Autoimmune Encephalitis Presenting With Malignant Catatonia in a 40-Year-Old Male Patient With COVID-19

Back to table of contents Previous article Next Clinical Case ConferenceFull AccessAutoimmune Encephalitis Presenting With Malignant Catatonia in a 40-Year-Old Male Patient COVID-19Jan Mulder, Ph.D., Amalia Feresiadou, M.D., David Fällmar, Robert Frithiof, Johan Virhammar, Annica Rasmusson, Elham Rostami, Eva Kumlien, Janet L. Cunningham, Ph.D.Jan MulderSearch for more papers by this author, FeresiadouSearch FällmarSearch FrithiofSearch VirhammarSearch RasmussonSearch RostamiSearch KumlienSearch CunninghamSearch Ph.D.Published Online:22 Jun 2021https://doi.org/10.1176/appi.ajp.2020.20081236AboutSectionsPDF/EPUB ToolsAdd favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail A 40-year-old man who had previously symptoms and positive test COVID-19, but no other previous medical or psychiatric conditions medication, presented the emergency unit with acute debut agitation, grimacing, repetitive speech movements (verbigeration stereotypies); his behavior was bizarre, disorganized, hyperkinetic, uncooperative met DSM-5 criteria catatonia.Twenty-two days before admission, patient developed COVID-19-related respiratory fatigue, which did not require hospital care. He tested SARS-CoV-2 RNA nasopharyngeal swab using Abbott RealTime assay on m2000 platform (day 14; Figure 1A). Anosmia ageusia were present. During several he suffered from headache. On admission 22), longer have fever (38.4°C). made eye contact, reflexes normal, Babinski’s sign absent. Treatment antibiotics acyclovir initiated until tests excluded bacterial infection herpes encephalitis. Brain CT, MRI, blood unremarkable. The lightly sedated midazolam, followed dexmedetomidine. Neuroleptics used.Lumbar puncture showed high red cell count (19,000 cells×106/L) secondary traumatic lumbar puncture. CSF indicated pleocytosis, 23×106/L mononuclear 8×106/L polymorphonuclear cells. Signs blood-brain barrier disruption present, elevated albumin levels CSF, at 838 mg/L; reference, <400 mg/L) CSF/serum quotient 15.6 (reference, <6.8). Interleukin-6 (IL-6) 102.1 pg/mL <5 pg/mL), neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), tau normal. PCR repeatedly negative swabs. Antineuronal antibodies against N-methyl-d-aspartate receptor (NMDAR), glutamic acid decarboxylase, contactin-associated protein-like 2, leucine-rich, glioma inactivated 1, ganglioside serum (Euroimmune, Lübeck, Germany).Hours later, patient’s state deteriorated, temperature rose 39°C. became mutistic signs autonomic instability, recurrent episodes fluctuating heart rate arterial pressure periods oxygen desaturation (Figure 1B). hypertension difficult treat, despite doses clonidine labetalol. Plasma lactate varied between 0.6 8 mmol/L 0.8–2.0 mmol/L), myoglobulin creatine kinase myocardial band (CKMB) remained pupil size, reaction light, oculocephalic reflex Slow, horizontal roving noted. displayed decorticate posturing increased tonus; resisted movement arms jaw normal tonus legs. Hyperreflexia bilateral foot clonus neck stiffness. Anesthesia induced propofol facilitate endotracheal intubation. D-Dimer slightly (1.2 reference <0.5 mg/L), without thromboembolic events. Respiration cardiovascular function stable. Continuous EEG monitoring nonspecific slowing left hemisphere predominance epileptiform activity. An episode asystole spontaneous recovery, bradycardia 27 bpm repeated P waves QRS complexes interpreted as third-degree atrioventricular block.Signs autoimmune encephalitis case meet proposed (1, 2). Standard radiological findings discrete pleocytosis nonspecific. Although diagnosis uncertain, para-infectious still suspected. Plasmapheresis three times over 4 days. After two courses, extubated autonomically Eye normalized hyperreflexia less prominent, persisted. 1 g methylprednisolone per day.On day 28, dramatic improvement. awake, oriented, communicative memories past distracted complex visual hallucinations black white figures (animals famous people) appearing right side. described them being mirror (suspected polyopia). These often stationary could make gestures. also an experience feeling that world different—strange unreal, brighter colors hyperchromatopsia derealization). frequent failing recognize hand leg own experienced their unexpected (alien syndrome). denied presence perceptual disturbances. His understanding Swedish, second language, seemed intact, responses mostly monosyllabic. name children give personal identification number slow mistakes naming months. Mild object agnosia Simultanagnosia deficits isolating tangled pictorial array, depict details global features pictures. recall one objects after short delay draw correct clock required repetitions instructions. difficulty mirroring performing fine movements. Finally, neglect read text. normal.A 10 cells ×106/L, IgG index, oligoclonal bands represented serum, indicating intrathecal production antibodies. IL-6 level normalized. GFAP NFL 1,030 ng/L <890 ng/L). MRI standard neurological examination 31 frequent. emotional lability mental disturbed short-term memory decision making. found it challenging voices faces acquaintances. Serology 33 strongly (index 8.88 S/CO [signal/cutoff]) analyzed CE-labeled kit nucleoprotein-based antigen Architect i2000SR Analyzer Laboratory Microbiology, Uppsala University Hospital, (3). [18F]fluorodeoxyglucose ([18F]FDG) PET scan 35 (after treatment) uptake striatum (caudate nucleus putamen) compared cortex 1C).Using immunohistochemistry research lab, we detected autoantibodies mouse brain neuronal proteins collected Neuronal labeling intensity strongest CA3 hippocampal formation, layer V somatosensory cortex, paraventricular reticular thalamus. subset ependymal located ventricle wall choroid plexus revealed strong immunoreactivity (peri)nuclear compartment cytoplasm. Immunoreactivity neuropil most intense caudate putamen, revealing processes spine-like structures. Posttreatment notably reduced, reaching serum.FIGURE 1. Timeline, hemodynamics, malignant SARS-CoV-2aa Panel is timeline evaluations, treatments, progression symptoms. ICU=intensive care unit; PCR=polymerase reaction; PET=positron emission tomography; PLEX=plasmapheresis; LP=lumbar B shows original 12-hour chart recording taken plasmapheresis (PLEX) 23) peripheral saturation (% SpO2), (BP), (HR). vertical lines represent hours. initially intravenous dexmedetomidine infusion. hypoxic event unknown origin noted (arrow 1). Blood generally variable, hypotension associated hyperlactatemia 2) 3). Hypotension treated crystalloid fluid noradrenalin. Induction anesthesia intubation 3) 4) persisted treatment bolus propofol, morphine, clonidine, intubation, regimen changed morphine. C 60 minutes injection 209 MBq 13 treatment. putamen bilaterally prominent than cortex. This observation cortical decrease metabolism symmetrical hypermetabolism striatum. inspection, there regions focal anomalies.FIGURE 2. tissue Profiling tissue. (diluted 1:4) first moderate neuron-like all investigated regions. map following panels. In observed pyramidal neurons (panel B) nucleus, soma, proximal dendrites stratum lucidum (arrowheads panel C). small layer, oriens D), polymorph dentate gyrus B). similar staining pattern E), thalamus F) dorsolateral ventrolateral thalamic nuclei (panels G H). subpopulation lining dorsal third I) reveals nuclear cytoplasm staining. highest J). Note dotted (arrows K) P) L Q) same remarkably reduced when compared. Reference 1:4; panels M N) 1:1,000; R S) age-matched men bipolar I disorder manic phase. Quantification shown respective O T). CA1–CA3=cornu ammonis, areas 1–3; CPU=caudate putamen; CTX=cerebral cortex; DG=dentate gyrus; DL=dorsolateral thalamus; DM=dorsomedial fi=fimbria hippocampus; HIFO=hippocampal formation; ic=internal capsule; LV=lateral ventricle; or=oriens layer; PV=paraventricular nucleus; pyr=pyramidal rad=radiatum Rt=reticular Slu=stratum lucidum; THAL=thalamus; VL=ventrolateral thalamus.Cases rapid onset diffuse corticospinal tract been reported conjunction COVID-19 (4, 5). Neurological patients include few cases catatonia (6–8), mutism (9), dysfunction (10). Several forms autoimmunity are emerging (11), coronavirus may join neurotropic viruses risk factor encephalitis.Malignant severe form spectrum perhaps recognized typical immobility, waxy flexibility, stupor (12, 13). Neurologists preferably used term “acute encephalopathy,” problem divergent nomenclature specializations acute, disturbance cognition current topic discussion (14). recent review identified 124 infections, 38% viral co-occurred conditions, especially NMDAR (15). symptom presentation our involvement tracts congruent pathological supratentorial structures intact brainstem. simultanagnosia appeared regressed together, suggesting common mechanism. prosopagnosia indicate involvement, specifically posterior network (16). Prosopagnosia (17). evidence structural damage, [18F]FDG consistent local neurons, cells, both. Striatal has caused voltage-gated potassium channel complex, well IgG4-related disease (18–23). staining, clinical presentation, radiology synaptic target highly present striatum, where binding leads loss inhibition both.We conclude potentially life-threatening instability can occur COVID-19. patient, condition responded improvement minimal damage. autoreactive both actions (24). presenting changes speech, weeks SARS-CoV-2, these should be potential manifestation We aware types such distinct raise possibility novel SARS-CoV-2.Department Neuroscience, Karolinska Institute, Stockholm (Mulder); Department Neurology (Feresiadou, Kumlien), Surgical Sciences, Radiology (Fällmar), Intensive Care (Frithiof), Psychiatry (Rasmusson, Cunningham), Neurosurgery (Rostami), University, Uppsala, Sweden.Send correspondence Dr. Cunningham ([email protected]).Supported Swedish Research Council, Bissen Brainwalk, Medical Training Agreement University.The authors report financial relationships commercial interests.References1 Pollak TA , Lennox BR Müller S et al. : Autoimmune psychosis: international consensus approach management psychosis suspected . Lancet 2020 ; 7 93 – 108 Crossref, Medline, Google Scholar2 Graus F Titulaer MJ Balu Neurol 2016 15 391 404 Scholar3 Lidström A-K Sund Albinsson Work inpatient units infection: cross-sectional study 8679 healthcare workers Sweden Ups J Med Sci 125 305 310 Scholar4 Helms Kremer Merdji H Neurologic N Engl 382 2268 2270 Scholar5 Mao Jin Wang manifestations hospitalized 2019 Wuhan, China JAMA 77 683 690 Scholar6 Caan MP Lim CT Howard Psychosomatics 61 556 560 Scholar7 Gouse BM Spears WE Nieves Archibald immune-mediated mechanism Behav Immun 89 529 530 Scholar8 Varatharaj Thomas Ellul MA neuropsychiatric complications 153 patients: UK-wide surveillance 875 882 Scholar9 Pilotto Odolini Masciocchi Steroid-responsive Ann 88 423 427 Scholar10 Logmin K Karam Schichel T Non-epileptic seizures initial 267 2490 2491 Scholar11 Ehrenfeld Tincani Andreoli Autoimmun Rev 19 102597 Scholar12 Saddawi-Konefka D Berg SM Nejad SH ICU: important underdiagnosed cause altered status: series literature Crit 2014 42 e234 e241 Scholar13 Wilson JE Niu Nicolson SE diagnostic structure Schizophr Res 2015 164 256 262 Scholar14 Slooter AJC Otte WM Devlin JW Updated delirium encephalopathy: statement ten societies 46 1020 1022 Scholar15 Rogers JP Blackman immune system: 6 620 630 Scholar16 Boccia Barbetti Piccardi Neuropsychology aesthetic judgment ambiguous non-ambiguous artworks (Basel) 2017 Scholar17 Bowles DC McKone E Dawel Diagnosing prosopagnosia: effects ageing, sex, participant-stimulus ethnic match Cambridge Face Memory Test Perception Cogn Neuropsychol 2009 26 455 Scholar18 Biyi Ait Sahel Mejjad Nucl Cent East Eur 2018 21 (doi: 10.5603/NMR.2018.0018 ) Scholar19 Lersy de Sèze COVID-19: retrospective observational 297 E242 E251 Scholar20 Kandemirli SG Dogan Sarikaya ZT intensive E232 E235 Scholar21 Rey Koric Guedj limbic 2012 259 1106 1110 Scholar22 Moloney Boylan Elamin Semi-quantitative analysis cerebral FDG-PET striatal VGKCC Neuroradiol 30 160 163 Scholar23 Baumgartner Rauer Mader Cerebral encephalitis: correlation autoantibody 2013 260 2744 2753 Scholar24 Reeves HM Winters JL mechanisms action plasma exchange Br Haematol 342 351 Scholar FiguresReferencesCited byDetailsCited byFirst-episode psychotic disorders wake pandemic: descriptive casereports31 March 2022 | Acta Neuropsychiatrica, Vol. 34, No. 6SARS-CoV-2 neurodegenerative diseases: what know don’t17 April Journal Neural Transmission, 129, 9Central neuroinflammation Covid-19: systematic 182 encephalitis, disseminated encephalomyelitis, necrotizing encephalopathies17 September 2021 Reviews Neurosciences, 33, 4Catatonia scoping review7 June BJPsych Bulletin, 33Neuroimmune COVID-1930 Neurology, 269, 6Concurrent experiential account challenges tertiary IndiaAsian Psychiatry, 69AI-CoV Study: Associated Its Vaccines—A Systematic ReviewJournal 18, central nervous system damageNeural Regeneration Research, 17, 6Unraveling Mystery Surrounding Post-Acute Sequelae Frontiers Immunology, 12 Volume 178Issue 2021Pages 485-489 Metrics KeywordsNeuroimmunologyNeuroimagingPsychosisSchizophrenia Spectrum Other Psychotic DisordersCatatoniaEncephalitisPDF download History Received 17 August Revised 3 October Accepted Published online 22 print