Expanded neuromuscular morbidity in Hodgkin lymphoma after radiotherapy

Abstract

Our study aims to quantitate neuromuscular morbidity from radiotherapy in Hodgkin lymphoma including: (i) frequency and (ii) time of onsets for neurological localizations; (iii) degree of disabilities and (iv) number of clinical visits compared to cardiopulmonary Hodgkin lymphoma-radiation complications. Medical records from Mayo Health systems were retrieved; identifying neuromuscular radiation treated Hodgkin lymphoma-complications from 1 January 1994 to 31 December 2016. Of an estimated 4100 post-radiotherapy Hodgkin lymphoma patients, 4.6% (189) were identified with complications. Mean latency to physician visit for symptoms was 23.7 years (range: 1–50). Most commonly identified complications included: head drop 10% (19) with or without myopathy, myopathy 39% (73), plexopathy 29% (54), myelopathy 27% (51) and polyradiculopathy 13% (24). Other findings included benign and malignant nerve sheath tumours 5% (9), phrenic and long thoracic mononeuropathies 7% (14) and compressive spinal meningioma 2% (4). Patients frequently had multiple coexisting complications (single = 76% [144], double = 17% [33], triple = 4% [8], quadruple = 2% [4]). Cardiac 28% (53) and pulmonary 15% (29) complications were also seen in these patients. History of Hodgkin lymphoma was initially overlooked by neurologists (14.3%, 48/336 clinical notes). Hospital and outpatient visits for complications were frequent: neuromuscular 19% (77/411) versus cardiopulmonary 30% (125/411). Testing was largely exclusionary, except when imaging identified secondary malignancy. Modified Rankin score at diagnosis varied: 0–1 (55.8%), 2–3 (5.8%) and 4–5 (38.3%). Neuromuscular complications among post-radiation Hodgkin lymphoma are diverse, occurring in ∼1 of 20 having markedly delayed onsets often eluding diagnosis. Frequent care visits and major morbidity are common. Survivorship recommendations should recognize the diverse neurological complications.

Quantitative analysis of myokymic discharges in radiation versus nonradiation cases

“…Although a myopathic process on its own is not expected to give rise to myokymic discharges, the radiation treatment presumably led to both a peripheral nerve irritability giving rise to myokymic discharges, as well as a superimposed radiation-induced myopathy within the field of radiation. [9][10][11] The conspicuous absence of myokymic discharges in hand muscles among radiation-associated cases is also noteworthy. It is unknown whether this difference was because the innervating axons happened to be spared from the field of radiation in these cases because of the greater anatomical distance from the field of radiation (as most radiation beams are directed at axial structures), or due to some intrinsic resilience to hyperexcitability of these muscles after radiation damage to their innervating nerves.…”

“…Interestingly, two patients in the postradiation group were noted to have myopathic motor unit potentials on EMG, and in both instances the electromyographer commented on probable underlying radiation‐induced myopathy. Although a myopathic process on its own is not expected to give rise to myokymic discharges, the radiation treatment presumably led to both a peripheral nerve irritability giving rise to myokymic discharges, as well as a superimposed radiation‐induced myopathy within the field of radiation 9‐11 …”

Clinical, Neurophysiologic, and Pathologic Features in Patients With Early-Onset Postradiation Neuropathy

“…2 A recent review of the lifetime risk of neuromuscular complications in 4,100 radiation-treated cases with Hodgkin lymphoma identified that approximately 1 of 20 patients had neurologic radiation-induced complications including neuropathy, plexopathy, myopathy, and myelopathy. 3 Radiation-induced brachial 4,5 and lumbosacral plexopathies 6 occur in diverse cancer types. The symptom onset for radiation-induced neuropathies is typically delayed occurring on average 20 years postradiation.…”

“…The symptom onset for radiationinduced neuropathies is typically delayed occurring on average 20 years postradiation. 3,7 Chronic progressive weakness is typical, without neuropathic pain or sensory symptoms, and no cure is currently available. [3][4][5][6][7][8][9] The pathogenic mechanism behind chronic postradiation neurologic complications is believed to relate to microvascular injury from the radiation exposure leading to fibrosis in both neural and non-neural tissues.…”

“…3,7 Chronic progressive weakness is typical, without neuropathic pain or sensory symptoms, and no cure is currently available. [3][4][5][6][7][8][9] The pathogenic mechanism behind chronic postradiation neurologic complications is believed to relate to microvascular injury from the radiation exposure leading to fibrosis in both neural and non-neural tissues. 9 The specific role inflammation plays in this process is unclear in the peripheral nervous system, but subacute-onset inflammation and angiogenesis have been reported in radiation-induced necrosis of the brain.…”