A Review of Items in the Interview

        To review each item in sequence, refer to the flow sheet. Some of these times are self-explanatory whereas other require clarification. Recurrent erythema migrans rash is sometimes seen in the chronic Lyme population and has diagnostic significance. On rare occasions, chicken pox and other conditions can bring out the bull’s eye rash. For example, patients with a chronic Lyme infection who become infected with chickenpox sometimes show the bull’s eye rash around the chickenpox lesions.

        The cognitive symptoms are particularly noteworthy when NPLD is suspected. When we attempt to correlate SPECT or PET findings with areas of deficit which are demonstrated in a clinical exam, cognitive deficits are easier to localize than emotional one. Many of these patients give a history of an acquired attention deficit disorder. Auditory hyperacusis is particularly noteworthy.

        Memory deficits are more selective for working memory, short-term memory, slowness of retrieval, and sequential memory (2). Long-term memory for information prior to the onset of the encelopathy is usually relatively preserved until very last in the course of the illness. Memory encoding errors sometimes exist with the creating of some false memories, some of which occur during dissociative episodes. Working spatial memory can be impaired, i.e.: patients may have difficulty with the spatial awareness of where their front and back doors are in their house. One patient had a panic attack when they were lost in their garage and had lost the spatial awareness of the location of the door. The slowness of retrieval is evidenced as these patients grope to retrieve words and names. In the later stage of this disease they also have difficulty recalling motor sequences, (2,30) i.e., a recall of the sequential steps needed to tie their shoelaces. They are able to tie their shoelaces but must think out each sequential step. Many Lyme patients state "I feel like I have become dyslexic." Impairment of reading comprehension is an earlier sign with the later addition of auditory comprehension difficulties. Acquired left/right confusion is seen with some of these patients displaying what appears to be an acquired Gerstmann’s Syndrome or some variant of this syndrome. They have problems with calculations and often complain of errors when trying to calculate their checkbooks. Fluency of speech is a very significant problem. When interviewing these patients, this is a clearly evident symptom. Stuttering is seen in many of these patients, a finding which may correlate with left caudate/striatum involvement. Slurred speech is significant and can lead to the false impression that these patients are intoxicated which has, on occasion, led to motor vehicle charges. Handwriting declines and a comparison of writing samples can be useful to confirm this finding. Optic ataxia (41) is another important finding. Sometimes it can be bilateral or unilateral. This is an upper parietal function involving the contra-lateral side. When this symptom is present, patients have trouble targeting, and they may bump into doorways, place objects incorrectly, and have problems driving in congested traffic.

        Agnosia is a late appearing symptom. One patient was unable to recognize her own car in a parking lot. After receiving IV antibiotic treatment, she could recognize her car but was not able to recognize which key unlocked the car and which one started her car. Some of these patients display intrusive images which are more commonly of an aggressive nature but sometimes can be of a sexual or other nature. Occasionally these images are of a homicidal nature. The hallucinations are quite different from those commonly seen in schizophrenia. NPLD hallucinations are correlated with better reality testing.

        Executive function and thought process are severely impaired with Lyme patients. This is very significant in contributing to the disability, which is seen in these patients, especially those accustomed to doing five things at once in their usual professional capacities. A small impairment in a patient who assumes a high level of responsibility can result in severe consequences. Cognitive tracking deficits, commonly called brain fog is a symptom that most of these patients describe. It is very different from the concentration impairment seen in clinical depression. Brain fog is a slowness and sluggishness of internal thought. Patients describe this as though their thought processes are shrouded in a fog.

        The emotional and behavioral symptoms caused by Lyme disease are more complex to understand than the cognitive impairments. Let’s first review the physiology of emotion. The different emotional functions have a hierarchy of circuitry, which includes stimulatory pathways, opposing inhibitory pathways, and a hierarchy of modulation centers. The basic hierarchy is pre-frontal cortex, para limbic association areas, limbic structures, and brain stems - hypothalamus. Lyme encephalopathy can result in dysfunction of the modulation centers, inhibitory pathways, and stimulatory pathways. Autopsies, animal studies, and brain imaging tests have contributed to this understanding. The presenting symptoms of NPLD are sometimes emotional in nature, and include obsessive-compulsive disorder, depression, and aggression, panic disorder, and other phobic disorders.

        In considering the behavioral symptoms, these patients can become suddenly suicidal and there have been completed suicides attributed to Lyme disease. Homicidal ideation, urges, and behavior occur in some of these patients. Some adult patients describe struggling to not act on these urges. When these patients act on a homicidal urge, more commonly it is a child becoming assaultive to a sibling. Dissociative episodes sometimes occur with these patients occasionally accompanied with aggressive behavior and loss of memory.
Compensatory compulsions are common in an effort to compensate for the memory deficits. NPLD can imitate a number of common psychiatric syndromes. It can be difficult to differentiate Lyme disease from rapid cycling Bipolar illness or Posttraumatic Stress Disorder. Eating disorders are common. Invariably these patients either gain or lose weight. Sometimes massive weight gain is also seen.

        Neurological symptoms have been previously recognized as a component of Lyme disease (31-46). Cranial nerve findings begin before the cognitive changes are seen and can intensify again late in the course of the illness. There are times when the cranial nerve findings are more evident late in the day when the patient becomes tired and they acquire double vision, choke on food, or lose their ability to talk. Grand mal seizures are more significant with congenital Lyme cases, while complex partial seizures are seen in a notable percent of other NPLD patients. These seizures are effectively controlled with both anticonvulsants and antibiotics. Some neurological findings are common such as numbness, tingling, sensory loss, burning, weakness, tremors, myoclonic jerks. torticollis, and fainting. Ataxia is common in these patients who are often clumsy, which leads to frequent accidents. Myotonia is uncommon but I have been this in a few patients, and Parkinson’s syndrome caused by Lyme disease can also seen, although it is uncommon. A number of these patients have herniated discs after having Lyme disease for several years. I suspect, but cannot prove, there is a causal relationship between Lyme disease and herniated discs. Burning is quite specific to NPLD, but is also seen in herpes infections. The patient describes a sensation that a blowtorch is burning the skin. It can affect any part of the body. In some patients the burning migrates, while in others it remains in a given area. Both antibiotics and anticonvulsants relieve this symptom.

        Joint pain, swelling, and tightness is an earlier manifestation of Lyme disease and is often more effectively treated than the central nervous system symptoms. Knees are the joints most commonly involved (47). Bone pain as a result of periostitis affects certain bones, such as the tibias. The periostium is spongy on examination. Chronic fatigue and fibromyalgia may be seen as part of Lyme disease (48). Of course, these two syndromes can be caused by other conditions as well. Chondritis of the ear and nose and costochondritis are sometimes seen with these patients.

        The cardiac symptoms (49-57) are quite prominent early on in the disease although more commonly with alternating episodes of racing pulse and bradycardia. Conduction defects can be fatal in some cases. Other cardiac complications including cardiomyopathy can be a later manifestation of this disease. Irritable bladder is common. Chronic Lyme patients frequently acquire a number of autonomic nervous system problems which were not present prior to the onset of the disease. Alcohol intolerance is common and most patients state "I don’t drink any more." Some other physical manifestations are quite uncommon.

        The Jarish Herxheimer reaction is seen when antibiotics are having a therapeutic effect. There can be a worsening in the symptoms, which may include the periostitis, and the psychiatric and cognitive symptoms. Some patients become very impulsive, aggressive, depressed, and suicidal during a Herxheimer reaction and may require close monitoring during these times.

        Progression of symptoms is a significant item. After working with these patients, it is clear there are common patterns in which different symptoms appear in a different sequence. This item is checked when the symptoms are appearing in a sequence that is seen in the progression of Lyme disease, i.e.: it begins with a tick bite, then a bull’s eye rash associated with a flu like illness, then there may be some of the disseminated symptoms such as the joint pain. The cranial nerve symptoms may be seen. Later there is the development of the cognitive symptoms that gradually increase over time. Then the psychiatric symptoms develop later in the course of the illness with an intensification of the cognitive and neurological symptoms. Not every stage is seen in all patients. Although many similarities exist between patients, no two patients display the exact same symptoms; and there are many variants in the manner in which the disease presents. There is some evidence that different clusters of symptoms are associated with different strains of the bacteria, and there are many variants in the manner in which this disease presents.

        Although diagnosis is the major focus of this article, I would like to say a few words about the role of psychiatry in the treatment of Neuropsychiatric Lyme Disease. The effective treatment of psychiatric symptoms in these patients helps improve their overall prognosis and reduce their need for antibiotic treatment. Let’s review the physiology.

        In a state of stress, the body’s resources are allocated away from immune and regenerative functions towards stress related functions (58). If we reduce the symptoms related to the state of stress, the body will then allocate more resource towards immune and regenerative functions. Therefore, the treatment of sleep disorder, depression, anxiety, ADD, etc. associated with neuropsychiatric Lyme disease helps the patient recover. The treatment of sleep disorder is particularly significant. Chronic fatigue and fibromyalgia whether or not caused by Lyme disease are associated with a deficiency of slow wave sleep (62). Improvement of sleep quality, particularly slow wave sleep is strongly correlated with improvement of the chronic fatigue and fibromyalgia components of Lyme disease, which in turn benefits overall prognosis. In a milder case, this psychiatric treatment may lead to a total remission. In more severe cases this treatment merely buys time and gradually becomes less effective as the infection progresses, and the psychiatric symptoms become increasingly difficult to treat. When this trend exists, antibiotics and other treatments need to be combined with the psychiatric treatment. Some patients clearly need extended and repeated courses of antibiotic treatment (l, 59, 60). Although it is sometimes stated that most patients respond to conservative courses of antibiotic treatment, many of the patients I see have shown inadequate responses to such approaches and some have responded better to more aggressive, well-monitored antibiotic treatments. As with any treatment, the administration of antibiotics is an individualized risk verses benefit clinical decision. For effective treatment often intramuscular and intravenous antibiotics are needed, sometimes for extended period of time. It is well recognized such treatments have potential risks and a methodical risk vs. benefit assessment is needed. This decision should only be made by physicians who have assumed clinical responsibility, have personally examined the patient, and who have adequate knowledge of the illness and the therapeutic agents. Other treatments include nutritional approaches and physical therapy. Hyperbaric oxygen is a treatment that is showing increasing potential in the treatment of Lyme disease. It is currently speculated that many of the symptoms seen in chronic disease are attributable to an inflammatory process rather than active infection. Although it is clear some inflammatory symptoms exist (61), it is difficult to accept this belief to explain the majority of the progressive symptoms seen in these patients. The Jarish Herxheimer reaction appears to be inflammatory in nature and is of fairly brief duration after antibiotic treatment is discontinued. Many of the symptoms perceived as "inflammatory" improve in response to antibiotic treatment. The inflammatory view is not without risk when steroids are administered which can increase the progression of active infection.

        As with any other invisible disability, many of the chronic patients feel demoralized after being exposed to stigma and abuse from those who cannot understand or those who are biased for a variety of reasons. Neuropsychiatric Lyme disease patients are the recipients of double stigmas - that of Lyme disease as well as mental disorder. Some patients are contending with illness while also stating there is a lack of support from family, health care providers, employers, and/or insurance companies. When such conditions exist, the stress level is magnified and the progression of the illness tends to increase.

        We can also assist our patients by helping to understand the nature of this condition, resolving conflict, and offering input towards advocacy efforts. Lyme disease is an illness that has proven managed care to be a catastrophic failure. Early, effective treatment is critical. Managed care short-term cost containment techniques have resulted in very expensive long-term direct and indirect costs. Most of the indirect costs have been shifted to the general public.

        In summary, my experience with Neuropsychiatric Lyme Disease has led me to ask the question - How much of mental disorders are caused by a chronic infectious process? Nervous system tissue is of ectodermal embryological origin and has similarities to skin that are also of ectodermal origin. Herpes simplex lies dormant in skin for extended periods of time and becomes symptomatic during times of stress causing fever blisters.

        Might a similar process occur in the central nervous system with this or other infectious agents? Does an expending bull’s eye, erythema migrans process occur in the central nervous system as it does in skin? Why is this a benign disease in some people, while malignant in others?

        Microbes evolve faster than people. For this reason, infectious disease will always exist. Many poorly understood diseases were later found to have an infectious disease basis. Infectious agents are continually evolving. New organisms are being recognized, and old ones develop new capabilities. As we develop new therapeutic agents, microbes evolve defenses against this technology. We are seeing increasing problems with infectious disease in humans and animals. Why? Are we losing ground in the "arms war"? Is this due to increased exposure to otherwise remote part of the globe? Is it a natural cycle of infectious disease? Is it a result of a declining global environment? Has the irresponsible use of technology contributed to this problem? Why is Lyme disease more prevalent now? How much of what is called "Lyme disease" is some other infectious disease? Could some of these patients be infected with seronegative syphilis? What can we do to reduce the number of infected ticks in our environment?