When examined by EEG, CT, and MRI, CT and MRI scans were normal, but EEG scans were abnormal in 30 patients.
Susac syndromeIn Susac syndrome, an autoimmune reaction damages blood vessels in the brain, retina, and cochlea, leading to loss of neurological function. People with the syndrome often have hearing and vision loss and higher concentrations of lymphocytes and proteins in their cerebrospinal fluid. Treatment with corticosteroids such as prednisone, plus azathioprine, can gradually restore some function, in some cases within a few weeks.
The most appropriate way to treat an increased lymphocyte count is to treat the underlying disease.
Treatment methods
Drugs used to target viral or bacterial infections that cause an increase in lymphocytes have been found to be effective. Because herpes infection often causes lymphocytosis, acyclovir and valacyclovir are often prescribed. When lymphocytosis is caused by an autoimmune reaction, immunosuppressants such as prednisone may be used.
Detection of lymphocytosis became possible with the advent of diagnostic lumbar puncture and the development of microbiologic, biochemical, and immunological tests for analysis of cerebrospinal fluid. Although the first lumbar puncture was performed in the late 19th century, tests that revealed elevated numbers of lymphocytes in the cerebrospinal fluid were not available until later. Modern lumbar puncture tests lymphocyte counts to diagnose or rule out certain diseases such as meningitis and to determine if there is infection in the cerebrospinal fluid.
What unsolved scientific mysteries are hidden behind lymphocytosis?
