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.

A New Animal Model of Brachial Plexus Neuralgia Produced by Injection of Cobra Venom into the Lower Trunk in the Rat.

BACKGROUND: To establish a new animal model for the study of neuropathic pain developed by administration of cobra venom to the brachial plexus (BP) lower trunk. METHODS: Fifty-eight adult male Sprague-Dawley rats were randomly divided into 5 groups. Under pentobarbital sodium anesthesia, cobra venom was injected into the lower trunk or sham operation was performed in the animals. On postoperative day 1 and day 12, pregabalin was administered intragastricly at 30 mg/kg in two groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were used to analyze the spontaneous behaviors. Meanwhile, our model was confirmed by observing ultrastructural alterations of the BP and cervical cord (C8-T1) via electron microscope examination. RESULTS: In comparison to the blank and sham-operated group, cobra venom-treated rats showed a profound decrease in the MWT, exploratory and increase in grooming behaviors (P<0.05). The changes were long-lasting (up to 60 days), in both ipsilateral and contralateral paws. Furthermore, it was observed under microscopic examination that the myelin sheath was demyelinated in the BP and cervical cord (C8-T1) after injection of cobra venom to the lower trunk. Pregabalin group rats showed changes in MWT and spontaneous behaviors after pregabalin treatment at postoperative day 1 (P>0.05), compared with the control and sham-operated groups. In pregabalin test POD12 group, the decreased MWT and the increased grooming behavior were improved at 20 days after operation. However, pregabalin had no effect on exploratory activity. Results indicate that pregabalin effectively attenuates mechanical hyperalgesia in acute period. CONCLUSIONS: The cobra venom model can be used as a model to induce neuropathic pain and to enable study of the mechanism and treatment.

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.

Compressive neuropathy of the brachial plexus and long thoracic nerve: a rare complication of heparin anticoagulation.

We present a case of a 69-year-old woman who developed brachial plexopathy and long thoracic nerve palsy secondary to compression from a hematoma while receiving heparin therapy for the treatment of a stroke. The patient was treated conservatively with discontinuation of heparin and had complete resolution of her compressive neuropathy. This is the first report of a patient with long thoracic nerve palsy with a brachial plexopathy complicating anticoagulation. We review the literature on hematoma-induced compressive neuropathies and treatment options. Our review concludes by emphasizing the importance of clinical judgment in determining the best therapeutic modality.

The exacerbating effect of insulin-induced hypoglycemia on spontaneous peripheral neuropathy in aged B6C3F1 mice.

The effect of insulin-induced hypoglycemia on spontaneous peripheral neuropathy in aged mice was examined. Ninety-five-week-old female B6C3F1 mice were infused subcutaneously for 2 weeks with 40 or 80 IU/kg/day of insulin with a micro osmotic pump. Blood glucose level was decreased during the infusion (4.3-6.8 mmol/L in mice receiving 40 IU/kg/day of insulin or 2.4-5.4 mmol/L in mice receiving 80 IU/kg/day of insulin versus 6.5-7.6 mmol/L in control mice). In histopathological examination, axonal degeneration and/or remyelination were observed in a small number of nerve fibers of control mice. Similar nerve fiber lesions were observed in mice receiving 40 IU/kg/day of insulin, whereas severer lesions with an increase in segmental axonal degeneration of nerve fibers were observed in 4/7 mice receiving 80 IU/kg/day of insulin. These findings suggest that spontaneous peripheral neuropathy in aged mice is exacerbated by sustained hypoglycemia induced by insulin treatment.

[Carpal tunnel syndrome? Case report]. / ¿Síndrome del tunel carpiano? Case report.

A patient with an initial misdiagnosis of carpal tunnel syndrome is presented. The clinical manifestations were suggestive of such diagnosis, but there were some anamnesis and exploratory aspects requiring to establish a differential diagnosis. Painful syndrome was caused by a brachial plexus compression at the costoclavicular region due to a subclavicular hematoma in a patient under anticoagulant treatment. Carpal tunnel pathology is a frequent cause of neuropathy, however others diagnosis should be ruled out as shown in the present case.

[Complication belong to stellate ganglion blockade after cervical trauma]. / Boyun travmasi sonrasi yapilan stellat ganglion blokajina bagli komplikasyon.

Stellate ganglion block (SGB) is one of the most often used sympathetic blockade procedure. Despite performed by experienced physicians some complications may occur. The right brachial plexus injury was diagnosed in the patient who admitted to orthopedia clinic, with weakness in the right arm, and pain after motor vehicle accident. There was no response to medical treatment of fortyfour-years-old female patient and there was loosing of sensation from dis the right elbow joint to fingers on the radial and median nerve tracing. In the electromyelography; C5-T1 root avulsion, and MRI; Patient was evaluated as CPRS I (Complex regional pain syndrome) phase 1. In spite of medical treatment, SGB was performed. Respiratory arrest occurred 4-5 minutes after injection. Patient was breated with mechanical ventilator during 2 hours, and discharged 24 hours later with normal vital functions. One year later, the patient admitted the algology polyclinic with strong pain in the same area. Stellate ganglion Radyofreguency (RF) was planned. The first RF cannula was placed under fluoroscopy. Cerebrospinal fluid was seen in the second canula, and canula was withdrawn. Third cannula was placed in another region, and conventional RF was performed through two canuls. For anatomical structure defect, we planned cervical MR myelography. In the cervical MR myelography, traumatic pseudomeningocele was observed at the level of C6-T1 on the brachial plexus. Intraspinal block was thought to develop during blockade of stellate ganglion due to this.

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.

Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis.

BACKGROUND: Although patients with multiple sclerosis (MS) are advised to stop interferon (IFN) beta-1a therapy before becoming pregnant, some patients become pregnant while on treatment. METHODS: We examined individual patient data from eight clinical trials with IFNbeta-1a. RESULTS: Of 3,361 women in the studies, 69 pregnancies were reported, of which 41 were patients receiving (or who had stopped receiving within 2 weeks prior to conception) IFNbeta-1a (in utero exposure group), 22 were patients who discontinued IFNbeta-1a treatment more than 2 weeks before conception (previous exposure group), and six were patients receiving placebo. The 41 in utero exposure pregnancies resulted in 20 healthy full-term infants, one healthy premature infant, nine induced abortions, eight spontaneous abortions, one fetal death, and one congenital anomaly (hydrocephalus). One patient was lost to follow-up. The 22 previous exposure pregnancies resulted in 20 full-term healthy infants, one healthy premature infant, and one birth-related congenital anomaly (Erb palsy). CONCLUSIONS: The majority (21/31) of pregnancies that had the potential to go to full term produced healthy infants. The rate of spontaneous abortion was higher, but not significantly so, in the in utero exposure group compared to general population estimates. Until more exposure data become available, patients remain advised to stop IFNbeta therapy before becoming pregnant.

Acute rhabdomyolysis and brachial plexopathy following alcohol ingestion.

An unusual case of brachial plexopathy following alcohol-induced rhabdomyolysis is presented. The patient's rhabdomyolysis developed during sleep after an acute alcohol binge and there was no history of muscle trauma. It is thought that the brachial plexopathy developed due to direct compression of the plexus from swollen muscles of the shoulder girdle. The lack of similar reported cases despite the common clinical scenario of prolonged unconsciousness following excess alcohol intake suggests that other factors may be important in the development of muscle and nerve damage in susceptible individuals.