Category: Parkinson's Disease: Non-Motor Symptoms
Objective: Describe an unusual case of severe pain syndrome associated with a predisposing genetic mutation, and review literature on causes of enhanced pain in PD.
Background: Pain is a significant non-motor symptom in PD. Neuropathic pain impacts 5-14% of PD patients. Nigrostriatal denervation in PD alters nociceptive mechanisms that can affect pain anticipation and processing. Attention and motivation deficits in PD may contribute to pain sensitization. The SCN9A gene codes for voltage-gated sodium channel Nav1.7 expressed in autonomic and sensory neurons. SCN9A mutations can lead to pain syndromes or insensitivity to pain. SCN9A variants are associated with pain risk in PD. There is a greater likelihood of developing chronic pain symptoms with anxiety and mood disorders due to overlap in central dopamine signaling dysfunction.
Method: Case report and literature review.
Results: A 61 year old male veteran with tremor dominant PD (diagnosed age 52), anxiety, depression, PTSD with early prominent complaints of muscle pain in affected limb presented with progressive dysesthesias at age 59. Initial symptoms were paresthesias of left leg with right leg involvement two months later. Dysesthesias awoke him at night and limited ambulation to at most 15 minutes at a time. Pain was worst at the soles of feet, extended to both knees with swelling of bilateral ankles and calves. Paresthesias extended to wrists and hands, specifically with writing and holding a phone up to the ear. Symptoms pronounced in the OFF state and later in the day. Exam without weakness or dystonia. A1c 5.8%, B12, thiamine, vitamin E, TSH, SPEP, urine heavy metals, ceruloplasmin, ANA, RF, Sjogren antibodies were unrevealing. MRI brain was normal. EMG showed moderately severe axonal polyneuropathy. No significant pain relief after trials of various classes of multiple neuropathic agents. Genetic testing revealed a heterozygous variant of uncertain significance of the SCN9A gene c.3188G>T (p.Ser1063lle), a gene mutation shown to increase pain sensitivity in PD patients. He experienced moderate relief with carbamazepine 100/50 mg.
Conclusion: Case highlights a heterozygous variant of the SCN9A gene, novel in the literature in the setting of intractable dysesthesias in a PD patient. If workup had not included genetic testing, a potential mechanism behind the positive response to carbamazepine would not have been elucidated.
References: [1] Bennett DLH, Woods CG. Painful and painless channelopathies. Lancet Neurol. 2014; 13:587-599.
[2] Defazio G, Gigante A, Mancino P, Tinazzi M. The epidemiology of pain in Parkinson’s disease. J Neural Transm. 2013; 120:583-586.
[3] Fil A, Cano-de-la-Cuerda R, Muñoz-Hellín E, et al. Pain in Parkinson disease: A review of the literature. Parkinsonism and Related Disorders. 2013; 285-294.
[4] Greenbaum L, Tegeder I, Barhum Y, et al. Contribution of genetic variants to pain susceptibility in Parkinson Disease. Eur J Pain. 2012; 16(9):1243-1250.
[5] Jarcho JM, Mayer EA, Jiang ZK, et al. Pain, affective symptoms, and cognitive deficits in patients with cerebral dopamine dysfunction. Pain. 2012; 744-754.
[6] Krämer HH, Rebhorn C, Geber C, Birklein F. Sympathetic and sensory nerve fiber function in multiple system atrophy and idiopathic Parkinson’s disease. J of Neurol. 2021; 268:3435-3443.
[7] Young Blood MR, Ferro MM, Munhoz RP, et al. Classification and Characteristics of Pain Associated with Parkinson’s Disease. Parkinson’s Disease. 2016; 6067132-6067138.
To cite this abstract in AMA style:
J. Park, B. Barton. SCN9A Gene Variant in a PD Case with Refractory Dysesthesias [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/scn9a-gene-variant-in-a-pd-case-with-refractory-dysesthesias/. Accessed October 4, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/scn9a-gene-variant-in-a-pd-case-with-refractory-dysesthesias/