Summary Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Neurological Associations of COVID-19

Background and purpose COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection. Materials and methods Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared. Results Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p Conclusion Acute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.

https://svn.bmj.com/content/svnbmj/5/3/279.full.pdf

Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study

Background: The COVID-19 pandemic, caused by SARS-CoV-2, is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. Based on knowledge of other coronaviruses, especially those that caused the SARS and MERS epidemics, we might expect to see rare cases of central nervous system (CNS) and peripheral nervous system (PNS) disease caused by SARS-CoV-2.

Recent developments: A growing number of case reports and series describe a wide array of neurological manifestations, but many lack detail, reflecting the challenge of studying such patients. Encephalopathy is relatively common, being reported for 93 patients in total, including 16 (7.5%) of 214 hospitalised COVID-19 patients in Wuhan, China, and 40 (69%) of 58 in intensive care with COVID-19 in France. Encephalitis has been described in 8 patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 is detected in the cerebrospinal fluid of some patients. Anosmia and ageusia are common and may occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 1.6-6% of hospitalised COVID-19 cases. So far, 88 patients have been described, mostly with ischaemic stroke, who frequently have vascular events in the context of a pro-inflammatory hypercoagulable state with elevated CRP, D-dimer, and ferritin.

Where next?: Careful clinical, diagnostic and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease, such as hypoxic encephalopathy and critical care neuropathy, from those caused directly or indirectly by the virus; these include infectious, para- and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognising SARS-CoV-2 neurological disease in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will remain small. However, these patients may be left with severe neurological sequelae. With so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large. Healthcare planners and policymakers must prepare for this eventuality. The many ongoing studies investigating the neurological association will increase our knowledge base.

/pdf/neurological-associations-of-covid-19-o39p8yig6g.pdf

Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review.

The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted "stay in place" or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.

COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation.

Objective Acute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations. Here we present a series of four patients with COVID-19 that presented with acute stroke. Methods We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection. All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study. Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained. Results We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course. Conclusions Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should dawn appropriate personal protective equipment in every suspected patient. Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection.

/pdf/covid-19-presenting-as-stroke-2a0y4eddmp.pdf

COVID-19 presenting as stroke.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, this highly transmissible virus has since spread rapidly around the world. Though respiratory complication is the primarily reported manifestation though rare, yet serious neurological complications are being frequently reported in the literature. In selected coronavirus disease-2019 (COVID-19) cases neurologic complications may manifest as seizures. In this paper, we have reviewed current literature on seizures linked with SARS- COV 2 infection including published or pre-print original articles, review articles, and case reports. We have discussed the electroencephalogram (EEG), imaging, and Cerebrospinal fluid (CSF) findings in patients with COVID-19 presenting with seizure. We will be concluding the paper by briefly discussing the three mechanisms by which seizures can develop in patients infected with SARS- COV 2 - (a) Direct Mechanism (b) Indirect Mechanism and (c) Exacerbation of Seizure in Patients with Epilepsy (PWE). Our aim is to update the physicians working with COVID-19 patients about this potential complication and hope that understanding of these proposed mechanisms can provide an opportunity for the physicians for early diagnosis or even better, help prevent this complication.

Seizure And COVID-19: Association and Review of Potential Mechanism.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases were first reported in Wuhan, Hubei province of China in December, 2019. SARS- COV-2 primarily affects the cardio-respiratory system. Over the last few months, several studies have described various neurological sequelae of SARS-COV-2 infection. Neurological complications are more frequent in patients with severe respiratory infections. In this review, we have analyzed the current literature on neuromuscular complications associated with SARS-COV-2 and highlighted possible mechanisms of neuromuscular invasion. We reviewed 11 studies describing 11 cases of Guillain Barre syndrome (GBS), and 1 case each of Miller Fisher syndrome, Polyneuritis Cranialis, Acute myelitis, Oculomotor paralysis and Bell's Palsy associated with SARS-COV-2 infection. Mean age of patients with GBS was 61.54 years, with standard deviation (SD) 14.18 years. Majority patients had fever and cough as the first symptom of SARS COV-2 infection. Mean time for onset of neurological symptoms from initial symptoms in 11 patients was 8.18 days, with SD of 2.86 days. Mean time to performing electrodiagnostic study from onset of neurological symptom was 6 days with standard deviation of 3.25. Six patients had demyelinating pattern, three had acute sensory motor axonal neuropathy, and one had acute motor axonal neuropathy on electrodiagnostic studies.

/pdf/neuromuscular-complications-with-sars-cov-2-infection-a-2tw0g7lq16.pdf

Neuromuscular Complications With SARS-COV-2 Infection: A Review

Delayed post-hypoxic leukoencephalopathy (DPHL) is a unique clinical entity that presents with cognitive impairment days to weeks after an episode of acute hypoxic brain injury. Frequently hypoxia is unrecognized as a mechanism for clinical decline and extensive workup ensues. We present two cases of DPHL highlighting the neuroimaging findings. In both patients, a cerebral hypoxic event was followed by a recovery phase with subsequent delayed clinical decline. Patient 1 suffered hypoxia from drug-induced respiratory depression and lack of post-operative positive airway pressure (PAP) support. Her neurological exam on follow-up revealed progressive cognitive decline. Magnetic resonance imaging (MRI) brain showed bilateral white matter changes involving the centrum semiovale. Patient 2 developed a generalized tonic-clonic seizure during an endobronchial biopsy procedure and was found to have multiple air emboli on computed tomography (CT) head scan. She was initially in a drug-induced coma for her seizures. Electroencephalography (EEG) on day 14 of admission showed changes consistent with diffuse encephalopathy. MRI brain showed bilateral white matter changes particularly at the watershed zones and in the centrum semiovale. DPHL is a rare and under-recognized clinical entity that requires clinical suspicion and detailed evaluation for diagnosis. Neuroimaging studies can provide prognostic information regarding the extent of neurological injury.

Delayed Post-hypoxic Leukoencephalopathy: A Case Series and Review of the Literature.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, may mimic other conditions at presentation often resulting in delayed diagnosis. These conditions include infections, neoplasms, autoimmune, cardiovascular, and drug-induced diseases. This review highlights the most common sarcoidosis mimics that often lead to pitfalls in diagnosis and delay in appropriate treatment. Prior to invasive testing and initiating immunosuppressants (commonly corticosteroids), it is important to exclude sarcoid mimickers.

/pdf/sarcoidosis-pitfalls-and-challenging-mimickers-3to5tfqhzt.pdf

Naureen Narula

Papers

COVID-19 presenting as stroke.

Seizure And COVID-19: Association and Review of Potential Mechanism.

Neuromuscular Complications With SARS-COV-2 Infection: A Review

Delayed Post-hypoxic Leukoencephalopathy: A Case Series and Review of the Literature.

Sarcoidosis: Pitfalls and Challenging Mimickers.