Lyme disease may affect the brain in many ways, the most common of which is a disturbance in thinking (cognition). Other symptoms that occur frequently include headache, mood swings, irritability, depression, and marked fatigue. This section will describe some of the typical and less typical features of neuropsychiatric Lyme disease in adults.

Lyme Disease is transmitted by an Ixodes tick infected with Borrelia burgdorferi.

Borrelia burgdorferi		Ixodes Scapularis Tick

The spirochete which causes Lyme disease (Borrelia burgdorferi) can invade the central nervous system within days to a week of initial skin infection, as a result of dissemination through the blood stream. The majority of patients who are treated early with antibiotics do well and incur no long term problems. Patients who are not treated until later in the illness may have a more complicated course.

While the symptoms often seen among patients with neuropsychiatric Lyme Disease are not specific to Lyme Disease and can also be found in other disorders, knowing the typical clusters of symptoms can be helpful when considering Lyme Disease as a possible diagnosis. The more multi-systemic the symptom presentation and the more clinical features observed in a patient from the list below, the more strongly Lyme disease should be considered. Other diagnostic possibilities need to be considered in the differential diagnosis, such as mood or anxiety disorders, collagen vascular or autoimmune diseases, spinal cord compression, multiple sclerosis, metastatic diseases, endocrinological disorders, fibromyalgia, chronic fatigue syndrome, and residual damage from past brain trauma or toxin exposure.

A few points should be emphasized regarding late neuropsychiatric Lyme Disease. First, although arthritis is helpful in the diagnosis of Lyme disease, the majority of patients with cognitive troubles due to Lyme disease (Lyme Encephalopathy) do not have joint problems at the time their cognitive symptoms become manifest. This is not widely recognized among physicians, although it is well documented in the medical literature. Second, the bedside neurologic exam does not usually disclose neurologic findings and standard office-based cognitive screening tests may not detect cognitive impairment. To detect thinking problems, the more sensitive tool of comprehensive neuropsychological testing conducted by a neuropsychologist is needed. Third, lumbar puncture while important in the differential diagnosis should not be used to exclude neurologic Lyme disease, as roughly 20-40% of patients with confirmed neurologic Lyme Disease may test negative on routine CSF assays.

Among patients who develop chronic cognitive problems, the typical time course for the manifestation of Lyme symptoms is as follows:

• Very early: Erythema migrans (a red, round, expanding rash)
• 1-2 months after infection: cardiac or early neurologic involvement (meningitis, encephalitis, cranial neuropathies) with mild to marked neuropsychiatric symptoms 
• 6-10 months after infection: arthritis of multiple joints 
• 2-8 years after infection: chronic cognitive problems 

• Fatigue: this ranges from mild to severe, resulting at times in a need for prolonged sleep at night and additional naps during the day, much akin to chronic fatigue syndrome. 
• Low grade fevers 
• Night sweats 
• Migrating arthralgias (joint pains) or arthritis (joint inflammation or swelling) 
• Muscle pains 
• Sleep disturbance 
• Frequent and severe headaches 
• Cranial nerve disturbance. While facial nerve palsy or optic neuritis are not frequently seen, patients may more commonly report facial numbness and/or tingling. 




• Sharp, stabbing, deep/boring, burning, or lancinating (shooting) pains 
• Multifocal numbness or tingling in hands or feet (signs of peripheral neuropathy) 
• Thinking Problems: may include problems in attention, memory, verbal fluency, thinking speed. Patients may report problems with concentration or the need to rely on lists or others because of new memory problems. For more details about typical cognitive deficits, please see cognitive aspects in adults. 
• Cognitive overload: Some patients experience normal environmental stimulation as being excessive, resulting in a cognitive "short-circuiting" such that the patient may start to feel confused, lose focus, stutter, or panic. It is as if the normal filtering mechanism of the brain has been rendered ineffective, leaving the patient vulnerable to a confusing array of numerous stimuli. 
• Brain fog: Patients with Lyme disease often use this term to describe the lack of clarity in their cognitive processes. At times, this seems similar to "depersonalization or derealization" in which a person's sense of self and place are altered. 
• Sensory Hyperacuities: some patients experience a heightened sensitivity to sound or to light, particularly in the early phases of neurologic Lyme Disease. In the more severe cases, patients need to wear sunglasses indoors or earplugs to diminish sensory stimulation. 
• Spatial or Geographic Orientation problems: For example, patients may bump into the door jambs; go to place an object on a table only to see it fall to the floor due to a misjudgement of spatial distance; get lost in a familiar place. 
• Problems with Speech & Fluency: stuttering, reversing words (e.g., stating "tomorrow" when one means "yesterday") 
• Less common neurologic syndromes: partial complex seizures, multiple-sclerosis like illness, dementia-like illness, Guillain-Barre syndrome, strokes, Tullio phenomenon. 
• Psychiatric symptoms in Adults: irritability, poor frustration tolerance and mood swings are common. Less commonly: panic, obsessive/compulsive behaviors, or other anxiety states. Rarely: mania, paranoia (these usually occur among patients with encephalitis). 
• Neuropsychiatric Problems in Children: headaches, disturbances of behavior or mood, fatigue (falling asleep in class), problems with auditory and visual attention (with some children mistakenly being diagnosed as having attention deficit disorder) 
• Fluctuating Symptoms: worse on some days, remarkably better on others, without clear cause. 

Cognitive Aspects in Adults:

• Attention Problems: Easy distractibility; difficulty handling multiple tasks at the same time; trouble sustaining attention on tasks and completing tasks; trouble following the course of conversations or the text of a book. 
• Memory Problems: Retrieval difficulties are common in which patients may have a hard time recalling what they know; patients may forget conversations or children may forget that they've done homework assignments. At other times, patients experience a problem with the "working memory": as if the material can't be kept on board long enough. Patients may find themselves keeping multiple lists, but then they lose track of where they put their lists. 
• Slower Processing Speed: Patients may find it takes them longer to respond to questions or to complete tasks. Reaction time and thinking feel sluggish. 
• Verbal Fluency problems: the ability to engage in normal conversations is impaired by the inability to retrieve the right word for the moment or the ability to "name" well-known people or objects. Patients may experience word substitutions or "paraphasias". A patient trying to refer to a "microwave" might, for example, say "radiator". Or, trying to refer to "Amazon.com" the patient might say, "AOL". Or, trying to refer to "fireworks", the patient might say "skylights". Patients may also experience an impairment in speech production, such that they stutter, particularly at times of sensory overload. 

Irritability and moodiness are common. These tend to be most severe in neurologic Lyme disease before treatment, during the first few days or weeks of treatment, and during resurgences or relapses of active Lyme Disease. Antibiotic therapy can be very helpful at these times. Symptoms that persist despite appropriate antibiotic therapy should be treated with psychiatric medications. It is very important for patients to take advantage of all opportunities for therapeutic benefit. These include consultation with a psychiatrist for both medication and therapy. Psychotherapy with a psychiatrist, psychologist, or social worker can be very helpful to help the individual cope with the effects of a serious illness. Family and couples therapy can also be vitally important, particularly when family members are confused by the changed behavior or personality of the patient. Psychiatric medication can be very helpful to combat mood and sleep disturbances, to enhance attention, to decrease central nervous system hyperacuities, to decrease excessive worry and fear, and to contribute to overall good health by countering the negative impact of neuropsychiatric disorders on the immune system.

• Mood Lability: spontaneous swings of mood; spontaneous tearfulness. At times, patients with these symptoms may appear to have a Bipolar II disorder. 
• Irritability: an inability to tolerate normal frustrations, with quick bursts of anger. Patients may seem to have undergone a personality change in that previously mild-mannered individuals may now become quite difficult. 
• Panic attacks: tachycardia, flushing, chest pain, , numbness and tingling, shortness of breath, choking feeling with the sensation of loss of control and/or of fear of death. Needs to be distinguished from tachyarrhythmias. Panic attacks unrelated to Lyme disease are usually 10-20 minutes in duration. Lyme-related panic attacks may last for an hour or more. 
• Less commonly: manic or psychotic episodes (during encephalitic phase), paranoia, tics, obsessive/compulsive symptoms (may trigger a milder pre- existing condition or bring on symptoms de novo) 

As noted among adults, when Lyme Disease is treated early in children, few children develop long term problems. When Lyme Disease is not treated until later in the course of the illness, the clinical manifestations may be more neuropsychiatric and the response to treatment less robust. In a large series of children with Lyme disease referred to a pediatric neurologist (Belman et al), headaches were the most commonly reported symptom. The second most common symptom were disturbances of behavior and mood. MRI abnormalities may be seen in some children following Lyme infection, located predominantly in the deep white matter, which is consistent with reports of MRI lesions seen in adults with neuroborreliosis. These findings are similar to the MRI findings of children with parainfectious or postinfectious acute disseminated encephalomyelitis. Children in particular may appear to have "pseudo-tumor cerebri" because of an elevated opening pressure at lumbar puncture. Complex partial seizures may also occur more commonly among children with neurologic Lyme Disease than among adults. Like adults, these children may appear to have chronic fatigue syndrome due to an extraordinary capacity for prolonged sleep at night and need for naps during the day.

Cognitive. In a study by Adams et al, children with relatively early manifestations of Lyme Disease appropriately treated with antibiotics were found to have an excellent prognosis for short-term and long-term (4 years) unimpaired cognitive functioning. In contrast, a study by Bloom et al reported on an evaluation of 86 children for possible late manifestations of lyme disease, 12 of whom had neurocognitive symptoms thought to be related to Lyme infection. Of these 12, 5 had past or present B. burgdorferi infection in serum and CSF and had developed neurocognitive symptoms either at the time of onset of Lyme infection or months after classic manifestations of the disease. The most prevalent neurocognitive symptoms were behavioral changes, forgetfulness, declining school performance, headache and fatigue. Two of these children had developed complex partial seizures. A comprehensive neuropsychological battery revealed that these children had normal intellectual functioning, but particular deficits related to auditory or visual sequential processing. These deficits, as well as many other symptoms, gradually improved following ceftriaxone therapy, although two of the children continued to have auditory sequential processing deficits.

A controlled study by Dr. Tager at our Lyme Disease Research Program, reported at the 1999 VIII International Lyme Disease Conference in Munich Germany, revealed that chronic Lyme Disease in children may be accompanied by cognitive and psychiatric disturbances, resulting in significant impairment in psychosocial and academic functioning. The most prominent cognitive problems involved the domains of attention and learning specifically related to perceptual/organizational abilities, visual scanning, and sequential tracking.

Psychiatric.Two studies from different institutions found that children with Lyme Disease may develop late problems with visual and auditory attention. These children may be mistakenly diagnosed as having primary attention deficit disorder as opposed to attentional deficits secondary to a systemic infection. Other findings in children include new onset phobias (e.g., fear of the dark, separation anxiety), depression, listlessness and irritability, oppositional behavior, obsessive-compulsive behaviors, and/or Tourettes Disorder.