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European LNB - Long-term follow-up (Norway)

Posted: Sun 8 Jul 2012 3:36
by RitaA
Original Link: (in Norwegian)

Translated below to English: ... CG0Q7gEwCQ
Long-term health problems after the tick bite

Randi Eikeland defends Friday, June 2012 for the PhD degree at South Coast Hospital / University of Bergen on:

"European neuroborreliosis-long term follow-up".

Although very few people get sick after a tick bite, there are some who get Borrelia bacteria in the blood and develops borreliosis, or Lyme disease. In approximately 10 percent occur spread to organs, most commonly the nervous system, and the condition neuroborreliosis may develop. Lyme disease is treated with antibiotics, and most are cured, but some are long-term ailments. The scope and significance of such long-term pain is controversial.

In our study, 50 patients examined and treated neuroborreliosis followed up for 30 months and examined by lumbar puncture, neurological examination, neuropsychological assessment and questionnaires regarding quality of life, fatigue and depression. Fifty Southerners without evidence of neuroborreliosis were used as controls.

We found that the first in Europe, that some of the patients had impaired quality of life, fatigue, and minor neurological outcomes after neuroborreliosis, and that a small group had cognitive problems that can cause problems with everyday life. Depression and pain or continued infection of the nervous system does not seem to be able to explain this. More severe signs and symptoms prior to treatment, lack of recovery 4 months after infection, and delayed initiation of therapy increases the risk of long-term ailments.


Randi Eikeland (f.1966) grew up in Birkeland in Aust-Agder and took medical degree at the Rhein-Westfälische Technische Hochscule in Aachen, Germany. She is a neurologist specialist since 2002 and has since 1997 worked as a researcher and neurologist at the Southern Hospital in Arendal. Doctoral work emanates from a collaboration between the Clinical Medical Institute at the University of Bergen, the South-East and South Coast Hospitals, neurologic department. Dr. Treat Ljøstad has been the main supervisor, Professor Annie Mygland and Dr. Karen Herlofson has been bi-supervisors.
Here's a related Norwegian article: ... /22008018/

Translated below to English: ... CGEQ7gEwBA
[Photo] NEW FINDINGS: Neurologist Specialist Randi Eikeland found in his [actually her] doctoral thesis, which is the first in Europe, that some Borrelia patients do not recover, even after being treated with antibiotics for two weeks - a treatment in line with European guidelines.

MORE misdiagnosed: According to Public Health will be between 200 and 300 people seriously ill after being infected with the bacterium Borrelia by ticks each year. They estimate that between 2000 and 3000 have transmitted the disease each year, and they have long warned that the risk of getting sick increases. Ten percent of those who have received treatment for Lyme disease after being bitten by ticks, is disabled as a result of the disease.

(Dagbladet): Ten percent of those who have received treatment for Lyme disease after being bitten by ticks, is disabled as a result of the disease.

These people believe that the disease is the only reason why they can not continue in their jobs, according to neurologist specialist Randi Eikeland (46), which is part of a Borrelia-expert at the Southern Hospital.

As the first in Europe, she has her doctorate demonstrated that some Borrelia patients do not recover, even after being treated with antibiotics for two weeks - a treatment in line with European guidelines.

Read the story of Oddvar Skarbø that after eleven months of "hell pain" and several false tests had proven Lyme disease. Maj-Britt Hovland Grevstad was sick for 14 years before she was diagnosed the same disease, and doctors ticks sick Madeleine thought that something was wrong with the girl mentally , and sent her to therapy in BUP.

Surprised researchers

Half of the 50 southern patients in the study reported that they were still sick 30 months after treatment. They struggled mainly with neuro-cognitive problems such as poor concentration and fatigue, according to Eikeland. 50 Southerners with Lyme disease were used as controls.

- 50 percent said they were not fresh, and 16 percent of them said they were so sick that they had problems in everyday life. There were more than expected. It's okay that we have ascertained that there are long-term ailments, the study is an important piece of the puzzle, she says to Dagbladet.

Patients in the study were on average 53 years when they were diagnosed, and Eikeland think it is typical that the disease affects men in this age group. Ten percent said they were so sick that they are no longer able to work.

She therefore believes that the bacterium must now be taken seriously. The previous studies from the United States demonstrated long-term problems in Borrelia patients, but this is a different type of Borrelia than in Norway.

- Ticks are in progress throughout Europe, and it is clear that the risk of becoming ill increases , said Public Health.

- Do not hypochondriac group

Of the 50 subjects, only seven pieces, which were now afraid to walk in the woods.

- This was not a hypochondriac group, and they were no more depressed or had more psychological distress than the control group, she said.

Eikeland emphasizes that there is no good cure for Lyme patients with long-term ailments, and she believes it is useless to give a longer course of antibiotics.

-Borreliaen is sensitive to antibiotics, and according to four major American studies go further rebehandling greater side effects than efficacy. On this basis, we can not recommend further treatment.

60 percent remembered that they had been bitten by ticks, and 22 percent said they had the characteristic red ring on the skin.

Disagree guidelines

Managing Director of Norwegian Center borreliosis, Rolf Luneng, said Dr. task match his experience with many patients.

He disagrees with the European guidelines for the treatment of Lyme disease, and provide their patients antibiotics up to 6 to 12 months, if necessary to get the patients recover completely.

He is critical of the four American studies, and believes that they are between 40 and 50 studies showing that long-term therapy required to enable more patients to be healthy.

- Research reports may diverge, and if side effects are worse with prolonged antibiotics, my patients were getting worse and worse treatment. Over 50 percent of our patients are much better or completely healthy, he says, and continues:

-Many of these have been long term sick leave and resume work again. But there are a few patients who can not tolerate antibiotics, and these can not carry out such treatment.

At the Karolinska Institute in Stockholm, researchers have found that every fourth child in the emergency room with diffuse neurological symptoms had Borrelia or TBE.

Remains of disability

Luneng think the reason why some do not recover from a long-term antibiotics, because they have developed lasting health effects of chronic Borrelia disease, and that they will always have symptoms.

- Tuberculosis is a chronic infection, which is given antibiotics for six months to two years. Even those who have a positive tuberculin skin test, but who are healthy and symptom free, have in case automatic three to six months of antibiotic treatment to avoid getting sick. Why do you do it, if it is as dangerous to long-term treatment?

He tells of patients who for years has been work disability, and who can not get back to work despite the fact that they have been cured with prolonged antibiotic therapy.

- They are too old to work after many years of illness and is no longer competitive in today's professional life. This is a great paradox.

Difficult Disease

Director Ingeborg Aaberge of Public Health emphasizes the importance of good studies because Lyme disease in some cases difficult to diagnose.

- Clinical picture is different, and it is important to study to gain insight into the problems of Lyme disease.

Preben Ottesen of Public Health report that normal ticks summer so far this year. He has already collected ticks at three sites, and believes that the number of ticks is "almost stable".

- It is early summer, and most cases of Lyme are enrolled in September and October. It is only the most serious cases are reported to us.

In Norway, researchers at Bioforsk looking at Hillsborough to set out the fungus to combat ticks . On the South Coast, scientists have started a project in which they will determine if the sheep tick, cleanse the Borrelia, such as the blood of elk and deer are doing.
Edited to improve formatting.

Re: European LNB - Long-term follow-up (Norway)

Posted: Sun 8 Jul 2012 3:42
by RitaA
Here are a few published articles from Norway:
Eur J Neurol. 2010 Jan;17(1):118-23. Epub 2009 Jul 23.

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

Ljøstad U, Mygland A.
Department of Neurology, Sørlandet Hospital HF, Kristiansand, Norway.

To chart remaining complaints 1 year after treatment for neuroborreliosis, and to identify risk factors for a non-favorable outcome.

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.

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 >or=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 >or=6 weeks. No difference in outcome was observed between patients treated with IV ceftriaxone and patients treated with oral doxycycline.

Remaining complaints are common after neuroborreliosis. The majority of the complaints are subjective. Pre-treatment symptom duration >or=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.

[PubMed - indexed for MEDLINE]
Acta Neurol Scand. 2011 Nov;124(5):349-54. doi: 10.1111/j.1600-0404.2010.01482.x. Epub 2011 Feb 9.

European neuroborreliosis: quality of life 30 months after treatment.

Eikeland R, Mygland A, Herlofson K, Ljøstad U.
Department of Neurology, Sørlandet Hospital, Arendal, Norway.

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.

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.

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.

European persons treated for LNB have poorer health-related QoL and have more fatigue than persons without LNB.

© 2011 John Wiley & Sons A/S.

[PubMed - in process]
Eur J Neurol. 2012 Mar;19(3):480-7. doi: 10.1111/j.1468-1331.2011.03563.x. Epub 2011 Oct 15.

European neuroborreliosis: neuropsychological findings 30 months post-treatment.

Eikeland R, Ljøstad U, Mygland A, Herlofson K, Løhaugen GC.
Department of Neurology, Sørlandet Hospital, Arendal Department of Neurology, Sørlandet Hospital, Kristiansand Institute of Clinical Medicine, University of Bergen, Bergen, Norway.

The aim of this study was to compare neuropsychological (NP) functioning in patients with Lyme neuroborreliosis (LNB) 30months after treatment to matched controls.

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.

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).

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.

© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

[PubMed - indexed for MEDLINE]
Acta Neurol Scand. 2012 Jun 12. doi: 10.1111/j.1600-0404.2012.01690.x. [Epub ahead of print]

Risk factors for a non-favorable outcome after treated European neuroborreliosis.

Eikeland R, Mygland A, Herlofson K, Ljøstad U.
Department of Neurology, Sørlandet Hospital, Arendal, Norway.

To identify possible risk factors for reduced health-related quality of life (HRQoL) and fatigue after treated Lyme neuroborreliosis (LNB).

We included 50 patients with LNB and analyzed associations between their demographic, clinical, and laboratory characteristics at baseline and outcome at 30 months assessed by the self-report questionnaires Short Form-36 (SF-36) and Fatigue Severity Scale (FSS).

Lower scores in the SF-36 domain Physical Component Summary were associated with pretreatment symptom duration >6 weeks (B = -11.0, P = 0.001) and non-complete recovery at 4 months (B = -5.5, P = 0.037) (R(2) = 0.35). Lower scores in the SF-36 domain Mental Component Summary were associated with non-complete recovery at 4 months (B = -8.9, P = 0.01 (R(2) = 0.14). Higher FSS scores were associated with pretreatment symptom duration >6 weeks (B = 1.4, P = 0.006), high scores on the composite clinical score pretreatment (B = 0.1, P = 0.003), and non-complete recovery at 4 months (B = 1.6, P = 0.005) (R(2) = 0.46). No laboratory test results were associated with these predefined outcomes.

Delayed treatment start, more symptoms and findings before treatment, and non-complete recovery at 4 months after treatment are possible predictors of a poorer HRQoL and more fatigue 30 months after treated LNB. We did not find age, gender, educational level, involvement of the central nervous system, coexisting diseases, or cerebrospinal fluid findings to be associated with reduced HRQoL or fatigue. Our findings should be replicated in future studies before any conclusions can be drawn.
© 2012 John Wiley & Sons A/S.

[PubMed - as supplied by publisher]

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 0:56
by X-member
I activate this thread since the numbers of patients with symptoms after treatment for neuroborreliosis is discussed in the thread/topic below:

Quality of life: the same all around ... f=6&t=5962

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 1:22
by X-member
Maybe this also belong in this thread?

Scand J Infect Dis. 2005;37(6-7):449-54.
Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis.
Borg R1, Dotevall L, Hagberg L, Maraspin V, Lotric-Furlan S, Cimperman J, Strle F.
This prospective, open-label, non-randomized trial at the University Departments of Infectious Diseases in Ljubljana, Slovenia, and Göteborg, Sweden, was conducted to compare the kinetics of the cerebrospinal fluid (CSF) mononuclear cell count after 10-14 d of ceftriaxone or doxycycline for treatment of Lyme neuroborreliosis. 29 patients were treated with intravenous ceftriaxone 2 g daily in Ljubljana and 36 patients with oral doxycycline 400 mg daily in Göteborg. The study protocol included lumbar puncture before and 6-8 weeks after treatment initiation. There was a marked decrease (1.2 log10 x 10(6)/l) of the median CSF mononuclear cell count following treatment. With the assumption of a linear regression of the logarithmic mononuclear cell counts between the 2 lumbar punctures, no significant difference between the 2 antibiotic treatments could be found. All patients were clinically much improved after treatment. At 6 months follow-up 23 (79%) of the ceftriaxone- and 26 (72%) of the doxycycline-treated patients were completely recovered. Intravenous ceftriaxone or oral doxycycline was found to be effective, safe, and convenient for treatment of Lyme neuroborreliosis.

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 1:25
by X-member
And maybe this also belong in this thread?

Lancet Neurol. 2008 Aug;7(8):690-5. doi: 10.1016/S1474-4422(08)70119-4. Epub 2008 Jun 21.
Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial.
Ljøstad U1, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, Mygland A.
Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis.
From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with, number NCT00138801.
Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events.
Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 1:42
by admin
Moved topic from "General" to "Science", since it's about medical research and scienctific publications.

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 1:43
by duncan
There are lots of good data and insights in this thread, X-member. Thank you for "resurrecting" it. Also, I think you are right: it is clearly relevant to the hv808ct Quality of Life thread we are discussing.

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 2:44
by Lorima
Very relevant to QoL thread. Thanks X-member.

Re: European LNB - Long-term follow-up (Norway)

Posted: Thu 1 Oct 2015 18:39
by X-member
Maybe this also belong in this thread?

Europeisk nevroborreliose - hvordan går det etter behandling? (Eikeland, Norway) ... behandling

A (not perfect) translated quote:
Most people with NB notice a rapid improvement of outcomes and symptoms weeks to a few months after antibiotic therapy, but 10-50% report fatigue, cognitive problems such as memory, attention and mental speed, or musculoskeletal ailments even years after treatment . If one has a clear NB diagnosis that is treated with the appropriate guidelines, can not be explained by any other condition and is severe enough to give disability, the condition is proposed called Post Lyme Disease Syndrome (PLDS). This expression is better than chronic Lyme, which rather brings to mind an active infection, which we do not find at PLDS.

Re: European LNB - Long-term follow-up (Norway)

Posted: Fri 2 Oct 2015 18:55
by X-member
And perhaps this also belong in this thread?

Scand J Infect Dis. 2002;34(6):421-5.
5-y Follow-up study of patients with neuroborreliosis.
Berglund J1, Stjernberg L, Ornstein K, Tykesson-Joelsson K, Walter H.
The objective of this follow-up study was to determine the long-term outcome of strictly classified cases of neuroborreliosis treated with antibiotics. A 1-y prospective population-based survey of Lyme borreliosis was conducted in southern Sweden between 1992 and 1993. A total of 349 identified cases with suspected neuroborreliosis were followed up 5 y later. Medical records were reviewed and all participants filled in a questionnaire. Of those patients classified with definite neuroborreliosis, 114/130 completed the follow-up, of whom 111 had completed the initial antibiotic treatment. Of the 114 patients followed up, 86 (75%) had recovered completely and 70 (61%) had recovered within 6 months. Residual neurological symptoms, such as facial palsy, concentration disorder, paresthesia and/or neuropathy, were reported by 28/114 patients. No significant differences between different antibiotic treatments were observed in terms of the occurrence of sequelae. To conclude, we found that 25% (95% confidence interval 17-33%) of the patients suffered from residual neurological symptoms 5 y post-treatment. However, the clinical outcome of treated neuroborreliosis is favorable as only 14/114 (12%) patients had sequelae that influenced their daily activities post-treatment. Early diagnosis and treatment would seem to be of great importance in order to avoid such sequelae.