Parkinson disease following COVID-19: Report of six cases.

BACKGROUND AND PURPOSE: Core clinical manifestations of COVID-19 include influenza-like and respiratory symptoms. However, it is now evident that neurological involvement may occur during SARS-CoV-2 infection, covering an extensive spectrum of phenotypical manifestations. A major challenge arising from this pandemic is represented by detecting emerging neurological complications following recovery from SARS-CoV-2 infection. To date, a few post-COVID-19-infected subjects diagnosed with Parkinson disease (PD) have been described, raising the possibility of a connection between the infection and neurodegenerative processes. Here, we describe a case series of six subjects who developed PD after COVID-19. METHODS: Patients were observed at Scientific Institute for Research and Health Care Mondino Foundation Hospital, Pavia (Italy), and San Paolo University Hospital of Milan (Italy) between March 2021 and June 2022. In all subjects, SARS-CoV-2 infection was confirmed by means of reverse transcriptase polymerase chain reaction from a nasopharyngeal swab. Subjects underwent an accurate neurological evaluation, and neuroimaging studies were performed. RESULTS: We describe six subjects who developed PD with an average time window after SARS-CoV-2 infection of 4-7 weeks. Apparently, no relationship with COVID-19 severity emerged, and no overt structural brain abnormalities were found. All subjects experienced unilateral resting tremor at onset and showed a satisfactory response to dopaminergic treatment. CONCLUSIONS: Immune responses to SARS-CoV-2 infection have been shown to shape the individual susceptibility to develop long-term consequences. We hypothesize that, in these subjects, COVID-19 has unmasked a latent neurodegenerative process. Characterization of the neuroinflammatory signatures in larger cohorts is warranted, which might provide novel insights into the pathogenesis of PD.

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series.

INTRODUCTION: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG). MATERIALS AND METHODS: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers. RESULTS: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%). CONCLUSION: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Putative Role of the Lung-Brain Axis in the Pathogenesis of COVID-19-Associated Respiratory Failure: A Systematic Review.

The emergence of SARS-CoV-2 and its related disease caused by coronavirus (COVID-19) has posed a huge threat to the global population, with millions of deaths and the creation of enormous social and healthcare pressure. Several studies have shown that besides respiratory illness, other organs may be damaged as well, including the heart, kidneys, and brain. Current evidence reports a high frequency of neurological manifestations in COVID-19, with significant prognostic implications. Importantly, emerging literature is showing that the virus may spread to the central nervous system through neuronal routes, hitting the brainstem and cardiorespiratory centers, potentially exacerbating the respiratory illness. In this systematic review, we searched public databases for all available evidence and discuss current clinical and pre-clinical data on the relationship between the lung and brain during COVID-19. Acknowledging the involvement of these primordial brain areas in the pathogenesis of the disease may fuel research on the topic and allow the development of new therapeutic strategies.

Critical illness neuropathy in severe COVID-19: a case series.

INTRODUCTION: Neurological complications of SARS-CoV-2 disease have received growing attention, but only few studies have described to date clinical and neurophysiological findings in COVID patients during their stay in intensive care units (ICUs). Here, we neurophysiologically assessed the presence of either critical illness neuropathy (CIP) or myopathy (CIM) in ICU patients. MATERIALS AND METHODS: Patients underwent a neurophysiological assessment, including bilateral examination of the median, ulnar, deep peroneal and tibial motor nerves and of the median, ulnar, radial and sural sensory nerves. Needle electromyography (EMG) was performed for both distal and proximal muscles of the lower and upper limbs. In order to differentiate CIP from CIM, Direct Muscle Stimulation (DMS) was applied either to the deltoid or tibialis anterior muscles. Peak to peak amplitudes and onset latencies of the responses evoked by DMS (DMSamp, DMSlat) or by motor nerve stimulation (MNSamp, MNSlat) were compared. The ratio MNSamp to DMSamp (NMR) and the MNSlat to DMSlat difference (NMD: MNSlat - DMSlat) were also evaluated. RESULTS: Nerve conduction studies showed a sensory-motor polyneuropathy with axonal neurogenic pattern, as confirmed by needle EMG. Both MNSamp and NMR were significantly reduced when compared to controls (p < 0.0001), whereas MNSlat and NMD were markedly increased (p = 0.0049). CONCLUSIONS: We have described COVID patients in the ICU with critical illness neuropathy (CIP). COVID-related CIP could have implications for the functional recovery and rehabilitation strategies.

Brainstem neuropathology in two cases of COVID-19: SARS-CoV-2 trafficking between brain and lung.

INTRODUCTION: SARS-CoV-2 might spread through the nervous system, reaching respiratory centers in the brainstem. Because we recently reported neurophysiological brainstem reflex abnormalities in COVID-19 patients, we here neuropathologically assessed structural brainstem damage in two COVID-19 patients. MATERIALS AND METHODS: We assessed neuropathological features in two patients who died of COVID-19 and in two COVID-19 negative patients as controls. Neuronal damage and corpora amylacea (CA) numbers /mm2 were histopathologically assessed. Other features studied were the immunohistochemical expression of the SARS-CoV-2 nucleoprotein (NP) and the Iba-1 antigen for glial activation. RESULTS: Autopsies showed normal gross brainstem anatomy. Histopathological examination demonstrated increased neuronal and CA damage in Covid-19 patients' medulla oblongata. Immunohistochemistry disclosed SARS-CoV-2 NP in brainstem neurons and glial cells, and in cranial nerves. Glial elements also exhibited a widespread increase in Iba-1 expression. Sars-Co-V2 was immunohistochemically detected in the vagus nerve fibers. DISCUSSION: Neuropathologic evidence showing SARS-CoV-2 in the brainstem and medullary damage in the area of respiratory centers strongly suggests that the pathophysiology of COVID-19-related respiratory failure includes a neurogenic component. Sars-Co-V2 detection in the vagus nerve, argues for viral trafficking between brainstem and lung.