Vol 56, No 1 (2022)
Letter to the Editors
Published online: 2022-01-05

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Acute-onset chorea and confusional state in 77-year-old COVID-19 patient: a case report

Katarzyna Sawczyńska12, Kamil Wężyk23, Magdalena Bosak12, Jeremiasz Jagiełła12, Szymon Andrasik2, Alicja Kępińska-Wnuk12, Małgorzata Dec-Ćwiek12, Agnieszka Słowik12
Pubmed: 34985113
Neurol Neurochir Pol 2022;56(1):106-110.

Abstract

Not available

Acute-onset chorea and confusional state in 77-year-old COVID-19 patient: a case report

Katarzyna Sawczyńska12Kamil Wężyk23Magdalena Bosak12Jeremiasz Jagiełła12Szymon Andrasik2Alicja Kępińska-Wnuk12Małgorzata Dec-Ćwiek12Agnieszka Słowik12
1Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
2Department of Neurology, University Hospital in Krakow, Poland
3Department of Physiotherapy, Jagiellonian University Medical College, Krakow, Poland

LETTER TO THE EDITORS

Neurologia i Neurochirurgia Polska

Polish Journal of Neurology and Neurosurgery

2022, Volume 56, no. 1, pages: –110

DOI: 10.5603/PJNNS.a2022.0003

Copyright © 2022 Polish Neurological Society

ISSN: 0028-3843, e-ISSN: 1897-4260

Address for correspondence: Katarzyna Sawczynska, Jagiellonian University Medical College, Department of Neurology, Jakubowskiego 2, 30–688 Krakow, Poland; e-mail: katarzyna.sawczynska@gmail.com

Received: 4.10.2021 Accepted: 24.11.2021 Early publication date: 5.01.2022

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

Key words: COVID-19, chorea, autoimmune encephalitis, involuntary movements
(Neurol Neurochir Pol 2022; 56 (1): –110)

To the Editors

SARS-CoV-2 has a proven neurotropic potential and can cause various neurological complications [1]. Involuntary movements represent a rare manifestation of COVID-19. We present a case report of COVID-19-associated chorea. This is to the best of our knowledge the first such case to be reported in a Polish population.

A 77-year-old woman was admitted to the University Hospital due to involuntary movements of acute onset. Two weeks before, she had received her first dose of COVID-19 mRNA vaccine. Soon afterwards, she had a close contact with a SARS-CoV-2-infected person. Five days before admission, she developed disturbances in attention, consciousness, and cognition — she was hyperactive, occasionally delusional, and slight involuntary movements of the face appeared. On the next day, infection symptoms (i.e. cough, fever) also appeared. Her neurological condition worsened and fluctuated — involuntary movements spread to the limbs and a confusional state progressed. On admission, a routine COVID-19 antigen test from nasopharyngeal swab had been performed, confirming SARS-CoV-2 infection.

The patient had a history of arterial hypertension, diabetes mellitus, hypothyroidism, and urinary incontinence, and had three malignancies in remission (skin melanoma, thyroid and colon cancer). According to her family, for several months before her current deterioration she had required some help with everyday activities and had experienced slight problems with cognition. She did not take any medication with known potential to induce chorea (Tab. 1).

In neurological examination on admission, psychomotor slowing, orofacial dyskinesia and involuntary chorea-type movements of the trunk and all limbs (more pronounced on the left) were observed.

Non-contrast computed tomography (CT), CT angiography and perfusion CT of the brain were performed, showing no relevant abnormalities. Chest high-resolution CT revealed bilateral pneumonia (Fig. 1A). Head magnetic resonance imaging (MRI) (Fig. 1B) demonstrated marked features of cerebral small vessel disease — diffuse white matter hyperintensities, cortical and subcortical atrophy — with no acute ischaemic or contrast-enhancing lesions, nor oedema of the basal ganglia. Cerebrospinal fluid (CSF) and serum tests were unremarkable except for elevated serum inflammation markers (CRP 79.60 mg/dL) and mild dyselectrolytemia (Na+ 134 mmol/L, K+ 3.03 mmol/L, Ca2+ 2.09 mmol/L). Neuroinfection, hypoxic-ischaemic encephalopathy, metabolic, hormonal and autoimmune systemic diseases, paraneoplastic syndrome and prion disease were excluded. Antistreptolisin-O level was not elevated. Laboratory test results are summarised in Table 1. Electroencephalography (EEG) could not be performed on the COVID-19 ward.

A preliminary diagnosis of non-infectious encephalitis was made. Empirical treatment with steroids (methyloprednisolone 1 g i.v. per day for five days), symptomatic with diazepam and antiviral treatment with remdesivir (200 mg i.v. on day 1, and 100 mg i.v. for the following four days) were introduced, with significant improvements — the involuntary movements disappeared and her mental status improved. After steroids and remdesivir were stopped, slight, fluctuating, chorea reappeared and left-sided hemiparesis and hemineglect were noted. A control MRI reconfirmed the absence of acute ischaemic and contrast-enhancing lesions. The symptoms were interpreted as inflammation progression and second line treatment with intravenous immunoglobulins (IVIG; 2 g/kg over the course of five days) was started, with complete and permanent resolution of the chorea within the first days of therapy.

Figure 1. A. Chest high-resolution CT with bilateral pneumonia — distribution characteristic for SARS-CoV-2; B. Brain MRI: marked features of cerebral small vessel disease (cSVD), cortical and subcortical atrophy; C. EEG: frontal intermittent rhythmic delta activity (FIRDA) pattern.
CT — computed tomography; EEG — electroencephalography; MRI — magnetic resonance imaging

Having fulfilled the criteria for COVID-19 recovery, she was transferred to the General Neurology and Internal Medicine wards where further treatment and diagnostic tests were performed. During hospitalisation, several episodes of transient loss of consciousness (lasting for a few minutes) occurred. These were interpreted as symptomatic seizures secondary to encephalitis, and therefore antiepileptic treatment was introduced. Electroencephalography showed a frontal intermittent rhythmic delta activity (FIRDA) pattern (Fig. 1C). Control MRI imaging was stable, and CSF examinations were unremarkable.

Table 1. Differential diagnoses of involuntary movements in 77-year-old patient with COVID-19 infection

Medications

Infectious encephalitis

Autoimmune encephalitis

Systemic inflammatory and autoimmune disorders

Metabolic disorders

Parenoplastic syndrome

Creutzfeldt- -Jakob Disease

No information about involuntary movements in summaries of product characteristics of the following medications:

amlodipine, indapamide, perindopril, bisoprolol, metformin, levothyroxine, solifenacin, azithromycin, zolpidem

CSF culture:

negative

Viral encephalitis (screening molecular tests for CMV, HSV 1, HSV2, VZV, Enterovirus, parechovirus, HSV6, HSV7, parvovirus B19, human adenovirus):

negative

Bacterial encephalitis (screening molecular tests for Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitis):

negative

HIV infection:

HIV p24: negative

Syphilis:

RPR/VDRL: negative

neuro-COVID:

SARS-CoV-2 PCR-RT test: negative

Neuroborreliosis: IgG, IgM Borrelia serum (ELISA test): negative

IgG, IgM Borrelia-CSF (ELISA test): negative

Tick-Borne Encephalitis: IgM-TBE: negative

Serum

antibodies

(all negative):

Anti-NMDA

Anti-CASPR2

Anti-AMPA1/2

Anti-LG11,

Anti-DPPX,

Anti-GABA B

Anti-cardiolipin antibodies IgG, IgM: negative

anti-β2-glycoprotein 1 antibodies IgG, IgM: negative

Anti-neutrophil cytoplasmic antibodies (ANCA):

1:20 titre, p-ANCA pattern

Antinuclear antibodies (ANA):

speckled (s-ANA) 1:320 titre,

Nucleolar (N-ANA) 1:640 titre,

Cytoplasmic (C-ANA) 1:160 titre;

Immunoblot ANA Profile + DFS70 (all negative):

Anti-Ku, Anti-Mi-2, Anti-nRNP, Anti-Sm, Anti-SSA, Anti-SSB, Anti-Scl-70, Anti-Jo-1, Anti-Ro-52, Anti-PM-Scl 100, Anti-Centromer B, Anti-PCNA, Anti-dsDNA, Anti-Nucleosome, Anti-Histone, Anti-ribosomal protein P, Anti-mitochondria-M2, Anti-DFS70,

Lupus anticoagulant (LA): negative

Anti-streptolysin O titre 116.00 IU/mL [< 200]

Glucose serum level:

2.59–9.0 mmol/L

Electrolyte imbalance:

serum potassium:

hypocalemia at admission

(2.7 mmol/L)

serum sodium: mild hyponatremia at admission (134 mmol/L)

serum calcium: mild hypocalcemia on first days of hospitalisation

(2.09 mmol/L)

serum magnesium: normal (0.78 mmol/L)

Hypo-/hyperthyroidism:

TSH 2.890 uIU/mL

[0.270–4.200]

Hypo-/hyperparathyroidism:

PTH 18.3 pg/mL

[14.90–56.90]

Vitamin B12 deficiency:

hypervitaminosis, B12 level: 1,067.0 pg/mL [191.0–663.0]

Hepatic disease:

AST, ALT: normal

HBsAg, anti-HCV: negative

Whole-body CT (head, chest, abdomen and pelvis): no tumour detected

Gastroscopy and colonoscopy: no tumour detected

Bronchoscopy: no tumour detected

Paraneoplastic antibodies serum (all negative):

anti-Amphiphysin, anti-CV2, anti-PNMA2 (Ma2/Ta), anti-Ri (Nova1), anti-Yo (cdr62), anti-Hu (HuD), anti-Recoverin, anti-SOX1, anti-Titin, anti-Zic4, anti-GAD65, anti-Tr (DNER)

Cerebrospinal fluid (all negative): anti-Yo, anti-Hu, anti-Ri, anti- MAG, anti-Amphiphysin, anti-Myelin

14-3-3 protein:

negative

RT-Quick:

negative

Brain-MRI:

no typical imaging findings

The patient required prolonged hospitalisation due to multiple non-neurological complications — new onset atrial fibrillation, bacterial pneumonia, urinary tract infection, sepsis, pulmonary embolism, and reactive arthritis. Involuntary movements have not reappeared during a three-month follow up. Left-sided hemiparesis was persistent (with intensity depending on the patient’s general condition).

Chorea has only rarely been reported as a manifestation of COVID-19. A literature review by Brandão et al. [2] identified 93 cases of new-onset movement disorders in COVID-19 patients, with the most common of these being myoclonus (63.4%) and only one case of chorea. In a recent systematic review by Hirschfeld [3], among 49 cases of hyperkinetic movement disorders in adult, non-intubated COVID-19 patients without a pre-existent movement disorder or organic brain injury, the most common one was ataxia (83.67%); no cases of chorea were included. Ataxia-myoclonus syndrome has emerged as a complication of COVID-19 infection, and two cases were reported in Poland by Przytuła et al. [4]. In a prospective study by Ray et al. [8] on the prevalence of COVID-19 neurological manifestations among 1,334 children, two cases of acute chorea were reported. Byrnes et al. [9], Hassan et al. [5] and Cotta Ramusino et al. [10] reported COVID-19-associated chorea in adults, most probably due to non-infectious encephalitis. Ghosh et al. [11] reported a case of chorea in the course of diabetic ketoacidosis triggered by SARS-CoV-2 infection. Yüksel et al. [12] and DeVette et al. [13] reported cases of chorea in children with COVID-19 — with either a history of Sydenham’s chorea or a concomitant streptococcal infection. We found no literature report of new onset involuntary movements developing after COVID-19 mRNA vaccine in patients without a pre-existent movement disorder.

Brandão et al. [2] reviewed diagnostic test results in patients with COVID-19-associated movement disorders. 72.7% of available brain MRIs showed no abnormalities or non-related findings. From available CSF analyses, pleocytosis was present in 26.7% and slightly elevated protein in 49.9% of cases. Among available EEG results, abnormalities appeared in 76.7% (most commonly background slowing — in 59.3%).

Several studies have evaluated EEG abnormalities in patients with COVID-19 encephalopathy. In their meta-analysis, Kubota et al. [14] reported that abnormal background activity and generalised slowing are common (96.1% of analysed patients), although they occur in many different encephalopathies. In our patient, we recorded FIRDA, a pattern that can result from several potential aetiologies, including metabolic and hypoxic encephalopathy, neurodegenerative disease, systemic infection, and encephalitis [14]. In their systemic review, Antony and Haneef [6] demonstrated, however, that frontal EEG patterns (i.e. focal slowing, periodic discharges and rhythmic delta activity) are characteristic of COVID-19 encephalopathy.

The differential diagnosis of acute-onset chorea is wide, including vascular, metabolic, infectious, post-infectious, paraneoplastic, autoimmune, and medication-induced disorders [7]. In our patient, COVID-19-associated autoimmune encephalitis seems to be the most probable cause of chorea. There was an evident time correlation between the onset of involuntary movement and the beginning of SARS-CoV-2 infection, and a marked improvement after immunosuppressive therapy and infection treatment.

It is significant that when treatment with steroids was stopped, fluctuating chorea reappeared and our patient required second line treatment with IVIG. We found no other possible causes of chorea except for dyselectrolytemia, although this is less likely due to the lack of severity and the lack of a time correlation between its treatment and the intensity of involuntary movements.

Conflict of interest: None.

Funding: None.

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