- •Patients with coronavirus disease 2019 (COVID-19) may variably develop neurological manifestations.
- •Neuroinflammation and autoimmunity may underlie COVID-19 neurological complications.
- •COVID-19 neuroimmunological complications include Guillain-Barré syndromes, myopathy, and encephalomyelitis.
- •Immunotherapy may variably improve outcome in COVID-19 related neuroimmunological complications.
Abbreviations:angiotensin-converting enzyme 2 (ACE-2), acute disseminated encephalomyelitis (ADEM), anti-epileptic drugs (AEDs), acute inflammatory demyelinating polyneuropathy; (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), acute necrotizing encephalopathy (ANE), activated partial thromboplastin time (aPTT), aquaporin-4 (AQ4), acute respiratory distress syndrome (ARDS), blood-brain barrier; (BBB), creatinine kinase (CK), central nervous system (CNS), coronavirus disease 2019 (COVID-19), C-reactive protein (CRP), cytokine release syndrome (CRS), cerebrospinal fluid (CSF), dipeptidyl peptidase 4 (DPP4), diffusion-weighted imaging (DWI), electroencephalography (EEG), electromyography/nerve conduction study (EMG/NCS), erythrocyte sedimentation rate (ESR), fluid attenuated inversion recovery (FLAIR), Guillain-Barré syndrome (GBS), granulocyte-macrophage colony stimulating factor (GMCSF), hemagglutinating encephalomyelitis virus (HEV), intensive care unit (ICU), interleukin (IL), intravenous immunoglobulin (IVIG), olfactory receptor neurons (ORN), olfactory endothelia (OE), macrophage activation like syndrome (MAL), Middle East respiratory syndrome (MERS), Miller-Fisher syndrome (MFS), myelin oligodendrocyte glycoprotein (MOG), mouse hepatitis virus (MHV), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), peripheral nervous system (PNS), personal protective equipment (PPE), prothrombin time (PT), real-time reverse transcription polymerase chain reaction (rRT-PCR), severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), secondary hemophagocytic lymphohistiocytosis (sHLH), single-stranded RNA (ss-RNA), toll-like receptors (TLRs), transmembrane protease, serine 2 (TMPRSS2), tumor necrosis factor-α (TNF-α), TNF receptor-associated factor 6 (TRAF6), TIR-domain-containing adapter-inducing interferon-β (TRIF), white blood cell (WBC), World Health Organization (WHO)
- World Health Organization (WHO)
1.1 General virology
- Woo P.C.
- Lau S.K.
- Lam C.S.
- Lau C.C.
- Tsang A.K.
- Lau J.H.
- et al.
1.2 Epidemiology and transmission mode
- World Health Organization (WHO)
2. Route to the nervous system
2.1 Olfactory pathway
- Coolen T.
- Lolli V.
- Sadeghi N.
- Rovaï A.
- Trotta N.
- Taccone F.S.
- et al.
2.2 Pathways through other cranial nerves
2.3 Hematogenous pathway
3. Mechanisms of CNS involvement
3.1 Direct infection
3.3 Other mechanisms
4. Neurologic manifestations
- Xiong W.
- Mu J.
- Guo J.
- Lu L.
- Liu D.
- Luo J.
- et al.
- Xiong W.
- Mu J.
- Guo J.
- Lu L.
- Liu D.
- Luo J.
- et al.
|Region||Patients||Median (IQR) age, yr||Gender F (%)||Neurological Symptoms (%)||Other Symptoms (%)||Abnormal lab results (%)||CSF (% of cases)||Results of nervous system imaging or EEG (% of cases)||Ref|
|Wuhan, China (total 799)||113 death||68 (62–77)||30 (27)||Myalgia (19), headache (10), dizziness (9), impaired consciousness (22)||Fever (92), cough (70), fatigue (57), anorexia (27), dyspnea (62), chest tightness (49), pharyngalgia (4), hemoptysis (4), nausea (7), vomiting (5), abdominal pain (10)||Leukocytosis (50), lymphocytopenia (39); albumin (65) & ↓ K+ (12); ↑ AST (52), ALT (27), K+ (22), Na+ (18), D-dimer (35), LDH (82), CRP (60), IL-1β (9), IL-2R (81), IL-6 (100), IL-8 (28), IL-10 (70), TNF-α (77), pro-BNP (85) & cardiac troponin I (72).|
Higher ESR, ferritin & PT, and lower TSH in this group.
Chen et al., 2020b)
|161 recovery||51 (37–66)||73 (45)||Myalgia (24), headache (12), dizziness (7), impaired consciousness (1)||Fever (90), cough (66), fatigue (45), anorexia (22), dyspnea (31), chest tightness (30), pharyngalgia (5), hemoptysis (2), nausea (10), vomiting (6), abdominal pain (12)||Leukocytosis (4), lymphocytopenia (5), ↓ albumin (14) & K+ (11), ↑ AST (16), ALT (19), K+ (4), Na+ (2), D-dimer (2), LDH (14), CRP (14), IL-1β (12), IL-2R (37), IL-6 (60), IL-8 (8), IL-10 (19), TNF-α (47), pro-BNP (18) & cardiac troponin I (14).||NR||NR|
|Wuhan, China||214||Mean (SD) 52.7 (15.5)||127 (59.3)||Dizziness (16.8), headache (13.1), skeletal muscle injury (10.7), impaired consciousness (7.5), ageusia (5.6), anosmia (5.1), stroke (2.8, ischemic [66.3], hemorrhagic [16.7]), nerve pain (2.3), visual change (1.4), ataxia (0.5), seizure (0.5)||Fever (61.7), cough (50), anorexia (31.8), diarrhea (19.2), throat pain (14.5), abdominal pain (4.7)||Lower lymphocyte & platelets, & higher BUN levels in cases with CNS symptoms; no differences in cases with PNS symptoms; higher CK, CRP, D-dimer & neutrophils with lower lymphocytes in cases with skeletal muscle injury.||NR||NR||(Mao, Jin, 2020)|
|Wuhan, China||41||49 (41–58)||11 (29)||Headache (8), myalgia or fatigue (44)||Fever (98), cough (76), hemoptysis (5), diarrhea (3), dyspnea (55)||Leukopenia (25), lymphocytopenia (63), thrombocytopenia (5), ↑ AST (37), creatinine (10), CK (33), LDH (73), troponin I (12) & procalcitonin (8); overall ↑ IL-1β, IL-1Rα, IL-7, IL-8, IL-9, IL-10, FGF, GCSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNFα, & VEGF.|
Higher PT & D-dimer in ICU cases than non-ICU.
Huang et al., 2020b)
|Wuhan, China (total 710)||52 critical ill||Mean (SD) 59.7 (13.3)||17 (33)||Headache (6), myalgia (11.5), malaise (35)||Fever (98), cough (77), dyspnea (63.5), rhinorrhea (6), arthralgia (1), chest pain (2), vomiting (4), ARDS (67)||AKI (29), cardiac injury (23), liver dysfunction (29), hyperglycemia (35)||NR||NR||(|
Yang et al., 2020b)
|Wuhan, China||138||56 (42–68)||63 (45.7)||Fatigue (69.6), myalgia (34.8), dizziness (9.4), headache (6.5)||Fever (98.6), cough (59.4), anorexia (39.9), dyspnea (31.2), pharyngalgia (17.4), diarrhea (10.1), nausea (10.1), vomiting (3.6), abdominal pain (2.2), ARDS (19.6)||Acute cardiac injury (7.2), AKI (3.6).|
Higher WBCs, neutrophils, D-dimer, CK, & creatine in ICU cases than non-ICU.
Wan et al., 2020;
Wang et al., 2020a)
|Wuhan, China||99||Mean (SD) 55.5 (13.1)||32 (32)||Myalgia (11), confusion (9), headache (8)||Fever (83), cough (82), dyspnea (31), sore throat (5), rhinorrhea (4), chest pain (2), diarrhea (2), nausea/vomiting (1), ARDS (17)||Leukocytosis (24), lymphocytopenia (35), thrombocytosis (4), thrombocytopenia (12), anemia (51), ↓ albumin (98), ↑ neutrophils (38), aPTT (6), PT (5), D-dimer (6), ALT (28), AST (35), BUN (6), CK (13), LDH (76), myoglobin (17), procalcitonin (6), IL-6 (52), ESR (23.4), ferritin (63) & CRP (86); hyperglycemia (51), AKI (3).||NR||NR||(|
Chen et al., 2020a)
|Wuhan, China||452||58 (47–67)||217 (48)||Myalgia (21.4), confusion (0.7), headache (11.4), dizziness (8.1), fatigue (46.4)||Fever (92.6), cough (33.3), hemoptysis (2.6), dyspnea (50.8), rhinorrhea (1.8), pharyngalgia (4.8), anorexia (21), nausea/vomiting (9.2), diarrhea (26.7), abdominal pain (5)||Most cases: lymphocytopenia, ↑ procalcitonin, ESR, ferritin, CRP, TNF-α, IL-2R, & IL-6. ↓ helper T cells (CD3 + CD4+) and suppressor T cells (CD3 + CD8+).||NR||NR||(Qin, Zhou, 2020)|
|Wuhan, China||140||Median (range): 57 (25–87)||69 (49.3)||Fatigue (75)||Fever (91.7), cough (75), chest tightness/dyspnea (36.7), nausea (17.3), diarrhea (12.9), anorexia (12.2), abdominal pain (5.8), belching (5), vomiting (5)||Leukocytosis (12.3), leukopenia (19.6), lymphocytopenia (75.4), ↑ D-dimer (43.2), CRP (91.9), amyloid A (90.2), procalcitonin (34.7) & CK (6.7).||NR||NR||(|
Zhang et al., 2020b)
|Wuhan, China (fatal cases)||85||Mean (SD): 65.8 (14.2)||23 (27.1)||Fatigue (58.8), myalgia (16.5), headache (4.7)||Fever (91.8), dyspnea (70.6), anorexia (56.5), cough (22.4), diarrhea (18.8), vomiting (4.7), abdominal pain (3.5), chest pain (2.4), pharyngalgia (2.4), ARDS (74.1)||Leukocytosis (44.7), leukopenia (11.8), ↑ neutrophils (60), neutropenia (12.9), lymphocytopenia (77.6), thrombocytosis (7.1), thrombocytopenia (41.2), ↓ albumin (78.8), ↑ D-dimer (65.9), aPTT (25.9), PT (25.9), fibrinogen (47.1), ALT (16.5), AST (32.9), BUN (49.4), creatinine (18.8), CK (36.5), LDH (82.4), procalcitonin (22.4) & CRP (91.8); hypoglycemia (3.5), hyperglycemia (78.8).||NR||NR||(|
Du et al., 2020)
|Wuhan, China||221||Median (range): 55 (39–66.5)||113 (51.1)||Fatigue (70.6), headache (7.7),||Fever (90.5), cough (61.5), anorexia (36.2), dyspnea (29), diarrhea (11.3), pharyngalgia (10), abdominal pain (2.3), ARDS (21.7)||Leukocytosis (10.4), leukopenia (33), lymphocytopenia (17.6), thrombocytosis (5.4), thrombocytopenia (13.4), ↑ procalcitonin (5.9).||NR||NR||(|
Zhang et al., 2020d)
|Sichuan, Wuhan & Chongqing in China||917||Mean 48.7 (17.1)||417 (44.8)||Impaired consciousness (2.7), stroke (1.1), muscle cramp (0.2), headache (0.2), occipital neuralgia (0.1), tremor/tic (0.2)||NR||NR||3 cases: normal||Head CT scan (28 cases): new abnormal findings (32.1) including stroke (25%), brain tumor (3.6) & traumatic brain injury signs (3.5)||(Xiong, Mu, 2020)|
|Zhejiang, China||645||NR||317 (49.1)||Myalgia (11), fatigue (18.3), headache (10.4)||Fever (83.7), cough (65.9), sputum (34.9), hemoptysis (1.7), sore throat (15.04), dyspnea (4). diarrhea (8.2), nausea or vomiting (3.4)||NR||NR||NR||(|
Zhang et al., 2020e)
|Zhejiang, China||91||50 (36.5–57)||54 (59.34)||Fatigue (44), headache (7.7), myalgia (5.5), back discomfort (3.3)||Fever (71.4), cough (60.4), sputum (33), dyspnea (11), anorexia (25.3), diarrhea (23.1), nausea (12.1), vomiting (6.6)||Leukocytosis (4), leukopenia (15.4), lymphopenia (31.8), thrombocytopenia (11), ↑ CRP (53.8), procalcitonin (15.4), fibrinogen (24.2), D-dimer (24.2), ALT (7.7), AST (9.9)||NR||NR||(|
Qian et al., 2020)
|Zhejiang, China||62||41 (32–52)||27 (43.5)||Headache (34), myalgia or fatigue (52)||Fever (77), cough (81), sputum (56), diarrhea (8), hemoptysis (3), dyspnea (3)||Leukopenia (31), lymphocytopenia (42), ↑ AST (16), procalcitonin (11)||NR||NR||(|
Xu et al., 2020c)
|Guangdong, China||90||Mean (range): 50 (18–86)||51|
|Fatigue/weakness (21), myalgia (28), headache (4)||Fever (78), cough (63), sputum (12), sore throat (26), chills (7), diarrhea (6), nausea (6), vomiting (2)||Leukocytosis (3), leukopenia (21),↑ CRP (42)||NR||NR||(|
Xu et al., 2020b)
|Wenzhou, China||149||Mean (SD): 45.11 (13.35)||68 (45.6)||Headache (8.7), myalgia (3.4)||Fever (76.5), cough (58.4), sputum (32.2), dyspnea (1.3), sore throat (14.1), snotty (3.4), chest pain (3.4), chest tightness (10.8), chill (14.1), diarrhea (7.4), nausea or vomiting (1.3)||Leukocytosis (1.34), leukopenia (24.2), neutropenia (28.2), lymphocytopenia (35.6), thrombocytosis (5.4), thrombocytopenia (13.4), ↑ D-dimer (14.1), ALT (12.1), AST (18.1), LDH (30.2), CRP (23) & creatinine (28.9), & prolonged PT (11.4) or aPTT (26.9)||NR||NR||(|
Yang et al., 2020a)
|Hubei, China||137||Median (range): 57 (20–83)||76 (55.5)||Myalgia or fatigue (32.1%), headache (9.5)||Fever (81.8), cough (48.2), dyspnea (19), diarrhea (8), palpitation (7.3)||Leukocytosis (19), lymphocytopenia (72.3), ↑ CRP (83.9)||NR||NR||(|
Liu et al., 2020a)
|Beijing, China||13||34 (34–48)||3 (23.1)||Myalgia 3 (23.1), headache (23.1)||Fever (92.3), cough (46.3), upper airway congestion (61.5), diarrhea (7.7), rhinorrhea (7.7)||Lymphocytosis & ↑ CRP (some cases)||NR||NR||(|
Chang et al., 2020)
|Beijing, China||262||Median (range): 47.5 (1–94)||216 (82.4)||Fatigue (26.3), headache (6.5),||Fever (82.1), cough (45.8), dyspnea (6.9)||NR||NR||NR||(|
Tian et al., 2020)
|China||1099||47 (35–58)||459 (41.9)||Headache (13.6), fatigue (38.1), myalgia/arthralgia (14.9)||Admission fever (43.8), in-hospital fever (88.7), conjunctival congestion (0.8), nasal congestion (4.8), cough (67.8), sore throat (13.9), hemoptysis (0.9), dyspnea (18.7), nausea/vomiting (5), diarrhea (3.8), chills (11.5), tonsil swelling (2.1), ARDS (3.4)||Leukocytosis (5.9), leukopenia (33.7), lymphocytopenia (83.2), thrombocytopenia (36.2), AKI (0.5), DIC (0.1), rhabdomyolysis (0.2); ↑ CRP (most cases) & ↑ AST, ALT, CK & D-dimer (some cases).||NR||NR||(|
W-J and Z-Y, 2020)
|China||50||Mean (range): 43.9 (3–85)||21 (42)||Headache (10), myalgia (16), fatigue (16)||Fever (76), cough (40), sputum (14), sore throat (8), dyspnea (8), diarrhea (2)||Lymphocytopenia (28), ↑ CRP (52)||NR||NR||(|
Xu et al., 2020d)
|South Korea||28||Mean (range): 42.6 (20–73||13 (46.1)||Myalgia (14.3), fatigue (10.7)||Fever (32.1), sore throat (32.1), cough (17.9), chills (17.9)||NR||NR||NR||(2020)|
|New Delhi, India||21||Mean (range): 40.3 (16–73)||7 (33.3)||Headache (14.3)||Fever (42.9), cough (42.9), sore throat (23.8), dyspnea (4.8)||Leukopenia (4.8)||NR||NR||(|
Gupta et al., 2020)
|South Iran||113||Mean (range): 53.75 (20–99)||42 (37.2)||Fatigue (66.4), myalgia/arthralgia (61.1), headache (53.1), dizziness/vertigo (39.8),||Fever (59.3), cough (64.6), sputum (21.4), dyspnea (51.3), chest pain (38.1), sore throat (31.9), hemoptysis (6.2), chills (59.3), rhinorrhea (23), abdominal pain (21.2), diarrhea (22.1), nausea (42.5), vomiting (25.7), anorexia (66.4)||Leukocytosis (10.8), leukopenia (9), lymphocytopenia (12.6), thrombocytosis (11), thrombocytopenia (15.6), ↑ CRP (25), ESR (15.9), creatinine (35.5), & prolonged PT (77.9) or aPTT (45.8)||NR||NR||(|
Shahriarirad et al., 2020)
|Istanbul, Turkey||27 cases with brain MRI |
|Median (range): 63 (34–87)||6 (22)||Not specified||NR||NR||5 cases: ↑ protein (80), normal WBC, glucose, IgG index & albumin (100), negative RT-PCR for SARS-CoV-2 (100)||Brain MRI: abnormal (44.4); cortical FLAIR signal abnormality (37), increased cortical DWI with corresponding low ADC values (26), subtle leptomeningeal enhancement (18), punctate cortical blooming artifact (11).||(Kandemirli, Dogan, 2020)|
|Strasbourg, France||58||63||NR||On ICU admission (14); After neuromuscular blockers/sedations hold (67): agitation (69), confusion (65), corticospinal tract signs (hyperreflexia, ankle clonus & Babinski signs) (67), dysexecutive syndrome (36)||Fever (16), ARDS (100)||NR||7 cases: 0 WBC (100), + oligoclonal band with the same pattern in serum (29), ↑ IgG & protein (14), ↓ albumin (57), negative RT-PCR for SARS-CoV-2 (100)||Brain MRI (13 cases): leptomeningeal enhancement (62), bilateral frontotemporal hypoperfusion (11 cases, 100), ischemic stroke (23).|
EEG (8 cases): diffuse bifrontal slowing consistent with encephalopathy (12.5)
|(Helms, Kremer, 2020)|
|Region||Age, Gender||Neurological symptoms on admission (day from admission)||Other symptoms (onset day prior neurologic symptoms)||Admission serum labs (or day from admission)||CSF (day from admission)||Imaging or NCS/EMG (day from admission)||Treatments received||Outcome||Ref|
|Madrid, Spain||50, M||Two-day anosmia, ageusia, right INO, right fascicular oculomotor palsy, perioral paresthesia, ataxia, & areflexia||Fever, cough, malaise, headache & lumbar pain (5 days prior)||Lymphocytopenia, ↑ CRP; positive anti-GD1b IgG antibody||↑ Protein (80 mg/dL), 0 WBC, normal glucose, negative culture / COVID-19 rRT-PCR||Head CT scan: normal|
|IVIG (0.4 g/kg/day for 5 days)||Favorable; recovery in 2 weeks with residual anosmia & ageusia||(Gutiérrez-Ortiz, Méndez, 2020)|
|Madrid, Spain||39, M||Same-day ageusia, bilateral abducens palsy, & areflexia||Low-grade fever & diarrhea (3 days prior)||Leukopenia; normal LFT, RFT & cardiac enzymes||↑ Protein (62 mg/dL), 2 WBC, normal glucose, negative culture / COVID-19 rRT-PCR||Head CT: normal.|
|Supportive care||Favorable, complete recovery in 2 weeks||(Gutiérrez-Ortiz, Méndez, 2020)|
|Malaga, Spain||51, F||Eleven-day radicular thoracic/lumbar back & all limbs pain; 7-day rapidly progressive lower limb weakness & binocular diplopia, left external rectus muscle & bifacial weakness, areflexia, & autonomic dysfunction (dry eyes/mouth, diarrhea, labile blood pressure)||Diarrhea, odynophagia & cough (15 days prior)||Positive SARS-CoV-2 IgG, negative COVID-19 rRT-PCR||↑ Protein (70 mg/dL), 5 WBC, negative antiganglioside antibodies||EMG/NCS (day 4): asymmetric prolonged F wave latency for the lower limbs, low A-wave amplitude on the left leg, altered bilateral R1 responses in the Blink-Reflex, ↓ poor activity in right rectus-anterior femoral muscle & little spontaneous denervation activity in left rectus-anterior femoral (RAF) muscle on EMG, overall suggestive of demyelination in early stage.|
Repeat EMG/NCS (day 20): low F-wave amplitude & disintegrated morphology, similar alteration of Blink-Reflex & spontaneous denervation activity in bilateral RAF & left anterior tibialis.
|IVIG (0.4 g/kg/day for 5 days), gabapentin (total 900 mg/day)||Favorable||(Reyes-Bueno, García-Trujillo, 2020)|
|Acute Inflammatory Demyelinating Polyneuropathy (AIDP)|
|Jingzhou, China||61, F||One-day rapidly progressive ascending paraparesis & areflexia; evolving to tetraparesis & distal numbness (day 3)||No prior symptoms (had trip to Wuhan 7 days prior), later fever & cough (admission day 8)||Lymphocytopenia, thrombocytopenia, positive COVID-19 nasopharyngeal swab.||Day 4: ↑ protein level (124 mg/dL), 5 WBC, negative COVID-19 rRT-PCR.||EMG/NCS (day 5): prolonged left ulnar & bilateral tibial/peroneal distal motor latencies, absent ulnar/tibial/peroneal F waves, normal left median/ulnar & bilateral sural/superficial peroneal SNAPs, overall suggestive of demyelination.||IVIG (0.4 g/kg/day for 5 days); Day 8: arbidol, lopinavir & ritonavir||Favorable; complete recovery within 1 month||(Zhao, Shen, 2020a)|
|Northern Italy||76, M||One-day lumbar pain followed & rapidly progressive paraparesis; evolving tetraplegia, areflexia, & ataxia (day 4)||Cough &|
anosmia (5 days prior), fever (prior IVIG)
|Lymphocytopenia, ↑ CRP, ketonuria; positive serum SARS-CoV-2 IgG (64.59 AU/mL), positive COVID-19 nasopharyngeal swab.||Day 5: normal with negative COVID-19 rRT-PCR.||Brain/Spine MRI: normal.|
EMG/NCS (day 2): prolonged tibial /ulnar distal motor latencies, ↓ tibial/ulnar CMAP amplitudes, slow tibial/ulnar motor conduction velocities, prolonged tibial F wave, normal sural/ulnar SNAPs, normal EMG, overall suggestive of demyelination.
|IVIG (0.4 g/kg/day for 5 days)||Incomplete recovery, upper limb improvement but unable to stand (one month later)||(|
Toscano et al., 2020)
|Northern Italy||61, M||One-day rapidly progressive paraplegia, lower limb paresthesia & areflexia; evolving to tetraplegia, bifacial weakness & dysphagia (day 3), & respiratory failure (day 4)||Cough, ageusia, & anosmia (7 days prior)||Lymphocytopenia, ↑ CRP, LDH & AST; ketonuria; negative anti-GM1, GQ1b & GD1b antibodies; positive serum SARS-CoV-2 IgG (50.92 AU/mL), negative COVID-19 nasopharyngeal swab.||Day 3: normal protein (40 mg/dL), 3 WBC, negative COVID-19 rRT-PCR and viral/bacterial panel.||EMG/NCS (day 3): prolonged tibial and normal ulnar distal motor latencies, ↓ tibial/ulnar CMAP amplitudes, slow tibial/ulnar motor conduction velocities, absent tibial F wave, ↓ ulnar SNAP amplitude with sural sparing, fibrillation potentials on EMG, overall suggestive of demyelination.||IVIG (0.4 g/kg/day for 5 days) & plasma|
|Poor, prolonged ICU stay (> 1 month), bacterial|
pneumonia during IVIG therapy delaying plasma exchange
|(Toscano, Palmerini, 2020)|
|Monza, Italy||71, M||Three-day rapidly progressive distal paresthesia, lumbar pain, tetraparesis & areflexia||Low-grade fever (7 days prior), severe hypoxia on admission||Positive COVID-19 nasopharyngeal swab.||Admission: ↑ protein (54 mg/dL), 9 WBC, negative COVID-19 rRT-PCR.||Head CT scan: normal.|
EMG/NCS (on admission): absent bilateral sural SNAPs & tibial CMAP, prolonged peroneal motor distal latency, slow conduction velocity, & ↓ amplitude with temporal dispersion/conduction block, ulnar/radial CMAP temporal dispersion, slow radial CMAP conduction velocity, ↓ ulnar SNAP amplitude, normal radial SNAP, overall suggestive of demyelination.
|IVIG (0.4 g/kg/day; only received one dose), lopinavir, ritonavir, hydroxychloroquine||Death within 24 h due to progressive respiratory failure||(Alberti, Beretta, 2020)|
|Trento, Italy||66, F||Three-day rapidly progressive paraplegia, upper limb distal & unilateral facial weakness, gait instability, & areflexia||Self-resolved mild fever & cough (10 days prior)||↑ CRP (70.6 mg/L) & D-dimer (506 μg/L); normal CBCdiff, LFT, RFT, CK, PT, INR & LDH; positive COVID-19 nasopharyngeal swab||↑ Protein (108 mg/dL), 0 WBC||EMG/NCS (day 7): diffuse prolonged left tibial/common peroneal & right median distal motor latencies, reduced distal CMAP amplitudes & slight slow conduction velocities, absent left tibial/common peroneal & right median F-waves, absent right median/ulnar/radial/sural SNAPs, overall suggestive of demyelination.||IVIG (0.4 g/kg/day for 5 days); lopinavir, ritonavir, hydroxychloroquine||Poor, progressive weakness, dysesthesia, intermittent confusion / psychomotor agitation, intubation due to respiratory failure, multiorgan failure, leg DVT & pneumonia||(|
Ottaviani et al., 2020)
|Ravenna, Italy||70, F||One-day progressive limbs weakness, distal limb paresthesia, gait instability, areflexia; evolving to respiratory failure & intubation (day 4)||Fever & cough (24 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.|
Admission: mild leukocytosis, normal D-dimer, CK, LFT, RFT, ESR, & CRP.
|Day 4: mild ↑ protein (48 mg/dL), 1 WBC; COVID-19 rRT-PCR not done.||EMG/NCS (day 4): prolonged left median/right ulnar/bilateral tibial distal latencies, absent right median CMAP, slow median/ulnar/tibial motor conduction velocities, absent median/ulnar/tibial F waves, absent left median/left ulnar/bilateral superficial peroneal SNAPs, ↓ right ulnar/sural SNAP amplitudes, neurogenic pattern on EMG, overall suggestive of demyelination||IVIG (0.4 g/kg/day for 5 days)||Poor, ICU stay & intubation due to respiratory failure||(|
Padroni et al., 2020)
|Milan, Italy||60s, M||Three-day progressive tetraparesis, distal paresthesia, areflexia; evolving to bifacial weakness, hypophonia and dysarthria (day 8)||Self-resolved fever, headache, myalgia followed by anosmia & ageusia (20 days prior)||↑ IL-6, ferritin, LDH & fibrinogen; normal CBCdiff, CRP, CK, LFT & RFT; negative antiganglioside antibodies; negative COVID-19 nasopharyngeal swab, positive SARS-CoV-2 IgG.||Day 3: normal protein & WBC, negative COVID-19 rRT-PCR & other viral / bacterial panels.||Cervical spine MRI: normal|
EMG/NCS (day 5): prolonged right peroneal/median motor distal latencies, slow left tibial/bilateral peroneal/right ulnar motor conduction velocities, ↓ right median CMAP amplitude, abnormal temporal dispersion of peroneal CMAP, absent F waves, absent median/ulnar SNAPs with sural sparing, overall suggestive of demyelination.
|IVIG (0.4 g/kg/day for 5 days)||Incomplete with slow recovery||(|
Riva et al., 2020)
|Zaragoza, Spain||56, F||Acute hand paresthesia & gait instability; evolving to lumbar pain, progressive proximal paraparesis & areflexia (within 2 days of admission); following by tetraparesis, bifacial & bulbar weakness on IVIG.||Fever, cough & dyspnea (15 days prior)||Positive COVID-19 nasopharyngeal swab.||↑ Protein (86 mg/dL), 3 WBC, negative COVID-19 rRT-PCR.||Spine MRI: brainstem and cervical meningeal enhancement.|
EMG/NCS (day 11): prolonged distal latencies and absent F waves, suggestive of demyelination.
|IVIG (0.4 g/kg/day for 5 days)||Initial worsening on IVIG but partial recovery in 7 days||(Sancho-Saldaña, Lambea-Gil, 2020)|
|Ciudad Real, Spain||43, M||Acute rapidly progressive tetraparesis, distal paresthesia & areflexia; evolving to bifacial paresis & dysphagia (day 2)||Self-resolved diarrhea & cough (10 days prior)||Positive COVID-19 nasopharyngeal swab||Not done||EMG/NCS: prolonged distal motor latencies & slow sensory conduction velocities, prolonged F waves for right L5 and S1 roots, overall suggestive of demyelination||IVIG (0.4 g/kg/day for 5 days), hydroxychloroquine, lopinavir, ritonavir, amoxicillin, corticosteroids||Favorable||(|
Velayos Galán et al., 2020)
|Paris, France||64, M||Four-day rapidly progressive paraparesis, areflexia, distal hypoesthesia||Cough, dyspnea, diarrhea & fever (26 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.|
Admission: negative antiganglioside & anti-neuronal antibodies
|Day 6: ↑ protein (165 mg/dL), normal WBC, negative COVID-19 rRT-PCR||Head CT scan: normal.|
EMG/NCS (day 2): prolonged bilateral median & ulnar/left peroneal motor distal latencies, slow median/ulnar/peroneal/tibial motor conduction velocities and normal CMAP amplitudes, conduction blocks in bilateral peroneal/tibial CMAPs, absent SNAPS except for radial/ left median at palm, overall suggestive of demyelination.
|IVIG (0.4 g/kg/day for 5 days)||Favorable||(|
Arnaud et al., 2020)
|La Tronche, France||43, M||Four-day progressive ascending paraparesis, areflexia, limbs paresthesia &|
ataxia; evolving to right facial weakness (admission day)
|Self-resolved cough, asthenia, leg myalgia, acute anosmia, ageusia & diarrhea (21 days prior)||Normal CBCdiff & CRP; negative antiganglioside antibodies; positive COVID-19 nasopharyngeal swab||Admission: ↑ protein (94 mg/dL), 1 WBC, negative COVID-19 rRT-PCR.||Brain/spine MRI (day 3): multiple cranial neuritis (III, V, VI, VII, & VIII), radiculitis, & brachial/lumbar plexitis.|
EMG/NCS (day 5): bilateral peroneal conduction blocks, tibial/peroneal slow motor conduction velocities, sural sparing pattern, absent H-reflex, mildly prolonged F-waves, overall suggestive of demyelination
|IVIG (0.4 g/kg/day for 5 days)||Favorable, rapid improvement||(Bigaut, Mallaret, 2020)|
|La Tronche, France||70, F||Three-day rapidly progressive tetraparesis, areflexia, forelimb / perioral paresthesia; evolving to respiratory failure (admission day) & left facial weakness (day 6)||Self-resolved diarrhea, mild asthenia & myalgia with continuous anosmia and ageusia (10 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.|
Admission: ↑ CRP (22 mg/L); negative antiganglioside antibodies
|Admission: ↑ protein (106 mg/dL), 6 WBC, negative COVID-19 rRT-PCR.||EMG/NCS (day 4): left median conduction block & temporal dispersion, prolonged median/ulnar motor distal latencies, diffuse slow, motor/sensory conduction velocities, neurogenic pattern on EMG, overall suggestive of demyelination.||IVIG (0.4 g/kg/day for 5 days)||Slow recovery||(Bigaut, Mallaret, 2020)|
|Lausanne / Geneva, Switzerland||52, F||Acute lumbar pain, rapidly progressive proximal limb weakness, ataxia, distal paresthesia, dysgeusia & cacosmia; evolving to respiratory failure, dysautonomia & tetraplegia with areflexia (day 4)||Fever, cough, odynophagia, arthralgia & diarrhea (15 days prior)||Admission: normal CBCdiff, LFT & RFT, negative anti-GM1, GQ1b & GD1a antibodies.|
Day 14: positive serum SARS-CoV-2 IgM, positive COVID-19 nasopharyngeal swab (4th test)
↑ protein (60 mg/dL), 3 WBC, negative COVID-19 rRT-PCR.
|Spine MRI: normal.|
EMG/NCS (day 4): prolonged tibial/peroneal/median/ulnar distal motor latencies & slow conduction velocities, absent F waves, no sural sparing, overall suggestive of demyelination
Repeat EMG/NCS (days 7 & 14): slower conduction velocities & temporal dispersions.
|IVIG (0.4 g/kg/day for 5 days)||Favorable, initially worsening (day 4) while on IVIG, but recovery within 5 weeks||(|
Lascano et al., 2020)
|Lausanne / Geneva, Switzerland||63, F||Acute lower limb pain & weakness with normal reflexes; evolving to tetraparesis, distal paresthesia & areflexia (day 5)||Cough, shivering, odynophagia, dyspnea & chest pain (7 days prior)||Admission: negative COVID-19 nasopharyngeal swab;|
Day 7: positive COVID-19 nasopharyngeal swab.
Mild lymphocytopenia, mild ↑ AST (65 U/L), normal RFT.
|Day 6: normal protein (40|
mg/dL), 2 WBC; COVID-19 rRT-PCR not done.
|EMG/NCS (day 9): conduction block in tibial/peroneal/ulnar CMAPs, absent F waves, normal insertional/spontaneous activity on EMG, overall suggestive of demyelination.||IVIG (0.4 g/kg/day for 5 days), 5-day amoxicillin & clarithromycin (pneumonia)||Favorable, complete motor recovery residual distal paresthesia & areflexia (5 weeks)||(Lascano, Epiney, 2020)|
|Lausanne / Geneva, Switzerland||61, F||Four-day rapidly progressive lower limb weakness, distal paresthesia, dizziness, dysphagia, bifacial weakness & areflexia; evolving to dysautonomia (one day prior admission)||Fever, cough, myalgia, headache, vasovagal syncope, diarrhea, nausea & vomiting (22 days prior)||Prior to admission: positive COVID-19 nasopharyngeal swab.|
Admission: lymphocytopenia, hyponatremia, normal LFT & RFT.
|Day 1: ↑ protein (140 mg/dL), 4 WBC, negative COVID-19 rRT-PCR.||Brain MRI: normal.|
Spine MRI: lumbosacral nerve root enhancement.
EMG/NCS (day 4): prolonged peroneal/median motor distal latencies, slow tibial/peroneal/median/ulnar conduction velocities, ↓ tibial/peroneal/median CMAP amplitudes, absent F waves, overall suggestive of demyelination.
|IVIG (0.4 g/kg/day for 5 days), duloxetine||Favorable, residual allodynia & mild lower limb weakness after 5 weeks||(Lascano, Epiney, 2020)|
|Geneva, Switzerland||70s, M||Four-day rapidly progressive paraparesis, distal allodynia & areflexia; evolving to voiding problem & constipation||myalgia, fatigue & cough (6 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.||Day 1: ↑ protein, normal WBC, negative COVID-19 rRT-PCR, negative antiganglioside antibodies.||Spine MRI: normal.|
EMG/NCS (day 1): sensorimotor demyelinating polyneuropathy with sural sparing pattern, absent or prolonged F waves in tested nerves.
|IVIG (0.4 g/kg/day for 5 days)||Favorable within 11 days||(|
Coen et al., 2020)
|Selters, Germany||54, F||Ten-day progressive proximal>distal paraparesis, four limbs numbness & paresthesia, gait instability, & areflexia; evolving to paraplegia & dysphagia (day 2).||No symptoms; transient anosmia/ageusia (14 days prior); exposed to a case with PCR-positive COVID-19||Prior admission: positive COVID-19 nasopharyngeal swab (3 weeks prior), Admission: normal CRP, CBCdiff, TSH, electrolytes & vitamin B12 level; negative repeat COVID-19 nasopharyngeal swab.||↑ Protein (140 mg/dL), normal WBC; negative serology, Lyme antibody & COVID-19 rRT-PCR||Cervical spine MRI: normal.|
EMG/NCS (admission day): prolonged distal motor latencies and temporal dispersion of bilateral common peroneal nerve CMAPs, normal bilateral tibial nerve F wave latencies with pathological intermediate latency responses (complex A waves), overall suggestive of demyelination.
|IVIG (0.4 g/kg/day for 5 days)||Favorable, complete recovery, unchanged repeat EMG/NCS (14 days later)||(|
Scheidl et al., 2020)
|Pittsburgh, USA||72, M||One-day rapidly progressive ascending weakness, areflexia, distal paresthesia; evolving to respiratory failure and intubation (day 3), dysautonomia with labile blood pressure & tachycardia (day 4) with tetraplegia (day 6)||Self-resolved diarrhea, anorexia & chills (7 days prior)||Admission: leukocytosis, normal LFT, RFT, CK, & Lyme antibody; negative anti-GM1, GD1b, GQ1b and acetylcholine receptor binding, voltage-gated Ca2+ channel, ANA, & ANCA antibodies; positive COVID-19 nasopharyngeal swab.|
Day 8: SIADH with hyponatremia
Day 28: negative COVID-19 nasopharyngeal swab.
|Day 8: ↑ protein (313 mg/dL), 1 WBC, negative COVID-19 rRT-PCR & other viral / bacterial panels.||Head CT scan: normal.|
EMG/NCS (day 13): prolonged right ulnar & bilateral tibial/peroneal motor distal latencies with slow conduction velocities, absent F waves, ↓ right ulnar/peroneal CMAP amplitudes, absent right ulnar/bilateral sural SNAPs, normal EMG with poor effort, overall suggestive of demyelination.
|IVIG (0.4 g/kg/day for 4 days)||Poor, prolonged ICU (> 1 month) stay||(|
|Bursa, Turkey||53, F||3-day history of dysarthria associated|
with progressive weakness and numbness of the lower extremities
3-day history of dysarthria associated
with progressive weakness and numbness of the lower extremities
Three-day dysarthria & progressive lower limbs weakness & numbness, & areflexia
|No symptoms prior, mild fever (day 5 after neurological symptoms)||Admission: mild neutropenia, normal electrolytes, LFT, RFT & CRP.|
Day 5: mild lymphocytopenia, ↑ CRP, positive COVID-19 nasopharyngeal swab.
|Day 7: normal protein (32.6 mg/dL), 0 WBC, negative COVID-19 rRT-PCR.||Thoracic/lumbar spine MRI: asymmetrical thickening and hyperintensity of post-ganglionic roots supplying the brachial and|
lumbar plexuses in STIR sequences.
EMG/NCS: conduction blocks and temporal dispersion in right median/ulnar/peroneal CMAPs, normal right median/ulnar/peroneal F waves with decreased persistence, normal right sural/median/ulnar SNAPs, overall suggestive of demyelination.
|Plasma exchange (5 sessions every other day), hydroxychloroquine||Favorable, recovery within 2 weeks||(|
Oguz-Akarsu et al., 2020)
|Acute Motor and Sensory Axonal Neuropathy (AMSAN)|
|Northern Italy||77, F||Same-day rapidly progressive tetraplegia, facial weakness, areflexia, upper limb paresthesia (36 h later), & respiratory failure (day 6)||Fever, cough & ageusia (7 days prior)||Lymphocytopenia, ↑ CRP & LDH, ketonuria; negative anti-GM1, GQ1b & GD1b antibodies; positive COVID-19 nasopharyngeal swab.||Day 2: normal.|
Day 10: ↑ protein (101 mg/dL), 4 WBC, negative COVID-19 rRT-PCR in both days.
|Brain MRI: normal.|
Spine MRI: caudal nerve roots enhancement.
EMG/NCS (day 3): ↓ tibial/ulnar CMAP amplitudes, absent tibial/ulnar F waves, ↓ ulnar SNAP amplitude with sural sparing & fibrillation potentials on EMG, overall suggestive of AMSAN.
|2 cycles of IVIG (0.4 g/kg/day for 5 days)||Poor; persistent tetraplegia & dysphagia||(Toscano, Palmerini, 2020)|
|Northern Italy||23, M||Two-day progressive bifacial weakness & areflexia, evolving to lower limb paresthesia, ageusia & sensory ataxia||Fever & sore throat (10 days prior)||Lymphocytopenia, ↑ CRP, ferritin, LDH & AST; positive COVID-19 nasopharyngeal swab||Day 3: ↑ protein (123 mg/dL), 0 WBC, negative COVID-19 rRT-PCR.||Brain MRI: focal contrast enhancement at the internal|
acoustic meatus (bilateral facial nerve).
Spinal MRI: normal.
EMG/NCS (day 12): ↓ tibial/facial but normal ulnar CMAP amplitudes, prolonged ulnar distal latency, absent tibial F waves, ↓ ulnar SNAP amplitude with sural sparing, & fibrillation potentials on EMG, overall suggestive of AMSAN.
|IVIG (0.4 g/kg/day for 5 days)||Favorable; residual ataxia & facial weakness||(Toscano, Palmerini, 2020)|
|Casablanca, Morocco||70, F||Ten-day rapidly progressive tetraplegia, distal limbs paresthesia, areflexia||Self-resolved cough (3 days prior)||Lymphocytopenia, positive COVID-19 nasopharyngeal swab.||↑ protein (100 mg/dL), normal WBC, COVID-19 rRT-PCR not done.||EMG/NCS (day 10): markedly ↓ or absent motor and sensory nerve amplitudes in all four limbs, relatively normal conduction velocities and latencies, fibrillation potentials on EMG, overall suggestive of AMSAN.||IVIG (0.4 g/kg/day for 5 days), hydroxychloroquine, azithromycin||No improvement after one week||(|
El Otmani et al., 2020)
|Sari, Iran||65, M||Five-day rapidly progressive ascending tetraparesis, bifacial weakness, areflexia, & distal limbs numbness||Fever, cough, intermittent dyspnea (14 days prior)||↑ ESR & CRP, normal LFT, RFT & electrolytes, positive COVID-19 nasopharyngeal swab||Not done||Cervical spine MRI: only mild herniation of 2 intervertebral discs.|
EMG/NCS (day 9): ↓ bilateral median/ulnar/tibial CMAP amplitudes, absent bilateral peroneal CMAP, absent tibial F waves, absent bilateral median/ulnar/right sural SNAPs, ↓ recruitment on EMG, overall suggestive of AMSAN.
|IVIG (0.4 g/kg/day for 5 days)||NR||(|
Sedaghat and Karimi, 2020)
|Acute Motor Axonal Neuropathy (AMAN)|
|Northern Italy||55, M||Two-day rapidly progressive tetraparesis, limb paresthesia, neck pain, & areflexia; evolving to bifacial weakness & respiratory failure (day 5)||Fever & cough (12 days prior)||Lymphocytopenia, ↑ CRP, LDH, AST & GGT, ketonuria; negative anti-GM1, GQ1b & GD1b antibodies; positive serum SARS-CoV-2 IgG (32.5 U/mL), positive COVID-19 nasopharyngeal swab.||Day 3: ↑ protein (193 mg/dL), 0 WBC, negative COVID-19 rRT-PCR.||Brain MRI: normal.|
Spinal MRI: contrast enhancement of caudal nerve roots.
EMG/NCS (day 11): ↓ tibial/ulnar CMAP amplitudes, absent tibial/ulnar F waves, normal ulnar/sural SNAPs, & fibrillation potentials on EMG, overall suggestive of AMAN.
|2 cycles of IVIG (0.4 g/kg/day for 5 days)||Poor; prolonged (> 1 month) ICU stay due to neuromuscular|
respiratory failure & tetraplegia
|(Toscano, Palmerini, 2020)|
|Unspecified GBS variant (No EMG/NCS available)|
|Madrid, Spain||61, M||Same-dame right facial weakness; evolving to bifacial weakness next day||Fever & cough (10 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.||Mild ↑ protein (44 mg/dL), 0 WBC, negative COVID-19 rRT-PCR.||Head CT scan & Brain MRI: normal.||Low dose oral prednisone, hydroxychloroquine, lopinavir, ritonavir||Favorable, recovery after 2 weeks||(|
Juliao Caamaño and Alonso, 2020)
|Pamplona, Spain||76, F||Ten-day radicular lumbar pain, progressive tetraparesis, distal hypoesthesia, areflexia; evolving to bulbar weakness & respiratory failure within 4–12 h of admission||Fever & cough (8 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.|
Admission: mild thrombocytopenia, ↑ fibrinogen & D-dimer
|Not done||Head/cervical spine CT scan: only vertebral bodies degenerative signs.||Supportive||Death within 12 h of admission due to respiratory failure||(Marta-Enguita, Rubio-Baines, 2020)|
|Pittsburgh, USA||54, M||Two-day rapidly progressive ascending paraparesis & numbness, lower limbs areflexia, upper limbs hyporeflexia, later urinary retention||Fever & cough (7 days prior), Clostridium difficile colitis diarrhea (2 days prior), dyspnea & intubation||Normal CBCdiff & electrolytes, positive COVID-19 nasopharyngeal swab||Not done||Thoracic/lumbar MRI: normal.||IVIG (0.4 g/kg/day for 5 days), hydroxychloroquine||Favorable, residual lower limb weakness||(|
Virani et al., 2020)
|Skeletal Muscle Injury|
|Wuhan, China||60, M||Admission day 9: proximal lower limb weakness, myalgia & tenderness||Fever & cough (6 days prior), continued fever till admission day 6||Admission: leukopenia, ↑ CRP (111 mg/L), ↑ LDH (280 U/L), normal CK, LFT, RFT, positive COVID-19 nasopharyngeal swab.|
Day 7: ↑ CRP (206 mg/L).
Day 9: ↑↑ myoglobin (>12,000 μg/L), CK (11,842 U/L), LDH (2347 U/L), ALT (111 U/L) & AST (213 U/L), normal RFT & electrolytes.
Day 12: negative COVID-19 nasopharyngeal swab.
|NR||NR||Admission: opinavir, moxifloxacin & interferon nebulization; Day 6: meropenem & methylprednisolone|
Day 9: IV fluid, plasma transfusion, IVIG & supportive care
|Favorable; recovery within few days||(|
Jin and Tong, 2020)
|New York, USA||88, M||Acute progressive proximal lower limb weakness & myalgia||Low-grade fever & tachypnea (on admission)||↑↑ CK (13,581 U/L), ↑ LDH (364 U/L), positive COVID-19 nasopharyngeal swab; AKI (day 7)||NR||NR||IV fluid, hydroxychloroquine||Favorable; ↓ CK within 6 days (368 U/L)||(|
Suwanwongse and Shabarek, 2020)
|New York, USA||75, F||Four-day generalized weakness; evolving to lethargy, acute encephalopathy, & respiratory distress requiring ICU admission (day 3)||Concurrent ↓ appetite||Admission: ↑ CK (2767 U/L), ↑ troponin (0.663 ng/mL), normal EKG, hypernatremia (152 mM/L), AST (198 U/L), ALT (63 U/L), BUN (31 mg/dL) & creatinine (1.2 mg/dL); normal CBCdiff.|
Day 2: positive COVID-19 nasopharyngeal swab, ↑ LDH (497 U/L), CRP (37 mg/L), D-dimer (573 μg/L) & ferritin (2134 μg/L)
|NR||NR||Day 2: azithromycin, hydroxychloroquine, vancomycin & cefepime.|
Day 3: IV fluid, supportive care in ICU
Chan et al., 2020)
|New York, USA||71, M||On admission: intermittent leg twitching with tingling/numbness at the lateral upper thigh radiating down to the posterior mid-calf.||No prior symptoms, fever on admission; Day 2: spike fever and AKI|
Day 3: tachypnea, tachycardia, AF with RVR, AKI & ARDS requiring intubation
|Admission: ↑ CK (1859 U/L), BUN (78 mg/dL), creatinine (3.6 mg/dL), troponin (0.249 ng/mL), LDH (538 U/L), CRP (18.8 mg/L), D-dimer (989 μg/L) & ferritin (1003 μg/L); normal CBCdiff; EKG: new AF, positive COVID-19 nasopharyngeal swab.|
Day 2: ↑↑ creatinine (5.6 mg/dL)
|NR||Head CT scan: old right lacunar infarct.||Admission: doxycycline, ceftriaxone, hydroxychloroquine, IV fluid; heparin and metoprolol for new AF.|
Day 3: hemodialysis for AKI
|Poor, prolonged ICU stay & intubated.||(Chan, Farouji, 2020)|
|New York, USA||16, M||Four-day generalized myalgias, fatigue, & 2-day dark-colored urine; evolving to continued myalgia (day 4)||Fever, concurrent dyspnea on exertion (4 days), pharyngeal erythema & abdominal pain (on exam)||Mild leukocytosis & thrombocytopenia; ↑ AST (839 U/L) & ALT (157 U/L); normal creatinine, GGT, & electrolytes; positive COVID-19 nasopharyngeal swab, ↑↑↑ CK (427,656 U/L).|
Repeat CK (296,396 U/L), hyponatremia (130 mM/L), ↓ albumin (3.2 g/dL), normal creatinine & ferritin, ↑ procalcitonin (0.22 μg/L), LDH (2184 U/L), CRP (24.9 mg/L), troponin (0.58 ng/mL) & HgA1C (8.2%).
|NR||NR||IV fluid with sodium bicarbonate &|
|Favorable; recovery with ↓ CK (6526 U/L) and no myalgia at discharge (day 12)||(Gefen, Palumbo, 2020)|
|Region||Age, Gender||Neurological symptoms on admission (day from admission)||Other symptoms (onset day prior neurologic symptoms)||Admission serum labs (or day from admission)||CSF (day from admission)||Imaging or EEG (day from admission)||Treatments received||Outcome||Ref|
|Madrid, Spain||26 days, M||Two paroxysmal episodes: 1st, several-minute upward eyes rolling & generalized hypertonia associated with a feeding; 2nd, several-minute generalized hypertonia & facial cyanosis during sleep. No abnormal movements.||12-h fever, rhinorrhea, & vomiting||Mild ↑ CK (380 U/L), LDH (390 U/L) & fibrinogen (4.18 mg/dL); normal CBCdiff, BMP, LFTs, CRP, & BCx/UCx; positive COVID-19 nasopharyngeal swab||Normal||Cranial ultrasound: normal.|
cEEG: continuous background patters with sleep-wake cycles without electrical and clinical seizures.
|Six-day hospitalization with supportive care||Favorable||(|
Chacón-Aguilar et al., 2020)
|New York, USA||6 weeks, M||Two brief 10–15 s episodes of upward gaze & bilateral leg stiffening. No abnormal movements.||Fever & cough||Leukopenia (5.07 K/μL), ↑ procalcitonin (0.21 ng/mL), normal BMP; positive for rhinovirus / enterovirus PCR; positive COVID-19 nasopharyngeal swab||Normal||Brain MRI: normal.|
cEEG: Excess of temporal sharp transients for age & intermittent vertex delta slowing with normal sleep-wake cycling.
Dugue et al., 2020)
|Brooklyn, USA||72, M||Altered mental status requiring intubation (admission); followed by multiple episodes of generalized tonic colonic movements (day 3)||Dyspnea||Lymphocytopenia (0.5 K), leukopenia (4 K), ↑ CRP (61 mg/L) & LDH (230 U/L), negative nasopharyngeal swab for influenza A and B, positive COVID-19 nasopharyngeal swab||NR||Head CT scan: chronic microvascular ischemic changes with no acute changes.|
Brain MRI: not done due to patient unstable condition.
cEEG: Six left temporal seizures & left temporal sharp waves which were epileptogenic.
|Transient oseltamivir; hydroxychloroquine, azithromycin, vancomycin, piperacillin tazobactam, versed & levetiracetam with additional valproate||Death due to cardiac arrest (day 5)||(|
Sohal and Mossammat, 2020)
|Encephalitis / Meningoencephalitis|
|Yamanashi, Japan||24, M||Multiple generalized seizures, unconsciousness & neck stiffness||Fever & generalized fatigue (9 days prior); headache & sore throat (5 days prior)||↑ WBC (mainly neutrophils) & CRP; negative HSV1/VZV IgM; negative COVID-19 nasopharyngeal swab||Day 3: ↑ pressure (320 mmH2O), 12 WBC (10 mononuclear), positive COVID-19 rRT-PCR||Head CT scan: normal.|
Brain DWI MRI: hyperintensity along the wall of inferior horn of right lateral ventricle; FLAIR MRI: hyperintense signal changes in the right mesial temporal lobe & hippocampus with slight hippocampal atrophy with no contrast enhancement, suggestive of right lateral ventriculitis & encephalitis mainly on right mesial lobe & hippocampus; T2-weighted image: pan-paranasal sinusitis.
|Transient ceftriaxone, vancomycin, acyclovir & steroids; levetiracetam; favipiravir||Poor; ongoing (>15 days) ICU stay due to encephalitis & bacterial pneumonia||(Moriguchi, Harii, 2020)|
|Wuhan, China||NR, M||Acute confusion, nuchal rigidity, Kernig, Brudzinski & Babinski signs.||Fever, dyspnea & myalgia (12 days prior)||↓ WBC (lymphocytopenia), positive COVID-19 nasopharyngeal swab.||Mild ↑ pressure (220 mmHg), normal protein (80 mg/dL), 1 WBC, negative COVID-19 rRT-PCR, IgM & IgG||Head CT scan: normal.||Supportive care, mannitol infusion||Favorable; complete recovery within 14 days||(Ye, Ren, 2020a)|
|Nanjing, China||64, M||Acute lethargy & unresponsiveness, positive ankle clonus (left>right), left Babinski & Chaddock signs, & mild neck stiffness||Fever, cough (13 days prior), insomnia & myalgia (11 days prior)||↑ CRP (10.74 mg/L), normal WBC, positive COVID-19 nasopharyngeal swab.||Day 6: pressure (200 mmH2O), normal protein (27.5 mg/dL), 1 WBC, negative COVID-19 rRT-PCR||Head CT scan: normal.||NR||Favorable; recovery within 14 days||(Yin, Feng, 2020)|
|Brescia, Italy||60, M||Five-day progressive irritability, confusion, asthenia, cognitive fluctuations; evolving to severe akinetic mutism, positive palmomental & glabella reflexes, & nuchal rigidity||Fever & cough (3 days after onset of neurologic symptoms)||↑ D-dimer (968 μg/L); normal CBCdiff, CRP, fibrinogen & ferritin; negative autoimmune encephalitis antibody panel; positive COVID-19 nasopharyngeal swab||Admission: ↑ protein (69.6 mg/dL), 18 WBC (100% lymphocytes), negative culture/viral/COVID-19 rRT-PCR.|
Repeat one day after steroid: ↑protein (127.2 mg/dL), 18 WBC (100% lymphocytes); ↑ IL-6, IL-8, TNF-α & β2-microglobulin; normal tau & neurofilament light; negative culture / viral / COVID-19 rRT-PCR
|Head CT scan: normal.|
Brain MRI: normal.
EEG: generalized slowing with decreased reactivity to acoustic stimuli.
|Lopinavir, ritonavir, hydroxychloroquine, ampicillin & acyclovir, 5-day methylprednisolone (1 g/day), post-discharge oral prednisone with rapid taper||Favorable; residual mild disinhibition & fluctuating alertness; normal exam on day 11||(Pilotto, Odolini, 2020)|
|Varese, Italy||22, F||Admission: acute loss of consciousness, hypocapnia & hypoxia, requiring intubation.|
Day 15: acute flaccid paraparesis, lower hyperreflexia, urine/bowel incontinence, & lower limbs hypoesthesia
|Dyspnea & fever (concurrent)||Leukocytosis (28.7 K), ↑ CRP (136.1 mg/L), D-dimer (>9000 μg/L), glucose (744 mg/dL), LDH (729 U/L) & AST (144 U/L); normal RFT; positive COVID-19 nasopharyngeal swab||Day 18: mild ↑ protein (53 mg/dL), normal WBC, negative COVID-19 rRT-PCR.||Head CT / CT angiogram (admission): a tiny right frontal parenchymal hemorrhage; no vascular malformations.|
Brain & Spine MRI: Only a late subacute phase tiny frontal hemorrhage (8mm of maximum diameter)
|Antiviral & immunomodulatory therapies||Favorable; recovery after 15 days||(|
Giorgianni et al., 2020)
|Barcelona, Spain||25, M||One-day headache, left-sided paresthesia, & ipsilateral paresis, evolving to confusion & agitation (12h)||Concurrent fever||Mild ↑ D-dimer (600 μg/L), normal CBCdiff||↑ protein (105.5 mg/dL), IL-1β (14.8 pg/mL), IL-6 (190 pg/mL) & ACE (15.5 U/L); normal WBC, negative COVID-19 rRT-PCR.||Head CT scan / brain MRI: normal.||Acyclovir, ampicillin, & ceftriaxone||Favorable, recovery within 1 day||(|
Bodro et al., 2020)
|Barcelona, Spain||49, M||7-day myalgia with acute difficulty naming objects, temporospatial disorientation, confusion, & agitation||Persistent fever, myalgias & cough (7 days prios)||Mild lymphocytopenia, mild ↑ D-dimer (600 μg/L), LDH (254 U/L) & ferritin (428 μg/L)||↑ protein (115.5 mg/dL), IL-6 (25 pg/mL) & ACE (10.9 U/L); normal WBC, negative COVID-19 rRT-PCR.||Head CT scan / brain MRI (day 2): normal.||Acyclovir, ampicillin, & ceftriaxone||Favorable, recovering within 3 days||(Bodro, Compta, 2020)|
|Lausanne, Switzerland||64, F||Acute psychosis, tonic-clonic seizure followed by disorientation, attention deficit, verbal and motor perseverations, bilateral grasping, alternating with psychotic symptoms (hyper-religiosity with mystic delusions, visual hallucinations).||Mild fatigue, myalgia, cough (5 days prior)||Positive COVID-19 nasopharyngeal swab||↑ Protein (466 mg/dL), 17 WBC, negative culture, viral PCR & COVID-19 rRT-PCR & anti-NMDA|
|Brain MRI: normal.|
Admission EEG: nonconvulsive, focal status epilepticus (abundant bursts of anterior low-medium voltage irregular spike-and waves superimposed on an irregularly slowed theta background)
Repeat EEG at 56 h: normal.
|IV clonazepam & valproate||Favorable; recovery within 96 h||(Bernard-Valnet, Pizzarotti, 2020)|
|Lausanne, Switzerland||67, F||Intense wake-up headache followed by drowsiness and confusion, motor perseverations, bilateral grasping, aggressiveness and left hemianopia and sensory hemineglect||Mild respiratory symptoms with confirmed COVID-19 (17 days prior)||Positive COVID-19 nasopharyngeal swab||↑ Protein (461 mg/dL), 21 WBC, negative culture, viral PCR & COVID-19 rRT-PCR||Brain MRI: normal.||Transient ceftriaxone, amoxicillin &|
|Favorable; recovery within 24 h||(Bernard-Valnet, Pizzarotti, 2020)|
|Istanbul, Turkey||6 cases (22–59 age range), one F||Encephalopathy, failure in gaining consciousness, developing agitation & delirium upon extubation||ARDS requiring intubation||Leukocytosis (11–42 K); ↑ CRP (32–732 mg/L), D-dimer (730–7930 μg/L), LDH (271–1110 U/L), ferritin (555–5235 μg/L), ↑ IL-6 (3 patients checked, 481–9192 pg/mL)||↑ Protein (5 cases, 57–131 mg/dL), 0 WBC, normal glucose, ↑ IgG (5 cases checked), negative oligoclonal bands & culture / viral PCR / COVID-19 rRT-PCR.||Brain MRI (3 cases): cortical/white matter hyperintensities, contrast enhancement, and sulcal hemorrhagic features, compatible with meningoencephalitis.|
Brain MRI (3 cases): normal
|Plasmapheresis||Early gain of consciousness in 4 patients; one death due to COVID-19 worsening & cardiac arrest; prolonged ICU stay in one case due to CMV infection||(Dogan, Kaya, 2020)|
|Boca Raton, USA||74, M (originally from Netherland)||Headache & progressive altered mental status||Fever & cough (one day prior)||Negative blood culture, urinalysis & Influenza A and B tests; positive COVID-19 nasopharyngeal swab||Mild ↑ protein (68 mg/dL), 4 WBC; negative culture, viral panel & COVID-19 rRT-PCR negative||Head CT scan: a left temporal region encephalomalacia, related to prior history of embolic stroke.|
EEG: bilateral slowing & focal slowing in the left temporal region with sharply countered waves.
|Hydroxychloroquine, lopinavir, ritonavir, vancomycin, meropenem & acyclovir.||Poor; critically ill||(Filatov, Sharma, 2020)|
|Telford, UK||40, M (originally from Nigeria)||On admission day 3: gait instability; evolving to diplopia, oscillopsia, limb ataxia, right arm numbness, hiccups, bifacial/tongue weakness, upbeat nystagmus & normal reflexes (day 4)||Fever, dyspnea & malaise (10 days prior)||Admission: marginally ↑ CRP (50 mg/L), ALT (88 U/L) & GGT (107 U/L); normal CBCdiff; positive COVID-19 nasopharyngeal swab.|
Later: ↑ LFTs; Liver ultrasound: an inflammatory diffusely hypoechoic liver with a raised periportal & pericholecystic echogenicity.
|Normal protein (42.3 mg/dL), 0 WBC; COVID-19 rRT-PCR not done (low volume tap)||Brain/cervical spine MRI: hyperintensity in the right inferior cerebellar peduncle, extending to involve a small portion of the upper cord, measuring 13 mm in|
maximum cross-sectional area and 28 mm in longitudinal extent, swelling at the affected tissue and associated microhemorrhage; suggestive of inflammatory rhombencephalitis & myelitis.
|Supportive care, gabapentin (300 mg twice daily)||Favorable; recovery with residual oscillopsia & ataxia||(Wong, Craik, 2020a)|
|New York, USA||74, M||Acute confusion following falls; evolving to combative behavior in hospital.||Admission: fever|
Day 5: new atrial fibrillation
|Admission: thrombocytopenia (122K), positive COVID-19 nasopharyngeal swab.|
Day 3: ↑ D-dimer (740 μg/L)
Day 7: ↑ CRP (183.5 mg/L), ferritin (2837 μg/L)
Day 10: ↑ D-dimer (5850 μg/L)
|NR||Head CT scan: unchanged nonspecific patchy subcortical & periventricular hypodensities.|
Brain autopsy: 80 to 110 nm viral particles in frontal lobe brain sections with Pleomorphic spherical viral-like particles observed in small vesicles of endothelial cell, distended cytoplasmic vacuoles containing enveloped viral particle in neural cell bodies, positive COVID-19 rRT-PCR.
|Admission: Hydroxychloroquine (4 days), enoxaparin S.C.|
Day 5: tocilizumab & metoprolol
|Death at day 1 due to pneumonia and respiratory failure related to COVID-19||(|
Paniz-Mondolfi et al., 2020)
|Los Angeles, USA||41, F||Same-day headache, new onset seizure, lethargy, neck stiffness & photophobia||Admission: fever||↑ lactic acid (4.8 mM/L); normal WBC, CK, LFT & RFT; negative nasopharyngeal swab for influenza A and B viruses; positive COVID-19 nasopharyngeal swab.||↑ Protein (100 mg/dL), 70 WBC (100% lymphocytes), negative culture & viral PCR, positive COVID-19 rRT-PCR,||Head CT scan: normal.|
EEG: generalized slowing with no epileptic discharges.
|Transient ceftriaxone, vancomycin & acyclovir; levetiracetam; hydroxychloroquine||Favorable; recovery within 12 days||(|
Duong et al., 2020, Huang, Jiang, 2020b)
|Acute necrotizing hemorrhagic encephalopathy|
|Detroit, USA||Late 50, F||Three-day altered mental status||Fever & cough (concurrent)||Positive COVID-19 nasopharyngeal swab||Limited data due to traumatic LP, negative culture & viral PCR; unable to test COVID-19 rRT-PCR.||Head CT scan: symmetric hypoattenuation within the bilateral medial thalami.|
Head CT angiogram / venogram: normal.
Brain MRI: hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions.
|IVIG||NR||(Poyiadji, Shahin, 2020)|
|Acute CNS demyelination: Brain and/or Spinal Cord|
|Wuhan, China||66, M||Same-day rapidly progressive paraparesis, hyporeflexia, bladder & bowel incontinence, sensory loss below T10 level||Fever & fatigue (6 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab.|
Admission: Leukocytosis (11.8 K), lymphocytopenia; ↑ IL-6 (56.7 pg/mL), CRP (278 mg/L), amyloid (1844 mg/L), procalcitonin (4.33 ng/mL), AST (50 U/L) & ALT (56.4 U/L); normal CK, LDH, troponin & RFT
|Not done||Head CT scan: bilateral basal ganglia and paraventricular lacunar infarction & brain atrophy.|
Brain MRI: not done.
|Ganciclovir, lopinavir, ritonavir, moxifloxacin, meropenem, glutathione, dexamethasone, IVIG (15 g/day for 7 days), mecobalamin & pantoprazole||Favorable; partial recovery after 7 days||(|
Zhao et al., 2020b)
|Denmark||28, F||Severn-day persistent lumbosacral pain, progressive ascending paresthesia/sensory loss mid-chest below the nipple line, bilateral upper extremities, and tip of tongue; evolving to urinary retention, nausea & vomiting in 48 h; Lhermitte's sign & wide-based gait||Cough, fever, lumbar pain, myalgias & rhinorrhea (7 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab||↑ Protein (60 mg/dL) & 125 WBC;||Spine MRI: Widespread elongated signal changes throughout the spinal cord to the conus medullaris and involving the medulla, overall suggestive of longitudinally extensive acute transverse myelitis||Prednisone & 2 plasmapheresis sessions||Favorable; improvement within 8 days||(|
Sarma and Bilello, 2020)
|Marseille, France||54, F||Admission: altered mental status|
Day 10: slight improvement in mental status, but right hemiplegia
|Fever, asthenia, dyspnea (8 days prior)||Admission: ↑ CRP (346 mg/L), LFTs & ferritin, positive COVID-19 nasopharyngeal swab||Admission: traumatic LP but normal protein and WBCs, negative culture/viral/ COVID-19 rRT-PCR.|
Repeat (day 9): Unchanged.
|Head CT scan (day 2): hypodense lesions involving supratentorial white matter & pallidum bilaterally.|
EEG: slowed background activity.
Brain MRI (day 7): Multiple supratentorial punctiform and tumefactive lesions involving the white matter bilaterally and showing hypersignal on coronal FLAIR, axial T2-weighted, & DWI with low ADC. Some periventricular lesions or involving the corpus callosum with a mass effect on the left lateral ventricle. No intracranial vessels abnormalities.
Repeat MRI (day 10): unchanged, but all homogenous contrast enhancement without any sign of hemorrhage in all lesions.
Spine MRI: normal.
|Hydroxychloroquine, azithromycin, amoxicillin/clavulanic acid; Day 12: steroid therapy after negative COVID-19 nasopharyngeal swab||NR||(Brun, Hak, 2020)|
|Brescia, Italy||54, F||Acute unconsciousness at home; evolving to hypoxia & intubation||No symptoms; anosmia & ageusia (several days prior)||Lymphocytopenia, ↑ CRP (41.3 mg/L) & fibrinogen (520 mg/dL); positive COVID-19 nasopharyngeal swab||Normal, negative COVID-19 rRT-PCR||Head CT scan: normal.|
EEG: two seizures starting from right frontotemporal region & diffusing in homologous contralateral hemisphere.
Brain MRI: numerous periventricular white matter alterations, confluent with each other & compatible with demyelinating lesions, adjacent to the temporal, frontal & occipital horns & to the trigones, hyperintense in T2, without restriction of diffusion & without contrast enhancement.
Cervical/thoracic spine MRI: numerous focal hyperintense intramedullary signal alterations in T2 & without contrast enhancement, located at the bulb-medullary junction, at C2 and from C3 to T6 levels.
|Hydroxychloroquine, lacosamide, levetiracetam, phenytoin, dexamethasone (10-day 20 mg/day & 10-day 10 mg/day)||Favorable, recovery after 12 days||(Zanin, Saraceno, 2020)|
|Genova, Italy||64, F||Acute bilateral vision impairment, right leg numbness, headache, mild irritability, bilateral RAPD, ageusia & anosmia, right abdominal sensory level, left lower limb hyperreflexia & Babinski sign.||Flu-like symptoms, & persistent ageusia & anosmia (25 days prior)||Negative COVID-19 nasopharyngeal swab, positive anti-SARS-CoV-2 IgG, negative AQ4 & anti-MOG antibody||Mild ↑ protein (45.2 mg/dL), 22 WBC (T-lymphocytic), negative COVID-19 rRT-PCR||Brain/spine MRI: multiple T1 post-contrast enhancing lesions of the brain, associated with a single spinal cord lesion at T8 level & with bilateral optic nerve enhancement, suspicion about ADEM.|
Follow-up MRI: a partial improvement with a reduction in the number of contrast-enhancing lesions.
|Methylprednisolone (1 g/day for 5 days) oral prednisone (75 mg/day), IVIG (2 g/kg for 5 days)||Favorable; improvement after 14 days of treatment||(Novi, Rossi, 2020)|
|Esslingen, Germany||60, M||Two-day urinating problem, progressive spastic paraparesis, hypesthesia below T9 level & Babinski's sign||Respiratory symptoms (8 days prior)||Prior admission: positive COVID-19 nasopharyngeal swab|
Admission: normal CRP, negative COVID-19 nasopharyngeal swab
|Admission: ↑ protein (79.3 mg/dL), 16 WBC (lymphocytic), no oligoclonal band.|
Repeat: ↑ protein (117.7 mg/dL), 27 WBC (lymphocytic); negative COVID-19 rRT-PCR both times, negative SARS-CoV-2 IgG.
Day 12: ↑ protein (73.4 mg/dL), 3 WBC
|Brain MRI: normal.|
Spine MRI: T2 signal hyperintensity of the thoracic spinal cord at T9 level, suggestive of acute transverse myelitis.
Spine MRI (day 6): patchy hyperintensity of the thoracic myelin at T9-T10 & T3-T5 level, suggestive of transverse myelitis.
|Transient acyclovir & ceftriaxone; Day 7: methylprednisolone (100 mg/day) with taper after discharge||Favorable; recovery within 13 days with slight spastic paraparesis & hypesthesia below T9 level||(Munz, Wessendorf, 2020)|
|Ann Arbor, USA||61, F||Two-day progressive distal limbs paresthesia & paraparesis; evolving to sensory loss till abdomen level, constipation & lower hyporeflexia on admission||Rhinorrhea & chills (5 days prior)||Lymphocytopenia, positive COVID-19 nasopharyngeal swab||Day 11: ↑ Protein (87 mg/dL), 3 WBC, no oligoclonal band, negative encephalitis antibody panel, negative COVID-19 rRT-PCR.|
Day 20 (repeat): ↑ Protein (153 mg/dL), 1 WBC, negative COVID-19 rRT-PCR.
|Spine MRI: Extensive ill-defined patchy hyperintense signal throughout the central aspect of the spinal cord on STIR, T2-weighted axial indicating mild enlargement of the spinal cord caliber & hyperintense signal without contrast enhancement.||Methylprednisolone (1 g/day for 5 days) & plasmapheresis (5 sessions)||Poor, incomplete recovery||(Valiuddin, Skwirsk, 2020)|
|Dubai, UAE||32, M||One-day progressive paraparesis, lower hyporeflexia & urinating problem||Fever & flu-like symptoms (2 days prior); PE (one day after admission)||Normal ESR, WBC & ferritin; ↓ Hgb (10.7 g/dL); ↑ CRP (42 mg/L), D-dimer (2000 μg/L) & procalcitonin (0.13 μg/L); mild ↑ CK (252 U/L), prolonged PT (16.8 s), aPTT (51.3 s) & INR (1.33), positive Lupus anticoagulant antibody; positive COVID-19 nasopharyngeal swab||NR||Spine MRI: Diffuse hyperintensity predominantly in cervical, dorsal, & lumbar gray matter, mild enlargement & swelling of cervical cord, no cord or nerve root enhancement; DWI & ADC showing restricted diffusion, overall suggestive of acute myelitis.||Methylprednisolone (1 g/day for 5 days), acyclovir, & enoxaparin||Favorable; improvement after steroid therapy||(AlKetbi, AlNuaimi, 2020)|
|Acute Necrotizing Myelitis|
|Terrassa, Spain||68, F||Seven-day radicular neck pain, left hand numbness/weakness, & imbalance; evolving to both hand weakness / numbness & paraparesis with sphincter incontinence (few days after steroid therapy)||Fever & cough (8 days prior)||Negative AQ4 & anti-MOG antibody; positive COVID-19 nasopharyngeal swab||↑ Protein (283 mg/dL), 75 WBC (98% lymphocytes), no oligoclonal bands, negative neuronal surface antibodies,||Brain MRI: normal.|
Spine MRI: T2-hyperintensity extending from the medulla oblongata to C7, involving most of the cord with diffuse patchy enhancing lesions, suggesting acute transverse myelitis.
Repeat MRI (7 days): transversally & caudally progression until T6 level with similar enhancement & a new area of central necrosis at the T1 level with peripheral enhancement.
Repeat MRI (after plasmapheresis): significant decreases of both myelitis extension & enhancement, with necrosis area in evolution.
|2 cycles of methylprednisolone (1 g/day for 5 days) with oral prednisone taper, plasma exchange||Favorable; slow recovery||(|
Sotoca and Rodríguez-Álvarez, 2020)
4.1 Guillain-Barré syndromes
4.2 Skeletal muscle injury
- Madia F.
- Merico B.
- Primiano G.
- Cutuli S.L.
- De Pascale G.
- Servidei S.
4.3.1 Viral vs autoimmune meningoencephalitis
4.3.2 Toxic metabolic encephalopathy
4.4 Acute myelitis
5. Psychiatric manifestations
6. Therapeutic strategies
Declaration of Competing Interest
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