What is chronic inflammatory demyelinating polyneuropathy (CIDP) and its pathophysiology?

What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?

CIDP is an acquired autoimmune demyelinating disorder of the peripheral nervous system characterized by progressive or relapsing symmetric proximal and distal weakness affecting both upper and lower extremities, sensory dysfunction, and reduced or absent deep tendon reflexes that evolves over at least 8 weeks. 1, 2, 3

Clinical Definition and Time Course

• The hallmark distinguishing feature is progression beyond 2 months, which separates CIDP from acute inflammatory demyelinating polyneuropathy (AIDP/Guillain-Barré syndrome) that progresses over days to 4 weeks 1, 2
• The onset is typically insidious with symptoms developing over at least 8 weeks, often following a relapsing-recovery pattern 4, 5
• Classic CIDP presents with progressive bilateral weakness with areflexia affecting both proximal and distal muscles symmetrically 1

Core Clinical Features

• Motor symptoms: Progressive symmetric weakness affecting both proximal and distal muscles of upper and lower limbs, with motor-dominant manifestation 1, 3
• Sensory symptoms: Paresthesias and sensory dysfunction affecting at least two limbs 3, 4
• Reflex changes: Decreased or absent deep tendon reflexes in affected limbs 1, 3
• Additional manifestations: Imbalance, ataxia, neuropathic pain, cranial nerve involvement, autonomic symptoms, and impaired ambulation leading to substantial disability 6, 4

Pathophysiology

Immune-Mediated Demyelination

CIDP is fundamentally an autoimmune disease involving both innate and adaptive immune system components that target peripheral nerve myelin, resulting in macrophage-mediated demyelination with lymphocytic infiltration. 1, 5

Cellular and Molecular Mechanisms

• Adaptive immunity: Involves T-cell dysfunction and B-cell mediated antibody production targeting myelin and nodal/paranodal proteins 5
• Innate immunity: Macrophages play a central role in the demyelination process through direct myelin destruction 1, 5
• Complement activation: The complement system contributes to nerve damage in certain CIDP subtypes 5

Antigenic Targets

• Myelin proteins: Possible self-antigens include myelin protein 0, myelin protein 2, peripheral myelin protein 22, Connexin 32, and myelin basic protein 4
• Nodal and paranodal proteins: Antibodies targeting contactin-1, contactin-associated protein 1 (CASPR1), and neurofascin-155 have been identified, leading to reclassification of these cases as demyelinating nodo-paranodopathies 4, 5
• Important caveat: Despite these discoveries, triggering antigens and correlative antibodies for most CIDP cases remain undiscovered 5

Environmental and Genetic Factors

• The etiology is multifactorial with both genetic predisposition and environmental triggers 4
• Infectious associations: Case reports link CIDP with Hepatitis B and C viruses, Bartonella henselae, Mycoplasma pneumoniae, HIV, Cytomegalovirus, and Epstein-Barr virus 4
• Demographics: Unlike many autoimmune diseases, CIDP generally affects older individuals and shows male predominance 4

Diagnostic Confirmation

Cerebrospinal Fluid Analysis

• Cytoalbuminologic dissociation (elevated protein with normal cell count) is the characteristic CSF finding 1, 2

Electrophysiological Studies

• Nerve conduction studies demonstrate demyelinating features including prolonged distal latencies, slowed conduction velocities, and conduction block 1, 2, 7
• These studies are necessary for diagnosis and help distinguish CIDP from other neuropathies 2

Additional Diagnostic Tools

• MRI of brachial or lumbosacral plexus can identify focal or diffuse peripheral nerve abnormalities 2
• Nerve biopsy may be useful in evaluating atypical forms of CIDP 2

CIDP Variants

• Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM/Lewis-Sumner Syndrome): Characterized by asymmetric involvement with preserved reflexes in unaffected areas 2
• Chronic neurovisceral variants: Present with slower progression of neurological symptoms 2
• Autoimmune nodopathies: The updated EAN/PNS 2021 guideline no longer considers these as CIDP since patients do not meet hallmark CIDP criteria, creating an unmet need for treatment guidance 3

Key Distinguishing Features from Other Neuropathies

Versus Mononeuritis Multiplex

• CIDP: Symmetric involvement with diffuse abnormalities on nerve conduction studies 7
• Mononeuritis multiplex: Asymmetric sensory/motor deficits in non-contiguous distribution with stepwise sequential nerve involvement, prominent pain, and focal abnormalities on electrodiagnostic testing 7

Versus Guillain-Barré Syndrome

• Time course is the key differentiator: GBS progresses over days to 4 weeks, while CIDP progresses beyond 2 months 1, 2