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Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

Koutsis G, Karadima G, Floroskoufi P, Raftopoulou M, Panas M - Case Rep Neurol Med (2015)

Bottom Line: Cys64Tyr) which was recently reported by our group.This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars).Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, 74 Vasilissis Sophias Avenue, 11528 Athens, Greece.

ABSTRACT
We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

No MeSH data available.


Related in: MedlinePlus

Brain and spinal cord MRI of the patient with CMTX and MS and brain MRI of his first cousin with CMTX and asymptomatic diffuse CNS involvement. (a) Axial FLAIR brain MRI of the patient demonstrating periventricular lesions characteristic of MS. (b) Sagittal T2 brain MRI of the patient revealing lesions in the corpus callosum characteristic of MS. (c) Axial T2 brain MRI of the patient demonstrating a lesion in the left middle cerebellar peduncle. (d) Axial T2 cervical cord MRI of the patient demonstrating a spinal cord lesion. (e) Axial T1 with IV contrast brain MRI of the patient showing periventricular gadolinium-enhancing lesions suggesting inflammation. (f) Axial FLAIR brain MRI of the patient's first cousin revealing diffuse white matter hyperintensity more prominent posteriorly.
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fig1: Brain and spinal cord MRI of the patient with CMTX and MS and brain MRI of his first cousin with CMTX and asymptomatic diffuse CNS involvement. (a) Axial FLAIR brain MRI of the patient demonstrating periventricular lesions characteristic of MS. (b) Sagittal T2 brain MRI of the patient revealing lesions in the corpus callosum characteristic of MS. (c) Axial T2 brain MRI of the patient demonstrating a lesion in the left middle cerebellar peduncle. (d) Axial T2 cervical cord MRI of the patient demonstrating a spinal cord lesion. (e) Axial T1 with IV contrast brain MRI of the patient showing periventricular gadolinium-enhancing lesions suggesting inflammation. (f) Axial FLAIR brain MRI of the patient's first cousin revealing diffuse white matter hyperintensity more prominent posteriorly.

Mentions: We present a case of a 52-year-old man diagnosed with MS five years previously, who had a family history of peripheral neuropathy with no male-to-male transmission. He reported pes cavus since childhood, but no other significant early symptoms. Nerve conduction studies confirmed the presence of a hereditary neuropathy with intermediate velocities. At age 46, he developed left-sided optic neuritis (ON). Brain MRI revealed multiple focal periventricular, callosal, and brainstem lesions, some gadolinium-enhancing, strongly suggestive of MS (Figures 1(a), 1(b), 1(c), and 1(e)). Visual evoked potentials were prolonged ipsilaterally. CSF analysis revealed no oligoclonal bands (OCB) and normal IgG index. The ON remitted following corticosteroid treatment but relapsed a few months later and was further treated successfully with steroids. Later that year, the patient developed gait unsteadiness, with further MRI evidence of disease activity. This remitted with corticosteroid treatment. He was then started on prophylactic treatment with beta-interferon. Two years later, he had an episode of numbness affecting the extremities. Spinal cord MRI revealed a cervical T2 lesion compatible with demyelination (Figure 1(d)). The episode was treated successfully with corticosteroids. Following a further relapse with vertigo and gait unsteadiness, combined with MRI evidence of disease activity, he was switched to natalizumab and has remained relapse-free since. On examination, he had difficulty with tandem gait, saccadic pursuit, extensor plantars, brisk upper limb tendon reflexes, reduced knee jerks, absent Achilles reflexes, mild peripheral atrophy in upper and lower limbs, reduced vibration sense peripherally in the lower limbs, pes cavus, and hammer toes. The patient came to our attention after examining other members of his family who had CMTX and evidence of asymptomatic CNS involvement on brain MRI (diffuse white matter hyperintensity, Figure 1(f); patient's first cousin) or clinically (extensor plantars; patient's aunt). More specifically, brain MRI of the patient's cousin revealed nonenhancing, symmetrical, diffuse white matter abnormalities, which were clearly detectable at the level of the centrum semiovale and periventricularly, were more prominent posteriorly, and involved the splenium of the corpus callosum, as previously described [7]. There were no focal lesions suggestive of inflammatory demyelination, in contrast to the patient. Both relatives were found to carry a novel c.191G>A point mutation in GJB1 (p. Cys64Tyr) [7]. This mutation was subsequently also identified in our patient with MS.


Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

Koutsis G, Karadima G, Floroskoufi P, Raftopoulou M, Panas M - Case Rep Neurol Med (2015)

Brain and spinal cord MRI of the patient with CMTX and MS and brain MRI of his first cousin with CMTX and asymptomatic diffuse CNS involvement. (a) Axial FLAIR brain MRI of the patient demonstrating periventricular lesions characteristic of MS. (b) Sagittal T2 brain MRI of the patient revealing lesions in the corpus callosum characteristic of MS. (c) Axial T2 brain MRI of the patient demonstrating a lesion in the left middle cerebellar peduncle. (d) Axial T2 cervical cord MRI of the patient demonstrating a spinal cord lesion. (e) Axial T1 with IV contrast brain MRI of the patient showing periventricular gadolinium-enhancing lesions suggesting inflammation. (f) Axial FLAIR brain MRI of the patient's first cousin revealing diffuse white matter hyperintensity more prominent posteriorly.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4390163&req=5

fig1: Brain and spinal cord MRI of the patient with CMTX and MS and brain MRI of his first cousin with CMTX and asymptomatic diffuse CNS involvement. (a) Axial FLAIR brain MRI of the patient demonstrating periventricular lesions characteristic of MS. (b) Sagittal T2 brain MRI of the patient revealing lesions in the corpus callosum characteristic of MS. (c) Axial T2 brain MRI of the patient demonstrating a lesion in the left middle cerebellar peduncle. (d) Axial T2 cervical cord MRI of the patient demonstrating a spinal cord lesion. (e) Axial T1 with IV contrast brain MRI of the patient showing periventricular gadolinium-enhancing lesions suggesting inflammation. (f) Axial FLAIR brain MRI of the patient's first cousin revealing diffuse white matter hyperintensity more prominent posteriorly.
Mentions: We present a case of a 52-year-old man diagnosed with MS five years previously, who had a family history of peripheral neuropathy with no male-to-male transmission. He reported pes cavus since childhood, but no other significant early symptoms. Nerve conduction studies confirmed the presence of a hereditary neuropathy with intermediate velocities. At age 46, he developed left-sided optic neuritis (ON). Brain MRI revealed multiple focal periventricular, callosal, and brainstem lesions, some gadolinium-enhancing, strongly suggestive of MS (Figures 1(a), 1(b), 1(c), and 1(e)). Visual evoked potentials were prolonged ipsilaterally. CSF analysis revealed no oligoclonal bands (OCB) and normal IgG index. The ON remitted following corticosteroid treatment but relapsed a few months later and was further treated successfully with steroids. Later that year, the patient developed gait unsteadiness, with further MRI evidence of disease activity. This remitted with corticosteroid treatment. He was then started on prophylactic treatment with beta-interferon. Two years later, he had an episode of numbness affecting the extremities. Spinal cord MRI revealed a cervical T2 lesion compatible with demyelination (Figure 1(d)). The episode was treated successfully with corticosteroids. Following a further relapse with vertigo and gait unsteadiness, combined with MRI evidence of disease activity, he was switched to natalizumab and has remained relapse-free since. On examination, he had difficulty with tandem gait, saccadic pursuit, extensor plantars, brisk upper limb tendon reflexes, reduced knee jerks, absent Achilles reflexes, mild peripheral atrophy in upper and lower limbs, reduced vibration sense peripherally in the lower limbs, pes cavus, and hammer toes. The patient came to our attention after examining other members of his family who had CMTX and evidence of asymptomatic CNS involvement on brain MRI (diffuse white matter hyperintensity, Figure 1(f); patient's first cousin) or clinically (extensor plantars; patient's aunt). More specifically, brain MRI of the patient's cousin revealed nonenhancing, symmetrical, diffuse white matter abnormalities, which were clearly detectable at the level of the centrum semiovale and periventricularly, were more prominent posteriorly, and involved the splenium of the corpus callosum, as previously described [7]. There were no focal lesions suggestive of inflammatory demyelination, in contrast to the patient. Both relatives were found to carry a novel c.191G>A point mutation in GJB1 (p. Cys64Tyr) [7]. This mutation was subsequently also identified in our patient with MS.

Bottom Line: Cys64Tyr) which was recently reported by our group.This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars).Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, 74 Vasilissis Sophias Avenue, 11528 Athens, Greece.

ABSTRACT
We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

No MeSH data available.


Related in: MedlinePlus