Post Prepared by Dr. Mohammed Nasir Yousuf Shah,
PGY-3 Internal Medicine, Monmouth Medical Center
A 36 year old otherwise healthy male noticed a facial droop when he woke up one morning and looked in the mirror. There was associated pain at the angle of the right jaw like a “toothache” and also numbness to along right side of tongue.
He had been experiencing occipital headache with neck pain for the previous 3 days. The headache was throbbing in character, worse when laying his head back on a pillow. He denied any other neurological symptoms.
Further questioning revealed that 2 months ago he suffered 2 tick bites on his thigh; but did not experience any fever, chills or rash at that time.
Physical examination showed prominent facial droop in the lower half of the right side of the face with inability to puff the cheek on the right and some mild weakness in the upper half of the right side of the face with reduced wrinkling of the forehead. He also had impaired taste sensation along the right side of the tongue. The rest of the neurological exam was normal.
His brain imaging study was normal, but CSF analysis revealed low glucose and elevated protein and pleocytosis with increased lymphocytes indicating a diagnosis of aseptic meningitis.
Given the history of tick bite 2 months prior and the characteristic 7th cranial nerve palsy, a presumptive diagnosis of neurological Lyme disease was made and the patient was started on intravenous ceftriaxone.
Meanwhile Lyme serologies and antibodies to B. Burgdorferi in CSF were tested and the patient was discharged on IV ceftriaxone.
The results of the serological and CSF testing returned positive for Lyme disease a few days later.
Borrelia burgdorferi is the organism responsible for Lyme disease which affects several organ systems and is transmitted by the bite of infected ticks belonging to the genus Ixodes.
Skin, the site of inoculation, is involved in 80 percent or more of infected individuals followed by joint involvement.
The third most common site is the nervous system, which is involved in 10 to 15 percent.
Nervous system involvement begins during early disseminated Lyme disease, when spread of the spirochetes can result in meningeal seeding. Acute neurologic involvement usually occurs weeks to several months after the tick bite and may be the first manifestation of Lyme disease. In contrast, certain neurologic problems, such as a more indolent, disseminated polyneuropathy, may develop months to a few years after the initial infection.
Lymphocytic meningitis, cranial neuropathy and radiculoneuritis constitute the classic triad of acute, early neurologic Lyme disease.
Clinical findings of nervous system Lyme disease are divided into disorders of the peripheral vs. central nervous system.
Peripheral nervous system
In early disease, two peripheral nerve manifestations are particularly common and form part of the classic triad.
Cranial neuropathies: These tend to occur early in infection and are usually abrupt in onset. Virtually any cranial nerve can be involved, but the seventh (facial) is by far the most common, occurring in 8 percent of cases.
Since facial nerve palsy is uncommon in young children, Lyme disease should be strongly considered as the cause of facial nerve palsy affecting a child who has been in an endemic area. In adults in endemic areas, during spring through fall, a significant percentage of facial nerve palsies are attributable to Lyme disease. Involvement can be bilateral and because bilateral facial nerve palsies are generally uncommon, Lyme disease should be suspected in patients with potential recent exposure.
Radiculoneuritis: This is reported in 3 percent of cases of Lyme disease and is often missed. It can mimic a mechanical radiculopathy (eg, sciatica) with radicular pain in one or several dermatomes, accompanied by corresponding sensory, motor and reflex changes. This disorder should be considered in patients in endemic areas presenting in spring through autumn with severe limb or truncal radicular pain without an apparent mechanical precipitant.
Central nervous system
The most common form of CNS involvement is lymphocytic meningitis. Rarely, inflammation of the brain and/or spinal cord parenchyma (an encephalomyelitis) can occur.
Meningitis: Lymphocytic meningitis, alone or in combination with cranial nerve or spinal nerve root involvement, represents the most common form of central nervous system involvement. Clinically it is indistinguishable from viral meningitis, with headache, fever, other systemic symptoms, photosensitivity, and neck stiffness.
Encephalopathy: Patients may experience fatigue, cognitive slowing, and memory difficulty. However, these symptoms are nonspecific and are frequent concomitants of many inflammatory disorders.
The diagnosis of nervous system Lyme disease rests on three elements:
- Since the disease is transmitted exclusively by bites of Ixodes ticks, there must be the possibility of exposure
- The clinical disorder should include objective evidence of nervous system Lyme disease
- Laboratory testing (positive two tier Lyme serologies with or without positive CSF Lyme antibodies)
Serologic testing: With the exception of the first 4 to 6 weeks of infection, when the specific immune response may not yet have developed sufficiently to provide a measurable antibody response, serologic testing for antibodies to B. burgdorferi is highly sensitive and specific for the diagnosis of Lyme disease and thus in such cases the absence of detectable antibodies in the serum is strong evidence against the diagnosis.
The two-tier strategy, which is recommended by the US Centers for Disease Control and Prevention, uses a sensitive enzyme-linked immunosorbent assay (ELISA) followed by a Western blot. If the ELISA is positive or equivocal, then the same serum sample should be tested by Western blot. If the ELISA is negative, the sample needs no further testing.
CSF analysis: In Lyme meningitis the CSF typically has a modest pleocytosis of up to several hundred lymphocytes and/or monocytes per microL. The CSF protein concentration is usually moderately elevated, and is typically no greater than about 200 to 300 mg/dL (2 to 3 g/L).
CSF antibodies: The sensitivity for testing the CSF for intrathecal production of antibodies to B. burgdorferi is poor and a negative test does not exclude CNS Lyme disease if clinical circumstances support the diagnosis.
Imaging: Since Lyme encephalomyelitis is so rare, MRI of the brain and spine is only rarely abnormal in Lyme disease. When present, the MRI reveals areas of increased signal on T2 and FLAIR sequences.
Electrophysiologic testing: In patients with a peripheral neuropathy, electrophysiologic assessment (electromyography and nerve conduction studies) can be helpful and typically reveal findings consistent with a patchy axonal polyneuropathy (ie, a mononeuropathy multiplex).
Approach to diagnostic testing
Assessment of the patient with possible nervous system Lyme disease must be tailored to the specific presentation. It can be sufficient to simply administer oral antibiotics to patients with recent exposure, a positive serology and an appropriate clinical syndrome. However a lumbar puncture may still be necessary if there is a strong clinical suspicion of meningitis, primarily to exclude other, potentially more dangerous pathogens.
CSF studies should include cell count, protein and glucose concentrations, and gram stain and bacterial cultures.
CSF and serum should both be sent for anti-B. burgdorferi antibodies and VDRL should be measured.
Neuroimaging, preferably by MRI, should precede the lumbar puncture if the patient has clinical evidence of parenchymal brain involvement. Depending on the findings on imaging,
Lyme meningitis is generally self-limited, even without treatment.
Oral doxycycline is effective for early disseminated Lyme disease with neurologic manifestations, including meningitis. Doxycycline has moderately good penetration into the CSF and has oral bioavailability >98 percent, making oral dosing equivalent to intravenous dosing.
Lyme patients with isolated facial nerve palsy are treated with oral doxycycline (100 mg orally twice daily). Antibiotic therapy does not have a major impact on the outcome of facial palsy. However, treatment is recommended to prevent other complications of disseminated Lyme disease. The majority of patients with Lyme facial palsy recover. The prognosis is worse for patients with bilateral facial palsy compared with unilateral palsy.
Lyme patients with radiculoneuritis, meningitis or other neurologic complications are typically treated using parenteral therapy with ceftriaxone (2 g intravenously once daily) for at least 14 days.
There are no diagnostic tests that can determine clearance of infection or predict the success of therapy. Resolution of neurological symptoms is often delayed and persistence of symptoms is not necessarily indicative of treatment failure.
Treatment recommendations are the same for both the early and late neurologic manifestations of Lyme disease.