The earliest documented report of a chronic corticosteroid-responsive polyneuropathy dates back to 1958, when James Austin described two patients whose recurrent polyneuropathy responded to adrenocorticotropic hormone (ACTH) therapy.(1) Decades later, Dyck and colleagues formally introduced the term chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to describe this spectrum of disorders. (2) Since its initial characterization, the clinical and electrophysiological landscape of CIDP has significantly expanded, encompassing a wide array of phenotypes and disease trajectories.

CIDP is a chronic, acquired demyelinating polyneuropathy that manifests as a relapsing or progressive neurological disorder, presumed to be of autoimmune origin. It primarily affects adults between 40 and 60 years of age but has also been reported, though less frequently, in children. (3,4) Pathologically, CIDP is marked by longstanding, multifocal demyelination affecting spinal nerve roots, major nerve plexuses, and proximal peripheral nerves. (1-3,5,6)

Despite its heterogeneous presentation and variable course, timely recognition and diagnosis of CIDP remain crucial, as it is one of the few peripheral neuropathies amenable to treatment. The disease is potentially lifelong and can be disabling, with more than 50% of affected individuals experiencing temporary disability, and approximately 10% suffering persistent deficits or even mortality due to disease complications.(7)

Key diagnostic indicators of CIDP include electrophysiological evidence of acquired multifocal, non-uniform demyelination; cerebrospinal fluid (CSF) analysis showing albuminocytological dissociation; and nerve biopsy findings demonstrating inflammatory demyelination and remyelination. Several diagnostic frameworks have been proposed, including criteria from the American Academy of Neurology (AAN), the Saperstein criteria, the Inflammatory Neuropathy Cause and Treatment (INCAT) group, and the European Federation of Neurological Societies (EFNS). (8-12)

CIDP encompasses a number of clinical variants based on disease distribution and temporal progression. The primary distributional subtypes include distal acquired demyelinating symmetric neuropathy (DADS), multifocal motor neuropathy (MMN), and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). These atypical forms often differ significantly in presentation, disease trajectory, and treatment response. CIDP associated with comorbidities—particularly diabetes mellitus (CIDP-D)—is increasingly recognized and poses unique diagnostic and therapeutic challenges.

The present study was undertaken to comprehensively evaluate the clinical, electrophysiological, and biochemical profiles of patients diagnosed with CIDP over a 22-year period. It also aims to compare clinico-electrophysiological characteristics between typical and atypical CIDP, and between diabetic and idiopathic forms. In addition, we sought to assess the diagnostic accuracy of various clinical criteria within our patient population, with a focus on sensitivity and specificity.

This was a retrospective observational study conducted at a tertiary care center in South India. Medical records of patients admitted to the Medical Neurology ward of the Department of Neurology between January 1995 and December 2016 (a 22-year period) were reviewed. A total of 124 patients diagnosed with definite or probable Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) based on the American Academy of Neurology (AAN) criteria were included.

Inclusion and Exclusion Criteria

Patients with a diagnosis of CIDP as per AAN criteria were included. Those with other confirmed etiologies for chronic polyneuropathy, incomplete clinical or diagnostic evaluation, or less than one year of documented follow-up were excluded.

 Data Collection

Data were extracted using a structured proforma. This included: Demographic details, Clinical profile, Comorbidities, particularly diabetes mellitus, Electrophysiological studies (nerve conduction studies, NCS), Cerebrospinal fluid (CSF) analysis, Nerve biopsy findings (if available), Details of immunomodulatory therapy (agents used, dosages), Functional status at follow-up (using Hughes Disability Score), Occurrence of relapses.

Clinical and Electrophysiological Classification

Patients were categorized into typical and atypical CIDP based on clinical and electrophysiological features:

Typical CIDP was defined as having at least two months of motor and/or sensory dysfunction involving more than one limb in association with areflexia or hyporeflexia, along with electrophysiological evidence fulfilling at least three of the following criteria: partial conduction block in at least one motor nerve; reduced conduction velocity in two or more motor nerves, defined as less than 80% of the lower limit of normal (LLN) if the CMAP amplitude was greater than 80% of LLN or less than 70% of LLN if the CMAP amplitude was below 80% of LLN; prolonged distal latency in two or more motor nerves, defined as greater than 125% of the upper limit of normal (ULN) if the CMAP amplitude was greater than 80% of LLN or greater than 150% of ULN if the CMAP amplitude was below 80% of LLN; or abnormal F‑wave latency in at least two motor nerves, defined as absent or greater than 125% of ULN if the CMAP amplitude was greater than 80% of LLN or greater than 150% of ULN if the CMAP amplitude was below 80% of LLN. Cerebrospinal fluid analysis showing fewer than 10 cells/mm³ and, where available, nerve biopsy evidence of demyelination or remyelination were also considered supportive. Atypical CIDP was defined as a chronic, progressive, stepwise, or relapsing sensorimotor syndrome of more than two months’ duration presenting as one of several clinical variants, namely distal symmetric sensory CIDP (DADS), asymmetric multifocal sensorimotor CIDP (MADSAM), pure motor CIDP corresponding to multifocal motor neuropathy with conduction block (MMNCB), or pure sensory radiculoneuropathy.

Treatment and Follow-Up

Patients received first-line or second-line immunomodulatory therapy as per standard clinical guidelines and based on the discretion of the treating neurologist. All patients were followed up for at least one year.

Clinical improvement or deterioration was documented during follow-up visits using standardized neurological assessments. The primary outcome measures were:

1. Remission: Defined as a Hughes disability score of 0 or 1 while off treatment.
2. Relapse: Defined as clinical or electrophysiological deterioration after initial improvement.

STATISTICAL ANALYSIS

All statistical analysis were performed using SPSS version 21.0.Armonk, NY: IBM Corp. Descriptive analysis was performed to express the continuous variables as mean ± standard deviation or the median (interquartile range), and categorical variables were presented as numbers and percentages. Baseline characteristics were compared between the typical and atypical CIDP as well as diabetic and non-diabetic CIDP. Differences in continuous variables were assessed by one-way analysis of variance and differences between proportions were assessed by the Chi square test. Significance was considered at p ≤ 0.05.

Of the 124 patients who met the inclusion criteria, 81 (65.3%) were male. The mean age at presentation was 45.02 years (SD ±16.15; range: 2 to 80 years).

The most common presenting complaint was paresthesias of the feet (38.7%), followed by lower limb weakness (36.3%), paresthesias of the hands (12.9%), and upper limb weakness (9.6%). A small proportion (2.4%) presented initially with tremulousness of the hands.

An acute onset resembling Guillain–Barré Syndrome (GBS) was observed in 22 patients (17.7%). The clinical pattern was sensorimotor in 70.2% of patients, predominantly motor in 22.6%, and predominantly sensory in 7.3%.

Based on clinical and electrophysiological criteria, 101 patients (81.5%) were classified as having typical CIDP, while 23 (18.5%) had atypical CIDP. Among the atypical variants, 11 had MADSAM (multifocal acquired demyelinating sensory and motor neuropathy), 8 had MMNCB (multifocal motor neuropathy with conduction block), and 4 had DADS (distal acquired demyelinating symmetric neuropathy).

Acute presentation was comparably seen in 18 (17.8%) of typical CIDP and 4 (17.4%) of atypical CIDP patients.

Cranial nerve involvement was documented in 13 patients (10.5%), most commonly as bifacial weakness. Two patients exhibited hypoglossal weakness, and one had a unilateral sixth nerve palsy. Among those with cranial nerve involvement, 12 (11.9%) had typical CIDP compared to 1 (4.3%) with atypical CIDP (p = 0.459).

Functional Status at Presentation

At the time of presentation, 73 patients (58.9%) had significant functional impairment with a Hughes grade ≥3. This included 62 patients (61.4%) in the typical CIDP group and 11 patients (47.8%) in the atypical CIDP group.

A summary of the clinical profile is presented in Table 1

TABLE 1: CLINICAL PROFILE OF CIDP PATIENTS.

The electrophysiological evaluation revealed prolonged distal latencies in ≥ 2 nerves in 93 patients (75.0%), reduced conduction velocities in ≥ 2 nerves in 73 patients (66.1%), absent F waves or prolonged F wave latencies in ≥ 2 nerves in 120 patients (96.8%), partial conduction block in atleastone nerve in 64 patients (51.61%) and temporal dispersion in atleast 1 nerve in 88 patients (71.0%). Sensory conduction parameters showed median sural dichotomy in only 13(10.5 %) patients.

TABLE 2: ELECTROPHYSIOLOGICAL PROFILE OF CIDP PATIENTS.

Among 64 patients with conduction block in atleast 1 nerve, 41 patients (64.06%) had Hughe’s grade 3 or more. Among 88 patients with temporal dispersion in atleast one nerve, 50 patients (56.82%) had Hughes grade ≥ 3. 61.6% of patients with reduced conduction velocities in ≥ 3 nerves and 62.7% of patients with prolonged distal latencies in ≥3 nerves had a Hughe’s grade ≥3. Comparison of electrophysiological parameters between typical and atypical CIDP patients is summarised in Table:3. The only parameter that showed a statistically significant difference was prolonged distal latencies in patients with typical CIDP.

TABLE 3: COMPARISON OF ELECTROPHYSIOLOGICAL PARAMETERS BETWEEN TYPICAL AND ATYPICAL CIDP PATIENTS.

Comparison between I-CIDP and CIDP-D.

39 (31.5%) patients had pre existing Diabetes mellitus (CIDP-D). 34 (33.7%) patients with typical CIDP vs 5 (21.7%) patients with atypical CIDP were diabetic. The mean age was 55.97±10.9 years in the CIDP-D group vs 40.89±15.9 years in the Idiopathic CIDP (I-CIDP) group (p <0.001) indicating that the CIDP-D patients were older compared to I- CIDP. 31 (79.9%) patients with CIDP-D were males vs 50 (58.8%) patients with I- CIDP (p =0.056).

CIDP-D patients were more commonly males.

23 (59.0%) patients with diabetic CIDP vs 50 (58.8%) with I-CIDP had Hughes grade ≥ 3 at presentation (p=0.812).

8 (20.5%) patients with CIDP-D had autonomic dysfunction vs 5 (5.9%) patients with I-CIDP (p=0.042).

Comparison of electrophysiological parameters between idiopathic and diabetic CIDP patients is summarized in Table:4

TABLE:4. COMPARISON OF ELECTROPHYSIOLOGICAL PARAMETERS BETWEEN CIDP-D AND I-CIDP.

TABLE 5: COMPARISON BETWEEN VARIOUS DIAGNOSTIC CRITERIA FOR CIDP.

CSF findings.

119 patients underwent CSF study. CSF cell count was less than 10 cells/mm3in 117 patients and protein was > 45 mg/dl in 104 (83.9%) patients. Albuminocytological dissociation was present in 93(92.1%) cases of typical CIDP vs 11 (47.8 %) of atypical CIDP that included 5 (45.5 %) MADSAM patients (p<0.001). 84.5 % of patients with Hughes grade 3 or more had albuminocytological dissociation and 18.3% had CSF protein >200 mg/dl. Hughe’s grade ≥ 3 did not show significant correlation with severity of electrophysiological involvement or CSF protein level.

88 patients had nerve biopsy findings suggestive of inflammatory demyelinating neuropathy consistent with CIDP.

62 patients (50%) were treated with steroids alone, 18 (14.5 %) with IvIG, 22(17.7%) with therapeutic plasma exchange and 22(17.7 %) with steroid sparing immunosuppressants. 13 patients (10.5%) had a progressive course, 40 (32.3%) had a relapsing remitting course and 71 (57.3%) had a stable course. 32 (31.7%) typical CIDP patients and 8 (34.8%) atypical CIDP patients had a relapsing remitting course. 10 (9.9%) of typical CIDP and 3 (13.0%) of atypical CIDP patients had a progressive course inspite of appropriate treatment (p=0.835).

Comparison of sensitivities of various diagnostic criteria.

75 (74.3%) patients with typical CIDP satisfied the AAN electrodiagnostic criteria for definite CIDP and 26 (25.7%) patients for probable CIDP.

13 (56.5%) patients with atypical CIDP satisfied the AAN electrodiagnostic criteria for definite CIDP and 10 (43.5%) patients for probable CIDP.

94 (93.1%) patients with typical CIDP satisfied the Saperstein electrodiagnostic criteria for definite CIDP and 7(6.9%) patients for probable CIDP.

19(82.6%) patients with atypical CIDP satisfied the Saperstein electrodiagnostic criteria for definite CIDP and 4(17.4%) patients for probable CIDP.

97(96.0%) patients with typical CIDP satisfied the INCAT electrodiagnostic criteria for definite CIDP and 4(4.0%) patients for probable CIDP.

All patients with atypical CIDP satisfied the INCAT electrodiagnostic criteria for definite CIDP.

Historically, CIDP was diagnosed clinically based on progressive motor and sensory deficits and the patient’s response to corticosteroid therapy. The present study aimed to explore the correlation between clinical characteristics and electrophysiological findings in CIDP. Data from 124 patients diagnosed and managed over the past 22 years, with a median follow-up of 1.1 years, were analyzed. All patients fulfilled electrodiagnostic criteria and underwent nerve conduction studies; 119 had cerebrospinal fluid (CSF) analysis, and 88 underwent nerve biopsy.

The most common CIDP subtype observed was typical CIDP (81.45%), followed by MADSAM (8.87%) and DADS (3.23%). These findings are consistent with prior international studies. A Japanese study (13) reported typical CIDP in 60% and MADSAM in 34% of cases, while a French cohort showed 51% typical CIDP and 15% MADSAM.(14) In a UK study, typical CIDP constituted 80.4%, MADSAM 15.2%, and DADS 6.5% of cases.(15)

Acute-onset CIDP mimicking Guillain-Barré Syndrome (GBS) was seen in 17.8% of our cohort, aligning with previous studies reporting a 16–18% acute presentation rate. Acute CIDP often presents with prominent sensory symptoms, less cranial nerve involvement, and rarely necessitates ventilatory support—features helpful in distinguishing it from GBS. (16,17)

Electrophysiologically, 96.8% of patients showed F-wave abnormalities (either absent or prolonged latencies in at least two nerves), making this the most consistent finding in CIDP. Distal latency prolongation was significantly more common in typical CIDP (79.2%) than in atypical CIDP (56.5%; p = 0.031). Although conduction block was more frequently noted in atypical CIDP (69.6% vs. 47.5%), this difference was not statistically significant (p = 0.056). Median–sural sensory dichotomy, considered a marker of acquired demyelination, was observed in 10.5% of patients, with 11.9% in typical CIDP versus 4.3% in atypical CIDP (p = 0.459). These rates are considerably lower than those reported in the Japanese cohort (53% in typical CIDP and 11% in MADSAM). This difference may be attributed to differential nerve segment involvement; median sensory studies assess distal nerve segments, whereas sural sensory studies evaluate intermediate trunks. As distal involvement is more characteristic of typical CIDP, this dichotomy appears more frequently in that subtype.

There was no significant correlation between clinical severity, as assessed by Hughe’s grading, and the degree of electrophysiological involvement.

Among CIDP variants, patients with diabetes-associated CIDP (CIDP-D) were generally older and predominantly male. While an Indian study by Kalita et al. reported that CIDP-D is often associated with axonal damage and autonomic dysfunction (18), our study did not find significant electrophysiological differences between idiopathic CIDP and CIDP-D. Autonomic features, however, were more frequently observed in CIDP-D patients.

CSF analysis revealed albuminocytological dissociation (elevated protein with normal cell count) in 94.9% of typical CIDP cases, consistent with previous literature. (5,19) Importantly, there was no correlation between CSF protein levels and clinical severity. A significantly higher proportion of typical CIDP patients (92.1%) exhibited albuminocytological dissociation compared to atypical CIDP patients (47.8%, p < 0.001), supporting its diagnostic specificity for typical CIDP. Notably, only 45.5% of MADSAM patients had elevated CSF protein in our study, whereas prior reports suggest rates between 60% and 80%.(20,21)

Treatment strategies included corticosteroids, intravenous immunoglobulin (IVIg), plasma exchange, steroid-sparing immunosuppressants, or combination therapies. The disease course was stable in 57.3% of patients, relapsing-remitting in 32.3%, and progressive in 10.5%. There was no significant difference in disease course between typical and atypical CIDP groups.

Although the American Academy of Neurology (AAN) criteria are widely used for CIDP diagnosis, their limited sensitivity may result in underdiagnosis. Alternative criteria, such as those proposed by INCAT or Saperstein, may offer improved diagnostic yield. The INCAT criteria are especially pragmatic, as they rely primarily on clinical and electrophysiological findings without mandating CSF or nerve biopsy.

This study’s strengths include the use of strict clinical and electrophysiological inclusion criteria, a substantial sample size, and systematic follow-up for at least one year, minimizing the likelihood of missed relapses. Importantly, this is one of the few large-scale studies examining the clinico-electrophysiological profile of CIDP in the Indian population, contrasting with most prior data from Western or other Asian cohorts.

However, the study has several limitations. It is retrospective, with non-randomized treatment allocation that evolved over time. Additionally, disease heterogeneity could have influenced treatment responses across subgroups.

This study demonstrates that albuminocytological dissociation in cerebrospinal fluid (CSF) is a highly specific marker for typical CIDP. Among the electrophysiological parameters, absence of F-waves or prolongation of F-wave latencies emerged as the most consistent and reliable findings across the CIDP spectrum. Importantly, the severity of clinical disability did not show a significant correlation with the extent of electrophysiological involvement. Furthermore, the diagnostic sensitivity of the various electrodiagnostic criteria tested did not differ significantly when applied to our study population, suggesting that current criteria are equally applicable in the Indian context.

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