Diagnosis of CIDP especially among variant subtypes can be challenging and misdiagnosis is not uncommon. For focal CIDP, there is no gold-standard diagnostic tool and meanwhile, reliable diagnostic biomarkers are lacking. Diagnosis is still mainly relied on specific clinical features and meeting electrodiagnostic criteria, which is the main diagnostic requirements as per recently updated EAN/PNS 2021 guideline (1). In this case report, we illustrated the practical example of application of revised guideline on a rare case of focal right lower limb monomelic CIDP where fulfilling electrodiagnostic criteria is limited by NCS pitfalls of lower limbs nerves.
Clinical diagnosis
On clinical grounds, suspicion of focal CIDP is less considered and diagnosis is often uncertain due to lacking in typical CIDP phenotype. The diagnostic hallmark of classical proximal and distal weakness involving all limbs in typical CIDP is absent in focal CIDP (2, 3). Involvement of only single limb often leads clinicians into prioritizing other more common etiologies of mononeuropathy such as lumbosacral radiculoplexopathy, vasculitis or compression. In majority of cases, disease runs on a more gradually progressive nature rather than the typical relapsing-remitting course (3). Therefore, unlike typical CIDP, the accuracy of clinical diagnosis in focal CIDP is less reliable and supportive electrodiagnostic findings of demyelination are required.
Electrodiagnostic Criteria
In practice, electrodiagnostic yield in CIDP is directly proportional to the number of limbs, nerves and the number of nerve segments studied (4). The revised criteria included sensory nerve study aimed to improve diagnostic sensitivity. For a confirmed diagnosis, at least 2 demyelinating features in two different motor nerves with sensory conduction abnormalities in at least 2 nerves in the affected limb are required (1). Although this is achievable for most typical CIDP cases, it is difficult to fulfill for focal variant as all the motor nerves in one lower limb are required to meet criteria of demyelination. On presentation, our patient demonstrated 1 motor and 2 sensory nerves conduction abnormality, sufficient only to fulfil possible diagnostic certainty. One can argue that with time and disease progression, more motor nerves might demonstrate demyelination changes and therefore, diagnostic certainty upgraded or changed to multifocal CIDP. However, most focal CIDP cases are slowly progressive, as demonstrated by our patients (3). Nevertheless, inclusion of sensory conduction criteria into the new guideline did not change diagnostic certainty and therefore its usefulness remains unknown. Recent validation study also demonstrated that the diagnostic value of sensory conduction criteria which is mandatory in the updated criteria did not change diagnostic sensitivity and specificity compared to the previous criteria (5).
From technical point of view, there are limited number of motor nerves (peroneal and tibial) and sensory nerve (sural) that can be tested in a single limb using routine NCS. For sensory study, only sural nerves are commonly tested. Other sensory nerves testing in the lower limb is not routinely done and their significance in CIDP is less well established. In addition, each nerve in the lower limbs comes with specific misdiagnosis pitfalls, making misinterpretation of demyelinating features difficult especially among the inexperienced (5). The accurate interpretation of electrophysiological demyelinating features of peroneal nerve needs to take into consideration of 2 factors i.e. first, conduction slowing and block due to fibula segment compression and secondly, low amplitude of distal CMAP at extensor digitorum brevis (EDB) in which small reduction due to axonal loss may led to difficulty in interpretation of distal latencies and conduction velocities. Likewise, for tibial CMAP, non-stringent interpretation of proximal CMAP may misinterpret false conduction block and temporal dispersion due to technical complexity from its anatomical impediment. Additionally, for both peroneal and tibial nerves, proximal nerve segments including the lumbosacral plexus are not reliably accessible by routine NCS technique. Till date, the use of special electrodiagnostic study including somatosensory evoker potentials, root stimulation and triple stimulation technique in CIDP are not well established.
Diagnosis Upgrade with Supporting Criteria
Traditionally, diagnostic criteria for CIDP have been based mainly on clinical and electrophysiology patterns. The updated 2021 EAN/PNS guideline allows the use of several supportive criteria to further optimise diagnostic accuracy of CIDP (1). This includes positive response from treatment trial with objective validated measures, imaging findings, cerebrospinal fluid examination and nerve biopsy. Our patient fulfilled possible diagnostic certainty on clinical and electrodiagnostic ground. With positive treatment response and elevated CSF protein, diagnosis of CIDP can be upgraded to fulfil focal CIDP diagnostic certainty. This in clinical practice addressed the limitation of clinical and electrodiagnostic criteria which is difficult to fulfil, particularly among patient with focal CIDP. However, questions remain on the weight and validity of these supporting criteria on various subtypes of CIDP. In many institutions, availability and expertise in performing these investigations are limited and therefore its universal applicability.
At present, the updated EAN/PNS diagnostic criteria for focal CIDP has its own limitations where clinically it is lacking in hallmark characteristic, and on electrodiagnostic ground, the requirement to fulfil demyelination is rather rigid. Although the inclusion of supportive criteria is a positive move in improving diagnosis in clinical practice, the reliability and accuracy of these criteria on various subtypes of CIDP requires future study.