Report Describes Boys Diagnosed with CMTX After Stroke-like Symptoms

Two boys with neurological deficits suggestive of acute ischemic stroke were ultimately diagnosed with Charcot-Marie-Tooth disease type X (CMTX) following the detection of white matter lesions characteristic with the disorder, a recent case report shows.

The study, “X-linked Charcot-Marie-Tooth Disease Presenting with Stuttering Stroke-like Symptoms,” appeared in the journal Neuropediatrics.

The team at the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine of the University of Pennsylvania presented the cases of two adolescents with CMTX whose mothers were asymptomatic but had sensory neuropathy (nerve damage) upon examination.

The first patient was a 13-year-old boy who presented with right facial weakness. He was diagnosed with Bell’s palsy and treated for Lyme disease with doxycycline. He had traveled to the mountains in New York and California the week prior to presentation and had had a transient episode of slurred speech and ataxia (lack of coordination).

He was admitted to the hospital and placed on standard stroke precautions following recurrent facial weakness, a speech disorder called dysarthria, and weakness and numbness in the right upper extremity.

A neurological exam found a mild, fluctuating right facial droop, reduced right-hand strength, brisk reflexes in the right biceps and right patellar tendon (which connects the kneecap to the shinbone), decreased ankle reflexes, pes cavus (or high-arched feet), and mild muscle wasting in the lower extremities.

As characteristic in CMTX, magnetic resonance imaging (MRI) showed asymmetric restricted diffusion — the hallmark imaging feature of acute cerebral infarction — in the bilateral centrum semiovale (an area of white matter underneath the cerebral cortex), posterior corona radiata — white matter tracts at the level of the brain’s lateral ventricles, or cavities — and in parts of the corpus callosum (which connects the two sides of the brain), extending to the left precentral gyrus, also known as the primary motor cortex.

Then, electromyography — recording the electrical activity of a muscle fiber in response to electrical stimuli — and nerve conduction studies revealed mild to moderate chronic sensorimotor demyelinating neuropathy consistent with CMTX. Demyelinating refers to loss of myelin, the protective layer of nerve fibers.

Subsequent genetic testing showed a hemizygous missense variant (L76P) — a change of a single nucleotide, the building blocks of DNA, in the X chromosome — in the GJB1 gene.

The second patient was a 14-year old boy who presented after two days of stuttering symptoms of tongue tingling and right facial weakness. He was treated with diphenhydramine for a possible allergic reaction, but after brief resolution, the symptoms reappeared, leading to treatment with prednisone for possible Bell’s palsy. The next morning, he was taken to the emergency room in Bermuda (where he was on a cruise), reporting right leg weakness. As with the first patient, this boy was managed according to a stroke protocol.

Upon transfer to CHOP, he further showed ankle weakness, decreased vibration sense in the lower extremities, no reflexes on the lower extremities, and pes cavus. His medical history included bilateral foot weakness since childhood.

Cerebrospinal fluid analysis showed high levels of protein. MRI revealed white matter lesions in the centrum semiovale, posterior corona radiata, around the ventricles, and in the corpus callosum.

As with the first patient, the boy showed evidence of demyelinating neuropathy, primarily in the arms, along with mixed demyelinating and nerve fiber neuropathy in the legs with chronic denervation — loss of nerve supply — throughout. He also had a hemizygous mutation in GJB1.

Overall, neither patient has experienced a recurrence. A follow-up MRI in the second boy at four months showed near-complete resolution of signal abnormalities. No follow-up MRI was performed on the first boy.

Given evidence that Bell’s palsy episodes may be triggered by traveling to high altitudes, the researchers hypothesized that the recent travel to altitude in the first boy and the flight to the cruise ship in the second may have caused the symptoms.

“Though rare, these cases illustrate the importance of comprehensive neurologic history, physical examination, and appropriate diagnostic evaluation,” the scientists said.