Peripheral Neuropathy Symptoms of Amyloidosis
Table of Contents
1. Introduction
Peripheral neuropathy is a common and disabling complication of amyloidosis, caused by the presence of amyloid deposits in peripheral nerves. It can substantially alter quality of life by inducing neuropathic pain, paresthesia, dysesthesia, and sensory loss.
Early diagnosis of these symptoms is important for timely diagnosis, focused therapy, and slowing disease progression. Peripheral neuropathy in amyloidosis can involve motor, sensory, and autonomic nerves, so symptom evaluation becomes challenging.
This article discusses the frequent symptoms, mechanisms, diagnostic strategy, and treatment modalities of peripheral neuropathy in amyloidosis.
2. Understanding Amyloidosis and Nerve Involvement
2.1 Pathophysiology
- Amyloid fibrils are deposited in endoneurium, perineurium, and blood vessels of peripheral nerves
- This results in axon degeneration, demyelination, and ischemic nerve injury
- Both sensory and motor fibers can be involved, and small fibers tend to be affected initially
2.2 Types of Amyloidosis with Neuropathy
- AL (light-chain) amyloidosis: Frequently involves small fibers with the result of neuropathic pain
- ATTR (hereditary or wild-type): Often presents with distal sensory-motor neuropathy
- AA amyloidosis: Rarely causes neuropathy
3. Common Symptoms of Peripheral Neuropathy in Amyloidosis
3.1 Neuropathic Pain
- Burning, shooting, or stabbing sensations
- Often worsens at night or with cold exposure
- Can significantly impair sleep and daily activities
3.2 Paresthesia
- Tingling or “pins-and-needles” sensations
- Usually begins in feet and hands (stocking-glove pattern)
- May progress proximally over time
3.3 Dysesthesia
- Abnormal or unpleasant sensations in response to light touch or temperature
- Can include hypersensitivity or pain from normally non-painful stimuli
3.4 Sensory Loss
- Reduced perception of touch, vibration, pain, or temperature
- Usually begins in the distal extremities and extends proximally
- Can cause balance problems, risk of falls, and injury
4. Involvement of motor and autonomic
4.1 Motor symptoms
- Distal muscle weakness, causing gait difficulty or difficulty performing fine activities
- Atrophy of muscles in severe cases
4.2 Autonomic symptoms
- Orthostatic hypotension: dizziness or fainting on standing
- Gastrointestinal dysmotility: nausea, diarrhea, or constipation
- Sweating abnormalities: reduced or excessive sweating
- Urinary or erectile dysfunction in certain patients
5. Patterns of Neuropathy
- Length-dependent neuropathy: Symptoms begin in distal extremities and migrate proximally
- Small fiber neuropathy: Pain, burning, and loss of temperature are predominant
- Large fiber neuropathy: Vibration and proprioception loss, weakness
- Mixed pattern: Frequent in AL amyloidosis
Case Example:
A 58-year-old patient with AL amyloidosis presented with burning feet, tingling of hands, and mild weakness, typical of distal symmetric sensorimotor neuropathy.
6. Diagnostic Approach
6.1 Clinical Examination
- Careful neurologic examination of sensory, motor, and autonomic function
- Assessment of reflexes, gait, and coordination
6.2 Electrophysiological Tests
- Nerve conduction studies (NCS): Are used to detect axonal loss and demyelination
- Electromyography (EMG): Is used to assess muscle involvement
6.3 Laboratory and Histopathologic Tests
- Serum and urine immunofixation for AL amyloidosis
- Genetic testing for hereditary ATTR amyloidosis
- Nerve biopsy in selected cases to prove amyloid deposition
6.4 Imaging
- MRI neurography: Visualizes nerve enlargement and amyloid deposits in advanced centers
7. Differential Diagnosis
- Diabetes mellitus and diabetic neuropathy
- Vitamin B12 deficiency
- Chronic kidney disease-related neuropathy
- Other hereditary or inflammatory neuropathies
- Early recognition of amyloidosis is crucial to avoid misdiagnosis
8. Management Strategies
8.1 Disease-Specific Therapy
- AL amyloidosis: Chemotherapy, stem cell transplant, or new anti-plasma cell agents
- ATTR amyloidosis: Tafamidis, patisiran, or inotersen
- Treatment at an early stage may stop progression and relieve symptoms
8.2 Symptomatic Treatment
- Neuropathic pain: Gabapentin, pregabalin, duloxetine, or tricyclic antidepressants
- Topical agents: Lidocaine patches or capsaicin cream
- Physical therapy: Balance training and strengthening
8.3 Autonomic Symptom Management
- Orthostatic hypotension: Fludrocortisone, midodrine, compression stockings
- Gastrointestinal symptoms: Prokinetic agents, dietary modifications
- Urinary issues: Bladder training, catheterization if needed
9. Prognosis and Quality of Life
- Peripheral neuropathy can persist even after disease-specific therapy
- Early recognition and intervention improve functional outcomes
- Symptom management improves daily living, independence, and quality of life
10. Case Studies and Real-World Evidence
- Case 1: Patient with small fiber neuropathy in AL amyloidosis improved with chemotherapy; pain decreased with gabapentin
- Case 2: ATTR patient with progressive paresthesia and autonomic dysfunction stabilized on tafamidis and supportive care
- These cases demonstrate the value of multimodal management
11. Patient Education and Lifestyle
- Educate patients on early symptoms of neuropathy
- Prevent injuries to the feet due to loss of sensation
- Promote consistent exercise in order to preserve strength and balance
- Compliance with medications and follow-up appointments
12. Future Directions
- Investigation on nerve-directed anti-amyloid drugs
- Utilization of biomarkers and imaging for early diagnosis
- Personalized pain management strategies for neuropathy relief
13. Conclusion
Peripheral neuropathy is a common and debilitating feature of amyloidosis, presenting with:
- Neuropathic pain
- Paresthesia
- Dysesthesia
- Sensory loss
Early recognition, accurate diagnosis, and multimodal management—including disease-specific therapy and symptom relief—can improve functional outcomes and quality of life.