Since 1953, we know that hemiplegia can change the expression of a chronic inflammatory disease on the affected side. This phenomenon has been studied multiple times during the last 70 years.

Other than in my recent “Expert Viewpoints” where typically one pillar article demonstrates a great jump ahead, I want to demonstrate the effect of hemiplegia on chronic inflammation through mentioning several individual articles in a chronological order.

With a look at clinical cases, the concept of neuronal regulation of inflammation is confirmed by reports of patients with hemiplegia and chronic inflammatory diseases, where the paralytic side is protected from inflammation. Cases have been reported in whom hemiplegia manifested long after outbreak of chronic inflammatory rheumatic disease or long before, leading to protection independent of the time point of disease onset. Table 1 demonstrates the respective historical literature. The natural experiment of hemiplegia clearly demonstrates the importance of the nervous systems in chronic inflammatory diseases.

Table 1. Role of neuronal innervation for the development of rheumatoid arthritis and other inflammatory diseases. Abbreviation: PMR, polymyalgia rheumatica; pSS, progressive systemic sclerosis; RA, rheumatoid arthritis.

In the early years of clinical science, case reports were the cornerstone of medical literature and academic advancement because they provided a “first line of evidence” for new discoveries. Before the dominance of large-scale, evidence-based methodologies, physicians and scientists used descriptive studies of individual patients—or small series of patients—to document novel diseases, unusual symptoms, new side effects, and inventive diagnostic techniques.

Clinical case reports are the essential heartbeat of personalized medicine, transforming unique patient encounters into vital, shared knowledge for the global medical community. They serve as a critical “early warning system,” often providing the very first evidence of emerging infectious diseases, rare drug side effects, or ingenious bedside innovations that standardized trials might overlook. By documenting the “n-of-1” experience, these reports bridge the gap between rigid, controlled research and the messy, unpredictable reality of human biology. They preserve the art of clinical observation, ensuring that rare insights—which might otherwise remain isolated to a single clinic—become permanent building blocks for future breakthroughs and therapy.

In the realm of education, case reports are an unparalleled pedagogical tool, teaching students, and residents the art of “clinical detective work.” They move beyond the abstractions of textbooks to show how symptoms manifest in real people, fostering critical thinking and diagnostic reasoning. Engaging with these reports trains the next generation of clinicians to recognize patterns, respect the nuance of individual patient stories, and contribute to the collective wisdom of their profession early in their careers.

Case reports of hemiplegia sparing a paralyzed limb from chronic inflammatory disease suggest a broader pathophysiological concept. These instances indicate that the peripheral nervous system—specifically sensory, sympathetic, or parasympathetic nerve fibers and their associated neurotransmitters/ neuropeptides—plays a crucial role in driving chronic inflammation. The observation that hemiplegia can alleviate existing disease manifestations strongly suggests that the peripheral nervous system exerts a direct, aggravating effect on chronic inflammation. Consequently, the sparing of a paralyzed limb serves as a significant, positive example of neuroimmunomodulation.

References

1. Jacqueline F. A case of evolutive polyarthritis with localisation controlateral to a hemiplegia. Rev Rhum Mal Osteoartic. 1953;20:323-4.
2. Thompson M, Bywaters EGL. Unilateral rheumatoid arthritis following hemiplegia. Ann Rheum Dis. 1962;21:370-.
3. Lilly GD. Effect of sympathectomy on development of chronic osteoarthritis: case report. Ann Surg. 1966;163:856-8.
4. Glick EN. Asymmetrical rheumatoid arthritis after poliomyelitis. Br Med J. 1967;3:26-8.
5. Bland JH, Eddy WM. Hemiplegia and rheumatoid hemiarthritis. Arthritis Rheum. 1968;11:72-80.
6. Garwolinska H. Effect of hemiplegia on the course of rheumatoid arthritis. Reumatologia. 1972;10:259-61.
7. Velayos EE, Cohen BS. The effect of stroke on well-established rheumatoid arthritis. Md State Med J. 1972;21:38-42.
8. Glynn JJ, Clayton ML. Sparing effect of hemiplegia on tophaceous gout. Ann Rheum Dis. 1976;35:534-5.
9. Yaghmai I, Rooholamini SM, Faunce HF. Unilateral rheumatoid arthritis: protective effect of neurologic deficits. AJR Am J Roentgenol. 1977;128:299-301.
10. Smith RD. Effect of hemiparesis on rheumatoid arthritis. Arthritis Rheum. 1979;22:1419-20.
11. Carcassi A, Boschi S, Tundo G, Macri P. Unilateral rheumatoid arthritis. Minerva Med. 1981;72:951-6.
12. Ueno Y, Sawada K, Imura H. Protective effect of neural lesion on rheumatoid arthritis. Arthritis Rheum. 1983;26:118.
13. Hamilton S. Unilateral rheumatoid arthritis in hemiplegia. J Can Assoc Radiol. 1983;34:49-50.
14. Sethi S, Sequeira W. Sparing effect of hemiplegia on scleroderma. Ann Rheum Dis. 1990;49:999-1000.
15. Veale D, Farrell M, Fitzgerald O. Mechanism of joint sparing in a patient with unilateral psoriatic arthritis and a longstanding hemiplegia. Br J Rheumatol. 1993;32:413-6.
16. Lience E, Ros C, Sellas A, Arderiu A. Rheumatoid arthritis and hemiplegia: remission of the arthritis in the paretic limbs and appearance of a subcutaneous nodule in the non paretic elbow. Med Clin (Barc ). 1993;101:518-9.
17. Nakamura K, Akizuki M, Kimura A, Chino N. A case of polyarthritis developed on the non-paralytic side in a hemiplegic patient. Ryumachi. 1994;34:656-61.
18. Dolan AL. Asymmetric rheumatoid vasculitis in a hemiplegic patient. Ann Rheum Dis. 1995;54:532.
19. Tarkowski E, Naver H, Wallin BG, Blomstrand C, Tarkowski A. Lateralization of T-lymphocyte responses in patients with stroke. Effect of sympathetic dysfunction? Stroke. 1995;26:57-62.
20. Lapadula G, Iannone F, Zuccaro C, Covelli M, Grattagliano V, Pipitone V. Recovery of erosive rheumatoid arthritis after human immunodeficiency virus-1 infection and hemiplegia. J Rheumatol. 1997;24:747-51.
21. Lee JC, Salonen DC, Inman RD. Unilateral hemochromatosis arthropathy on a neurogenic basis. J Rheumatol. 1997;24:2476-8.
22. Keyszer G, Langer T, Kornhuber M, Taute B, Horneff G. Neurovascular mechanisms as a possible cause of remission of rheumatoid arthritis in hemiparetic limbs. Ann Rheum Dis. 2004;63:1349-51.
23. Kane D, Lockhart JC, Balint PV, Mann C, Ferrell WR, McInnes IB. Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint). Ann Rheum Dis. 2005;64:325-7.
24. Bordin G, Atzeni F, Bettazzi L, Beyene NB, Carrabba M, Sarzi-Puttini P. Unilateral polymyalgia rheumatica with controlateral sympathetic dystrophy syndrome. A case of asymmetrical involvement due to pre-existing peripheral palsy. Rheumatology (Oxford). 2006;45:1578-80.

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