OBM Neurobiology is an international peer-reviewed Open Access journal published quarterly online by LIDSEN Publishing Inc. By design, the scope of OBM Neurobiology is broad, so as to reflect the multidisciplinary nature of the field of Neurobiology that interfaces biology with the fundamental and clinical neurosciences. As such, OBM Neurobiology embraces rigorous multidisciplinary investigations into the form and function of neurons and glia that make up the nervous system, either individually or in ensemble, in health or disease. OBM Neurobiology welcomes original contributions that employ a combination of molecular, cellular, systems and behavioral approaches to report novel neuroanatomical, neuropharmacological, neurophysiological and neurobehavioral findings related to the following aspects of the nervous system: Signal Transduction and Neurotransmission; Neural Circuits and Systems Neurobiology; Nervous System Development and Aging; Neurobiology of Nervous System Diseases (e.g., Developmental Brain Disorders; Neurodegenerative Disorders).

OBM Neurobiology publishes research articles, technical reports and invited topical reviews. Although the OBM Neurobiology Editorial Board encourages authors to be succinct, there is no restriction on the length of the papers. Authors should present their results in as much detail as possible, as reviewers are encouraged to emphasize scientific rigor and reproducibility.

Free Publication in 2019
Current Issue: 2019  Archive: 2018 2017
Open Access Case Report
Changes in SPECT Brain Imaging in Pediatric Patients with Suspected Neuroborreliosis: A Series of 6 Cases

Laura Alonso Canal 1, *, Cecilia Paredes Mercado 1, , María José Quiles Blanco 2, , Marco Motta Calderón 2, 

1. MIP Salud. Calle Conde de Aranda 15. 28001 Madrid, Spain

2. Pediatric Service, San Rafael Hospital. Calle Serrano 199. 28016 Madrid, Spain

† These authors contributed equally to this work.

Correspondence: Laura Alonso Canal

Academic Editor: Bart Ellenbroek

Received: April 01, 2019 | Accepted: May 05, 2019 | Published: May 14, 2019

OBM Neurobiology 2019, Volume 3, Issue 2, doi:10.21926/obm.neurobiol.1902028

Recommended citation: Alonso Canal L, Paredes Mercado C, Quiles Blanco MJ, Motta Calderón M. Changes in SPECT Brain Imaging in Pediatric Patients with Suspected Neuroborreliosis: A Series of 6 Cases. OBM Neurobiology 2019;3(2):7; doi:10.21926/obm.neurobiol.1902028.

© 2019 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

Lyme disease is a spirochetal illness transmitted primarily through the bite of ticks. The disease has a broad spectrum of comorbid conditions including osteoarticular, cardiovascular, and neurological involvement. In addition, clinical variability depends on the age of affected individuals.

The Center for Disease Control recognizes the disease as an epidemic and mentions it to be a major morbidity burden in our environment because of the frequent lack of diagnosis and early treatment. Scientific literature mentions that Lyme disease is related to conditions such as fibromyalgia, autism, or attention deficit hyperactivity disorder, among others.

Single-photon emission-computed tomography (SPECT) brain imaging is an indirect technique to measure cerebral blood flow and can be useful in diagnosing neuroborreliosis and monitoring treatment.

We present a series of 6 pediatric cases with varied neuropsychiatric symptoms and suspected neuroborreliosis that showed abnormal findings in the cerebral SPECT.

Keywords

Lyme disease; Borrelia; Lyme neuroborreliosis; chronic fatigue syndrome; attention deficit disorder with hyperactivity; SPECT

1. Introduction

Lyme disease is a spirochetal illness transmitted primarily through the bite of ticks (especially by Ixodes ricinus in Europe). The disease has a broad spectrum of comorbid conditions including osteoarticular, cardiovascular, and neurological involvement. In addition, clinical variability depends on the age of affected individuals.

There is a scientific debate about the existence of a condition called “Chronic Lyme Disease” (stage 3 of the disease despite prior recommended short-term antibiotic treatment, which according to those scientists who support it is caused by persistent active infection) versus the so‑called “Post-Treatment Lyme Disease” (in which it is accepted that individuals correctly treated remain symptomatic because of a concurrent autoimmune process and not because of the continuity of the infection) [1]. Studies have shown the in vitro resistance of Borrelia to regular antibiotic protocols [1]. In addition, the infection persists in chronically ill patients with a history of treated Lyme disease [2].

Regardless of our stance on this debate, two things are undeniable. Firstly, the disease has reached epidemic proportions as recognized by the Center for Disease Control (CDC). Secondly, Borrelia burgdorferi infection carries a very high burden of morbidity in our area because of the frequent lack of diagnosis and early treatment [3].

Scientific literature mentions that Lyme disease is related to conditions such as fibromyalgia, autism, or attention deficit hyperactivity disorder, among others [4,5]. The term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) has been revised to pediatric acute‑onset neuropsychiatric syndrome (PANS) to consider that other infectious agents might also cause neurotoxicity by inducing autoantibody production [6]. One of the microorganisms involved is Borrelia.

Magnetic resonance imaging (MRI) is often the first technique to be performed in cases of suspected neuroborreliosis. However, this technique is insensitive and nonspecific in most patients with a central nervous system involvement [7].

Single-photon emission-computed tomography (SPECT) of the brain is an indirect technique to measure cerebral blood flow. Its use in pediatric patients is uncommon because it requires cooperation from patients (use of sedation during the test may result in artifacts) and involves a certain degree of radiation. SPECT studies have added significant value in the diagnostic workup and clinical management of psychiatric neurologically involved patients [8].

SPECT can also be useful in the diagnosis of neuroborreliosis, especially in cases with negative serology; it is also useful for monitoring treatment response [9]. Neurological Lyme disease has no pathognomonic SPECT patterns, although there are suggestive findings (primarily parietal and/or temporal cortex hypoperfusion) [9].

Since the existence of vascular or toxic encephalopathies is anecdotal in pediatric patients, SPECT could be a highly valid tool for screening organic diseases in neuropsychiatric syndromes.

The numbers of CD57+ NK cells are low in patients with Borrelia infection; this finding could also be used for diagnosis  [10].

Finally, the levels of proinflammatory cytokines such as interleukin (IL)–8 or monocyte chemoattractant protein 1 are usually elevated in these encephalopathic syndromes [11].

2. Cases

We present a series of six cases (five boys and one girl) with varying neuropsychiatric symptoms. All these cases experienced fatigue, and all but one patient had inattention and/or hyperactivity. Three patients had a known history of a tick bite. Only two patients had serological results positive for Borrelia, and only one could have met the CDC diagnostic criteria for Lyme disease (positive serology and an equivocal Western blot; meaning the patient had positivity to 2 Western blot bands but without fulfilling the criteria for Lyme confirmation by that test according to the current guidelines). The remaining patients with negative serology had positive enzyme-linked immuno- spot (ELISpot) results, except for one patient in whom that test was not performed (Table 1).

SPECT studies were performed in all patients by administering age- and weight-appropriate doses of technetium Tc99m intravenously and capturing photon emission 20–30 min after the injection. All patients showed changes in SPECT brain imaging; in 5 patients, the pattern was suggestive of neuroborreliosis (it included parietal and/or temporal cortical hypoperfusion). Figure 1 is a SPECT image of patient 4 (dark brown areas represent hypoperfused areas while brilliant red or white areas represent normally perfused areas).

Based on the parents’ request, the brain MRI was performed after the SPECT findings only for patient 2. The result was normal.

Five of the six patients had below normal levels of CD57+ NK cells (normal range, 60–360 cells/μL).

Two patients had high IL–8 levels (these levels were not measured in other patients) (normal range, < 10 pg/mL). Informed consent was provided by all patients older than 12 years and by all parents before the publication of this manuscript.

Table 1 Clinical, analytical, and imaging data of the patients.

Figure 1 SPECT imaging of the brain for patient number 4.

3. Conclusions

Current diagnostic guidelines for Lyme disease require positive serology and confirmation with Western blotting. This diagnostic protocol has been questioned in some studies [5,9]. ELISpot for Borrelia burgdorferi is not currently considered suitable for the diagnosis of Lyme disease, although the test is considered suitable for other infections such as tuberculosis. Nevertheless, recent scientific evidence shows the utility of ELISpot in the diagnosis of Borrelia infection [12,13].

The known history of a tick bite is usually present in only 30% of patients affected by Lyme disease.

We suggest the need to review the diagnostic protocol of Lyme disease in Spain (after considering the use of more sensitive tools such as Borrelia ELISpot and sensitive Borrelia polymerase chain reaction testing tissues or blood or sensitive cultures). Organicity must be conclusively ruled out in pediatric neuropsychiatric syndromes. SPECT studies could play an important role for this purpose; physicians should suspect neuroborreliosis in children showing parietal and/or temporal hypoperfused zones in Lyme endemic areas. Misdiagnosing pediatric Lyme disease as a psychological illness can lead to inappropriate treatment not only by prescribing psychotropic drugs to a child who does not need them (along with frequent side effects of the drugs) but also by leaving an infectious agent without antimicrobial intervention.

Author Contributions

Laura Alonso Canal: main author of the paper. Rest of authors contributed equally to this work (by helping elaborate the manuscript and obtain references).

Funding

This investigation did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing Interests

The authors have declared that no competing interests exist.

References

  1. Feng J, Li T, Yee R, Yuan Y, Bai C, Cai M, et al. Stationary phase persister/biofilm microcolony of Borrelia burgdorferi causes more severe disease in a mouse model of Lyme arthritis: implications for understanding persistence, Post-treatment Lyme disease syndrome (PTLDS), and treatment failure. Discov Med. 2019; 27: 125-138.
  2. Middelveen MJ, Sapi E, Burke J, Filush KR, Franco A, Fesler MC, et al. Persistent borrelia infection in patients with ongoing symptoms of Lyme disease. Healthcare (Basel). 2018; 6: 33. [CrossRef]
  3. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014; 12: 1103-1135. [CrossRef]
  4. Fallon BA, Kochevar JM, Gaito A, Nields JA. The underdiagnosis of neuropsychiatric Lyme disease in children and adults. Psychiatr Clin North Am. 1998; 21: 693-703. [CrossRef]
  5. Kuhn M, Bransfield R. Divergent opinions of proper Lyme disease diagnosis and implications for children co-morbid with autism spectrum disorder. Med Hypotheses. 2014; 83: 321-325. [CrossRef]
  6. Swedo SE, Frankovich J, Murphy TK. Overview of treatment of pediatric acute-onset neuropsychiatric syndrome. J Child Adolesc Psychopharmacol. 2017; 27: 562-565. [CrossRef]
  7. Niksefat M, Albashiti B, Burke D, Moshayedi P, Patira R, Knepper L. Extensive meningeal enhancement in acute central nervous system Lyme: Case series and review of literature. J Clin Neurosci. 2019. doi: 10.1016/j.jocn.2019.03.048. [Epub ahead of print]. [CrossRef]
  8. Amen DG, Highum D, Licata R, Annibali JA, Somner L, Pigott HE et al. Specific ways brain SPECT imaging enhances clinical psychiatric practice. J Psychoactive Drugs. 2012; 44: 96-106. [CrossRef]
  9. Donta ST, Noto RB, Vento JA. SPECT brain imaging in chronic Lyme disease. Clin Nucl Med. 2012; 37: e219-e222. [CrossRef]
  10. Stricker RB, Winger EE. Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunol Lett (2001). Immunol Lett. 2001; 76: 43-48. [CrossRef]
  11. Ramesh G, Benge S, Pahar B, Philipp MT. A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi. J Neuroinflamm. 2012; 9: 72. [CrossRef]
  12. Jin C, Roen DR, Lehmann PV, Kellermann GH. An Enhanced ELISPOT Assay for Sensitive Detection of Antigen-Specific T Cell Responses to Borrelia burgdorferi. Cells. 2013; 2: 607-620. [CrossRef]
  13. Widhe M, Jarefors S, Ekerfelt C, Vrethem M, Bergstrom S, Forsberg P et al. Borrelia-specific interferon-gamma and interleukin–4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome. J Infect Dis. 2004; 189: 1881-1891. [CrossRef]
Newsletter
Download PDF

TOP