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Strokelike Episodes in a Patient With Chronic Gait Abnormalities

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 13-year-old boy with a longstanding history of gait imbalance presented with 2 episodes of acute-onset left hemibody weakness and dysarthria without changes in sensorium in a 24-hour period. Symptoms lasted approximately 60 minutes each before completely resolving; prior to the day of the events, he had never experienced similar phenomena. Initial examination following the second event revealed mild-to-moderate dysarthria, pes planovalgus and tight achilles tendons bilaterally, and decreased vibratory and fine touch sensation from the great toe up to the mid shin bilaterally. Reflexes were absent at the patella and achilles bilaterally. Bilateral dorsiflexion weakness was present (4 of 5). There were otherwise no motor deficits, muscle atrophy, or lateralizing neurologic abnormalities.

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C. X-linked Charcot-Marie-Tooth disease

The patient had no further events following his admission and neurodiagnostic workup. His examination was consistent with peripheral nerve pathology (diminished reflexes and decrements in sensorium), which appeared to be longstanding as demonstrated by pes planovalgus and tight Achilles tendons. The patient’s superimposed acute events were felt to be reflective of a strokelike phenomenon, given the duration and pattern of neurologic symptoms.

In reviewing the patient’s case, examination, and neuroimaging, it was determined that the patient’s clinical findings fit most closely with a diagnosis of Charcot-Marie-Tooth disease (CMTX). The imaging findings, particularly with prominent bilateral and symmetric restricted diffusion in the supratentorial white matter, were thought to be more characteristic of CMTX-related strokelike episode and would not be typical for leukodystrophies (specifically, metachromatic leukodystrophy, X-linked adrenoleukodystrophy, and Alexander disease). Given the symmetric pattern of involvement, mitochondrial disorders were considered although were thought to be less likely given the patient’s normal growth and development and lack of lactic acidosis and other laboratory abnormalities. Acute disseminated encephalomyelitis was considered, but the large-scale confluent lesions involving only the white matter were considered unusual as would be the symmetry of this pattern. Multiple sclerosis and neuromyelitis optica typically do not exhibit these patterns and were thought to be very low on the differential. Myelin oligodendrocyte antibody spectrum disorders can present with large T2-hyperintense lesions but are rarely symmetric or isolated to the white matter only. Although a classic mimic in nearly all central demyelinating disorders, central nervous system lymphoma was lower on the differential based on symmetry, age of patient, and lack of other findings.

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Article Information

Corresponding Author: Jonathan D. Santoro, MD, Department of Neurology, Massachusetts General Hospital, 55 Fruit St, ACC 708, Boston, MA 02115 (jdsantoro@mgh.harvard.edu).

Published Online: February 25, 2019. doi:10.1001/jamaneurol.2019.0057

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient’s family for granting permission to publish this information.

References
1.
Shy  ME, Siskind  C, Swan  ER,  et al.  CMT1X phenotypes represent loss of GJB1 gene function.  Neurology. 2007;68(11):849-855. doi:10.1212/01.wnl.0000256709.08271.4dPubMedGoogle ScholarCrossref
2.
Anand  G, Maheshwari  N, Roberts  D,  et al.  X-linked hereditary motor sensory neuropathy (type 1) presenting with a stroke-like episode.  Dev Med Child Neurol. 2010;52(7):677-679. doi:10.1111/j.1469-8749.2010.03674.xPubMedGoogle ScholarCrossref
3.
Hanemann  CO, Bergmann  C, Senderek  J, Zerres  K, Sperfeld  AD.  Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with novel connexin 32 mutation.  Arch Neurol. 2003;60(4):605-609. doi:10.1001/archneur.60.4.605PubMedGoogle ScholarCrossref
4.
Paulson  HL, Garbern  JY, Hoban  TF,  et al.  Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease.  Ann Neurol. 2002;52(4):429-434. doi:10.1002/ana.10305PubMedGoogle ScholarCrossref
5.
Rosser  T, Muir  J, Panigrahy  A, Baldwin  EE, Boles  RG.  Transient leukoencephalopathy associated with X-linked Charcot-Marie-Tooth disease.  J Child Neurol. 2010;25(8):1013-1016. doi:10.1177/0883073809352378PubMedGoogle ScholarCrossref
6.
McKinney  JL, De Los Reyes  EC, Lo  WD, Flanigan  KM.  Recurrent central nervous system white matter changes in charcot-Marie-tooth type X disease.  Muscle Nerve. 2014;49(3):451-454. doi:10.1002/mus.24108PubMedGoogle ScholarCrossref
7.
Al-Mateen  M, Craig  AK, Chance  PF.  The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.  J Child Neurol. 2014;29(3):342-348. doi:10.1177/0883073812474343PubMedGoogle ScholarCrossref
8.
Scherer  SS, Deschênes  SM, Xu  YT, Grinspan  JB, Fischbeck  KH, Paul  DL.  Connexin32 is a myelin-related protein in the PNS and CNS.  J Neurosci. 1995;15(12):8281-8294. doi:10.1523/JNEUROSCI.15-12-08281.1995PubMedGoogle ScholarCrossref
9.
Sargiannidou  I, Ahn  M, Enriquez  AD,  et al.  Human oligodendrocytes express Cx31.3: function and interactions with Cx32 mutants.  Neurobiol Dis. 2008;30(2):221-233. doi:10.1016/j.nbd.2008.01.009PubMedGoogle ScholarCrossref
10.
Kleopa  KA, Abrams  CK, Scherer  SS.  How do mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease?  Brain Res. 2012;1487:198-205. doi:10.1016/j.brainres.2012.03.068PubMedGoogle ScholarCrossref
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