Warning: this case is complicated and the medical stuff is hard to follow if you do not have a science or medical background.
I recently met a 50 year-old female who came into my office in a wheelchair seeking help for Lyme disease. She had been under the care of another “Lyme” doctor for 3 years. She suffered with a neurological disease causing progressive weakness. The illness started more than 15 years ago but has rapidly progressed over the last three years. Until 3 years ago she had been a patient at Johns Hopkins. At this point she states that she had a bad experience there, mostly within the department of neurology. Doctors had bandied her about and been unable to diagnose her. She feels that no one ever listed to her. According to various consulting physicians things did not fit together in her case. One physician told her he had finally figured out what was wrong with her: she had chronic fatigue syndrome and fibromyalgia! One of her S, reluctantly, prescribed IVIG which she stopped 3 years ago because it wasn’t helping.
For the past three years she had been under the care of a “Lyme doctor” who had treated her with a steady diet of supplements and antibiotics while her condition continued to worsen.
It is at this point she came to see me. Searching through the morass of medical records from “the Johns” I found a copy of an EMG/NCV performed several years ago. It showed a demyelinating peripheral neuropathy. She additionally informed me that she had a small fiber biopsy which was abnormal as well. Some of the puzzle pieces which did not fit together were: a diagnosis of neutrally mediated hypotension per tilt table test without POTS and other evidence of autoimmune disease. Of particular interest was the presence of elevated anti-GAD antibodies. She recalled that several years ago she was prescribed Klonopin which initially helped some of her symptoms but the effects were not durable. At Hopkins a Lyme test (ELISA only) was negative and this possibility was dismissed.
When she saw the Lyme doctor he ordered a test for Lyme from IgeneX which showed a weak positive response with two positive, specific IgG bands present. This was the sole basis for the Lyme diagnosis. When she took antibiotics she frequently experienced chills, sweats and low grade fevers followed by worsening of weakness which did not recover with continued therapy or with cessation of therapy.
My examination showed an ill appearing female seated in a wheelchair. She had a resting heart rate of 100 and a blood pressure of 150/80. (These vital signs were “normal” for her). The examination was remarkable for some muscle wasting in her upper extremities. Moderate weakness of both upper and lower extremities was present. An absence of deep tendon reflexes globally was present. The sensory exam was completely normal. The remainder of the neurological exam and the general physical exam was within normal limits.
Lab findings: Lyme Western Blots were sent to two reference laboratories, MDL and Stony Brook. The MDL strip showed a positive IgG 41 band only. The Stony Brook test showed a few non-specific IgG and IgM bands. The remainder of the test series was positive for an elevated anti-GAD antibody and otherwise unremarkable.
So what’s going on?
Discussion of case: This patient has a CIDP-like illness affecting only motor neurons. The diagnosis may be something called multifocal motor neuropathy. Features that favor the diagnosis are: demyelinating neuropathy, progressive nature of illness and the absence of deep tendon reflexes. Lyme is not the primary issue here. Lyme is known to cause primarily axonal neuropathy although I have seen both types of neuropathy in patients with Lyme disease. Which is which? Slowing with nerve conduction testing (the shock test) shows axonal dysfunction and reduced amplitude of wave on EMG (needle test) shows demyelinating neuropathy. CIDP is thought of as a chronic form of Guillain-Barre syndrome and MMN (multifocal motor neuropathy) is related to CIDP which stands for: chronic inflammatory demyelinating polyneuropathy. Neutrally mediated hypotension is a disorder of the central nervous system and should not be seen in any of these diseases which only involved the peripheral nervous system. At any rate, the peripheral neuropathy component is due to an autoimmune disease and IVIG is the appropriate therapy. Lyme on another infection may have incited the disease in someone with a genetic predisposition as is likely in this case. It certainly sounds like this is the case as she experiences classic Herxheimer reactions when she takes antibiotics. A worsening of symptoms in this scenario sometimes called a neurological Herxheimer reaction. The inflammation which ensues when the offending germs are killed causes a worsening of disease which does not improve even with cessation of therapy. In other words, the cure may be worse than the illness. The elevated anti-GAD antibodies is something of a red herring; it is evidence of a second, unrelated, autoimmune disorder and something which may respond to a different kind of therapy. Centrally mediated hypertension is another red herring as noted above, but this finding makes sense within the context of multisystem disease, especially Lyme disease.
Patient Lyme disease have weird symptoms and syndromes which cannot easily be connected in a linear fashion. Symptoms and syndromes which forgot to read the textbook followed by academic specialist.
The presence of anti-GAD antibodies is something seen in disorder called stiff man syndrome. These antibodies block the GABAergic system and drugs like Klonopin are the appropriate therapy.
One Lesson is: Do not be a hammer and see everything as a nail. Another is: if a treatment is making the patient worse, step back and take another look. If you are a Lyme doctor you have to be an expert in everything. Other medical specialists will not help since they do not believe in Lyme disease. Other physicians will give up when everything does not fit together and seem to inevitably reach into their bag of tricks and pull out the “go see a shrink” card. I have seen the same scenario unfurl repeatedly in multiple patients whereas many neurologist are unfamiliar with the disorders. There are some knowledgeable specialist who can be helpful out there – somewhere.
My recommendations: Do not take antibiotics at this time. Restart IVIG and do not stop, consider the treatment as indefinite (then consider antibiotic therapy) and start hyperbaric oxygen therapy and get a home unit: this will be a very long term form of therapy. Other supplemental therapies may be helpful but this is my core recommendation. I recommend the patient start low doses of drugs like Klonopin and /or Neurontin which may also help with neuropathy symptoms.
The idea that killing germs will fix everything is not only wrong but may be detrimental as well.
Keep in mind that hyperbaric oxygen heals nerves and also kills germs. Herxheimer responses are likely to occur.
A repeat EMG/NCV is needed to determine disease progression and other studies.
I think this patient will get better but it is going to take some time.