An Overview of Lyme Neuroborreliosis

Lyme neuroborreliosis (LNB), also known as neurological Lyme disease or simply neuroborreliosis, is a secondary symptom of Lyme disease involving the central nervous system. LNB is usually preceded by the classic symptoms of Lyme disease, after which the spread of the Borrelia bacterium throughout the body triggers neurological effects in some.

Among the most common symptoms of LNB are nerve pain, numbness, double vision, and facial palsy. It is not unusual for LNB symptoms to persist for weeks or even months.

LNB can be diagnosed with blood tests able to detect the Borrelia bacterium, followed by a differential diagnosis to exclude all other possible causes. Intravenous antibiotics are typically prescribed for 14–28 days to resolve the bacterial infection.

Symptoms

As with Lyme disease itself, the signs and symptoms of Lyme neuroborreliosis are often nonspecific and easily mistaken for other medical conditions.

Within days or weeks of the onset of the early infection, between 10% and 15% of untreated people will develop signs of LNB. These typically manifest within four to six weeks of the initial bite and can lead to an array of neurological symptoms, broadly described by four inflammatory conditions, which are:

• Lymphocytic meningitis is a form of meningitis caused when the Borrelia bacterium spreads (disseminates) through the lymphatic system. As the bacterium infiltrates the central nervous system, it can cause swelling of the membrane surrounding the brain and spinal cord (called the meninges) and lead to classic meningitis symptoms, including a stiff neck and extreme sensitivity to light. In children, lymphocytic meningitis can sometimes cause partial vision loss.
• Cranial neuritis is the inflammation of the cranial nerves that originate in the brain stem and are involved in everything from smell, hearing, taste, vision, and balance to facial expression, head turning, and tongue movement. With LNB, cranial neuritis most typically causes facial palsy (known as Bell's palsy), along with impaired blinking, smiling, and chewing on one or both sides of the face. Intermittent double vision (diplopia) is also possible.
• Radiculopathy is the inflammation of the spinal nerve roots that transmit signals from the brain to the peripheral nerves of the limbs and trunk. With LNB, radiculopathy can cause numbness, muscle weakness, and prickly, tingling, or burning sensations (paresthesia). Pain is a central feature of Lyme radiculopathy, often described as excruciating and migrating. The radicular pain is rarely symmetrical and tends to get worse at night, causing sleep disturbance. Most of the pain will be centralized near the site of the tick bite and, in some cases, serves as an early warning sign of Bell's palsy.
• Mononeuritis multiplex involves the inflammation of the peripheral nerves. This can result in extreme weakness, numbness, and pain, known as peripheral neuropathy, usually in the hands and feet. Mononeuritis multiplex may also cause a deep, aching pain in the lower back, hip, or leg, which can get worse at night.

Less commonly, LNB can cause inflammation of the brain (encephalitis) and spinal cord (myelitis). If this occurs, the symptoms will typically be more pronounced and may include confusion, tremors, impaired speech, abnormal gait (how you walk), and rapid, involuntary movements (ataxia) of the eye.

Although the acute symptoms of LNB will typically normalize over time, extreme cases—particularly those left untreated—can lead to permanent motor or sensory impairment, most often involving the lower limbs.

Causes

Lyme disease is a tick-borne infection involving the Borrelia bacterium. In the United States, the Ixodes scapularis tick (also known as the deer tick, black-legged tick, or bear tick) is the type commonly associated with Lyme disease.

There are different types of Borrelia bacterium prevalent in certain parts of the world. In North America, Borrelia burgorferi and Borrelia mayonii are the predominant types. In Europe and Asia, Borrelia afzelii and Borrelia garinii predominate. Of these genetic variations, LNB occurs most commonly with Borrelia garinii infections both in children and adults.

After transmission has occurred, bacteria will begin to migrate through the body via the bloodstream or lymphatic system. Of the two, the lymphatic system provides Borrelia with easy access to the central nervous system, allowing the bacterial particles to cross the blood-brain barrier and infiltrate cerebrospinal fluid (CSF). The invasion of CSF by Borrelia triggers an inflammatory response in the central nervous system, manifesting with the characteristic symptoms of LNB.

In North America, facial palsy accompanied by lymphocytic meningitis is the most common presentation of LNB. In Europe, a condition called Bannwarth syndrome, involving a combination of lymphocytic meningitis and radiculopathy, is seen in 36%–90% of people with Lyme disease.

LNB cases tend to occur seasonally between June and December (roughly two months after the start and end of tick season, which runs from April to October). It is less commonly seen in winter and early spring.

Diagnosis

Lyme neuroborreliosis usually is diagnosed with a combination of a physical exam and blood tests. Lyme disease cannot be diagnosed based on symptoms alone but instead requires serological tests that can detect Borrelia antibodies in the blood.

The diagnostic difficulty is due in part to Borrelia's ability to evade immune detection by "hiding" itself in the structural matrix of tissues and cells. At the same time, Borrelia secretes a protein that suppresses the production of antibodies that the body uses to target an immune attack.

Because of this, Borrelia can be difficult to detect with antibody-based tests, especially in the early stages of infection. During the so-called window period (from exposure to the appearance of symptoms), the sensitivity (the ability to designate an individual as positive) the sensitivity of current tests hovers only around 30%–40%.

Even with LNB, during which the dissemination of Borrelia is more widespread, the sensitivity of the tests can still fall short, ranging from as low as 54% to as high as 97%.

The serological testing of Lyme disease involves two steps:

1. A test called an enzyme-linked immunoassay (EIA) is used to screen for Borrelia antibodies in a sample of blood.
2. If antibodies are detected, a more sensitive Western blot test would be used to confirm the diagnosis. This test requires greater technical skill and is therefore only used if a positive EIA is returned.

The EIA and Western blot can also be performed on cerebrospinal fluid.

On the other hand, an early negative result does not rule out Lyme disease. In such cases, a follow-up test should be performed in three to four weeks, by which time enough antibodies will have been produced to elicit an accurate result.

Differential Diagnosis

When testing for Lyme disease, the doctor will need to consider multiple factors to ensure that the correct diagnosis is achieved. The most crucial of these is the exposure history. Around 90% of cases involve travel to—or residency in—a region where Lyme disease is common. The seasonality of the symptoms should also be considered.

To avoid misdiagnoses, doctors may order additional tests to exclude other possible causes. Referred to as a differential diagnosis, the tests will screen for diseases that mimic LNB, such as:

• Alcoholic neuropathy
• Alzheimer's disease
• Aseptic meningitis
• Brain tumor
• Chronic fatigue syndrome
• Diabetic neuropathy
• Disc herniation
• Fibromyalgia
• Guillain-Barre syndrome
• HIV
• Lupus
• Multiple sclerosis
• Neurosyphilis
• Post-herpetic neuralgia
• Sarcoidosis
• Tangier's disease
• Transient ischemic attack (TIA)

Treatment

Lyme neuroborreliosis is treated with intravenous antibiotics such as penicillins, ceftriaxone, and cefotaxime. By delivering the antibiotics into a vein with a drip, the drug can better penetrate the blood-brain barrier that isolates the brain from the rest of the circulatory system.

Generally speaking, the course of therapy is 14 days for early-stage LNB and 14–21 days for later-stage LNB. Depending on the antibiotic used, the drug may be prescribed in three to four daily doses. Dosages in children are based on weight and usually prescribed as a daily dose.

Most of the current evidence suggests that longer courses of treatment yield no better results. There also appears to be no significant difference in the effectiveness of the recommended antibiotics (although drug allergy may exclude certain agents).

Post-Treatment Lyme Disease Syndrome

Even after the completion of therapy, as many as 10% of people with Lyme disease will experience persistent symptoms, referred to a post-treatment Lyme disease syndrome (PTLDS). While the reasons for this are unclear, some scientists believe that certain antibiotic-resistant Borrelia strains are able to elude detection and persist despite treatment.

In people with LNB, general symptoms of Lyme disease (such as fatigue and joint pain) are more common during PTLDS than neurologic ones.

In people with PTLDS, a combination of antibiotics may be prescribed, the most effective of which may include doxycycline and antibiotics Cefobid (cefoperazone) and Cubicin RF (daptomycin).

Prevention

As a general rule, Lyme neuroborreliosis can be avoided by seeking treatment during the early stages of Lyme disease. By treating the infection before the bacteria can disseminate, you will be better able to avoid the inflammatory effects of the disease on the central and peripheral nervous systems.

You can also take steps to prevent Lyme disease—and, in turn, LNB—by reducing your exposure to disease-carrying ticks. Among the things you can do:

• Avoid tick-infested areas: This is especially true during the warm spring and summer months when ticks are actively breeding.
• Dress appropriately: If you are in a tick-infested region, keep yourself well-covered with long pants, long socks, and long sleeves. For added protection, tuck your shirt into your pants and the cuffs of your pants into your socks.
• Use tick repellent: Choose a brand that contains a 20%–50% concentration of DEET (N-diethyl-meta-toluamide).
• Apply pesticides around your home: If you live in areas where deer are common, a single application of a tick-killing pesticide (called an acaricide) in the early spring can keep your home safe for the entire tick season.
• Check for ticks after being outdoors: Even if you do find a tick on you, removing it within the first 12–24 hours may avert an infection. After returning home, remove and check all of your clothing and examine your body from head to toe, especially moist areas, such as the armpits, back of the knees, scalp, groin, buttocks, waist, and nape of the neck.