Neurological Sciences (2022) 43:3–40 https://doi.org/10.1007/s10072-021-05662-9 COVID-19 Spectrum of neurological complications following COVID‑19 vaccination Ravindra Kumar Garg1  · Vimal Kumar Paliwal2 Received: 4 August 2021 / Accepted: 8 October 2021 © Fondazione Società Italiana di Neurologia 2021 / Published online: 31 October 2021 Abstract COVID-19 vaccines have brought us a ray of hope to effectively fight against deadly pandemic of COVID-19 and hope to save lives. Many vaccines have been granted emergency use authorizations by many countries. Post-authorization, a wide spectrum of neurological complications is continuously being reported following COVID-19 vaccination. Neurological adverse events following vaccination are generally mild and transient, like fever and chills, headache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. The most devastating neurological post-vaccination complication is cerebral venous sinus thrombosis. Cerebral venous sinus is frequently reported in females of childbearing age, generally following adenovector-based vaccination. Another major neurological complication of concern is Bell’s palsy that was reported dominantly following mRNA vaccine administration. Acute transverse myelitis, acute disseminated encephalomyelitis, and acute demyelinating polyneuropathy are other unexpected neurological adverse events that occur as result of phenomenon of molecular mimicry. Reactivation of herpes zoster in many persons, following administration of mRNA vaccines, has been also recorded. Considering the enormity of recent COVID-19-vaccinated population, the number of serious neurological events is miniscule. Large collaborative prospective studies are needed to prove or disprove causal association between vaccine and neurological adverse events occurring vaccination. Keyword COVID-19; SARS-COV-2; Vaccination; Cerebral venous sinus thrombosis; Thrombocytopenia SARS-CoV-2 is a novel coronavirus that can rapidly affect human beings and can result in coronavirus disease (COVID-19). COVID-19 is dominantly characterized by lung damage and hypoxia. The first case of COVID-19, in Wuhan, China, was reported on December 8, 2019. Later, the World Health Organization announced COVID-19 as a worldwide health emergency, on January 30, 2020. On March 11, 2020, COVID-19 was declared a pandemic. As per the latest World Health Organization report, there were 196,553,009 confirmed cases as on August 1, 2021 along with 4,200,412 deaths [1]. * Ravindra Kumar Garg garg50@yahoo.com Vimal Kumar Paliwal dr_vimalkpaliwal@rediffmail.com 1 Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India PIN-226003 2 Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareli road, Lucknow, India Early this year, COVID-19 vaccines has brought a ray of hope to effectively fight against this deadly pandemic and save precious human lives. Currently, four major vac- cine types are being used. These vaccine types include viral vector-based vaccines, COVID-19 mRNA-based vaccines, inactivated or attenuated virus vaccine, and protein-based vaccines. In viral vector-based vaccines, adenovirus is used to deliver a part of SARS-COV-2 genome to human cells. Human cells use this genetic material to produce SARS- COV-2 spike protein. Human body recognizes this protein to start a defensive response. The mRNA-based vaccines consist of SARS-COV-2 RNA. Once introduced, genetic material helps in making SARS-COV-2-specific protein. This protein is recognized by human body to start defen- sive immune reaction. In inactivated or attenuated vaccines, killed or attenuated SARS-COV-2 virus triggers immune response. Protein-based vaccines use the spike protein or its fragments for inciting immune response. These COVID- 19 vaccines have received emergency approvals in different countries for human use [2]. As per the latest World Health Organization report, until August 1, 2021, globally, a total Vol.:(0123456789) 1 3 4 Neurological Sciences (2022) 43:3–40 of 3,839,816,037 COVID-19 vaccine doses have been glob- ally administered [1]. In fact, all kinds of vaccines are associated with the risk of several serious neurological complications, like acute dis- seminated encephalomyelitis, transverse myelitis, aseptic meningitis, Guillain-Barré syndrome, macrophagic myofas- ciitis, and myositis. Influenza vaccine has been found associ- ated with narcolepsy in young persons. Several pathogenic mechanisms, like molecular mimicry, direct neurotoxic- ity, and aberrant immune reactions, have been ascribed to explain these vaccines associated with neurological com- plications [3]. Even COVID-19 vaccines are not free from neurological complications. In this article, we have focused on the neurological complications following COVID-19 vaccination that were reported after their emergency use authorizations. Search strategy We reviewed available data regarding neurological compli- cations (post-authorization) described following the World Health Organization–approved COVID-19 vaccination. We classified COVID-19 vaccination associated with neurologi- cal complications in two broad groups: (1) common but mild and (2) rare but severe. We searched PubMed, Google, and Google Scholar databases using the keywords “COVID‐19” or “SARS‐CoV‐2” and “vaccination” or “vaccine,” to iden- tify all published reports on neurological complications of COVID‐19 vaccines. We in this review will focus on spec- trum of published neurological adverse events following COVID-19 vaccination. Last search was done on August 1, 2021. Mild neurological events Neurological adverse events following COVID-19 vaccina- tion are generally mild and transient, like fever/chills, head- ache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. These mild neurologi- cal symptoms are common following administration of all kinds of COVID-19 vaccines. Anxiety-related events, like feeling of syncope and/or diz- ziness, are particularly common. For example, Centers for Disease Control and Prevention, in a report published on April 30, 2021, recorded 64 anxiety-related events (syncope in 17) among 8,624 Janssen COVID-19 vaccine recipients. None of the event was labeled as serious [4]. In Mexico (data available in form of preprint) among 704 003 subjects who received first doses of the Pfizer-BioNTech mRNA COVID-19 vaccine, 6536 adverse events following immunization were recorded. Among those, 4258 (65%) had at least one neurologic manifestation, mostly (99.6%) mild and transient. These events included headache (62·2%), tran- sient sensory symptoms (3·5%), and weakness (1%). In this study, there were only 17 serious adverse events, seizures (7), functional syndromes (4), Guillain-Barré syndrome (3), and transverse myelitis (2) [5]. In South Korea, Kim and co-workers collected data of post-vaccination adverse events following first dose of adenovirus vector vaccine ChAdOx1 nCoV-19 (1,403 sub- jects) and mRNA vaccine BNT162b2 (80 subjects) vaccina- tions. Data were collected daily for 7 days after vaccination. Authors noted that 91% of adenovirus-vectored vaccine and 53% of mRNA vaccine recipients had mild adverse reac- tions, like injection-site pain, myalgia, fatigue, headache, and fever [6]. A mobile-based survey among healthcare workers (265 respondents) who received both doses of the BNT162b2 mRNA vaccine was conducted. The most com- mon adverse effects were muscle ache, fatigue, headache, chills, and fever. Adverse reactions were higher after the second dose compared with that after the first dose [7]. Headache Headache is one of the most frequent mild neurological complaints reported by a large number of COVID-19 vac- cine recipients, soon after they receive vaccine. A review of headache characteristic noted that among 2464 participants, headache begun 14.5 ± 21.6 h after Astra- Zeneca adenovirus vector vaccine COVID-19 vaccination and persisted for 16.3 ± 30.4  h. Headaches, in majority, were moderate to severe in intensity and generally local- ized to frontal region. Common accompanying symptoms were fatigue, chills, exhaustion, and fever [8]. In a multi- center observational cohort study, Göbel et al. recorded clinical characteristic of headache occurring after the mRNA BNT162b2 mRNA COVID-19 vaccination. Generally, head- ache started 18.0 ± 27.0 h after vaccination and persisted for 14.2 ± 21.3 h. In majority, the headaches were bifrontal or temporal, dull aching character and were moderate to severe in intensity. The common accompanying symptoms were fatigue, exhaustion, and muscle pain [8]. Severe neurological adverse events Serious adverse reaction following immunization is defined as a post-vaccination event that are either life-threatening, requires hospitalization, or result in severe disability. The World Health Organization listed Guillain-Barré syndrome, seizures, anaphylaxis, syncope, encephalitis, thrombocy- topenia, vasculitis, and Bell’s palsy as serious neurologic adverse events. Instances of serious adverse events follow- ing COVID-19 vaccinations are continuously pouring in the 1 3 Neurological Sciences (2022) 43:3–40 5 current scientific literature and are source of vaccine hesi- tancy in many persons [9] (Fig. 1). Functional neurological disorders Functional neurological disorders are triggered by physical/ emotional stress following an injury, medical illness, a sur- gery, or vaccination. Functional neurological disorders often remain misdiagnosed despite extensive workup. After availability of COVID-19 vaccine, many YouTube videos depicted continuous limb and trunk movements and difficulty walking immediately after COVID-19 vaccine administration. These videos were of concern as they were the source of “vaccine hesitancy” [10]. Kim and colleagues reviewed several such social media videos demonstrating motor movements consistent with functional motor symp- toms occurring after administration of COVID-19 vaccine. Motor movements were bizarre asynchronous and rapidly variable in frequency and amplitude consistent with func- tional neurological disorder. The Functional Neurological Disorder Society has lately clarified that movement disorder is consistent with functional in nature. The spread of these videos are important because these functional disorders cre- ated concerns for vaccine hesitancy [11]. Several other kinds of functional neurological disorders have also been reported. Butler and colleagues described two young ladies, who presented with functional motor defi- cits mimicking stroke. Both these patients had variability in weakness and had many non-specific symptoms. A detailed workup and neuroimaging failed to demonstrate any specific abnormality [12]. Ercoli and colleagues described a mid- dle-aged man who, immediately after vaccine administra- tion, reported bilateral facial paralysis along with failure to blink. These manifestations resolved quickly within 40 min. Immediately after administration of second dose of vaccine, he complained of respiratory distress and swollen tongue. Again, all these symptoms resolved quickly following treat- ment with corticosteroids, however, he developed new symp- toms in the form of right hemiparesis. Two weeks later, he developed facial hypoesthesia. A detailed workup of the patient failed to demonstrate any abnormality. A diagnosis of functional neurological disorder was, finally, made [13]. Cerebral vascular events As a matter of concern, increasing number of reports about adenoviral vector vaccine-induced cerebral vascular adverse events, like cerebral venous thrombosis, arterial stroke, and intracerebral hemorrhage, is getting published in leading medical journals. These reports are alarming as post-vacci- nation vascular events culminate either in severe disability or death. Vaccine-induced cerebral vascular adverse events are generally associated with severe immune-mediated thrombotic thrombocytopenia. Thrombocytopenia gener- ally clinically manifests within 5 to 30 days after admin- istration of adenovirus vector-based vaccines. In post-vac- cination thrombotic thrombocytopenia, a picture similar to that of heparin-induced thrombocytopenia is encountered. When heparin binds platelet factor 4, there is generation of antibodies against platelet factor 4. Antibodies against platelet factor 4 result in platelet destruction and trigger the intravascular blood clotting [14]. The post-mortem exami- nation, in patients with vaccine-induced thrombocytopenia, demonstrated extensive involvement of large venous vessels. Microscopic findings showed vascular thrombotic occlusions occurring in the vessels of multiple body organs along with marked inflammatory infiltration [15]. The vector-based vaccines contain genetic material of SARS-COV-2 that is capable of encoding the spike glycoprotein. Possibly, leaked Fig. 1 A flow diagram depicts the spectrum of severe neuro- logical complications follow- ing COVID-19 vaccinations (ADEM, acute disseminated encephalomyelitis; CVST, cer- ebral venous sinus thrombosis; LETM, longitudinally extensive transverse myelitis; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders; PRES, posterior reversible encephalopathy syn- drome; TIA, transient ischemic attacks) 1 3 6 Neurological Sciences (2022) 43:3–40 genetic material binds to platelet factor 4 that subsequently activates formation of autoantibodies. These autoantibodies destroy platelets [16, 17]. Cerebral venous thrombosis Cerebral venous thrombosis is the one of the most feared devastating COVID-19 vaccine-associated neurological complication. Cerebral venous thrombosis should be sus- pected in all vaccinated patients, who has persistent head- ache. Headache is generally unresponsive to the analgesics, and some patients may have focal neurological deficits. Affected patients are generally females of younger ages (Table 1) [18–46]. In Europe, since March 2021, cases of cerebral venous thrombosis started pouring in following COVID-19 vac- cination, particularly after administration of viral vector based (AstraZeneca ChAdOx1 nCoV-19 and the Johnson and Johnson Ad26. COV2.S) vaccines [22]. Scully and colleagues recently reported findings of 23 patients, who presented with thrombosis and thrombocytopenia (plate- let counts below 10 × 109/L). These patients developed thrombosis and thrombocytopenia 6 to 24 days after they received the first dose of the viral vector-based vaccines. In a significant observation, authors, in majority of patients, demonstrated the presence of autoantibodies against platelet factor 4. Additionally, D-dimer levels were found elevated [20]. Tiede and co-workers reported five German cases of prothrombotic immune thrombocytopenia after vaccina- tion with viral vector-based vaccine (Vaxzevria). In these patients, acute vascular events clinically manifested as cer- ebral venous sinus thrombosis, splanchnic vein thrombo- sis, arterial cerebral thromboembolism, and/or thrombotic microangiopathy within 2  weeks post vaccination. All five patients had low platelet counts and markedly raised D-dimer. In all, autoantibodies against platelet factor 4 were also demonstrated [30]. Pottegård et al. in Denmark and Norway evaluated inci- dence of arterial events, venous thromboembolism, throm- bocytopenia, and bleeding among vaccinated population. The vaccinated cohorts comprised of 148,792 Danish peo- ple and 132,472 persons from Norway. All has received their first dose of viral vector-based vaccine (ChAdOx1-S). An excess rate of venous thromboembolism (like cerebral venous thrombosis) was observed among vaccine recipients, within 28 days of vaccine administration. Authors estimated an increased rate for venous thromboembolism correspond- ing to 11 excess events per 100,000 vaccinations with 2.5 excess cerebral venous thrombosis events per 100,000 vac- cinations [47]. Krzywicka et al., from the Netherlands, collected data of 213 cases with post-vaccination (187 after adenoviral vec- tor vaccines and 26 after a mRNA vaccine) cerebral venous sinus thrombosis; they noted thrombocytopenia in 107/187 (57%) post-vaccination  cerebral venous sinus thrombo- sis cases. Thrombocytopenia was not recorded in any of patients, who received an mRNA-based vaccine. Cerebral venous sinus thrombosis after adenoviral vector vaccines carried poorer prognosis. Approximately, 38% (44/117) patients in adenoviral vector vaccine group died, while in mRNA vaccine group, 20% (2/10) had died [48]. Recently published National Institute for Health and Care Excellence (NICE) guidelines recommend that the patients with clinical diagnosis of vaccine-induced immune thrombo- cytopenia and thrombosis should be treated with intravenous administration of human immunoglobulin, at a dose of 1 g/ kg. If there is no response or there is further deterioration, second dose of human immunoglobulin should be given. In patients with insufficient response, methylprednisolone 1 g intravenously for 3 days or dexamethasone 20 to 40 mg for 4 days can be used [49]. Heparin needs to be avoided, instead alternative antico- agulants like argatroban, bivalirudin, fondaparinux, rivar- oxaban, or apixaban should be used for anticoagulation [49–51]. NICE guidelines further recommend that patients with very low platelet count should be treated either alone with a argatroban or a combination of argatroban and platelet transfusion [49]. Arterial events Several acute arterial events, like arterial thrombosis, intrac- erebral hemorrhage, transient global amnesia, and spinal artery ischemia, have also been reported following vaccina- tion [31]. Simpson and colleagues, in Scotland, estimated the inci- dence of vaccine-associated thrombocytopenia and vascular events following administration of first dose of viral vector- based vaccine (ChAdOx1) or mRNA (BNT162b2 Pfizer- BioNTech or mRNA-1273 Moderna) vaccination. First dose of viral vector-based vaccine was associated with small enhanced risk of idiopathic thrombocytopenic purpura; in addition, up to 27 days after vaccination, there was possibil- ity of an increased risk for thromboembolic and hemorrhagic events. No such adverse associations were noted with mRNA vaccines [52]. The reports of COVID-19 vaccine-related intracerebral hemorrhage and ischemic stroke are summa- rized in Table 2 [53–61]. Intracerebral hemorrhage Athyros and Doumas reported a 71-year-old female. who developed intracerebral hemorrhage after she received the first dose of the Moderna mRNA vaccine. 1 3 Neurological Sciences (2022) 43:3–40 7 n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R n o i t a n i c c a v r e t f a s n o i t a c i l p 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a s i s o b m o r h t s u n i s s u o n e v l a r b e r e c d e p o l e v e d o h w s t n e i t a p f o s l i a t e d e m o c t u o d n a , s g n i d n fi g n i g a m i e c n a n o s e r c i t e n g a m , l a c i n i l C 1 e l b a T - n e c n o c n e g o n i r b i F l a m y h c n e r a p - a r t n I t h g i r , e h c a d a e h e r e v e S s y a d   0 1 e n i c c a v 9 1 - D V O C I M / 0 5 y l a t I s u o n e v l a r b e r e C ] 8 1 [ . l a   t e i l l e t s a C e g a h r r o m e h y d a e t s n u , s i s e r a p i m e h a c e n e Z a r t s A s i s o b m o r h t s u n i s e v i s s e r p m o c e d l a r e - t a l i b a ) l a t o t s t i n u ) l a t o t g   0 1 ( e t a r t 4 ( t e l e t a l p d n a y m o t c e i n a r c s u o n e v d i o m g i s d n a e s r e v s n a r t - m o r h t s e s u n i s - g o i g n a T C t f e l = y h p a r s i s o b s y a d   4 f o t n e m r i a p m i U C I d e d e e n t n e i t a P l a c i n a h c e m d n a e r a c l a u s i v d n a , t i a g n o i t a l i t n e v r a l i s a b s e g a h r - r o m e h r a b o l - r a c o y M s i s e r a p i m e h n o i t c r a f n i l a i d s i s o b m o r h t y r e t r a h t i w d e t a i c o s s a l a n e r d a l a r e t a l i B e g a h r r o m e h s u n i s l a t t i g a s r o i r e p u s e h t s i s o b m o r h t s u o n e v l a r b e r e c s i s o b m o r h t s u n i s y h p a r g o i g n A e g a h r r o m e h t i n u e r a c e v i s n e t n I e t u c a b u s e l p i t l u M d n a m u i r o s n e s d e r e t l A s y a d   2 1 a c e n e Z a r t s A e h T F / 4 5 y l a t I s u o n e v l a r b e r e C . l a   t e o n i t s o g A D ’ e n i c c a v a i n e p a c e n e Z a r t s A t i n u e r a c e v i s n e t n I l a m y h c n e r a p - a r t n I - o t y c o b m o r h t a m o C s y a d   7 e n i c c a v 9 1 - D V O C I M / 0 5 y l a t I s u o n e v l a r b e r e C . l a   t e i n i h c n a r F s u o n e v l a r b e r e c h t i w s t n e i t a p 3 1 s i s o b m o r h t ) a c e n e Z a r t s A ( e n i c c a v 9 1 e l b a l i a v a t o N e l b a l i a v a t o N s y a d   4 2 o t 6 - V o C n 1 x O d A h C ) n a i d e M ( s r a e y   2 1 n o d n o L a i n e p o t y c o b m o r h T t r o p e r ( . l a   t e y l l u c S d n a s i s o b m o r h t d e t a n i m e s s i d r a l u c s a v a r t n i n o i t a l u g a o c s u o n e v l a r b e r e C 3 1 ( s i s o b m o r h t ) s t n e i t a p s i s o b m o r h t ) s t n e i t a p 3 2 ( ) s t n e i t a p 3 2 f o   ] 9 1 [ ] 0 2 [ ] 1 2 [ 1 3 8 Neurological Sciences (2022) 43:3–40 r e t f a y l e t a i d e m m i e v i s s e r p m o c e d V I y m o t c e i n a r c n i l u b o l g o n u m m i x u n i r a p a d n o F s i s o b m o r h t , s n i e v r a l u g u j t f e l e h t f o - r e p u s d n a p e e d l a r b e r e c l a i c fi t f e l d n a , n i e v l a t e i r a p o t n o r f - 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u m m i s u o n e v a r t n I s u o n e v l a r b e r e C , e h c a d a e h g n i n e s r o W s y a d   1 2 - c a V 9 1 - D V O C I M / 4 5 m o d g n i K d e t i n U s u o n e v l a r b e r e C . l a   t e y n e d m a R n i l u b o l g o n s i s o b m o r h t s u n i s l a r e t a l i n u d n a g n i s i u r b a c e n e Z a r t s A e n i c s i s o b m o r h t s u n i s ] 4 2 [ 1 3 Neurological Sciences (2022) 43:3–40 9 t f e l e h t n i h t i w d n a e s r e v s n a r t s u n i s d i o m g i s f o e v i t s e g g u s t o l c e s n e d r o d r o c l a r b e r e c T C n g i s a t l e d y t p m e d n a e h t n i h t i w n g i s l a t t i g a s r o i r e p u s g n i d n e t x e s u n i s a l u c r o t e h t o t n i t f e l , i l i h p o r e H , s u n i s e s r e v s n a r t d i o m g i s d n a l a m i x o r p o t s u n i s r a l u g u j l a n r e t n i a y h p a r g o n e v - t n e m g e s g n o l t c e f e d g n i l l fi n i e v t f e l e h t f o s i s o b d n a e s r e v s n a r t s u n i s d i o m g i s t f e l e h t o t n w o d r a l u g u j l a m i x o r p - a r c a r t n i l a t e i r a p e g a h r r o m e h l a i n y h p a r g o i g n a T C s i s o b m o r h t e v i s - n e t x e d e l a e v e r - o r o p m e T n i e v c i r e t n e s e m e h t f o n i e v l a t r o p d n a d e v o r p m i e n a e k i l d r o c d e w o h s n o i t a u n e t t a r e p y h e h c a d a e h e t a r e d o m s s e n i d d i g d n a - S R A S A N R m e n i c c a v 2 - V o C - x e l C s u o e n a t u c b u S n i a r b e h t f o ) T C o t d l i m f o t e s n o w e N s y a d   6 1 f o e s o d t s r i F M / 9 4 a i s y a l a M s u o n e v l a r b e r e C ] 5 2 [ . l a   t e a i r a k a Z n o i t a n i c c a v r e t f a n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R s i s o b m o r h t s u n i s s n o i t a c i l p ) d e u n i t n o c ( 1 e l b a T s n i l u b o l g o n n a b o r t a g r A - m o r h t s i s e m e t a m e h a i n e p o t y c o b l a r b e r e c d e w o h s d n a g n i s i u r b a i n e p o t s u n i s s u o n e v o t y d o b i t n A e a i h c e t e p s i s o b m o r h t 4 r o t c a f t e l e t a l p - c a V 9 1 - D V O C I ( - n e Z a r t s A e n i c ) a c e a c e n e Z a r t s A , 9 1 s i s o b m o r h t s u n i s s i s o b m o r h t s u n i s - u m m i e s o d - h g i H - m o r h t e t e l p m o C d n a e h c a d a e h e r e v e S s y a d   9 - v o C n 1 x O d A h C M / 9 2 y n a m r e G s u o n e v l a r b e r e C ] 7 2 [ . l a   t e f a r G n a b a x i p A m a r g o n e v R M - y c o b m o r h t e h c a d a e H s y a d   0 1 2 2 2 1 D Z A F / 5 3 d n a l e r I s u o n e v l a r b e r e C ] 6 2 [ . l a   t e n a y R 1 3 10 Neurological Sciences (2022) 43:3–40 d n a s u n i s d i o m r a l u g u j l a n r e t n i - g i s e s r e v s n a r t n i e v s u o n e v l a r b e r e c f o s i s o b m o r h t l a n r e t n i t f e l e h t - g i s , n i e v r a l u g u j d n a , s u n i s d i o m l a t t i g a s r o i r e p u s e g a h r r o m e h s u n i s , ) T V S ( s i s o b m o r h t l a r b e r e c l a i r e t r a , m s i l o b m e o b m o r h t n i e v c i n h c n a l p s - o r c i m c i t o b m o r h t d n a - o b m o r h t y h t a p o i g n a - i t n a o t u A a i n e p o t y c t e l e t a l p t s n i a g a s e i d o b 4 r o t c a f s u o n e v a r t n I ) n i d u r n i l u b o l g e n u m m i ) G V I I ( - i l a v i b ( r o t i b i h n i t f e l e h t g n i v l o v n i o t y d o b i t n A a i n e p o t n i b m o r h t t c e r i d A s i s o b m o r h t s u o n e V - y c o b m o r h t   e h c a d a e H s y a d   7 - v o C n 1 x O d A h C a c e n e Z a r t s A , 9 1 4 r o t c a f t e l e t a l p n o i t a n i c c a v r e t f a n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R F / 0 4 A S U s u o n e v l a r b e r e C ] 8 2 [ . l a   t e e g r o e G s i s o b m o r h t s u n i s s n o i t a c i l p ) d e u n i t n o c ( 1 e l b a T e n o N l a t n o r f l a r e t a l i B d e t a i c o s s a e h c a d a e H s y a d   1 1 f o e s o d t s r i F F / 9 6 e c n a r F s u o n e v l a r b e r e C ] 9 2 [ . l a   t e e m m a J l a r o i v a h e b h t i w s m o t p m y s - a r t s A – d r o f x O e n i c c a v a c e n e Z s i s o b m o r h t s u n i s s d i o r e t s o c i t r o c n a b o r t a g r A n i i b m o r h t f o s l e s s e v r o j a m , 2 2 2 1 D Z A ( e n i c - c a v 9 1 - D V O C I ) a i r v e z x a V - u m m i s u o n e v a r t n I s a m o t a m e h n i a r B s u n i s s u o n e v l a r b e r e C r e t f a s y a d   1 1 o t 5 1 x O d A h C s r a e y   7 6 d n a 1 4 y n a m r e G s u o n e v l a r b e r e C t r o p e r ( . l a   t e e d e i T r o n i l u b o l g o n e c n e s e r p , s t c r a f n i , ) T S V C ( s i s o b m o r h t n o i t a n i c c a v t s r fi s e l a m e f l l A s i s o b m o r h t s u n i s ] 0 3 [ ) s t n e i t a p 5 f o , s i s e r e h p a m s a l p , s d i o r e t s o c i t r o c s t n a l u g a o c i t n a , s n i l u b o l g o n u m m i s i s o b m o r h t s t n e i t a p l l a n o i t a n i c c a v d n a , 1 x O d A h C s u o n e v a r t n I s u o n e v l a r b e r e C n i a i n e p o t y c o b m o r h T f o s y a d   0 3 n i h t i W , 2 b 2 6 1 T N B y n a m r e G s u o n e v l a r b e r e C t r o p e r ( . l a   t e z l u h c S s i s o b m o r h t ] 1 3 [ ) s e s a c 5 4 f o 3 7 2 1 - A N R m 5 3 / ) n a e m ( s e l a m e f s r a e y   5 . 6 4 1 3 Neurological Sciences (2022) 43:3–40 11 n o i t a n i c c a v r e t f a n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R s i s e r e h p a m s a l P c i g a h r r o m e h h t i w n i l u b o l g o n u m m i e k o r t s y r e t r a - l a r b - c u r t s b o , n o i s n e t r e p y h a c e n e Z a r t s A , 9 1 ] 2 3 [ s u o n e v a r t n I - e r e c e l d d i m t h g i R , s u t i l l e m s e t e b a i D s y a d   2 1 - v o C n 1 x O d A h C M / 9 6 a d a n a C e e r h t t r o p e r A . l a   t e n o n g i u g r u o B d a h e n o s t n e i t a p s u o n e v l a r b e r e c s i s o b m o r h t s u n i s s n o i t a c i l p ) d e u n i t n o c ( 1 e l b a T n o i t a m r o f s n a r t l a r b e r e c t h g i R d n a e s r e v s n a r t , s e s u n i s d i o m g i s l a n r e t n i t h g i r , n i e v r a l u g u j d n a , n i e v c i t a p e h b m i l - r e w o l l a t s i d y r a n o m l u p ; n i e v m s i l o b m e n i a r b t u o h t i w l a m y h c n e r a p t n e m e v l o v n i s i s o b m o r h t d n a l a r o p m e t r a l l e b e r e c - t f e l l a r b e r e c a r t n i e g a h r r o m e h s i s o b m o r h t s u n i s t f e l e h t g n i v l o v n i , s e s u n i s d i o m g i s d n a e s r e v s n a r t l a n r e t n i t f e l e h t o t n i g n i d n e t x e n i e v r a l u g u j - d a e H r e c n a c e t a t s o r p d e s o n g a i d y l t n e c e r , a e n p a p e e l s e v i t n o i s u f n o c d n a e h c a s s e n k a e w d e d i s - t f e l a i n e p o t y c o b m o r h T - c a f t e l e t a l p t s n i a g a s e i d o b i t n a o t u A 4 r o t n i l u b o l g o n s u n i s e s r e v s n a r t a i n e p o t y c o b m o r h t ) L / ] 8 [ 0 1 × 4 8 ( - u m m i s u o n e v a r t n I / d i o m g i s t f e L s y a d   2 e c n i s e h c a d a e H s y a d   8 - c a v t s r fi e h T F / 9 3 a i r t s u A s u o n e v l a r b e r e C . l a   t e r e g n i r t t a G s i s o b m o r h t s u n i s ] 3 3 [ n i l u b o l g o n u m m i d n a e s r e v s n a r t - l u c ffi i d c i t s e n m a d n a n a b o r t a g r a s u n i s l a d i o m g i s a i s a h p a s a l l e w s a s e i t s u o n e v a r t n I t f e l e h t f o T S V C , a i x a t a t i a G e h c a d a e H - t f e l a h t i w f o a i n e p o t y c o b m o r h T L µ / 0 0 0 7 3 f o e s o d t s r fi e h T F / s   0 3 y l r a e y n a m r e G s u o n e v l a r b e r e C ] 4 3 [ . l a   t e g r e b n e k I s i s o b m o r h t s u n i s - u m m i s u o n e v a r t n I n i l u b o l g o n a i n e p o t y c o b m o r h t s i s o b m o r h t s u n i s n o i s u f n i n i d u r i l a v i B s u o n e v l a r b e r e C s e h c a d a e h g n i n e s r o W s y a d   5 S . 2 V O C . 6 2 d A e h T F / 0 4 A S U s u o n e v l a r b e r e C ] 5 3 [ . l a   t e k r a l C - v o C n 1 x O d A h C ) a c e n e Z a r t s A ( 9 1 h t i w n o i t a n i c - v o C n 1 x O d A h C ) a c e n e Z a r t s A ( 9 1 ) n e s n a J / n o s n h o J & n o s n h o J ( e n i c c a v 1 3 12 Neurological Sciences (2022) 43:3–40 - u l c c o l a r e t a l i b l a t e i r a p f o n o i s , s n i e v l a c i t r o c , s u n i s t h g i a r t s , n e l a G f o n i e v l a r b e r e c l a n r e t n i - e f n i d n a , s n i e v . s u n i s l a t t i g a s r o i r d n a l a t e i r a p t h g i R s u o n e v e v i s n e t x e n a s e b o l l a t e i r - a p o t n o r f t f e l h t i w n o i t c r a f n i c i g a h r r o m e h 4 r o t c a f - t e l e t a l P n o i t a m r o f s n a r t n i r a p e h – ) 4 F P ( s e i d o b i t n a G g I - m o r h t d e t a v e l e – a i n e p o t y c o b r o i r e p u s n i s i s o b d n a s u n i s l a t t i g a s s u n i s e s r e v s n a r t l a t t i g a s r o i r e p u s h t i w s i s o b m o r h t l a c i t r o c d e n e k c i h t - t a l i b d n a s n i e v - i s n e d o p y h l a r e l a t e i r a p e h t n i s e i t s e b o l n i l u b o l g o n u m m i n a b o r t a g r a s u o n e v a r t n I h t i w s i s o b m o r h t d n a s s e n k a e w d e d i s s e c n a b r u t s i d l a u s i v d e t a r o i r e t e d y l d i p a r - n o c d e s a e r c e d h t i w - t h g i r s g u r d o t e v i s s s e n s u o i c s n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R n o i t a n i c c a v r e t f a s n o i t a c i l p e n o s a h t e m a x e D s u o n e v l a c o f i t l u M - n o p s e r - n o n e h c a d a e h s y a d   4 1 - V o C n 1 x O d A h C F / 6 2 y l a t I s u o n e v l a r b e r e C ] 6 3 [ . l a   t e o t a n o B e n i c c a v 9 1 s i s o b m o r h t s u n i s ) d e u n i t n o c ( 1 e l b a T - i m e s s i D a i n e p o t y c o b r a l u c s a v a r t n i d e t a n n o i t a l u g a o c - u m m i s u o n e v a r t n I y h p a r g o n e v R M e h c a d a e h d n a r e v e F s y a d   7 n o i t a n i c c a v t s r i F F / 1 4 n a w i a T s u o n e v l a r b e r e C ] 7 3 [ . l a   t e g n a W n i l u b o l g o n l a r b e r e c d e l a e v e r s u n i s s u o n e v s i s o b m o r h t a i n e p o t y c o b m o r h t 4 F P - i t n a e v i t i s o p s e i d o b i t n a n i r a p e h t h g i e w - m o r h t d e l a e v e r t e l e t a l P a m e d e l l i p a p - r a l u c e l o m w o L - y h p a r g o n e v R M n o i s i v e l b u o d e h c a d a e H l a m r o n s a w t n u o c 1 x O d A h C h t i w 9 1 - V o C n s i s o b m o r h t s u n i s D L E I H S I s i s o b m o r h t s u n i s s y a d   6 - V O C f o e s o d - t s r i F M / 1 5 a i d n I s u o n e v l a r b e r e C ] 8 3 [ . l a   t e a t t u D n i r a p e h t h g i e w ) T C ( y h p a r g o m o t r e p p u t f e l e h c a d a e h e r a c U C I d e w o h s n a c s - m o r h t s s e n k a e w b m i l - V o C n 1 x O d A h C e n i c c a v 9 1 s i s o b m o r h t s u n i s - r a l u c e l o m w o L - d e t u p m o c n i a r B e r e v e s d n a g n i t i m o V s y a d   4 1 e h t f o e s o d t s r i F F / 6 3 a i b a r A i d u a S s u o n e v l a r b e r e C ] 9 3 [ . l a   t e n i d d a l A 1 3 Neurological Sciences (2022) 43:3–40 13 - i p i c c o g n i v l o v n i l a r o p m e t d n a l a t d e t a i c o s s a s e b o l - h c a r a b u s h t i w e g a h r r o m e h d i o n n i t c r a f n i s u o n e V - o n e V i r y g c i d n a l - o r i r e p l a r e t a l i b d e m r fi n o c m a r g s u o n e v l a r b e r e c s i s o b m o r h t s u n i s e e r h t l l a n i d n a a e s u a n , e h c a d a e h p a l c r e d n u h t e r e v e s , e h c a d a e h g n i t i m o v g n i s i u r b t n e t s i s r e p d a h l l a e a i h c e t e p d n a a i n e p o t y c o b m o r h t n i e v l a t r o p e s i a l a m - m o r h t s i s o b m o r h t d n a a i n e p o t y c o b t e l e t a l p - i t n A y h t a p o l - u g a o c n o i t p m u s n o c e r e w s e i d o b i t n a d e t c e t e d s e i t i l a m r o n b a r e h t o y l n o t n e i t a p , g n i t i m o v , a e s u a n l a n i m o d b a d a h e a i h c e t e p d n a g n i s i u r b - a r t s A , 9 1 - V o C n 1 x O d A h C ( ) a c e n e Z n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R n o i t a n i c c a v r e t f a s n o i t a c i l p n i l u b o l g o n e n o n i s i s o b m o r h t , e h c a d a e h a y b d e w o l s y a d   4 1 s y a d   3 2 F / 5 3 s i s o b m o r h t s u n i s - u m m i s u o n e v a r t n I s u n i s s u o n e v l a r u D - l o f e c n a b r u t s i d l a u s i V s y a d   6 1 s y a d   0 1 e n i c c a v a i r v e z x a V F / 0 5 M / 8 3 F / 9 2 d n a l e r I s u o n e v l a r b e r e C a ( . l a   t e n i v a L ) d e u n i t n o c ( 1 e l b a T ] 0 4 [ ) s t n e i t a p 4 f o s e i r e s n i r a p a z n i T l a m r o N l a r e n e g d n a e h c a d a e H - V o C n 1 x O d A h C F / 0 3 K U s u o n e v l a r b e r e C n e s n e r ø S l l ø b l ø T 9 1 s i s o b m o r h t s u n i s ] 1 4 [ . l a   t e n i r a p e h t h g i e w e v i s s e r p m o c e d y m o t c e i n a r c l a t e i r a p - o r o p m e t - n e r a p a r t n i e b o l - r o m e h l a m y h c e t u c a d n a g n i t i m o v s i s e r a p i m e h t f e l - t i m o v d n a e h c a d a e H t h g i r e t u c A e g a h r - i m e h c i x a t a t h g i R g n i d e e l b l a r b e r e c o n s a w e r e h T s i s e r a p a i n e p o t y c o b m o r h t - r a l u c e l o m w o L - t h g i r e g r a l A d n a e h c a d a e h e r e v e S s y a d   9 y a d   1 A N R m 2 b 2 6 1 T N B F / 0 6 F / 2 6 M / 4 5 e r o p a g n i S s u o n e v l a r b e r e C a (   ] 2 4 [ . l a   t e n a F s y a d   8 n o i t a n i c c a v s i s o b m o r h t s u n i s 3 f o s e i r e s ) s t n e i t a p 1 3 14 Neurological Sciences (2022) 43:3–40 l a r b e r e c t n a c fi i n m a r g o n e v T C - g i s d e m r fi n o c s u n i s s u o n e v s i s o b m o r h t , l a t t i g a s r o i r e p u s d e l a e v e r y h p a r f o s i s o b m o r h t , l a r e t a l t h g i r , e s r e v s n a r t , s e s u n i s d i o m g i s n i e v r a l u g u j d n a d i o m g i s t f e l d n a r e h t e g o t , s u n i s l a t n o r f t h g i r h t i w d i o n h c a r a b u s d n a e g a h r r o m e h s u o n e v l a c i t r o c a I R M n i a r B t c r a f n i l a c i t r o c y t i x e v n o c - m o r h t d e w o h s h g i h f o s i s o b r o i r e p u s , s n i e v t h g i r , l a t t i g a s d n a , e s r e v s n a r t s u n i s d i o m g i s n i e v r a l u g u j d n a - e t a l p - i t n A a i n e p o t y c e r e w s e i d o b i t n a t e l d e t c e t e d n e d d u s a a i b o h p o t o h p r e w o l t h g i r n e d d u S y b d e w o l l o f , s t n e m - e v o m c i n o l c b m i l t i c fi e d r o t o m t f e l f o s s o l , t i c fi e d r o t o m d n a s s e n s u o i c s n o c a i n e p o t y c o b m o r h t o n - d o b i t n a t e l e t a l p - i t n A d e t c e t e d t o n e r e w s e i s a w e r e h T e h c a d a e h - u m m i s u o n e v a r t n i - b u s h t i w d e e l b s u o m y n o m o h w e n d n a s n i l u b o l g o n n o i s n e t x e l a r u d - o b m o r h T a i p o n a i m e h d n a n a r t a g i b a D l a m y h c n e r a p e t u c A e h c a d a e h g n i n e s r o W s y a d   2 - V O C n 1 x O d A h C M / 7 2 K U s u o n e v l a r b e r e C   y e h c t e P d n a h s e r u S e n i c c a v 9 1 s i s o b m o r h t s u n i s ] 3 4 [ n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R n o i t a n i c c a v r e t f a s n o i t a c i l p ) d e u n i t n o c ( 1 e l b a T g m   0 0 5 m a t e c a r i t e n i r a p a x o n e d n a d i b - v e L n i r a p a x o n e d n a e d i m a l o z a t e c A - g o n e v h t i w I R M d n a a e s u a n , e h c a d a e H s y a d   3 s y a d   6 A N R m 2 b 2 6 1 T N B F / 7 6 F / 7 4 l a g u t r o P s u o n e v l a r b e r e C s e i r e s a ( . l a   t e s a i D 2 - V o C - S R A S e n i c c a v s i s o b m o r h t s u n i s ] 4 4 [ ) s t n e i t a p 2 f o 1 3 Neurological Sciences (2022) 43:3–40 15 n i e v e s n e d d n a t f e l e h t t a n g i s d n a e s r e v s n a r t s e s u n i s d i o m g i s m a r g o n e v T C t a T S V C d e l a e v e r e s r e v s n a r t t f e l e h t d n a s e s u n i s d i o m - g i s d n a s u n i s l a n r e t n i t f e l e h t f o s i s o b m o r h t n i e v r a l u g u j d e d i v o r p t o n - d u l c n i , s u n i s e h t - y c o b m o r h t e h c a d a e h n g i s d r o c g n i r o t c a f t e l e t a l P a i n e p o t d e t c e t e d s e i d o b i t n a 4 - v o C n 1 x O d A h C ) a c e n e Z a r t s A ( 9 1 e m o c t u O n a b a x i p A f o y t i s n e d r e p y H p a l c r e d n u h t d n a a e s u a N s y a d   0 1 f o e s o d t s r fi e h T M / 2 5 n a w i a T s u o n e v l a r b e r e C ] 5 4 [ . l a   t e n a u G n o i t a n i c c a v r e t f a n e v i g t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C t e s n o f o n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R s i s o b m o r h t s u n i s s n o i t a c i l p ) d e u n i t n o c ( 1 e l b a T x u n i r a p a d n o f s u o d e v o r p m i t n e i t a P e n o s i t r o c o r d y h - e n a t u c b u s d n a s n i l u b o l g o n u m m i s u o n e v l a r b e r e c s i s o b m o r h t n o i s u f n o c d l i m d n a y r a t n e m g e s l a r e t a l B m s i l o b m e y r a n o m l u p - d o b i t n a t e l e t a l p - i t n A a i n e p o t y c o b m o r h T d e t c e t e d e r e w s e i - c a v 9 1 - D V O C I ) 1 x O d A h C ( d e s a b - r o t c e v e n i c s i s o b m o r h t s u n i s y r a m i r p d n a - f u s n i l a n e r d a y c n e i c fi s u o n e v a r t n I h t i w t n e t s i s n o C , e c n e l o n m o s , e h c a d a e H s y a d   0 1 l a r i v o n e d A M / 7 4 n i a p S s u o n e v l a r b e r e C ] 6 4 [ . l a   t e a n o r a V 1 3 Neurological Sciences (2022) 43:3–40 e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v 16 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a ) s i s o b m o r h t s u o n e v l a r b e r e c n a h t r e h t o ( s e k o r t s d e r e ff u s o h w s t n e i t a p f o s l i a t e d e m o c t u o d n a g n i g a m i o r u e n , l a c i n i l C e d i m e s e g a h r r o m e h d e i D - o r u f , e n i d i n o l C a i l g n a g l a s a b t f e L , a i g e l p i m e h t h g i R s y a d   3 F / 1 7 e c e e r G l a r b e r e c a r t n I - u o D d n a s o r y h t A l a c i g o l o r u e N n o i t a c i l p m o c 2 e l b a T e c n e r e f e R e g a h r r o m e h ] 3 5 [ s a m e g a h r r o m e h ] 4 5 [ d e i D t n e m e g a n a m U C I l a r b e r e c a r t n i t h g i R , h c e e p s d e r r u l S s y a d   9 - n e Z a r t s A F / s e i t r i h T y a w r o N l a r b e r e c a r t n I g n e v u T - d a t s n r ø j B n o e g a h r r o m e h s i s o b m o r h t , T C e s r e v s n a r t n i - o m l u p d n a s u n i s n o y r e t r a y r a n m e t r o m t s o p c i m l a h t h p o r o i r s i s o b m o r h t n i e v d e w o h s I R M n A t f e l e h t n i e k o r t s l a r b e r e c e l d d i m , y r o t i r r e t y r e t r a d e t c i r t s e r h t i w , e b o l l a t e i r a p c i m e h c s i n a n o i s u ff i d a i s o n g a , a i s a h p a - n e t r e p y h e t u c A s i s i r c e v i s , s i s e r a p i m e h t f e l s s e n s u o i c s n o c d e c u d e r d n a n o i s i v , a i p o l p i d , t n e i s n a r t a , s s o l d e d i s - t h g i r , d l i m d n a , s i s e r a p i m e h l a c o f , a i s a h p a s e r u z i e s 9 1 - D V O C I - i t n a a n r e d o M e n i c c a v e n i c c a v s ’ a c e 1 x O d A h C 9 1 - V o C n e n i c c a v 9 1 1 x O d A h C 9 1 - V o C n e n o s a h t e m a x e d s t n a l u g a o c i t n A s e i t i l i b a e v i s s e r p m o c e D y m o t c e i n a r c l a m y h c n e r a p e b o l l a t n o r f a m o t a m e h d n a , g n i t i m o v e c n e l o n m o s - s i d h t i w d e v i v r u S t n e m e g a n a m U C I p e e d t h g i r e g r a l A , s i s e r a p i m e h t f e L s y a d   5 - V o C n 1 x O d A h C F / 7 5 l i z a r B l a r b e r e c a r t n I a v l i S o l é M e d ] 5 5 [ . l a   t e d e v o r p m I s u o n e v a r t n I - e p u s d e w o h s I R M , s s e n l l i e k i l - u l F s y a d   0 1 — 2 - V o C - S R A S F / 5 5 y n a m r e G r o i r e p u s l a r e t a l i B ] 6 5 [ . l a   t e s a y a B h t i w e g a h r r o m e h r a l u c i r t n e v a r t n i n o i s n e t x e n i e v c i m l a h t h p o , e k o r t s c i m e h c s i , s i s o b m o r h t e n u m m i d n a - o t y c o b m o r h t a i n e p - u b o l g o n u m m i s u o n e v a r t n I n i l n i l u b o l g o n u m m i y m o t c e i n a r c s u o n e v a r t n I l a r e t a l i B t c r a f n i y r e t r a l a r b e r e c r e d r o b e t u c a s t c r a f n i e n o z - e l d d i m t f e L y r e t r a l a r b e r e c t c r a f n i s s e n i s w o r d d n a t f e l , e h c a d a e H s s e n k a e w g e l , s s o l d l e fi l a u s i v t f e l , n o i s u f n o c s s e n k a e w m r a a i s a h p s y D s y a d   1 2 1 x O d A h C e n i c - c a v 9 1 - V o C n - c a v 9 1 - V o C n e n i c c a v 9 1 1 x O d A h C e n i c d e v o r p m I d e i D e l b a t S - i m e h e v i s - s e r p m o c e D - e l d d i m t h g i R , m r a , e c a f t f e L s y a d   2 1 s y a d   1 1 - V o C n 1 x O d A h C F / 3 4 F / 7 3 F / 5 3 n o d n o L e k o r t s c i m e h c s I . l a   t e i n a h y a M - l A - y c o b m o r h t h t i w a i n e p o t   ] 7 5 [ 1 3 Neurological Sciences (2022) 43:3–40 17 t h g i r e h t f o n o i s d i t o r a C . l a n r e t n i - u l c c o d e w o h s y r e t r a s u b m o r h t ) A C I ( y r e t r a d i t o r a c t f e l e h t n i g n i e b o l l a r o p m e t , t n e r e h d a - l l a w A e l d d i m f o n o i s y r e t r a l a r b e r e c g n i d u l c c o - n o n l a r e t a l i s p i e h t n i s u b m o r h t s a w   b l u b d i t o r a c d e t o n A s e g a h r r o m e h c i m e h c s i d e d i s - m o r h T e k o r t s t h g i r e v i s s a m a i n e p o t y c o b 4 r o t c a f t e l e t a l P e v i t c a e r ) 4 ‐ F P ( s e i d o b i t n a s s e n d e d a e h - t h g i l - e p o t y c o b m o r h t f o g n i l g n i t d n a s s e n b m u n a i n t h g i r d n a e c a f r e h m r a , s e h c a y d o b d l i m , s l l i h c d n a a e n p s y d y t l u c ffi i d g n i d a e r a i s a h p a r a p h t i w a i s a h p a r o t o m a i s a h p a d n a t n u o c t e l e t a l P - o n i r b fi d n a e r e w l e v e l n e g d n a , a i s a h p a s i s e r a p i m e h l a m r o n 2 b 2 6 1 T N B e n i c - O B I / r e z fi P ( ) H C E T I 9 1 - D V O C n o s S . 2 V O C . 6 2 d A n o i t a n i c c a v - A N R m n a f o - S R A S d e s a b e n i c c a v 2 - V o C - v o C n 1 x O d A h C e n i c c a v 9 1 e s o d t s r i F e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v e r a c e v i t a i l l a P t i n u e r a c e v i s n e t n I y h p a r g o i g n A l a n e r d a l a r e t a l i B s y a d   7 - c a v d e s a b - A N R m M / 0 6 k r a m n e D e k o r t s c i m e h c s I . l a   t e t d l e f n e u a l B l a c i g o l o r u e N n o i t a c i l p m o c ) d e u n i t n o c ( 2 e l b a T e c n e r e f e R d e v o r p m I x u n i r a p a d n o F l a n r e t n i t h g i R , r e v e f , e h c a d a e H s y a d   0 1 - n h o J d n a n o s n h o J F / 3 4 A S U c i m e h c s i t n e i s n a r t ] 9 5 [ . l a t e   k i l a M k c a t t a t n e i t a p d n a d e v l o s d e v o r p m i s i s y l o b m o r h t V I f o t r a t s - s i d s u b m o r h T r e t f a h   1 n i h t i W - u l c c o m e t s n i a M , e h c a d a e h e t u c a y n a m r e G e k o r t s c i m e h c s I ] 1 6 [ . l a   t e r e t l a W l a r b e r e c e l d d i m f o n o i s u l c c o m e t s n i a M y r e t r a d e v o r p m I e v i t r o p p u S - d e e l b r a b o l A t e s n o - n e d d u S s y a d   7 e s o d d n o c e s e h T M / 2 5 a i r t s u A a i s a h p A n r o K d n a r e r e t s n i F ] 8 5 [ ] 0 6 [ 1 3 18 Neurological Sciences (2022) 43:3–40 On the third post-vaccination day, the patient devel- oped right hemiplegia, aphasia, and agnosia along with accelerated hypertension. Computed tomography revealed a hematoma in the left basal ganglia. On the 9th day, she died [53]. In another report, Bjørnstad-Tuveng et al. described a young woman, who had a fatal cerebral event following vaccination with AstraZeneca’s ChAdOx1 nCoV-19 vac- cine. She was found to have severe thrombocytopenia. The patient died the next day of the event. Post-mortem exami- nation revealed antibodies against platelet factor 4 and the presence of small thrombi in the transverse sinus, frontal lobe, and pulmonary artery [54]. Acute ischemic stroke Bayas and co-workers described a case that presented with superior ophthalmic vein thrombosis, ischemic stroke, and immune thrombocytopenia, after administration of viral vector-based vaccine. Intravenous dexamethasone resulted in marked improvement in platelet count [56]. Al-May- hani et al. described three cases of vaccine-induced throm- botic thrombocytopenia, all presented with arterial strokes. Authors opined that young patients with arterial stroke after receiving the COVID-19 vaccine should always be evaluated for vaccine-induced thrombotic thrombocytopenia. Other laboratory tests, like platelet count, D-dimers, fibrinogen level, and testing for platelet factor 4 antibodies, should also be performed [57]. Blauenfeldt et al. described a 60-year-old woman, who presented with intractable abdominal pain, 7  days after receiving the adenoviral (ChAdOx1) vector-based COVID- 19 vaccine. Abdominal computed tomography revealed bilateral adrenal necrosis. Later, a massive right cerebral infarction, secondary to occlusion of the right internal carotid artery, occurred that led to death of the patient. Blood tests showed thrombocytopenia, elevated in D-dimer and platelet factor 4 antibodies [58]. Many reports of acute brain disorders like encephalopa- thy, seizures, acute disseminated encephalopathy, neurolep- tic malignant syndrome, and post-vaccine encephalitis were described secondary to COVID-19 vaccine. These are sum- marized in Table 3 [62–75]. Encephalopathy Some patients developed encephalopathy following admin- istration of COVID-19 vaccines. Acute encephalopathy is defined as rapidly evolving disorder of the brain. Acute encephalopathy clinically manifests either with delirium, decreased consciousness, or coma. Delirium Delirium is characterized with fluctuating disturbance in attention and awareness. Zavala-Jonguitud and Pérez-García described an 89-year-old man, who developed delirium after mRNA vaccination. Within 24 h, patient developed confu- sion, fluctuating attention, anxiety, and inversion of the sleep–wake cycle. Patient had many comorbidities (diabetes mellitus, hypertension, and chronic kidney disease). Patient improved after he was treated with quetiapine [68]. Neuroleptic malignant syndrome Neuroleptic malignant syndrome is a life-threatening com- plication of many antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dys- function. In an isolated report, neuroleptic malignant syn- drome, in a 74-year-old female with dementia and bipolar disorder 16 days after COVID-19 vaccination, has been described [69]. Acute disseminated encephalomyelitis Acute disseminated encephalomyelitis (ADEM) is an acute inflammatory demyelinating disorder of the central nervous system. In the majority, ADEM is a post-infectious entity; in many cases, it even develops after vaccination [76]. In two cases, acute disseminated encephalomyelitis follow- ing COVID-19 vaccination has been reported. In first such case a 46-year-old woman received  Sinovac inactivated SARS-CoV-2 vaccine before onset of clinical manifesta- tions. Patient was presented with seizures, and magnetic resonance imaging revealed multiple, discrete T2/FLAIR periventricular. hyperintense lesions. Patient improved fol- lowing methylprednisolone treatment [70] Another patient was a 24-year-old female who presented with encephalopa- thy along with limb weakness of 1-day duration. Two weeks prior, patient was vaccinated with inactivated SARS-CoV-2 vaccine. Magnetic resonance imaging revealed multiple, dis- crete T2/FLAIR hyperintense lesions in the brain. Patient improved following treatment with antiepileptics and intra- venous immunoglobulins [71]. Post‑vaccinal encephalitis Zuhorn et al. reported a case series 3 patients, who pre- sented with post-vaccinal encephalitis, akin to autoim- mune encephalitis, 7 to 11  days after administration of adenovirus-based ChAdOx1 nCov-19 vaccine. All patients fulfilled the diagnostic criteria for possible auto- immune encephalitis. One interesting case had presented with opsoclonus-myoclonus syndrome. Two patients pre- sented with cognitive decline, seizures, and gait disorder. 1 3 Neurological Sciences (2022) 43:3–40 19 e s a e r c n i t n a c fi i n n i k u e l r e t n i f o h t o b n i 6 - ) L I ( m u r e s d n a F S C r e v e - t s r fi r e v e f d e z i l a r e n e g - i e s c i n o l c – c i n o t , m a p e z a r o l e r u z , m a t e c a r i t e v e l n i o t y n e h p d n a l o r t n o c o t d e l i a f - d i k c i n o r h c   , n o i t d n a e s a e s i d y e n e t u c a h t i w s u t i l y h t a p o l a h p e c n e n o i s u f n o c e t u c A - l a h l a u s i v h t i w G E E s n o i t a n i c u l - l e m s e t e b a i d e v i s l u v n o c - n o n - i p e s u t a t s l a c o f e t u c A s u c i t p e l y h t a p o l a h p e c n e d e t a r t s n o m e d - n o n h t i w s u t a t s e v i s l u v n o c s u c i t p e l i p e e c n a b r u t s i d p e e l s , s n o i t a n i c u l l a h d n a , n o i t a t i g a t s n i a g a n o i t a n i c c a v r e t f a ) e k o r t s l a i r e t r a d n a s i s o b m o r h t s u o n e v l a r b e r e c n a h t r e h t o ( r e d r o s i d n i a r b e t u c a n a h t i w d e t n e s e r p o h w s t n e i t a p f o s l i a t e d e m o c t u o d n a g n i g a m i o r u e n , l a c i n i l C e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v s d i o r e t s o c i t r o C l a m r o N - g i s A m u i r i l e D y a d   1 M / 7 7 y l a t I e l b i s r e v e R ] 2 6 [   . l a t e i l l e d l a B e n i c c a v 9 1 - V o C n ) a c e n e Z a r t s A ( 1 x O d A h C f o e s o d t s r fi e h T e n i c c a v 9 1 y h t a p o l a h p e c n e l a c i g o l o r u e N n o i t a c i l p m o c 2 - V o C - S R A S 3 e l b a T e c n e r e f e R s u t a t s y r o t s u c i t p e l i p e ] 3 6 [ h a r d e v o r p m I d n a m a l o z a d i M e h t n i e s a e r c n I d n a e h c a d a e H s y a d   0 1 - V o C n 1 x O d A h C F / 2 4 a i b a r A i d u a S - c a r f e r t e s n o - w e N - i h S d n a n i d d a l A a m s a l P l o f o p o r p I R A L F n o l a n g i s e g n a h c x e i p m a c o p p i h l a r e - t a l i b t a s e g a m i a l u s n i d n a l a c i t r o c d n a y h p o r t a s i s o i a r a o k u e l   r a l e r u z i e s r o t o m d e v o r p m i h t o B c i t p e l i p e i t n A l a m r o N - c n u f s y d c i l o t s a i D s y a d   1 2 s y a d   7 - I D V O C a n r e d o M M / 3 7 F / 6 8 A S U h t i w d e t a i c o s s A o w t (   ] 5 6 [ . l a   t e u i L U C I d n a y p a r e h t e r a c e n i c c a v 9 1 s u c i t p e l i p e s u t a t s e v i s l u v n o c - n o n ) s e s a c d e v o r p m I m a t e c a r a v i r b - u c i r t n e v i r e P - n o n t e s n o l a c o F s y a d   4 e n i c c a v d l e i h s i v o C M / 8 6 a i d n I s e r u z i e S ] 4 6 [ . l a   t e h s o h G d e v o r p m I d n a l o d i r e p o l a H e n o N , n o i s u f n o c e t u c A f o e s o d t s r fi F / 8 8 y e k r u T m u i r i l e D c s a T d n a i c r a h a N e n o d o z a r t ] 6 6 [ d e t a v i t c a n i n a - - – c a V a n o r o C 9 1 - D V O C I e n i c c a v 1 3 20 Neurological Sciences (2022) 43:3–40 f o h   5 r e t f a r e v e f d a h e m o r d n y s - s s e l t s e r r o t o m d e v l o s e r s s e n h   4 2 r e t f a - n e t t a g n i t a u t c u fl d n a y t e i x n a , n o i t e h t f o n o i s r e v n i e l c y c e k a w – p e e l s e p y t f o y r o t s i H - l e m s e t e b a i d 2 b ‐ I I I e g a t s , n o i s - n e t r e p y h , s u t i l y e n d i k c i n o r h c c i t a t s o r p , e s a e s i d a i s a l p r e p y h r e d r o s i d r a l o p i b - v i e c e r s a w d n a , e n i t n a m e m g n i d n a , l i z e p e n o d d n a a i t n e m e d h t i w d e t n e s e r p , m u i r i l e d , r e v e f d n a , y t i d i g i r K P C d e t a v e l e e n i p a i t e u q e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C d e v o r p m I e n o N e n o N y d o b s s e l t s e R f o h   4 2 n i h t i W h c e T N o i B - r e z fi P F / 6 3 A S U a i s i h t a k a t n e i s n a r T ] 7 6 [ . l a t e   s a n i l a S n o i t a n i c c a v e s o d d n o c e s e n i c c a v l a c i g o l o r u e N n o i t a c i l p m o c ) d e u n i t n o c ( 3 e l b a T e c n e r e f e R d e v o r p m I e n i p a i t e u Q e n o d t o N , n o i s u f n o c e t u c A h   4 2 f o e s o d t s r fi e h T M / 9 8 o c i x e M m u i r i l e D d u t i u g n o J - a l a v a Z A N R 2 b 2 6 1 T N B e n i c c a v ] 8 6 [ . l a   t e d e v o r p m I c i t a m o t p m y S l a m r o N f o e s a c d l O s y a d   6 1 A N R m 2 b 2 6 1 T N B F / 4 7 t i a w u K - g i l a m c i t p e l o r u e N . l a   t e y w a h s fi A l - c a v 9 1 - D V O C I e n i c e m o r d n y s t n a n ] 9 6 [ f o e c n e r r u c e r o N - o s i n d e r p l y h t e M I R A L F , 2 T l a m r o n , s e r u z i e S h t n o M 1 - S R A S d e t a v i t c a n I F / 6 4 y e k r u T - i m e s s i d e t u c A l i g n g n e K n e z O s e r u z i e s e n o l n o i t a n i m a x e ] 0 7 [ . l a   t e d e v o r p m I - u b o l g o n u m m i V I e t i h w R A L F / 2 T I d n a e c n e l o n m o S s k e e w   2 - c a V 2 - V o C - S R A S F / 4 2 a n i h C - i m e s s i d e t u c A ] 1 7 [ n e R d n a o a C d n a , s u m a l a h t n i y t i s n e t n i r e p y h a t a i d a r a n o r o c n i l - n i r e p y h r e t t a m , e n i l c e d   y r o m e m h t o b n i y t i s n e t s e b o l l a r o p m e t F S C n i s e g n a h c y r o t a m m a fl n i 1 1 - E S M M e n i c c a v 2 - V o C c a v o n i S f o , ) l l e C o r e V ( e n i c d e t a v i t c a n I - a h p e c n e d e t a n e k i l s i t i l e y m o l s n o i s e l I R M - o l a h p e c n e d e t a n s i t i l e y m 1 3 Neurological Sciences (2022) 43:3–40 21 - r e p y h r e t t a m n i y t i s n e t n i r a l l e b e r e c   t f e l - d e r p e l c n u d e p d e v o r p m i e n o s i n e r e w s e c n e u q e s I R A L F e h t , d e v r e s b o e h t n i t s e g r a l m u r t n e c t f e l e l a v o i m e s - i z z i d , e h c a d a e h e l b u o d d n a s s e n r e t a l ; h s a r d e z i o t g n i d a e l n o i s i v - t i m r e t n I y h t a p o l - a h p e c n e e r e v e s d n a s t n e m e v o m l a i c a f o r o t n e t - l a r e n e g d n a - m e r t x e r e p p u s u n o l c o y m y t i d e w o h s F S C s l l e c d e s a e r c n i n i k S . n i e t o r p d n a d e w o h s y s p o i b s i t i l u c s a v s e g n a h c t f e l n o s s e n k a e w t f e l , b m i l r e p p u t i a g c i x a t a - i m e h d l i M , s u m g a t - s y n   d e k o v e e n o l e n o l r a l u c i r t n e v i r e p - r e p y h r e t t a m n i s e i t i s n e t n i n o i g e r e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v d e v o r p m I - o s i n d e r p l y h t e M e t i h w R A L F / 2 T I d e w o l l o f m u i r i l e D s k e e w   3 A N R m 2 b 2 6 1 T N B M / 5 5 h s e d a l g n a B - i m e s s i d e t u c A - n o c f o s s o l y b s s e n s u o i c s - c a v 9 1 - D V O C I e n i c - o l a h p e c n e d e t a n s i t i l e y m n a m a z z u n k a R ] 2 7 [ . l a   t e l a c i g o l o r u e N n o i t a c i l p m o c ) d e u n i t n o c ( 3 e l b a T e c n e r e f e R d e v o r p m I - o s i n d e r p l y h t e M l a m r o N r e v e f , n o i s u f n o C y a d   1 - c a v 3 7 2 1 - A N R m M / 7 7 A S U , s i t i l a h p e c n e e t u c A a t s o c A - a b l a e r r o T e n i c d n a s u n o l c o y m e m o r d n y s t e e w S ] 3 7 [ . l a t e d e v o r p m I e n o s i n d e r P e t i h w R A L F / 2 T I - e z a g l a t n o z i r o H s k e e w   2 h c e T M o i B - r e z fi P F / 6 5 y l a t I - i m e s s i d e t u c A ] 4 7 [ . l a   t e g i r g o V ) y t a n r i m o C ( e n i c - c a v 9 1 - D V O C I - o l a h p e c n e d e t a n s i t i l e y m 1 3 22 Neurological Sciences (2022) 43:3–40 - u e n e v i s s e r g o r p - p m y s l a c i g o l o r g n i d u l c n i s m o t d n a n o i t n e t t a n o i t a r t n e c n o c d n a s e i t l u c ffi i d F S C e r u z i e s a c i t y c o h p m y l s i s o t y c o e l p a t l e d w o l s G E E m h t y h r a d n a r e d r o s i d y d o b r e h r e v o l l a g n i h c t i w t - s u n o l c o s p O s u n o l c o y m F S C e m o r d n y s c i t y c o h p m y l s i s o t y c o e l p a t l e d w o l s G E E m h t y h r , r e d r o s i d t i a G e c n a l i g i v a G E E s i s o t y c o e l p F S C r e v e f d n a c i t y c o h p m y l l a m r o n d e v o r p m I - o s i n d e r p l y h t e M l a m r o N s y a d   6 - v o C n 1 x O d A h C F / 3 6 e n o l e n i c c a v 9 1 t n e m e v o r p m i d l i M - t a e r t o n e t i p s e d t n e m e n o N l a m r o N a i s a h p a d e t a l o s I s y a d   8 - v o C n 1 x O d A h C M / 3 6 e n i c c a v 9 1 e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C d e v o r p m I e n o s i n d e r P l a m r o N d n a e h c a d a e H s y a d   5 - v o C n 1 x O d A h C F / 1 2 y n a m r e G l a n i c c a v t s o P ] 5 7 [ . l a   t e n r o h u Z n o i t a n i c c a v e h t e n i c c a v 9 1 e s o d t s r fi l a c i g o l o r u e N n o i t a c i l p m o c s i t i l a h p e c n e o t r a l i m i S e n u m m i o t u a s i t i l a h p e c n e ) d e u n i t n o c ( 3 e l b a T e c n e r e f e R 1 3 Neurological Sciences (2022) 43:3–40 23 Neuroimaging did not reveal any abnormality. CSF pleocytosis was noted in all three patients. All patients responded well to corticosteroids [75]. Bell’s palsy Transverse myelitis Acute transverse myelitis is an inflammatory spinal cord disorder that clinically manifests with the paraparesis/ quadriparesis, transverse sensory level, and bowel or bladder dysfunction. Acute transverse myelitis usually is a postinfectious disorder. Magnetic resonance imaging demonstrates T2/FLAIR hyperintensity extending several spinal cord segments. Autoimmunity via mechanism of molecular mimicry is usually responsible for spinal cord dysfunction. Adenoviral vector-based COVID-19 vaccines are more frequently associated with causation of trans- verse myelitis. In isolated cases, even inactivated virus vaccine and mRNA-based vaccines had precipitated acute demyelination spinal cord syndromes, like multiple scle- rosis and neuromyelitis optica. Reports of myelitis associ- ated with vaccination for SARS-CoV-2 are summarized in Table 4 [77–83]. Malhotra and colleagues reported a 36-year-old patient, who had short-segment myelitis 21 days after first dose of adenoviral vector-based (Oxford/AstraZeneca, COV- ISHIELD™) vaccine. Patient recovered completely after treatment with methylprednisolone [77]. Fitzsimmons and Nance reported another patient of acute transverse myeli- tis following Moderna vaccine (an mRNA vaccine). The 63-year-old patient developed symptoms of acute myelop- athy within 24 h of vaccination. MRI revealed increased T2 cord signal seen in the distal spinal cord and conus. Patient improved considerably following treatment with methylprednisolone and intravenous immunoglobulin [78]. Earlier, in phase III trial of Oxford/AstraZeneca vac- cine, 2 patients had developed transverse myelitis. One of the case of transverse myelitis was reported 14 days after booster vaccination. The expert committee considered that this case was the most likely an idiopathic, short segment transverse myelitis. The second case was reported 68 days post-vaccination. Experts believed that in this case, trans- verse myelitis was not likely to be associated with vac- cination. This patient was earlier diagnosed as a case of multiple sclerosis [84, 85]. The pathogenesis of acute transverse myelitis following COVID-19 vaccination remains unknown. Possibly, SARS- CoV-2 antigens present in the COVID-19 vaccine or its adenovirus adjuvant induce immunological reaction in the spinal cord. The occurrence of 3 reported acute transverse myelitis adverse effects among 11,636 participants in the vaccine trials was considered high and a cause of concern [86]. Several cases of Bell’s palsy have occurred following COVID-19 vaccination. (Table 5) [87–95]. The instances of Bell’s palsy are most often associated with mRNA vaccines [96]. Vaccine-associated Bell’s palsy generally responds very well to the oral corticosteroids. The exact pathogenesis remains speculative. In a case–control study, Shemer et al. compared clinical parameters of patients with Bell’s palsy following mRNA vaccination with that of patients with Bell’s palsy without vaccination. Out of 37 patients, 21 had received vaccina- tion. Bell’s palsy developed within 2 weeks following first dose of COVID-19 vaccination. There was no difference in any of the clinical parameter between vaccinated or unvac- cinated groups [97]. Earlier, in the Pfizer-BioNTech clinical trial, which included 44,000 participants, 4 people had Bell’s palsy. No case of Bell’s palsy was reported in the placebo arm. In the Moderna trial, which included 30,400 participants, 3 vaccine recipients reported Bell’s palsy. One person was in the placebo arm [98]. An article, published in the Lancet, analyzed the combined phase 3 data of Pfizer and Moderna trials and noted that the rate of Bell’s palsy was higher than expected [98]. Other cranial nerve involvement In isolated instances, mRNA vaccines were found associ- ated with olfactory dysfunction and sixth cranial nerve palsy (Table 6) [99–104]. Olfactory dysfunction Olfactory dysfunction is the most frequent neurological complication of COVID-19. Konstantinidis and colleagues reported two cases of smell impairment after second dose of the BioNTechBNT162b2 vaccine (Pfizer) administra- tion [51]. Keir and colleagues reported phantosmia follow- ing administration of Pfizer COVID-19 vaccine. Patient complained of constantly “smelling smoke” and head- aches. MRI of brain of the patient showed enhancement of the olfactory bulbs and bilateral olfactory tracts [100]. Abducens nerve palsy Reyes-Capo et al. reported a 59-year-old lady, who pre- sented with an abducen nerve palsy 2 days post-vaccination 1 3 Neurological Sciences (2022) 43:3–40 y a d n o i t a n i c c a v n o i t a n i c 24 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a t n e m e v l o v n i d r o c l a n i p s h t i w d e t n e s e r p o h w s t n e i t a p f o s l i a t e d e m o c t u o d n a , g n i g a m i o r u e n , l a c i n i l C 4 e l b a T e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C - c a v r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R n o i t a c i l p d e v o r p m I - o s i n d e r p l y h t e M e s n e t n i r e p y h - 2 T - a s n e s l a m r o n b A - t s o p h t 8 e h t n O M / 6 3 a i d n I s i t i l e y m e s r e v s n a r T ] 7 7 [ . l a   t e a r t o h l a M e n o l 6 C t a d r o c l a n i p s l a r b e t r e v 7 C d n a f o t c e p s a l a s r o d e h t n i n o i s e l s l e v e l - n u r t h t i w s b m i l r e w o l n i s n o i t l e v e l l a c h t i w d r o c l a n i p s d n a l a i x a e d i w g n i h c a e r t n e t x e 2 h T o t 3 C m o r f l a n i d u t i g n o l l a n g i s d e t a c o l s e i t i s n e t n i e h t t u o h g u o r h t l a n i p s   c i c a r o h t d r o c e n o l o s i n t n e m g e s 3 - 2 C e h t d r o c l a n i p s e h t m o r f g n i d n e t x e r e p p u e h t o t n i n o i g e r c i c a r o h t e h t f o l a n g i s y r a n i r u d n a n i a p n o i t n e t e r n i a i s e h t s e r a p d n a , t e e f h t o b r e w o l n i n i a p - f i d s e i t i m e r t x e g n i k l a w n i y t l u c fi y r a n i r u d n a n o i t n e t e r d e s a e r c n i F S C s l l e c t n e s b a h t i w , a i g s e x e fl e r n o d n e t , s g e l e h t n i d n a , e c n e n i t n o c n i t i c fi e d y r o s n e s a s e i t i l a u q l l a r o f F S C . 5 h T w o l e b d n a s i s o t y c o e l p n i e t o r p d e t a v e l e e r e v e s d e w o h s d e v o r p m I e n o l o s i n d e r P e s n e t n i r e p y h 2 T k c a b c i c a r o h T s y a d   1 1 - I D V O C e s o d t s r i F M / 5 4 y n a m r e G y l l a n i d u t i g n o L d n a n i l u b o l g o n - o s i n d e r p l y h t e m e h t n i n e e s l a n g i s d r o c l a n i p s l a t s i d e n o l s u n o c d n a d e v o r p m I - u m m i s u o n e v a r t n I d r o c 2 T d e s a e r c n I , n i a p k c a b r e w o L y a d   1 n i h t i W e h t f o e s o d d n o c e S M / 3 6 A S U s i t i l e y m e s r e v s n a r T d n a s n o m m i s z t i F ] 8 7 [ e c n a N - d e r p l y h t e m d n a n i n e e s l a n g i s y h t a p o l e y m e s r e v d e v o r p m I e g n a h c x e a m s a l P d r o c 2 T d e s a e r c n I - s n a r t d r o c l a c i v r e C s y a d   0 1 S . 2 V O C . 6 2 d A F / 4 4 A S U s i t i l e y m e s r e v s n a r T ] 9 7 [ . l a   t e r i h a T s i s e r e h p a m s a l p y l l a r t n e c l a n i d u t d e v o r p m I d n a s d i o r e t s o c i t r o C - i g n o l d e s a e r c n I - e l p a r a p s s e n d n i l B s k e e w   2 , a c e n e Z a r t s A F / 0 4 y n a m r e G h t i w s i t i r u e n c i t p O . l a   t e n e h c m l e H - s n a r t e v i s n e t x e s i t i l e y m e s r e v ] 0 8 [ r e y e m d ü S d n a f p o k n e g a P n i s i t i l e y m e s r e v - s n a r t e v i s n e t x e e l p i t l u m e l b a t s l a n i d u t i g n o l s i s o r e l c s ] 1 8 [ - V o C n 1 X O d A h C , d e r o t c e v - l a r i V t n a n i b m o c e r d l e i h s i v o C 9 1 - a r t s A (   e n i c c a v e n i c c a v a c e n e Z - i t s n I m u r e S y b ) a i d n I f o e t u t e n i c c a v a n r e d o M - n h o J & n o s n h o J ( e n i c c a v ) n o s e n i c c a v - 9 1 , 2 2 2 1 D Z A ( ) a c e n e Z a r t s A a i r v e z x a V ; ® e n i c - c a V 9 1 D V O C I 1 3 Neurological Sciences (2022) 43:3–40 25 , ) 0 2 > ( e l p i t l u m - u fl n o c y l l a i t r a p h t i w s n o i s e l t n e t u b n o i t a n i m e s m u i n i l o d a g o n . t n e m e c n a h n e - s i d l a i t a p s - c n a h n e - t s a r t n o C e h t t a n o i s e l g n i - s e g g u s , l e v e l 6 T s i t i l e y m f o e v i t a m e r t s o p a e r a l a r e t a l i b d n a s u m a l a h t o p y h s n o i s e l e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C - c a v r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - m o c l a c i g o l o r u e N e c n e r e f e R a m s a l p d n a e n o l e g n a h c x e s d n a b l a n o l c - o g i l o s i t i l e y M n o i t a n i c - c a v 9 1 - D V O C I e n i c e l p i t l u m f o n o i t s i s o r e l c s n o i t a c i l p d e v o r p m I - o s i n d e r p l y h t e M d e l a e v e r I R M e s o d t s r fi s y a d   6 h c e T N o i B - r e z fi P F / 8 2 y n a m r e G - a t s e f i n a m t s r i F ] 2 8 [ . l a   t e a l v a H ) d e u n i t n o c ( 4 e l b a T d e v o r p m I - o s i n d e r p l y h t e M f o g n i n n a c s I R M d n a s s e n i z z i D s y a d   3 f o e s o d t s r fi e h T d e g a - e l d d i M a n i h C s i t i l e y m o r u e N ] 3 8 [ . l a   t e n e h C e n o l d e l a e v e r n i a r b e h t g n i k l a w y d a e t s n u e v i t i s o p - 4 P Q A s u r i v d e t a v i t c a n i e n i c c a v e l a m e f m u r t c e p s a c i t p o r e d r o s i d (Pfizer-BioNTech mRNA vaccine). Neuroimaging in this patient was normal.. Otologic manifestations A variety of otologic manifestations has been noted fol- lowing COVID-19 vaccination. Parrino and colleagues described three patients with sudden unilateral tinnitus following BNT162b2 mRNA vaccine administration. Tin- nitus rapidly resolved in 2 cases. Wichova and colleagues in a retrospective review recorded 30 patients, who either had significantly exacerbated otologic symptoms or had a new symptom after getting mRNA vaccine. Post-vacci- nation otologic manifestations included hearing loss with tinnitus, dizziness, or with vertigo. In some patients, with Menière's disease or autoimmune inner ear disease, vaccine led to exacerbation of the pre-existing otologic symptoms [102,105]. Acute vision loss Santovito and Pinna reported an unusual patient, who developed acute visual impairment following the 2nd dose of the Pfizer-BioNTech COVID-19 vaccine. Prior to visual symptoms, patient experienced unilateral headache. He also reported mild confusion, asthenia, and profound nausea. His symptoms got relieved after taking analgesics. Possibly, patient had an acute attack of migraine with aura that got precipitated by the vaccine [106]. Guillain‑Barré syndrome Guillain-Barré syndrome is a post-infectious disorder of peripheral nerve manifesting with lower motor neuron type of sensory-motor quadriparesis. Acute motor weakness is frequently preceded by an antecedent microbial infection. There are numerous reports indicating that COVID-19 infec- tion can trigger Guillain-Barré syndrome. The US Food and Drug Administration has recently expressed its concern regarding a possible association between the Johnson and Johnson COVID-19 vaccine with Guillain-Barré syndrome [107]. After emergency use approvals, all kinds of COVID-19 vaccines were found associated with Guillain-Barré syn- drome. Adenovector-based vaccines were more frequently associated with Guillain-Barré syndrome. Earlier, in phase 3 trial of Johnson and Johnson adenovirus vector-based COVID-19 vaccine, 2 patients developed Guillain-Barré syndrome. One patient belonged to vaccine group and other to placebo group. Both patients had Guillain-Barré syn- drome within 2 weeks of receiving injections. The Guillain- Barré syndrome in the vaccine arm was preceded by chills, nausea, diarrhea, and myalgia [108, 109]. 1 3 26 Neurological Sciences (2022) 43:3–40 s u c i m l a h t h p o r e t s o z r e t s o z s e p r e h d n a s u c i t o a i s u e g a y s l a p s ’ l l e B s s e n k a e w l a i c a F n i y s l a p s ’ l l e B t h g i r a d e p o l e v e d e h S - g e r p g n i r u d 2 1 0 2 ) h t n o m h t 5 ( y c n a n y s l a P s ’ l l e B 4 e r o c s s i h f o e d i s t f e l e h t e c a f d n a d o o l b n i t n e s e r p 2 - V o C - S R A S s i s e r e w s e i d o b i t n a F S C e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C - c a v r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - i l p m o c l a c i g o l o r u e N 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a y s l a p s ’ l l e B m o r f d e r e ff u s o h w , s t n e i t a p d e t r o p e r f o y r a m m u S n o i t a c 5 e l b a T e c n e r e f e R n e v i g t o N s d i o r e t s o c i t r o C e n o N - k a e w l a i c a f e t u c A t s r fi r e t f a s y a d   0 3 – 4 - S R A S 2 b 2 6 1 T N B 6 8 – 5 3 l e a r s I y s l a p s ’ l l e B t r o p e r a ( . l a   t e r e m e h S s e p r e h d a h e n O s s e n d n 2 d e v i e c e r 3 e s o d e n i c c a v 2 - V o C ] 7 8 [ ) s e s a c 9 f o n o i t a n i c e s o d ) 4 = F d n a 5 = M ( d e v o r p m I e n o s i n d e r P e n o N f o s e d o s i p e s u o i v e r p 3 e s o d d n o c e s r e t f a h   6 3 h c e T N o i B - r e z fi P F / 7 5 A S U y s l a p s ' l l e B ] 8 8 [ . l a   t e c i j a p e R d e v o r p m I s d i o r e t s o c i t r o C e n o d t o N s s e n k a e w l a i c a f e t u c A e s o d t s r fi r e t f a s y a d   5 M / 7 3 y l a t I y s l a p s ’ l l e B ] 9 8 [ . l a t e   a l l e l o C d e v o r p m I s d i o r e t s o c i t r o C e n o N y s l a p l a i c a f I I I e d a r G s y a d   2 I 9 1 - D V O C a n r e d o M F / 4 3 n i a p S y s l a p s ’ l l e B . l a   t e s e r a l l i V - n i t r a M d e v o r p m I s d i o r e t s o c i t r o C l a m r o N n o s s e n k a e w e l c s u M s y a d   9 2 b 2 6 1 T N B - r e z fi P M / 0 5 n i a p S y s l a p s ’ l l e B s o r e r r e T e d z e m ó G e n o N e n o N l a m r o N n n a m k c a r B - e s u o H s y a d   0 2 - c a v S . 2 V O C . 6 2 d A F / 2 6 n a p a J y s l a p s ’ l l e B ] 1 9 [ . l a   t e a w a z i h s i N e h t h t o b d e v o r p m I e m i t e n o l o s i n d e r P l a m r o N - n o c e t e r c s i d o w T t f e L h   5 , y s l a p t h g i R s e s o d d n o c e s d n a t s r i F K U - t a l a r t n o c l a i t n e u q e S ] 3 9 [ . l a t e   s w o r r u B y s l a p s ’ l l e B f o s e d o s i p e l a r e t a l a r t s y a d   2 r e t f a y s l a p e v r e n l a i c a f l a r e s e i s l a p d e v o r p m I e n o l o s i n d e r P l a m r o N - y l a r a p e l c s u m l a i c a F y a d   2 - S R A S f o e s o d t s r i F F / 1 2 y n a m r e G y s l a p s ’ l l e B ] 4 9 [ . l a t e   n n a m r e b O ] 0 9 [ ] 2 9 [ . l a   t e A N R r e g n e s s e m e n i c c a v ) A N R m ( A 9 1 - D V O C I e n i c c a v A N R m 2 b 2 6 1 T N B e n i c c a v e n i c c a v A N R m n o i t a n i c - N o i B - r e z fi P e h t f o I 9 1 - D V O C h c e T e n i c c a v y t a n r i m o C e n i c c a v - N o i B , 2 b 2 6 1 T N B ( A N R m 2 - V o C ) r e z fi P / h c e T - c a v   3 7 2 1 - A N R m e n i c d e v o r p m I e n o l o s i n d e r P l a m r o N y s l a p l a i c a F y a d   1 e h t f o e s o d d n o c e S M / 6 3 r a t a Q y s l a p s ’ l l e B ] 5 9 [ . l a   t e r a h k i t f I 1 3 Neurological Sciences (2022) 43:3–40 27 s e t a r t s n o m e d - e c n a h n e t n i a f - c a f l o t f e l t n e m I R M t c a r t y r o t f o t n e m e c n a h n e r e t a e r g t f e l e h t - c a f l o t h g i r n a h t d n a b l u b y r o t - c a f l o l a r e t a l i b s t c a r t y r o t s t i b r o d n a n i a r b s e d o s i p e m o d n a r h t i w , d e u g i t a f h t i w d e t a i c o s s a a i m s o p y h ’ ’ e k o m s g n i - l l e m s ‘ ‘ f o e s o d - e c n a h n e h t a e h s 3 V e h t f o t n e m e h t f o t n e m g e s l a r u e n i r e p d n a I R M e h T e v r e n l a n i m e g i r t t f e l l a c i v r e c e h t f o d e l a e v e r e n i p s c i t o l y d n o p s s e g n a h c d e l a e v e r e v r e n n i a p d n a g n i g n i n e k c i h t e c a f t f e l e h t r e v o k c e n d n a d e b r u t s i d d n a s u t - r a e h l a m r o n e h t r e v e f h g i h g n i d n a s l l i h c h t i w a i g l a y m e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a ) y s l a p s ’ l l e B n a h t r e h t o ( t n e m e v l o v n i e v r e n l a i n a r c m o r f d e r e ff u s o h w , s t n e i t a p d e t r o p e r f o y r a m m u S d n o c e s r i e h t e s o d d n o c e s 2 b 2 6 1 T N B d e v o r p m I g n i n i a r t y r o t c a f l O e n o N r e t f a a i m s o p y H r e t f a s y a d   5 d n a 3 h c e T N o i B - r e z fi P e l a m e f h t o B e c e e r G - s y d y r o t c a f l O . l a   t e s i d i n i t n a t s n o K l a c i g o l o r u e N n o i t a c i l p m o c 6 e l b a T e c n e r e f e R n o i t c n u f 2 f o t r o p e R ] 9 9 [ s t n e i t a p e n o N e n o N T C t s a r t n o c t s o P , k a e w g n i l e e F e n o N h c e T N o i B - r e z fi P F / 7 5 A S U a i m s o t n a h P ] 0 0 1 [ . l a   t e r i e K - c a v 9 1 - D V O C I d n o c e S n o i t a n i c e s o d d e n i a m e r n o i t n i d e g n a h c n u p u - w o l l o f t n e c e r - a n i m a x e r o t o m - y r o s n e S e l b a l i a v a t o N f o I R M l a m r o N y a d   1 r o f r e v e F s y a d   2 h c e T N o i B - r e z fi P F / 9 5 A S U s n e c u d b a e t u c A . l a   t e o p a C - s e y e R y b d e w o l l o f a i p o l p i d - c a v 9 1 - D V O C I e n i c y s l a p e v r e n ] 1 0 1 [ o w t n i s u t i n n i t s y a d   7 e n i c c a v - A N R m l l a d e v o r p m I , s d i o r e t s o c i t r o C I R M l a m r o N l a r e t a l i n u n e d d u S h   0 2 e s o d t s r fi h - 7 2 b 2 6 1 T N B M / 0 3 / 3 6 F / 7 3 y l a t I s u t i n n i T ] 2 0 1 [ . l a   t e o n i r r a P d e v o r p m I s d i o r e t s o c i t r o C e n o d t o N - i n n i t h c t i p - h g i H h   5 f o e g a s o d t s r i F M / 2 3 n a w i a T e l b i s r e v e R ] 3 0 1 [ . l a t e   g n e s T a c e n e Z a r t s A e h t - c a v 9 1 - D V O C I e n i c d n a s u t i n n i t y h t a p o e l h c o c 3 3 1 , 7 9 2 , 4 3   : I D M P d e v o r p m I n i l a b a g e r P l a n i m e g i r t f o I R M - l l e w s , s s e n b m u N e s o d t s r fi h   3 h c e T N o i B - r e z fi P F / 2 5 e r o p a g n i S d n a l a n i m e g i r T . l a t e   u l a h m i s a r a N ) n a r e m a n i z o t ( n o i t a n i c c a v - u c i d a r l a c i v r e c s i t i l ] 4 0 1 [ 1 3 28 Neurological Sciences (2022) 43:3–40 s s o l y r o s n e s d e w o h s F S C - o t y c o n i m u b l a - a i c o s s i d c i g o l n o i t a i g e l p i d l a i c a f c i x e fl e r A d n a s i s e r a p i r d a u q d e w o h s F S C - o t y c o n i m u b l a - a i c o s s i d c i g o l n o i t - s u m g n i d n e c s a s s e n k a e w e l c - r e t a l i b c i x e fl e r a r e w o l e h t n i y l l a s b m i l e v i s s e r g o r p , l a c i r t e m m y S r e w o l l a r e t a l i b d n a s e i t i m e r t x e e h s , 6 y a d y b r e g n o l o n d l u o c / g m   2 6 1 n i e t o r p e s o c u l g d n a L d a = F S C k l a w ) L d / g m   9 4 ( - t a l i b a i g a h p s y d d n a l a t n o r f l a r e e h c a d a e h l a h c u n b m i l r e w o l s s e n k a e w s t o o r e v r e n n i l a n i u q e a d u a c l a t s i d h t i w s i s e r e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a r e d r o s i d e v r e n l a r e h p i r e p e t u c a n a d e p o l e v e d o h w , s t n e i t a p d e t r o p e r f o y r a m m u S d e v o r p m I - u b o l g o n u m m i V I f o t n e m e c n a h n e - a p a r a p c i x e fl e r A s k e e w   2 h c e T N o i B - r e z fi P F / 2 8 A S U é r r a B - n i a l l i u G . l a   t e d e e h a W l a c i g o l o r u e N n o i t a c i l p m o c 7 e l b a T e c n e r e f e R e m o r d n y s ] 0 1 1 [ n i l a n i u q e a d u a c s t o o r e v r e n d e v o r p m I - u b o l g o n u m m i V I f o t n e m e c n a h n E , a i g e l p o m l a h t h p O s k e e w   2 & n o s n h o J F / 0 6 A S U é r r a B - n i a l l i u G a z o L z e u q r á M e m o r d n y s ] 1 1 1 [ . l a   t e n i l u b o l g o n u m m i t n e m e c n a h n e t o o r e v r e n d e v o r p m I s u o n e v a r t n I a n i u q e a d u a C s k e e w   2 9 1 - D V O C I M / 7 3 K U é r r a B - n i a l l i u G ] 2 1 1 [ . l a   t e l e t a P e m o r d n y s d e v o r p m I G V I I e n o N l a r e t a l i b e t u c A d n o c e S s y a d   0 2 h c e T N o i B - r e z fi P M / 3 7 r a t a Q é r r a B - n i a l l i u G ] 3 1 1 [ . l a   t e k o z a R e s o d - c a v 9 1 - D V O C I e m o r d n y s d e v o r p m I s u o n e v a r t n I e n o N r e h n i s s e n k a e W y a d   1 h c e T N o i B - r e z fi P F 3 / 6 8 S U é r r a B - n i a l l i u G . l a   t e r o b e b g O n i l u b o l g o n u m m i - c a v 9 1 - D V O C I e m o r d n y s ] 4 1 1 [ A N R r e g n e s s e m A 9 1 - D V O C I - c a v ) A N R m ( e n i c . 6 2 d , n o s n h o J t n a n i b m o c e r a , S . 2 V O C - o r e s s u r i v o n e d a ) 6 2 d A ( 6 2 e p y t e n i c c a v r o t c e v - c a v 1 x O d A h C - i v o n e d a e n i c d e r o t c e v - s u r d r o f x O e n i c c a v a c e n e Z a r t s A e n i c e n i c n i l u b o l g o n u m m i - c a v 9 1 - D V O C I e n i c é r r a B - n i a l l i u G e m o r d n y s d e v o r p m I s u o n e v a r t n I e n o N d n a   a i s e h t s e r a P s y a d   8 d e s a b - r o t c e v A M / 2 3 a i r t s u A g n i t a b r e c a x E ] 5 1 1 [   r e r e t s n i F 1 3 Neurological Sciences (2022) 43:3–40 29 d n u o b d e b l l i t s x i s n i l u b o l g o n u m m i d n a n i a r b I R M e s o d t s r fi e h t t s e R d e r e v o c e r e n O s u o n e v a r t n I , s t n e i t a p o w t n I s t n e i t a p l l A f o s k e e w   2 n i h t i W e r e w e n i p s l a m r o n n o i t a n i c c a v e n i c c a v d e s a b - r o t c e v o n e d a / S - 1 x O d A h C 9 1 - V o C n e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C a i d n I é r r a B - n i a l l i u G t e   m o t a m m a r a M e m o r d n y s t r o p e R ] 6 1 1 [ . l a s e s a c 7 f o l a c i g o l o r u e N n o i t a c i l p m o c ) d e u n i t n o c ( 7 e l b a T e c n e r e f e R , s d i o r e t s l a r o , n i l t n e m t a e r t o n r o - u b o l g o n u m m i n i l u b o l g o n u m m i l a c i n a h c e m d n a n o i t a l i t n e v n i l u b o l g o n u m m i d e w o h s t s a r t n o c f o t n e m e c n a h n e e v r e n l a i c a f e h t t h g i r e h t n i h t i w y r o t i d u a l a n r e t n i l a n a c 2 a i g e l p i r d a u q d e r i u q e r s e s a c l a c i n a h c e m l l A n o i t a l i t n e v d a h s e s a c 7 l a i c a f l a r e t a l i b r u o F s i s e r a p ) % 7 5 ( s t n e i t a p d e p o l e v e d o s l a l a i n a r c r e h t o s e i h t a p o r u e n ) h t 5 d n a h t 4 ( d e s s e r g o r p c i x e fl e r a o t - u b l a - o t y C 1 n i - a i c o s s i d c i n i m s i s e r a p i r d a u q l l a n i n o i t h t i w s i s e r a p i r y s l a p r a b l u b - i l e y m e d - V C N n r e t t a p g n i t a n h t i w s i s e r a p i r a i g e l p i d l a i c a f - t a n i l e y m e d - V C N n r e t t a p g n i d e v o r p m i l l A s u o n e v a r t n I n i a r b e h t f o I R M s s e n k a e w l a i c a F s k e e w   3 n i h t i W - n e Z a r t s A - d r o f x O s e l a m l l a 7 5 – 0 2 K U é r r a B - n i a l l i u G ] 7 1 1 [ . l a   t e n e l l A e l o h w d n a h t i w e n i p s - e l p i d l a i c a f 1 n i c i x e fl e r a 3 n i a i g 2 V o C - S R A S a c e e n i c c a v - i r a v e m o r d n y s 4 f o t r o p e R t n a s e s a c d e v o r p m I s u o n e v a r t n I e n o N - d a u q c i x e fl e r A s y a d   6 , d l e i h s i v o C M / 1 7 a i d n I é r r a B - n i a l l i u G ] 8 1 1 [ . l a   t e i l h o K d e v o r p m I s u o n e v a r t n I l a m r o N - d a u q c i x e fl e r A s y a d   5 1 f o e s o d t s r fi e h T M / 7 6 K U é r r a B - n i a l l i u G ] 9 1 1 [ . l a   t e m a z A , a c e n e Z a r t s A f o y t i s r e v i n U d r o f x O a c e n e Z a r t s A e h t I 9 1 - D V O C e m o r d n y s e m o r d n y s 1 3 30 Neurological Sciences (2022) 43:3–40 e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C U C I e h t n i n i l u b o l g o n u m m i s n i a m e r t n e i t a p e h T s u o n e v a r t n I l a m r o N f o s s e n k a e W F / 2 6 K U é r r a B - n i a l l i u G ] 0 2 1 [ . l a t e   n a s a H l a c i g o l o r u e N n o i t a c i l p m o c e m o r d n y s ) d e u n i t n o c ( 7 e l b a T e c n e r e f e R r e w o l l a r e t a l i b d e d e c e r p s b m i l a i s e h t s e r a p y b s s e n b m u n d n a e p y t - d i c c a fl a - i l e y m e d - V C N n r e t t a p g n i t a n - n i m u b l a - F S C a i g e l p a r a p l a c i g o l o t y c n o i t a i c o s s i d h t i w s i s e r a p i r a i g e l p i d l a i c a f - i l e y m e d - V C N n r e t t a p g n i t a n n i n r e t t a p g n i t a n - i l e y m e d - V C N s t n e i t a p 4 h t i w s i s e r a p i r a i g e l p i d l a i c a f - 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u d a r g t e e f e h t g n i d a e r p s y l l a s e v l a c e h t o t y l l a m i n i m d n a s d n a h e h t o t n i y s p o i b e v r e N ( l l a m s d e v o r p - a p o r u e n r e b fi ) y h t - I D V O C d r o f x O t s r i F e n i c c a v 9 1 , a c e n e Z a r t s A f o y t i s r e v i n U e s o d d n o c e S ( e n i c c a v ) A N R m ( A N R r e g n e s s e m A 9 1 - D V O C I ) e s o d n i l u b o l g o n u m m i - i n d e r p l a r o d n a e n o l o s e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C n o i t a n i c c a v d e v o r p m I s u o n e v a r t n I l a m r o N a i g e l p i d l a i c a F s y a d   0 1 a i r v e z x a V M / 8 4 a t l a M é r r a B - n i a l l i u G d n a n a e K c M l a c i g o l o r u e N n o i t a c i l p m o c ) d e u n i t n o c ( 7 e l b a T e c n e r e f e R e m o r d n y s ] 5 2 1 [ p o c r i h C t n e m e v o r p m i c i t a m o t p m y S n i t n e p a b a G e n o N g n i n r u b e s n e t n I t e s n o e t u c a b u S h c e T N o i B - r e z fi P F / 7 5 A S U - u e n r e b fi l l a m S . l a   t e d e e h a W K U é r r a B - n i a l l i u G . l a   t e o i c a f i n o B e m o r d n y s t r o p e r a ( ] 6 2 1 [ ) s e s a c 5 f o y h t a p o r ] 7 2 1 [ 1 3 32 Neurological Sciences (2022) 43:3–40 e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C e p y t e n i c c a V x e s / e g A y r t n u o C - i l p m o c l a c i g o l o r u e N n o i t a r u D - c a v r e t f a n o i t a n i c 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v r e t f a y h p o r t o y m a c i g l a r u e n d e p o l e v e d o h w , s t n e i t a p d e t r o p e r f o y r a m m u S n o i t a c 8 e l b a T e c n e r e f e R d e v o r p m I s d i o r e t s o c i t r o C l a m r o N e r e v e s f o t e s n o n e d d u S s y a d   7 2 b 2 6 1 T N B 9 1 - D V O C I M / 0 5 A S U r e n r u T - e g a n o s r a P ] 8 2 1 [ . l a   t e n a j a h a M n o i t a n i c c a v e m o r d n y s s e g n a h c e v i t a r e n e g e d l a n i m a r o f t u o h t i w d l i m d e w o h s y h p a r - g o m o t d e t u p m o c g n i w o r r a n t f e l d l i m a d e l a e v e r - i d n e t l a i m o r c a b u s y h t a p o n y g o l o i s y h p o r t c e l E l a i h c a r b d e t s e g g u s y h t a p o x e l p e s o d t s r fi r e t f a   n i a p e h t r e t f a k e e w e n O r a l u p a c s i r e p t f e l d e p o l e v e d t n e i t a p d n a p i r g d n a h t f e l e h t , e s o d d n o c e s n o i s n e t x e t s i r w t f e l - o r t c e l E . s s e n k a e w d e w o h s y h p a r g o y m t i n u r o t o m d e s a e r c e d t n e m t i u r c e r , s s e n k a e w m r a t f e l - r a p d n a , s s e n b m u n s a i s e h t s e d e v o r p m I e n o s i n d e r p e s o d - h g i H e n i p s l a c i v r e C s s e l n i a p t e s n o - w e N s y a d   9 h c e T N o i B - r e z fi P F / 5 3 A S U c i h t a p o i d i s s e l n i a P . l a   t e a r r a g e S - z a i D e n i c c a v 9 1 - D V O C I - o r t o y m a c i g l a r u e n y h p ] 9 2 1 [ d e v o r p m I e n o l o s i n d e r p l y h t e M r e d l u o h s e h t f o I R M n i a p m r a d n a r e d l u o h S s y a d   4 - n e Z a r t s A ( a i r v e z x a V M / 8 3 n i a p S r e n r u T - e g a n o s r a P - i r u B o p s e r C o i n o t n A ) a c e e m o r d n y s ] 0 3 1 [ . l a   t e o l l 1 3 Neurological Sciences (2022) 43:3–40 33 t f e l e h t n o h s a r s u o t - a m e h t y r e d n a r a l k c a b r e p p u h s a r l a m o t a m r e d - n i a p , s u o t a m e h t y r E c i t i r u r p d n a , l u f t s e h c n o s n o i s e l s e s a e s i d c i t a m u e h r y r o t a m m a fl n i n i s u c i m l a h t h p o r e t s o z s e p r e H s e p r e h l a c n u r T e n o s r e h t o n i r e t s o z - a m e h t y r e n a n o p u - y p u c c o e s a b s u o t s i h n o a e r a n a g n i s n o i s e l r a l u c i s e v y r a m m a m t h g i r k c a b d n a n o i g e r o t g n i d n o p s e r r o c s e m o t a m r e d 5 T – 3 T n i e l c i s e v d n a s e l u n r e t t a p l a m o t a m r e d n i e l c i s e v d n a s e l u n r e t t a p l a m o t a m r e d e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C - 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z e u g í r d o R t r o p e r A   ] 5 3 1 [ . l a   t e s e s a c 5 f o ) r e z fi P ( e n i c c a v - I D V O C d e t a v i t c a n I e n i c c a v 9 1 M / 8 7 y e k r u T r e t s o z s e p r e H - i c i l a Y d n a n a t s o B ] 7 3 1 [ n a g a m A r A N A N e n o d t o N e n u m m i o t u a d a h l l A s y a d   4 1 - 3 A N R m 2 b 2 6 1 T N B s e l a m e f l l A 1 6 – 6 3 l e a r s I r e t s o z s e p r e H a (   ] 8 3 1 [ . l a   t e r e r u F n o i t a n i c c a v ) s e s a c 6 f o t r o p e r d e v o r p m I - r a p r i v o l c y c a l a V e n o d t o N d e d a e h n i p e l p i t l u m s y a d   5 d e t a v i t c a n i e h T M / 8 6 y e k r u T r e t s o z s e p r e H k r ü t z Ö d n a u s k A l o m a t e c a e n i c c a v 9 1 - D V O C I ] 9 3 1 [ . l a   t e d e v o r p m i l l A r i v o l c y c a l a r O e n o d t o N - p a p s u o t a m e h t y r E s y a d   2 s y a d   7 s y a d   2 2 b 2 6 1 T N B - r e z fi P M / 2 4 M / 6 4 M / 1 7 n a w i a T r e t s o z s e p r e H a (   ] 0 4 1 [ . l a   t e u i h C d e v o r p m i l l A r i v o l c y c a l a V e n o d t o N - p a p s u o t a m e h t y r E s y a d   6 – 3 ™ y t a n r i m o C s ’ r e z fi P A N l a g u t r o P r e t s o z s e p r e H e p i l i F d n a o ã h l a p l A ) s e s a c 3 f o t r o p e r ) s e s a c 4 f o t r o p e r a (   ] 1 4 1 [ . l a   t e e l b a l i a v a t o N e l b a l i a v a t o N e n o d t o N h s a r l a m o t a m r e d A s y a d   3 - d o M ( 3 7 2 1 - A N R m M / 1 8 A S U r e t s o z s e p r e H ] 2 4 1 [ . l a   t e a n n a h C - d o M d n a A N R m 3 7 2 1 - A N R m a n r e - n e Z a r t s A e n i c c a v ™ a i r v e z x a V a c e e n i c c a v 9 1 - d i v o C ) a n r e e n i c c a v 1 3 34 Neurological Sciences (2022) 43:3–40 e l c s u m l a n o i s e l i r e p h t i w e l c s u m k e e w e n O a m e d e d e w o h s T C , r e t a l g n i t a u n e t t a o p y h a - d o n r a l u c s u m a r t n i l a n r e t n i h t i w e l u s n o i t a c fi i c l a c - a m e d e s a w e l c s u m d i o t l e d e h t r e v o t s a r t n o c n O . s u o t , g n i d r a u g , e l c s u m d e t i b i h x e e l c s u m , t n e m e c n a h n e t n e m e c n a h n e m r a d n a r e d l u o h s e h t f o n o i t c u d b a d e s a e r c e d d n a - m a fl n i g n i t a c i d n i d e t a v e l e h t i w g n o l a n o i t a m K P C i i h c a r b e h t f o s r e b fi s s a m e l b a p l a p l a m i x o r p e h t n d n a s s e n e r o s , n i a p , a i r u t a m e h k n a r f K C a i g l a y m d n a f o n o i t a r t n e c n o c / d n a L U 0 0 0 , 5 0 1 r e v i l d e g n a r e d T L A ( s t s e t n o i t c n u f T S A d n a L U 0 0 3 / / ) L U 6 9 4 1 d n a , a e s u a n , s e h c a d e t a v e l e g n i t i m o v K C h g i h t l a r e t a l t f e l s i h o t n o i t a i d a r h t i w ) K P C ( e s a n i k o h p - s o h p e n i n i t a e r C n a h t e r o m l e v e l / L U 0 0 0 , 2 2 d e v o r p m I - a r t n i s u o u n i t n o C e s o r t x e d s u o n e v h g i h a d n a % 0 1 t e i d e t a r d y h o b r a c e m o c t u O t n e m t a e r T g n i g a m i o r u e N s e r u t a e f l a c i n i l C - c a v r e t f a n o i t a r u D e p y t e n i c c a V x e s / e g A y r t n u o C - i l p m o c l a c i g o l o r u e N n o i t a n i c n o i t a c 2 - V o C - S R A S t s n i a g a n o i t a n i c c a v g n i w o l l o f r e d r o s i d r a l u c s u m e t u c a n a d e p o l e v e d o h w , s t n e i t a p d e t r o p e r f o y r a m m u S 0 1 e l b a T e c n e r e f e R e n o N , g n i t i m o v , r e v e F , h t a e r b f o s s e n t r o h s a c e n e Z a r t s A h   5 e n i c c a v 9 1 - D V O C I M / 7 2 K U s i s y l o y m o d b a h R ] 3 4 1 [ . l a   t e n a T h t i w t n e i t a p a n i - i m l a p e n i t i n r a C I I e s a r e f s n a r t l y o t y c n e i c fi e d d e v o r p m I s d i u fl V I e n o N y d o b d e z i l a r e n e G s y a d   2 f o e s o d d n o c e S M / 0 8 A S U s i s y l o y m o d b a h R ] 4 4 1 [ . l a   t e k c a M d e v o r p m I s d i u fl V I l a m r o N n i a p k c a b e r e v e S y a d   1 - N o i B / r e z fi P t s r i F M / 1 2 A S U s i s y l o y m o d b a h R ] 5 4 1 [ . l a   t e r a s s a N - I D V O C a n r e d o M e n i c c a v 9 1 I 9 1 - D V O C h c e T e n i c c a v d e v o r p m I c i t a m o t p m y S d i o t l e d e h t , I R M n O s s e n r e d n e t s a w e r e h T d n o c e s r e t f a s y a d   8 A N R m d e fi i d o M F / 6 5 e c e e r G s i t i s o y M . l a   t e u o r o d o e h T e s o d e n i c c a v 9 1 - D V O C I ] 6 4 1 [ d e v o r p m I I s D A S N e l u d o n r a l u c s u m a r t n I m r a r e p p u t h g i R s h t n o m   3 M / 1 5 l i z a r B s n a c fi i s s o s i t i s o y M ] 7 4 1 [ . l a   t e y o d o G 1 3 Neurological Sciences (2022) 43:3–40 35 Post-vaccination Guillain-Barré syndrome generally affects older adults within 2 weeks of vaccine administra- tion. Clinical presentation is similar to acute demyelinating neuropathy; nerve conduction studies show demyelinating pattern, and CSF examination shows cyto-albuminic dis- sociation. Many patients present only with facial diplegia. Response to immunotherapy is generally good. (Table 7) [110–126]. Proposed pathogenesis of Guillain-Barré syndrome is an autoantibody-mediated immunological damage of peripheral nerves via mechanism of molecular mimicry between struc- tural components of peripheral nerves and the microorgan- ism. Lately, several cases of Guillain-Barré syndrome fol- lowing COVID-19 vaccination have also been reported. Small fiber neuropathy Myositis and rhabdomyolysis There are reports, which have indicated that COVID-19 vaccines have potential to damage the skeletal muscles as well (Table 10) [143–147]. Tan and colleagues described a patient with a known carnitine palmitoyltransferase-II defi- ciency disorder, who developed fever, vomiting, shortness of breath, frank haematuria, myalgia and muscle weak- ness within four hours of receiving AstraZeneca COVID- 19 vaccine [143]. Theodorou and colleagues described a 56-year-old woman who, 8 days after a second dose of vaccine administration, developed severe left upper arm pain along restricted shoulder movements. Her serum cre- atine kinase was elevated suggesting skeletal muscle dam- age. MRI revealed severely edematous deltoid muscles. Contrast-enhanced imaging demonstrated enhancement of deltoid muscles suggestive of myositis [146]. Waheed et al. described a 57-year-old female, who presented with painful neuropathy following administration of the mRNA COVID-19 vaccine. Patient subacutely presented with intense peripheral burning sensations. Electrodiag- nostic studies were normal. Skin biopsy proved small fiber neuropathy. Patient responded to gabapentin.(Table 7) [127]. Conclusion Parsonage‑Turner syndrome Parsonage-Turner syndrome or neuralgic amyotrophy is clinically manifested with acute unilateral shoulder pain fol- lowed by brachial plexopathy. Parsonage-Turner syndrome is usually triggered by any infection, surgery, or rarely vac- cination. In many reports, Parsonage-Turner syndrome has been described following COVID-19 vaccination.(Table 8) [128–130]. Herpes zoster Herpes zoster occurs following reactivation of varicella zos- ter virus. Patients with herpes zoster present with the classic maculopapular rash, which is unilateral, confined to a single dermatome. The rash disappears in 7 to 10 days. Posther- petic neuralgia is the frequent complication of herpes zoster, which is noted in 1 in 5 patients. McMahon and co-workers recorded 414 cutaneous reactions to mRNA COVID-19 vac- cines, and 5 (1.9%) were diagnosed with herpes zoster [131]. Other types of COVID-19 vaccines are infrequently associ- ated with post-vaccination reactivation of herpes zoster. It has been suggested that vaccine-induced immunomodula- tion, resulting in dysregulation of T cell function, is respon- sible for reactivation of herpes zoster virus [132,  133]. Reports of herpes zoster reactivation after vaccine against SARS-CoV-2 are summarized in Table 9 [134–142]. Post-authorization, a wide spectrum of serious neurologi- cal complications has been reported following COVID- 19 vaccination. The most devastating neurological com- plication is cerebral venous sinus thrombosis that has been reported in females of childbearing age following adenovector-based vaccines. Another major neurological complication of concern is Bell’s palsy that was reported dominantly following mRNA vaccine administration. Transverse myelitis, acute disseminated encephalomyeli- tis, and Guillain-Barré syndrome are other severe unex- pected post-vaccination complications that can occur as result of molecular mimicry and subsequent neuronal dam- age. Most of other serious neurological complications are reported in either in form of isolated case reports or small cases series. A causal association of these adverse events is controversial; large collaborative prospective studies are needed to prove causality. Declarations Ethical approval None References Conflict of interest The authors declare no competing interests. 1. World Health Organization. 12 January 2021. WHO Coronavi- rus (COVID-19) Dashboard. &It; The World Health Organiza- tion https:// covid 19. who. int/. Accessed 1 Aug 2021. 1 3 36 Neurological Sciences (2022) 43:3–40 2. Jeff Craven. 10 June 2021. COVID-19 vaccine tracker. &It; https:// www. raps. org/ news- and- artic les/ news- artic les/ 2020/3/ covid- 19- vacci ne- track er. 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