Report A0367582A describes the occurrence of encephalitis in a 41 year old female who received Lyme disease vaccine recombinant OspA. This report was received as part of the litigation proceedings, with forwarding of medical records. The medical history included Lyme disease (July 1999) with severe headache, Bell's palsy, a large lymph node in the left cervical region, numbness over the left side of her face, left shoulder pain, weight loss and diarrhea. Results from a cerebrospinal fluid examination were consistent with either a lymphocytic meningitis or low grade lymphoma. The subject was treated with oral amoxicillin and then ceftriaxone sodium IV. While she was on ceftriaxone sodium, all symptoms resolves except for the headaches and some tingling over the top of her head. However, within three months of stopping the ceftriaxone, these symptoms resolved. Of note, several months prior to this, the subject had an insect bite on the left cheek and left hand followed by dramatic rubor/dolor in both locations (insect was not a tick). Other medical history included papilledema, vertigo, sinus infections, ear infections, probable adhesions, hypothyroid, excess sweathing when exerting, endometriosis, uterine fibroid, premature ovarian failure, degenerative disc disease, posterolateral disc herniation L2/L3, myofascial dysfunction of the cervical spine treated with trigger point injections, hallux valgus deformity, groin pain, internal derangement of knee, rheumatoid arthritis, osteopenia, insomnia, pneumonia, liver hemangioma, Grave's disease treated with radioiodine ablation, and irritable bowel syndrome. Surgical history included laparotomy for endometriosis, lysis of adhesions via laprascopy, abdominal hernia repair, and breast reduction surgery at age 16. The subject had an extensive travel history. She was allergic to nortriptyline and had environmental allergies. Concurrent medications included fluoxetine, sertraline hydrochloride, amitriptyline hydrochloride, levothyroxine sodium, fexofenadine, lorazepam, ethinylestradiol, scopolamine, calcium, vitamin B complex, evening primrose oil, vitamin C, multi-vitamin, kava kava, and acidophilus. Following the reported onset of headache, the subject experienced upper respiratory infection, rapid heart beats, calf pain when walking, pain stiffness, or swelling in the back, joints, or muscles, loss of more than 10 pounds over six months, sweats, auditory sensitivity, depression. These events were not reported as adverse events due to vaccine administand ration, but were found during the course of review of the vaccinee's medical records. On 2/3/00, the subject received her first injection of LYMErix (lot LY130B9). Her second injection was administered on 3/7/00 (lot LY130B9). In a statement of injuries, the attorney alleged that the subject suffers from numbness in her head and side of the face and joint pain in her legs, arms, neck, jaw, and left shoulder. The subject experiences chronic headaches, left ear pain and tingling sensations in her head. She also suffers from tremors, dizziness, diarrhea (from medication), thyroid complications, microscopic colitis and encephalitis. In addition, she suffers from fatigue, sleeplessness and weight gain. From 3/23/00 to at least 2/14/02, the subject was under the care of an endocrinologist. During this time, the subject reported that she experienced a syndrome of lightheadedness, shortness of breath, chest pressure, perspiration constantly but no fever, a headache very similar to the Lyme headache, total body aches, palpitations, felt weak, arthritis, shakiness, swelling of feet and legs, diarrhea, weight loss, and her nerve endings were on fire. She also experienced hypotension and bradycardia (possibly related to the scoplamine patch for which she was sent to the ER for hydration on 3/23/00. During this time period, the physican noted tremor with outstretched arms, excellent muscle strength, negative Asterixis, Babinski and Romber, no dysmetria, ablated thyroid, normal pulses, no lid lag or stare, normal gait. Laboratory analysis performed during this time revealed acutely elevated thyroid function tests. An echocardiogram was normal. Results from thyroid uptake and scan revealed that the radioiodine uptake was well below the range of normal. The physician's initial impression was that the subject had hypothyroidism and scopalamine poisoning. Other impressions included eythyroid and palpitations syndrome but the exact cause of the syndrome remains unclear. He also stated that another physician's impression was either recurrence of Lyme disease or autoimmune reaction to Lyme vaccine. As of 2/14/02, the endocrinologist's impression was hypothyroidism and Lyme disease. During this time, thyroid medication was briefly held. The physician later prescribed a low dose of levothyroxine sodium but recommended to the subject that she minimized her medications. As of 2/14/02, the subject was not feeling particularly better. On 4/3/00, the subject called her vaccine provider complaining of headache, dizziness, myalgias, evening sweats, shortness of breath, and increased auditory sensitivity since 3/18/00. She reported wearing a scopolamine patch for one week while on a cruise prior to removal on 3/18/00 and was also taking fexofenadine while on the cruise. She reportedly experienced visual symptoms while wearing the patch. Fexofenadine was discontinued. She was advised to see a neurologist if symptoms continued. The subject was seen by her neurologist on an emergent basis on 4/18/00. The physician noted she has pain in the left paraspinals of the neck, left trapezius, and a tender point is noted in the left triceps. The neurologist stated that this isn't Lyme. The patient took amitriptyline hydrochloride. Back and extremities examination revealed mild joint swelling and total muscle tenderness. Impression: probably Lyme reaction; positive Lyme Western Blot; negative Bell's, now with recurrence of chronic headache, fibromyalgia. An MRI of the brain was negative. Central spinal fluid Lyme antibodies were positive. The patient agreed not to get third LYMErix dose. On 4/25/00, the subject received paravertebral and trapezius trigger point injections of 80mg Depomedrol mixed with 30cc of 0.5% bupivacaine injected into separate sites. Myofascial stretching done followed by TENS nerve stimulation and heat. Diagnosis: myofascial pain syndrome. On 6/21/00, the subject was seen by her physician concerning Lyme disease. The physician noted since the LYMErix injections, she has been experiencing severe heaache, lightheadedness, vertigo, and left shoulder/trapezius/deltoid pain. She was treated with azithromycin for one week. A second MRI was negative. On 7/12/00, the Lyme disease cerebrospinal fluid Western Blot IgM antibodies were negative; the IgG antibodies were indeterminate. The Lyme Western Blot serum IgM antibodies were positive; the IgG antibodies were indeterminate. Lyme serum ELISA and Lyme CSF ELISA were both reactive. On 7/15/00, the Lyme disease serum and cerebrospinal fluid serologies were reactive. Lyme IgM Western Blot performed on 8/13/00 was negative; Lyme IgG had two hands present. On 9/19/00 the subject was seen by her primary care physician for follow-up She had been on sertraline hydrochloride 100 mg for approximately one week. There has been substantial improvement in many respects though not necessarily with respect to headache. Her mood is definately better. She feels much less tense. She states that her relationships with both her husband and children are improved as a result of this. She generally has a sense of well being to a much greater degree than in the past. She has begun exercising again. She does admit to having fewer bad days with respect to headache than she did previously, although she cannot say that her headaches are any less frequent than they were prior to beginning Zoloft. She is using estazolam 1 mg at bedtime for sleep with very good results. Upon physical examination, the physician noted there was not nystagmus. Coordination was good on finger to nose testing bilaterally. There was moderate postural tremor in the right upper extremity and a milder tremor in the left upper extremity. Power was normal throughout. Deep tendon reflexes were all normal. The station and gait were normal. The physician planned to increase the subject's daily dose of Zoloft by 25 mg each week until she reached a final dose of 200 mg. In 10/00, the subject underwent a sigmoidoscopy. She had been experiencing diarrhea and abdominal pain for the past four weeks. Biopsies were consistent with microscopic colitis. Treatment with mesalazine was initiated. A second physician believed that the subject's severe left lower quadrant pain was likely secondary to pelvic adhesions or endometriosis. Stool culture was negative for clostridium difficile. From 11/20/00 to at least 11/16/01, the subject was treated by a gastroenterologist. During this time, the subject complained of anxiety, stress, severe headaches, and a ten pound weight gain. Her diarrhea had improved on Asacol. Upon physician examination, the subject's abdomen was soft, nontender, and mildly dstended. The physician's impression was lymphcytic colitis and Lyme disease. He recommended she continue Asacol. The subject was evaluated by an infectious disease specialist on 12/19/00. Her chief complaint was post Lyme vaccination encephalopathy/neuropathy. The patient reported that she gradually re-developed the same headache that she had with the Lyme disease as well as the same trapezial and left upper arm discomfort, however she was able to move her arm pretty well. She also noted a subtle change in the nasolabial fold on the right and felt her face was just a little bit drooped. She also complained of blurred vision but reportedly had her eyes checked and was told everything was fine. The subject was seen by a Lyme disease specialist who entertained the thought that her headaches could be related to the Lyme vaccine. The infectious disease specialist did not feel that she had recurrent Lyme disease. An MRI of the brain on 4/18/00 was normal. In 5/00, and MRI of the C-spine showed a small C5-6 herniation without encroachment along with degenerative disc disease. Since August 2000, she had alot of trouble with achiness in her arms, legs, back and shoulders. Upon physician examination, the physician noted significant tenderness and muscle spasm of the left trapezial area, tenderness of the posterior neck and the occipitut. She had a little bit of bilateral paraspinal tenderness but did not have any other trigger points for fibromyalgia. There was no clear out evidence of seventh nerve palsy, although her mouth was minimally asymmetric. The physician's impression/plan included the following:  her headaches sound like muscle contraction headaches. Her physician may want to try trazodone for the insomnia. He planned to send the patient for progressive muscle relaxation for the left sided cervical and trapezial myalgias. It certainly sounds like she had early disseminated Lyme disease back in the summer of 1999. This was adequately treated and should not be playing any role in her current headaches. There is also no good evidence that the Lyme vaccine is playing a role in her headaches and myalgias. On 12/20/00, the subject was seen by her neurologist. The impression was chronic headache in setting of previously treated CNS Lyme disease. Patient's neurologic exam is normal at this time. Spinal fluid exam this summer was normal which would suggest absence of recurrent CNS Lyme disease at this time. Cause of the persistent headache at this time is not clear. Persistent CNS Lyme disease, I suppose, is still a possibility. There is no strong evidence of this, however. A CSF leak resulting in chronic headaches is a possibility given her history of two previous lumbar punctures, but her headaches were fairly bad before her last lumbar puncture, making this less likely. The patient seemed most concerned that these symptoms may be the result of the Lyme vaccine, but at this time we have no proof that this is the case. On 12/21/00, the subject was evaluated by a physical therapist. History of present illness: this is a 41 year old female with a nine month complaint of pain starting from the frontal bone with a banding sensation with migration to bilateral parietal bones where the pain turns into a vice. The pain then travels to neck and left shoulder where she describes the pain as a stabbing pain. She reports that the pain is always there. Aggravating factors include noise. Ameliorating factors are nothing. There is no pattern to her pain and she can identify no obvious stressors. She has not checked to see of allergies are a contributor. She is currently not working. She walked on a treadmill two times a week. Past medical history: osteoporosis, history of degenerative disc disease in the cervical and lumbar spines. Impression/report/plan: Impression: headache with undetermine etiology. There may be a component of cervical tension myalgia involving the upper cervical spine. Report: physical exam remarkable for significant muscle guarding during segmental testing of the upper cervical spine and C-3. There is also guarding with the rest of the normal cervical spine. She has pain when testing for forward and backward movement with sidebending and rotation motions of OA and AA. There is point tenderness at C-2 at the muscular attachments of the cervical paraspinals. Motion of the neck is normal with pain associated with all motions. Again there is continued muscular guarding. Rest of exam unremarkable for impingement or other neurologic deficits. Plan: we have given her stretches for the upper and normal cervical spine as well as deep flexion retraining strengthening exercises. Dismissed with home exercise program. On 12/22/00, the neurologist wrote a follow up evaluation following the subjects' MRI of the head, performed on 12/21/00, which was negative. Impression/report/plan: 1. Headaches, 2. History of CNS Lyme disease. At this time, there is no evidence of progressive CNS borreliosis. She does have significant headaches and left shoulder pain. Perhaps this is related to injury of the nerve endings in the dura from her previous bout with CNS Lyme disease. The subject was prescribed gabapentin and she was referred to a Lyme disease specialist who entertained the idea that the subject's symptoms were related to LYMErix, thought a trial of gabapentin would be warranted. If this were to fail, I would never favor a trial of Depakote. On 12/20/00, the subject's chart was reviewed by her primary care physician. The Impression/Report/Plan was: 1. Chronic headaches. The patient was seen by the neurologist. The neurologist examination was essentially normal except for a slight static tremor of the right upper extremity and slight reduction in the lower extremity reflexes. He thought that the headaches and left shoulder pain could be related to injury of the nerve endings in the dura from her previous bout with CNS Lyme disease. He recommended a trial of gabapentin. 2. Cervical tension myalgias. The patient saw a physicial therapist who found evidence of this. He though that there may be a compoment of cervical tension myalgia to her headaches and prescribed a home therapy program. The diagnoses were: 1. Chronic headaches, 2. Cervical tension myalgias, 3. Insomnia, 4. History of Lyme disease, 5. Grave's disease treated with radioactive iodine, 6. Primary ovarian failure, 7. Microscopic colitis, 8. Osteopenia. On 1/23/01, the subjects returned to the neurologist for evaluation of diagnosis of nerve damage from Lyme disease. At the visit, the subject complained of severe fatigue and chronic, daily headaches. She stated, pain and fatigue have interfered with her ability to lead a normal life. Neurologic examination revealed normal speech, language, and memory. Cranial nerves II through XII were normal. Motor bulk, tone, and strength were normal with no arm drift. Sensation was intact for all modalities. There was a fine tremor of both hands on sustension, right more than left. Coordinative functions were otherwise normal. Gait was normal. Reflexes were 1 to 2- throughout with downgoing toes. The physician's assessment included: The temporal relationship of the recurrent meningitis symptom complex and the Lyme vaccine suggests a post vaccinal syndrome, likely of auto-immune mechanism, perhaps similar in nature to the post infectious encephalitis that resembles infectious encephalitis in clinical symptoms and signs but without the infectious agent in the nervous system, the syndrome and pathology believed to be of auto-immune origin. To date, no medication is effective in controlling symptoms that have adversely impacted this patient's life. I recommend evaluation for other tick-bourne agents, Babesia and Ehrlichia, and a SPECT of brain. We discussed a possible trial of intravenous immune globulin dependent on laboratory results. The rationals for the treatment is that the history strongly suggests a post vaccinal syndrome complex that occurred within the time frame consistent with an immune mechanism. Diagnosis: 1. Lyme meningitis, 2. Lyme vaccine, 3. Post-vaccinal chronic fatigue syndrome and headache, 4. History of Grave's disease, 5. Primary ovarian failure, 6. Microscopic colitis, 7. History of endometriosis, 8. Osteopenia. On 1/31/01, the patient underwent a brain SPECT. Results were consistent with encephalitis or vasculitis. The anti-DNA antibodies were normal, total complement was elevated, the serum HCG was normal; the anti-thyroglobulin and antimicrosomal antibodies were normal, the parvovirus IgG and IgM were normal, the Ehrlichia IgG and IgM were negative, the thyroid peroxidate was normal, and the Lyme indes was negative. See Laboratory Data section. Workman's compensation note on 2/22/01 indicated that thyroid finally leveled out. On 6/18/01, the microplasm subtying by PCR was positive for M. fermentans, the Bartonella henselae Qualitative by PCR was negative, the general Chlamydia was positive for C. pneumonia, the Lyme disease by PCR was positive, the Babesia by PCR was negative. On 6/21/01, the vaccinee was seen by a physician, who was a Master of Public Health. His impression was that the patient clearly had a clinical relapse of symptoms directly after receiving the second dose of LYMErix, identical to those she initially presented with when she developed acute Lyme. These had resolved with treatment prior to the vaccine. The repeat testing at the time did not support CNS Lyme. Despite this, she has become disabled and now has left sided weakness and a diffusely abnormal SPECT. She does not have cognitive symptoms, however, which is unusual in CNS Lyme. She is alsy clearly clinically depressed now, although this can clearly be explained by her medical condition. I agree with your initial assessment that she probably has an auto-immune response to the vaccine, but your request for IV gammaglobulin has been denied. I have sent another PCR panel including mycoplasma and chlaydia PCR's as well as a more complete auto-immune tests are positive, I would start Plaquenil and try to get approval for the gammaglobulin again. For symptomatic relief, I have suggested a regimen of vitamins and Physical Therapy. Laboratory results revealed a negative C6 Lyme Peptide ELISA. The subject was started on IV Rocephin. On 6/26/01, the patient was seen by a physical therapist. The diagnosis was fibromyalgia and Lyme disease. Chief complaint: the patient reports the following symptoms: extreme fatigue, neck pain radiating into the upper arm, headaches, multiple joint and muscle aches. Patient states that she has a headache constantly. The degree of pain varies with her position and activity. Current status: cervical range of motion diminished as follows: end range flexion restrictions with pulling pain, 50% side bend with left cervical pain, 25% rotation left, 50% rotation right with left sided pain. Significant myofascial component also limiting mobility. Posture: very forward head, rounded shoulders, flat lumbar spine. Difficulty maintaining upright posture. Strength: grossly functional strength, however patient fatigues easily and short term activity will elicit considerable muscle pain. Poor postural/trunk strength. Patient reports trying her TM at home and was able to tolerate 4 minutes. Reports lower extremity symptoms x 1 day. Palpation: tender trigger points occiput, upper trapezius muscles, pectoral muscles, SIJ and gluteal muscles. Tenderness to a lesser degree in rhombids, pectoral, and biceps muscles. Assessment/Plan: Patient to begin physical therapy with a plan of modalities to reduce pain and local inflammation. The physician has restricted activity at this time. Patient educated in posture, body mechanics, and self-care. We will add exercise when directed and patient's plan of care is established. The subject received physician therapy until 10/3/01. The 6/29/01 workman's compensation form noted that the patient was still not on IV gammaglobulin. On 9/14/01, the medical record noted that the patient had been on Rocephin for 10 weeks. ? no benefit. Treatment was changed to oral doxycycline. The subject was seen by her primary care physician on 12/10/01. The physician noted she has finally turned the corner. The subject functional status was better although fatigue was still a problem. She still had hand tremors but muscuskeletal pain was better. Her headaches were much improved but she still had problems with forgetfulness. The subject was reportedly treated with accupuncture from 12/12/00 to at least 1/14/02 with only slight improvement in her headaches. Of note, she had received accupuncture since 4/29/99 prior to LYMErix injections due to back pain. As of 9/24/02, the thyroid dysfunction resolved. The outocme of other events were unknown.