Table 5.
CO-VAN study: scoping review of literature. Spectrum of COVID19 vaccine associated neurological disorders (Co-VAN) – a review of the literature.
| Spectrum of COVID19 vaccine associated neurological disorders (Co-VAN) | ||||||
|---|---|---|---|---|---|---|
| Author | Vaccine type | Neurological diseases | Age/Sex | Dose of vaccine | Interval from last dose & Symptoms | Description and observation |
| Guillain Barre Syndrome | ||||||
| Fernandez et al. 2021[31] | Pfizer-BioNTech (BNT162b2) = 22Moderna (mRNA1273) = 9AstraZeneca (ChAdOx1) = 3Janssen = 3 andJohnson & Johnson = 1 | GBS | 24 cases | 1st | 7 days (average) | 7 patients had CSF albuminocytological dissociation, andAll had a predominant demyelinating pattern |
| Maramattom et al. 2021[32] | AstraZeneca (ChAdOx1) = 7 | GBS | Seven cases of GBS | 1st | 2 weeks | All patients developed severe GBS. The frequency of GBS was 1.4- to 10-fold higher than that expected. |
| Woo et al. 2021[43] | Jannsen (Ad26.COV2.S) = 130 | GBS | Median age = 56 years; (IQR, 45–62 years) | Median time to onset of GBS following vaccination = 13 days (IQR, 10–18 days) | Estimated absolute rate increase of 6.36 per 100 000 person-years | |
| Dang et al. 2021[52] | Miller-Fisher Syndrome and Guillain-Barre Syndrome overlap syndrome | 63/M | 1st | 9 days laterExperienced new-onset lower back pain and 5 days after developed bilateral oculomotor nerve palsy, ataxia, facial diplegia and lower limb weakness. Later developed diplopia on lateral gaze bilaterally. Examination revealed impaired adduction, restricted upward gaze and intorsion with down gaze bilaterally, consistent with partial cranial nerve III palsies. | LP-CSF: Protein- 2.99 g/L Cells- 5/hpf: Albuminocytological dissociation. NCS- long-standing axonal neuropathy with reduced motor and sensory amplitudes. EMG- and length-dependent chronic neurogenic changes. MRI Brain- enhancement of the facial and oculomotor nerves bilaterally. Serum anti-GQ1b antibody- negative. Showed partial improvement with IvIg 2 g/kg over 5 days. | |
| Kim et al. 2022[53] | Pfizer-BioNTech (BNT162b2) | Pediatric Case of Sensory PredominantGuillain-Barré Syndrome | 16/F | 2nd | 2 days afterAscending numbness and paresthesia of her bilateral lower and upper extremities | MRI – mild thickening and enhancement of the anterior and posterior spinal nerve roots of the cauda equine. LP-CSF: 1cell/cmm, Protein- 112 mg/dlNCS- prolonged latency and slowed conduction velocity in multiple sensory and motor nerves |
| David et al. 2021[54] | Pfizer-BioNTech (BNT162b2) | Recurrence of GBS | Out of 702 patients of previous GBS, 1 had recurrence. | NCS s/o sensorimotor demyelinating polyneuropathy. Was treated with PLEX and improved. | ||
| Demyelination | ||||||
| Ismail et al. 2022[60] | Pfizer-BioNTech (BNT162b2) = 11AstraZeneca (ChAdOx1) = 8Moderna (mRNA-1273) = 6Sinovac/ Sinopharm = 5 Sputnik = 1Johnson&Johnson = 1 | Transverse myelitisADEMMS-like illnessNMOSD | 32 cases of with demyelination. Female predominance (68.8 %) and median age of 44 years. | 71.8 % occurred after the first dose of the vaccine, with a median of 9 days. | Types: Transverse myelitis = 12/32MS-like pictures (first diagnosis or a relapse) = 12/32ADEM- like 5/32NMOSD- like = 3/32. | Most MS-like episodes (9/12) were triggered by mRNA-based vaccines, TM occurred following both viral vector and mRNA-based vaccines. |
| Netravathi et al. 2022[59] | AstraZeneca (ChAdOx1) = 27COVAXIN (BBV152) = 2 | MOGAD& other demyelinations | Myelitis = 11, Optic neuritis = 6, Acute demyelinating encephalomyelitis = 5, Brainstem demyelination = 3, andMultiaxial involvement = 4 | MOG positive = 10Postvaccinial cases were found to have a significantly higher-Mean age, Presence of encephalopathy (p value:0.0007), CSF pleocytosis (p value: 0.0094) andRaised CSF protein (p value: 0.0062). | ||
| Chen et al. 2021[58] | Inactivated virus vaccine | NMOSD | A middle aged female | 1st | After 3 days of vaccine developed mild fever, vomiting, diarrhoea, cough and unsteadiness and dizziness. | MIR Brain- area postrema and bilateral hypothalamus lesions without Gd enhancement. Investigations: leucopenia of 2.36 × 109/Land positive antibodies for AQP4, ANA, SSA, SSB, Ro-52, and p-ANCA. CSF- Mononuclear pleocytosis with normal protein and negative OCB. Treated with intravenous steroid pulse and patient responded well. |
| Khayat-Khoei et al. 2021[61] | Pfizer-BioNTech (BNT162b2) = 4Moderna (mRNA-1273) = 3 | Exacerbation of known stable MS = 4, New onset MS = 2, New onset NMO = 1 | 24 to 64 (mean 39.1) years. Male = 2, Female = 5 | First (n = 2), Second(n = 5) | 1–21 daysSymptoms: visual loss, dysmetria, gait instability, paresthesias, sphincter disturbance, and limb weakness. | All responded to corticosteroid (n = 7) or plasma exchange (n = 1) therapy. |
| Arnao et al. 2022[65] | AstraZeneca (ChAdOx1) | Bilateral optic neuritis | A middle aged female, | After 2 weeks | First dose of vaccine. Developed headache and painful blurred vision worsened by movement in both eyes, decreased bilateral vision acuity. | MRI of the brain in FLAIR axial showed increased signal of the left optic nerve. LP-CSF analysis normal cells and protein. Aquaporin 4 (AQP4)-IgG and MOG-IgG negative. Treated with intravenous steroid pulse and patient responded well. |
| Ancau1 et al. 2022[64] | AstraZeneca (ChAdOx1) | Acute HemorrhagicEncephalomyelitis (AHEM) | 61Y/M | 1st | 2daysp/w- fever, headache and apathy followed by seizure and coma. | MRI Brain- bilateral confluent cortical and subcortical FLAIR hyperintense lesions with haemorrhagic involvement of the basal ganglia. CSF- revealed normal cell counts (1 leukocyte per μl) and moderate disturbance of the blood–brain-barrier. Treated with PLEX and IVMP, poorly responded. |
| 25Y/F | 1st | 9 days. P/w severe cephalgia, thoracic back pain, mild weakness and ascending numbness in her legs. | MRI- longitudinal edema throughout the thoracic spinal cord exhibiting mild contrast enhancement as well as focal central haemorrhages and brain showed bi-hemispheric white matter lesions with focal contrast enhancement. CSF- granulocytic pleocytosis | |||
| VITTS and associated strokes: CSVT | ||||||
| Sangli et al. 2021[26] | Moderna (mRNA-1273) | VITTS with CSVT | 65/F | 2nd | 10 days after. With symptoms of headache, lower limb discomfort and breathing difficulties. | She was found to have catastrophic thrombosis including deep venous and cerebral sinus venous thrombosis. |
| See et al. 2022[27] | AstraZeneca (ChAdOx1) Janssen (Ad26.COV2.S) | VITTS and venous and/or arterial ischemic strokes/ intracerebral haemorrhage | Younger age (median age 46), female preponderance and 12 days as median time after vaccination are reported. | Vaccine-induced immune thrombotic thrombocytopenia (VITT) is mainly reported in adenovirus vector based vaccines, ChAdOx1 CoV-19 vaccine and Ad26.COV2.S. According to VARES data the incidence of VITT is approximately 1 in 263,000 recipients of Ad26.COV2.S. (PMID 35,038,274) | ||
| Krzywicka et al. 2021[30] | AstraZeneca (ChAdOx1) Jannsen (Ad26.COV2.S) Pfizer-BioNTech (BNT162b2) Moderna (mRNA-1273) | CVST | Vaccine types | Absolute risk of CVST within 28 days of per million of first-dose vaccination | The absolute risk of CVST with thrombocytopenia within 28 days of per million of first-dose vaccination | Age group between 18 and 24 years had the highest absolute risk of CSVT, with thrombocytopenia (7.3 per million, 95 % CI 2.8–18.8) or without thrombocytopenia (3.7 per million, 95 % CI 1.0–13.3). |
| ChAdOx1 nCov-19 | 7.5 (95 % confidence interval [CI] 6.9–8.3) | 4.4 (95 % CI 3.9–4.9) | ||||
| Ad26.COV2.S | 0.7 (95 % CI 0.2–2.4) | 0.7 (95 % CI 0.2–2.4) | ||||
| BNT162b2 | 0.6 (95 % CI 0.5–0.7) | 0.0 (95 % CI 0.0–0.1) | ||||
| mRNA-1273 | 0.6 (95 % CI 0.3–1.1) | 0.0 (95 % CI 0.0–0.2) | ||||
| Stroke-Arterial | ||||||
| Author | Vaccine type | Neurological diseases | Age/Sex | Dose of vaccine | Interval from last dose | Description and observation |
| Walter et al. 2021[94] | AstraZeneca (ChAdOx1) | Thrombosis of Carotid Artery | 31/M | 1st | 8 days. with acute headache, aphasia, and hemiparesis. | MRI brain showed main stem occlusion of middle cerebral artery. Had elevated d-dimer, normal platelet and fibrinogen level. Positive IgG PF4 antibody. |
| Tiede et al. 2021[95] | AstraZeneca (ChAdOx1) | Ischemic stroke-arterial | Ischemic stroke in ICA and MCA territory with haemorrhagic transformation in one patient and another had cortical infarctions and aortic arch thrombi. Both had thrombocytopenia, increased d-dimer level, and positive anti-PF4 antibody. | |||
| Al-Mayhani et al. 2021[96] | AstraZeneca (ChAdOx1) | Strokes | 3 patients with MCA infarct, ICA infarct and CVST, and MCA infarct respectively. All had thrombocytopenia, positive anti-PF4 antibody, and increased d-dimer level. | |||
| Cari et al. 2021[97] | AstraZeneca (ChAdOx1), Jannsen (Ad26.COV2.S) | Post vaccinal thrombosis | Most of the ChAdOx-1 and Ad26.COV2.S vaccine associated venous thrombotic serious adverse events were not associated with thrombocytopenia. | |||
| Bell’s Palsy | ||||||
| Burrows et al. 2021[66] | Pfizer-BioNTech (BNT162b2) | Sequential contralateral facial nerve palsies | 61/M | 1st | 5 h. Developed unilateral LMN facial palsy. | 2 days after the 2nd dose – contralateral LMN facial palsy. Significant improvement with oral steroid course in either occasions. |
| Wan et al. 2022[67] | Number of cases | Age-standardised incidence (cases per 100 000 person-years) | Age-standardiseddifference for the incidence compared with the background population | Equivalent to additional cases per 100 000 people | Odds ratio | |
| CoronaVac | 28 | 66·9 | 41·5 | 4.8 cases | 2·385 (95 % CI 1·415 to 4·022) | |
| Pfizer-BioNTech (BNT162b2) | 16 | 42·8 | 17·0 | 2·0 cases | 1·755 (0·886 to 3·477) | |
| Olfactory dysfunction | ||||||
| Author | Vaccine type | Neurological diseases | Age/Sex | Dose of vaccine | Interval from last dose | Description and observation |
| Konstantinidis et al. 2021[74] | Pfizer-BioNTech (BNT162b2) | Hyposmia | 42y/F | 2nd dose | 3 days after presented with decreased olfactory ability. | Showed partial improvement on olfactory testing after olfactory training with four odors (lemon, rose, eucalyptus, and cloves). |
| 39y/F | 2nd dose | 5 days of 2nd dose of vaccine presented with hyposmia. | Improved within a week after the initial assessment. | |||
| Keir et al. 2021[75] | Pfizer-BioNTech (BNT162b2) | Phantosmia | 57y/F | 2nd dose | Complaining of constantly ‘‘smelling smoke’’ and headaches. Associated with hyposmia to additional odorants and was affecting her quality of life. | CTA postcontrast showed a faint enhancement of left olfactory tract. MRI brain – Asymmetric enlargement and increased T2 hyperintensity in the left olfactory bulb and tract extending posteriorly and thickened, clumped olfactory nerve filia. |
| Vestibulo-cochlear nerve dysfunction | ||||||
| Jeong et al. 2021[84] | AstraZeneca (ChAdOx1) | Sudden sensorineural hearing loss | 64/F | 1st | 1 day afterSudden hearing loss in the right ear. | Initially treated with oral steroid and followed by intratympanic steroid following which had complete recovery |
| Pfizer-BioNTech (BNT162b2) | 42/M | 1st | Same daysudden hearing loss in the left ear | Responded oral steroid and followed by intratympanic steroid injection. | ||
| Pfizer-BioNTech (BNT162b2) | 18/M | 2nd | 2 days aftersudden hearing loss in the right ear | Temporal magnetic resonance imaging showed normal findings. Detriment on steroid therapy. | ||
| Parrino et al. 2021[82] | Pfizer-BioNTech (BNT162b2) = 3 | Tinnitus | 37y/F | 1st dose | 7 h after had right ear tinnitus | |
| 63/M | 1st dose | 20 h after had left tinnitus associated to hyperacusis and dysacusis, | ||||
| 30y/M | 2nd dose | 1 week after vaccine presented with left tinnitus, hyperacusis and dysacusis. | ||||
| P -T Tseng et al. 2021[81] | AstraZeneca (ChAdOx1) | Cochleopathy | 37Y/M | 1st dose | 5 h. Iintermittent, right ear, high-pitch tinnitus which progressed into continuous high-pitch tinnitus and disturbed the normal hearing along with fever and myalgia. | Audiological evaluation s/o cochleopathy. Responded to short course of steroid. |
| Zhao et al. 2021[85] | Sinovac Coronavirus vaccine = 2 | SNHL | 30Y/M, and 64Y/F | 1st dose | 4 daysDeveloped hearing loss in the right ear with tinnitus and dizziness. | CT temporal bone and MRI brain were normal. Blood investigations were not remarkable. Poorly responded to vitamin B12 and steroid. |
| Mauro et al. 2022[83] | Pfizer-BioNTech (BNT162b2) = 23 | Objective vertigo = 16Subjective vertigo = 14Dizziness = 3 | Associated ENT symptoms: Hearing loss = 4 Tinnitus = 6Ear fullness = 2Hypersensitivity to noise = 1 | No presence of nystagmus = 7Presence of horizontal or rotatory nystagmus = 9Presence of positive HST/ “central HINTS” or vertical or oblique nystagmus/ “central HINTS”= 17 | Probable clinical diagnosis: No presence of vestibular impairment or central etiology of vertigo/dizziness = 7Benign paroxysmal positional vertigo = 9Probable central etiology = 17 | |
| AstraZeneca (ChAdOx1) = 5 | ||||||
| Moderna (mRNA-1273) = 4 | ||||||
| Jannsen (Ad26.COV2.S) = 1 | ||||||
| Abducens nerve palsy | ||||||
| Author | Vaccine type | Neurological diseases | Age/Sex | Dose of vaccine | Interval from last dose | Description and observation |
| Reyes-Capo et al. 2021[79] | Pfizer-BioNTech (BNT162b2) | Abducens nerve palsy | 59Y/F | 2 days, after vaccineAcute binocular and painless, horizontal diplopia. And had h/o fever for 1 day. | Mild elevation in ESR and CRP. MRI and other blood investigations were unremarkable. Had persistent deficit on follow up. | |
| Pawar et al. 2021[80] | AstraZeneca (ChAdOx1) | Recurrent Abducens nerve palsy | 23Y/M | 1st | 1 weekWith sudden-onset diplopia along with severe headache of 1 week’s duration. On examination had left esotropia with limited abduction of the left eye (LE 6th cranial nerve palsy) | MRI and blood investigations were unremarkable. Improved in follow up. H/o 2 episodes of similar 6th nerve palsy, one 5 years back following a febrile illness and another 2 years back following chicken pox. |
| Oculomotor nerve palsy | ||||||
| Cicalese et al 2021[77] | Moderna (mRNA-1273) | Third cranial nerve palsy | 88/M | 1st | 3 daysWith objective dizziness, diplopia andgait instability. k/c/o IHD, HTN, Paroxysmal AF. Non diabetic. | Brain CT scan, CT angiographyand MRI ruled out a vascular accident. Treated with oral steroid, made complete recovery. Later vaccinated again with different vaccine at different injection site. |
| Kerbage et al. 2021[78] | Pfizer-BioNTech (BNT162b2) | Oculomotor nerve palsy | 84/F | 1st | 1 day, Presented with mydriasis, ptosis, and a “down and out” gaze. | MRI Brain (plain) normal. Serum anti AChR Ab, ANA screening and EMG were unremarkable. Treated with prednisone 40 mg daily for 5 days, followed by valacyclovir 500 mg twice daily for 7 days. On 2 months follow up patient improved completely. |
| Encephalitis | ||||||
| Zuhorn et al. 2021[86] | AstraZeneca (ChAdOx1) | Postvaccinal Encephalitis (Possible Autoimmune Encephalitis) | 21/F | 1st | 1 day afterdeveloped headache and progressive neurological symptoms includingattention and concentration difficulties starting on day 5 after vaccination, resulting in admission to hospital11 days after vaccination. Subsequently had seizure. | MRI Brain- NormalCSF- 46 leukocytes/cmm(lymphocytic). EEG- diffuse abnormally slow thetarhythms without epileptiform activity. Responded to steroid therapy. |
| 63/F | 1st | 2 days later diagnosed to have DVT in left left- started on anticoagulation. 6 days post vaccination – gait deteriorated, she developed a vigilance disorder and a twitching all over her body. Later developed severe immobilizing opsoclonusmyoclonus syndrome. | MRI Brain- NormalCSF- 115 leukocytes/cmm(lymphocytic). EEG- diffuse abnormally slow theta and delta rhythms without epileptiform activity. No response to initial antibiotic therapy. Later, Responded to steroid therapy. | |||
| 63/M | 8 days afterisolated aphasia and fever. | MRI Brain- NormalCSF- 7 leukocytes/cmm(lymphocytic). Testing for neurotropic viruses in serum and CSF- Negative. EEG- NormalResponded to steroid therapy. | ||||
| Baldelli et al. 2021[87] | AstraZeneca (ChAdOx1) | Hyperacute reversible encephalopathy | 77/M | 1st | 1 day afterConfusion and agitation consistent with delirium with extreme agitation. k/c/osarcoidosis and polymyalgiarheumatica in clinical remission with Methylprednisolone 4 mg/day. Mild COVID-19 five months prior to vaccination. | CRP- elevatedEEG – moderate diffuse slowingCT (contrast)- unremarkableCSF: cell-3, protein-119 mg/dl, glucose-52 mg/dl, IL6-194(high), IL8-162(high) Microbiological testing on CSF-negativeCSFoligoclonal bands, CSF and serum autoimmune encephalitis antibodies, serum onconeural, antinuclear and antineutrophil cytoplasmic antibodies: Negative. Responded to intravenous methylprednisolone pulse therapy. |
| Moslemi et al. 2022[88] | AstraZeneca (ChAdOx1) | Herpes simplex encephalitis | 27/M | 1st | 3 days aftersevere headache and altered mental status began to appear, including slowed psychomotor activity and loss of alertness. Subsequently severeheadache, agitation, delirium, and disorientation | LP-CSF: protein levels (3.05 mg/dl), WBC count of 600 per mm3 (predominance of lymphocyte) CSF HSV PCR- +veMRI brain and EEG- Unremarkable. Treated with antiviral, and improved over 21 days. |
| Al-Mashdali et al. 2021[89] | Moderna (mRNA-1273) | Acute hyperactive encephalopathy | 32/M | 1st | 2 days afterdeveloped acuteconfusion, memory disturbances, and auditory hallucination | EEG showed features of encephalopathy, CSF: elevated protein levels (0.76 gm/L, reference range = 0.15–0.45) with average cell counts (white blood cells of 3 u/L) and glucose levels., MRI brain- UnremarkableCSF autoimmune encephalitis (including anti-aquaporin-4, anti-myelin basic protein, anti-myelin oligodendrocyte glycoprotein, anti-glial fibrillary acidic protein, anti-NMDAR, anti-GAD, andother autoimmune encephalitis antibodies) was negative. Responded to intravenous steroid pulse therapy. |
| Autoimmune Encephalitis | ||||||
| Zlotnik et al. 2022[91] | Pfizer-BioNTech (BNT162b2) | LGI-1 associated autoimmune encephalitis | 48/M | 2nd | 2.5 weeks later, Started to have memory deficits and anterograde amnesia. O/E- Montreal Cognitive Assessment (MoCA) score of 18/30 | Serum sodiumlevel of 132 mEq/ L (normal range 135–145), Tumor markers (CEA, AFP, CA125, CA19–9, CA15–3) andParaneoplastic neuronal antibodiesincluding anti-Hu, Ri, Yo, Ma/Ta, Amphiphysin, CV2, SOX1, Tr (Euroimmun) were negative. EEG- UnremarkableMRI Brain – intense signal on both medial temporal lobes (more on the left) including theparahyppocampal gyrus on T2/FLAIR and DWI. Whole body CT- liver cyst and adrenal adenoma. CSF- Cell, protein and sugar normal. CSF- LGI-Ab + Treated with methylprednisolone (1gramdailyfor5consecutivedays) with a good response. |
| Shi et al. 2022[90] | AstraZeneca (ChAdOx1) | Autoimmune encephalitis | 35/F | 1st | 5 days afterDeveloped dysarthria, abnormalMovements, extreme anxiety, and reduced voluntary movements | MRI brain- mild swelling of the right hippocampus without abnormal enhancementin contrast-enhanced fluid-attenuated inversion recovery (FLAIR) and T1-weightedimages. CSF- WBC-37/cmm (poly 67.6 %, mono 32.4 %)CSF- RBC-14800/cmmCSF-Protein- 50.7 mg/dl, Glucose-68 mg/dlSerum paraneoplastic antibodies, anti-myelin oligodendrocyte (MOG) antibody, serum and CSF synaptic antibodies, serum antiganglioside anti-bodies, and CSF oligoclonal band: Negative. Treated with weekly rituximab. |
| Meningitis | ||||||
| Fernandes et al. 2021[92] | AstraZeneca (ChAdOx1) | Ascetic Meningitis retention syndrome | 61/F | 1st | 18 daysWith headache, fever, paresthesias of the calves and thighs bilaterally and an unsteady gait, diplopia, and urinary retention. O/E: Neck stiffness + | MRI brain- non-enhancing, nonspecific deep white matter lesions. CSF − 200 WBCcells per mm3 with lymphocytic predominance, Mildly elevated protein (65 mg/dl, reference 12–60 mg/dl) and glucose CSF to serum ratio of 0.5. Infection work up and paraneoplastic panel were negative. Treated with IV steroid, responded partially. |
| Kang et al. 2022[93] | Pfizer-BioNTech (BNT162b2) | Ascetic Meningitis | 32/M | 2nd | 2 week afterHeadache for 1 week, O/E: Neck stiffness + | LP-CSF: Cells-480/cmm(90 %Lymphocyte) Protein- 118 mg/dlSugar- 56 mg/dl (RBS-91 mg/dl) No response to intravenpus acyclovir. Responded to methylprednisolone. |
| Myositis | ||||||
| Author | Vaccine type | Neurological diseases | Age/Sex | Dose of vaccine | Interval from last dose | Description and observation |
| Faissner et al. 2021[100] | Moderna (mRNA-1273) = 12 | Myositis | 28Y/F, | 1st dose | 5 days after the first dose of vaccine presented with muscle pain of herthigh muscles, radiating to the lower legs, accompanied by an asymmetrical weakness of the lower limbs. Creatine kinase (CPK) was 17,959 U/l (normal range 26–140 U/l). | Myositis profile was negative. MRI muscles- left-dominant edematous signal alterations with contrast enhancement of the quadriceps muscles sparing the M. rectus femoris, and diffuse subcutaneous fluid retention with contrast enhancement, suggestive of fasciitisTreated with steroid, patient improved. |
| Maramattom et al. 2021[101] | AstraZeneca (ChAdOx1) = 3 | Inflammatory myositis | 74/M | 1st | 48hoursPresented with a 3-week history of intermittent low-grade fever and polyarthralgia. ESR-123 mm/hr (<15 mm/ hr) CRP-269 (<5mg/L) CPK-24 (25 – 170 U/L) ANCA- negativeANA- negativeMyositis profile- negative | 18FDG-PET-CT: a tree-root-like uptake pattern in the lower limbs suggestive of small–medium vessel vasculitis. Whole-body short tau inversion recovery (STIR)-MRI showed diffuse ill-defined muscle hyperintensities suggestive of inflammatory myositis. EMG- fibrillations, positive sharp waves, and complex repetitive discharges in the distal leg muscles. Skin and muscle biopsy showed features of small–medium vessel vasculitis. Remission achieved with oral steroid therapy. |
| 75/F | 1st. | 2 days afterFever, arthralgia, myalgia, tachycardia. ESR-120 (<15 mm/ hr) CRP-271 (<5mg/L) CPK-30 ((25 – 170 U/L) ANCA- negativeANA- negativeMyositis profile- negative | 18 FDG-PET CT- Day 25; Diffuse patchy minimallyincreased FDG avidity in skeletal muscles moreevident in lower limb. Arteries show ‘tree root’patterns. MRI – Day 27-Multiple patchy areas of STIRhyperintensity involving the muscles of both thighsincluding all compartments, posterior compartment ofboth legs and pelvic girdle. Treated with Oral Prednisolone 1 mg/ kg + Mycophenolate mofetil. Achieved remission. | |||
| 80/F | 2nd | 2 days. Fever, fatigue, tachycardia. CPK-40 ((25 – 170 U/L) ESR-59 (<15 mm/ hr) CRP-102 (<5mg/L) Myositis profile/ ANCA- negative. | MRI- Hyperintense signal in STIR MRI in mostmuscles of both upper and lower limbs. Treated with oral steroid. Achieved remission. | |||
| Rhabdomyolysis | ||||||
| Gelbenegger et al. 2021[98] | Janssen (Ad26.COV2.S) | Rhabdomyolysis | 18/M | 1st | 2 days aftermyalgia, muscle weakness, and darkened urine. Creatine kinase (CK) level of 15,638 U/L, serum creatinine of 1.06 mg/dL, a lactate dehydrogenase (LDH) level of 428 U/L and elevated liver enzymes (aspartate transaminase (AST) 340 U/L, alanine transaminase (ALT) 70 U/L), C-reactive protein 1.61 mg/ dL | ANA profile and myositis panel was negative. With symptomatic management (fluid therapy) CPK increased in first week and normalized by 15 days. |
| Nassar et al. 2021[99] | Pfizer-BioNTech (BNT162b2) | Rhabdomyolysis | 21/M | 1st | 1 day afterprogressively worsening pain and swelling in the lower back. O/E- tenderness to the paraspinal lumbar area upon palpation. | CPK- 22000U/LAldolase- 97.8U/LAST-675U/LALT-165U/LCRP-6.4 mg/LLDH-1525U/LUrine blood + Myositis profile- NegativeHydrated with high volume IV normalSaline and pain controlled with morphine. Improved. |
| Parsonage Turner Syndrome | ||||||
| Mahajan et al. 2021[102] | Pfizer-BioNTech (BNT162b2) | Parsonage Turner syndrome | 50/M | 2nd | 1weekPain and left hand grip and left wrist extension weakness with no sensory disturbances or other symptoms. Examination – weaknessof left finger extension and left hand grip. Weak(MRC 3/5) – left dorsal interossei, extensor digitorum, extensorindicis, and flexor carpi ulnaris. DTR- mildly brisk b/l and symmetrical. | MR brachial plexography and NCS- was normal (done early in the disease course). Treated with oral steroid and patient responded significantly. |
| Shields et al. 2021[103] | Pfizer-BioNTech = 4, Moderna = 2 | Parsonage Turner Syndrome | 36/F, 74/M, 50/M53/M, 84/F, 46/F | 2 patient after 1st dose4 after 2nd dose | Mean duration of 17 days (5 days–8 weeks). Initial symptom was pain in the shoulder girdle/upper limb, followed within days by muscle weakness. | Examination and investigation s/o- upper trunk brachial plexopathy in 2 patients, lower trunk plexopathy in 1 patient, posterior cord brachial plexopathy in 1 patient, andanterior/posterior interosseous nerve involvement in 2 patients. All patients either improved or attained complete resolution of the arm pain at follow-up. |
| Queler et al. 2021[106] | Pfizer-BioNTech (BNT162b2) = 1, Moderna (mRNA-1273) = 1 | Parsonage Turner Syndrome | 49/M | 1st | 13 hoursPain followed by weakness of left upper limb. | MR Neurography- Within the arm, four severe hourglass- like constrictions and T2-weighted signal hyperintensity of the anteromedially positioned fascicular bundle of the median nerve were detected; this bundle represents the PT/FCR bundle based on the known topographic fascicular arrangement of the median nerve. EDx- severe denervation and no motor unit recruitment within thePT or FCR muscles. 3 month follow up- pain decreased but weakness increased. |
| 44/M | 2nd | 18 days after developed sudden-onset, Intense, cramping pain in the left lateral deltoid region. Examination- severe weakness in left shoulder abduction (2/5) and external rotation (3/5) Reported hyperesthesias in the left lateral shoulderAnd had diminished sensation to pinprick in the radial nerve distribution. | NCS- mild slowing of the left median and radial sensory responses. EMG- denervation and poor motor unit recruitment in the infraspinatus muscle. MRI- left brachial plexus MR neurography demonstrated enlargement, T2-weighted signal hyperintensity and multiple focal hourglass-like constrictions of the suprascapular nerve with accompanying denervation edemapattern of the supraspinatus and infraspinatus muscles. | |||
| Other Neuropathies | ||||||
| Waheed et al. 2021[107] | Pfizer-BioNTech (BNT162b2) | Small fiber neuropathy | 57/F | 2nd | 1weekWith subacute onset of intense burning dysesthesias in the feet, gradually spreading to the calves and minimally into the hands, unaccompanied by other neurological or constitutional symptoms. Nerve conduction study was unremarkable. | Skin biopsies showed multifocal involvement. Relevent workups for neuropathy were negative. Treated with gabapentin and improved in 2 weeks. |
| Souza et al. 2022[108] | AstraZeneca (ChAdOx1) = 4 | Acute onset- Chronic inflammatory demyelinating polyneuropathy (aCIDP) | Between 51 and 72 years. All male | 1st | 2–3 weeks | In aCIDP a/w COVID vaccination: the acute illness may be severe and associated with cranial nerve dysfunction, particularly bifacial weakness. |
| Spataro et al. 2022[109] | AstraZeneca (ChAdOx1) | Reversible radiculomyelitis | Woman in her 20 s | 1st | 3–4 days after, subacute onset of legs’ weakness, cramping pain and fever (38 °C − 39 °C). O/E: Power LL- 2/5 (b/l) Spastic LLPlantar- equivocalVery brisk patellar, abductor and Achilles tendon reflexes with horizontal and vertical extension, and legs paraesthesia. Tactile and pinpricksensation was decreased from T4 dermatomedownward. Passive and active leg movementselicited rigidity and tenderness. | CSF- Albuminocytological dissociationOCB (CSF and Serum): Pattern IVMRI Brain & Spine- NormalElectromyography and electroneurography – NegativeNear complete recovery in 2 months of steroid therapy. |
| Myasthenia gravis | ||||||
| Chavez et al. 2021[110] | Pfizer-BioNTech (BNT162b2) | Myasthenia | 82/M | 2nd | 2 days afterWith intermittent bulbar symptoms, present in the evenings. history of laryngeal cancer status post hemi-laryngectomy 40 years previously, Barrett’s esophagus, and stage 3a chronic kidney disease | Ach receptor binding Ab 11.4 (normal < 0.02) RNST- Decrement patternSecondary evaluation for thymoma was negative. Treated with pyridostigmine and IVIG. Had improving course. |
| Galassi et al. 2022[111] | AstraZeneca (ChAdOx1) | Ocular Myasthenia | 73/M | 1st | 8 days laterPainless left-sided ptosis without diplopia. K/c/o Psoriasis and hypertension, IHD | MRI Brain- NormalPositive rheumatoid factor (240 IU/ml, normal < 20 IU/ml). Low-frequency repetitive nerve stimulation − 14.7 % decrement in amplitude of nasalis muscle of the compound muscle action potential. Serum titer of anti- AChR antibodies (Day 20 after vaccine) = 1.9 nmol/l (normal < 0.25 nmol/L). Positive pyridostigmine test. |
| Lee et al. 2022[112] | Triggering of Early-Onset Myasthenia Gravis | 33/F | 2nd | On the same day: bilateral ptosis and binocular diplopia. On 3rd day: Developed bilateral ptosis. On 4th day: difficulty in raising her arms and moving her neck with a diurnal fluctuation. | RNST- Significant decremental response. CT- Mild thymic hyperplasia. Anti AchR Ab and anti MUSK Ab – NegativeNeostigmine test- Positive. Responded to pyridostigmine. | |
| Movement disorders | ||||||
| Salinas et al 2021[113] | Pfizer-BioNTech (BNT162b2) | Transient akathesia | 36/F | 2nd | 12 hoursStarted to experience an urge to move which she described as “restless body syndrome.”. k/c/o atopic dermatitis, allergic rhinitis and anxiety (on sertraline 50 mg/day) | She derived temporary relief of symptoms from volitional movement but the internal discomfort and urge to move would soon return. Her movements were alleviated by flexing/extending her trunk and legs as well as getting up and constantly moving. This was followed by fever and myalgia. Her symptoms improved after 24 h. |
| Dysautonomia | ||||||
| Galougahi et al. 2021[114] | AstraZeneca (ChAdOx1) | Autonomic dysfunction | 29/M | 1st | 4 days afterWith intermittent paraesthesia in extremities, which gradually became persistent. Initially was treated with vitamin b12 injection and amitriptyline. 2 months after had increased heart rate, with a significant change when standing (80– 120b.p.m.) vs lying (50–60b.p.m.) and skin colour changes (dark-blue/white/ dark-red) in acral areas (hands/ feet/penis) which is intermittent. | Antinuclear antibody (ANA) was positive at low titre (speckled pattern, 1:40) with elevated IgA level [5.06 g/L (0.60–3.96)]. MRI brain and nerve conduction study was unremarkable. Treated with short course of oral steroid. His postural tachycardia improved, but paraesthesia and skin colour changes persisted at 6-months. |
| Reddy et al. 2021[115] | Pfizer-BioNTech (BNT162b2) | Postural orthostatic tachycardia syndrome (POTS) | 42/M | 1st | 1 week after vaccination presented with sinus tachycardia, dizziness, headaches, and fatigue that are often triggered after a large meal or standing for a longer duration. | Investigations were not remarkable. Treated with life style modification. |
| Hadache | ||||||
| Oonk et al. 2022[116] | Pfizer-BioNTech (BNT162b2) | Thunderclap headache | 62/M | Recurrent episodic thunderclap headache. k/c/o- ocular melanoma. | Laboratory analysis, brain CT and MRI, EEG and CSF analysis including blood pigment and cytologyanalysis were all unremarkable. | |
| AstraZeneca (ChAdOx1) | 21/F | 1st | 2 h afterDeveloped general malaise with subfebrile temperature6hours later experienceda thunderclap headache, with nausea and vomiting | Neurological examination, blood analysis, and brain CT including CTangiography and venography were all normal. Symptoms improved over 1 day with paracetamol, NSAIDs, intravenous morphine, and oxygen therapy | ||
| Mattiuzzi et al. 2021[117] | Rate of headache/migraine episodes (per 100,000) voluntarily reported by recipients of COVID-19 vaccines up to May 9, 2021: | Risk of developing headache/migraine episodes(Odds) | ||||
| AstraZeneca | 129 | AstraZeneca | 3.50; 95 % CI, 3.12–3.93; P < 0.001 | |||
| Pfizer | 103 | Pfizer | 2.78; 95 % CI, 2.47–3.13; P < 0.001 | |||
| Moderna | 21 | Moderna | 0.58; 95 % CI, 0.49–0.68; P < 0.001 | |||
| The cumulative rate of headache/migraine episodes after receiving all COVID-19 vaccines was 2.25-fold higher than the daily frequency of headache disorders (odds ratio, 2.25; 95 % CI, 0.83–6.11). | ||||||
| Suwanwela et al. 2022[118] | Corona Vac | Prolonged migraine aura resemblingischemic stroke | Age between 24 and 48 years and 75 % female. | Interval from vaccination: within the first 24 h: 75 %between 1 and 7d:25 %. | All presented with lateralizedsensory deficits, motor deficits, or both, of 2–14 day duration. Migraine headache occurred in half of the patients. | MRI brain during and after the attacks did not demonstrate any abnormalities suggesting ischemic stroke. All patients showed moderately large regions of hypoperfusion and concurrent smaller regions of hyperperfusion on SPECT imaging while symptomatic. None developed permanent deficits or structural brain injury. |
| Reactivation of Varicella Zoster | ||||||
| Desai et al. 2021[119] | mRNA vaccine = 45/54 (86.27 %)Inactivated COVID-19 vaccine = 5/54 (5.88 %)Non-replicatingviral vector = 4/51 (7.84 %) | Reactivation of Varicella Zoster cutaneous infection | 27 male and 27 female | 2nd dose = 36 | Mean interval = 7.64 (6.92) days | Based on the criteria of temporal connection with vaccination anda plausible biological link, HZ appears to be a “possible”. |
| Maldonado et al. 2021[120] | Pfizer-BioNTech (BNT162b2) | 79/M | 1st | 4 days afterelevated erythematous lesions with vesicles on his right-handsidelumbar area that quickly spread to his lower back, hip, groin, and right-hand-side front and inner thigh, corresponding to L1, L2 and L3 dermatomes. K/c/o Hypercholesterolemia, hyperuricemia and hypertension | Responded to: 800 mg/day of acliclovir for one week; 50 mg of acyclovir applied topically onthe vesicles. | |
| Pfizer-BioNTech (BNT162b2) | 56/F | 2nd | 16 days afterFever, with haemorrhagic vesicles upon an erythematous base spreading on her arm, hand, and left side ofher chest, with chest pain, and pain in her arm on the same side | Treated with 400 mg/8h of gabapentin and 25 mg/12 h of a vitamin B complex. | ||
| Functional Neurological Disorders (FND) | ||||||
| Butler et al. 2021[125] | Pfizer-BioNTech (BNT162b2) | Functional Neurological disorder | 38/F | 1st | After twenty minutes of receiving the vaccine, developed an odd sensation that she described as “weakness” around her left ear. During the rest of the day, this weakness spread to her mouth, left arm, and leg. | The next morning, she had difficulty moving the left side of her face and experienced heaviness in her left leg. Her hoover's sign, hip abduction test results, were positive and symptoms were variabile. Investigations including neuroimaging was unremarkable. |
| Moderna (mRNA-1273) | Functional Neurological disorder | 36/F | 1st | Few minutes after experienced weakness in her right hand and new right-leg limping, which lasted about 2 h. On the second day after vaccination, she experienced severe bilateral leg heaviness and difficulties in fine movements of the right hand. In addition, she had exertional fatigue after walking short distances. | These symptoms persisted for several days. Examination and neuroimaging, routine investigations were unremarkable. | |
| Ercoli et al. 2021[126] | Functional Neurological disorder | 41/M | 1st followed by second dose | After a few minutes fromthe injection, reported bilateral facial paralysis withdifficulty to blink and move the facial muscles properly. All the symptoms resolved spontaneously within 40 min. Three weeks later, a few minutes after the second dose, he complained of swollen tongue and respiratory impairment, which was quickly resolved by corticosteroid therapy. Later he developed right-sided weakness, at the same side of the injection, lasting for about 40 min. | Few weeks later, he suddenly manifested left-sided facial hypoesthesia. Examination- midline splitting of sensory deficit in the face with tacto-dolorific hypoesthesia. Brain MRI, CT, & carotid artery Doppler ultrasonography: Normal. Sensory disturbance resolved, and the neurological examination become normal in next 2 weeks. | |
| Fasano et al. 2022[127] | Pfizer-BioNTech (BNT162b2) | PNES | 2nd dose | 20 min aftershort episode of generalised tonic–clonic psychogenic non-epileptic seizures (PNES) which was followed byanother episode of-inability to move the whole body with preserved level of consciousness). No post-ictal period followed these episodes. | VEEG during few events- normal. | |
| AstraZeneca (ChAdOx1) | Subjective sensory symptoms- FND | 2 weeks afterpersistent dizziness and a subjective loss of tactile sensitivity in the right arm and leg. | Brain CT- Normal | |||
| Others | ||||||
| Author | Vaccine type | Neurological diseases | Age/Sex | Dose of vaccine | Interval from last dose | Description and observation |
| Finsterer et al. 2021[128] | Moderna (mRNA-1273) | Reversible cerebral vasoconstriction syndrome (RCVS) | 38/F | 2nd | 18daysdeveloped visual impairment due to scotomas and thunderclapheadache. | Multimodal cerebral MRI: Acute cortical ischemic lesion in the territory of the right PCA on T2- weighted images, DWI,ADC maps and absence of the PCA on MRA. Partially responded to Nimodipine(90 mg/d) and Levetiracetam (1 g/d). |
| Youn et al. 2021[129] | Pfizer-BioNTech (BNT162b2) | Cytotoxic Lesion of the Corpus Callosum (CLOCCs) | 22/M | 1st dose | 3 daysWith febrile sensation and headache around the eyes and forehead. CSF- Normal cells and protein. | MRI brain- oval shaped restricted diffusion in the corpus callosum with low apparent diffusion coefficient (ADC) values and lack of contrast mediated enhancement |
| Scott et al. 2021[130] | Pfizer-BioNTech (BNT162b2) | Gastroparesis | 57/M | 1st | 5daysStarted to have nausea, intractable vomiting and hiccups. Treated with metoclopramide, and erythromycin. Recurred again after receiving the second dose. | Investigation showed significant delay in gastric emptying. No response to H2 receptor blocker, but responded to oral steroid. |
| Zavala-Jonguitud et al. 2021[131] | Pfizer-BioNTech (BNT162b2) | Delirium | 89/M | 1st | 2 dayswith a 24-h history of confusion, fluctuating attention, anxiety and inversion of the sleep–wake cycle. | K/c/o type 2 diabetes mellitus, hypertension, stage III-b chronic kidney disease, prostatic hyperplasia, mild hearing impairment and depressive disorder. Managed with antipsychotic, improved in 1 week. |
| Aladdin et al. 2021[132] | AstraZeneca (ChAdOx1) | New-onset refractory status epilepticus (NORSE) | 42/F | 1st | 10 days of vaccination presented with f headache and subjective fever that started one day prior and a rising epigastric, jamais vu and followed by new onset generalized tonic-clonic seizure. Brain MRI showed a subtle increase in the signal on FLAIRimages at bilateral hippocampi and insula that was correlating with Postictal changes. | Cerebrospinal fluid analysis showed normal cell count, normal protein at 0.31 g/L, elevated glucose at 4 mmol/L, and negative microbial cultures and serological tests. EEG showed moderate slowing. Treated with 3 AEDs levetiracetam, phenytoin and lacosamide. Responded to pulse intravenous steroid followed by two sessions of plasma exchange on alternate days. |
| Liu et al. 2021[133] | Moderna (mRNA-1273) = 2 | Encephalopathy Associated With Nonconvulsive Status Epilepticus | 86/F | 1st | 7dayswith acute confusion with visual hallucinations and left frontal headache. k/c/o: diastolic dysfunction, chronic kidney disease stage 3, glaucoma, cataracts, and Type 2 diabetes mellitus. | CSF studies, including meningitis/encephalitis panel NAAT, oligoclonal bands, and Lyme antibody, were negative except for West Nile virus IgG but no IgM antibodies with minimal protein elevation. CT head without contrast and MRI brain with and without contrast showed no acute findings. Continuous EEG –non-convulsive focal status epilepticus treated with lorazepam and fosphenytoin. |
| 73/M | 1st | 21 dayswith staring episodes, restlessness, and cognitive deficits. K/c/o Crohn’s, hereditary hemochromatosis, hypertension, and hyperlipidemia | CSF studies, including meningitis/encephalitis panel Nucleic Acid Amplification Tests (NAAT), autoimmune encephalitis, and toxoplasma, were negative except for mildly elevated protein and glucose. CT head and MRI brain showed no acute findings. EEG- non-convulsive status epilepticus, which was treated with lorazepam and levetiracetam loading and maintenance. | |||
| Chuang et al. 2021[134] | Moderna (mRNA-1273) | Tolosa-Hunt Syndrome (THS) | 45/M | 7 days after severe left-sided headache, pain with progressive ptosis in left eye, decreased vision, and binocular diplopia. | Had left RAPD and left eye complete ophthalmoplegia. MRI brain s/o THS. | |
| Lin et al. 2021[135] | Moderna (mRNA-1273) | Triggered Moyamoya disease with Sjogren disease andautoimmune thyroiditis | 40/F | 2nd | 3 days aftersevere headaches with a decreased level ofconsciousness and a tonic-clonic seizure. k/c/o- Sjogren disease andautoimmune thyroiditisO/E- Febrile with high Blood pressure and PR. | Elevated CRP, anti-PF4 Ab, SSA, fibrinogen, CT Brain – left caudate nucleus, temporal lobe IVH and ICH with hydrocephalusDSA- bilateral distal ICAsteno-occlusion with the constricted flow in middle cerebral arteries and anterior cerebral arteries with cortical collateralization pattern from the external carotid artery system that was consistent with typical moyamoya angiopathy (MMA)-Willis and the Suzuki staging system was stage V. |
| Murvelashvili et al. 2021[137] | Moderna (mRNA-1273) | Hypophisitis | 51/M | 2nd | 3 days after vaccination with headache, nausea, vomiting, malaise, and diffuse arthralgias | MRI brain suggestive of diffusely enlarged pituitary gland consistent with acute hypophysitis |
Abbreviations: GBS- Guillain-Barré syndrome; NMOSD- Neuromyelitis optica spectrum disorders; MOGAD- Myelin oligodendrocyte glycoprotein antibody-associatd disease; MS- Multiple sclerosis; CSVT- Cerebral Venous Sinus Thrombosis; RCVS- Reversible cerebral vasoconstriction syndrome; PNES- Psychogenic Nonepileptic Seizures; POST- Postural orthostatic tachycardia syndrome; MRI- Magnetic resonance imaging; O/E- On examination; k/c/o- Known case of; LP-CSF- Lumbar puncture cerebrospinal fluid; CSF- cerebrospinal fluid; EEG- Electroencephalogram; CT- computerized tomography; ADC- Apparent diffusion coefficient; FLAIR- fluid attenuation inversion recovery DWI- Diffusion weighted imagine.