Clinical Reasoning: A 26-Year-Old Woman With Recurrent Pain, Weakness, and Atrophy in Bilateral Upper Limbs During Pregnancy and Puerperium

Section 1

A 26-year-old woman developed tingling in her right upper limb during the second month of pregnancy that progressed to her left upper limb within several days. The pain, which first appeared at night, worsened during cold weather and improved when it was hot. Two weeks later, she developed proximal weakness in her right more than left arm. She also noticed progressive difficulty lifting her arms, using chopsticks, and buttoning clothes. There was no history of antecedent trauma, infection, or vaccination. The patient did not take any medication and was referred for rehabilitation therapy. The pain gradually resolved 3 months later, and the weakness in both arms slowly improved. She was eventually able to manage her daily activities without assistance, but had mild residual weakness.

One week after giving birth, the patient experienced another attack. She developed severe pain in the left shoulder and arm, numbness in the left hand, and could not raise her left arm. After a few days, she developed weakness and pain in both upper limbs. No neck pain, bowel/bladder dysfunction, or muscle fasciculations were reported. She denied weakness or sensory change in her lower limbs. She reported having 2 similar episodes at ages 5 and 10 years, after which she fully recovered. Regarding family history, her mother also reported a similar single episode that started with muscle weakness in the right upper extremity 1 month after parturition, from which she recovered 8 months later.

On examination, mental status was normal and cranial nerves were intact. Strength in the upper extremities was decreased (Figure, A). The patient had normal strength in the lower extremities. Tone was decreased in the arms and normal in the legs. Significant atrophy of bilateral infraspinatus, teres minor, and deltoid muscles were observed in addition to decreased sensation to pinprick along the radial aspect of the forearms. No fasciculations were noted. Deep tendon reflexes (DTRs) were 1+ in the upper limbs and 2+ in the lower limbs. No pathologic reflexes were found. The patient had a similar facial appearance as her mother because both had hypotelorism (measured pupil-to-pupil with a ruler) (Figure, B).

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Figure Clinical and Gene Findings

(A) Strength in the upper extremities (Medical Research Council); (B) Dysmorphic features; (C) A heterozygous single nucleotide change c.316C > T in exon 3 of the SEPT9 gene, resulting in the amino acid change p.Rl06W; (D) Pedigree: Female individuals are shown as circles, male individuals as squares. Filled symbols represent affected individuals with an exon 3 missense variation of the SEPT9 gene. Open symbols indicate nonaffected individuals and a slanting arrow the index patient. III-1 is without attack so far.

Section 2

The severe pain, numbness, and weakness with focal muscle atrophy in the bilateral upper limbs and depressed reflexes suggest involvement of the peripheral nervous system. The CNS is less likely involved in the absence of upper motor neuron signs. Therefore, we considered a multilevel radicular process involving multiple nerve roots (C5-T1), brachial plexopathy, or neuropathy (radial, median, axillary, suprascapular, and musculocutaneous nerves). The patient also experienced significant pain during each attack. The differential diagnosis based on localization might involve the following:

1. Radiculopathy, which can be caused by trauma or various inflammatory or neoplastic disorders but does not typically involve the bilateral upper extremities simultaneously.

2. Plexopathy, such as Parsonage-Turner syndrome or diabetic radiculoplexus neuropathies, which can be associated with severe pain at the onset of weakness.

3. Multiple mononeuropathies, which can be caused by vasculitis, inflammation, or diabetic neuropathy and result in neuropathic pain.

Section 3

Needle electromyography (EMG) and nerve conduction studies (NCS) were performed after the fourth attack. EMG revealed neurogenic damage in the bilateral upper limbs. Sensory nerve conduction studies also showed a low-amplitude right radial nerve sensory nerve action potential (SNAP) and slow sensory conduction velocity of the right median nerve and bilateral radial nerves. The motor nerve conduction testing showed decreased compound muscle action potential (CMAP) amplitudes elicited bilaterally from the axillary, radial, and musculocutaneous nerves and right median nerve (Table). The abovementioned findings revealed dysfunction in the middle and upper trunci of the bilateral brachial plexus.

The patient's clinical manifestations and auxiliary examination suggested a brachial plexus neuropathy; however, she had no history of recent infection, trauma, vaccination, cancer, toxic exposure, diabetes, or radiation therapy. Laboratory tests, including erythrocyte sedimentation rate, antinuclear antibodies, and antineutrophil cytoplasmic antibodies, were within normal limits. CSF tests were normal. Immunologic testing for antiganglioside and anti-Hu paraneoplastic antibodies showed negative results. Contrast-enhanced MRI of the brachial plexus and cervical spine was normal. Considering the high rate of recurrence, family history, and presence of dysmorphic features, a hereditary disease was suspected.

Section 4

When evaluating patients for a genetic disease involving the brachial plexus, hereditary neuralgic amyotrophy (HNA) should be considered. Gene analyses were performed for HNA. We identified a heterozygous single nucleotide change c.316C > T in exon 3 of the SEPT9 gene (GRCh37/hg19 chr17:75398380), resulting in the amino acid change p.R106W (Figure, C). This variation was also found in the patient's mother and son (Figure, D). The son was 2 months old during genetic testing.

Disclosure

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.