What is distal axonal sensory predominant neuropathy?

Distal Axonal Sensory Predominant Neuropathy

Distal axonal sensory predominant neuropathy is a length-dependent peripheral nerve disorder characterized primarily by damage to sensory nerve axons, affecting small and large sensory fibers with predominant distal distribution, resulting in sensory symptoms like pain, paresthesia, and proprioceptive deficits that typically begin in the feet and progress proximally in a stocking-and-glove pattern.

Clinical Characteristics

Sensory Manifestations

• Stinging sensations, numbness, and paresthesia (tingling) that initially affect the toes and sometimes fingers, potentially extending proximally 1
• Positive sensory symptoms in a stocking-and-glove distribution 1
• Reduced deep tendon reflexes proportional to sensory loss 1
• Changes in proprioception and vibratory sensitivity 1
• Elevated touch detection threshold and impaired sharpness detection 1
• Altered thermal sensation (elevated thresholds for skin warming and heat pain) 1
• Pain that typically does not subside between episodes 1

Motor Involvement

• Motor impairment is relatively rare but can occur in approximately 10% of cases 1
• When present, motor symptoms typically manifest as mild to severe distal weakness in the lower limbs 1
• Severe motor involvement is uncommon but can be life-threatening in rare cases 1

Autonomic Features

• Dysautonomic features may be present in about 10% of patients 2
• Orthostatic hypotension is the most common autonomic manifestation 1
• Can be difficult to recognize and manage, often dose-dependent in medication-induced cases 1

Electrophysiological Findings

The hallmark electrophysiological findings include:

• Low amplitude of sensory action potentials 1
• Relative preservation of nerve conduction velocities 1
• Pattern consistent with length-dependent, sensory, axonal polyneuropathy 1
• Predominant small-fiber involvement in many cases 1
• Electrodiagnostic studies (EMG and nerve conduction studies) are essential for confirming the axonal pattern and quantifying severity 2

Etiologies

Distal axonal sensory predominant neuropathy can result from various causes:

1. Metabolic disorders

   • Diabetes mellitus (affects up to 50% of patients with diabetes) 2

2. Toxic exposures

   • Chemotherapeutic agents (30-40% of treated patients) 2
   • Particularly with agents like taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib 2

3. Immune-mediated disorders

   • Paraproteinemias (including monoclonal gammopathies) 2
   • Anti-MAG antibodies may be present in some cases 1

4. Infectious causes

   • Hepatitis C virus (up to 50% of cases) 2
   • HIV-related neuropathy 2

5. Idiopathic

   • Approximately half of cases are initially considered idiopathic despite thorough evaluation 3

Diagnostic Approach

1. Clinical assessment

   • Evaluate for stocking-and-glove distribution of sensory symptoms
   • Test proprioception, vibration sense, and thermal sensation
   • Assess deep tendon reflexes
   • Evaluate for possible motor involvement

2. Electrodiagnostic studies

   • Nerve conduction studies to confirm axonal pattern
   • Quantify severity of polyneuropathy 2

3. Laboratory testing

   • Complete blood count
   • Comprehensive metabolic panel
   • HbA1c
   • Vitamin B12 levels
   • Serum protein electrophoresis
   • Testing for hepatitis B, C, and HIV 1
   • Consider anti-MAG antibodies if demyelinating features are present 1

4. Specialized testing

   • Skin biopsy with intraepidermal nerve fiber (IENF) density assessment may be helpful, especially in small fiber neuropathy 1
   • The sensitivity of decreased IENF density for polyneuropathy diagnosis ranges from 45-90% with high specificity (95-97%) 1

Management

Treatment should focus on:

1. Addressing the underlying cause

   • Strict glycemic control for diabetic neuropathy 2
   • Dose reduction or alternative regimens for chemotherapy-induced neuropathy 2
   • Antiviral therapy for HCV-related neuropathy 2
   • Optimization of antiretroviral therapy for HIV-related neuropathy 2
   • Immunotherapy (rituximab, IVIG, or plasma exchange) for paraproteinemic neuropathies 2

2. Symptomatic management of neuropathic pain

   • Medications such as pregabalin, gabapentin, and duloxetine 2
   • For severe cases, combination therapy may be necessary

3. Rehabilitation

   • Proprioceptive rehabilitation including active and passive movement training 2
   • Somatosensory stimulation and discrimination training 2

Prognosis

The prognosis depends primarily on the underlying cause:

• Toxic neuropathies may improve with removal of the causal agent 2
• Metabolic neuropathies often stabilize with adequate control of the underlying condition 2
• Idiopathic forms typically progress slowly over time 2
• Regular neurological evaluation is recommended to monitor disease progression 2

Common Pitfalls and Caveats

1. Misdiagnosis: Distal axonal sensory neuropathy can be confused with other conditions like radiculopathy or sensory neuronopathy. Unlike sensory neuronopathy, distal axonal sensory neuropathy has a length-dependent pattern 4.

2. Incomplete evaluation: Approximately half of cases initially considered idiopathic may have identifiable causes that emerge later as new symptoms develop or with advanced testing 3.

3. Overlooking small fiber involvement: Small fiber involvement may not be detected by standard nerve conduction studies and may require specialized testing like skin biopsy 1.

4. Delayed treatment: Early recognition and treatment of potentially treatable causes is crucial for better outcomes 4.