Parkinson's disease after COVID-19

Dear Editor,

A few cases of “Parkinson's disease” (PD) have been recently reported following COVID-19 infection (Table 1 ). The authors propose various hypotheses about the relationship of COVID-19 and the subsequent parkinsonism, but they do not mention the possibility of a prodromal (pre-symptomatic) PD that became symptomatic as a result of biologic or psychologic stress related to the COVID-19. Thus, in the reported cases of COVID-19 related PD the cause-and-effect relationship could not be established with certainty [1].

Table 1.

COVID-19 Related Cases of Parkinsonism.

Publication	Age	COVID-19 severity	Days to Parkinsonian features after initial COVID symptoms	Parkinsonian features	Imaging of dopaminergic uptake	Prodromal symptoms
Cohen et al. [9]	45	Moderate requiring hospitalization	2 to 3 weeks	Right more than left tremor, bradykinesia, rigidity	Decreased uptake in bilateral putamen more apparent on the left	None
Mendéz-Guerrero et al. [7]	58	Severe with desaturation requiring ICU admission	32 days	Right hypokinetic-rigid syndrome with rest and postural tremora	Decreased uptake in bilateral putamen more apparent on the left	None
Faber et al. [10]	35	Mild	10 days	Right rigidity, bradykinesia and hypophonia, hypomimia, slow saccades and gait impairment	Decreased left putamen uptake	None
Baylor Case	64	Mild	5 days	Left bradykinesia rigidity and rest tremor with hypomimia	Decreased right putamen uptake	Constipation

^aAlso experienced decreased level of consciousness, roving eye movements, myoclonic jerks, opsoclonus and vertical gaze palsy.

We recently evaluated a 64-year-old woman who 5 days after onset of fever, fatigue and loss of smell, attributed to COVID-19 and confirmed by positive PCR test, experienced rest tremor in her left arm. Her examination was notable for minimal hypomimia and mild left-sided bradykinesia and rigidity, consistent with the diagnosis of PD, supported by DaTscan which revealed decreased uptake in the right putamen. It is intriguing to conclude that PD in this case is a direct consequence of COVID-19 infection due to its acute onset within days of COVID-19 related symptoms. We suggest that our patient, similar to other COVID-19 related cases of parkinsonism, had prodromal parkinsonism that became symptomatic as a result of COVID-19. This hypothesis is supported by the presence of decreased DaTscan uptake which would be unlikely to occur within such a short period of time (days or weeks). Evidence of decreased dopaminergic innervation in the basal ganglia before the onset of motor symptoms has been demonstrated in individuals who were carriers of PD-related gene mutations and in patients with REM sleep behavior disorder [2]. Indeed, our patient reported a 10-year history of constipation prior to the onset of parkinsonian symptoms, a common non-motor prodromal feature [3].

The possibility of postencephalitic parkinsonism has been entertained since Von Economo recognized mysterious increase in patients suffering with Parkinson's symptoms few years after the influenza pandemic [4]. The possibility of a relationship between postencephalitic parkinsonism and coronaviruses was supported by the demonstration of infection of the basal ganglia by a coronavirus in mice and by the presence of coronavirus antibodies in cerebrospinal fluid (CSF) of patients with PD [5]. Besides implication of coronavirus in post-encephalitis parkinsonism, COVID-19 related parkinsonism, and PD, another overlapping feature shared among the three conditions is the “olfactory vector hypothesis” [3,6]. Besides conversion from prodromal to symptomatic PD directly or indirectly related to COVID-19, our and other reported cases raise the possibility of postencephalitic parkinsonism in patients who recover from COVID-19, similar to the patients encountered after the 1918 pandemic. In addition to viral or autoimmune encephalitis other possible mechanisms that may predispose COVID-19 patient to the development of subsequent parkinsonism include hypoxic or vascular damage to the basal ganglia. In this regard, it is noteworthy that one of the reported cases suffered severe COVID-19 syndrome with presumed hypoxia due to desaturation and subsequently developed myoclonus, opsoclonus and rigidity within a context of encephalopathy [7]. None of the reported cases provided CSF evidence of COVID-19, and neither revealed a lesion subsequent to the viral infection [8]. Until clinical-etiopathogenic correlation can be established, the reports of COVID-19 related PD must be interpreted with caution.