Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis

Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence of their intrathecal production in conjunction with the white cell count in the CSF and typical clinical symptoms is the traditional diagnostic gold standard of Lyme neuroborreliosis (LNB). Few data are available on the CSF lactate concentration in European adults with the diagnosis of acute LNB. The objective of the study was to investigate the CSF changes during acute LNB. Routine CSF parameters [leukocyte count, protein, lactate and albumin concentrations, CSF/serum quotients of albumin (Q_Alb), IgG, IgA and IgM, and oligoclonal IgG bands] and the Borrelia burgdorferi (BB)-specific antibody index were retrospectively studied in relation to the clinical presentation in patients diagnosed with acute LNB. A total of 118 patients with LNB were categorized into the following groups according to their symptoms at presentation; group 1: polyradiculoneuritis (Bannwarth’s syndrome), group 2: isolated facial palsy and group 3: predominantly meningitic course of the disease. In addition to the CSF of patients with acute LNB, CSF of 19 patients with viral meningitis (VM) and 3 with neurolues (NL) were analyzed. There were 97 patients classified with definite LNB, and 21 as probable LNB. Neck stiffness and fever were reported by 15.3% of patients. Most of these patients were younger than 50 years. Polyradiculoneuritis was frequently found in patients older than 50 years. Lymphopleocytosis was found in all patients. Only 5 patients had a CSF lactate ≥3.5 mmol/l, and the mean CSF lactate level was not elevated (2.1 ± 0.6 mmol/l). The patients with definite LNB had significantly higher lactate levels than patients with probable LNB. Elevated lactate levels were accompanied by fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF protein concentration and CSF/serum quotients of albumin than LNB patients. In acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts. In contrast to infections by other bacteria, CSF lactate was lower than 3.5 mmol/l in all but 5 patients. The CSF findings did not differ between polyradiculoneuritis, facial palsy, and meningitis. The CSF in LNB patients strongly differed from CSF in VM patients with respect to protein concentration and the CSF/serum albumin quotient.     

European neuroborreliosis: quality of life 30 months after treatment

Eikeland R, Mygland Å, Herlofson K, Ljøstad U. European neuroborreliosis: quality of life 30 months after treatment.
Acta Neurol Scand: 2011: 124: 349–354.
© 2011 John Wiley & Sons A/S. Objectives – The prognosis after Lyme neuroborreliosis (LNB) is debated. The aim of this study was to assess health‐related Quality of Life (QoL) and neurological symptoms 30 months after treatment in European patients with LNB. Materials and methods – In a prospective case–control designed study, we investigated 50 well‐characterized patients with LNB who had participated in a treatment trial for LNB 30 months earlier and 50 matched control persons with the health QoL questionnaire Short‐Form 36 (SF‐36), the Fatigue Severity Scale (FSS), the Montgomery and Åsberg Depression Rating Scale (MADRS), the Starkstein Apathy Scale (SAS), and the Mini Mental State (MMS). Clinical and demographic data were collected by semi‐structured interviews and clinical neurological examination. Results – Lyme neuroborreliosis‐treated patients scored lower than control persons in the SF‐36 domains physical component summary (PCS) (44 vs 51 P < 0.001) and mental component summary (MCS) (49 vs 54 P = 0.010). They also scored lower than control persons in all the SF‐36 subscales, except for bodily pain, and on FSS (3.5 vs 2.1 P < 0.001), but not on MMS (28 vs 29 P = 0.106). There was a difference in MADRS (3.1 vs 0. 8 P = 0.003) and SAS (13 vs 11 P = 0.016), but the scores were low in both groups. Fatigue was the most frequently reported symptom among LNB‐treated patients (50%). Patients who reported complete recovery (56%) after LNB had similar QoL scores as the controls. Conclusion – European persons treated for LNB have poorer health‐related QoL and have more fatigue than persons without LNB.     

Variable CSF findings in early and late Lyme neuroborreliosis: A follow-up study in 47 patients

The cerebrospinal fluid (CSF) of 37 patients with early Lyme neuroborreliosis (ELN) and of 10 patients with late Lyme neuroborreliosis (LLN, duration of symptoms 7 months) was investigated for typical features differentiating between acute and chronic courses of disease. Individual patients were studied after 2 and 4 weeks, and 3, 6, and 12 months. Patients with ELN presented predominantly with symptoms of the peripheral nervous system, while patients with LLN generally suffered from symtoms of the central nervous system. At the first lumbar puncture, patients with ELN revealed a more intense pleocytosis in the CSF (P < 0.02) and a higher intrathecal synthesis of total IgM (P < 0.0003) and ofBorrelia burgdorferi-specific IgM antibodies (P < 0.01). At the same time, in patients with LLN, the blood-CSF barrier was more severely impaired (P = 0.03), and local production of total IgG (P = 0.0001), ofB. burgdorferi-specific IgG antibodies (P = 0.03) and of total IgA (P = 0.001) was more markedly increased. The quantity of intrathecally producedB. burgdorferi-specific IgA antibodies did not differ between the two study groups. Clinical recovery was usually accompanied by a considerable improvement of the blood-CSF barrier function and pleocytosis. After 6 months, the intrathecal synthesis of total IgG had significantly decreased in patients with ELN but not in those with LLN. At the same time, the CSF of most patients in both study groups still contained intrathecally producedB. burgdorferi-specific IgG antibodies. In the absence of clinical illness or symptoms of inflammation 6 and 12 months after treatment,B. burgdorferi-specific IgG antibodies in the CSF might simply indicate an anamnestic reaction to a previous infection of the central nervous system. Six months after antibiotic treatment, patients with ELN still revealed evidence of intrathecal synthesis of total IgM, whereas those with LLN did not. These antibodies, however, were not related toB. burgdorferi.     

EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis

Background:  Lyme neuroborreliosis (LNB) is a nervous system infection caused by Borrelia burgdorferi sensu lato ( Bb ).
Objectives:  To present evidence-based recommendations for diagnosis and treatment.
Methods:  Data were analysed according to levels of evidence as suggested by EFNS.
Recommendations:  The following three criteria should be fulfilled for definite LNB, and two of them for possible LNB: (i) neurological symptoms; (ii) cerebrospinal fluid (CSF) pleocytosis; (iii) Bb -specific antibodies produced intrathecally. PCR and CSF culture may be corroborative if symptom duration is <6 weeks, when Bb antibodies may be absent. PCR is otherwise not recommended. There is also not enough evidence to recommend the following tests for diagnostic purposes: microscope-based assays, chemokine CXCL13, antigen detection, immune complexes, lymphocyte transformation test, cyst formation, lymphocyte markers. Adult patients with definite or possible acute LNB (symptom duration <6 months) should be offered a single 14-day course of antibiotic treatment. Oral doxycycline (200 mg daily) and intravenous (IV) ceftriaxone (2 g daily) are equally effective in patients with symptoms confined to the peripheral nervous system, including meningitis (level A). Patients with CNS manifestations should be treated with IV ceftriaxone (2 g daily) for 14 days and late LNB (symptom duration >6 months) for 3 weeks (good practice points). Children should be treated as adults, except that doxycycline is contraindicated under 8 years of age (nine in some countries). If symptoms persist for more than 6 months after standard treatment, the condition is often termed post-Lyme disease syndrome (PLDS). Antibiotic therapy has no impact on PLDS (level A).     

Large cerebral vessel occlusive disease in Lyme neuroborreliosis

We report on a 12-year-old, previously healthy girl with an acute hemiparesis as the predominant clinical manifestation of Lyme neuroborreliosis (LNB). The diagnosis of LNB was based on cerebrospinal fluid (CSF) studies, laboratory findings and the clinical course whereas the patient's history and the lack of characteristic skin lesions obscured the diagnosis in the beginning. After four weeks of antibiotic and physiotherapeutic treatment, the hemiparetic symptoms had completely resolved. Although evidence of vasculitic and perivascular inflammation in LNB has been described in the literature, large cerebral vessel occlusive disease represents a rare finding. Appropriate treatment strategies can lead to good clinical rehabilitation, as shown in this case, making the timely diagnosis a crucial issue. We conclude that LNB should be considered in every stroke-like episode of unknown origin in children, even in the absence of a history of a tick bite or typical skin lesions.     

Clinical usefulness of intrathecal antibody testing in acute Lyme neuroborreliosis

The aim of the study was to examine diagnostic sensitivity and temporal course of intrathecal Borrelia burgdorferi (Bb) antibody production in acute Lyme neuroborreliosis (LNB). We recruited consecutive adult patients with LNB diagnosis based on strict selection criteria. Serum and cerebrospinal fluid (CSFs) were obtained, and clinical examination was performed pre-treatment, and 13 days and 4 months post-treatment. Pre-treatment positive Bb antibody index (AI) was detected in 34 of 43 (79%). All nine pre-treatment Bb AI negative patients, and 26 of 34 pre-treatment Bb AI positive patients reported symptom duration <6 weeks. Eight patients, all Bb AI positive, reported symptom duration of 6 weeks or longer. Consequently, pre-treatment diagnostic sensitivity of Bb AI was 74% when symptom duration was <6 weeks, and 100% when 6 weeks or longer. Three patients converted from negative to positive Bb AI status post-treatment. The six patients who were persistently Bb AI negative had lower CSF cell count and protein at presentation, when compared with the patients with positive Bb AI. In conclusion, the diagnostic sensitivity of Bb AI is suboptimal in acute early LNB. Repeated post-treatment Bb AI testing, to confirm or reject LNB diagnosis, is unreliable, as the majority of initial Bb AI negative patients remained negative at follow-up.     

Acute and chronic neuroborreliosis with and without CNS involvement: a clinical,MRI, and HLA study of 27 cases

Summary Of the 96 serologically confirmed neuroborreliosis cases seen in our clinic between 1983 and 1988, 11 patients had mild to moderate and 4 patients had serious cerebral and/or spinal cord symptoms. Nine of these 15 patients with CNS involvement exhibited a primary chronic course of the illness. After high-dose intravenous therapy with penicillin, doxycycline or cefotaxime, given mostly in combination with cortisone, gradual recovery occurred with normalization of CSF findings characteristic of neuroborreliosis, and normalization of significantly elevated Borrelia burgdorferi IgG antibody titres in CSF and serum. Brain MRI and CT showed evidence of or were suggestive of vascular involvement which correlated with clinical symptoms in 11 of the 15 patients with CNS involvement. Brain MRI changes that were similar but much slighter in number and intensity were seen in 5 of 12 neuroborreliosis patients without clinical signs of CNS involvement (lymphocytic meningoradiculitis; Bannwarth's syndrome). The frequencies of the HLA-DR7 (75%), HLA-B44 (50%) and HLA-A29 (33%) antigens in 12 neuroborreliosis patients with clinical symptoms of CNS involvement were significantly different from the frequencies in 12 neuroborreliosis patients without CNS involvement and in 100 control subjects. Diagnostic criteria of active neuroborreliosis are proposed.     

Plasma neurofilament light significantly decreases following treatment in Lyme neuroborreliosis and is not associated with persistent symptoms

Background and purpose

Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15%–20%), the variable clinical course and the long-lasting Borrelia burgdorferi antibodies. The aim was therefore to evaluate plasma neurofilament light chain (pNfL) as a marker for disease activity in LNB.

Methods

This was a prospective cohort of definite LNB (N = 36) with blood samples and clinical evaluation including Glasgow Outcome Score at treatment initiation and 3 and 6 months’ follow-up. Consecutive plasma was retrospectively analysed for the content of neurofilament light chain by Quanterix® kits (Simoa® NF-light Kit).

Results

Plasma neurofilament light chain significantly decreased between treatment initiation and the 3-month follow-up (median 83 pg/ml vs. median 14 pg/ml (25 pairs), p < 0.0001). No significant change was observed between 3 and 6 months’ follow-up (median 14 pg/ml vs. median 12 pg/ml (21 pairs), p = 0.33). At treatment initiation 90% had pNfL above the age-defined reference compared to only 23% and 7% respectively at 3 and 6 months’ follow-up. Decreases in pNfL were mirrored by increasing Glasgow Outcome Score. Reporting persistent symptoms at the 6-month follow-up was not associated with pNfL (relative change from reference or actual values) at baseline or at 6 months’ follow-up.

Conclusion

Plasma neurofilament light chain decreases following antibiotic treatment in LNB and is not associated with reporting persistent symptoms. It was therefore speculated that it may prove useful as a treatment response biomarker in LNB.     

European neuroborreliosis: neuropsychological findings 30 months post-treatment

Background: The aim of this study was to compare neuropsychological (NP) functioning in patients with Lyme neuroborreliosis (LNB) 30 months after treatment to matched controls. Methods: We tested 50 patients with LNB and 50 controls with the trail‐making test (TMT), Stroop test, digit symbol test, and California Verbal Learning test (CVLT). A global NP sumscore was calculated to express the number of low scores on 23 NP subtasks. Results: Mean scores were lower amongst LNB‐treated patients than amongst controls on tasks assessing attention/executive functions: (Stroop test 4: 77.6 vs. 67.0, P = 0.015), response/processing speed (TMT 5: 23.4 vs. 19.2, P = 0.004), visual memory (digit symbol recall: 6.6 vs. 7.2, P = 0.038), and verbal memory (CVLT list B: 4.68 vs. 5.50, P = 0.003). The proportion of patients and controls with NP sumscores within one SD from the mean in the control group (defined as normal) and between one and two SD (defined as deficit) were similar, but more LNB‐treated patients than controls had a sumscore more than two SD from the mean (defined as impairment) (8 vs. 1, P = 0.014). Conclusions: As a group, LNB‐treated patients scored lower on four NP subtasks assessing processing speed, visual and verbal memory, and executive/attention functions, as compared to matched controls. The distribution of NP dysfunctions indicates that most LNB‐treated patients perform comparable to controls, whilst a small subgroup have a debilitating long‐term course with cognitive problems.     

Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors

Background and purpose: To chart remaining complaints 1 year after treatment for neuroborreliosis, and to identify risk factors for a non‐favorable outcome. Methods: We followed patients treated for neuroborreliosis prospectively, and assessed outcome by a composite clinical score. The impact on outcome of clinical, demographic and laboratory factors were analyzed by univariate analyses and logistic regression. Results: Out of 85 patients 41 (48%) had remaining complaints; 14 had objective findings and 27 subjective symptoms. Remaining complaints were associated with pre‐treatment symptom duration ≥6 weeks (OR = 4.062, P = 0.044), high pre‐treatment cerebrospinal fluid (CSF) cell count (OR = 1.005, P = 0.001), and female gender (OR = 3.218, P = 0.025). Presence of CSF oligoclonal bands (OCBs) was not analyzed in the logistic regression model due to many missing observations, but was found to be more frequent both pre‐treatment (P = 0.004) and after 12 months (P = 0.015) among patients with remaining complaints as compared to patients with complete recovery. Further evaluation showed that objective remaining findings, and not subjective symptoms, were associated with pre‐treatment symptom duration ≥6 weeks. No difference in outcome was observed between patients treated with IV ceftriaxone and patients treated with oral doxycycline. Conclusion: Remaining complaints are common after neuroborreliosis. The majority of the complaints are subjective. Pre‐treatment symptom duration ≥6 weeks, high pre‐treatment CSF cell count, and female gender seem to be risk factors for remaining complaints. Presence of CSF OCBs may also predict a non‐favorable outcome, but this should be further studied. Whether subjective and objective complaints are associated with different risk factors is also an issue for future studies.     

Immunological differentiation between neuroborreliosis and multiple sclerosis

Summary Neuroborreliosis, a tick-borne spirochaetosis of the central nervous system, is diagnosed by the presence of intrathecally synthesized Borrelia burgdorferispecific antibodies. Multiple sclerosis and neuroborreliosis can show similarities in clinical symptoms as well as lymphocytic cell reactions and oligoclonal bands in the isoelectric focusing of cerebrospinal fluid. To differentiate between multiple sclerosis and neuroborreliosis we tested intrathecally synthesized IgM and virus antibodies. The IgM indices were higher for most of the neuroborreliosis patients studied than for those with multiple sclerosis, and cell counts were also significantly higher in the acute stage of the disease. In 84% of multiple sclerosis patients we were able to demonstrate intrathecal antibody production against measles, rubella or mumps virus. Neuroborreliosis patients had no intrathecal virus antibody synthesis. The specification of oligoclonal bands resulting from isoelectric focusing of cerebrospinal fluid with an ELISA for B. burgdorferi can further substantiate the diagnosis of neuroborreliosis or help to rule it out in multiple sclerosis patients with positive borreliaspecific serology.     

Chronic fatigue syndrome in patients with Lyme borreliosis

Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past. To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies. Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology.     

Lyme neuroborreliosis

Neuroborreliosis, an infection of the nervous system caused by spirochetes of the genus Borrelia, has achieved worldwide attention in the last decade as part of the clinical spectrum of Lyme disease. This disorder, caused by Borrelia burgdorferi, has increased in incidence to become the most frequent arthropod-borne infection in North America and Europe. As a result of this rapid rise in incidence and of its protean neurological manifestations, this disease has created an important challenge to modern neurology. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. This review takes a chronological approach to clinical neuroborreliosis to summarize its most important aspects. The limitations as well as the benefits of laboratory diagnosis are also considered, with the aim of providing assistance in this area. Recent advances in neuroimmunology regarding the pathogenesis of neuroborreliosis that may elucidate its protean clinical spectrum are summarized.     

Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge

We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided.     

CSF B – lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis

Recent studies have suggested a diagnostic role of the B-lymphocyte attracting chemokine (CXCL13) in the cerebrospinal fluid (CSF) in Lyme neuroborreliosis (LNB). Our aim was to evaluate diagnostic accuracy of CSF CXCL13 in a cohort of 59 consecutive patients referred to hospital for suspected LNB. Thirty-seven patients were classified as definite LNB and used as the reference standard. Seven were classified as probable, and seven as possible LNB. Eight patients did not fulfil case definitions and were used as controls. At presentation, CSF CXCL13 was elevated in all patients with definite LNB, as compared to a positive CSF B. burgdorferi (Bb) antibody index (AI) in 33 of 37. Pre-treatment sensitivity of elevated CSF CXCL13 and positive CSF Bb AI was 100 % (95 % CI = 91–100) and 78 % (95 % CI = 75–96) respectively (p = 0.053). Among the eight control patients, CSF CXCL13 was normal in five and only slightly elevated in three, and Bb AI was negative in five. Specificity of CSF CXCL13 and Bb AI was similar 63 % (95 % CI = 31–86) (p = 1.0). CSF CXCL13 was elevated in 6/7 patients with probable LNB and 3/7 patients with possible LNB. Bb AI was negative in all these 14 patients. An additional control group consisted of 31 patients with multiple sclerosis (MS), 11 with non-inflammatory neurological diseases, and ten with verified non-Lyme meningitis and high CSF cell count. CSF CXCL13 was slightly elevated in 15 MS patients, and in nine meningitis patients. Mean CSF CXCL13 was higher in definite LNB (3524 ng/g CSF protein) than in MS (27 ng/g) and non-Lyme meningitis (23 ng/g) (p < 0.001). Four months post-treatment CSF CXCL13 was normalized in 82 % of patients with definite LNB, as compared to a negative Bb AI in 10 % (p < 0.001). CSF CXCL13 may be a useful supplement in early diagnosis of acute LNB.     

Lyme neuroborreliosis: infection, immunity, and inflammation

Lyme neuroborreliosis (LNB), the neurological manifestation of systemic infection with the complex spirochaete Borrelia burgdorferi, can pose a challenge for practising neurologists. This Review is a summary of clinical presentation, diagnosis, and therapy, as well as of recent advances in our understanding of LNB. Many new insights have been gained through work in experimental models of the disease. An appreciation of the genetic heterogeneity of the causative pathogen has helped clinicians in their understanding of the diverse presentations of LNB.     

Neuroborreliosis

Neuroborreliosis, a manifestation of infection with the spirochete Borellia burgdorferi, has become the most frequently recognised arthropod-borne infection of the nervous system in Europe and the USA. The best criterion of an early infection with B. burgdorferi is erythema migrans (EM), but this is present in only about 40–60 % of patients with validated borreliosis. Therefore use of the duration of the disease as a classification criterion for neuroborreliosis is increasing, the chronic form being distinguished from the acute when symptoms persist for more than 6 months. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. In Europe, meningopolyradiculoneuritis (Bannwarth’s syndrome) represents the most common manifestation of acute neuroborreliosis, with the facial nerve being affected much more frequently than the other cranial nerves. Clinical symptoms affecting the central nervous system are rarely observed and then mostly in chronic courses. By far the most common manifestation of chronic neuroborreliosis is encephalomyelitis with spastic-ataxic disturbances and a disturbance of micturition. The current diagnosis of neuroborreliosis is a clinical one, which has to be confirmed by laboratory testing. In most patients, examination of the cerebrospinal fluid (CSF) reveals lymphocytic pleocytosis, damage to the blood-CSF-barrier and an intrathecal synthesis immunoglobulin (Ig) M, IgG, and sometimes IgA. Confirmation of a borrelial infection of the nervous system requires demonstration of an intrathecal synthesis of borrelial-specific antibodies in the CSF or detection of borrelial DNA in the CSF by polymerase chain reaction (PCR). There is no generally accepted therapeutic regime for the treatment of neuroborreliosis, but recent studies have shown ceftriaxone 2 g/day and cefotaxime 6 g/day to be effective in acute and chronic courses. Penicillin G 20 mega units/day and doxycycline 200 mg/day may be suitable for uncomplicated meningopolyneuritis, without involvement of the central nervous system. The duration of treatment – at least 2 weeks in the acute forms and 3 weeks in the chronic forms of neuroborreliosis – is very important for successful treatment. Corticosteroids are recommended only for patients with severe pain that does not respond to antibiotics an analgesics. Received: 24 December 1997 Accepted: 6 January 1998     

Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years

Summary In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5–27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an immunological scar syndrome. Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis.     

Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis

Is Lyme neuroborreliosis, even in its early phase, a parenchymatous disorder in the central nervous system (CNS), and not merely a meningitic process? We quantified cerebrospinal fluid (CSF) levels of four nerve and glial cell marker proteins in Lyme neuroborreliosis patients with pretreatment durations of 7–240 days. AH 23 patients had meningo-radiculitis, and six had objective signs of encephalopathy. Glial fibrillary acidic protein (GFAp) pretreatment levels in CSF, and the light subunit of neurofilament protein (NFL) levels were related to clinical outcome and declined significantly after treatment (P < 0.001 and P < 0.01, respectively). NFL was detectable in 11 out of 22 patients, and pre-and post-treatment NFL levels were associated with the duration of neurological symptoms within 100 days prior to treatment. Neuron-specific enolase (NSE) concentrations also decreased after therapy (P < 0.001), while CSF levels of glial S-100 protein remained unchanged. The pretreatment duration of disease was related to postinfectious sequelae. GFAp, NSE and NFL levels in CSF are unspecific indicators of astroglial and neuronal involvement in CNS disease. The findings in the present study are in agreement with the hypothesis that early and late stages of Lyme neuroborreliosis damage the CNS parenchyma.     

Intrathecal antibody production in a mouse model of Lyme neuroborreliosis

Intrathecal antibody (ITAb) production is a common feature of neurological diseases, yet very little is known about its mechanisms. Because ITAb is prominent in human Lyme neuroborreliosis (LNB), in the present study we established a mouse model of LNB to study ITAb production. We injected different strains of Borrelia burgdorferi into a variety of mouse strains by the intracerebral (i.c.) route to develop the model. Spirochetal infection and ITAb production were identified by complementary methods. This study demonstrates that the mouse model of LNB can be utilized to test hypotheses related to the mechanisms of ITAb production.