CIDP - Chronic Inflammatory Demyelinating Polyneuropathy

Clinical Presentation and Phenotypic Variability

CIDP presents with a characteristic clinical pattern but exhibits significant phenotypic variability.

Typical Symmetric Form

• Muscle Weakness: Symmetrical, both proximal and distal; progressive for >8 weeks.

• Distribution: Affects both upper and lower limbs, involving both flexor and extensor muscles.

• Severity: Ranges from mild impairment to severe quadriparesis (tetraparesis).

• Progression: Slow, with either a relapsing-remitting or a steadily progressive course.

Sensory Manifestations

• Positive Symptoms: Paresthesias, tingling, and neuropathic pain.

• Sensory Loss: Affects vibratory and proprioceptive sensation (leading to an ataxic pattern).

• Distribution: Symmetrical and distal, occasionally proximal.

• Pain: Present in approximately 60% of patients, presenting as neuropathic pain in the limbs or trunk.

Neurological Signs

• Areflexia/Hyporeflexia: Diffuse and early-onset; ankle reflexes are consistently absent.

• Sensory Ataxia: Gait instability with a positive Romberg sign.

• Postural Tremor: Fine tremor of the upper limbs, correlated with demyelination.

• Facial Weakness: Occasional and asymmetric.

Atypical Variants

• MADSAM (Multifocal Acquired Demyelinating Sensory and Motor neuropathy):

  • Asymmetric distribution: Presents as mononeuropathy multiplex.

  • Involvement: Commonly affects the median, ulnar, peroneal, and tibial nerves.

  • Conduction blocks: Persistent and localized.

• DADS (Distal Acquired Demyelinating Symmetric neuropathy):

  • Distal involvement: Predominantly affects the hands and feet.

  • Association: Frequently associated with monoclonal gammopathy (e.g., anti-MAG antibodies).

  • Therapeutic response: Limited compared to the typical form.

• Lewis-Sumner Syndrome:

  • Mononeuropathy multiplex: Asymmetric, typically with an upper limb onset.

  • Progression: Slow, with persistent deficits.

  • Electrophysiology: Characterized by conduction blocks and temporal dispersion.

System and Organ Involvement

• Respiratory System: Rare, occurring in severe forms (5–10% of patients).

• Autonomic System: Occasional, leading to symptoms like orthostatic hypotension.

• Cranial Nerves: Affects CN VII, III, or VI in 10–15% of cases.

• Spinal Roots: Proximal involvement, often showing nerve root enhancement on MRI.

Diagnostic Criteria & Clinical Evaluation

• Diagnostic Criteria: European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021*, based on a combination of clinical, electrophysiological, laboratory, and imaging data.

• Clinical Evaluation: History (progression >8 weeks, potential triggers), neurological examination (strength, sensation, reflexes), and functional scales (INCAT disability scale, grip strength).

Electrophysiology (Essential Criterion)

• Key Findings: Reduced motor nerve conduction velocity (<70% of the lower limit of normal), conduction blocks (>50% reduction in CMAP amplitude), temporal dispersion (duration >130% of normal), and prolonged distal latencies.

• Electrophysiological Pattern: Primary demyelination, multifocal involvement, motor and sensory nerve affection, and prolonged or absent F-waves.

Laboratory & Imaging Studies

• Laboratory Tests: Elevated cerebrospinal fluid (CSF) protein (>45 mg/dL) with normal cell count (<10/μL) [albuminocytologic dissociation], serum/urine immunoelectrophoresis (to check for monoclonal gammopathy), and specific antibodies (anti-NF155, anti-CNTN1, anti-CASPR1).

• Specialized Imaging: Nerve MRI (gadolinium enhancement, thickening), brachial/lumbosacral plexus MRI (root enhancement), and nerve ultrasound (thickening, hypoechogenicity).

• Nerve Biopsy: Rarely necessary, indicated only for atypical cases; shows segmental demyelination, inflammation, and “onion bulb” formations.

Rating Scales & Differential Diagnosis

• Evaluation Scales: INCAT disability scale (0–10), Overall Neuropathy Limitations Scale (ONLS), MRC sum score, and Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale.

• Differential Diagnosis: Guillain-Barré syndrome (progression <4 weeks), genetic neuropathies (Charcot-Marie-Tooth type 1 / CMT1), paraproteinemic, vasculitic, diabetic, and toxic neuropathies.