Neurological Manifestations

NEUROLOGICAL MANIFESTATIONS OF LYME DISEASE IN CHILDREN

Dorothy M. Pietrucha, M.D., P.A.

Pediatric Neurology 3318 Route 33 Neptune, New Jersey 07753

INTRODUCTION

Lyme Disease is transmitted by an arthropod, the Ixodes dammini tick. The spirochete causing the disease is the Borrelia burgdorferi.

Over the past nine years, we have treated over three hundred children for Lyme Disease in the hospital because they had significant neurologic manifestations of Lyme Disease or, in the minority of cases, an arthritis necessitating hospitalization for intravenous antibiotics.

It is impossible to know how many children have Lyme Disease in our area. One pediatrician with a very large practice sees at least three ECM rashes a day and places the children on either Amoxicillin or penicillin for twenty-one days. Obviously, the majority of the children who are seen early on who manifest the rash do not go on to have chronic problems, but a small percentage do.

In some of our communities with populations of 20,000-25,000 people, as many as sixty percent of the ticks are carrying the Borrelia spirochete so the chance for an infection is very high.

Since 1982, I have seen a large number of children who have had neurologic symptoms due to Lyme Disease. Many of these children are not diagnosed initially because their complaints are vague and thought to be all functional. I have treated a patient who has been sick for five years. Others were sick three and four years before being diagnosed. Recently, we have become more concerned about children with, what are considered, vague symptoms and are becoming more aggressive in diagnosing and treating.

I have seen children develop neurologic symptoms within a few weeks after a tick bite. Others will not develop the symptoms for one year or more.

Less than fifty percent of the children even remember being bitten by a tick and even a smaller percentage than that remember any ECM rash.

The parents recall the children having a flu-like illness that preceded their developing these rather persistent symptoms and usually that flu-like illness will occur six weeks or more after the tick bite or the exposure to the ticks. Many parents claim that after this "flu-like illness," the child never was well again. The majority, over ninety percent, of the children that we have treated complain of headache. The headache, in a few cases, has been very acute accompanied by papilledema but in the majority of cases the headache comes on gradually, becomes quite persistent and does not respond to over-the-counter analgesics.

In addition to the headache, the children complain of photophobia, dizziness, a stiff neck, backache, somnolence and, those that are in school, have problems with memory and difficulty concentrating. Some patients have developed progressive weakness.

The parents complain that preschoolers develop mood swings and become very irritable and they see a personality change.

Among the children that are school-age and those who are in adolescence, chest pain is a very frequent complaint. At least seventy percent have complained of chest pain. About fifty percent have complained of abdominal pain. More than half the children have arthralgia usually involving the knee and sometimes the wrist.

Other complaints include palpitations, tingling, numbness, rashes that come and go, usually malar rashes, and sore throats that are excruciatingly painful.

It is easy to see how this long list can be very non-specific and many of these children are thought to have functional problems.

Children present with central or peripheral nervous system manifestations frequently. The central nervous system manifestations include an encephalopathy. These children have difficulty with memory, concentration and learning new material in school. They have an excessive amount of fatigue and have a wake-sleep disturbance, either becoming hypersomniac or insomniac.

Rarely, we have seen children present with an encephalitic picture.

There have been reports of individuals having stroke from Lyme. We have one child who presented with the sudden onset of a hemiplegia and aphasia.

Patients may have involvement of the optic nerve with an optic neuritis or a papillitis, resultant vision loss.

Peripheral neuropathy with distal parasthesias, subtle weakness, diminished deep tendon reflexes have also been seen.

The laboratory work-up is rather unrevealing. CBC's are almost always normal. Sed Rates of greater than 30 have occurred in only ten percent of the patients and we have had only two patients who have Sed Rates of 100 or more. EEG's have been abnormal in one-third of the patients showing bilateral sharp waves and some slowing. The CAT Scans have been normal but a number of MRI's have been abnormal showing evidence of increased signal in the white matter.

The decision to do a spinal tap on a patient with Lyme Disease is based on the physical findings. Obviously, if a patient has papilledema, they will be tapped after a CAT Scan or MRI shows no mass lesion. But in other cases, the decision to do the tap is based primarily on the need for additional diagnostic information or where there is a question as to whether the diagnosis is something other than Lyme. We have tapped about twenty-five [sic] patients so far. The majority have had normal spinal fluid findings. Usually, they have no elevation of their white cells. Protein and sugars are normal. Cultures are negative. Interestingly, however, at least fifty percent of them show increased pressure with opening pressures greater than 200, sometimes as high as 400. Every patient with papilledema has had a pressure of at least 300 or more except for one girl whose opening pressure was 260 but she had obvious papilledema and also loss of vision in her left eye. Eight of the patients had a pleocytosis with cells ranging from 60 to 700, predominantly lymphocytes. Only two patients showed a positive CSF titer.

The diagnosis of Lyme Disease is a clinical one. The serology, if positive, is helpful. We consider a positive serology as a 1:128 IFA; ELISA that is greater than .79. Urine antigens can also be measured. The tests on urine antigens are still considered investigational.

We will treat patients with negative serologies without hesitation if they truly have a number of the symptoms and are incapacitated by them. We have had children who have been out of school for an entire year because they have been too sick to leave the house.

Other children have had to give up all extracurricular activities, sports, etc. because they are too sick and too weak to participate. Every patient we have treated with the diagnosis of Neurologic Lyme Disease has had persistent complaints. These children have a headache and frequently chest pain. Many of them have seen numerous doctors without any specific diagnosis being made and many of them have had antibiotics for various reasons along the way, sore throats, otitis media, rash and, therefore, never developed an antibody response to their spirochetal infection.

The diagnosis of Neurologic Lyme Disease is a clinical one, not a laboratory one. If the patient's symptoms are compatible with the diagnosis, the patient is ill, the disease is having a significant effect on the person's ability to function, then they deserve treatment. I believe it is safer to be aggressive and treat someone under those circumstances than to allow them to continue suffering indefinitely.

Treatment consists of intravenous antibiotics, ceftriaxone, cefotaxime, ampicillin given for as long as is necessary, minimum of four-six weeks initially. Many patients are treated for months if they continue to be clinically ill.

Patients can take Benadryl if they develop pruritis. I encourage them to eat yogurt to try to prevent diarrhea while they are on the antibiotics. Aspirin is the best medication to relieve the pain but, because of the reluctance in the past of physicians to prescribe aspirin in children, many of them are given other NSAIDS.

During treatment and even afterward, they need to rest. They cannot resume full activity as soon as they have been treated. About twenty-five percent of the patients we have treated have had to be re-treated and of these re-treated, the vast majority then do well. Usually, if I treat them initially with ceftriaxone, I will re-treat them with either ceftriaxone or cefotaxime or ampicillin.

Many of the children I have seen with these complaints have been given the benefit of antibiotics by mouth to no avail. Once the patients have these neurologic complaints and, in some cases the positive neurologic findings, they truly deserve a course of aggressive intravenous antibiotic treatment, perhaps more than one time.

CASE HISTORIES

The following are some illustrative cases:

In June of 1982, a seven year old boy with a three day history of severe headaches who was sleeping twenty-four hours a day, no fever, recalls a tick bite three months prior to that, had a rash, no diagnosis was made. When seen in June, he had papilledema, a CSF opening pressure of 450 mm of water. He was assumed to have a pseudotumor, given Decadron and lost to follow-up. In January of 1983, he developed arthritis and was treated with antibiotics by mouth along with NSAIDS. He returned in 1985 because of a chronic headache that had been going on for two years. He had an entirely normal neurologic examination; no papilledema. Lyme titer at that time was 1:256. He had an elevated CSF pressure of 250 with no cells. He was given a fourteen day course of aqueous penicillin intravenously. During the course of the treatment, his headache went away and eventually he had no more bouts of arthritis. So in 1985, we were able to successfully treat a patient who had obviously been ill for three years with the diagnosis being missed in 1982 when he had the tick bite and the rash. Keep in mind that at the time he was seen in 1982, he was given steroids.

In 1983, an eleven year old boy with a history of ECM rash two months prior to being seen. Chief complaint when he was seen was severe pain in both thighs. Within a few days he developed a facial palsy and then a bilateral facial palsy. He had brisk reflexes and up-going toes. Spinal fluid revealed 300 white cells and an elevated protein of 81. He was started on intravenous penicillin and was treated for fourteen days. There was a dramatic improvement with complete resolution of the facial palsy. There was no more pain. His reflexes were all physiologic. His Lyme titer was weakly positive. At that time, it took more than seven weeks to get a Lyme titer and he was treated before the results were available because he was so ill.

In 1984, a ten year old boy had a sudden onset of headache with fever. He recalls no tick bite or rash. Examination was unremarkable. There was no papilledema. Spinal fluid: opening pressure was 190, only 7 cells. Lyme titer was sent to the State laboratory. Seven weeks later, the results were available. His titer was 1:2048. He was readmitted to the hospital. This time, spinal fluid white count was 100 cells. He was given aqueous penicillin for fourteen days with a dramatic improvement. Headache went away. Eventually, his Lyme titer was 1:64. He occasionally complains of knee pain but is otherwise doing well. During the weeks that we waited for his Lyme titer results, he was ill with a very, very severe headache.

A nine year old girl had a complaint of progressive weakness of her extremities following a flu-like illness. She was seen in May of 1988. She had been sick almost two months by then. Her examination revealed a girl who had to hold on to the wall as she walked into the office because she was so weak. She had the clinical diagnosis of the Guillain Barre Syndrome. She had absent deep tendon reflexes and weakness. Her spinal fluid protein was 80. Her Lyme titer was 1:128. She was given intravenous ceftriaxone, 2 grams a day for fourteen days with gradual improvement and by November of 1988 she was, again, fully active, participating in everything with no weakness and no complaints but still had absent deep tendon reflexes. She lived in an area where there were many ticks.

A five year old boy had a two year history of weakness and arthralgia and fatigue. He was seen initially in June of 1988. He had been bitten by a tick in February of 1986. Following that bite, he developed fever, joint pain, abdominal pain, rashes. Following that, he developed weakness, more so on the right than on the left and, indeed, did have a very mild right hemiparesis. The weakness became more progressive and eventually, at his mother's insistence, not the physician's, a Lyme titer was done which was 1:1024. He was given a course of ceftriaxone and then had to be retreated with another course so he received a total of twenty-eight days. He finished his treatment in the summer of 1988 and by December the was able to run, climb up and down stairs and climb up onto an examining table. He still had hypoactive reflexes but his strength had returned and he was considerably better.

A two year old little girl whose parents felt she had become excessively irritable was seen. She had a diaper rash that responded to no treatment that the pediatrician had prescribed. Because of her exposure to field mice and the fact that they do carry the tick, her parents insisted on a Lyme titer which was positive - 1:512. Because she was irritable and because of the persistent rash, she was given fourteen days of ceftriaxone with dramatic improvement in her behavior. The rash cleared and never returned.

A six year old girl was seen in September, 1987 with a very mild left facial weakness. She does not recall a tick bite but had exposure to ticks. She lives in a wooded area. Her Lyme titer was positive - 1:128. Her spinal fluid protein was 137 mgs. with no cells and a glucose of 63. Because of the mild left facial weakness and also headache, she was treated for Lyme and responded and did well. She received two courses of treatment for a total of twenty-eight days of ceftriaxone.

A sixteen year old boy who woke up with bilateral facial palsy was seen. He was unable to talk and unable to eat. Also had headache. He had been bitten by ticks. Lyme titer was 1:128. He was given twenty-one days of intravenous ceftriaxone with a dramatic improvement and an unremarkable neurologic examination four weeks after the initiation of the treatment. In addition to the ceftriaxone, he was also given Prednisone.

A nine year old girl was seen in 1985 initially complaining of headache, joint pain and photophobia. Spinal fluid: opening pressure was 230, 13 cells and a protein of 50. Titer was 1:256. Treated initially with aqueous penicillin. Retreated with ceftriaxone. Has been treated again in 1986, 1987 and 1988. She has persistently abnormal electroencephalograms and a significant fall-off in school performance. She now requires remedial help. She continues to have occasional headaches and joint pain. She continues to have abnormal EEG's and a persistently positive Lyme titer - 1:256. She will probably require more treatment.

A twelve year old boy was seen initially in 1987 for headache. Extensive work-up was done including a spinal tap, EEG and CAT Scan, all of which were normal. Lyme titer was done and was negative. It was elected not to treat him for Lyme because he had nothing else other than the headache and the titer was negative. This was unfortunate. During the course of that year, his performance in school fell off. He had been an exceptionally good student. By the following summer, he had a repeat Lyme titer which was 1:256. His examination was unremarkable. He was given intravenous ceftriaxone for two weeks and responded. During the course of the next year, he did better in school but by the end of the school year he was, again, complaining of headache. Now he also developed severe chest pain and diffuse myalgia. He, again, had a positive Lyme titer of 1:256 and his Borrelia urine antigen was also significantly elevated. He was then put in the hospital and placed on a continuous infusion of aqueous penicillin to be treated for twenty-eight days. After about the fifth or sixth day, his symptoms began to improve and the chest pain went away and he no longer has a headache.

A fourteen year old boy was seen who had a headache for two weeks and then developed double vision but no more headache. On examination, he only had a mild sixth nerve palsy on the left. Again, denied any headache and said he felt well but was concerned about the double vision. His Lyme titer was 1:512. His spinal fluid revealed 700 lymphocytes. He was started on ceftriaxone and treated for twenty-one days with complete resolution of the double vision and he has done well since then.

A nine year old girl complained of headache. On examination, she was found to have papilledema. CAT Scan was normal. Spinal tap revealed opening pressure of 280. She was started on steroids and Diamox. Lyme titer was positive - 1:128 after being negative twice a few weeks before when she first developed the headache. She was placed on intravenous ceftriaxone and is now being treated to complete a twenty-one day course. She has had some loss of vision in her left eye but her papilledema is resolving.

A thirteen year old girl was developing progressive weakness of the lower extremities with mild spasticity and brisk reflexes, back pain and headache as well as mood swings and depression. Again, at the parents' insistence, a titer was done which was positive - 1:256. It has been persistently positive. CSF titer was positive - 1:512. This girl has been treated now three times, initially with ceftriaxone for two courses, fourteen days each, and then a course of cefotaxime, twenty-one days. There has been some modest improvement but she still complains of weakness and still has brisk reflexes and probably will require further treatment.

A twenty month old boy was bitten by a tick on the right buttock. Within forty-eight hours, had a classic EM rash. He was seen by an infectious disease physician who indicated to the mother that this was classic for Lyme. He started the child on Amoxil by mouth. Forty-eight hours later, the patient developed fever and a febrile convulsion and became very irritable and looked pale. He was admitted to the hospital. Spinal fluid revealed normal opening pressure, 6 cells, cultures negative. Peripheral white count was normal except for a shift to the right. Sedimentation was normal. ELISA, at that time, was positive as was the IFA. The IFA was 1:128. The ELISA was 1.23. These titers were obtained less than two weeks after the patient became ill. Patient was started on intravenous Rocephin and is now in the process of being treated. He is slowly responding but continues to be irritable.

A college senior first became ill with Lyme disease at the age of about 15. She had numerous courses of treatment because of severe headache, arthralgia, rashes, weight gain, weakly positive Lyme titer and ultimately began to do better following about four courses of intravenous antibiotics. She was placed on Suprax, then ERYC by mouth and went to college. She did well and had an excellent year in school with only occasional complaints of some headache. That summer she developed sudden onset of a peroneal palsy, had a foot drop while driving the car. She was admitted to the hospital where here work-up revealed normal CBC and Chemistry Battery and Sed Rate but now she had a definitely positive Lyme titer, higher than the titers had been before and, in addition to this, had cells in her spinal fluid. She was started back on intravenous Rocephin and within forty-eight hours, the peroneal palsy began to improve and she completed a course of intravenous antibiotics for approximately six weeks and then went back on medication by mouth and is now, again, doing well.

A six year old girl was diagnosed initially as having Juvenile Rheumatoid Arthritis and was treated with medication for the arthritis and developed headache, abdominal pain and chest pain. The abdominal pain was thought to be due to a gastritis from all the aspirin she was taking. Her Lyme titers at that time were positive. She was started on Rocephin given, at that time, only a fourteen day course but then had another course for twenty-one days on Claforan. After that, she seemed well but one year later developed optic neuritis and arthralgia and chest pain. She required another course of treatment and was also given steroids. Her vision returned and she then relapsed again and required a much longer course of treatment. Following the longer course of treatment during which time she received intravenous Claforan, she gradually improved. Her visual acuity went back to 20/20. She was essentially asymptomatic and doing so well that she was able to do cartwheels. She felt fine and then relapsed again about six months later with, again, a complaint of vision loss, headache and some joint pain. At that time, she had an abnormal VERS, a weakly positive Lyme titer. Her optic discs were slightly swollen. Her opening spinal fluid pressure was normal and spinal fluid was completely negative. She was then placed on intravenous Claforan again along with steroids and again the visual acuity improved. Now her EEG's are abnormal and she will, of course, have a follow-up VERS and visual acuity will be followed.

It is controversial as to whether these patients should be treated more than one time. Since I have seen patients do better after receiving more than one course of treatment, I am willing to retreat rather than just let them live with their symptoms. It is impossible to know for how long a person should be treated although I am beginning to feel that we were probably undertreating when we only gave fourteen or twenty-four days so I am now recommending four-six weeks and, in some cases, even a longer course than that.

I hope that these clinical case studies and the information provided will be of some help to you in dealing with this, at times, very frustrating, puzzling and challenging problem with what appear to be vague complaints.

TREATMENT GUIDELINES -- NEUROLOGIC LYME IN CHILDREN

I.V. Rocephin (ceftriaxone): 2 grams a day, either 2 grams at one time or 1 gram every 12 hours. In children, it is preferable to give 1 gram every 12 hours. If it is an infant weighing less that 40 lbs. (or less than 20 kilograms), give 100 mg. per kg. per day in two divided doses.

I.V. Claforan (cefotaxime): 2 grams every 8 hours or 180 mg. per kilogram per day in three divided doses.

I.V. ampicillin: Give a maximum of 2 grams every 4 hours in a very big, older child such as a teenager; lower doses in younger children such as 1 gram every 6 hours or 1 gram every 4 hours.

P/O. antibiotics:

1. Amoxil can be used. Give the total dose once a day, such as a gram or even 1500 mgs. if the patient is older, even going up to as much as 2 grams a day.

2. Suprax: 400 mgs a day, increasing to 600 and even 800 mgs. a day.

3. ERYC: 250 mgs. PO qid.

Patients, again, may require anywhere from four-six weeks or longer of treatment depending upon how they are responding.

After completing a course of intravenous antibiotics, the patient should then be placed on antibiotics by mouth for as long as it is necessary. They can be given Amoxil, Suprax, a combination of Suprax, ERYC. Some physicians are now even considering the use of Bactrim, combining Bactrim and ERYC. There are a number of medications used, either singly or in combination, that help some patients some of the time. The decision may be made on the basis of the patient's clinical response and how well they tolerate the medication.

In addition to these antibiotics, give the patients B-6, 25-50 mgs. a day, depending upon their age and size; a multi-vitamin every day; Benedryl or Atarax if they have some itching or a mild rash from the medication; yogurt or acidophilus to prevent diarrhea.

The Suprax can be given all in one dose but the other medications may have to be given in divided doses.

Diamox can be given if the patient has increased intracranial pressure and in unusual circumstances steroids may be necessary but these should only be given if the patient is also on an antibiotic and, again, the use of steroids with Lyme is controversial. The pain is difficult to treat. Patients may, however, benefit from a trial on tricyclic medications such as Elavil and, of course, NSAIDS are used frequently.