CONTENTS
- Limitations of this chapter
- Brief word on pathogenesis
- General clinical principles
- Encephalopathy
- Diffuse leukoencephalopathy with diffusion restriction
- Acute necrotizing encephalopathy (ANE)
- Mild encephalopathy with reversible splenial lesion (MERS)
- Acute disseminated encephalomyelitis (ADEM) & Acute hemorrhagic leukoencephalitis (AHLE)
- Myelitis
- Autoimmune encephalitis
- Posterior reversible encephalopathy syndrome (PRES)
- Stroke
- Guillain-Barre syndrome (GBS)
- Cranial neuropathy
- Myositis
- Podcast
- Questions & discussion
- Pitfalls
To date there have been over a quarter of a million publications about COVID, with >25,000 publications touching on neurologic aspects of the disease. Evidence is emerging rapidly. Obviously, it is impossible to perform an exhaustive review of this data.
Even more challenging is the ongoing evolving nature of COVID. Neurological manifestations of COVID pose a continually moving target for several reasons: new variants of the virus, rising levels of natural and vaccine-mediated immunity, and shifts in disease management (e.g., with broader use of early dexamethasone and JAK inhibitors). Articles inevitably make an implicit assumption that neurologic sequelae will remain similar over time (an assumption which is required in order to write any sort of summary article). Hopefully this assumption is valid enough to make this chapter clinically useful, but in reality the assumption is at best an approximation of reality.
At this point in time, there are one or more case reports linking COVID to essentially every neurological disorder. Given that COVID has infected over half a billion people, it shouldn't be surprising that COVID has occurred concurrently with every neurologic disorder. Furthermore, COVID causes critical illness and organ dysfunction – nonspecific stressors which promote a variety of neurological complications. This leaves us in an awkward position wherein it is frequently impossible to sort out neurologic manifestations of COVID from random coincidence or association.
Finally, there is virtually no high-quality evidence regarding the management of neurological manifestations of COVID. Some suggestions are provided below, but please note the dearth of definitive information regarding treatment.
Direct viral invasion of the brain parenchyma doesn't seem to be a significant mechanism whereby COVID causes neurologic disease. A couple of reports describe finding virus in the brain parenchyma, but it's often unclear whether this represents contamination (due to the presence of virus in the blood and endothelium). Furthermore, when one considers the large number of investigations spent looking for virus in the brain, then it's notable how few found anything.(34788237)
Commonly implicated causes of neurologic dysfunction include the following:
- Endothelial activation and hypercoagulability, leading to vascular dysfunction.
- Systemic inflammation, with elevated levels of circulating cytokines.
- Nonspecific effects of critical illness (e.g., physiological stress, hypoxemia, renal failure, hypotension).
- Medication side effects (e.g., sedation, paralysis, steroid use).
The mechanisms underlying neurologic disease are generally unclear and potentially multifactorial. In some cases, we may get a sense that one mechanism may be predominating.
(1) start with the basics
- Review all the data and perform a thorough examination.
- Maintain a broad differential diagnosis.
- When in doubt, follow the standard diagnostic approaches.
- Avoid derailing your investigation due to COVID precautions (e.g., if the patient needs an MRI scan, then work to overcome logistic hurdles involved in obtaining a scan).
(2) don't assume that abnormalities are due to COVID
- COVID may cause some unique presentations, but more commonly patients will have common disorders.
- Initial investigation should focus on evaluating for common and treatable entities (e.g., hypoglycemia, intracranial hemorrhage, ischemic stroke).
(3) the treatment of any specific disorder is usually the same
- COVID is associated with a variety of specific neurological disorders (e.g., intracranial hemorrhage, ischemic stroke, posterior reversible encephalopathy syndrome, Guillain-Barre syndrome, acute disseminated encephalomyelitis).
- If the patient is diagnosed with a specific neurologic disorder, the treatment is generally the same as usual. However, there are a few potential exceptions:
- B-cell depleting agents (e.g., rituximab) may cause prolonged and refractory COVID infection, so these may be avoided or delayed.
- Plasma exchange is likely to remove antibodies that provide protection against COVID. Thus, plasma exchange may be undesirable, especially in the context of an active COVID infection.(34155186)
🔑 When in doubt, do the usual stuff that you normally do.
general clinical aspects of encephalopathy
- Encephalopathy is a nonspecific term used to encompass a variety of syndromes resulting from brain dysfunction (e.g., delirium, stupor, and coma).
- Encephalopathy is the most common neurologic finding in patients hospitalized with COVID. This may affect most COVID patients admitted to the ICU.(35461991) Alternatively, occasional patients may present to the hospital with altered mental status (without symptoms of COVID pneumonia).
potential causes of encephalopathy in COVID may include:
- (1) General causes of encephalopathy:
- Hypoxemia.
- Metabolic abnormalities (e.g., uremia).
- Medications (e.g., opioids, sedative infusions, steroid).
- (2) Specific neurologic syndromes due to COVID:
- Acute necrotizing encephalopathy (ANE).
- Acute disseminated encephalomyelitis (ADEM).
- (3) Cerebrovascular disease (e.g., acute or hemorrhagic stroke).
- More information on the differential diagnosis:
evaluation
- Evaluation depends on the specifics of patient presentation.
- If a lumbar puncture is performed, pleocytosis should not be attributed to COVID (as this is not usually seen in encephalopathy due to COVID). However, mildly elevated protein with oligoclonal bands may occur in COVID patients with encephalopathy; these features appear to be nonspecific.(35667743)
basics
- Occasionally, critically ill patients with COVID develop a pattern of diffuse leukoencephalopathy with restricted diffusion. The usual clinical scenario is an extremely ill patient who initially requires intubation due to respiratory failure. Some weeks later when the patient is failing to awaken off sedation, investigation eventually reveals diffuse leukoencephalopathy.(33093131) Patients are generally intubated, comatose, have renal failure, and are often obese.(33414226)
- The pathophysiology is unclear. This doesn't appear to solely reflect hypoxemia, given a distribution that differs from leukoencephalopathy caused by hypoxemia.(33414226) Additionally, the pattern has been reported in some patients without any known history of hypoxemia. Potential causative factors may include blood-brain barrier dysfunction due to systemic inflammation, endothelial dysfunction, and/or thrombotic microangiopathy.(33093131)
- Laboratory data from a few patients suggests that CSF may reveal a normal cell count, often with elevated protein.(33414226, 35538434, 33977501, 32788252)
radiological findings
- CT scan may be normal; diagnosis is based on MRI.
- Core findings:
- Confluent, symmetric white matter lesions involving the deep supratentorial white matter and middle cerebral peduncle (while sparing the juxtacortical white matter).(34788237)
- Lesions are hyperintense on T2/FLAIR sequences, with diffusion restriction.(33414226)
- About half of patients may also have involvement of the cerebellum and/or brainstem.(33093131)
- Compared to control patients, there doesn't seem to be an increase in the number of microbleeds, corpus callosum involvement, or U-fiber involvement.(33414226)
- Over time, white matter necrosis with cavitation may occur in some patients, leading to cystic leukoencephalomalacia.(34664111)
management and prognosis
- There is no defined therapy for this entity. Leukoencephalopathy is generally diagnosed some weeks after admission when patients are failing to wake up, a time point which may be too late to alter the underlying disease process.
- Prognosis appears to be heterogeneous, with limited long-term follow-up data. Larger case series suggest a poor prognosis, with many patients developing white matter necrosis and failing to awaken. However, some case reports describe patients who gradually recover.(35538434, 34664111) Serial MRI studies demonstrating necrosis and cystic leukoencephalomalacia probably indicates a poor outcome (figure below).
This section provides a general discussion of acute necrotizing encephalopathy, which may be caused by a variety of different viruses in addition to COVID.
basics
- Acute necrotizing encephalopathy (ANE) is a rare, severe syndrome which typically occurs following viral infection.
- The pathophysiology remains unclear, but ANE seems to result from systemic hypercytokinemia (especially interleukin-6) that disrupts the blood-brain barrier and causes inflammation within the brain.(Toledano 2022)
- Pathophysiologically, ANE has numerous parallels to hemophagocytic lymphohistiocytosis (HLH), especially virus-associated hemophagocytic lymphohistiocytosis. Some cases of ANE have been reported as a consequence of hemophagocytic lymphohistiocytosis.(16638510, 32307298)
causes
- COVID-19 (Increased tendency to involve the medial temporal lobes and subinsular regions has been reported.) (34324121)
- Influenza (especially Influenza A, and in particular H1N1 influenza).
- Human Herpesvirus 6 (HHV6).
- Influenza B.
- VZV.
- Enterovirus.
- Mycoplasma pneumoniae.
clinical presentation
- Patients have an infectious prodrome, with may vary depending on the causative infection (as listed above). ANE is more of a parainfectious disorder that typically begins 1-3 days after the onset of a viral illness.(34324121)
- The development of ANE is heralded by somnolence, behavioral changes, seizures, focal deficits, or coma.
- Malignant cerebral edema may occur, which often leads to death.
- Most patients are febrile. Other clinical features of systemic inflammation may be present (e.g., thrombocytopenia, disseminated intravascular coagulation, and elevated transaminases).
- CSF usually shows no pleocytosis, with a protein elevated >100 mg/dL.(35058867)
neuroimaging
- Symmetric, bilateral deep gray matter lesions are present with edema, necrosis, and sometimes hemorrhage.(35058867) The bilateral thalami are most frequently involved, with other potential sites of involvement including caudate head, putamen, brainstem, internal and external capsules, and cerebellar white matter.
- CT scan typically shows hypodense edema in the affected regions (e.g., thalami). Intracranial hemorrhage may occasionally be seen.
- MRI findings may include:
- Other findings on imaging may include:
- Focal or generalized cerebral edema.
- Posterior reversible encephalopathy may occur.
- More on imaging features in Radiopaedia: 🌊
differential diagnosis
- Diseases that especially involve the bilateral thalami:
- Acute ischemic stroke involving the artery of Percheron or the basilar artery.
- CVT (cerebral venous thrombosis) involving the vein of Galen or straight sinus.
- Wernicke encephalopathy.
- Variant Creutzfeldt-Jakob disease.
- Toluene inhalation.
- Other differential diagnoses to consider:
- Direct viral infection of the deep gray matter (e.g., due to various arboviruses).
- Metabolic disorders (e.g., carbon monoxide poisoning).
- Acute disseminated encephalomyelitis (ADEM).
- Posterior reversible encephalopathy syndrome (PRES).
treatment
- Optimal treatment remains unknown. Based on parallels to hemophagocytic lymphohistiocytosis (HLH), immunomodulation might be expected to be beneficial.📖
- Early steroid administration may correlate with improved outcomes. Case reports describe the use of pulse-dose steroid.(35058867, 34324121)
- Tocilizumab (an IL-6 inhibitor) has appeared to be beneficial.(35058867)
- Other therapies which have been utilized include plasma exchange or intravenous immune globulin.(34623104)
- Seizures may require supportive management.
clinical presentation
- Mild encephalopathy with reversible splenial lesion (MERS) is a clinico-radiologic syndrome which usually occurs following a viral infection. Some alternative names include:
- “Reversible splenial lesion syndrome” (RESLES), in recognition that it is not invariably mild.(31588684)
- “Reversible splenial lesions during febrile illness” (RESLEF), in recognition that the syndrome is usually preceded by a febrile illness.
- “Cytotoxic lesions of the corpus callosum” (CLOCC)
- The pathophysiology of MERS appears to relate to systemic inflammation.(35518813)
- MERS is often seen as a transient post-viral syndrome with the following clinical manifestations:
neuroimaging
- The most obvious abnormality is often in the splenium of the corpus callosum. This is notable for T2/FLAIR hyperintensity, strong diffusion restriction, and lack of contrast enhancement.
- T2 hyperintensity may extend into other regions of the white matter (e.g., adjacent white matter and the genu of the corpus callosum).
- Although MERS is usually defined in terms of MRI findings, CT scan may occasionally reveal abnormalities.
differential diagnosis & management
- MERS may be caused by a variety of conditions, including several medications. Potential causes should be considered and avoided if possible.
- Some reports describe the use of steroid and immunomodulators (e.g., tocilizumab) to treat acute MERS due to COVID.(35518813) However, the natural history of MERS is that it tends to resolve spontaneously. This explains other reported cases of MERS which have improved without immunomodulatory therapy.(34604837)
- More on the differential diagnosis & management of MERS here: 📖
acute disseminated encephalomyelitis (ADEM) & acute hemorrhagic leukoencephalitis (AHLE)
acute disseminated encephalomyelitis (ADEM) & acute hemorrhagic leukoencephalitis (AHLE)
basics
- Acute disseminated encephalomyelitis (ADEM) is an acute, post-viral, demyelinating disorder characterized by numerous asymmetric lesions involving the white matter (although the basal ganglia and thalami may also be involved). Many patients with ADEM have antibodies against myelin-oligodendrocyte glycoprotein (anti-MOG antibodies). ADEM is one component of a larger constellation of neurologic disorders due to anti-MOG antibodies that also includes transverse myelitis and optic neuritis. Some patients with ADEM may also have transverse myelitis and/or optic neuritis.
- Acute hemorrhagic leukoencephalitis (AHLE) is an unusually severe form of ADEM. It is similar to ADEM, but patients additionally have hemorrhage and often develop markedly elevated intracranial pressure (ICP). Clinically, patients may develop coma and herniation.
clinical presentation
- Neurologic symptoms occur following COVID, with a lag time of ~1-3 weeks. The initial COVID infection may range from mild to severe. About half of patients are admitted to the hospital with a neurological chief complaint, whereas other patients may be initially admitted due to respiratory failure.(34978621)
- Various multifocal neurologic deficits may occur, depending on lesion location. ~85% of patients have encephalopathy (which may be higher than usual compared to ADEM caused by other etiologies among adults).(34978621)
- Patients may have concomitant optic neuritis and/or myelitis.(34788237)
laboratory evaluation
- CSF is often relatively bland:(34978621)
- Cell count is often normal or minimally elevated.
- Protein may be elevated, but this is a nonspecific finding. In acute hemorrhagic leukoencephalitis, protein is often substantially elevated (with a median level of 230 mg/dL).
- Oligoclonal bands are found in ~20% of patients.
- Serology is generally negative for anti-MOG antibodies.(34978621)
neuroimaging
- Acute disseminated encephalomyelitis (ADEM)(34623104)
- CT scan may reveal hypodensity due to edema, but doesn't reveal the extent of disease.
- MRI reveals numerous T2/FLAIR hyperintensities in the deep white matter and gray-white interface. Unlike many other disorders described here, lesions are often asymmetrically distributed.(33904434)
- Contrast enhancement is variable (when present, enhancement may be punctate, ring-enhancing, or have an open-ring pattern).
- 70% of patients have a concurrent spinal cord lesion.(34978621)
- Acute hemorrhagic leukoencephalitis (AHLE): In addition to the above findings, some patients may have striking hemorrhagic changes.
management
- Usual treatment regimens for ADEM may be utilized, including administration of steroid.(34623104)
- Neurological outcomes are often poor. This could argue for an aggressive approach to treatment (e.g., with a combination of steroid plus IVIG, or steroid plus plasma exchange).(34978621)
More information on ADEM & AHLE: 📖
- Acute transverse myelitis has been described within ~2 weeks of COVID infection, often following mild infections.
- Clinicoradiologic patterns may vary:
- Myelitis is usually longitudinally extensive (involving at least three segments of the spinal cord).(34623104)
- The thoracic cord is most often involved, followed by the cervical cord.(34060708)
- Involvement of the central cord is most often reported. However, other patterns have also been reported (e.g., ventral horn-predominant involvement causing flaccid myelitis, or selective involvement of the posterior and lateral tracts).(34413066)
- Reports generally describe a favorable outcome when treated with pulse-dose steroid, with or without plasma exchange.(35106196; 34060708)
- Myelitis may also occur as one component of acute disseminated encephalomyelitis (ADEM), which is described in the section above. 📖
- Post-COVID patients may rarely have a combination of transverse myelitis plus Guillain-Barre syndrome of the acute motor axonal neuropathy (AMAN) form.(34060708) This may cause diagnostic confusion, as most diagnostic algorithms are designed based on the assumption that the patient has only a single process.
- More on acute transverse myelitis: 📖
- Various types of autoimmune encephalitis have been reported in the context of COVID, especially limbic encephalitis (with involvement of the temporal lobes) and basal ganglia encephalitis.(34224248) Some cases have identified causative antibodies (e.g., anti-NMDA receptor antibodies and anti-GD1a antibodies).
- It has recently been recognized that autoimmune encephalitis is more common than previously thought (for example, with an incidence similar to HSV encephalitis in some series). Consequently, it is possible that COVID infection is merely coincidental in some or all of these cases.
- More on autoimmune encephalitis here: 📖
basics
- PRES has been reported in the context of COVID, even in the absence of hypertension.
- A tendency to develop PRES likely reflects endothelial dysfunction (a central pathomechanism of PRES). Of course, even in the absence of COVID, about 20% of patients with PRES may lack any documented hypertension.
clinical manifestations
- Case reports describe PRES as often being diagnosed 2-3 weeks after hospital admission due to COVID.(34840779)
- Common presenting symptoms include:(34840779)
- Altered mental status (60%).
- Seizures (50%). 📖
- Visual changes (including blurry vision, blindness)(20%).
- Headache.
- Hemiparesis, tetraparesis.
diagnosis
- PRES is a clinicoradiologic diagnosis, as shown in the figure above.
- Radiographic findings in PRES are discussed further here: 📖
- Patients with COVID and PRES may display a tendency towards the development of hemorrhage within affected areas.(32439646) However, lobar hematomas and/or punctate microhemorrhages may be caused by PRES even in the absence of COVID.
management
- Treatment is generally the same as for PRES due to other causes, as described further here: 📖
- Some authors have suggested that, given an increased risk of hemorrhage, anticoagulation should be avoided in these patients.(34291313)
More on PRES here: 📖
- Roughly ~1-2% of patients with COVID may develop an acute ischemic stroke (with exact numbers varying, depending on population characteristics). There may be a proclivity towards the development of large vessel occlusions (LVOs).
- Causes of ischemic stroke among COVID patients may include:
- Hypercoagulability.
- Cerebrovascular arteriopathy.(35461991)
- Cardiac complications of COVID (e.g., myocarditis, atrial fibrillation).
- Acute physiologic stress.
- Management should follow standard protocols for acute ischemic stroke.(35461991)
- More on acute ischemic stroke: 📖
intraparenchymal hemorrhage
- Acute intracranial hemorrhage may occur in patients with COVID. However, this is considerably less common than acute ischemic stroke (with the exception of patients on ECMO).(34623104; 35461991, 33089707)
- There may be an increased predilection for lobar hemorrhages.(33904434)
- Management should follow usual protocols for acute intracranial hemorrhage.
- More on acute intracranial hemorrhage: 📖
microbleeds (aka petechial hemorrhages or microhemorrhages)
- Microbleeds refer to tiny punctate hemorrhages which are primarily visible on MRI sequences dedicated to the detection of blood (e.g., SWI or GRE).
- Microbleeds are typically located within the corpus callosum, juxtacortical and subcortical regions of the cerebral hemispheres, the cerebellum, and the brainstem. (34623104, 34224248)
- Microbleeds may be seen in roughly ~20% of COVID patients who are intubated due to ARDS (with higher rates among sicker cohorts). Microbleeds correlate with systemic inflammation, potentially reflective of endothelial dysfunction causing cerebral microangiopathy.(35677326; 33904434)
- Some authors have suggested an association between microbleeds and diffuse leukoencephalopathy (a pattern discussed above). 📖 However, a study which compared COVID patients with and without diffuse leukoencephalopathy found that there was not actually an increase in microbleeds among patients with diffuse leukoencephalopathy.(33414226) Thus, microbleeds and diffuse leukoencephalopathy appear to be distinct phenomena, although they both tend to affect the same patient population.
- Optimal management of microbleeds is unknown. Currently, this seems to represent an epiphenomenon of severe COVID infection without any definitive management implications.
- Cerebral venous thrombosis is uncommon among patients with COVID, with one large series finding this to occur among ~1/1,000 patients.(35667743) However, this may be several orders of magnitude more common than some of the rare immunological complications listed above, such as acute disseminated encephalomyelitis (ADEM).(34978621)
- Presentations may be atypical, including simultaneous thrombosis of several cerebral veins.(33904434)
- Given that patients with COVID may have increased risk of cerebral venous thrombosis as well as large vessel occlusive strokes, it may be reasonable to consider broader utilization of vascular imaging in these patients (e.g., rather than obtaining a noncontrast head CT scan, a CT scan with the addition of angiography and venography might be obtained).(35667743)
- 💡 Consider obtaining a CT scan with CT angiogram and CT venogram up front to avoid serial road trips to the CT scanner.
- More on cerebral venous thrombosis: 📖
clinical presentation
- GBS generally occurs within two weeks after the initiation of other COVID-19 symptoms (coincident with development of adaptive immunity).(33647239)
- Some patients may lack respiratory symptoms due to COVID upon presentation, presenting instead with weakness or even back pain as a primary complaint.
- Demyelination may have been reported most frequently (AIDP – acute inflammatory demyelinating polyneuropathy), but axonal variants and Miller Fisher variant may also occur.(33647239)
diagnosis
- Diagnosis can be challenging for patients who are already admitted with COVID pneumonia, since GBS will tend to blend in with other causes of respiratory dysfunction present in these patients (e.g., critical illness neuropathy/myopathy, COVID pneumonia, pulmonary embolism, ventilator-acquired pneumonia). In some patients, GBS could be an occult cause of inability to wean from mechanical ventilation.
- CSF albuminocytologic dissociation was present in 71% of cases in one series (elevated CSF protein without pleocytosis).(34623104)
management
- Management is the same as for GBS due to other causes.
- Intravenous immune globulin (IVIG) is often the front-line therapy for Guillain-Barre syndrome (with equal efficacy compared to plasmapheresis and with superior tolerability). IVIG might also have the advantage of avoiding the removal of protective anti-COVID antibodies, which could theoretically occur with plasma exchange.
- More on GBS here: 📖
- Reports include involvement of various cranial nerves (e.g., facial nerve, abducens nerve, hypoglossal nerve) or multiple cranial neuropathies. Neuroimaging may reveal cranial nerve enhancement.(34388683)
- Oculomotor palsies have been reported in conjunction with the Miller Fisher variant of Guillain-Barre syndrome.(34788237)
- When approaching a COVID patient with cranial nerve abnormalities, the first concern should always be that the cranial nerve abnormality may reflect severe CNS pathology (e.g., brainstem infarction). Peripheral involvement of the cranial nerves is thus a diagnosis of exclusion.
myositis
- Myositis is rare, but can occur at any point during the illness and may be severe.
- Symptoms may include proximal muscle weakness and myalgia.
- MRI may show edema in the muscle (T2 hyperintensity), as well as diffuse enhancement post-contrast. This may be incidentally observed on a spine MRI performed to investigate pain or weakness.(34388683)
- Reports describe inflammatory infiltrates seen on histology resembling dermatomyositis, which appeared to respond to treatment with steroid.(34623104; 34155186)
rhabdomyolysis
- Rhabdomyolysis may occur in ~15% of hospitalized patients, with even higher rates among ICU patients.(33575135; 33975028) Creatine kinase levels may peak a median of six days following admission.(33975028) It's unclear to what extent this may relate primarily to COVID itself, to therapeutic paralysis with prone ventilation, or to various myelotoxic medications.
- More on the management of rhabdomyolysis: 📖
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- Avoid assuming that a neurological abnormality represents a rare COVID-related abnormality (e.g., acute necrotizing encephalopathy). Statistically, patients are most likely to have common disorders (e.g., stroke).
- Avoid attributing any neurologic abnormalities to nonspecific encephalopathy due to COVID. Patients often may have specific, treatable neurological disorders.
- Whenever possible, try to follow standard ICU protocols and procedures (e.g., sedation weaning, early mobilization).
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References
- 32439646 Franceschi AM, Ahmed O, Giliberto L, Castillo M. Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection. AJNR Am J Neuroradiol. 2020 Jul;41(7):1173-1176. doi: 10.3174/ajnr.A6595 [PubMed]
- 33089707 Pergolizzi JV Jr, Raffa RB, Varrassi G, Magnusson P, LeQuang JA, Paladini A, Taylor R, Wollmuth C, Breve F, Chopra M, Nalamasu R, Christo PJ; NEMA Research Group. Potential neurological manifestations of COVID-19: a narrative review. Postgrad Med. 2022 May;134(4):395-405. doi: 10.1080/00325481.2020.1837503 [PubMed]
- 33093131 Agarwal S, Conway J, Nguyen V, Dogra S, Krieger P, Zagzag D, Lewis A, Melmed K, Galetta S, Jain R. Serial Imaging of Virus-Associated Necrotizing Disseminated Acute Leukoencephalopathy (VANDAL) in COVID-19. AJNR Am J Neuroradiol. 2021 Jan;42(2):279-284. doi: 10.3174/ajnr.A6898 [PubMed]
- 33414226 Rapalino O, Pourvaziri A, Maher M, Jaramillo-Cardoso A, Edlow BL, Conklin J, Huang S, Westover B, Romero JM, Halpern E, Gupta R, Pomerantz S, Schaefer P, Gonzalez RG, Mukerji SS, Lev MH. Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy. AJNR Am J Neuroradiol. 2021 Apr;42(4):632-638. doi: 10.3174/ajnr.A6966 [PubMed]
- 33647239 Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barré syndrome. Lancet. 2021 Mar 27;397(10280):1214-1228. doi: 10.1016/S0140-6736(21)00517-1 [PubMed]
- 33904434 Garg RK, Paliwal VK, Malhotra HS, Sharma PK. Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review. Neurol India. 2021 Mar-Apr;69(2):260-271. doi: 10.4103/0028-3886.314531 [PubMed]
- 33977501 Vines BL, Agnihotri SP. Delayed post-hypoxic leukoencephalopathy in an adult with COVID-19. J Neurovirol. 2021 Jun;27(3):514-518. doi: 10.1007/s13365-021-00982-0 [PubMed]
- 34060708 Schulte EC, Hauer L, Kunz AB, Sellner J. Systematic review of cases of acute myelitis in individuals with COVID-19. Eur J Neurol. 2021 Oct;28(10):3230-3244. doi: 10.1111/ene.14952 [PubMed]
- 34155186 Suh J, Amato AA. Neuromuscular complications of coronavirus disease-19. Curr Opin Neurol. 2021 Oct 1;34(5):669-674. doi: 10.1097/WCO.0000000000000970 [PubMed]
- 34224248 Bahranifard B, Mehdizadeh S, Hamidi A, Khosravi A, Emami R, Mirzaei K, Nemati R, Nemati F, Assadi M, Gholamrezanezhad A. A review of neuroradiological abnormalities in patients with coronavirus disease 2019 (COVID-19). Neuroradiol J. 2022 Feb;35(1):3-24. doi: 10.1177/19714009211029177 [PubMed]
- 34291313 Motolese F, Ferrante M, Rossi M, Magliozzi A, Sbarra M, Ursini F, Marano M, Capone F, Travaglino F, Antonelli Incalzi R, Di Lazzaro V, Pilato F. Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature. J Neurol. 2021 Dec;268(12):4407-4414. doi: 10.1007/s00415-021-10709-0 [PubMed]
- 34324121 Breit H, Radaideh Y, John S. Acute necrotizing encephalopathy due to SARS-CoV-2 in a pregnant female. Neurol Sci. 2021 Oct;42(10):3991-3994. doi: 10.1007/s10072-021-05518-2 [PubMed]
- 34388683 Kanmaniraja D, Le J, Hsu K, Lee JS, Mcclelland A, Slasky SE, Kurian J, Holder J, Gunther MS, Chernyak V, Ricci ZJ. Review of COVID-19, part 2: Musculoskeletal and neuroimaging manifestations including vascular involvement of the aorta and extremities. Clin Imaging. 2021 Nov;79:300-313. doi: 10.1016/j.clinimag.2021.08.003 [PubMed]
- 34413066 Huang HY, Shah LM, McNally JS, Sant T, Hutchins TA, Goldstein ED, Peckham ME. COVID-19-Associated Myelitis Involving the Dorsal and Lateral White Matter Tracts: A Case Series and Review of the Literature. AJNR Am J Neuroradiol. 2021 Oct;42(10):1912-1917. doi: 10.3174/ajnr.A7256 [PubMed]
- 34416121 Hensley MK, Markantone D, Prescott HC. Neurologic Manifestations and Complications of COVID-19. Annu Rev Med. 2022 Jan 27;73:113-127. doi: 10.1146/annurev-med-042320-010427 [PubMed]
- 34604837 Mathew T, John SK, Kumar G G S. Acute SARS-CoV-2 infection and reversible splenial hyperintensity: A stroke mimic. J Am Coll Emerg Physicians Open. 2021 Sep 27;2(5):e12562. doi: 10.1002/emp2.12562 [PubMed]
- 34623104 Nath A. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Continuum (Minneap Minn). 2021 Aug 1;27(4):1051-1065. doi: 10.1212/CON.0000000000000992 [PubMed]
- 34664111 Lang M, Chang YS, Mehan WA Jr, Rincon SP, Buch K. Long-term neuroimaging follow-up of COVID-19-related leukoencephalopathy. Neuroradiology. 2021 Dec;63(12):2153-2156. doi: 10.1007/s00234-021-02829-1 [PubMed]
- 34744963 Sklinda K, Dorobek M, Wasilewski PG, Dreżewski K, Dȩbicka M, Walecki J, Mruk B. Radiological Manifestation of Neurological Complications in the Course of SARS-CoV-2 Infection. Front Neurol. 2021 Oct 20;12:711026. doi: 10.3389/fneur.2021.711026 [PubMed]
- 34788237 Marsiglia M, Chwalisz BK, Maher M. Neuroradiologic Imaging of Neurologic and Neuro-Ophthalmic Complications of Coronavirus-19 Infection. J Neuroophthalmol. 2021 Dec 1;41(4):452-460. doi: 10.1097/WNO.0000000000001454 [PubMed]
- 34840779 Iftikhar S, Rehman AU, Ameer MZ, Nawaz A, Aemaz Ur Rehman M, Farooq H, Asmar A, Ebaad Ur Rehman M. The association of posterior reversible encephalopathy syndrome with COVID-19: A systematic review. Ann Med Surg (Lond). 2021 Dec;72:103080. doi: 10.1016/j.amsu.2021.103080 [PubMed]
- 34978621 Gelibter S, Bellavia G, Arbasino C, Arnò N, Glorioso M, Mazza S, Murelli R, Sciarretta M, Dallocchio C. Encephalopathy as a prognostic factor in adults with acute disseminated encephalomyelitis following COVID-19. J Neurol. 2022 May;269(5):2293-2300. doi: 10.1007/s00415-021-10947-2 [PubMed]
- 35058867 Shukla P, Mandalla A, Elrick MJ, Venkatesan A. Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury. Front Neurol. 2022 Jan 4;12:628811. doi: 10.3389/fneur.2021.628811 [PubMed]
- 35106196 Qazi R, Memon A, Mohamed AS, Ali M, Singh R. Post-COVID-19 Acute Transverse Myelitis: A Case Report and Literature Review. Cureus. 2021 Dec 22;13(12):e20628. doi: 10.7759/cureus.20628 [PubMed]
- 35518813 Arıkan FA, Akdağ G, Çetiner M, Uysal N, Kabay SC. Isolated corpus callosum lesion associated with cytokine storm in COVID-19. Proc (Bayl Univ Med Cent). 2022 Mar 9;35(3):337-338. doi: 10.1080/08998280.2022.2044655 [PubMed]
- 35353232 Ariño H, Heartshorne R, Michael BD, Nicholson TR, Vincent A, Pollak TA, Vogrig A. Neuroimmune disorders in COVID-19. J Neurol. 2022 Jun;269(6):2827-2839. doi: 10.1007/s00415-022-11050-w [PubMed]
- 35461991 Hingorani KS, Bhadola S, Cervantes-Arslanian AM. COVID-19 and the brain. Trends Cardiovasc Med. 2022 Apr 21:S1050-1738(22)00064-0. doi: 10.1016/j.tcm.2022.04.004 [PubMed]
- 35538434 Kojima H, Sakamoto N, Kosaka A, Kobayashi M, Amemiya M, Washino T, Kuwahara Y, Ishida T, Hikone M, Miike S, Oyabu T, Iwabuchi S, Nakamura-Uchiyama F. COVID-19-associated leukoencephalopathy in the absence of severe hypoxia with subsequent improvement: a case report. BMC Infect Dis. 2022 May 10;22(1):444. doi: 10.1186/s12879-022-07426-y [PubMed]
- 35667743 Dangayach NS, Newcombe V, Sonnenville R. Acute Neurologic Complications of COVID-19 and Postacute Sequelae of COVID-19. Crit Care Clin. 2022 Jul;38(3):553-570. doi: 10.1016/j.ccc.2022.03.002 [PubMed]