Diagnostic Challenges in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Filip Eftimov; Ilse M. Lucke; Luis A. Querol; Yusuf A. Rajabally; Camiel Verhamme

Disclosures

Brain. 2020;143(11):3214-3224. 

In This Article

Abstract and Introduction

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consists of a spectrum of autoimmune diseases of the peripheral nerves, causing weakness and sensory symptoms. Diagnosis often is challenging, because of the heterogeneous presentation and both mis- and underdiagnosis are common. Nerve conduction study (NCS) abnormalities suggestive of demyelination are mandatory to fulfil the diagnostic criteria. On the one hand, performance and interpretation of NCS can be difficult and none of these demyelinating findings are specific for CIDP. On the other hand, not all patients will be detected despite the relatively high sensitivity of NCS abnormalities. The electrodiagnostic criteria can be supplemented with additional diagnostic tests such as CSF examination, MRI, nerve biopsy, and somatosensory evoked potentials. However, the evidence for each of these additional diagnostic tests is limited. Studies are often small without the use of a clinically relevant control group. None of the findings are specific for CIDP, meaning that the results of the diagnostic tests should be carefully interpreted. In this update we will discuss the pitfalls in diagnosing CIDP and the value of newly introduced diagnostic tests such as nerve ultrasound and testing for autoantibodies, which are not yet part of the guidelines.

Introduction

Chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) consists of a spectrum of immune-mediated neuropathies, causing weakness and sensory symptoms in a progressive, relapsing-remitting or monophasic fashion (Van den Bergh et al., 2010). Early diagnosis is important, as induction of treatment can prevent axonal damage and permanent disability (Bouchard et al., 1999; Eftimov et al., 2013; Mehndiratta et al., 2015; Hughes et al., 2017). Diagnosis is often challenging, because of the heterogeneous presentation. Clinical presentation and nerve conduction studies (NCS) play a major role in diagnosing CIDP, supplemented with diagnostic tests such as CSF examination, MRI, nerve biopsy and somatosensory evoked potentials (SSEP) (Van den Bergh et al., 2010). Recently, nerve ultrasound and testing for autoantibodies were introduced (Goedee et al., 2017b; Vural et al., 2018). Despite diagnostic guidelines, in clinical practice both mis- and underdiagnosis are common. Misdiagnosis is a major problem, leading to the inappropriate use of expensive and potentially harmful treatment; underdiagnosis means that patients may not get effective treatment (Boukhris et al., 2004; Ayrignac et al., 2013; Allen and Lewis, 2015; Lucke et al., 2019a). In this update we will discuss the frequent pitfalls in diagnosing CIDP and the value of newly introduced diagnostic tests such as nerve ultrasound and testing for autoantibodies.

Clinical Signs and Symptoms

Typical CIDP is defined as proximal and distal weakness and sensory dysfunction of all extremities, with absent or reduced tendon reflexes in all four limbs, with a progressive, relapsing-remitting or monophasic course, typically progressing over months. Atypical CIDP may be divided, based on clinical presentation, in the asymmetric, focal, distal, pure motor and pure sensory variants (Van den Bergh et al., 2010). Misdiagnosis is common and is reported in up to 50% of patients referred with a CIDP diagnosis, mainly in patients with an atypical presentation (Allen and Lewis, 2015). In patients with a typical presentation of proximal and distal weakness, diagnosing CIDP is often straightforward. It was even suggested to base diagnosis on a typical presentation without further investigations (Koski et al., 2009). However, none of the typical findings are specific for CIDP.

Diagnostic Criteria Sets

Consensus on the diagnostic criteria for CIDP has proven difficult, which led to many different sets throughout the years. One North American study (Breiner and Brannagan, 2014) compared 15 diagnostic criteria sets, including the revised European Federation of Neurological Societies/Peripheral Nerve Society (PNS/PNS) criteria (Van den Bergh et al., 2010), the van den Bergh and Piéret criteria (2004), the American Academy of Neurology (AAN) criteria (American Academy of Neurology, 1991) and the Koski criteria (Koski et al., 2009) in 57 CIDP patients and 37 patients with diabetic neuropathy and 39 patients with amyotrophic lateral sclerosis as control subjects (Table 1). The EFNS/PNS criteria had the highest sensitivities, with good specificities. Another European study (Rajabally et al., 2009) investigated the specific electrodiagnostic criteria, including the 2006 EFNS/PNS criteria (Hughes et al., 2006), the van den Bergh and Piéret criteria (2004), the AAN criteria (American Academy of Neurology, 1991) and the Koski criteria (Koski et al., 2009) in 151 CIDP patients and 162 patients with axonal neuropathies as control subjects. The EFNS/PNS electrodiagnostic criteria had the highest sensitivity of 81% for definite or probable CIDP, with specificities ranging from 79% to 96%, depending on the extent of the NCS. The specificity of the criteria sets are likely overestimated, as all studies used control patients with clear clinical phenotypes of axonal neuropathies or motor neuron diseases instead of the ideal control population with initially suspected CIDP with alternative diagnosis. As the EFNS/PNS 2010 criteria seem the most accurate and widely used set of criteria, this review will further mainly focus on this set (Rajabally et al., 2014). All diagnostic tests have their pitfalls and should be interpreted in the clinical context, including considering alternative causes of a demyelinating neuropathy (Table 2).

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