Amyotrophe Lateral Sclerosis was actually Babesiosis and Borreliosis

This report summarizes what we believe to be the first verifiable case of a significant and progressive motor neuron disease (MND) consistent with amyotrophic lateral sclerosis that resolved during treatment with i.v. ceftriaxone plus oral atovaquone and mefloquine.

The rationale for use of these antibiotics was (i) positive testing for Borrelia burgdorferi
and (ii) red blood cell ring forms consistent with Babesia species infection. The patient has continued to be free of MND signs and symptoms for 15 months, although some symptoms consistent with disseminated Borreliosis remain.

In April 2003, a healthy 62-year-old Colorado (USA) physician developed diffuse musculoskeletal pain and weakness with impaired mobility and gait. He rapidly became unable to dress or drive without assistance, making travel complicated and
medical retirement functionally mandatory.

Initial hospital evaluation revealed limited range-of motion of both shoulders, widespread fasciculations in both calves and hyperactive reflexes in all extremities. Extensive laboratory, imaging and electrophysiological studies were non-diagnostic.

Discharge diagnosis was upper and lower MND of unclear cause – possibly ALS.
Clinical neurological follow-up showed progression over the next 2 months, with increasing weakness, fasciculations in all extremities and tongue, moderate atrophy of shoulder girdle, leg and arm muscles, and an associated 15-pound weight loss.

Hyperactive reflexes became crossed and ascending. Two of four consulting academic neurologists diagnosed almost certain ALS; two with more limited involvement supported the MND diagnosis but disagreed as to certainty. Regardless, professional judgment was consistent that this was an MND, with the rate of progression suggesting demise as early as 12–18 months Based on the atypical presentation with concurrent inflammatory polyarthropathy and sporadic published reports of serologically negative Lyme disease with ALS features,(13–15) an empirical trial of doxycycline, 200 mg/day for 1 month was given in June 2003 without apparent benefit. In December 2003, serum Western blot (WB) and antibiotic-provocative urinary PCR studies for Borrelia were  performed.

Although IgG and IgM WB remained negative, the urine PCR was positive for B. Burgdorferi plasmid DNA. Except for a small gammopathy, cerebrospinal fluid was normal, with negative Borrelia PCR and WB. In peripheral blood, occasional red blood cell ring forms were detected by light microscopy, possibly considered to be a Babesia species.

In the absence of proven beneficial therapy for MNDs, empirical treatment was undertaken for Borreliosis with IV ceftriaxone, 4 gm/day, four sequential days weekly in early 2004. The protocol was based on a previous successful 12-week Borreliosis (non-MND) treatment regimen (Cichon M, Autonomous Clinical Researcher, Temple Terrace, FL, pers. comm.), and on dosing safety recommendations of the drug manufacturer.

Ursodiol was also given to prevent ceftriaxone-induced bile sludging. The patient was concurrently placed on an accepted oral anti-Babesia regimen of Atovaquone, 750 mg BID for 21 days in each of the first 3 months. Azithromycin was withheld to assess
ceftriaxone effectiveness as a substitute. Patient improvement was rapidly evident. By
10 weeks of therapy, improved stamina, mobility, vitality, initiative and social engagement were unmistakable. Objective muscle strength was significantly improved and muscle atrophy was visibly diminishing. After 12 weeks of ceftriaxone and atovaquone, assistance was no longer required for mobility, and squats became possible for the first time since presentation. Muscle cramps, myoclonus and fasciculations were diminished, but reflexes remained hyperactive and crossed. All arthropathy resolved early, despite cessation of prior methotrexate injections.

After the patient’s initial 12-week IV ceftriaxone course (Feb–May, 2004), that drug was
continued intermittently at 2 or 4 g daily. Sporadic ceftriaxone cessation after 12 weeks resulted in partial return of signs and symptoms typical of disseminated Borreliosis (14, 16), but with improvement on re-infusion. Atovaquone was discontinued after three 21-day courses followed by a 1-month hiatus, then oral mefloquine, 250 mg weekly for 6 months (ending November, 2004). Motor neuron signs and symptoms continued improving. In February 2005, 1 year after initiating antibiotic therapy, the patient’s ALS experienced neurologist found him to be apparently free of objective MND signs. Resolution of the patient’s MND has persisted on periodic examinations to the present (June, 2006).

The patient remains on intermittent ceftriaxone only to control non-motor neuron symptoms. Notably, no adverse effects have been seen related to prolonged use of IV ceftriaxone or the anti-Babesia drugs.

Serology drawn 09/13/ 2005 revealed a negative Borrelia IgM WB (no positive bands), negative Borrelia IgG WB (bands P39 and P41 only were positive), negative B. microti FISH, IFA and PCR, and negative Babesia WA-1 IFA.

Our case presents three additional factors that are novel in the treatment of MND: (i) ceftriaxone was used at a higher level than in the past (4 g daily), (ii) two infectious
agents emerged as credible participants and (iii) anti-Babesia antibiotics were used. Coinfection with Borrelia and Babesia has produced more severe clinical symptoms and prolonged illness in patients with these tick-borne diseases (24). Thus, the aetiology of MND may involve more than one infectious agent, and treatment of MND may require diligent screening for these infections and a more complicated antibiotic regimen than previously envisioned.

We have documented the full neurological recovery in a patient with an unrecoverable MND. The successful clinical outcome was associated with antibiotic therapy in response to evidence of two concurrent infections. We suggest that MND may be associated with an infectious trigger in certain cases. The use of antibiotic therapy in MND merits further evaluation.