COVID-19 Vaccination in Young People with Functional Neurological Disorder: A Case-Control Study
Abstract
:1. Introduction
- Acute anxiety-related responses that manifest just prior to, during, or after the administration of the vaccine (e.g., fainting [vasovagal response], palpitations, hyperventilation, and fear cognitions) [29].
- Acute-onset functional neurological symptoms (±nonspecific functional symptoms) that manifest hours or days after the vaccination (e.g., weakness or paralysis, shaking, twitching and abnormal movements, limb posturing, gait irregularities, speech difficulties, and functional seizures) [29,31,32,33]. Using European terminology, the World Health Organization calls acute-onset functional neurological symptoms dissociative neurological symptom reactions (DNSRs) [29]. We retain the terms functional neurological symptoms and functional neurological disorder, which are used by the large majority of researchers in the field.
2. Methods
2.1. Participants
2.2. Data Acquisition
2.3. Analysis of Clinical Characteristics and Self-Report Data
3. Results
3.1. Participant Characteristics
3.2. Self-Report Measures and Heart Rate on Admission to the Research Program
3.3. Health Status at Time of Vaccination (or Option of Vaccination)
3.4. Vaccination Rates in Young People with FND and Healthy Controls
3.5. Rates of FND Symptoms in Response to the COVID-19 Vaccine as Reported by the Young Person and Family
- Case 1. Relapse of FND symptoms post COVID-19 vaccination in a child whose FND had resolved
- Case 2. Relapse of FND symptoms post COVID-19 vaccination in a young woman whose FND had resolved but who had experienced a number of short relapses with stress
- Case 3. Worsening of FND symptoms in unresolved FND
- Case 4. Worsening of FND symptoms in unresolved FND
- Case 5. New-onset FND following COVID-19 vaccination
- Case 6. New-onset FND following COVID-19 vaccination
3.6. Rate of COVID-19 Infection in Young People with FND and Healthy Controls
4. Discussion
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Perez, D.L.; Nicholson, T.R.; Asadi-Pooya, A.A.; Begue, I.; Butler, M.; Carson, A.J.; David, A.S.; Deeley, Q.; Diez, I.; Edwards, M.J.; et al. Neuroimaging in functional neurological disorder: State of the field and research agenda. Neuroimage Clin. 2021, 30, 102623. [Google Scholar] [CrossRef] [PubMed]
- Rai, S.; Foster, S.; Griffiths, K.R.; Breukelaar, I.A.; Kozlowska, K.; Korgaonkar, M.S. Altered resting-state neural networks in children and adolescents with functional neurological disorder. Neuroimage Clin. 2022, 35, 103110. [Google Scholar] [CrossRef] [PubMed]
- Chung, J.; Mukerji, S.; Kozlowska, K. Cortisol and alpha-amylase awakening response in children and adolescents with functional neurological (conversion) disorder. Aust. N. Z. J. Psychiatry 2022, 48674221082520. [Google Scholar] [CrossRef]
- Yang, T.; Roberts, C.; Brown, T.-W.; Lloyd, M.; Kwan, P.; O’Brien, T.J.; Velakoulis, D.; Rayner, G.; Malpas, C.B. Childhood trauma in patients with epileptic versus non-epileptic seizures. Epilepsia 2022. [Google Scholar] [CrossRef]
- Keynejad, R.C.; Frodl, T.; Kanaan, R.; Pariante, C.; Reuber, M.; Nicholson, T.R. Stress and functional neurological disorders: Mechanistic insights. J. Neurol. Neurosurg. Psychiatry 2019, 90, 813–821. [Google Scholar] [CrossRef] [Green Version]
- Espay, A.J.; Aybek, S.; Carson, A.; Edwards, M.J.; Goldstein, L.H.; Hallett, M.; LaFaver, K.; LaFrance, W.C., Jr.; Lang, A.E.; Nicholson, T.; et al. Current concepts in diagnosis and treatment of functional neurological disorders. JAMA Neurol. 2018, 75, 1132–1141. [Google Scholar] [CrossRef]
- Kozlowska, K.; Scher, S.; Helgeland, H. Functional Somatic Symptoms in Children and Adolescents: A Stress-System Approach to Assessment and Treatment; Palgrave Macmillan: London, UK, 2020. [Google Scholar]
- Henningsen, P.; Gundel, H.; Kop, W.J.; Lowe, B.; Martin, A.; Rief, W.; Rosmalen, J.G.M.; Schroder, A.; van der Feltz-Cornelis, C.; Van den Bergh, O.; et al. Persistent physical symptoms as perceptual dysregulation: A neuropsychobehavioral model and its clinical implications. Psychosom. Med. 2018, 80, 422–431. [Google Scholar] [CrossRef] [PubMed]
- Jungilligens, J.; Paredes-Echeverri, S.; Popkirov, S.; Barrett, L.F.; Perez, D.L. A new science of emotion: Implications for functional neurological disorder. Brain 2022, 145, 2648–2663. [Google Scholar] [CrossRef] [PubMed]
- Edwards, M.J.; Adams, R.A.; Brown, H.; Parees, I.; Friston, K.J. A Bayesian account of ‘hysteria’. Brain 2012, 135, 3495–3512. [Google Scholar] [CrossRef] [PubMed]
- Diez, I.; Larson, A.G.; Nakhate, V.; Dunn, E.C.; Fricchione, G.L.; Nicholson, T.R.; Sepulcre, J.; Perez, D.L. Early-life trauma endophenotypes and brain circuit-gene expression relationships in functional neurological (conversion) disorder. Mol. Psychiatry 2021, 26, 3817–3828. [Google Scholar] [CrossRef]
- Our World in Data. Coronavirus (COVID-19) Vaccinations. 2021. Available online: https://ourworldindata.org/covid-vaccinations (accessed on 2 September 2022).
- Australian Technical Advisory Group on Immunisation (ATAGI). ATAGI Statement Regarding Vaccination of Adolescents Aged 12–15 Years. Australian Government Department of Health. 2021. Available online: https://www.health.gov.au/news/atagi-statement-regarding-vaccination-of-adolescents-aged-12–15-years (accessed on 12 November 2022).
- Frenck, R.W., Jr.; Klein, N.P.; Kitchin, N.; Gurtman, A.; Absalon, J.; Lockhart, S.; Perez, J.L.; Walter, E.B.; Senders, S.; Bailey, R.; et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N. Engl. J. Med. 2021, 385, 239–250. [Google Scholar] [CrossRef] [PubMed]
- Ali, K.; Berman, G.; Zhou, H.; Deng, W.; Faughnan, V.; Coronado-Voges, M.; Ding, B.; Dooley, J.; Girard, B.; Hillebrand, W.; et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N. Engl. J. Med. 2021, 385, 2241–2251. [Google Scholar] [CrossRef] [PubMed]
- Rakusa, M.; Ozturk, S.; Moro, E.; Helbok, R.; Bassetti, C.L.; Beghi, E.; Bereczki, D.; Bodini, B.; Di Liberto, G.; Jenkins, T.M.; et al. COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper. Eur. J. Neurol. 2022, 29, 2163–2172. [Google Scholar] [CrossRef]
- Fasano, A.; Daniele, A. Functional disorders after COVID-19 vaccine fuel vaccination hesitancy. J. Neurol. Neurosurg. Psychiatry 2022, 93, 339–340. [Google Scholar] [CrossRef] [PubMed]
- Tabakman, R. Long COVID-19 in Children and Adolescents: What Do We Know? 2022. Available online: https://www.medscape.com/viewarticle/976788 (accessed on 12 November 2022).
- Lewis, D. Long COVID and kids: Scientists race to find answers. Nature 2021, 595, 482–483. [Google Scholar] [CrossRef] [PubMed]
- Berg, S.K.; Palm, P.; Nygaard, U.; Bundgaard, H.; Petersen, M.N.S.; Rosenkilde, S.; Thorsted, A.B.; Ersboll, A.K.; Thygesen, L.C.; Nielsen, S.D.; et al. Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (Long COVID Kids DK): A national, cross-sectional study. Lancet Child Adolesc. Health 2022, 6, 614–623. [Google Scholar] [CrossRef]
- Berg, S.K.; Nielsen, S.D.; Nygaard, U.; Bundgaard, H.; Palm, P.; Rotvig, C.; Christensen, A.V. Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (Long COVID Kids DK): A national, cross-sectional study. Lancet Child Adolesc. Health 2022, 6, 240–248. [Google Scholar] [CrossRef]
- Frontera, J.A.; Simon, N.M. Bridging knowledge gaps in the diagnosis and management of neuropsychiatric sequelae of COVID-19. JAMA Psychiatry 2022, 79, 811–817. [Google Scholar] [CrossRef]
- Nafilyan, V.; Bermingham, C.; Ward, I.L.; Morgan, J.; Zaccardi, F.; Khunti, K.; Stanborough, J.; Banerjee, A. Risk of Death Following SARS-CoV-2 Infection or COVID-19 Vaccination in Young People in ENGLAND: A Self-Controlled Case Series Study. medRxiv 2022. [Google Scholar] [CrossRef]
- United Kingdom Government Department of Health & Social Care. Universal Vaccination of Children and Young People Aged 12 to 15 Years against COVID-19. 2021. Available online: https://www.gov.uk/government/publications/universal-vaccination-of-children-and-young-people-aged-12-to-15-years-against-covid-19/universal-vaccination-of-children-and-young-people-aged-12-to-15-years-against-covid-19 (accessed on 12 November 2022).
- United Kingdom Government. COVID-19 Vaccination: A Guide for Eligible Children and Young People Aged 12 to 17 (Print Version 3). 2021. Available online: https://www.gov.uk/government/publications/covid-19-vaccination-resources-for-children-and-young-people (accessed on 12 November 2022).
- Butler, M.; Tamborska, A.; Wood, G.K.; Ellul, M.; Thomas, R.H.; Galea, I.; Pett, S.; Singh, B.; Solomon, T.; Pollak, T.A.; et al. Considerations for causality assessment of neurological and neuropsychiatric complications of SARS-CoV-2 vaccines: From cerebral venous sinus thrombosis to functional neurological disorder. J. Neurol. Neurosurg. Psychiatry 2021, 92, 1144–1151. [Google Scholar] [CrossRef]
- Goss, A.L.; Samudralwar, R.D.; Das, R.R.; Nath, A. ANA investigates: Neurological complications of COVID-19 vaccines. Ann. Neurol. 2021, 89, 856–857. [Google Scholar] [CrossRef] [PubMed]
- Assiri, S.A.; Althaqafi, R.M.M.; Alswat, K.; Alghamdi, A.A.; Alomairi, N.E.; Nemenqani, D.M.; Ibrahim, Z.S.; Elkady, A. Post COVID-19 Vaccination-associated neurological complications. Neuropsychiatr. Dis. Treat. 2022, 18, 137–154. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Causality Assessment of an Adverse Event Following Immunization (AEFI): User Manual for the Revised WHO Classification, 2nd ed.; World Health Organization: Geneva, Switzerland, 2019; Available online: https://apps.who.int/iris/handle/10665/340802 (accessed on 12 November 2022).
- Linden, S.C.; Carson, A.J.; Wessely, S. Functional neurological disorder after vaccination: A balanced approach informed by history. J. R. Coll. Physicians Edinb. 2021, 51, 330–331. [Google Scholar] [CrossRef]
- Marchetti, R.L.; Gallucci-Neto, J.; Kurcgant, D.; Proenca, I.; Valiengo, L.; Fiore, L.A.; Pinto, L.F.; Maranhao, A.G.K.; Oliveira, M.; de Oliveira, L.H. Immunization stress-related responses presenting as psychogenic non-epileptic seizures following HPV vaccination in Rio Branco, Brazil. Vaccine 2020, 38, 6714–6720. [Google Scholar] [CrossRef]
- Lin, C.Y.; Peng, C.C.; Liu, H.C.; Chiu, N.C. Psychogenic movement disorder after H1N1 influenza vaccination. J. Neuropsychiatry Clin. Neurosci. 2011, 23, E37–E38. [Google Scholar] [CrossRef] [PubMed]
- Yang, T.U.; Kim, H.J.; Lee, Y.K.; Park, Y.J. Psychogenic illness following vaccination: Exploratory study of mass vaccination against pandemic influenza A (H1N1) in 2009 in South Korea. Clin. Exp. Vaccine Res. 2017, 6, 31–37. [Google Scholar] [CrossRef] [Green Version]
- Kozlowska, K.; Rampersad, R.; Cruz, C.; Shah, U.; Chudleigh, C.; Soe, S.; Gill, D.; Scher, S.; Carrive, P. The respiratory control of carbon dioxide in children and adolescents referred for treatment of psychogenic non-epileptic seizures. Eur. Child Adolesc. Psychiatry 2017, 26, 1207–1217. [Google Scholar] [CrossRef] [Green Version]
- Arnsten, A.F. Stress weakens prefrontal networks: Molecular insults to higher cognition. Nat. Neurosci. 2015, 18, 1376–1385. [Google Scholar] [CrossRef]
- Hofmann, S.G.; Ellard, K.K.; Siegle, G.J. Neurobiological correlates of cognitions in fear and anxiety: A cognitive-neurobiological information-processing model. Cogn. Emot. 2012, 26, 282–299. [Google Scholar] [CrossRef] [Green Version]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th ed.; American Psychiatric Association: Arlington, VA, USA, 2013. [Google Scholar]
- Kozlowska, K.; Mohammad, S. Functional neurological disorder in children and adolescents: Assessment and treatment. In Symptom Based Approach to Pediatric Neurology; Sivaswamy, L., Kamat, D., Eds.; Springer Nature: Berlin/Heidelberg, Germany, forthcoming in 2022.
- Lovibond, S.H.; Lovibond, P.F. Manual for the Depression Anxiety Stress Scale; Psychological Foundation of Australia: Sydney, Australia, 1995. [Google Scholar]
- Patrick, J.; Dyck, M.; Bramston, P. Depression anxiety stress scale: Is it valid for children and adolescents? J. Clin. Psychol. 2010, 66, 996–1007. [Google Scholar] [CrossRef]
- Cohen, R.A.; Hitsman, B.L.; Paul, R.H.; McCaffery, J.; Stroud, L.; Sweet, L.; Gunstad, J.; Niaura, R.; MacFarlane, A.; Bryant, R.A.; et al. Early life stress and adult emotional experience: An international perspective. Int. J. Psychiatry Med. 2006, 36, 35–52. [Google Scholar] [CrossRef] [PubMed]
- Kozlowska, K.; Sawchuk, T.; Waugh, J.L.; Helgeland, H.; Baker, J.; Scher, S.; Fobian, A. Changing the culture of care for children and adolescents with functional neurological disorder. Epilepsy Behav. Rep. 2021, 16, 1004486. [Google Scholar] [CrossRef] [PubMed]
- Chung, I.H.; Chin, W.C.; Huang, Y.S.; Wang, C.H. Pediatric narcolepsy: A practical review. Children 2022, 9, 974. [Google Scholar] [CrossRef]
- Kornum, B.R.; Knudsen, S.; Ollila, H.M.; Pizza, F.; Jennum, P.J.; Dauvilliers, Y.; Overeem, S. Narcolepsy. Nat. Rev. Dis. Prim. 2017, 3, 16100. [Google Scholar] [CrossRef] [PubMed]
- Bassetti, C.L.A.; Adamantidis, A.; Burdakov, D.; Han, F.; Gay, S.; Kallweit, U.; Khatami, R.; Koning, F.; Kornum, B.R.; Lammers, G.J.; et al. Narcolepsy—Clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat. Rev. Neurol. 2019, 15, 519–539. [Google Scholar] [CrossRef]
- Plazzi, G.; Clawges, H.M.; Owens, J.A. Clinical characteristics and burden of illness in pediatric patients with narcolepsy. Pediatr. Neurol. 2018, 85, 21–32. [Google Scholar] [CrossRef]
- American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed.; American Academy of Sleep Medicine: Darien, IL, USA, 2014. [Google Scholar]
- Liblau, R.S.; Vassalli, A.; Seifinejad, A.; Tafti, M. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy. Lancet Neurol. 2015, 14, 318–328. [Google Scholar] [CrossRef] [PubMed]
- Partinen, M.; Kornum, B.R.; Plazzi, G.; Jennum, P.; Julkunen, I.; Vaarala, O. Narcolepsy as an autoimmune disease: The role of H1N1 infection and vaccination. Lancet Neurol. 2014, 13, 600–613. [Google Scholar] [CrossRef] [PubMed]
- Partinen, M.; Saarenpaa-Heikkila, O.; Ilveskoski, I.; Hublin, C.; Linna, M.; Olsen, P.; Nokelainen, P.; Alen, R.; Wallden, T.; Espo, M.; et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS ONE 2012, 7, e33723. [Google Scholar] [CrossRef] [Green Version]
- Han, F.; Lin, L.; Warby, S.C.; Faraco, J.; Li, J.; Dong, S.X.; An, P.; Zhao, L.; Wang, L.H.; Li, Q.Y.; et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann. Neurol. 2011, 70, 410–417. [Google Scholar] [CrossRef]
- Hatmal, M.M.; Al-Hatamleh, M.A.I.; Olaimat, A.N.; Mohamud, R.; Fawaz, M.; Kateeb, E.T.; Alkhairy, O.K.; Tayyem, R.; Lounis, M.; Al-Raeei, M.; et al. Reported adverse effects and attitudes among arab populations following COVID-19 Vaccination: A large-scale multinational study implementing machine learning tools in predicting post-vaccination adverse effects based on predisposing factors. Vaccines 2022, 10, 366. [Google Scholar] [CrossRef]
- Hyams, J.S.; Di Lorenzo, C.; Saps, M.M.; Shulman, R.J.; Staiano, A.; van Tilburg, M. Childhood functional gastrointestinal disorders: Child/adolescent. Gastroenterology 2016, 150, 1456–1468. [Google Scholar] [CrossRef]
- Perez, D.L.; Aybek, S.; Popkirov, S.; Kozlowska, K.; Stephen, C.D.; Anderson, J.; Shura, R.; Ducharme, S.; Carson, A.; Hallett, M.; et al. A review and expert opinion on the neuropsychiatric assessment of motor functional neurological disorders. J. Neuropsychiatry Clin. Neurosci. 2021, 33, 14–26. [Google Scholar] [CrossRef]
- Viswanathan, N.; Benbadis, S.R. The diagnosis of functional seizures: VideoEEG in the context of a complete clinical picture remains the gold standard for diagnosis of functional seizures. Pract. Neurol. 2022, 63–66. [Google Scholar]
- Wieder, L.; Brown, R.; Thompson, T.; Terhune, D.B. Suggestibility in functional neurological disorder: A meta-analysis. J. Neurol. Neurosurg. Psychiatry 2021, 92, 150–157. [Google Scholar] [CrossRef]
- Helgeland, H.; Savage, B.; Kozlowska, K. Hypnosis in the treatment of functional somatic symptoms in children and adolescents. In Routledge International Handbook of Clinical Hypnosis; Linden, J.H., De Benedittis, G., Sugarman, L.I., Varga, K., Eds.; Routledge Taylor & Francis: London, UK, Forthcoming 2023.
- Stone, J. Functional neurological disorders: The neurological assessment as treatment. Pract. Neurol. 2016, 16, 7–17. [Google Scholar] [CrossRef]
- Godoy, L.D.; Rossignoli, M.T.; Delfino-Pereira, P.; Garcia-Cairasco, N.; de Lima Umeoka, E.H. A comprehensive overview on stress neurobiology: Basic concepts and clinical implications. Front. Behav. Neurosci. 2018, 12, 127. [Google Scholar] [CrossRef] [Green Version]
- McEwen, B.S.; Gray, J.D.; Nasca, C. Redefining neuroendocrinology: Stress, sex and cognitive and emotional regulation. J. Endocrinol. 2015, 226, T67–T83. [Google Scholar] [CrossRef] [Green Version]
- Dantzer, R. Neuroimmune interactions: From the brain to the immune system and vice versa. Physiol. Rev. 2018, 98, 477–504. [Google Scholar] [CrossRef]
- Gianaros, P.J.; Wager, T.D. Brain-body pathways linking psychological stress and physical health. Curr. Dir. Psychol. Sci. 2015, 24, 313–321. [Google Scholar] [CrossRef]
- Edwards, R.R.; Kronfli, T.; Haythornthwaite, J.A.; Smith, M.T.; McGuire, L.; Page, G.G. Association of catastrophizing with interleukin-6 responses to acute pain. Pain 2008, 140, 135–144. [Google Scholar] [CrossRef]
- Lazaridou, A.; Martel, M.O.; Cahalan, C.M.; Cornelius, M.C.; Franceschelli, O.; Campbell, C.M.; Haythornthwaite, J.A.; Smith, M.; Riley, J.; Edwards, R.R. The impact of anxiety and catastrophizing on interleukin 6 responses to acute painful stress. J. Pain Res. 2018, 11, 637–647. [Google Scholar] [CrossRef] [Green Version]
- Shephard, B. A War of Nerves: Soldiers and Psychiatrists in the Twentieth Century; Harvard University Press: Cambridge, MA, USA, 2001. [Google Scholar]
- Han, V.X.; Kozlowska, K.; Kothur, K.; Lorentzos, M.; Wong, W.K.; Mohammad, S.S.; Savage, B.; Chudleigh, C.; Dale, R.C. Rapid onset functional tic-like behaviours in children and adolescents during COVID-19: Clinical features, assessment and biopsychosocial treatment approach. J. Paediatr. Child Health 2022, 58, 1181–1187. [Google Scholar] [CrossRef]
- Clements, C.J. Mass psychogenic illness after vaccination. Drug Saf. 2003, 26, 599–604. [Google Scholar] [CrossRef]
- Huang, W.T.; Hsu, C.C.; Lee, P.I.; Chuang, J.H. Mass psychogenic illness in nationwide in-school vaccination for pandemic influenza A(H1N1) 2009, Taiwan, November 2009–January 2010. Euro Surveill. 2010, 15, 19575. [Google Scholar] [CrossRef] [Green Version]
- Paredes-Echeverri, S.; Maggio, J.; Begue, I.; Pick, S.; Nicholson, T.R.; Perez, D.L. Autonomic, endocrine, and inflammation profiles in functional neurological disorder: A systematic review and meta-analysis. J. Neuropsychiatry Clin. Neurosci. 2022, 34, 30–43. [Google Scholar] [CrossRef]
- Kozlowska, K.; Palmer, D.M.; Brown, K.J.; McLean, L.; Scher, S.; Gevirtz, R.; Chudleigh, C.; Williams, L.M. Reduction of autonomic regulation in children and adolescents with conversion disorders. Psychosom. Med. 2015, 77, 356–370. [Google Scholar] [CrossRef]
- Chudleigh, C.; Savage, B.; Cruz, C.; Lim, M.; McClure, G.; Palmer, D.M.; Spooner, C.J.; Kozlowska, K. Use of respiratory rates and heart rate variability in the assessment and treatment of children and adolescents with functional somatic symptoms. Clin. Child Psychol. Psychiatry 2019, 24, 29–39. [Google Scholar] [CrossRef]
- Kozlowska, K.; Chung, J.; Cruickshank, B.; McLean, L.; Scher, S.; Dale, R.C.; Mohammad, S.S.; Singh-Grewal, D.; Prabhuswamy, M.Y.; Patrick, E. Blood CRP levels are elevated in children and adolescents with functional neurological symptom disorder. Eur. Child Adolesc. Psychiatry 2019, 28, 491–504. [Google Scholar] [CrossRef]
- Kozlowska, K.; Melkonian, D.; Spooner, C.J.; Scher, S.; Meares, R. Cortical arousal in children and adolescents with functional neurological symptoms during the auditory oddball task. Neuroimage Clin. 2017, 13, 228–236. [Google Scholar] [CrossRef]
- Kozlowska, K.; Spooner, C.J.; Palmer, D.M.; Harris, A.; Korgaonkar, M.S.; Scher, S.; Williams, L.M. “Motoring in idle”: The default mode and somatomotor networks are overactive in children and adolescents with functional neurological symptoms. Neuroimage Clin. 2018, 18, 730–743. [Google Scholar] [CrossRef] [PubMed]
- Radmanesh, M.; Jalili, M.; Kozlowska, K. Activation of functional brain networks in children and adolescents with psychogenic non-epileptic seizures. Front. Hum. Neurosci. 2020, 14, 339. [Google Scholar] [CrossRef] [PubMed]
- Andersen, S.L. Neuroinflammation, Early-life adversity, and brain development. Harv. Rev. Psychiatry 2022, 30, 24–39. [Google Scholar] [CrossRef]
- Frank, M.G.; Weber, M.D.; Watkins, L.R.; Maier, S.F. Stress-induced neuroinflammatory priming: A liability factor in the etiology of psychiatric disorders. Neurobiol. Stress 2016, 4, 62–70. [Google Scholar] [CrossRef] [Green Version]
- Brenhouse, H.C.; Danese, A.; Grassi-Oliveira, R. Neuroimmune impacts of early-life stress on development and psychopathology. Curr. Top. Behav. Neurosci. 2019, 43, 423–447. [Google Scholar] [CrossRef]
- Frank, M.G.; Fonken, L.K.; Watkins, L.R.; Maier, S.F. Microglia: Neuroimmune-sensors of stress. Semin. Cell Dev. Biol. 2019, 94, 176–185. [Google Scholar] [CrossRef]
- Frank, M.G.; Fonken, L.K.; Watkins, L.R.; Maier, S.F. Acute stress induces chronic neuroinflammatory, microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation. Brain. Behav. Immun. 2020, 89, 32–42. [Google Scholar] [CrossRef]
- Araque, A.; Navarrete, M. Glial cells in neuronal network function. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2010, 365, 2375–2381. [Google Scholar] [CrossRef]
- Angulo, M.C.; Le Meur, K.; Kozlov, A.S.; Charpak, S.; Audinat, E. GABA, a forgotten gliotransmitter. Prog. Neurobiol. 2008, 86, 297–303. [Google Scholar] [CrossRef]
- Velez-Fort, M.; Audinat, E.; Angulo, M.C. Central role of GABA in neuron-glia interactions. Neuroscientist 2012, 18, 237–250. [Google Scholar] [CrossRef]
- Um, J.W. Roles of glial cells in sculpting inhibitory synapses and neural circuits. Front. Mol. Neurosci. 2017, 10, 381. [Google Scholar] [CrossRef] [PubMed]
- Thion, M.S.; Ginhoux, F.; Garel, S. Microglia and early brain development: An intimate journey. Science 2018, 362, 185–189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ginhoux, F.; Garel, S. The mysterious origins of microglia. Nat. Neurosci. 2018, 21, 897–899. [Google Scholar] [CrossRef] [PubMed]
- Bellavance, M.A.; Rivest, S. The HPA–immune axis and the immunomodulatory actions of glucocorticoids in the brain. Front. Immunol. 2014, 5, 136. [Google Scholar] [CrossRef] [Green Version]
- Stephenson, C.P.; Baguley, I.J. Functional neurological symptom disorder (conversion disorder): A role for microglial-based plasticity mechanisms? Med. Hypotheses 2018, 111, 41–48. [Google Scholar] [CrossRef] [PubMed]
- Kozlowska, K.; Griffiths, K.R.; Foster, S.L.; Linton, J.; Williams, L.M.; Korgaonkar, M.S. Grey matter abnormalities in children and adolescents with functional neurological symptom disorder. Neuroimage Clin. 2017, 15, 306–314. [Google Scholar] [CrossRef] [PubMed]
- Agorastos, A.; Pervanidou, P.; Chrousos, G.P.; Baker, D.G. Developmental trajectories of early life stress and trauma: A narrative review on neurobiological aspects beyond stress system dysregulation. Front. Psychiatry 2019, 10, 118. [Google Scholar] [CrossRef] [Green Version]
- Zannas, A.S.; Chrousos, G.P. Epigenetic programming by stress and glucocorticoids along the human lifespan. Mol. Psychiatry 2017, 22, 640–646. [Google Scholar] [CrossRef]
- Boyce, W.T.; Levitt, P.; Martinez, F.D.; McEwen, B.S.; Shonkoff, J.P. Genes, environments, and time: The biology of adversity and resilience. Pediatrics 2021, 147, e20201651. [Google Scholar] [CrossRef]
- Fobian, A.D.; Long, D.M.; Szaflarski, J.P. Retraining and control therapy for pediatric psychogenic non-epileptic seizures. Ann. Clin. Transl. Neurol. 2020, 7, 1410–1419. [Google Scholar] [CrossRef]
- Edwards, M.J. Functional neurological disorder: Lighting the way to a new paradigm for medicine. Brain 2021, 144, 3279–3282. [Google Scholar] [CrossRef] [PubMed]
- Stager, L.; Morriss, S.; McKibben, L.; Grant, M.; Szaflarski, J.P.; Fobian, A.D. Sense of control, selective attention and cognitive inhibition in pediatric functional seizures: A prospective case-control study. Seizure 2022, 98, 79–86. [Google Scholar] [CrossRef] [PubMed]
- Kleckner, I.R.; Zhang, J.; Touroutoglou, A.; Chanes, L.; Xia, C.; Simmons, W.K.; Quigley, K.S.; Dickerson, B.C.; Barrett, L.F. Evidence for a large-scale brain system supporting allostasis and interoception in humans. Nat. Hum. Behav. 2017, 1, 0069. [Google Scholar] [CrossRef] [Green Version]
- Vassilopoulos, A.; Mohammad, S.; Dure, L.; Kozlowska, K.; Fobian, A.D. Treatment approaches for functional neurological disorders in children. Curr. Treat. Options Neurol. 2022, 24, 77–97. [Google Scholar] [CrossRef]
Adverse Child Experience | Number Reporting ACEs | Percentage |
---|---|---|
Bullying/rejection by peers | 34 | 56.7% |
Parental separation/divorce | 22 | 36.1% |
Family conflict | 20 | 32.8% |
Other trauma | 19 | 31.1% |
Emotional abuse | 17 | 27.9% |
Born prematurely/birth complications | 16 | 26.2% |
Domestic violence | 13 | 21.3% |
Major surgery/repeated hospitalization | 12 | 19.7% |
Separated long period parent/sibling | 12 | 19.7% |
Natural disaster first-hand witness | 11 | 18.0% |
Physical abuse | 10 | 16.4% |
Life-threatening illness parent/sibling | 7 | 11.5% |
Sexual abuse | 6 | 9.8% |
Extreme poverty or neglect | 5 | 8.2% |
Life-threatening illness of injury | 4 | 6.6% |
Death of parent/sibling | 4 | 6.6% |
House destroyed by fire/other means | 3 | 4.9% |
Adopted | 0 | 0% |
Witness warfare | 0 | 0% |
Group | Number in Group | Comorbid Mental Health Condition | Comorbid Functional Syndrome |
---|---|---|---|
FND resolved | 31 | n = 20 Anxiety (n = 15) Depression (n = 7) PTSD (n = 2) | n = 4 POTS (n = 2) Complex/chronic pain (n = 1) Functional abdominal disorder (n = 1) |
FND resolved but pattern of short-lived relapsed with stress | 7 | n = 6 Anxiety (n = 6) Depression (n = 1) | n = 0 |
FND unresolved | 21 | n = 19 Anxiety (n = 12) Depression (n = 10) PTSD (n = 2) | n = 3 POTS (n = 2) Functional abdominal disorder (n = 2) |
FND triggered by vaccine | 2 | n = 2 Depression (n = 2) Anxiety (n = 1) PTSD (n = 1) | n = 1 Functional abdominal disorder (n = 1) |
Healthy controls | 46 | n = 0 | n = 0 |
Year and Vaccine Administered | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Case 1 | 2003 Infanrix HepB PedvaxHIB Poliomyelitis | 2004 Infanrix HepB PedvaxHIB Poliomyelitis | 2004 Infanrix HepB Poliomyelitis | 2004 PedvaxHIB Priorix | 2004 Meningitec | 2005 Prevenar 7 | 2005 Prevenar 7 | 2005 Varilrix | 2008 Infanrix IPV Priorix | 2016 Gardasil | 2016 Boostrix Gardasil | 2016 Gardasil Varilrix | 2021 Pfizer Comirnaty | 2021 Pfizer Comirnaty | 2022 Moderna Spikevax |
Case 2 | 2004 Infanrix HepB PedvaxHIB Poliomyelitis | 2004 Infanrix HepB PedvaxHIB Poliomyelitis | 2005 PedvaxHIB Poliomyelitis | 2005 Menjugate PedvaxHIB Prevenar 7 Priorix | 2005 Prevenar 7 Varilrix | 2008 Infanrix IPV Priorix | 2017 Boostrix Gardasil | 2017 Gardasil Varilrix | 2020 Afluria Quad | 2021 Pfizer Comirnaty | 2021 Pfizer Comirnaty | 2022 Pfizer Comirnaty | |||
Case 3 | 2003 Infanrix HepB Oral Polio PedvaxHIB | 2004 Infanrix HepB Oral Polio PedvaxHIB | 2004 Infanrix HepB Oral Polio | 2004 PedvaxHIB | 2004 Meningitec | 2008 Infanrix IPV Priorix | 2016 Boostrix Gardasil | 2016 Gardasil | 2017 Gardasil | 2021 Pfizer Comirnaty | 2021 Pfizer Comirnaty | 2022 Moderna Spikevax | |||
Case 4 | 2007 Infanrix Hexa Prevenar 7 | 2008 Infanrix Hexa Prevenar 7 Rotarix | 2008 Infanrix Hexa Prevenar 7 | 2008 Hiberix Meningitec Priorix | 2009 Varilrix | 2010 Panvax | 2010 Panvax | 2011 Infanrix IPV Priorix | 2021 Pfizer Comirnaty | 2021 Pfizer Comirnaty | |||||
Case 5 | 2005 Infanrix HepB PedvaxHIB Poliomyelitis Prevenar 7 | 2005 Infanrix HepB PedvaxHIB Poliomyelitis Prevenar 7 | 2005 Infanrix Hexa Prevenar 7 | 2006 Hiberix Meningitec Priorix | 2007 Varilrix | 2008 Vaxigrip | 2009 Infanrix IPV Priorix | 2018 Boostrix Gardasil 9 | 2019 Gardasil | 2021 Nimenrix | 2021 Pfizer Comirnaty | ||||
Case 6 | 2010 Infanrix Hexa Prevenar 7 Rotarix | 2010 Infanrix Hexa Prevenar 7 Rotarix | 2010 Infanrix Hexa Prevenar 7 | 2011 Hiberix Meningitec Priorix | 2011 Varilrix | 2012 Prevenar 13 | 2013 Infanrix IPV MMR II | 2018 FluQuadri | 2022 Pfizer Comirnaty | 2022 Pfizer Comirnaty |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lim, N.; Wood, N.; Prasad, A.; Waters, K.; Singh-Grewal, D.; Dale, R.C.; Elkadi, J.; Scher, S.; Kozlowska, K. COVID-19 Vaccination in Young People with Functional Neurological Disorder: A Case-Control Study. Vaccines 2022, 10, 2031. https://doi.org/10.3390/vaccines10122031
Lim N, Wood N, Prasad A, Waters K, Singh-Grewal D, Dale RC, Elkadi J, Scher S, Kozlowska K. COVID-19 Vaccination in Young People with Functional Neurological Disorder: A Case-Control Study. Vaccines. 2022; 10(12):2031. https://doi.org/10.3390/vaccines10122031
Chicago/Turabian StyleLim, Natalie, Nicholas Wood, Archana Prasad, Karen Waters, Davinder Singh-Grewal, Russell C. Dale, Joseph Elkadi, Stephen Scher, and Kasia Kozlowska. 2022. "COVID-19 Vaccination in Young People with Functional Neurological Disorder: A Case-Control Study" Vaccines 10, no. 12: 2031. https://doi.org/10.3390/vaccines10122031