Epilepsy and Migraine Shared Genetic and Molecular Mechanisms: Focus on Therapeutic Strategies

Gotra, Palvi; Bhardwaj, Nidhi; Ludhiadch, Abhilash; Singh, Gagandeep; Munshi, Anjana

doi:10.1007/s12035-021-02386-x

Cited by 14 publications

(8 citation statements)

References 58 publications

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“…Some possible hypotheses were suggested for this comorbidity including neuronal excitation/inhibition imbalance (in favor of cortical hyperexcitability) and cortical spreading depression (CSD) in both conditions, shared genetic susceptibility between epilepsy and migraine, neurotransmitter, and ion channel dysfunctions ( 14 , 30 , 31 ). All these hypotheses contribute to the concept of migraine-epilepsy as a continuum, reflecting the two different faces of shared pathophysiology ( 13 , 14 , 30 , 32 ). The possible effects of this frequent comorbidity on the clinical presentation of epilepsy and migraine are still obscure, and studies about the outcomes are limited.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the fact that both migraine and epilepsy are strongly heritable disorders points out the importance of the genetic variants, leading to susceptibility to these disorders ( 6 , 11 – 13 ). Also, the fact that both disorders are often responsive and can be treated with antiseizure medications (ASMs) is another supportive factor of the presence of common underlying mechanisms ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria

et al. 2023

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BackgroundMigraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert.MethodsIn this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis.ResultsLonger headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone.ConclusionLonger headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria

et al. 2023

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“…The abnormally high glutamate tone in synaptic cleft caused by hypo-function NMDA could be offset by reduced evoked exocytosis mediated through P/Q channels to some extent, thus relieving the ictal activity 13 . Meanwhile, antagonisms produced in thalamocortical synchrony 41,42 and T-type calcium currents 41,43,44 between calcium channel P/Q and NMDAR might be other plausible explanations.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of CACNA1A deficiency against seizure in the CACNA1A-CELSR2 digenic knockdown flies

Liu

Lin

Zhang

et al. 2023

Preprint

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The vast majority of medically intractable epilepsy cases can be traced to polygenic backgrounds, and pathogenic variants contribute to genetic risk in the complex inheritance of this common disorder. We generated monogenic and digenic drosophila models by knock-down of two epilepsy-associated genes, CACNA1A and CELSR2, with impacts on intersynaptic calcium activities. Monogenic knockdown of CACNA1A or CELSR2 could induce seizure-like behavior in flies. Interestingly, seizure behavior tests showed that CACNA1A deficiency could attenuate the seizure-like activities of the CACNA1A-CELSR2 digenic knockdown flies. The protective effect of CACNA1A deficiency was quantitatively fitted with multiple linear regression equation based on the seizure rates. In calcium imaging results, CACNA1A monogenic knockdown flies showed higher frequency of large spikes calcium activity than that of wild-type flies. That would be the neural base of the seizure in CACNA1A deficiency flies. However, the area under curve of calcium activity showed no difference between CACNA1A monogenic knockdown flies and wild-type flies. The calcium imaging results could partially illustrate the mechanism of the protective effect of CACNA1A deficiency. Furthermore, our study could be an ideal strategy to study polygenic effect on epilepsy by using animal model.

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“…Some of the neurological disorders where glia are relevant for their pathophysiology have shared mechanisms with migraine. For instance, migraine has been hypothesised to be associated with brain hyperexcitability, a characteristic seen in patients with epilepsy that, as mentioned above, has been linked to astrocyte dysfunction [ 25 , 26 , 27 ]. Chronic migraine shares several important features with chronic pain too, and the latter has been shown to have a strong glial component [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies

Vila-Pueyo,

Gliga,

Gallardo

et al. 2023

IJMS

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Migraine is a complex and debilitating neurological disease that affects 15% of the population worldwide. It is defined by the presence of recurrent severe attacks of disabling headache accompanied by other debilitating neurological symptoms. Important advancements have linked the trigeminovascular system and the neuropeptide calcitonin gene-related peptide to migraine pathophysiology, but the mechanisms underlying its pathogenesis and chronification remain unknown. Glial cells are essential for the correct development and functioning of the nervous system and, due to its implication in neurological diseases, have been hypothesised to have a role in migraine. Here we provide a narrative review of the role of glia in different phases of migraine through the analysis of preclinical studies. Current evidence shows that astrocytes and microglia are involved in the initiation and propagation of cortical spreading depolarization, the neurophysiological correlate of migraine aura. Furthermore, satellite glial cells within the trigeminal ganglia are implicated in the initiation and maintenance of orofacial pain, suggesting a role in the headache phase of migraine. Moreover, microglia in the trigeminocervical complex are involved in central sensitization, suggesting a role in chronic migraine. Taken altogether, glial cells have emerged as key players in migraine pathogenesis and chronification and future therapeutic strategies could be focused on targeting them to reduce the burden of migraine.

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Epilepsy and Migraine Shared Genetic and Molecular Mechanisms: Focus on Therapeutic Strategies

Cited by 14 publications

References 58 publications

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria

Protective effect of CACNA1A deficiency against seizure in the CACNA1A-CELSR2 digenic knockdown flies

The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies

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