Misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) appears to be common. In 2018, a study by Allen and colleagues reported that about 45% of patients referred with a diagnosis of CIDP did not have this disorder. These misdiagnoses may result partly from the clinical and electrodiagnostic similarities between CIDP and other disorders. Immunoglobulin M (IgM) neuropathy, for example, entails demyelination and distal slowing, and these features also are observed in CIDP. Diagnostic modalities such as nerve ultrasound may have the potential to clarify diagnosis and provide pathogenic information.
To determine whether IgM neuropathy has a pattern of nerve involvement distinct from that of CIDP or other neuropathies, H. Stephan Goedee, MD, PhD, of the Brain Center Rudolf Magnus at University Medical Center Utrecht in the Netherlands, and colleagues examined 106 consecutive adult patients with nerve ultrasound. The researchers included 32 patients with IgM neuropathy, 42 patients with CIDP, and 32 patients with chronic axonal polyneuropathies in their study. Twenty-six patients overall were women, and the three groups of patients did not differ significantly in age or sex ratio.
Dr. Goedee and colleagues performed routine ancillary testing on all patients, including standardized grading of muscle strength, nerve conduction studies, and laboratory testing. The researchers categorized sensory and motor features as sensory dominant (i.e., exclusively sensory or sensory with subtle distal muscle weakness), sensorimotor (i.e., sensory with moderate distal muscle weakness), or motor dominant (i.e., pronounced muscle weakness).
H. Stephan Goedee, MD, PhD
Many nerve measures were similar among patients
The most common clinical finding among patients with IgM neuropathy was distal symmetric sensory dominant and sensorimotor involvement. Among patients with CIDP, a proximal-distal motor dominant phenotype was common. In contrast, 6% of patients with IgM neuropathy had this presentation.
Many nerve measures were similar between patients with CIDP and those with IgM neuropathy. Regardless of their diagnosis, almost all patients had enlargement of nerves at common sites of nerve compression, such as the median nerve at the carpal tunnel. About 81% of patients with IgM neuropathy and 80% of patients with CIDP had enlargement of the brachial plexus. No patients with chronic axonal polyneuropathies, however, had this finding. The magnitude of hypertrophy in the fibular and posterior tibial nerves was similar between patients with IgM neuropathy and those with CIDP, but sural nerve hypertrophy was greater in the former group than in the latter group. One potential explanation for the similar sonographic findings between IgM and CIDP is that humoral and cellular immune-mediated mechanisms might each disrupt the myelin sheath, thus resulting in nerve thickening, the investigators wrote.
“We found widespread and homogeneous enlargement of multiple nerves in both IgM neuropathy and CIDP,” Dr. Goedee and colleagues wrote.
Median nerve axial ultrasound scan in CIDP patients at different disability states. (a) Male, 60 years old; disease duration 64 months; upper limbs score on the Inflammatory Neuropathy Cause And Treatment (INCAT) disability scale: 1. (b) Male, 63 years old; disease duration 72 months; INCAT upper limbs score: 2. (c) Male, 62 years old; disease duration 79 months; INCAT upper limbs score: 4.
Credit: Merola A et al. Neurol Res Int. 2016. doi: 10.1155/2016/9478593.
In addition, most nerve conduction study variables were similar between patients with IgM neuropathy and those with CIDP. However, Dr. Goedee and colleagues observed longer distal motor latency in median and ulnar nerves and lower terminal latency index in patients with IgM neuropathy, compared with patients with CIDP. Furthermore, the sensory nerve action potential of the sural nerve was more often absent in IgM neuropathy than in CIDP, and conduction block was more common in CIDP than in IgM neuropathy.
What is the role of terminal latency index?
The European Federation of Neurological Societies and the Peripheral Nerve Society guideline recommends using a terminal latency index (TLI) of 0.25 or less for median and ulnar nerves as a criterion for identifying IgM neuropathy, as opposed to CIDP. However, Dr. Goedee and colleagues found that this criterion identified 56% of patients with IgM neuropathy. Furthermore, 31% of patients with CIDP met this criterion. A nerve ultrasound sum-score greater than 70 mm2 for the size of median nerves over four anatomical sites, however, identified 92% of patients with IgM neuropathy, compared with 10% of patients with CIDP.
Peripheral nerve ultrasound is a promising technique when used in association with EMG, but it cannot replace it
“We found widespread and homogeneous enlargement of multiple nerves in both IgM neuropathy and CIDP,” Dr. Goedee and colleagues wrote. “Only the nerve ultrasound sum of nerve size in median nerves (forearm and upper arm segments in both arms) showed promise in distinction between IgM neuropathy and CIDP, but additional studies are required to validate this finding and evaluate whether it can complement nerve conduction studies.”
“Peripheral nerve ultrasound is a promising technique when used in association with EMG, but it cannot replace it,” Aristide Merola, MD, PhD, associate professor of neurology at Ohio State University in Columbus said when asked for comment on the study. “I don’t think available data are sufficient to provide a robust differential diagnosis between anti-MAG [IgM neuropathy] and CIDP in the common clinical practice. … A technique that is worthy to be referenced is the TLI between the ulnar and median nerves, which has greater consensus in the differential diagnosis of these two conditions. This parameter should be used as a reference in all future studies on the topic.”
Aristide Merola, MD, PhD