Clinical Reasoning: A young man with reversible paralysis, cerebral white matter lesions, and peripheral neuropathy

Abstract

A 17-year-old boy experienced 3 consecutive episodes of transient tetraplegia or monoparesis over the course of 5 days, after a week of low-grade fever. He was alert but had dysarthria and diplopia during the attacks. The paresis persisted for 5 to 7 hours and resolved completely.Three years prior, he had presented with a 1-day episode of transient right hemiparesis and dysarthria, and recovered completely without any treatment. At that time, cerebral MRI showed bilateral symmetric confluent hyperintense lesions in the parieto-occipital region and splenium and genu of the corpus callosum on T2-weighted images (figure). Three months later, these MRI abnormalities were markedly reduced (figure).Family history is significant for a maternal grandfather with progressive claudication since his 30s. He is 65 years old now, has amyotrophy in the lower limbs, but still can walk. He never received a diagnosis for these symptoms. The patient's mother denied any neuropathy.On examination, no abnormalities were found in his upper and lower limbs. The results of motor examination, including strength, tone, posture, involuntary movements, and reflexes, were normal. The sensory examination was unremarkable. Cerebral MRI showed white matter lesions in approximately the same distribution as on the MRI performed 3 years prior, but increased in severity (figure). These lesions spared the subcortical U-fibers and did not enhance.EMG performed 1 week after the onset showed prolonged distal motor latencies (median 10.6, ulnar 8.7 [ms, normal value Ͻ3. The sensory potential of the right sural nerve was not detected. These abnormalities suggested both myelin dysfunction and axonal damage. Laboratory tests, including electrolytes, lactate, and CSF, were all normal. Aortocranial angiography and EEG were normal. Questions for consideration:1. What is the differential diagnosis? 2. Virtually all categories of pathology may cause white matter lesions. Does the imaging appearance limit the differential diagnosis? SECTION 2The clinical features of this patient included cerebral white matter lesions, recurrent paralysis, and peripheral neuropathy. As the patient had confluent cerebral white matter lesions, acute disseminated encephalomyelitis (ADEM) and adrenoleukodystrophy were considered. ADEM is a demyelinating disease that is thought to be of autoimmune origin. It usually occurs after a recent infectious prodrome.

The Electrophysiological Features in X-Linked Charcot-Marie-Tooth Disease With Transient Central Nervous System Deficits

“…Of the 21 electrophysiological examinations, 14 cases had detectable electrophysiological parameters, and 7 cases had normal laboratory values ( 9 – 12 , 14 , 15 ). Supplementary Table 1 summarizes 21 electrophysiological examinations in CMTX1 patients with transient central nervous system deficits.…”

A Review of X-linked Charcot-Marie-Tooth Disease

“…Relapse or recurrent phases may occur 3 months after the first attack. 34 GuillainBarré syndrome is also a monophasic disease, associated with either simultaneous or sequential cerebral demyelination. 79 Symptoms usually reach maximum severity after 4 weeks.…”

“…After Nicholson and Corbett 33 reported abnormal prolonged brainstem auditory evoked responses in a few patients with CMTX1 in 1996, several CMTX cases with transient central nervous system involvement were reported and are now well recognized. In 2012, the authors 34 reported on a young man who presented with transient neurological manifestations, white matter lesions observed by cerebral magnetic resonance imaging (MRI) and atypical CMTX1 features associated with a new-found missense mutation (Asn54Ser) of the connexin 32 gene. As of this writing, 42 articles have been published on PubMed.…”

“…As of this writing, 42 articles have been published on PubMed. 26,34 –39,41 –51,53,55 –61,63 –77 Among these cases, 74 patients had CMTX1 with central nervous system involvement and are presented in Table 2. In these cases, every central nervous system manifestation is a variant combination of dysarthria, dysphagia, hemiparesis, tetraparesis or complete paralysis, ataxia, cranial nerve deficits, expressive or motor aphasia, diplopia, vertigo, and dyspnea, and some have acute disseminated encephalomyelitis–like attacks.…”

Systematic review of CMTX1 patients with episodic neurological dysfunction

“…Finally, we identified 47 cases from 38 articles that met the criteria of our systematic review. 11‐48 The gradual selection and exclusion process of the studies is shown in Figure 1.…”