Difficulties of CIDP Diagnosis

Abbreviations: CIDP: Chronic Inflammatory Demyelinating Polyneuropathy; NCS: Nerve Conduction Study; CSF: Cerebrospinal Fluid; GBS: GuillainBarré syndrome; HNPP: Hereditary Neuropathy with Pressure Palsies; MMN: Multifocal Motor Neuropathy; IVIg: Intravenous Immunoglobulin; DADS: Distal Acquired Demyelinating Symmetric Neuropathy; MADSAM: Multifocal Acquired Demyelinating Sensory and Motor Neuropathy; INCAT: Inflammatory Neuropathy Cause and Treatment


Chronic inflammatory demyelinating polyneuropathy (CIDP)
is an autoimmune neuropathy characterized by weakness and/or sensory symptoms developing over more than 8 weeks and hipo or areflexia. It is worth emphasizing that CIDP is the most common treatable neuropathy in the world [1]. It is important to include it in the differential diagnosis, as some studies suggest that CIDP is misdiagnosed in up to 47% of patients [2]. The reason of this phenomen is multifactorial, from diverse clinical presentation, especially misleading in atypical variants, through electrodiagnostic pitfalls to objective estimation of the treatment response. In this article we discuss the difficulties of diagnosis CIDP with particular emphasis on atypical variants.

CIDP Epidemiology and Diagnostic Criteria
The prevalence of CIDP is 0.46 -1.83 persons per 100.000 [3,4]. The disease occurs in all age groups, but the incidence increases with age, peaking in middle-aged people and is slightly more common in men [4]. In most cases symptoms progress over 2 months, however, in about 18% of patients the development of symptoms can be acute, mimicking Guillain-Barre syndrome (less than 4 weeks) or subacute (4-8 weeks) [5]. CIDP as an autoimmune disease can be preceded by an infection, mostly respiratory tract infection or gastroenteritis [6].
The typical clinical presentation is progressive, recurrent or stepwise symmetrical proximal and distal weakness with sensory symptoms in all extremities, in some cases additional cranial nerves involvement can also occur [7]. The course of the disease in younger patients is often relapsing-remitting, whereas in the elderly it is chronic progressive [8]. Nerve conduction study (NCS) demonstrates demyelinating changes: slowing of conduction velocity, prolongation of distal latency, prolongation or absence of F-wave, partial motor conduction block, abnormal temporal dispersion and prolongation of distal CMAP duration [7]. Supportive criteria include the cytoalbuminologic dissociation neuropathy associated with diabetes mellitus or vasculitis [5]. Based on the clinical and electrophysiological criteria CIDP diagnosis can be definite, possible or probable [7]. The first-line treatment are intravenous immunoglobulin (IVIg) or corticosteroids [7]. If the drugs are added [7]. The prognosis is rather good, however, most of the patients require long term treatment [7].

Atypical Variants of CIDP -Clinical Criteria Pitfalls
As mentioned in the Background an atypical presentation can be misleading and cause delay in the diagnosis. Initially 31-48% of patients present with an atypical CIDP, but over time most of them develops the typical clinical features, leaving only 18% patients with an atypical CIDP variant in the long-term follow-up [9]. The criteria for atypical CIDP has changed throughout the years [10].

Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM; Lewis-Sumner Syndrome)
In the MADSAM symptoms are multifocal, asymmetric, sensory loss is distal, while weakness usually affects upper more often than lower limbs, and is asymmetric [7]. Cranial nerves palsy has been described in MADSAM. Ataxia, cramps or autonomic dysfunction cam also coexist [10].

Focal CIDP
Focal CIDP affects motor and sensory fibers of one limbs' nerves, in the plexus or more peripherally [7]. In Table 1 there are summarized most characteristic information regarding atypical variants of CIDP and the most common mimics [5].

Pure Motor
This variant includes only motor symptoms and may involve cranial nerves but sensory disturbances or dysautonomia are never present [10].

Electrodiagnostic and Supplementary Criteria Pitfalls
One of the most important steps to an accurate diagnosis of CIDP is examining a sufficient number of peripheral nervesaccording to the EFNS recommendations at least 4 nerves (median, ulnar, peroneal and tibial) or more, if the diagnostic criteria are not met [7]. Study by Rajabelly et al. [11] has proved that assessing 5-8 nerves is associated with almost 100% diagnostic sensitivity.
Still, in cases where only the proximal nerves' segments, within the plexus or spinal roots are involved, these changes may not be confirmed in a routine NCS [9]. Other tests such as the CSF parameters can aid the diagnosis, but eg. protein concentration in CSF may be influenced by factors such as age, comorbid conditions including spinal stenosis or diabetes mellitus [9]. In the patients with diabetes mellitus a score created with the combination of clinical and laboratory features has been developed to aid CIDP diagnosis [12].  [9]. Relying only on the patient's impression may often be misleading [9].

Summary
To sum up the typical CIDP should not cause diagnostic difficulties with the appropriate work-up. Diagnosis of atypical variants may be misleading. It is important to remember about the diverse clinical and electrophysiological presentation as well as results from ancillary tests. The incorrect diagnosis is associated with the lack of treatment or the unnecessary, costly and potentially harmful therapy.