White Matter Hyperintensities in Patients with Sporadic Hemiplegic Migraine

Nagarajan, Elanagan; Bollu, Pradeep C.; Sivaraman, Manjamalai; Yelam, Anudeep; Qureshi, Adnan I

doi:10.1111/jon.12656

Cited by 4 publications

(7 citation statements)

References 47 publications

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“…Other MRIs reveal a reversible decrease in water diffusion, due to cytotoxic oedema 11. These alterations are located in the hemisphere contralateral to the motor weakness12 and often disappear over some weeks or months, following neurological deficits resolution 13. Some patients present white matter hyperintensities (WMHs) on MRI T2 sequences, especially in the posterior regions 10 12 14 15.…”

Section: Discussionmentioning

confidence: 99%

“…These alterations are located in the hemisphere contralateral to the motor weakness12 and often disappear over some weeks or months, following neurological deficits resolution 13. Some patients present white matter hyperintensities (WMHs) on MRI T2 sequences, especially in the posterior regions 10 12 14 15. A recent study compared the occurrence of WMHs in 50 patients with SHM and migraine headache, showing that WMHs are significantly more common in the SHM group, especially in the parietal lobe 12.…”

Section: Discussionmentioning

confidence: 99%

“…Some patients present white matter hyperintensities (WMHs) on MRI T2 sequences, especially in the posterior regions 10 12 14 15. A recent study compared the occurrence of WMHs in 50 patients with SHM and migraine headache, showing that WMHs are significantly more common in the SHM group, especially in the parietal lobe 12. WMHs could be the result of a transient hypercoagulative state during an acute HM attack, with consequent silent infarcts appearing as hyperintense lesions on T2-weighted images 14.…”

Section: Discussionmentioning

confidence: 99%

“…WMHs could be the result of a transient hypercoagulative state during an acute HM attack, with consequent silent infarcts appearing as hyperintense lesions on T2-weighted images 14. Their predilection for parietal lobe in SHM patients may be explained by taking into account that sensory auras are more frequent than motor ones, since obstacles like central sulcus may prevent cortical depression wave progression 12. This suggests a possible role for hypoperfusion occurring during aura in generating WMHs, even if some studies found no significant differences in their prevalence among subjects with and without aura 12 14.…”

Section: Discussionmentioning

confidence: 99%

“…Their predilection for parietal lobe in SHM patients may be explained by taking into account that sensory auras are more frequent than motor ones, since obstacles like central sulcus may prevent cortical depression wave progression 12. This suggests a possible role for hypoperfusion occurring during aura in generating WMHs, even if some studies found no significant differences in their prevalence among subjects with and without aura 12 14. In our patient, mild gadolinium enhancement and alterations in water diffusion were present in the first MRI.…”

Section: Discussionmentioning

confidence: 99%

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Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

et al. 2019

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Hemiplegic migraine (HM) is a rare subtype of migraine with aura in which attacks include transient motor weakness or hemiparesis that can last several days. HM is linked to mutations in three different genes, CACNA1A, ATP1A2 and SCN1A, which encode for ion transporters. The clinical spectrum includes atypical symptoms such as impaired consciousness, epileptic seizures, permanent cerebellar ataxia or mental retardation. We describe a novel mutation found in the ATP1A2 gene in a patient with late-onset HM. His attacks were characterised by motor weakness associated with altered mental status, diplopia and ataxia. He also showed up MRI abnormalities and incomplete response to prophylactic therapy with verapamil. Late-onset HM should be considered among the possible causes of focal neurological deficits even in older patients with cerebrovascular risk factors when a stroke appears to be more likely.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

et al. 2019

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Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study

Wee

Zhao

et al. 2020

Journal of the Neurological Sciences

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A de novo EGR2 variant, c.1232A > G p.Asp411Gly, causes severe early-onset Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy)

Grosz

Golovchenko

Ellis

et al. 2019

Sci Rep

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EGR2 (early growth response 2) is a crucial transcription factor for the myelination of the peripheral nervous system. Mutations in EGR2 are reported to cause a heterogenous spectrum of peripheral neuropathy with wide variation in both severity and age of onset, including demyelinating and axonal forms of Charcot-Marie Tooth (CMT) neuropathy, Dejerine-Sottas neuropathy (DSN/CMT3), and congenital hypomyelinating neuropathy (CHN/CMT4E). Here we report a sporadic de novo EGR2 variant, c.1232A > G (NM_000399.5), causing a missense p.Asp411Gly substitution and discovered through whole-exome sequencing (WES) of the proband. The resultant phenotype is severe demyelinating DSN with onset at two years of age, confirmed through nerve biopsy and electrophysiological examination. In silico analyses showed that the Asp411 residue is evolutionarily conserved, and the p.Asp411Gly variant was predicted to be deleterious by multiple in silico analyses. A luciferase-based reporter assay confirmed the reduced ability of p.Asp411Gly EGR2 to activate a PMP22 (peripheral myelin protein 22) enhancer element compared to wild-type EGR2. This study adds further support to the heterogeneity of EGR2-related peripheral neuropathies and provides strong functional evidence for the pathogenicity of the p.Asp411Gly EGR2 variant. Charcot-Marie-Tooth (CMT) neuropathy is group of degenerative motor and sensory peripheral neuropathies which are clinically and genetically heterogenous. Pathogenic variants in over 90 genes cause CMT, and whole-exome sequencing (WES) is now an effective tool for screening known causative genes in unsolved CMT families. Pathogenic variants in the EGR2 gene (early growth response 2) cause a broad spectrum of peripheral neuropathy phenotypes. This includes two forms of severe early-onset peripheral neuropathy, Dejerine-Sottas neuropathy (DSN/CMT3) 1-3 and congenital hypomyelinating neuropathy (CHN/CMT4E) 4,5 , as well as adult-onset demyelinating CMT1D with mild-moderate symptoms 3-12 and variable-onset axonal CMT with varied symptom severity 13,14. EGR2 encodes a C 2 H 2-type zinc-finger transcription factor that regulates the expression of genes involved in the formation and maintenance of myelin, including GJB1 (gap junction beta 1), MPZ (myelin protein zero), MBP (myelin basic protein), MAG (myelin associated glycoprotein), PRX (periaxin), and PMP22 (peripheral myelin protein 22) 4,15-18. Approximately half of the reported disease-associated EGR2 variants are de novo and are associated with a severe phenotype 13. Here, we report a sporadic de novo EGR2 variant in the third zinc-finger domain, c.1232A > G p.Asp411Gly, discovered through WES candidate gene screening. This variant manifested as a severe DSN phenotype with early onset at two years of age.

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White Matter Hyperintensities in Patients with Sporadic Hemiplegic Migraine

Cited by 4 publications

References 47 publications

Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study

A de novo EGR2 variant, c.1232A > G p.Asp411Gly, causes severe early-onset Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy)

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