Case 32-2020: A 63-Year-Old Man with Confusion, Fatigue, and Garbled Speech

Authors:  Shibani S. Mukerji, M.D., Ph.D., Kevin L. Ard, M.D., Pamela W. Schaefer, M.D., and John A. Branda, M.D.

The following was obtained from the case presented in the link above in the New England Journal of Medicine.A 63-year-old retired government employee who lived with his wife in northern New England had recently traveled to Florida and to rural Canada to hunt was evaluated at the hospital because of:

  • fever
  • confusion
  • headache
  • garbled speech
  • fatigue
  • vision changes & floaters
  • lymphocytic pleocytosis
  • elevated protein level in the cerebrospinal fluid (CSF)
  • worsening proteinuria and hypertension
  • flash of light accompanied by transient sharp pain in the left retro-orbital area and forehead, with monocular blurry vision
  • garbled and nonsensical speech with impaired comprehension
  • word-finding difficulty
  • photophobia
  • sonophobia
  • staring spells that lasted for 1 minute
  • low-grade fever 
  • somnolence
  • generalized weakness
  • unsteadiness
  • mild neck stiffness
  • unintentional weight loss of 10 kg in the past 6 months
  • nocturia
  • cachectic appearing
  • perseverative thoughts
  • unable to name days of the week backward
  • when asked to remember three words, he could recall only one word after 5 minutes
  • he reported that nine quarters equaled $4.25
  • dilated-eye examination revealed edema in both optic nerves

Interestingly, after IV acyclovir, ceftriaxone, ampicillin, vancomycin, and thiamine, he developed myoclonic jerks with marked lethargy, and the photophobia, and nonsensical speech persisted. He was intermittently impulsive and uncooperative. After 4 days of IV treatment he reported feeling better and having increased strength, allowing him to walk. On the fifth hospital day, he was calm and cooperative; oriented to person, place, and time; and able to follow complex commands.

Administration of broad-spectrum antimicrobial agents resulted in rapid improvement in his clinical condition within days despite increasing neurologic symptoms over the course of several months, findings that suggested meningoencephalitis.  Despite an extensive evaluation for likely causes of meningoencephalitis, a definitive diagnosis was not established. This patient’s presentation and clinical course are emblematic of challenges faced by clinicians, given that the causative agent in meningoencephalitis is identified in only 30 to 60% of cases, despite extensive and invasive testing.1,2

There are three important clinical features of this patient’s presentation:

  • uveitis associated with meningoencephalitis
  • subacute cognitive decline
  • clinical improvement after the administration of antimicrobial therapy

A unique feature of this patient’s presentation is his exposure to rituximab, a humanized chimeric anti-CD20 monoclonal antibody that causes B-cell depletion. The effects of rituximab should be considered when interpreting the results of IgG and IgM serologic tests. This concern is relevant to testing for West Nile virus infection and eastern equine encephalitis, both of which can cause neuroinvasive viral encephalitis and are endemic in the northeastern United States. The antibody response during these infections can be delayed or absent in patients with B-cell depletion.4,5 Such a response may also occur in Powassan virus infection, an emerging cause of viral meningoencephalitis in the United States that is transmitted by ticks.6

A key question remains: What pathogen can cause uveitis and meningoencephalitis and result in rapid clinical improvement after the administration of vancomycin, ampicillin, ceftriaxone, and acyclovir?

The authors point out that spirochete infections can cause uveitis and meningoencephalitis.

Due to the patient’s history of living in an endemic area for tick-borne diseases, is an avid hunter, whose condition improved dramatically after IV antibiotics, infection with borrelia species seemed a logical diagnosis.

The authors point out the problem with testing:

Testing for Lyme disease occurs as a part of a two-tiered algorithm and measures a person’s antibody response to the spirochete. Whether treatment with rituximab delays formation of antibodies in blood and CSF is unknown, thus complicating the interpretation of this patient’s serologic test results.

They further state that those with neurological Lyme infection often have abnormal imaging findings of the head or spine but that this patient had neither.

Then they state that B. miyamotoi, another borrelia species, causes a symptom complex that is consistent with this patient and that there are two case reports of meningoencephalitis in immunocompromised patients receiving rituximab, where B. miyamotoi was the causative agent.  These patients received rituximab for hematologic cancers, and in both, Wright-Giemsa staining of CSF showed spirochetes, and a definitive diagnosis of B. miyamotoi infection was made based on nucleic acid testing of the blood.

The authors state the patient’s recurrent fever but lack of rash also support a B. miyamotoi infection, but that the opthalmologic findings do not.  They admit; however, that there is limited understanding of B. miyamotoi but since other spirochetes can cause eye issues, B. miyamotoi is likely no different. ( I must add here that I know many Lyme disease patients who get recurrent fevers and have never seen a rash.  This is a perfect example of how researchers and doctors have falsely pigeon-holed Lyme symptoms into a box of their own making).  For more:

Regarding testing, a lumbar puncture targeting the glpQ gene of borrelia that causes relapsing fever, which is absent in Lyme disease, was positive. Serum showed strong reactivity on the ELISA that detects IgG antibodies directed against the GlpQ protein of B. miyamotoi.  Corresponding IgM ELISA was negative, consistent of B. miyamotoi infection of several months duration.

Unfortunately there are no randomized controlled trials and no formal treatment recommendations.  Patients typically receive Lyme disease treatment.  An in vitro study showed B. miyamotoi was susceptible to doxycycline, azithromycin, and ceftriaxone but not amoxicillin. (Again, I must add that current Lyme disease treatment advocated by the CDC/IDSA only works for a small percentage of patients and that studies from the beginning have shown treatment failures using their approach.  For more:

The patient was sent home with 4 weeks of IV ceftriaxone but developed a facial rash and was switched to doxycycline.  After 3 weeks all symptoms had resolved but the blurry vision which improved slowly over 3 months.

This patient should be followed up for years, but won’t be.
And the question begging to be asked is: how many people with B. miyamotoi are falling through the cracks?  It isn’t even reportable to the CDC yet (which notoriously undercounts all things tick-borne-related).

For more:

This article points out the confusion with B. miyamotoi: 

  • many separate it from other tick-borne relapsing fevers
  • while it can cause relapsing fevers, it sometimes doesn’t
  • it appears to be the only TBRF transmitted from a hard bodied tick, unlike TBRF which is mainly transmitted from a soft bodied tick (I remain skeptical of this as ticks have repeatedly been found to transmit things they shouldn’t – just like they are found in places they shouldn’t be.)
  • symptoms often resemble Lyme disease
  • you can be infected with BOTH B. miyamotoi AND Lyme disease (as well as numerous other coinfections) which will complicate symptom presentation
  • testing for B. miyamotoi is just as abysmal as it is for Lyme/MSIDS:
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