What is Lymphocytic Pleocytosis?
Lymphocytic pleocytosis is an abnormal increase in white blood cells in the cerebrospinal fluid (CSF), specifically with lymphocytes as the predominant cell type, typically defined as more than 5 lymphocytes per microliter. 1
Definition and Characteristics
- Pleocytosis refers to an elevated white blood cell count in the CSF above normal levels (typically >5 cells/µL) 1
- Lymphocytic pleocytosis specifically indicates that lymphocytes are the predominant cell type in this elevated count, rather than neutrophils (polymorphonuclear cells) 1
- The cell count can range from mild elevations (tens of cells) to several hundred cells per microliter, depending on the underlying cause 1, 2
Clinical Significance
Common Causes
Viral infections are the most typical cause of lymphocytic pleocytosis:
- Herpes simplex virus (HSV) encephalitis commonly presents with lymphocytic pleocytosis, though polymorphonuclear cells may predominate early in the illness 1
- Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) can all cause lymphocytic pleocytosis 1
- Enteroviral infections frequently cause lymphocytic pleocytosis 1
Non-viral causes that must be considered:
- Tuberculosis meningitis characteristically produces lymphocytic pleocytosis with low CSF glucose and elevated protein 1
- Listeriosis can present with lymphocytic pleocytosis 1
- Partially treated bacterial meningitis may show a lymphocytic predominance rather than the typical neutrophilic pattern 1
- Tickborne rickettsial diseases (Rocky Mountain Spotted Fever, ehrlichiosis) can cause either neutrophilic or lymphocytic pleocytosis 1
- Fungal infections including histoplasmosis, coccidioidomycosis, and cryptococcosis typically produce lymphocytic pleocytosis 1
- Lyme neuroborreliosis causes a distinctive B-cell-predominant lymphocytic pleocytosis 3
Important Diagnostic Distinctions
Key accompanying CSF findings help differentiate causes:
- Normal glucose with lymphocytic pleocytosis suggests viral infection 1
- Low CSF:plasma glucose ratio (<0.5) with lymphocytic pleocytosis suggests tuberculosis, fungal infection, or partially treated bacterial meningitis 1
- Elevated protein (100-200 mg/dL) is common in many causes of lymphocytic pleocytosis 1
- CSF lactate <2 mmol/L effectively rules out bacterial disease 1
Clinical Pitfalls and Caveats
Early in viral infections, neutrophils may predominate before transitioning to lymphocytic predominance - this is particularly true for HSV encephalitis and enteroviral infections 1, 4
Approximately 5-10% of patients with proven HSV encephalitis may have normal initial CSF findings with no pleocytosis, especially early in illness or in immunocompromised patients 1
In cerebral malaria, the presence of CSF pleocytosis is rare enough that alternative or concurrent diagnoses should be strongly considered 5
Lymphocytic pleocytosis with atypical or plasmacytoid lymphocytes can mimic lymphoma - immunophenotyping showing polyclonal T-cells (typically CD4:CD8 ratio of 3:1) confirms benign reactive process 3, 6
Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis (PMP syndrome) is a rare benign condition causing recurrent neurological deficits with headache and marked lymphocytic pleocytosis (10-760 cells/mm³), resolving spontaneously 2
Prognostic Implications
The presence of lymphocytic pleocytosis itself does not predict worse outcomes in conditions like multiple sclerosis or viral CNS infections 4, 7
The specific underlying diagnosis and presentation (particularly encephalitis versus meningitis) are more important prognostic factors than the degree or type of pleocytosis 4