Steroid administration for post‐COVID‐19 Parkinsonism: A case report

Abstract

A 45‐year‐old man developed parkinsonism 3 weeks after being diagnosed with mild COVID‐19. Levodopa and benserazide failed to improve his symptoms, necessitating ropinirole, and steroid treatment, which included a 5‐day course of methylprednisolone followed by a 3‐month oral prednisolone taper. One month after initiating steroid treatment, his symptoms improved significantly.

1. INTRODUCTION

To date, at least 13 cases of parkinsonism associated with COVID‐19 infection have been reported. ¹ Potential etiologies include post‐infection immunological response, viral invasion of the central nervous system, underlying non‐symptomatic Parkinson's disease (PD), and hypoxic brain injury. ¹

2. CASE DESCRIPTION

A previously active 45‐year‐old man with a history of allergic rhinitis presented with a complaint of slow gait speed for over 2 months. No history of constipation or family history of PD was reported. However, 3 months earlier, the patient had experienced a sore throat and runny nose and was diagnosed with mild COVID‐19 by a rapid antigen test via nasopharyngeal swabbing. Since no fever or respiratory distress was evident, only supportive drug treatment was prescribed. After 10 days in home isolation, no symptoms remained.

Three weeks after the initial COVID‐19 diagnosis, the patient developed anxiety, fear, and difficulty breathing, especially in crowds and enclosed spaces. He also experienced difficulty moving his right limbs, resulting in a slow gait speed and inability to play soccer or ride motorcycles. He was diagnosed with agoraphobia with panic attacks by a psychiatrist and prescribed sertraline (50 mg/day), clorazepate (10 mg/day), and lorazepam (1 mg/day). Although his emotional state improved, motor impairments persisted, resulting in a referral to a neurology clinic. Neurological examination revealed hypomimia, bradykinesia (right > left), cogwheel rigidity (right > left), bilaterally reduced arm swing, shuffling gait, and en bloc turning (Video S1). Resting tremors and postural instability were not observed (Unified Parkinson's Disease Rating Scale Part III [UPDRS‐III], 46), and other neurological and systemic examinations were unremarkable. There were no symptoms of hyposmia, sleep problems, or autonomic dysfunction. The patient was diagnosed with post‐COVID‐19 parkinsonism and admitted to Buriram Hospital.

Laboratory tests included a coagulogram; complete blood count; blood chemistry; lipid profile; assessment of thyroid, kidney, and liver function; and quantification of intact parathyroid hormone, fasting blood glucose, creatinine phosphokinase, folate, vitamin B12, serum copper, serum ceruloplasmin, and 24‐h urinary copper concentrations. All biochemical values were unremarkable. Serology assays for human immunodeficiency virus, hepatitis B and C viruses, Treponema pallidum, and SARS‐CoV‐2 IgM were negative, but the assay for SARS‐CoV‐2 IgG was positive (>2080 AU/ml). Brain magnetic resonance imaging revealed no abnormalities. Cerebrospinal fluid (CSF) protein and glucose levels were 55.28 and 59.9 mg/dl, respectively, and no pleocytosis was observed (2 white blood cells/mm³ and 35 red blood cells/mm³ [minor traumatic tap]). CSF and serum paraneoplastic screening revealed negative findings.

After 1 week of levodopa (100 mg/day) and benserazide (25 mg/day) administration, clinical signs and symptoms showed no improvement. Despite increasing the dosages of levodopa (150 mg/day) and benserazide (37.5 mg/day), the patient still experienced difficulty walking and moving his right arm. Therefore, he was additionally treated with ropinirole (4 mg/day). Owing to the possibility of post‐viral immune‐mediated parkinsonism, we additionally administered methylprednisolone (1 g/day) for 5 days, followed by an oral prednisolone taper for 3 months (starting at 60 mg/day). One month after methylprednisolone administration, His symptoms improved significantly (UPDRS‐III, 19; Video S1).

3. DISCUSSION

The patient in our case presented with post‐COVID‐19 parkinsonism and agoraphobia, which might be associated with loss of dopamine innervation in the basal ganglia and limbic system. ² , ³ Morassi et al. ⁴ and Cohen et al. ⁵ reported cases of COVID‐19‐associated parkinsonism with decreased dopaminergic uptake in the bilateral putamen. However, further research is required to determine the precise location of neuronal death caused by COVID‐19‐associated parkinsonism. In previous reports, treatment consisted mainly of antiparkinsonian drugs. ¹ However, since our patient had no short‐term response to levodopa, it is unlikely that he would have had a long‐term response. Previous reports revealed five individuals with COVID‐19‐associated parkinsonism who received steroid therapy (Table 1), ³ , ⁴ , ⁵ , ⁶ three of whom had favorable outcomes. ³ , ⁵ , ⁶ These results support the post‐COVID‐19 immune‐mediated parkinsonism theory. Mice that recovered from COVID‐19 infection were more sensitive to a non‐lesion‐inducing dose of the parkinsonian toxin (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine [MPTP]), which induces substantia nigra pars compacta dopaminergic neuronal loss, than mice with COVID‐19 infection or MPTP exposure alone. ⁷ COVID‐19 infections might cause oxidative stress and neuroinflammation, leading to dopaminergic neuronal loss. ⁷

TABLE 1.

Steroid administration in COVID‐19‐associated parkinsonism

References	Sex	Age (years)	Underlying disease	MRI Brain	Functional imaging	CSF analysis	Anti‐parkinsonian medication	Steroid administration	Outcome
Ayele et al 3	Female	35	None	Symmetrical FLAIR and T2 hyperintense lesions in both pallidal regions	N/A	Unremarkable	levodopa, carbidopa	Dexamethasone (24 mg/day)	Good
Morassi et al. 4	Female	70	Hypertension, mixed anxiety‐depressive disorder	Slight enlargement of the ventricular system	Bilateral decrease in presynaptic dopamine uptake involving both putamens (left>right)	Decrease amyloid beta 42, increased total Tau protein	levodopa, carbidopa	Corticosteroid and intravenous immunoglobulin	Poor
Morassi et al. 4	Female	73	Type II diabetic mellitus, hypertension, mixed anxiety‐depressive disorder	Unremarkable	N/A	Elevate protein level (58 mg/dL) and present of CSF oligoclonal bands	Levodopa, carbidopa, amantadine	Corticosteroid and intravenous immunoglobulin	Poor
Cohen et al. 5	Male	45	Hypertension, asthma	Unremarkable	Decreased F‐fluorodopa uptake in both putamens (left>right)	6 white blood cells (83% mononuclear cells), with normal glucose (62 mg/dl) and protein (43 mg/dl)	pramipexole, biperiden	High dose of methylprednisolone for 5 days	Good
Ong et al. 6	Male	31	None	Bilateral symmetrical FLAIR and T2 thalamic hyperintensities with hemosiderin deposition and patchy contrast enhancement	N/A	Elevated protein level (65 mg/dl)	None	Methylprednisolone (1 g/day for 3 days)	Good
Our case	Male	45	None	Unremarkable	N/A	Elevated protein level (55.28 mg/dl)	levodopa, benserazide, ropinirole	Methylprednisolone 1 g/day for 5 days and prednisolone taper for 3 months	Good

Abbreviations: CSF, cerebrospinal fluid; MRI, magnetic resonance imaging.

Our patient had reportedly never experienced PD prodromal symptoms but developed parkinsonism 3 weeks after being diagnosed with COVID‐19, which corresponds to the onset of post‐viral inflammation. Increased CSF protein levels also suggested an inflammatory reaction. Based on the improvement in symptoms after steroid treatment in our case and previous reports, steroid medication may facilitate the management of post‐COVID‐19 parkinsonism.

FUNDING INFORMATION

None.

CONFLICT OF INTEREST

None.

Supporting information

Video S1

Mitarnun W, Apiwattanakul M, Thodthasri T, Tantisungvarakoon P, Pangwong W. Steroid administration for post‐COVID‐19 Parkinsonism: A case report. Neurol Clin Neurosci. 2023;11:49‐51. doi: 10.1111/ncn3.12679