Inflammation in the Pathogenesis of LNB

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
RitaA
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Inflammation in the Pathogenesis of LNB

Post by RitaA » Sat 18 Apr 2015 20:03

http://ajp.amjpathol.org/article/S0002- ... 6/abstract
Article in Press

Inflammation in the Pathogenesis of Lyme Neuroborreliosis

Geeta Ramesh
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, Louisiana

Peter J. Didier
Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana

John D. England
Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Lenay Santana-Gould
Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Lara A. Doyle-Meyers
Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana

Dale S. Martin
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, Louisiana

Mary B. Jacobs
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, Louisiana

Mario T. Philipp
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, Louisiana

Accepted: January 23, 2015; Published Online: April 16, 2015
DOI: http://dx.doi.org/10.1016/j.ajpath.2015.01.024
Publication stage: In Press Corrected Proof

Abstract

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis.
http://www.news-medical.net/news/201504 ... sease.aspx
Inflammation plays causal role in neurologic changes associated with Lyme disease

Published on April 17, 2015 at 1:52 AM

About 15% of patients with Lyme disease develop peripheral and central nervous system involvement, often accompanied by debilitating and painful symptoms. New research indicates that inflammation plays a causal role in the array of neurologic changes associated with Lyme disease, according to a study published in The American Journal of Pathology. The investigators at the Tulane National Primate Research Center and Louisiana State University Health Sciences Center also showed that the anti-inflammatory drug dexamethasone prevents many of these reactions.

"These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis," explained Mario T. Philipp, PhD, Professor of Microbiology and Immunology and chair of the Division of Bacteriology and Parasitology at Tulane National Primate Research Center (Covington, LA).

Lyme disease in humans results from the bite of a tick infected with the spirochete Borrelia burgdorferi (Bb). As Bb disseminates throughout the body, it can cause arthritis, carditis, and neurologic deficits. When the nervous system is involved, it is called Lyme neuroborreliosis (LNB). Clinical symptoms of LNB of the peripheral nervous system may include facial nerve palsy, neurogenic pain radiating along the back into the legs and feet, limb pain, sensory loss, or muscle weakness. Central nervous system involvement can manifest as headache, fatigue, memory loss, learning disability, depression, meningitis, and encephalopathy.

To understand further the neuropathologic effects of Bb infection, researchers infected 12 rhesus macaques with live B. burgdorferi; two animals were left uninfected as controls. Of the 12 Bb-inoculated animals, four were treated with the anti-inflammatory steroid dexamethasone, four with the non-steroidal anti-inflammatory drug (NSAID) meloxicam, and four remained untreated. Half of each group was studied for eight weeks postinoculation and the other half for 14 weeks.

The researchers examined the role of inflammation in the nervous systems of Bb-infected animals. Significantly elevated levels of the inflammatory mediators interleukin-6 (IL-6), IL-8, CCL2, and CXCL13 were observed, as well as pleocytosis (increased cell counts, primarily white blood cells) in the cerebrospinal fluid of all infected animals - except in those treated with dexamethasone. "Chemokines such as IL-8 and CCL2 are known to mediate the influx of immune cells in the central nervous system compartment during bacterial meningitis, and CXCL13 is the major determinant of B cell recruitment into the cerebrospinal fluid during neuroinflammation," explained Dr. Philipp.

Infection with Bb led to many histopathologic findings in infected animals not treated with dexamethasone, such as leptomeningitis, vasculitis, focal inflammation in the brain and spinal cord, and necrotizing focal neurodegeneration and demyelination in the cervical spinal cord. Evaluation of the dorsal root ganglia showed inflammation with neurodegeneration, along with significant apoptosis of neuronal and satellite glial cells (which surround sensory neurons), in all infected animals with the exception of those treated with dexamethasone. Researchers were able to quantify the protective effect of dexamethasone treatment in protecting both satellite glial cell and neuronal apoptosis; in contrast, meloxicam treatment was only effective in protecting against satellite glial cell apoptosis and only after prolonged administration.

The dorsal roots of animals infected with live Bb (but not treated with dexamethasone) showed the presence of abundant lymphocytes and monocytes. Interestingly, reactions near the injection sites were histologically different from the more diffuse inflammation found along the spinal cord. The pathology found in the dorsal root ganglia and sensory nerves may explain the localized pain and motor deficits that Lyme disease patients experience close to the origin of the tick bite.

Some patients with Lyme disease also show evidence of demyelinating neuropathy and slowing nerve conduction. Nerve conduction studies in motor and sensory nerves of the macaques showed that the Bb infection resulted in specific electrophysiological abnormalities (increased F wave latencies and chronodispersion) that could be prevented with dexamethasone.

Although antibiotics are the standard and necessary first-line treatment for Lyme disease, the results show the potential therapeutic impact of anti-inflammatory or immune-modulatory agents for Lyme-related neuroborreliosis. Most of the neuropathological changes produced by Bb infection were prevented by dexamethasone, a broad-spectrum steroidal anti-inflammatory drug, whereas the non-steroidal anti-inflammatory drug meloxicam was generally ineffective or only partially effective. Analyses of the differences in the mechanisms of action of both drugs may provide a blueprint for the development of new adjuvant treatments for LNB.

"Importantly, we found necrotizing myelitis and degeneration in the spinal cord, neurodegeneration in the dorsal root ganglia, and demyelination in the nerve roots only when lymphocytic inflammatory lesions were also observed in both the central nervous system and peripheral nervous system," stated Dr. Philipp. "Our results suggest that ongoing cytokine activation in the nervous system can contribute to the persistent symptoms of fatigue, pain, and cognitive dysfunction that patients sometimes experience despite having been treated for Lyme disease."
Does this mean dexamethasone (or perhaps other broad-spectrum steroidal anti-inflammatory drugs) may have a role to play in the treatment of Lyme neuroborreliosis -- possibly even after a course of antibiotic therapy for those who continue to suffer after IDSA-approved treatment?

I wonder how long it will take researchers to make the leap to human subjects in clinical trials.

RitaA
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Re: Inflammation in the Pathogenesis of LNB

Post by RitaA » Sat 18 Apr 2015 20:15

There is a 2012 thread about an earlier article by some of the same authors:

http://www.lymeneteurope.org/forum/view ... f=5&t=3805

RitaA
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Re: Inflammation in the Pathogenesis of LNB

Post by RitaA » Sat 18 Apr 2015 21:47

Some doctors are apparently already treating at least some of their LNB patients with steroids (in the following example prednisone) in addition to antibiotics. Here's just one example from a 2014 case report (previously posted in another thread):

http://www.ncbi.nlm.nih.gov/pubmed/25580319
The twenty-one-day therapy with ceftriaxone (2 g once daily) was administered, supported by prednisone and vitamin B preparations.
Here’s hoping that any future IDSA treatment guidelines will at least mention this treatment approach – i.e. when (and if) steroids may (or may not) have a beneficial role to play in some Lyme disease patients. Steroids are generally contraindicated in patients with known immune deficiency (e.g. CVID), however there may be exceptions to this general rule -- as noted in the following snippet:

http://emedicine.medscape.com/article/1051103-treatment
Common Variable Immunodeficiency Treatment & Management

In most patients, CVID responds well to Ig therapy. The recurrence of infections, arthritic symptoms, and the severity and/or incidence of the autoimmune disease are reduced. Gastrointestinal disease shows little improvement with IVIG. In some patients with severe autoimmune disease, the concurrent use of steroids or other immunosuppressive drugs may be needed.

duncan
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Re: Inflammation in the Pathogenesis of LNB

Post by duncan » Sat 18 Apr 2015 22:46

Thanks for posting this, Rita.

This study is a bit of a curiosity for me. There seems to be two main takeaways: There is inflammation in acute cases of LNB, and steroids, in conjunction with conventional abx therapy, helps mitigate that inflammation.

Ok, so, haven't we always known there is inflammation in acute NB? Geez, CXCL13 was promoted for a while as a bio-marker until it was more or less discarded because supposedly it only reliably appeared in acute cases.

Now, treating with steroids is different, and as you suggested Rita, I'd thought steroids were to be avoided at all costs. This represents a departure from that belief, and from Tulane no less.

They only did follow-up with the monkeys 14 weeks out. The obvious question is, did they muffle the cytokine/chemokine roar, only to empower an explosion of the cause of that immune response,i.e., Borrelia?
Last edited by duncan on Sat 18 Apr 2015 23:54, edited 2 times in total.

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ChronicLyme19
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Re: Inflammation in the Pathogenesis of LNB

Post by ChronicLyme19 » Sat 18 Apr 2015 23:06

duncan wrote:Now, treating with steroids is different, and as you suggested Rita, I'd thought steroids were to be avoided at all costs. This represents a departure from that belief, and from Tulane no less.
That's what I had heard as well, no steroids for lyme patients unless their adrenals were trashed. I wonder if there is a happy medium... Or like RitaA said, maybe it's warranted in cases for folks who have really strong inflammatory response post infection that just keeps going. I wonder if this would work for folks with other causes of chronic autoimmune nerve pain like guillain barre.

Thanks for posting, really intriguing stuff.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

lou
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Re: Inflammation in the Pathogenesis of LNB

Post by lou » Sun 19 Apr 2015 1:58

Well, what we really need is less inflammation in chronic lyme cases. What about concurrent antibiotics and steroids? I would have assumed that anyone with longterm chronic lyme has got various autoimmune markers, not to mention high levels of inflammation that are causing damage too.

RitaA
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Re: Inflammation in the Pathogenesis of LNB

Post by RitaA » Mon 20 Apr 2015 5:26

Here are two more case reports where steroids were used in addition to antibiotic treatment:

http://www.ncbi.nlm.nih.gov/pubmed/15698718
Diagn Microbiol Infect Dis. 2005 Feb;51(2):127-30.

Severe neuroborreliosis: The benefit of prolonged high-dose combination of antimicrobial agents with steroids--an illustrative case

Massengo SA1, Bonnet F, Braun C, Vital A, Beylot J, Bastard J.

Author information

1 Department of Neurology, Centre Hospitalier de Mont de Marsan, 40000 Mont de Marsan, France.

Abstract

Neuroborreliosis frequently occurs in endemic areas, whereas encephalomyelitis is uncommon. Treatment consists classically of 2 to 4 weeks of recommended antimicrobial agents with a generally good outcome. A severe case is reported combining an encephalomyelitis with an axonal polyneuropathy. Clinical improvement was observed only with the use of prolonged high dose of 2 antimicrobial agents combined with steroids.

PMID:
15698718
[PubMed - indexed for MEDLINE
http://www.ncbi.nlm.nih.gov/pubmed/22790802
Rinsho Shinkeigaku. 2012;52(6):411-5.

[Successful treatment of neuroborreliosis with combined administration of antibiotics and steroids: a case report].

[Article in Japanese]

Takado Y1, Shimohata T, Kawachi I, Tanaka K, Nishizawa M.

Author information

1 Department of Neurology, Brain Research Institute, Niigata University.

Abstract

A 66-year-old woman developed bilateral facial paralysis as well as sensory and motor disturbances of extremities. Two months after the onset of paralysis, she also developed sensory disturbance of her trunk and vesicorectal disturbance, and her symptoms worsened gradually. Because the interferon-γ level in the cerebrospinal fluid was elevated, we suspected that her symptoms were caused by polyneuropathy and myelitis associated with infection. Her serum IgM and IgG antibodies against Borrelia garinii and B. afzelli were positive. Therefore, we diagnosed her as having neuroborreliosis. Her symptoms gradually improved after the combined administration of antibiotics and steroids. The present case report showed that it might be better to consider the possibility of neuroborreliosis when there are increasing concentrations of cytokine and chemokine, and that combination treatment with antibiotics and steroids can be used for the treatment of this disease.

PMID:
22790802
[PubMed - indexed for MEDLINE]
What do current treatment guidelines have to say about the use of steroids?

http://icnapedia.org/guidelines/open/EF ... liosis.pdf
European Journal of Neurology 2010, 17: 8–16

Received 7 August 2009
Accepted 2 October 2009

doi:10.1111/j.1468-1331.2009.02862.x

EFNS GUIDELINES/CME ARTICLE

EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis
(Page 5)
Treatment

Early LNB

Early LNB with manifestations confined to the PNS and meninges

Effective agents

In 1983, two class IV, small case series indicated the effect of high dose intravenous (IV) penicillin [86,87]. Several class III and IV studies have reported response to 10- to 28-day courses of IV penicillin (20 million U daily), IV ceftriaxone (2 or 4 g daily), IV cefotaxime (3 g · 2 g or 2 g · 3 g daily) and oral doxycycline (200 mg daily for 2 days and 100 mg daily for 8 days) [14,88–91] (Table 3). IV ceftriaxone, cefotaxime and penicillin seem to have similar efficacy [88,90,91] (class III). First-generation cephalosporins were ineffective in vitro against Bb in an American study [92]. There are not enough data to support the use of the following: metronidazole, trimetoprim-sulfamethoxazole, fluconazole, isoniazid, combinations of antibiotics or steroids.
(Page 7)
Late LNB

Effective agents

There are no randomized treatment studies of European late LNB. Small subgroup analyses and case studies indicate the effect of IV ceftriaxone (2 g daily) given for 2–4 weeks, or IV penicillin (20 million U daily for 10 days) or doxycycline (200 mg daily) [16,91,101,105] (class IV). An American study showed better effect of ceftriaxone than penicillin [88] (class III). There are not enough data to support the use of steroids alone or in combination with antibiotics.
Here are the references to the use of steroids from the 2006 IDSA treatment guidelines:
Cranial nerve palsy has been treated satisfactorily with oral antibiotics [107, 155, 175]. One study suggested that the frequency and rate of recovery of seventh nerve palsy in patients treated with antibiotics appear to be the same as in untreated patients or in patients treated with corticosteroids, with or without concomitant antibiotic therapy [155]. In a study conducted in Europe, the authors concluded that oral doxycycline was effective for treatment of Lyme disease–associated seventh nerve palsy in patients with CSF pleocytosis [175]. Although seventh nerve palsy usually resolves with or without antibiotic treatment, untreated patients may be at especially high risk for development of Lyme arthritis, which was observed in 14 (87.5%) of 16 patients, according to one report [181]. Therefore, all patients with cranial nerve palsy in association with Lyme disease should receive antibiotic therapy, not primarily for the purpose of expediting recovery from the paralysis, which will usually resolve within a few weeks regardless of whether antimicrobial therapy is given, but rather to prevent later complications [181].
The presence of either papilledema or sixth cranial nerve palsy may indicate the presence of increased intracranial pressure. Although elevated intracranial pressure typically responds to systemic antibiotic therapy, other measures to lower pressure, such as serial lumbar punctures and use of corticosteroids or acetazolamide, may be considered in individual cases [160, 161]. CSF shunting was thought to be necessary in one patient to control increased intracranial pressure that appeared to be causing or contributing to loss of vision [160].
Anecdotally, some patients with antibiotic-refractory arthritis have appeared to benefit from intraarticular injections of corticosteroids, systemic administration of nonsteroidal anti-inflammatory agents (NSAIDs), or DMARDs, primarily hydroxychloroquine [206, 237, 238].
Patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy should be re-treated with another 4-week course of oral antibiotics or with a 2–4-week course of intravenous ceftriaxone (B-III) (tables 2 and 3). A second 4-week course of oral antibiotic therapy is favored by panel members for the patient whose arthritis has substantively improved but has not yet completely resolved, reserving intravenous antibiotic therapy for those patients whose arthritis failed to improve at all or worsened. Clinicians should consider waiting several months before initiating re-treatment with antimicrobial agents because of the anticipated slow resolution of inflammation after treatment. During this period, NSAIDs may be used, but intra-articular injections of corticosteroids are not recommended (D-III). If patients have no resolution of arthritis despite intravenous therapy, and if PCR results for a sample of synovial fluid (and synovial tissue, if available) are negative, symptomatic treatment is recommended (B-III). Symptomatic therapy might consist of NSAIDs, intra-articular injections of corticosteroids, or DMARDs, such as hydroxychloroquine; expert consultation with a rheumatologist is recommended. If persistent synovitis is associated with significant pain or limitation of function, arthroscopic synovectomy may reduce the duration of joint inflammation (B-II).
Last, but not least, here's an intriguing reference to the use of dexamethasone prior to antibiotics being administered in the treatment of bacterial meningitis:

http://en.wikipedia.org/wiki/Dexamethasone
Dexamethasone is often administered before antibiotics in cases of bacterial meningitis. It then acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases proinflammatory mediators that can cause a response which is harmful to the patient), thus improving prognosis and outcome.[7]

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ChronicLyme19
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Re: Inflammation in the Pathogenesis of LNB

Post by ChronicLyme19 » Mon 20 Apr 2015 13:55

So from what you posted it looks like the use of steroids may be dependent on the individual and on how bad their inflammatory response is. I'll add in maybe also if their adrenals are depleted.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

RitaA
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Re: Inflammation in the Pathogenesis of LNB

Post by RitaA » Mon 20 Apr 2015 17:19

It certainly does appear as though a risk versus benefit analysis needs to be done on a case-by-case basis.

Here's a case study where steroids were not administered despite increased intracranial pressure:

http://onlinelibrary.wiley.com/doi/10.1 ... 0849.x/pdf
Developmental Medicine & Child Neurology 2002, 44: 641–642

Developmental Medicine & Child Neurology Volume 44, Issue 9, Article first published online: 13 FEB 2007

Intracranial hypertension in neuroborreliosis

Christoph Härtel*;
Stefan Schilling, Department of Paediatrics;
Birte Neppert, Department of Ophthalmology;
Bettina Tiemer, Institute of Medical Microbiology;
Jürgen Sperner, Department of Paediatrics, University of
Lübeck Medical School, Lübeck, Germany.

Neuroborreliosis is an infection of the nervous system caused by the spirochete Borrelia burgdorferi, from which patients most commonly develop lymphocytic meningitis, radiculoneuritis, or cranial neuropathy. In this report a 9-year-old male with an unusual neurological complication of neuroborreliosis – benign intracranial hypertension (BIH) – is described. Clinical symptoms of BIH, which consist of increased CSF pressure in the absence of an intracranial mass or obstruction to the circulation of CSF, resolved completely after antibiotic therapy with ceftriaxone.

Benign intracranial hypertension (BIH) is a clinical entity characterized by: (1) increased intracranial pressure, (2)
papilledema and visual disturbances, and (3) no pathological findings in cranial CT or MRI. Various aetiological factors have been associated with BIH in children including obesity, arterial hypertension, otitis media, head injuries, antibiotics, corticosteroid withdrawal, deficiency or excess of vitamin A, iron deficiency anaemia, and disturbances of endocrinological metabolism (Cinceripini et al. 1999). However, in a significant number of children BIH has no detectable aetiology, therefore it is defined as idiopathic. In neuroborreliosis – an infection of the nervous system caused by the spirochete Borrelia burgdorferi – patients most commonly develop lymphocytic meningitis, radiculoneuritis, or cranial neuropathy. Many patients, however, present with unusual focal neurological symptoms. In this report we describe a 9-year-old male who had BIH with trochlear palsy due to neuroborreliosis.

Case report

A 9-year-old male with no history of significant illness was admitted to our children’s hospital in January 2001 because of diplopia. The patient’s mother remembered the child had received two tick bites during the previous summer, about 7 and 9 months earlier. Physical examination revealed no fever, no arthralgia, nor erythema, but an infection of the upper respiratory tract and a palsy of the left trochlear nerve resulting in vertical and torsional diplopia in the right gaze. The patient had visual acuity of 1.25 and intact visual fields in both eyes. In
ophthalmoscopic and ultrasound examination a marked bilateral papilledema (right > left, 1/0.6mm) of the optic disc was found (Fig. 1), whereas retinal, vascular, or chorioidal abnormalities were not obvious. Visually evoked potentials (VEP) revealed normal amplitudes for both eyes, however, a slight prolongation of latencies in both eyes was noted, which was not consistent with optic neuritis. On cranial CT and MRI examination there were no sellar or suprasellar abnormalities, normal-sized lateral ventricles, nor subarachnoid spaces. A lumbar puncture showed an elevated opening CSF pressure of 28cm H2O (horizontal position, no sedatives administered) with nine lymphocytes/μL and normal protein (0.25g/L), glucose (61mg/dL), and lactate (1.2μmol/L) concentrations. Furthermore, EEG and biochemical findings including differential blood cell count; blood coagulation; serum electrolytes; urine analysis; renal, hepatic, and thyroid functions; antibodies against cardiolipin; mitochondria; liver–kidney microsomes; and antinuclear antigens were normal. For treatment of BIH, a therapy with acetazolamide 10mg/kg body weight/day and furosemide 1mg/kg body weight/day was initiated. The patient was still disturbed by diplopia on gaze to the right after day 5 of therapy, when IgM and IgG antibodies in CSF and serum against Borrelia burgdorferi were proved to be highly positive by specific enzyme-linked fluorescent assay (Index 2.1, regarded as positive if >1; Vidas Lyme IgG and IgM Kit; bioMerieux, Paris, France). The diagnosis of neuroborreliosis was verified by immunoblot (IgM positive for Osp C and p41 protein-fragments; IgG positive for p83/100, p41, p39, Osp C protein-fragments) of serum and CSF. Serological findings for neurotropic viruses such as adenovirus, cytomegalovirus, herpes simplex, Coxsackie, measles, parotitis, and varicella zoster virus were not evident for an acute infection. Thus, an intravenous antibiotic therapy with 2g ceftriaxone (80mg/kg body weight/day) was initiated, while the treatment with acetazolamide and furosemide was withdrawn. After 14 days of ceftriaxone therapy the diplopia resolved promptly and the patient was discharged from the hospital. In a clinical control examination 3 months later, the trochlear nerve palsy, the bilateral papilledema, as well as the slight VEP latency prolongation were no longer evident and the child remains well until now.

Discussion

Neuroborreliosis has become the most frequently diagnosed arthropod-borne infection of the nervous system in Europe and the USA (Christen 1996). In children, the yearly incidence of neuroborreliosis is about five cases per
100 000 children. Lymphocytic meningitis and radiculoneuritis (Bannwarth syndrome) as well as cranial neuropathy with the facial nerve being much more affected than other cranial nerves, account for nearly 90% of all paediatric cases with neuroborreliosis. We described the rare association of neuroborreliosis presenting with BIH and an isolated unilateral trochlear nerve palsy. In our patient oral therapy with furosemide and acetazolamide was not beneficial for precipitation of BIH and therefore withdrawn. Several investigators recommend the use of steroids for BIH in order to prevent injury of the optic nerve (Cinceripini et al. 1999). However, the rapid resolution of neurological symptoms upon ceftriaxone in our patient did not support the additional use of steroids.

In summary, this case report clearly demonstrates that neuroborreliosis can masquerade as BIH (Kan et al. 1998).
Furthermore, it underlines the need to rule out infection, including by serology, for treatment of BIH before considering the use of steroids which could have serious consequence for progression of the infectious disease.

Accepted for publication 26th April 2002.

RitaA
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Re: Inflammation in the Pathogenesis of LNB

Post by RitaA » Mon 20 Apr 2015 20:58

Whew! I'm really glad I'm not a doctor who has to decide whether or not to use steroids while treating a patient with Lyme neuroborreliosis.

Have a look at the sometimes rather vague advice and contradictory statements contained in excerpts from just a few books. Please excuse any typos as I quickly scribbled down the text before keying it in.

https://books.google.ca/books?id=W8OVDN ... ds&f=false
Lyme Disease: An Evidence Based Approach

edited by John J. Halperin (2011)
Page 218:
Finally, over the years there has been concern about the role of corticosteroids (Pachner et al., 2001). As steroids are now of demonstrated efficacy in facial nerve palsies (Sullivan et al., 2007) and have been shown to help in painful Lyme radiculitis (Pfister et al., 1988), this becomes an important point. Although there are no systematic studies addressing this definitively, evidence in other bacterial meningitides (Brouwer et al., 2010) and non-systematic evidence in patients with neuroborreliosis suggest that, as long as appropriate antibiotics are also administered, steroids do not worsen the progression and may be considered judiciously in appropriate circumstances.
https://books.google.ca/books?id=GgQshX ... ds&f=false
Bacterial Infections of the Central Nervous System

edited by Karen L. Roos, Allan R. Tunkel (2010)

Page 202:
Spirochetal Infections by D. Cadavid

Treatment of Late Lyme Neuroborreliosis

Corticosteroids are not recommended in patients with Lyme neuroborreliosis. Although early reports suggested that steroid therapy resolved radicular pain in meningopolyneuritis, subsequent controlled trials showered that pain resolved almost as quickly with antimicrobial treatment alone (Pfisler et al., 1988). Furthermore, steroid use has been associated with subsequent antimicrobial treatment failure during late disease in humans (Dattwyler et al., 1988) and worsening of disease in experimental animals (Cadavid et al., 2000); Straubinger et al., 2000).

https://books.google.ca/books?id=CmAGBA ... ds&f=false
Infections of the Central Nervous System

By Michael W. Scheld, W. Michael Scheld, M.D., Richard J. Whitley, Christina M. Marra (2014)
Page 683:
Chapter 39 Neuroborreliosis: Nervous System Involvement with Borrelia Species

There has been considerable uncertainty about the best approach for initiating antibiotic therapy for patients with meningitis or cranial or peripheral nerve involvement suspected but not yet proven to be Lyme disease. If an EM skin lesion is present, antimicrobial treatment, typically with oral doxycycline, can be started immediately. Because most patients with meningitis, cranial neuritis, and other disorders do not have Lyme disease, and because no clinical features reliably identify the subset of these patients who have Lyme disease, laboratory confirmation is essential before planning definitive treatment if there are sound epidemiologic reasons to think the patient might have been exposed to B. burgdorferi-infected ticks. If test results can be obtained within 24 to 48 hours, and there are no contraindications to several days of empirical treatment with oral doxycycline, then this can be started pending test results. On the other hand, the likelihood of disease progression during the 1 to 2 days required to obtain tests results is small, making deferred treatment an equally valid option. Notably, if the patient presents with facial nerve palsy and is seen within the first 72 hours of symptoms, oral corticosteroids (typically prednisone 50 to 60 mg per day [or equivalent]) for 5 days followed by a rapid taper (123) should be started immediately as such therapy has been shown to improve outcomes in Bell palsy, the most common cause of seventh nerve palsy in the general population (123). In this setting, concurrent initiation of empirical oral doxycycline is reasonable, pending test results, although there is no evidence that brief courses of steroids make neuroborreliosis more difficult to treat.


https://books.google.ca/books?id=wGPOZi ... ds&f=false
Pediatric Neurology, Part II: Handbook of Clinical Neurology


edited by Olivier Dulac, Maryse Lassonde, Harvey B. Sarnat
Newnes, Apr 23, 2013 - Medical - 544 pages

Page 1008:
Although steroid therapy may challenge eradication of the infection, corticosteroids may be indicated in patients with significant radiculo-neuritic pain (Noseworthy, 2006).


https://books.google.ca/books?id=T5UMm9 ... ds&f=false
Neurology

Marco Mumenthaler, Heinrich Mattle
Thieme, Jan 1, 2011 - Medical - 992 pages

Steroids are useful in the treatment of painful neuroborreliosis.

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