Reader response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
VinodGupta, Physician, Migraine-Headache Institute, Gupta Medical Centre (New Delhi, India)
Submitted March 08, 2019
Biomarkers have not advanced comprehension of migraine pathophysiology, being unable to rationalize self-cycling onset and offset of migraine. These systemic diffuse brain deposits1,2 and non-lateralizing neuropeptides, from serotonin to calcitonin gene–related peptide, also face issues of blood-brain barrier crossing.
The greatest limitation of biomarkers has been the artificial, haphazard distinction that these laboratory findings have created between migraine with aura and migraine without aura, through a nosological splitting that can never be replicated or carry any meaning in a protean, almost chimerical human-rodent disorder. Much of extrapolation to humans comes from rodents, which cannot vomit—a major but completely overlooked limitation in trial designing/redesigning, replication, meta-analysis, and statistical sophistication.3
While venesection can remit cluster headache to a degree in hereditary hemochromatosis,4 there is no link between iron deficiency anemia and remission of migraine/cluster headache, other than that the elevated cardiac output may be lowered after ASD/PFO-closure therapy for migraine.3 Iron is essential for life, and is involved in the formation and destruction of reactive oxygen species.5 Iron-dependent cell death, termed ferroptosis, is crucial in acute traumas and chronic degenerative conditions, unlike migraine. Iron deposition in brain parenchyma in migraine is likely to be adaptive in nature.
Disclosure​
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Domínguez C, López A, Pedro Ramos-Cabrer P, et al. Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine. Neurology 2019;92:e1076–e1085.
Welch KMA, Nagesh V, Aurora SK, Gelman N. Periaqueductal gray matter dysfunction in migraine: Cause or the burden of illness? Headache 2001;41:629–637.
Gupta VK. Patent-foramen ovale closure and migraine: Science and sensibility. Expert Rev Neurother 2010;10:1409–1422.
Stovner LJ, Hagen K, Waage A, Bjerve KS. Hereditary haemochromatosis in two cousins with cluster headache. Cephalalgia 2002;22:317–319.
Dixon SJ, Sotckwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol 2014;10:9–17.
Biomarkers have not advanced comprehension of migraine pathophysiology, being unable to rationalize self-cycling onset and offset of migraine. These systemic diffuse brain deposits1,2 and non-lateralizing neuropeptides, from serotonin to calcitonin gene–related peptide, also face issues of blood-brain barrier crossing.
The greatest limitation of biomarkers has been the artificial, haphazard distinction that these laboratory findings have created between migraine with aura and migraine without aura, through a nosological splitting that can never be replicated or carry any meaning in a protean, almost chimerical human-rodent disorder. Much of extrapolation to humans comes from rodents, which cannot vomit—a major but completely overlooked limitation in trial designing/redesigning, replication, meta-analysis, and statistical sophistication.3
While venesection can remit cluster headache to a degree in hereditary hemochromatosis,4 there is no link between iron deficiency anemia and remission of migraine/cluster headache, other than that the elevated cardiac output may be lowered after ASD/PFO-closure therapy for migraine.3 Iron is essential for life, and is involved in the formation and destruction of reactive oxygen species.5 Iron-dependent cell death, termed ferroptosis, is crucial in acute traumas and chronic degenerative conditions, unlike migraine. Iron deposition in brain parenchyma in migraine is likely to be adaptive in nature.
Disclosure​
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References