Can tick-borne illnesses (TBI) mimic Amyotrophic Lateral Sclerosis (ALS)?

Can Tick-Borne Illnesses Mimic ALS?

Yes, certain tick-borne infections can present with neurological manifestations that superficially resemble ALS, but true ALS mimicry is exceedingly rare and limited to specific circumstances—primarily chronic tick-borne encephalitis (TBE) from Siberian/Far Eastern virus subtypes, not the common North American tick-borne diseases.

Key Distinctions Between Tick-Borne Disease and ALS

Chronic TBE Can Mimic ALS (Rare, Specific Subtype)

• Chronic TBE from Siberian and Far Eastern virus subtypes can manifest as an ALS-like syndrome with bulbar signs, progressive muscle weakness and atrophy, decreased reflexes, and respiratory failure 1
• This presentation has been documented decades after initial infection, with one case showing relapse 35 years after acute disease 1
• This chronic progressive form is not associated with the European TBE subtype commonly seen in Western Europe 1
• Chronic TBE is distinguished from postencephalitic syndrome by the presence of anti-TBEV antibodies in serum and antibodies to E protein and nonstructural protein NS1 in CSF 1

North American Tick-Borne Diseases Rarely Mimic ALS

• Lyme disease (Borrelia burgdorferi) does not cause ALS, and any association is coincidental rather than causal 2
• Evidence linking Lyme borreliosis to ALS is "scant, nonexistent, or coincidental" according to neurological literature 2
• Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis cause acute febrile illnesses with CNS manifestations (meningitis, encephalitis, cranial nerve palsies, focal weakness) that resolve with treatment, not progressive motor neuron disease 3

Clinical Features That Distinguish Tick-Borne Disease from True ALS

Acute Tick-Borne Rickettsial Diseases Present Differently

• Fever is nearly universal in acute ehrlichiosis and anaplasmosis, whereas ALS does not cause fever 3, 4
• Symptoms develop over 5-10 days after tick exposure, not the insidious progressive course of ALS 4
• CNS manifestations include altered sensorium (up to 20% of HME cases), seizures, meningismus, and cranial nerve palsies—not the pure motor neuron pattern of ALS 3
• Lymphocytic pleocytosis occurs in approximately 50% of HME patients who undergo lumbar puncture, which does not occur in ALS 3, 5
• Laboratory abnormalities include leukopenia, thrombocytopenia, and elevated hepatic transaminases—findings absent in ALS 4

Late/Chronic Tick-Borne Disease Presentations

• Severe motor deficits from late tick-borne disease with mixed infections (Borrelia, Babesia, Anaplasma, Bartonella) can cause paralysis but typically respond to long-term antibiotic/antiparasitic treatment, unlike ALS 6
• These cases show serological evidence of active infection and improvement with antimicrobial therapy—neither characteristic of ALS 6

Diagnostic Approach When Considering Tick-Borne Disease vs. ALS

Red Flags Suggesting Tick-Borne Disease Rather Than ALS

• Acute or subacute onset (days to weeks) rather than insidious progression over months 3, 4
• Fever, headache, myalgias, or systemic symptoms 4
• Recent outdoor exposure in endemic areas (south Atlantic, north central, south central, New England states for ehrlichiosis/anaplasmosis; specific regions for TBE) 3, 4
• CSF abnormalities including pleocytosis, which is absent in typical ALS 3, 5
• Response to doxycycline or other antimicrobial therapy 4

When to Test for Tick-Borne Disease

• Empiric doxycycline should be initiated immediately if tick-borne rickettsial disease is suspected based on clinical presentation and epidemiology, without waiting for laboratory confirmation 3, 4
• Acute and convalescent serology (2-4 weeks apart) for Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Borrelia burgdorferi in endemic areas 4
• PCR testing for tick-borne pathogens from whole blood if available 4
• For suspected chronic TBE: CSF antibodies to TBEV E protein and NS1, along with serum anti-TBEV antibodies 1

Critical Clinical Pitfall

The absence of reported tick bite should never exclude tick-borne disease from consideration—up to 40% of RMSF patients and 32% of ehrlichiosis patients report no tick bite history 3. However, this does not mean tick-borne disease commonly mimics ALS. The vast majority of tick-borne diseases present as acute febrile illnesses with multisystem involvement, not isolated progressive motor neuron degeneration.

Bottom Line for Clinical Practice

• If a patient presents with progressive motor neuron disease without fever, systemic symptoms, or CSF abnormalities, ALS remains the primary diagnosis and tick-borne disease is extraordinarily unlikely 2
• If neurological symptoms occur in the context of acute febrile illness with tick exposure, treat empirically for tick-borne disease with doxycycline while pursuing diagnostic confirmation 3, 4
• Chronic TBE mimicking ALS is a rare phenomenon limited to specific geographic regions (Siberia, Far East) and viral subtypes not found in North America 1