Demyelinating radiculopathy in the kearns‐sayre syndrome: A clinicopathological study

Abstract

In the few previously autopsied patients with the Kearns-Sayre form of progressive ophthalmoplegia, the most prominent abnormalities have been in muscle, with less conspicuous changes in the central nervous system, primarily in the brainstem. Similar findings were present in the case reported here, but in addition there was severe demyelination in the initial few millimeters of the cranial and spinal motor roots distal to the glial-Schwann cell junction. Milder demyelination was observed in the dorsal spinal and afferent cranial nerve roots, including the eighth nerve, but deafness was due to virtually total destruction of the organ of Corti. Our observations suggest that a radiculopathy may be a feature in some cases of Kearns-Sayre syndrome.

Kearns-Sayre syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related?) neurocristopathy?

“…Temporary and brainstem white matter involvement contributed to the neurosensory hearing loss observed in our patients. 15,17 In other mitochondrial OXPHOS diseases, as in Leigh disease, necroscopic findings were similar, involving also the putamen, sometimes associated with symmetric necrotic areas and features suggestive of developmental disorders or malformations antedating birth. [18][19][20][21][22] In KSS cases, it is not possible to state if white matter abnormalities are degenerative (leukodystrophies) or if they have a myelinogenesis defect component (leukodysplasia).…”

“…spongiform encephalopathy, which is constant, widespread and involving both gray and white matter, with a vacuolization of the central nervous system tissue in a sieve-like appearance; 6,7 in some cases, abnormalities of cranial and spinal nerve roots glia (demyelinating radiculopathy) are associated. 15 Proton-MRI spectroscopy showed low levels of n-acetylaspartate in CNS and increased cerebrospinal fluid lactate, which is the expression of prominent oligodendroglial vacuolar changes. 8 Low n-acetyl-aspartate was present in our patient.…”

“…2,3,6,7,8,[15][16][17] Mitochondrial enzymes are structurally present in early life in the human embryo, even if they become functionally normal only subsequently, often during the fetal and/or postnatal period. 6 In KSS, large mtDNA deletion 16 is the cause of reduced mitochondrial protein synthesis by the reduced tRNA molecules 18 and by the energy production deficiency, with consequent lactic acid accumulation, capillary proliferation, extensive spongiform changes in cerebrum, 1 cerebellum, 1 spinal cord, basal ganglia white matter and brainstem gray and white matter, 7,8 and predominant neuronal loss in cerebrum and cerebellum.…”

“…6 In KSS, large mtDNA deletion 16 is the cause of reduced mitochondrial protein synthesis by the reduced tRNA molecules 18 and by the energy production deficiency, with consequent lactic acid accumulation, capillary proliferation, extensive spongiform changes in cerebrum, 1 cerebellum, 1 spinal cord, basal ganglia white matter and brainstem gray and white matter, 7,8 and predominant neuronal loss in cerebrum and cerebellum. 8 CNS demyelination as a less prominent feature 18 and peripheral nerve demyelination 15,17 were reported. Cerebral white matter seems more sensitive to damage and is a primary target of the mitochondrial OXPHOS dysfunction, through a possible direct involvement of the membrane turnover 9 with hypomyelination, mainly during white matter myelination time 6 (first part of second trimester 6 and first postnatal months), when oligodendrocytes are more sensitive to energy failure, 9,15,18 but starting prior to onset of myelination, 9 because all main elements of brain structures are established in the early embryo.…”

“…8 CNS demyelination as a less prominent feature 18 and peripheral nerve demyelination 15,17 were reported. Cerebral white matter seems more sensitive to damage and is a primary target of the mitochondrial OXPHOS dysfunction, through a possible direct involvement of the membrane turnover 9 with hypomyelination, mainly during white matter myelination time 6 (first part of second trimester 6 and first postnatal months), when oligodendrocytes are more sensitive to energy failure, 9,15,18 but starting prior to onset of myelination, 9 because all main elements of brain structures are established in the early embryo. 6 Retinal-cortical transmission delay reported in our patient was the expression of the involvement of optical pathways and subcortical white matter, as demonstrated 18 by MRI.…”