What are the infective causes of Lateral Epicondylitis (LETM) of the elbow and their associated cerebrospinal fluid (CSF) findings?

Infective Causes of LETM and CSF Findings

I need to clarify an important point: LETM in medical terminology refers to Longitudinal Extensive Transverse Myelitis (a spinal cord condition), not Lateral Epicondylitis of the elbow. The evidence provided about lateral epicondylitis (tennis elbow) is not relevant to infectious causes or CSF findings, as lateral epicondylitis is a musculoskeletal degenerative condition without CNS involvement or CSF abnormalities 1, 2, 3.

Infectious Causes of Longitudinal Extensive Transverse Myelitis

Viral Pathogens

The most common viral causes of LETM include herpes viruses and enteroviruses, which should be tested first in all suspected cases.

• Herpes Simplex Virus (HSV-1 and HSV-2): CSF PCR has >95% sensitivity and specificity; culture is positive in <5% of cases 4
• Varicella Zoster Virus (VZV): CSF PCR (NAAT) is the diagnostic test of choice; can present with acellular CSF in immunocompromised patients 4
• Enteroviruses: CSF PCR sensitivity >95%, culture sensitivity 65-75%; may also culture from throat or stool 4
• Epstein-Barr Virus (EBV): Should be tested especially in immunocompromised patients; can cause acellular CSF 4
• Cytomegalovirus (CMV): Consider in immunocompromised patients; associated with acellular CSF 4

Bacterial Pathogens

• Mycobacterium tuberculosis: Culture sensitivity 25-70%; NAAT sensitivity is poor in non-respiratory specimens, so culture must also be requested; requires large CSF volumes (≥5 mL) for optimal yield 4
• Treponema pallidum (Syphilis): CSF VDRL and FTA testing indicated 4
• Listeria monocytogenes: Can present with lymphocytic pleocytosis mimicking viral infection 4

Fungal Pathogens

• Cryptococcus neoformans/gattii: CSF cryptococcal antigen test has >90% sensitivity and specificity; more sensitive on CSF than serum; false negatives can occur in HIV/AIDS patients 4
• Coccidioides: CSF complement fixation test is optimal; direct smear and culture often negative 4

Parasitic Pathogens

• Acanthamoeba species: Requires specialized testing 4
• Naegleria fowleri: Requires specialized testing 4

CSF Findings by Pathogen Type

Viral Infections - Typical CSF Profile

• Lymphocytic pleocytosis is characteristic 4
• Normal to mildly elevated protein 4
• Normal glucose ratio (CSF:serum glucose) 4
• HSV can cause hemorrhagic CSF with elevated red cell count in ~50% of cases 4
• Acellular CSF can occur with VZV, EBV, and CMV, particularly in immunocompromised patients 4

Bacterial Infections - Typical CSF Profile

• Tuberculous meningitis: Lymphocytic pleocytosis, low glucose ratio, higher protein than viral causes 4
• Partially treated bacterial meningitis: Can mimic viral pattern with lymphocytic pleocytosis 4
• CSF lactate <2 mmol/L effectively rules out bacterial disease 4
• CSF lactate elevation helps distinguish bacterial from viral CNS infections 4

Fungal Infections - Typical CSF Profile

• Cryptococcal meningitis: Variable pleocytosis; diagnosis primarily by antigen testing rather than cell count 4
• Coccidioidal meningitis: Diagnosis by complement fixation on CSF; cellular response variable 4

Diagnostic Algorithm

Initial CSF Testing for All Suspected Cases

All patients with suspected infectious LETM should have CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses, as this identifies 90% of known viral cases 4.

• Gram stain (sensitivity 60-80% in untreated patients, 40-60% in treated patients) 4
• Bacterial culture 4
• Cell count with differential 4
• Protein and glucose (with paired serum glucose) 4
• CSF lactate to distinguish bacterial from viral causes 4

Additional Testing Based on Clinical Context

• Chronic symptoms (≥4 weeks): AFB smear and culture (large volume ≥5 mL), fungal culture, cryptococcal antigen, Coccidioides serology 4
• Immunocompromised patients: EBV PCR, CMV PCR, fungal studies 4
• Travel history/endemic exposures: Directed testing for arboviruses, tick-borne encephalitis, specific fungal pathogens 4

Critical Pitfalls to Avoid

• Do not rely on NAAT alone for M. tuberculosis - culture must be performed due to poor NAAT sensitivity in non-respiratory specimens 4
• Obtain specimens before antimicrobial therapy whenever possible, as treatment reduces diagnostic yield 4
• Use large CSF volumes (5-10 mL) for mycobacterial and fungal cultures to maximize sensitivity 4
• In traumatic taps, subtract 1 white cell per 700 red blood cells, but recognize that blood-stained CSF in HSV may reflect hemorrhagic pathophysiology rather than traumatic tap 4