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Controversies in Neuroborreliosis

Updated October, 2002
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The objectives of this article are to cover issues related to Lyme disease that are not even-handedly addressed in the current literature. It will:

  1. Present a practical approach for making the diagnosis of neuroborreliosis,
  2. Explore the other side of the post-Lyme syndrome (i.e. the likelihood of chronic ongoing infection),
  3. Discuss the relationship between MS and Lyme,
  4. Critique the current regimens published for treating neuroborreliosis, and
  5. Present my own approach which may differ from some leading authorities.

“Anyone who, in discussion, relies upon authority uses not his understanding but rather his memory.”

Leonardo da Vinci, Notebooks (c. 1500)

It is hoped this data will provide the reader with a broader understanding of neuroborreliosis so that he or she may better use current and evolving knowledge for clinical decision making.

I.   NEUROBORRELIOSIS: MAKING THE DIAGNOSIS

Because of difficulties in making the diagnosis of neuroborreliosis, the physician will need a familiarity with the most common forms of presentations, which will be emphasized. The following points will help evaluate the patient for neuroborreliosis:

  1. For most patients, systemic features of disease coexist with, or predate, neurologic manifestations.
  2. Both central nervous and peripheral nervous system involvement is frequent with Lyme disease and typically occur together.
  3. Laboratory data may or may not confirm the diagnosis, and other disease in the differential diagnosis must be evaluated thoroughly in cases where diagnostic ncertainty exists.
  4. Although history of exposure to B. burgdorferi should be sought, for various reasons, patients may not remember a history of a tick bite, or the pathognomonic rash particularly if the disease is presenting years after the exposure.
  5. Early on, personality changes, psychiatric symptoms, or cognitive manifestations may be the first, and occasionally the only, symptoms that the patient or family is aware of.

CLINICAL DESCRIPTIONS OF NEUROBORRELIOSIS

CENTRAL NERVOUS SYSTEM INVOLVEMENT

  • Meningismus with normal CSF
  • Lymphocytic Meningitis
  • Meningoencephalomyelitis
  • Subacute Encephalopathy (SAE)

PERIPHERAL NERVOUS SYSTEM INVOLVEMENT

  • Cranial Neuropathy
  • Painful Radiculitis
  • Distal Neuropathy
  • Plexopathy
  • Myositis
  • Polymyalgia Rheumatica

CENTRAL NERVOUS SYSTEM

MENINGISMUS

Patients may present with headache and stiff neck without evidence of CSF inflammation. Since early CNS seeding has been described, as well as culture positivity during latent disease without concurrent CNS inflammatory changes, these symptoms probably indicate active infection. Stiff neck might alternatively be due to axonal degenerative changes of the cervical paraspinal musculature, but there should be other evidence of a more widespread neuropathy when this is the case.

LYMPHOCYTIC MENINGITIS

Lymphocytic Meningitis may appear to be indistinguishable from aseptic meningitis during early-disseminated disease (weeks to months after inoculation with B. burgdorferi). Most patients will have headaches that will fluctuate in intensity. Associated features may include a cranial neuropathy in about one-third. Low-grade encephalopathy is present in up to one-half, with mild memory concentration deficits, mood changes, and sleep disturbance.

MENINGOENCEPHALOMYELITIS

Rarely, focal parenchymal CNS lesions occur. The MRI may show punctate white matter lesions best seen on T2-weighted images; larger lesions occur infrequently. One brain biopsy showed increased numbers of microglia cells, rare spirochetes, and minimal inflammation. Transverse myelitis, movement disorders (extrapyramidal cerebellar, chorea and myoclonus), and hemiparesis can occur.

PSYCHIATRIC DISORDERS

Psychosis, mood swings (mild or bipolar), profound personality changes, depression, anorexia nervosa, obsessive-compulsive disorder, and panic attacks may occur. CSF may be normal.

SUBACUTE ENCEPHALOPATHY (SAE)

The most common chronic CNS manifestation is a SAE, characterized by memory problems and depression. Many patients (or their families) will complain of their excessive daytime sleepiness and extreme irritability. These patients generally come to the office disorganized (despite a supreme effort to be organized), unable to give a coherent history. They will bring copious notes, which are invariably in the wrong order. Most patients will complain of fatigue, and about one-half have headaches. Coincident polyneuropathy is very common with spinal or radicular pain, or distal paresthesias. Quantifiable deficits in memory, learning and retrieval, attention and concentration, perceptual-motor skills, and problem solving are common. MMPI testing generally shows a stable psychological pattern without significant psychopathology, similar to other medically ill patients.

ADDITIONAL CNS TESTING:
NEGATIVE TEST RESULTS DO NOT RULE OUT THE DIAGNOSIS OF NEUROBORRELIOSIS

Confirmation by CSF CULTURE is seldom practical because the organism is very fastidious, present in small numbers, takes a long time to grow out, and may undergo changes to forms which cannot be cultured easily.

CSF ANTIBODY TITERS may be present but are inconsistent and therefore their absence does not rule out CNS infection. The MRI is seldom abnormal and the findings, when present, are not specific for Lyme.

CSF PCR (test for spirochetal DNA) is a useful tool, but at present, because the capture of DNA is inconsistent, a few questions still need to be addressed.

OLIGLOCLONAL BANDS AND IGG INDEX — Looking for evidence of an intrathecal immune response may be helpful, but it is not specific. As a rule, oligoclonal bands and an elevated IgG index are not present in North American Lyme disease and their presence should suggest other diseases.

THE PERIPHERAL NERVOUS SYSTEM

Cranial neuropathy, painful radiculitis, distal neuropathy, and plexopathy are seen and generally reflect different clinical presentations of mononeuritis multiplex (polyneuropathy). Bell’s Palsy occurs in almost 11% of all Lyme patients and is bilateral in up to 1/3. Therefore, a bilateral Bell’s Palsy is very suspicious for Lyme in an endemic area. Painful radiculitis or cranial neuropathy can be seen with meningitis but also with normal CSF due to axonal neuropathy. Myositis may occur with Lyme as well as polymyalgia rheumatica. Symptoms of chronic involvement of the peripheral nervous system in a series of patients with chronic neurologic manifestations of Lyme disease developed a median of 16 months after the onset of infection, while CNS involvement began a median of 26 months after the onset of disease.

PERIPHERAL NERVOUS SYSTEM TESTING

Electrophysiological testing may show evidence of a mild peripheral neuropathy. Axonal degeneration and perivascular inflammatory infiltrates are noted on pathological specimens.

CHRONIC NEUROBORRELIOSIS

THE MOST COMMON PRESENTATION IS SAE, POLYNEUROPATHY, AND ARTHRITIS

Most typically, patients present with SAE, most often combined with polyneuropathy. Brief episodes of arthritis, primarily involving the knees, generally predate the symptoms and may persist after onset of neurological abnormalities. The TRIAD OF SAE, POLYNEUROPATHY, AND ARTHRITIS IS HIGHLY SUSPICIOUS FOR NEUROBORRELIOSIS.

Since serologies may be contradictory or negative, the physician will have to settle for treating if clinical suspicion is strong enough and assess whether the patient has “possible” or “probable” neuroborreliosis. Vigilant attempts to rule out other disorders should be undertaken. Screening should be done for collagen vascular disease, other infections, cancer, metabolic or endocrinological disturbances, etc. when a definite diagnosis cannot be made.

II.   CURRENT MEDICAL MYTHOLOGY

“YOU HAVE FIBROMYALGIA. YOU MIGHT HAVE HAD LYME DISEASE IN THE FIRST PLACE, AND EVEN IF YOU DID, YOU WERE GIVEN ENOUGH ANTIBIOTICS. RETREATMENT WILL NOT HELP.”

PERSISTENT INFECTION VERSUS POST-LYME SYNDROME

Many patients are sent home with antidepressants, muscle relaxers, but no antibiotics from doctors’ offices because they have symptoms of fibromyalgia. Pictures similar, or identical, to fibromyalgia may be part of the constellation of symptoms of Lyme; it may occur more rarely as an isolated symptom, or surface after what would otherwise be considered successful treatment.

Symptoms of fibromyalgia due to Lyme disease have not been cured with short-term oral or intravenous antibiotics, so some argue fibromyalgia is not due to active infection. I would question whether those particular antibiotic regimens were adequate to eliminate the infection, rather than assume the patient has developed “Post-Lyme Syndrome” (some yet to be defined immunologically triggered disorder).

THE SCOPE OF THE PROBLEM

Bujak et al. evaluated patients a mean of almost five years after treatment. 15% of these patients had symptoms of fatigue and arthralgia. Almost one-half met criteria for fibromyalgia or chronic fatigue syndrome. Fibromyalgia is thought to be a variant of the chronic fatigue syndrome. Of note, nearly all patients continued to complain of memory loss or concentration difficulties. One quarter had objective evidence of cognitive impairment, and 15% manifested depression.

SYMPTOMS OF FIBROMYALGIA AND CHRONIC FATIGUE SYNDROME IN LYME DISEASE MAY BE ATTENUATED FORMS OR CHRONIC MANIFESTATIONS OF THE FLU-LIKE SYMPTOMS ASSOCIATED WITH EARLY DISSEMINATION

All physicians experienced with treating Lyme disease have had patients who present with a recurrence of flu-like symptoms, months to years after they have completed the usual antibiotic course of therapy, oral or intravenous, and re-exposure had not occurred. These patients describe their flu-like symptoms as identical to their early-disseminated stage of Lyme disease. The flu-like symptoms may reoccur following what appears to be a trivial stressor, such as an uncomplicated viral URI. Patients may be able to “contain” their symptoms without specific antimicrobial therapy, but many will have to resume antibiotics. These patients complain of having to go to bed due to excessive fatigue or hypersomnolence. They cannot think straight, their muscles and joints ache, and they may have a low-grade fever. Do these symptoms sound like a “fibromyalgia-like syndrome” or “acute fatigue syndrome?” Prior medical experience suggests reactivation of infection. Despite what may appear to have been a previous “cure,” relapse of symptoms in this context would appear to be due to failure to eradicate the infection and with reactivation after a period of dormancy. Reoccurrence of symptoms due to immunologically triggered disease, INDEPENDENT of persistent infection seems unlikely. In reality, DISTINCTIONS BETWEEN FLU-LIKE SYNDROME, FIBROMYALGIA, AND CHRONIC FATIGUE BLUR. It seems more logical to postulate that fibromyalgia and chronic fatigue syndrome, when seen with Lyme disease, may be attenuated forms of chronic manifestations of earlier flu-like symptoms associated with early dissemination.

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