Muscle Cramps and Neuropathies in Patients with Allogeneic Hematopoietic Stem Cell Transplantation and Graft-versus-Host Disease

Abstract

ObjectiveGraft-versus-host disease (GVHD) is an immune-mediated multisystemic disorder and the leading cause of morbidity after allogeneic hematopoietic stem cell transplantation. Peripheral nervous system manifestations of GVHD are rare but often disabling. Whereas immune-mediated neuropathies are an established feature of GVHD, muscle cramps are not well characterized.MethodsIn a single-centre retrospective cohort we studied 27 patients (age 23 to 69 years) with GVHD (acute n = 6, chronic n = 21) who complained of symptoms suggestive of peripheral nervous system complications. Clinical, laboratory and neurophysiological findings were evaluated by descriptive statistics and regression analysis to detect factors associated with muscle cramps. Patient’s sera were examined for anti-neuronal antibodies.ResultsNine patients had polyneuropathy, 4 had muscle cramps, and 14 had both. Median onset of polyneuropathy and muscle cramps was 6 and 9 months after allogeneic hematopoietic stem cell transplantation, respectively. Neurophysiology revealed a predominantly axonal polyneuropathy in 20 of 26 patients. In 4 of 19 patients electromyography showed signs of myopathy or myositis. Muscle cramps were more frequent during chronic than acute GVHD and affected muscles other than calves in 15 of 18 patients. They typically occurred daily, lasted 1 to 10 minutes with medium to severe pain intensity, compromised daily activity or sleep in 12, and were refractory to therapy in 4 patients. Muscle cramps were less likely with tacrolimus treatment and signs of severe polyneuropathy, but more likely with myopathic changes in electromyography and with incipient demyelinating polyneuropathy, shown by increased high frequency attenuation of the tibial nerve. Serological studies revealed antinuclear or antimitochondrial antibodies in a subset of patients. Two of 16 patients had a serum reactivity against peripheral nervous tissue.ConclusionMuscle cramps are associated with chronic GVHD, often compromise daily activity, and correlate negatively with axonal polyneuropathy and positively with myopathy and incipient demyelination.

Peripheral nervous system involvement in lymphomas

“…Finally, peripheral nervous system involvement in course of chronic graft‐versus‐host disease (cGvHD), a major side effect of allogeneic hematopoietic stem cell transplantation, a procedure most often applied in heavily pre‐treated relapsed lymphoma patients, should be mentioned. It may present with different clinical manifestations, among which cramps, large and small fibers polyneuropathy of different degree of severity and impact on the quality of life . A recent prospective study on 27 patients with cGvHD reported that almost all (92.6%) the patients developed peripheral neuropathy, 6% with mixed large and small fibers neuropathies, the latter associated with pain.…”

Sleep Disruption in Hematopoietic Cell Transplantation Recipients: Prevalence, Severity, and Clinical Management

“…Insomnia is also a common side effects of taking corticosteroids particularly if the medication taken closer to bedtime. Muscle cramps and neuropathy have been found to be common among patients with GVHD and to disrupt sleep (41); neuropathy is also a risk factor for RLS (42). These factors and others can also perpetuate existing sleep problems and contribute to the development of persistent (lasting more than 3 months) or recurrent sleep problems.…”

Entrapment syndrome of multiple nerves in graft-versus-host disease

“…This case illustrates that cGVHD is not only associated with muscle cramps and polyneuropathies but can also cause peripheral nerve entrapment syndromes. The patient had long‐standing cGVHD affecting multiple organs, including fascia.…”

“…Chronic GVHD (cGVHD) can involve the peripheral nervous system and usually starts several months to years after allo‐HSCT . The clinical and electrophysiological presentation of cGVHD‐associated acute and chronic neuropathies is heterogeneous and can resemble Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, or chronic immune‐mediated axonal polyneuropathy . Although cGVHD is often associated with dermal and fascial sclerosis, entrapment neuropathies have not been described.…”