Biomedical reports · 2025
Расследование случайной или причинно-следственной связи церебрального венозного тромбоза и миэлина олигодендроцита гликопротеина противомоскитного заболевания: доклад о деле и обзор литературы.
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Marsico Oreste, Pascarella Angelo, Cutellè Roberta, Tedeschi Denise, Bulgari Alessandro, Ferlazzo Edoardo, Aguglia Umberto, Gasparini Sara
Аннотация
Myelin oligodendrocyte glycoprotein-сопутствующая антителу болезнь (MOGAD) — синдром демиелинирования центральной нервной системы (DS), обычно содержащий оптический неуриит или миелит. Связь между церебральным венозным тромбозом (CVT) и демиелинизирующими заболеваниями, включая множественный склероз (MS), является редкой. В настоящем исследовании 37-летний мужчина столкнулся с сенсорными нарушениями нижних конечностей и недержанием мочевого мозга в соответствии с миелитом. Диагностика MOGAD была подтверждена результатами наблюдений спинного магнитного резонанса и сывороткой антиМОГ с помощью клеточного анализа. Пациент успешно отреагировал на внутривенную кортикостероидную терапию. Однако вскоре после выздоровления у пациента возникла устойчивая головная боль, и у него был эпилептический приступ, который позже был приписан к CVT. Пациент был вылечен гепарином с низким молекулярным весом и лакосамидом, а затем вернулся к базовому состоянию здоровья без приступов в следующем году. Всеобъемлющий обзор литературы по КАПП, связанной с ОВ, включая 15 тематических докладов, две тематические серии и два исследования, подчеркивает редкость этого условия. Большинство зарегистрированных случаев CVT связаны с MS, а лишь три случая CVT, связанные с MOGAD, были зарегистрированы на сегодняшний день. В некоторых случаях имели место дополнительные факторы риска, такие, как прокол поясничной части и высокодозированная кортикостероидная терапия. Учитывая их общую провокационную основу, тромботически-воспалительный патогенный механизм, действующий между DS и CVT у предрасположенных людей, правдоподобен. Однако точная патогенная связь между этими условиями остается в значительной степени неясной, и нельзя исключать совпадений. Роль антиМОГ в этом редком состоянии также требует дальнейшего изучения.
Оригинал публикации
Investigation into the casual or causal association of cerebral venous thrombosis and myelin oligodendrocyte glycoprotein antibody‑associated disease: A case report and literature review.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a central nervous system demyelinating syndrome (DS) typically presenting with optic neuritis or myelitis. The association between cerebral venous thrombosis (CVT) and demyelinating diseases, including multiple sclerosis (MS), is rare. In the present study, a 37-year-old man presented with sensory disturbances in the lower limbs and urinary incontinence, consistent with myelitis. The diagnosis of MOGAD was confirmed by spinal magnetic resonance imaging findings and serum anti-MOG antibody positivity using a cell-based assay. The patient responded successfully to intravenous corticosteroid therapy. However, shortly after recovery, the patient developed a persistent headache and suffered an epileptic seizure, which was later attributed to CVT. The patient was treated with low molecular weight heparin and lacosamide and subsequently returned to baseline health status without seizure recurrence in the following year. Comprehensive review of the literature on CVT associated with DS, encompassing 15 case reports, two case series and two studies, underscores the rarity of this condition. Most reported cases of CVT have been linked to MS, while only three cases of CVT associated with MOGAD have been documented to date. Additional risk factors, such as lumbar puncture and high-dose corticosteroid treatment, have been implicated in some instances. Given their shared inflammatory basis, a thrombotic-inflammatory pathogenic mechanism acting between DS and CVT in predisposed individuals is plausible. However, the exact pathogenic association between these conditions remains largely unclear, and a coincidental association cannot be ruled out. The role of anti-MOG antibodies in this rare condition also warrants further investigation.
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Introduction
Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a rare autoimmune inflammatory demyelinating disorder, distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4)-seropositive neuromyelitis optica spectrum disorder (NMOSD). MOGAD can affect individuals of any age, with the highest incidence in children, and an equal distribution between males and females ( 1 ). The incidence of MOGAD ranges from 1.6 to 3.4 cases per million individuals per year, with an estimated prevalence of 20 cases per million ( 2 ). Clinical manifestations are diverse and include optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and encephalitis predominantly involving the cortex, brainstem and cerebellum ( 2 ). Approximately one-half of the patients experience a monophasic disease course, but relapses are also possible. Serum immunoglobulin G (IgG) antibodies against MOG, a protein expressed on the surface of central nervous system (CNS) myelin sheaths, are considered the hallmark of the disease. A prodromal infectious disease is considered to trigger an autoimmune response against the CNS through mechanisms such as molecular mimicry or epitope spreading ( 1 ). The gold-standard treatment of acute phase attacks is based on high-dose glucοcοrtiсοiԁѕ. Plasma exchange or intravenous immune globulin are suggested for refractory cases or incomplete responses. Immunosuppressive therapy is typically reserved for patients with relapsing disease ( 3 ). Autoimmune diseases are recognized as a risk factor for cerebral venous thrombosis (CVT), which is an uncommon cause of stroke ( 4 , 5 ). To date, few cases of CVT have been reported in the context of MS ( 6 ), and only three cases in association with MOGAD ( 6 , 7 ). The present study reports a case of CVT occurring in an adult with MOGAD.
Case report
A healthy, 37-year-old man who was a non-smoker presented to the Neurology Unit of ‘Bianchi-Melacrino-Morelli’ Hospital (Reggio Calabria, Italy) with a 2-week history of asthenia, gait difficulties, numbness of the lower limbs and urinary urgency. There was no history of recent vaccination, fever or systemic infections. Neurological examination revealed sensory ataxia, brisk tendon reflexes in all four limbs and hypoesthesia extending from the thoracic region (corresponding to the C5 sensory level) to the lower limbs. An urgent spinal magnetic resonance imaging (MRI) scan ( Fig. 1 ) showed a T2- and short-TI inversion recovery-hyperintense, continuous cord lesion from C2 to T1, without contrast enhancement (CE), consistent with longitudinally extensive myelitis (LETM). Additional multiple smaller dorsal cord hyperintensities showed CE, whereas brain and orbital MRI findings were normal. Blood tests revealed mild neutrophilic leukocytosis. A broad infectious and autoimmune work-up, including a COVID-19 test and antinuclear antibodies, was unremarkable. Cerebrospinal fluid (CSF) analysis of a specimen from a lumbar puncture (LP) revealed elevated protein levels (100 mg/dl; normal value, <43 mg/dl), with normal leukocyte count, CSF/serum albumin ratio and glucose levels. The CSF-Film Array assay was performed by the Department of Pathology of ‘Bianchi-Melacrino-Morelli’ Hospital and was negative for common infectious agents. No intrathecal-restricted synthesis of IgG oligoclonal bands was detected in the CSF. Serum anti-MOG antibodies, tested by the Department of Pathology of ‘Bianchi-Melacrino-Morelli’ Hospital using a fixed cell-based assay, were positive at a titer of 1:100, whereas antibodies against AQP4 in both CSF and serum were absent.
Spine magnetic resonance imaging. Hyperintense cervical cord lesions (arrows) in short-TI inversion recovery sagittal sequences.
A diagnosis of MOGAD was made according to the International MOGAD Panel criteria ( 1 ), based on a core clinical demyelinating event (myelitis) with supporting MRI features of LETM, positive MOG-IgG antibodies and seronegative AQP4-IgG, after excluding alternative diagnoses. The patient underwent high-dose intravenous methylprednisolone therapy (1,000 mg per day for 5 days), followed by oral prednisone (50 mg daily). The patient fully recovered and was discharged after 10 days with a prescribed tapering of prednisone over 1 month. However, at 3 days post-discharge, the patient returned to the Emergency Department of ‘Bianchi-Melacrino-Morelli’ Hospital due to a focal to bilateral epileptic seizure, preceded by 2 days of continuous right frontotemporal headaches. Neurological examination revealed mild left hemiparesis and drowsiness, with a National Institutes of Health Stroke Scale (NIHSS) score of 4( 7 ). An urgent brain computed tomography scan showed a right cortical parietal hypodense lesion. Brain MRI revealed a fluid-attenuated inversion recovery-hyperintense right frontoparietal lesion, and an MRI angiogram showed absence of flow in the right superficial cortical veins and superior sagittal sinus, confirming CVT ( Fig. 2 ).
Brain MRI and MR venography findings. MRI (A) axial and (B) coronal sequences showing right parietal fluid-attenuated inversion recovery hyperintensity involving postcentral and precentral gyri (arrowhead). MR venography displaying superior sagittal sinus stenosis (arrows) in (C) axial and (D) coronal views. MR, magnetic resonance; MRI, MR imaging.
Blood work-up for thrombophilia, including antinuclear antibodies, factor V Leiden and prothrombin mutation, and deficiencies in antithrombin, protein C and protein S, was unremarkable. Tests for COVID-19 and serum autoantibodies associated with antiphospholipid syndrome, systemic lupus erythematosus and Behçet's disease were also negative. Paroxysmal nocturnal hemoglobinuria was excluded. The patient was treated with subcutaneous low molecular weight heparin (4,000 IU, subcutaneously, twice daily) for 10 days and lacosamide (200 mg per day for 3 months) to prevent seizure recurrence. The patient achieved a complete recovery within 30 days and was discharged with 50 mg/day prednisone, which was slowly tapered and discontinued after 3 months. The patient's clinical condition remained stable over the following year, with unchanged MRI results at the 6- and 12-month follow-ups.
Discussion
The present report describes the rare co-occurrence of CVT in a patient diagnosed with MOGAD. The patient developed CVT in the context of an acute MOGAD attack shortly after undergoing a LP and receiving intravenous corticosteroids. Although the coincidental coexistence of MOGAD and CVT in the same patient should be considered, exploring the possible association is of interest due to the inflammatory nature of both conditions. The association between CVT and demyelinating syndromes (DS) has been infrequently reported in the literature.
A review of the literature was performed using the terms ‘MOGAD’ OR ‘Myelin oligodendrocyte glycoprotein-associated disease’ OR ‘Multiple Sclerosis’ OR ‘MS’ OR ‘anti-MOG’ OR ‘neuromyelitis optica spectrum disorder’ OR ‘NMOSD’ OR ‘demyelinating disorder’, in various combinations with ‘cerebral venous thrombosis’ OR ‘cerebral venous sinus thrombosis’, in PubMed ( https://pubmed.ncbi.nlm.nih.gov/ ) and Google Scholar ( https://scholar.google.com/ ) up to October 2024. Primary studies, case reports and case series were included, and English was the only language selected. A total of 19 studies were identified, nearly all of which were case reports, reporting a total of 31 patients with CVT associated with MS (26 patients), NMOSD (2 patients) or MOGAD (3 patients) ( Table I ) ( 6-25 ). Only 9 patients exhibited the most common risk factors for CVT (oral contraceptives in 8 cases and inherited prothrombotic disorders in 1 case) ( 6 , 10 , 12 , 13 , 18 , 19 , 21 ). In ~84% of cases, procedures such as LP and high-dose corticosteroid administration were reported, highlighting their role as predisposing factors for CVT development ( 6 , 19 , 21 , 12 ).
Table I Review of the literature for reported cerebral venous thrombosis cases in patients with demyelinating disorders. First author, year Study design Patients, n Sex Age, years DS type Risk factors for CVT CVT symptoms CVT outcome (Refs.) Malanga and Gangemi, 1994 Case report 1 F 35 MS Oral contraceptive Seizure Recovery ( 10 ) Al Bunyan and Ogunniyi, 1997 Case report 1 F 32 MS Bed confinement Asymptomatic Recovery ( 11 ) Aidi et al , 1999 Case report 2 F 30, 36 MS Oral contraceptive (n=1), LP (n=2), high-dose i.v. corticosteroid (n=2) Headache, diplopia Recovery ( 12 ) Albucher et al , 1999 Case series 3 2 F, 1 M 28, 45, 38 MS Oral contraceptive (n=1), LP (n=2), high-dose i.v. corticosteroid (n=3) Headache, seizure, focal motor deficit Recovery ( 13 ) Städler et al , 2000 Case report 2 n.a. n.a. MS LP, high-dose i.v. corticosteroid (n=2) n.a. Death (n=1), recovery (n=1) ( 14 ) Gunal et al , 2002 Case report 1 F 39 MS LP, high-dose i.v. corticosteroid Headache, seizures, hemianopia Recovery ( 15 ) Mouraux et al , 2002 Case report 1 F 35 MS LP Headache, seizures, hemiparesis Recovery ( 16 ) Kadayifçilar et al , 2003 Case report 1 F 44 MS Oral contraceptive, high-dose i.v. corticosteroid Headache, hemianopia and hemiparesis n.a. ( 17 ) Stolz et al , 2003 Observational study 6 n.a. n.a. MS (4), NMOSD (2) High-dose i.v. corticosteroid (n=6), LP (n=3) oral contraceptive (n=3), smoking (n=4) Headaches (5), seizures (4), focal motor deficits (3) n.a. ( 18 ) Vandenberghe et al , 2003 Case series 3 2 F, 1 M 40, 23, 49 MS No risk factor (n=2); oral contraceptive (n=2), high-dose i.v. corticosteroid (n=2), LP (n=2) Seizure, headache, focal motor deficit n.a. ( 6 ) Maurelli et al , 2005 Case report 1 F 48 MS LP, high-dose i.v. corticosteroid Headache, tetraparesis, coma, seizure Recovery ( 19 ) Kalanie et al , 2011 Prospective study 2 F 35, 39 MS High-dose i.v. corticosteroid (n=2) n.a. n.a. ( 20 ) Presicci et al , 2013 Case report 1 F 13 MS Thrombocytosis, thrombophilia, LP, high-dose i.v. corticosteroid Headache, seizure Improvement ( 21 ) Gazioglu et al , 2013 Case report 1 F 32 MS High-dose i.v. corticosteroid Headache Recovery ( 22 ) Soto-Insuga et al , 2016 Case report 1 F 6 MOGAD Infection (otitis) Headache, diplopia Recovery ( 8 ) Gasparini et al , 2020 Case report 1 M 40 MS Alemtuzumab Headache Recovery ( 23 ) Fontana et al , 2021 Case report 1 M 11 MOGAD LP, high-dose i.v. corticosteroid Headache, facial tics Recovery ( 9 ) Zhu et al , 2023 Case report 1 F 19 MS High-dose i.v. corticosteroid Headache Improvement ( 24 ) Virupakshaiah et al , 2024 Case report 1 M 35 MOGAD High-dose i.v. corticosteroid Focal motor deficit, speech distur- bance, impaired consciousness Improvement ( 25 ) CVT, cerebral venous thrombosis; DS, demyelinating disorders; LP, lumbar puncture; i.v., intravenous; MOGAD, myelin oligodendrocyte glycoprotein-associated disease; MS, multiple sclerosis; n.a., not available; NMOSD, neuromyelitis optica spectrum disorder.
Review of the literature for reported cerebral venous thrombosis cases in patients with demyelinating disorders.
CVT, cerebral venous thrombosis; DS, demyelinating disorders; LP, lumbar puncture; i.v., intravenous; MOGAD, myelin oligodendrocyte glycoprotein-associated disease; MS, multiple sclerosis; n.a., not available; NMOSD, neuromyelitis optica spectrum disorder.
Dural puncture is a rare but well-known risk factor for CVT. While the exact mechanism remains unclear, it is likely associated with intracranial hypotension, leading to venous dilation, displacement of intracranial vascular structures, stasis and congestion, thereby promoting a thrombotic process ( 12 ). A potential procoagulant effect of high-dose steroids in CVT development has also been suggested. This is primarily attributable to vascular endothelial cell injury and a hypercoagulable state, characterized by increased prothrombotic factors and impaired fibrinolytic activity, similar to what is observed in Cushing's syndrome ( 22 , 24 , 12 ). Accordingly, the administration of high-dose intravenous methylprednisolone and LP might have contributed to CVT development in the present case. However, the occurrence of CVT is reported in only a small percentage of individuals exposed to LP or corticosteroids, suggesting that additional risk factors are likely involved.
Moreover, cases of DS-associated CVT occurring without corticosteroid exposure or other recognized risk factors have been described ( 6 , 23 ). Given the shared inflammatory origin of both conditions, a thrombotic-inflammatory pathogenic mechanism between MOGAD and CVT in susceptible individuals is plausible ( 8 , 24 ). The autoimmune and inflammatory pathways implicated in DS may play a role in CVT pathogenesis ( 5 , 6 , 12 ). The interplay between inflammation, demyelination and coagulation, however, remains poorly understood. The presence of lymphocytic infiltration surrounding veins in DS supports evidence of vascular inflammation ( 6 ). Immune-mediated and inflammatory processes in DS may lead to endothelial dysfunction. Cytokines released during inflammation, such as IL-6( 25 ), could activate the clotting cascade, increasing the likelihood of CVT. Additionally, the severe and often rapid progression of MOGAD could result in brain swelling or lesions that compress adjacent venous sinuses, impairing blood flow and predisposing to thrombosis ( 25 ). Vascular damage, coupled with inflammation-induced hypercoagulability, may contribute to CVT development ( 5 ).
Despite these observations, the pathogenic association between these two conditions remains largely unknown. To date, there is insufficient evidence to confirm that MOGAD leads to CVT, and a fortuitous association cannot be excluded. Although CVT is rare in DS, the present case underscores the importance of closely monitoring patients for new or worsening headaches and the onset of epileptic seizures. Additionally, patients with MOGAD and identified pro-thrombotic conditions may benefit from careful observation and preventive measures, such as adequate hydration, to reduce CVT risk.
Only 1 year of follow-up was performed in the present study, which limits our understanding of long-term health in patients with MOGAD after CVT, as well as the assessment of disease progression and management strategies.
In conclusion, the current study presents a rare case of MOGAD with CVT in an adult patient. To date, the causal association between MOGAD and CVT lacks compelling evidence. Corticosteroid therapy and LP represent potential mediators or confounding factors, but the possible role of anti-MOG antibodies and the inflammatory pathways occurring in DS should be better ascertained in this uncommon condition. Further studies on pathophysiological mechanisms are required to establish whether a direct causal association exists.
Acknowledgements
Not applicable.
Funding Statement
Funding: The study was supported by #NEXTGENERATIONEU and funded by the Ministry of University and Research, National Recovery and Resilience Plan, project MNESYS (project no. PE0000006)-A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553; 11.10.2022).
Availability of data and materials
The data generated in the present study may be requested from the corresponding author.
Authors' contributions
OM and AP were responsible for study concept and design. Data curation, collection, analysis and interpretation was performed by OM, AP, RC, DT, AB and EF. OM, AP and SG drafted the manuscript. UA and SG advised on patient treatment, revised the manuscript critically for important intellectual content and gave the final approval of the version to be published. OM and AP confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
Ethics approval and consent to participate
The study was performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from the patient.
Patient consent for publication
The patient provided written informed consent concerning the publication of the case report and accompanying patient diagnostic images.
Competing interests
The authors declare that they have no competing interests.
References
Associated Data
Data Availability Statement
The data generated in the present study may be requested from the corresponding author.
Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a rare autoimmune inflammatory demyelinating disorder, distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4)-seropositive neuromyelitis optica spectrum disorder (NMOSD). MOGAD can affect individuals of any age, with the highest incidence in children, and an equal distribution between males and females ( 1 ). The incidence of MOGAD ranges from 1.6 to 3.4 cases per million individuals per year, with an estimated prevalence of 20 cases per million ( 2 ). Clinical manifestations are diverse and include optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and encephalitis predominantly involving the cortex, brainstem and cerebellum ( 2 ). Approximately one-half of the patients experience a monophasic disease course, but relapses are also possible. Serum immunoglobulin G (IgG) antibodies against MOG, a protein expressed on the surface of central nervous system (CNS) myelin sheaths, are considered the hallmark of the disease. A prodromal infectious disease is considered to trigger an autoimmune response against the CNS through mechanisms such as molecular mimicry or epitope spreading ( 1 ). The gold-standard treatment of acute phase attacks is based on high-dose glucοcοrtiсοiԁѕ. Plasma exchange or intravenous immune globulin are suggested for refractory cases or incomplete responses. Immunosuppressive therapy is typically reserved for patients with relapsing disease ( 3 ). Autoimmune diseases are recognized as a risk factor for cerebral venous thrombosis (CVT), which is an uncommon cause of stroke ( 4 , 5 ). To date, few cases of CVT have been reported in the context of MS ( 6 ), and only three cases in association with MOGAD ( 6 , 7 ). The present study reports a case of CVT occurring in an adult with MOGAD.
Case report
A healthy, 37-year-old man who was a non-smoker presented to the Neurology Unit of ‘Bianchi-Melacrino-Morelli’ Hospital (Reggio Calabria, Italy) with a 2-week history of asthenia, gait difficulties, numbness of the lower limbs and urinary urgency. There was no history of recent vaccination, fever or systemic infections. Neurological examination revealed sensory ataxia, brisk tendon reflexes in all four limbs and hypoesthesia extending from the thoracic region (corresponding to the C5 sensory level) to the lower limbs. An urgent spinal magnetic resonance imaging (MRI) scan ( Fig. 1 ) showed a T2- and short-TI inversion recovery-hyperintense, continuous cord lesion from C2 to T1, without contrast enhancement (CE), consistent with longitudinally extensive myelitis (LETM). Additional multiple smaller dorsal cord hyperintensities showed CE, whereas brain and orbital MRI findings were normal. Blood tests revealed mild neutrophilic leukocytosis. A broad infectious and autoimmune work-up, including a COVID-19 test and antinuclear antibodies, was unremarkable. Cerebrospinal fluid (CSF) analysis of a specimen from a lumbar puncture (LP) revealed elevated protein levels (100 mg/dl; normal value, <43 mg/dl), with normal leukocyte count, CSF/serum albumin ratio and glucose levels. The CSF-Film Array assay was performed by the Department of Pathology of ‘Bianchi-Melacrino-Morelli’ Hospital and was negative for common infectious agents. No intrathecal-restricted synthesis of IgG oligoclonal bands was detected in the CSF. Serum anti-MOG antibodies, tested by the Department of Pathology of ‘Bianchi-Melacrino-Morelli’ Hospital using a fixed cell-based assay, were positive at a titer of 1:100, whereas antibodies against AQP4 in both CSF and serum were absent.
Spine magnetic resonance imaging. Hyperintense cervical cord lesions (arrows) in short-TI inversion recovery sagittal sequences.
A diagnosis of MOGAD was made according to the International MOGAD Panel criteria ( 1 ), based on a core clinical demyelinating event (myelitis) with supporting MRI features of LETM, positive MOG-IgG antibodies and seronegative AQP4-IgG, after excluding alternative diagnoses. The patient underwent high-dose intravenous methylprednisolone therapy (1,000 mg per day for 5 days), followed by oral prednisone (50 mg daily). The patient fully recovered and was discharged after 10 days with a prescribed tapering of prednisone over 1 month. However, at 3 days post-discharge, the patient returned to the Emergency Department of ‘Bianchi-Melacrino-Morelli’ Hospital due to a focal to bilateral epileptic seizure, preceded by 2 days of continuous right frontotemporal headaches. Neurological examination revealed mild left hemiparesis and drowsiness, with a National Institutes of Health Stroke Scale (NIHSS) score of 4( 7 ). An urgent brain computed tomography scan showed a right cortical parietal hypodense lesion. Brain MRI revealed a fluid-attenuated inversion recovery-hyperintense right frontoparietal lesion, and an MRI angiogram showed absence of flow in the right superficial cortical veins and superior sagittal sinus, confirming CVT ( Fig. 2 ).
Brain MRI and MR venography findings. MRI (A) axial and (B) coronal sequences showing right parietal fluid-attenuated inversion recovery hyperintensity involving postcentral and precentral gyri (arrowhead). MR venography displaying superior sagittal sinus stenosis (arrows) in (C) axial and (D) coronal views. MR, magnetic resonance; MRI, MR imaging.
Blood work-up for thrombophilia, including antinuclear antibodies, factor V Leiden and prothrombin mutation, and deficiencies in antithrombin, protein C and protein S, was unremarkable. Tests for COVID-19 and serum autoantibodies associated with antiphospholipid syndrome, systemic lupus erythematosus and Behçet's disease were also negative. Paroxysmal nocturnal hemoglobinuria was excluded. The patient was treated with subcutaneous low molecular weight heparin (4,000 IU, subcutaneously, twice daily) for 10 days and lacosamide (200 mg per day for 3 months) to prevent seizure recurrence. The patient achieved a complete recovery within 30 days and was discharged with 50 mg/day prednisone, which was slowly tapered and discontinued after 3 months. The patient's clinical condition remained stable over the following year, with unchanged MRI results at the 6- and 12-month follow-ups.
Discussion
The present report describes the rare co-occurrence of CVT in a patient diagnosed with MOGAD. The patient developed CVT in the context of an acute MOGAD attack shortly after undergoing a LP and receiving intravenous corticosteroids. Although the coincidental coexistence of MOGAD and CVT in the same patient should be considered, exploring the possible association is of interest due to the inflammatory nature of both conditions. The association between CVT and demyelinating syndromes (DS) has been infrequently reported in the literature.
A review of the literature was performed using the terms ‘MOGAD’ OR ‘Myelin oligodendrocyte glycoprotein-associated disease’ OR ‘Multiple Sclerosis’ OR ‘MS’ OR ‘anti-MOG’ OR ‘neuromyelitis optica spectrum disorder’ OR ‘NMOSD’ OR ‘demyelinating disorder’, in various combinations with ‘cerebral venous thrombosis’ OR ‘cerebral venous sinus thrombosis’, in PubMed ( https://pubmed.ncbi.nlm.nih.gov/ ) and Google Scholar ( https://scholar.google.com/ ) up to October 2024. Primary studies, case reports and case series were included, and English was the only language selected. A total of 19 studies were identified, nearly all of which were case reports, reporting a total of 31 patients with CVT associated with MS (26 patients), NMOSD (2 patients) or MOGAD (3 patients) ( Table I ) ( 6-25 ). Only 9 patients exhibited the most common risk factors for CVT (oral contraceptives in 8 cases and inherited prothrombotic disorders in 1 case) ( 6 , 10 , 12 , 13 , 18 , 19 , 21 ). In ~84% of cases, procedures such as LP and high-dose corticosteroid administration were reported, highlighting their role as predisposing factors for CVT development ( 6 , 19 , 21 , 12 ).
Table I Review of the literature for reported cerebral venous thrombosis cases in patients with demyelinating disorders. First author, year Study design Patients, n Sex Age, years DS type Risk factors for CVT CVT symptoms CVT outcome (Refs.) Malanga and Gangemi, 1994 Case report 1 F 35 MS Oral contraceptive Seizure Recovery ( 10 ) Al Bunyan and Ogunniyi, 1997 Case report 1 F 32 MS Bed confinement Asymptomatic Recovery ( 11 ) Aidi et al , 1999 Case report 2 F 30, 36 MS Oral contraceptive (n=1), LP (n=2), high-dose i.v. corticosteroid (n=2) Headache, diplopia Recovery ( 12 ) Albucher et al , 1999 Case series 3 2 F, 1 M 28, 45, 38 MS Oral contraceptive (n=1), LP (n=2), high-dose i.v. corticosteroid (n=3) Headache, seizure, focal motor deficit Recovery ( 13 ) Städler et al , 2000 Case report 2 n.a. n.a. MS LP, high-dose i.v. corticosteroid (n=2) n.a. Death (n=1), recovery (n=1) ( 14 ) Gunal et al , 2002 Case report 1 F 39 MS LP, high-dose i.v. corticosteroid Headache, seizures, hemianopia Recovery ( 15 ) Mouraux et al , 2002 Case report 1 F 35 MS LP Headache, seizures, hemiparesis Recovery ( 16 ) Kadayifçilar et al , 2003 Case report 1 F 44 MS Oral contraceptive, high-dose i.v. corticosteroid Headache, hemianopia and hemiparesis n.a. ( 17 ) Stolz et al , 2003 Observational study 6 n.a. n.a. MS (4), NMOSD (2) High-dose i.v. corticosteroid (n=6), LP (n=3) oral contraceptive (n=3), smoking (n=4) Headaches (5), seizures (4), focal motor deficits (3) n.a. ( 18 ) Vandenberghe et al , 2003 Case series 3 2 F, 1 M 40, 23, 49 MS No risk factor (n=2); oral contraceptive (n=2), high-dose i.v. corticosteroid (n=2), LP (n=2) Seizure, headache, focal motor deficit n.a. ( 6 ) Maurelli et al , 2005 Case report 1 F 48 MS LP, high-dose i.v. corticosteroid Headache, tetraparesis, coma, seizure Recovery ( 19 ) Kalanie et al , 2011 Prospective study 2 F 35, 39 MS High-dose i.v. corticosteroid (n=2) n.a. n.a. ( 20 ) Presicci et al , 2013 Case report 1 F 13 MS Thrombocytosis, thrombophilia, LP, high-dose i.v. corticosteroid Headache, seizure Improvement ( 21 ) Gazioglu et al , 2013 Case report 1 F 32 MS High-dose i.v. corticosteroid Headache Recovery ( 22 ) Soto-Insuga et al , 2016 Case report 1 F 6 MOGAD Infection (otitis) Headache, diplopia Recovery ( 8 ) Gasparini et al , 2020 Case report 1 M 40 MS Alemtuzumab Headache Recovery ( 23 ) Fontana et al , 2021 Case report 1 M 11 MOGAD LP, high-dose i.v. corticosteroid Headache, facial tics Recovery ( 9 ) Zhu et al , 2023 Case report 1 F 19 MS High-dose i.v. corticosteroid Headache Improvement ( 24 ) Virupakshaiah et al , 2024 Case report 1 M 35 MOGAD High-dose i.v. corticosteroid Focal motor deficit, speech distur- bance, impaired consciousness Improvement ( 25 ) CVT, cerebral venous thrombosis; DS, demyelinating disorders; LP, lumbar puncture; i.v., intravenous; MOGAD, myelin oligodendrocyte glycoprotein-associated disease; MS, multiple sclerosis; n.a., not available; NMOSD, neuromyelitis optica spectrum disorder.
Review of the literature for reported cerebral venous thrombosis cases in patients with demyelinating disorders.
CVT, cerebral venous thrombosis; DS, demyelinating disorders; LP, lumbar puncture; i.v., intravenous; MOGAD, myelin oligodendrocyte glycoprotein-associated disease; MS, multiple sclerosis; n.a., not available; NMOSD, neuromyelitis optica spectrum disorder.
Dural puncture is a rare but well-known risk factor for CVT. While the exact mechanism remains unclear, it is likely associated with intracranial hypotension, leading to venous dilation, displacement of intracranial vascular structures, stasis and congestion, thereby promoting a thrombotic process ( 12 ). A potential procoagulant effect of high-dose steroids in CVT development has also been suggested. This is primarily attributable to vascular endothelial cell injury and a hypercoagulable state, characterized by increased prothrombotic factors and impaired fibrinolytic activity, similar to what is observed in Cushing's syndrome ( 22 , 24 , 12 ). Accordingly, the administration of high-dose intravenous methylprednisolone and LP might have contributed to CVT development in the present case. However, the occurrence of CVT is reported in only a small percentage of individuals exposed to LP or corticosteroids, suggesting that additional risk factors are likely involved.
Moreover, cases of DS-associated CVT occurring without corticosteroid exposure or other recognized risk factors have been described ( 6 , 23 ). Given the shared inflammatory origin of both conditions, a thrombotic-inflammatory pathogenic mechanism between MOGAD and CVT in susceptible individuals is plausible ( 8 , 24 ). The autoimmune and inflammatory pathways implicated in DS may play a role in CVT pathogenesis ( 5 , 6 , 12 ). The interplay between inflammation, demyelination and coagulation, however, remains poorly understood. The presence of lymphocytic infiltration surrounding veins in DS supports evidence of vascular inflammation ( 6 ). Immune-mediated and inflammatory processes in DS may lead to endothelial dysfunction. Cytokines released during inflammation, such as IL-6( 25 ), could activate the clotting cascade, increasing the likelihood of CVT. Additionally, the severe and often rapid progression of MOGAD could result in brain swelling or lesions that compress adjacent venous sinuses, impairing blood flow and predisposing to thrombosis ( 25 ). Vascular damage, coupled with inflammation-induced hypercoagulability, may contribute to CVT development ( 5 ).
Despite these observations, the pathogenic association between these two conditions remains largely unknown. To date, there is insufficient evidence to confirm that MOGAD leads to CVT, and a fortuitous association cannot be excluded. Although CVT is rare in DS, the present case underscores the importance of closely monitoring patients for new or worsening headaches and the onset of epileptic seizures. Additionally, patients with MOGAD and identified pro-thrombotic conditions may benefit from careful observation and preventive measures, such as adequate hydration, to reduce CVT risk.
Only 1 year of follow-up was performed in the present study, which limits our understanding of long-term health in patients with MOGAD after CVT, as well as the assessment of disease progression and management strategies.
In conclusion, the current study presents a rare case of MOGAD with CVT in an adult patient. To date, the causal association between MOGAD and CVT lacks compelling evidence. Corticosteroid therapy and LP represent potential mediators or confounding factors, but the possible role of anti-MOG antibodies and the inflammatory pathways occurring in DS should be better ascertained in this uncommon condition. Further studies on pathophysiological mechanisms are required to establish whether a direct causal association exists.
Acknowledgements
Not applicable.
Funding Statement
Funding: The study was supported by #NEXTGENERATIONEU and funded by the Ministry of University and Research, National Recovery and Resilience Plan, project MNESYS (project no. PE0000006)-A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553; 11.10.2022).
Availability of data and materials
The data generated in the present study may be requested from the corresponding author.
Authors' contributions
OM and AP were responsible for study concept and design. Data curation, collection, analysis and interpretation was performed by OM, AP, RC, DT, AB and EF. OM, AP and SG drafted the manuscript. UA and SG advised on patient treatment, revised the manuscript critically for important intellectual content and gave the final approval of the version to be published. OM and AP confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
Ethics approval and consent to participate
The study was performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from the patient.
Patient consent for publication
The patient provided written informed consent concerning the publication of the case report and accompanying patient diagnostic images.
Competing interests
The authors declare that they have no competing interests.
References
Associated Data
Data Availability Statement
The data generated in the present study may be requested from the corresponding author.