Neurological Studies (worldwide)

[itsybitsyone]

Hansel Y, Ackerl M, Stanek G., ALS-like sequelae in chronic neuroborreliosis
Wien Med Wochenschr. 1995;145(7-8):186-8. German.
“CSF investigation in a 61-year old female patient with clinical picture of motoneuron disease gave evidence for chronic infection with Borrelia burgdorferi. Improvement of clinical and CSF findings could be observed after antibiotic therapy. The diagnosis of amyotrophic lateral sclerosis which was initially suspected had to be revised and the disorder was interpreted as chronic neuroborreliosis.”



David S. Cassarino, MD, PhD,a Martha M. Quezado, MD,a Nitya R. Ghatak, MD,a and Paul H. Duray, MDa
Lyme-Associated Parkinsonism: A Neuropathologic Case Study and Review of the Literature, Archives of Pathology and Laboratory Medicine: Vol. 127, No. 9, pp. 1204-1206.
From the Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md (Drs Cassarino, Quezado, and Duray); and the Departments of Pathology and Neuropathology, Virginia Commonwealth University, Richmond (Dr Ghatak)
Accepted April 11, 2003
Neurological complications of Lyme disease include meningitis, encephalitis, dementia, and, rarely, parkinsonism. We present a case of striatonigral degeneration, a form of multiple system atrophy, in Lyme- associated parkinsonism. A 63-year-old man presented with erythema migrans rash, joint pains, and tremors. Serum and cerebrospinal fluid antibodies and polymerase chain reaction for Borrelia burgdorferi were positive. Clinical parkinsonism was diagnosed by several neurologists. Despite treatment, the patient continued to decline, with progressive disability, cognitive dysfunction, rigidity, and pulmonary failure. At autopsy, the brain showed mild basal ganglia atrophy and substantia nigra depigmentation, with extensive striatal and substantia nigral neuronal loss and astrogliosis. No Lewy bodies were identified; however, ubiquitin-positive glial cytoplasmic inclusions were identified in striatal and nigral oligodendroglia. There were no perivascular or meningeal infiltrates, the classic findings of neuroborreliosis. To our knowledge, this is the first report of striatonigral degeneration in a patient with B burgdorferi infection of the central nervous system and clinical Lyme-associated parkinsonism.



Fredrikson S, Link H. ,CNS-borreliosis selectively affecting central motor neurons. Acta Neurol Scand 1988;78:181-184
“A patient is described having Borrelia burgdorferi spirochetal infection clinically affecting central motor neurons selectively and without any sensory impairment.”



Halperin JJ, Kaplan GP, et al. Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Arch. Neurol 1990; 47: 586-594
“Cerebrospinal fluid was examined in 24 ALS patients--3 (all with severe bulbar involvement) appeared to have intrathecal synthesis of anti- B burgdorferi antibody.”



Reik L; Burgdorfer W; Donaldson JO, Neurologic abnormalities in Lyme disease without erythema chronicum migrans.:
American Journal of Medicine, 81:73. 1986.
“The occurrence of severe encephalitis resulting in dementia in two of these patients... enlarges the known spectrum of neurologic abnormalities due to infection with B. burgdorferi.”
Pachner AR. Borrelia burgdorferi in the nervous system: the new "great imitator". Annals of the New York Academy of Sciences, 539:56-64. 1988
“Six patients had relapsing-remitting episodes of focal CNS disease, sometimes mimicking multiple sclerosis”

[itsybitsyone]

Kohler J; Schneider H; Vogt A.
1989 High-dose intravenous penicillin G does not prevent further progression in
early neurological manifestation of Lyme borreliosis.
Infection, 17(4):216-7.
[From the abstract:] .We report two cases of Lyme borreliosis (LB) with erythema migrans (EM) and simultaneous meningopolyneuritis... EM and pain disappeared
completely under high-dose penicillin G therapy within few a days. Pathological findings in CSF improved. Nevertheless, during and after therapy, neurological signs
of LB developed: cranial nerve palsies as well as paresis of extremity muscles with radicular distribution."



Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature.
Oksi J, Kalimo H, Marttila RJ, Marjamaki M, Sonninen P, Nikoskelainen J, Viljanen MK.
Brain 1996 Dec; 119 ( Pt 6): 2143-54
www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
Case 1:
The patient was a 51-year old woman with a history of progressive lymphoedema of the left lower limb since 1954. She had suffered from erysipelas in the left lower leg and erythema nodosum in both legs, and had also had recurrent fever episodes several times a year. Lung fibrosis, heart insufficiency and chest pain atypical of coronary heart disease developed at the age of 30-35 years. She had received long-term corticosteroids and several courses of antimicrobial drugs.
In 1985, the patient had a 3 week period of fever and facial redness suggestive of lupoid erythema. Despite corticosteriod treatment, a spiking fever persisted. At hospital, no infection focus was found. Antimalarial drugs, combined with methylprednisolone were given for two years, but episodes of mild fever reappeared. Antinuclear antibodies and antibodies against extractable antigens were repeatedly negative. Anti-DNA-antibodies were found slightly positive.
After september 1988, she was hospitalized several times for prolonged vomiting, fatigue, fever, dizziness and progressive walking difficulties with ataxia and short gait. In addition, impairment of memory, taste, and hearing occurred. In february 1988, the erythrocyte sedimentation rate (ESR) was 125 mm/h serum C-reactive protein 83mg/ml (normal <10 mg/ml), and leucocytes 9.2 x 109 with 96% granulocytes. Sinus X-ray showed sinuitis, and the brain CT showed an empty sella. Despite treatment with methylprednisolone and i.v. erythromycin, the ESR and C-reactive protein remained elevated. At CSF examinations (February 1989 and January 1991), leucocyte counts and protein concentrations were normal, as was the IgG/albumin ratio, but one or two subfractions were observed with protein electrophoresis. In January 1991, MRI of the brain showed enlarged ventricles, cortical atrophy, and marked degenerative changes in the periventricular areas (Fig. 1A). Total serum immunoglobulins were normal, but immune electrophoresis showed an M-komponent (IgG lambda). Circulating immune complexes also occurred. Rheumatoid factor, antinuclear antibodies, anticardiolipin, TPHA (treponema pallidum haemagglutinations test), anti-phospholipid antibodies, and antibodies against B. burgdorferi were negative in serum. Leucocytes were 3.5 x 109 /l with an excess of band forms. In August 1991, CSF examination showed no inflammatory cells, a slightly elevated protein concentration of 762 mg/l, and no antibodies against B. burgdorferi. Culture of CSF in BSK-II medium showed very slow growth of spirochetes during 3 months. Using monoclonal antibodies, immunoflourescence and PCR, the spirochete was identified as B. burgdorferi s.l.
In December 1991, antimicrobial treatment with ceftriaxone (2g i.v. daily) was instituuted. The patient improved slightly, and therapy was continued after 3 weeks with oral amoxicillin (500 mg every 8 h) and oral probenecid (500 mg every 8 h).
After 1 week on amoxicillin the patient developed urticaria. Oral doxycycline (100 mg every 12 h) was substituted and continued until July 1992. During this treatment, the walking difficulties and fever episodes recurred. All cultures for fungi and common bacteria were negative. In January 1992, brain MRI showed slight progression of the periventricular lesions from the image obtained 1 year earlier. In March and July 1992, subdural haemorrhages of unknown origin were evacuated.
On August 7, 1992, plasma and bone marrow specimens were positive for B. burgdorferi PCR. Treatment with ceftriaxone (2g i.v. daily) was reinstituted, the patient reacting with high fever. Empirical antifungal therapy with amphotericin B was also started. These treatments were continued until the patient died on September 12, 1992.
At autopsy, the pathological changes were slighter than expected. The spleen was slightly enlarged. Chronic liver stasis and mild pulmonary oedema were detected. No signs of fungal infection were seen. Neuropathological examination showed a chronic left-sided subdural haematoma. Its structure was compatible with the haemorrhages ocurring 6 and 12 months before death. An increased number of plasma cells were present within the organizing connective tissue of the haematoma. In subcortical and periventricular white matter, diffuse demyelination with mild perivascular inflammation was seen (Fig. 1B and C). In one of the six analysed brain tissue specimens, B. burgdorferi DNA was detected by the PCR.
Case 2:
This 40-year old man had previously been healthy, apart from reactivation of a genital herpes infection some weeks before. He recalled no tick bites or erythema migrans. On December 26, 1992, he had a generalized seizure and was admitted to the hospital. Another seizure ocurred on the day of admission. Brain CT was normal. On admission, CSF examination showed an unremarkable increase of protein level (688 mg/l) with no inflammatory cells. The PCR assays for herpes simlex virus (HSV) and antibodies against viruses were negative in the CSF. Serum IgM antibodies against B. burgdorferi were found at a low level and IgG antibodies against Chlamydia pneumoniae were moderately elevated. Serum C-reactive protein was 50 mg/l, lactic dehydrogenase 927 U7l (normal value <20 U/l), but the changes were transient. Other labororatory tests were normal including serum hepatitis B surface antigen, antibodies against HIV and herpes virus. The EEG showed an irrative focus in the left hemisphere.
On December 30, MRI of the brain showed three small frontal lesions at the bottom of the left frontal lobe near the meninges. The imaging of these lesions was enhanced using contrast medium (Fig. 3A). In the right pleural cavity, a chest X-ray examination showed fluid, which disappeared in 2 weeks. The CT showed a central cystic lesion n the left kidney, but no abnormal findings were obtained in the mediastinum, lungs, or pleural cavities. On December 31, a CSF examination showed 4 x 106 /l lymphocytes, but protein (373 mg/l), and angiotensin convertase enzyme and lysozyme concentrations were normal. The CSF antibodies against herpesviruses, B. burgdorferi, and Treponema pallidum were negative as was antigen for HSV and PCR for B. burgdorferi. The PCR for HSV was positive with this specimen. Culture for viruses and mycobacteria remained negative.
On January 8, 1993, a frontally located lesion was resected for suspected malignancy. Histopathological studies showed lymphocytes in the walls of leptomeningeeal and small penetrating arteries as well as in the perivascular space of the latter (Fig. 2B). The adjacent cortex was slightly oedematous with very mild astrocytic gliosis. A PCR analysis of three separate brain specimens detected DNA of B. burgdorferi. The IgM (but not IgG) antibodies against B. burgdorferi were positive only in the first pretreatment sample serum samples, but negative thereafter. The circulating immune complexes and complement activation products were positive. The IgG antibodies against C. pneumoniae were elevated at a constant level, but IgM antibodies remained negative, indicating that the IgG antibodies were of earlier origin. A neuropsychological investigation showed memory impairment affecting verbal function anf slightly impaired fluency of verbal expression. Anticonvulsive therapy with carbamazepine was started. Table two shows changes in the antimicrobial treatment schedule and the development of the brain lesions appearing on MRI. During the antibiotic treatment, MRI of the brain showed new lesions, one enhancing lesion (2 cm in diameter), suggestive of focal vasculitis, located medially from the post-operative area, and later, enhancing lesions at the bottom of the right frontal lobe and a frontal lobe sulcus (Fig. 3A and B). However, the initial lesion at the bottom of the lest frontal lobe behind the orbita was now markedly smaller than at previous examination. Later images showed that the first lesion was constantly reducing in size, and five months after onset of antibiotic therapy all the new foci of the putative vasculitic process had also disappeared. The antibiotic therapy was discontinued on July 5, 1993.
The patient was asymptomatic at the end of therapy. Whole body bone scanning was carried out in June 1993 because of a history of pain in the thoracic spine some months earlier. Slightly increased uptake of isotope in the thoracic spine was seen, but the finding was considered unspecific. The EEG after sleep deprivation was normal in July 1993.
Five months after the end of antibiotic therapy, brain MRI showed a new focus located adjacent to the third ventricle (Fig. 3 A and B). Oral antibiotic treatment was started (the patient was asymptomatic: see table 2). The next MRI showed that the treatment had probably had beneficial effect on the former lesions, but again, a new focus in frontal sulcus and a relatively large pathological area in periventricular white matter were detected (Fig. 3B). On May 17, 1994, DNA of B. burgdorferi was detected by PCR in the patients plasma specimen (Table 2). Intravenous antibiotic therapy was reinstituted and continued for 100 days. Thereafter, on MRI studies of the brain, all lesions and perivascular enhancement have disapperared, and no new lesions have developed to date (Table 2). The antiepileptic therapy has been discontinued, and no new seizures have occurred.
Case 3:
In the summer of 1993, this previously healthy 11-year-old girl had visited an area in Southern Finland where Lyme borreliosis is endemic. In September 1993, occasional episodes of hyperactivity followed by headache were observed by her family. On October 1, she developed paresis of the right lower limb. On October 7, she was admitted to a local hospital and 1 week later to the Oulu University Central Hospital. Standing on the right leg alone was difficult, and walking was slightly impaired. On October 13, CT of the brain showed a periventricular low density enhancing lesion. 10x6 mm2 in diameter, and located in the left parietal lobe white matter. The lesion was suggestive of a neoplasm. On the next day, using MRI, the dimensions of the enhancing lesion were found to be 40x20x8 mm3 and the surrounding oedematous area was 20-30 mm thick (fig. 4A). The EMG was normal. Abdominal ultrasonography showed mild splenomegaly. On October 22, a craniotomy was carried out. In the area of the enhancing lesion, shown by MRI, elastic and stretchy tissue with abnormal white colour was detected. On histological examination, focal necrotic areas were found, surrounded by foamy macrophages, reactive astrocytes and oedema. (Fig 4B). An increased number of small vessels with thickened walls and prominent endothelial cells were also seen. Lymphocytes occurred in the walls of some vessels.
Haemoglobin, ESR and serum C-reactive protein values were normal. Serum total immunoglobulins were normal, except for a slightly increased value of IgM at 1.94 g/l (normal value 0.35-1.63 g/l). Serum rheumatoid factor, antinuclear antibodies extractable nuclear antigens, anti-DNA and anti-phospholipid antibodies were negative, and so were antibodies against several viruses. On November 4, lumbar puncture was carried out. The CSF specimen gave a negative virus culture as HSV PCR, but B. burgdorferi PCR was positive with two separate CSF specimens (detected at two separate runs).
December 21, 1993, antibiotic therapy with ceftriaxone (2 g i.v. daily) was started for 4 weeks followed by therapy with oral amoxicillin (500 mg every 8 h) combined with oral probenecid (500 mg every 8 h). On February 1, the antibiotic therapy was stopped because of bloody diarrhoea. Culture and toxn detection for Clostridium difficile were negative. The diarrhoe was cured with oral metronidazole.
On Februray 1, 1994, MRI of the brain showed reduction of abnormal tissue around the operative area. At this time, no enhancement was seen in the walls of the cavity. At a follow-up of 1 year, recovery was observed witho only a slight abnormality in walking. No new symptoms developed.