Demyelinating polyneuropathy combined with brachial plexopathy after nivolumab therapy for hodgkin lymphoma: a case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor that targets the programmed cell death-1 protein and is effective in treating advanced cancer. However, it is also associated with various immune-related neurological complications, including myasthenia gravis, Guillain-Barré syndrome, and demyelinating polyneuropathy. These complications can easily mimic other neurological diseases and have greatly varying therapeutic approaches depending on the underlying pathophysiology. CASE PRESENTATION: Here, we report a case of nivolumab-induced demyelinating peripheral polyneuropathy involving the brachial plexus in a patient with Hodgkin lymphoma. Approximately 7 months after nivolumab treatment, the patient experienced muscle weakness with a tightness and tingling sensation in the right forearm. Electrodiagnostic studies showed features of demyelinating peripheral neuropathy with right brachial plexopathy. Magnetic resonance imaging revealed thickening with a diffuse enhancement of both brachial plexuses. The patient was eventually diagnosed with nivolumab-induced demyelinating polyneuropathy involving the brachial plexus. Oral steroid therapy improved motor weakness and sensory abnormalities without aggravation. CONCLUSION: Our study indicates the possibility of nivolumab-induced neuropathies in cases involving muscle weakness with sensory abnormalities of the upper extremity following nivolumab administration in patients with advanced cancer. Comprehensive electrodiagnostic studies and magnetic resonance imaging are helpful in the differential diagnosis of other neurological diseases. Appropriate diagnostic and therapeutic approaches may prevent further neurological deterioration.

Oral Methadone for Patients With Neuropathic Pain Due to Neoplastic Brachial Plexopathy.

Background: The brachial plexus nerves originate from the cervical (C5-C8) and first thoracic (T1) spinal nerves, and innervate muscles and skin of the chest, shoulder, arm and hand. Brachial plexus injuries can occur as a result of shoulder trauma and inflammation. Malignant tumors can also cause neoplastic brachial plexopathy (NBP), and refractory neuropathic pain is the most common symptom of NBP. Methadone is a synthetic opioid with high efficacy as an opioid-receptor agonist, and its inhibitory effects on N-methyl-D-aspartate (NMDA) may play a role in pain relief. However, there is a need to examine if oral methadone exhibits safety and efficacy against neuropathic pain due to NBP. Case Presentations: NBP was diagnosed in 3 cases without brain or cervical spine metastasis. The clinical features of these patients were analyzed retrospectively. None of the cases had an indication for surgery because of advanced cancer and all had received radiation therapy that had an insufficient effect, prior to methadone treatment. All 3 patients had nociceptive and neuropathic pain. Methadone for refractory pain was initiated using the stop-and-go method. NRS pain scores decreased in all cases and there were no severe side effects. Discussion: For the purpose of pain relief, patients with NBP may receive surgery, radiation therapy and nerve block, but these are not always effective. Methadone was recently shown to be superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer in a RCT, and our findings suggest that methadone may also be effective for patients with NBP. Conclusion: More studies are necessary, but results in 3 cases suggest that oral methadone may be a safe analgesic agent for patients with neuropathic pain due to NBP.

Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom.

BACKGROUND: Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. OBJECTIVE: To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. RESULTS: Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not demonstrate significant differences. Meanwhile, on day 12 after surgery it was observed under light microscopy that the inflammatory response in the right brachial plexus and cervical cord (C8-T1) were significantly attenuated after EA stimulation. Furthermore, the demyelination of the brachial plexus and cervical cord (C8-T1) were also reversed. LIMITATIONS: Limitations include the fact that there was demyelination of the cervical cord (C8-T1) in the control group because of inappropriate manipulation. CONCLUSION: Repeated EA contributes significant analgesic effects in the treatment of BPN.

Transient brachial plexus palsy: an unusual complication of paravertebral infusion of local anesthetic.

A continuous infusion of 0.25% bupivaciane into the parevertebral space was used for postoperative pain relief after a lung resection. On postoperative day 1, a brachial plexus palsy developed, which resolved on discontinuation of the infusion. We believe this rare complication has not been reported previously. Awareness of this possibility may avoid unnecessary investigations.

Recovery potential after postnatal shoulder paralysis. An animal model of neonatal brachial plexus palsy.

BACKGROUND: Injury to the brachial plexus during birth results in paralysis of the upper extremity in as many as one in 250 births and can lead to substantial functional deficits in the shoulder. The goal of this study was to characterize the development of bone and joint deformities in paralyzed neonatal shoulders and to assess the improvement of these deformities after muscle function recovery with use of an animal model. METHODS: Intramuscular injections of botulinum toxin were used to paralyze the supraspinatus, infraspinatus, and posterior deltoid of the left shoulders of mice at birth. Seventy mice were divided into three groups: Botox, recovery, and normal. The twenty-five mice in the Botox group received botulinum toxin injections until they were killed. The twenty mice in the recovery group received botulinum toxin injections for different durations and then were allowed injection-free recovery periods until they were killed. The twenty-five mice in the normal group received saline solution injections until they were killed. Radiographs were used to measure shoulder and elbow contractures. Microcomputed tomography was used to examine anatomical parameters of the supraspinatus muscle, humerus, and scapula. RESULTS: The Botox group showed bone and joint deformities including delayed mineralization and flattening of the humeral head, hypoplasia, and introversion (i.e., anteversion) of the humerus, contractures of the shoulder and elbow, hypoplasia of shoulder muscles, hypoplasia of the scapula, and hypoplasia and retroversion of the glenoid. In the recovery group, a significant trend toward normal properties was observed with longer recovery periods (p<0.05). However, only soft-tissue contractures of the shoulder and elbow were resolved completely with the longest recovery period. CONCLUSIONS: This mouse model successfully simulates human neonatal brachial plexus palsy, reproducing most of the bone and joint deformities found in the human condition. The deformities started to develop early in the postnatal period in the paralyzed shoulders and progressed with longer durations of paralysis. Early restoration of muscle function completely resolved the soft-tissue contractures of the shoulder and elbow. However, osseous deformities of the humerus and scapula were never resolved completely. These findings demonstrate the time-dependence of reversibility of musculoskeletal deformities in developing shoulders with neurological deficits.