What is the initial approach to managing polyneuropathy presenting with asymmetric/multifocal neuropathies?

Management of Polyneuropathy with Asymmetric/Multifocal Presentation

The initial approach to managing polyneuropathy presenting with asymmetric/multifocal neuropathies should include autonomic testing, skin biopsy, and consideration of nerve biopsy in select cases to establish the diagnosis and guide treatment. 1, 2

Clinical Presentation

• Asymmetric/multifocal neuropathies present with asymmetric sensory and/or motor deficits affecting multiple individual nerves or nerve roots, with pain as a prominent feature, particularly in inflammatory or vasculitic causes 2
• Common presentations include mononeuritis multiplex, radiculopathies, and plexopathies, with involvement of multiple individual nerves in an asymmetric pattern 2
• May affect cranial nerves, causing focal deficits like facial weakness or visual disturbances 2
• Sexual dysfunction, such as erectile dysfunction in males, can occur 2

Diagnostic Approach

Initial Testing

• Nerve conduction studies are essential to document large fiber involvement and to distinguish between axonal and demyelinating processes 2
• Electromyography helps identify length-dependent patterns of abnormalities or multifocal involvement 2
• MRI may show nerve root enhancement or thickening in some cases 2

Specialized Testing

• Autonomic testing should be considered to document autonomic nervous system dysfunction, particularly for suspected autonomic neuropathy or small fiber sensory polyneuropathy 1
• A battery of validated autonomic tests rather than a single test is recommended to achieve the highest diagnostic accuracy 2
• Skin biopsy with intraepidermal nerve fiber (IENF) density assessment is a validated technique for determining small fiber involvement and may be considered for the diagnosis of distal symmetric polyneuropathy (DSP), particularly small fiber sensory polyneuropathy (SFSN) 1
• Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies such as suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP) 1

Management Considerations

Differential Diagnosis

• The distinction between polyneuropathy and multifocal mononeuropathy is crucial as they often have different underlying causes requiring different treatment approaches 2
• Consider CIDP variants, which can present with asymmetric features (MADSAM neuropathy) or multifocal motor neuropathy (MMN) 3
• Multifocal motor neuropathy may mimic amyotrophic lateral sclerosis or other motor neuron diseases but differs in treatment and prognosis 4

Treatment Strategies

• Polyneuropathy management typically focuses on treating the underlying cause and symptom management 2
• Multifocal neuropathy may require immunosuppressive therapy if caused by inflammatory processes 2
• For neuropathic pain, FDA-approved medications include duloxetine, which has demonstrated efficacy in diabetic peripheral neuropathic pain 5
• Intravenous immunoglobulin is efficacious in most patients with multifocal motor neuropathy, but long-term maintenance therapy does not prevent slowly progressive axonal degeneration 4

Special Considerations

Small Fiber Involvement

• Small fiber polyneuropathy often presents with prominent pain and autonomic symptoms, with minimal or absent motor findings 2
• Burning pain affecting the feet and erythromelalgia are characteristic 2
• Small-fiber polyneuropathy may have normal conventional nerve conduction studies and requires skin biopsy to detect decreased epidermal nerve fiber density 2

Autonomic Involvement

• Autonomic neuropathy can occur as a component of generalized polyneuropathy, as a distinct autonomic neuropathy, or as part of small fiber sensory polyneuropathy 2
• Cardiovascular manifestations include orthostatic hypotension 2
• Gastrointestinal manifestations include early satiety, nausea, vomiting, and gastroparesis 2
• Sudomotor dysfunction, with abnormal sweating patterns and circulatory instability in the feet, is common 2

Clinical Pearls and Caveats

• The electrophysiological finding of conduction block in the absence of abnormalities in sensory nerves is the hallmark of multifocal motor neuropathy but can be difficult to detect 4
• Chronic multifocal demyelinating neuropathy with persistent conduction block appears to be a variant of chronic acquired demyelinating polyneuropathy and may be immunologically mediated 6
• Once axonal degeneration has occurred, complete reversal is unlikely as the peripheral nervous system has limited regenerative capacity 7