Does the Lewis-Sumner variant of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) typically present with pure motor axonal involvement and onset in the lower limbs?

Lewis-Sumner Syndrome: Clinical Presentation and Motor Involvement

The Lewis-Sumner variant of CIDP typically does not present with pure motor axonal involvement with onset in the lower limbs. Instead, it characteristically presents with asymmetric, predominantly distal involvement of the upper limbs with both sensory and motor features, or sometimes purely sensory symptoms initially 1, 2.

Typical Clinical Presentation of Lewis-Sumner Syndrome

• Lewis-Sumner syndrome (LSS) is considered an asymmetric variant of chronic inflammatory demyelinating polyneuropathy (CIDP) 3, 1
• Initial symptoms typically start in the distal part of an upper limb in approximately 70% of patients 2
• Presentation is sensorimotor in 65% and purely sensory in 35% of patients at onset 2
• Distal involvement predominates, with subsequent lower limb involvement occurring in less than 40% of cases 1
• Pain is reported as a feature in about 20% of patients 1

Electrophysiological Features

• LSS is characterized by the presence of motor conduction blocks in arm nerves in about 90% of cases 1
• The electrophysiological pattern suggests focal motor fiber demyelination rather than axonal involvement 2
• Sensory fiber involvement is typically widespread 2
• Abnormal distal sensory potentials are found in 87% of patients 2

Distinguishing Features from Other CIDP Variants

• LSS differs from pure motor CIDP, which presents with selective involvement of motor fibers without sensory symptoms 4
• Unlike the paraparetic variant of GBS that affects the lower limbs, LSS predominantly affects the upper limbs 3
• LSS can be distinguished from multifocal motor neuropathy (MMN) by the presence of sensory involvement and absence of anti-GM1 antibodies 2

Disease Course and Progression

• The course is typically chronic progressive in 71% of patients and relapsing-remitting in others 2
• During follow-up, approximately half of patients progress with a multifocal pattern, maintaining a distribution similar to the initial presentation 2
• The other half show progression to other limbs, suggesting evolution into a more diffuse neuropathy sharing similarities with typical CIDP 2
• LSS patients have a less favorable therapeutic response rate and long-term outcomes compared to other CIDP variants 5

Treatment Response

• Over 80% of treated LSS patients respond to immune-mediated therapy 1
• Intravenous immunoglobulin (IVIG) may be more effective than steroids for LSS 1
• Approximately 54% of patients respond to IVIG compared to 33% who respond to oral steroids 2
• Some patients (40%) may eventually stabilize without treatment 1

Clinical Pitfalls and Considerations

• LSS may initially present with purely sensory symptoms and later develop motor involvement, making early diagnosis challenging 6
• The asymmetric nature of symptoms can lead to misdiagnosis as a focal compressive neuropathy 3
• CSF protein levels are raised in only about 40% of cases, which is less frequent than in other CIDP variants 1, 5
• The upper-limb-onset variant of LSS may represent a separate entity from other asymmetric forms of CIDP 1

In conclusion, while Lewis-Sumner syndrome shares features with other inflammatory neuropathies, its characteristic presentation involves asymmetric upper limb involvement with sensory or sensorimotor features, rather than pure motor axonal involvement with lower limb onset.