Neuropathic Complications in Parkinson's Disease Patients

Parkinson’s disease (PD) is primarily characterised by central dopaminergic neuronal loss, yet increasingly recognised non-motor features include a spectrum of neuropathic complications. These encompass peripheral sensory and motor neuropathies, autonomic fibre dysfunction and small-fibre neuropathy. Peripheral neuropathy in PD may arise as a direct consequence of neurodegeneration, from chronic levodopa therapy, or through systemic factors such as vitamin B deficiencies, hyperhomocysteinaemia and metabolic disturbance. Clinically, patients frequently report distal sensory loss, burning dysaesthesia, gait instability and orthostatic hypotension. Electrophysiological studies demonstrate axonal degeneration of large myelinated fibres, while skin biopsy and quantitative sensory testing reveal small-fibre impairment. Underpinning mechanisms include oxidative stress, mitochondrial dysfunction, chronic inflammation and nutritional deficits, notably of vitamin B12, folate and pyridoxine. High cumulative levodopa doses, particularly when administered via intestinal gel, have been linked to elevated homocysteine and B-vitamin depletion, exacerbating peripheral nerve injury. The global significance of these complications lies in their adverse impact on quality of life, fall risk and health-care costs, prompting exploration of targeted neuroprotective, anti-inflammatory and nutritional interventions.

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Neuropathic Complications in Parkinson's Disease Patients publication trend

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Technical terms

Peripheral neuropathy: Dysfunction of peripheral nerves leading to sensory loss, motor weakness or autonomic symptoms.

Small-fibre neuropathy: Selective damage to unmyelinated or thinly myelinated fibres causing pain, thermal dysaesthesia and autonomic disturbance.

Autonomic neuropathy: Impairment of autonomic nerve fibres resulting in orthostatic hypotension, gastrointestinal motility issues and sweating abnormalities.

Hyperhomocysteinaemia: Elevated homocysteine levels in blood, often linked to B-vitamin deficiency and associated with neurotoxicity and vascular injury.

Axonal degeneration: Progressive loss of the nerve fibre itself, leading to slowed conduction velocity and reduced amplitude on neurophysiological testing.

References

1. No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease. Cells (2024).
2. Neuropathy in Parkinson’s Disease Patients with Intestinal Levodopa Infusion versus Oral Drugs. PLOS ONE (2013).
3. Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy. Brain and Behavior (2017).
4. Small (autonomic) and large fiber neuropathy in Parkinson disease and parkinsonism. BMC Neurology (2016).