Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody‐associated disease

Abstract

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4‐NMOSD), and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4‐NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune‐associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4‐NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)‐like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM‐like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4‐NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most‐updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4‐NMOSD/MOGAD. Treatment cautions including drug‐drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

AQP4-independent TRPV4 modulation of plasma membrane water permeability

“…Reduced AQPs expression has been reported under pathological conditions ( Markou et al, 2022 ), including brain edema after stroke or trauma ( Papadopoulos et al, 2002 ; Clément et al, 2020 ; Dadgostar et al, 2022 ), neurological diseases ( Yang et al, 2011 ; Alvestad et al, 2013 ; Li et al, 2022 ), cancer progression and metastasis ( Lan et al, 2022 ), and inflammation. Of note, AQP1 and AQP4 are reported to be downregulated in the choroid plexus and the ependyma, respectively, of spontaneously hypertensive rat, as a putative compensatory mechanism to reduce the cerebrospinal fluid (CSF) production and volume ( Carnero Contentti and Correale, 2021 ; González-Marrero et al, 2022 ).…”

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

“…However, MOG-IgG has recently been associated with cortical encephalitis and seizures [ 20 ]. Seizures can arise in isolation in cases of single-antibody disorders and are also more frequently observed in male patients [ 1 , 21 , 22 ]. It has been reported in some rare cases that anti-NMDAR encephalitis and demyelinating diseases can coexist in the same patient while developing serological markers of autoimmune diseases and demyelinating (MOG abs), while we summarize the cases of seizures present in the course of the MNOS [ 3 , 7 – 16 ] in (see Supplementary file 1 ).…”

“…In addition to this, they found that anti-NMDAR abs seemed to contribute to cortical destruction and seizures in MOG-IgG patients. Specific MRI abnormalities are associated with acute symptomatic seizures in MOGAD [ 22 ], mainly including unilateral/bilateral cortical T2/fluid attenuation inversion recovery (FLAIR) high-signal lesions, leptomeningeal enhancement, etc., with unilateral cortical T2/FLAIR high-signal lesions (FLAMES) being more likely to have seizures. FLAMES has different radiologic manifestations and may show bilateral cortical and meningeal lesions that are different from the common manifestations [ 6 ].…”

New dimension of epilepsy complications: A literature systematic review of visual and retinal disorders

“…This issue was observed in stable seizures, drug-resistant seizures, generalized seizures, focal seizures and multi-focal seizures. The thickness of nerves ending in the retina was reduced and optic neuropathies such as visual, Neuromyelitis Optica Spectrum Disorder (NMOSD) (20) and optic neuritis were affected by seizure attacks (21). Visual acuity and contrast sensitivity are reduced under the in uence of these attacks (22), which deprive individuals of normal vision both in children and adults.…”