Case of Neurolymphomatosis Presenting to Sports Medicine Clinic as Worsening, Asymmetric Upper Extremity Weakness and Pain

Introduction Neuropathies in those with lymphoma present in a variety of clinical processes, with neoplastic, paraneoplastic, and iatrogenic being the most recognized (1). These neuropathies clinically manifest as paresis, paralysis, and even dysesthesias, which include pain and sensory loss (2,3). Neoplastic conditions can be primary or metastatic lymphomatous invasion of the nervous system and include lymphomatous meningitis and neurolymphomatosis (4). Paraneoplastic conditions include compression from tumors, onconeural antibodies, and demyelinating polyneuropathies while iatrogenic causes are typically from chemotherapeutic agents (5). Neurolymphomatosis is best defined as direct invasion of a peripheral nerve or plexus by malignant lymphoma, most commonly non–Hodgkin’s B-cell lymphoma. Neurolymphomatosis often takes months to diagnose and is often misdiagnosed. Once diagnosed, neurolymphomatosis can improve with chemotherapy (1,3,6). Here we describe a case of neurolymphomatosis that presented initially as left upper extremity weakness and pain. Case A right-handed, 79-year-old physically active male presented to a sports medicine clinic due to worsening unilateral left upper extremity weakness and pain. The patient had surgical history of cervical disk fusions of C5–6 and C6–7 4 years prior; ipsilateral trigger finger release and ipsilateral ulnar release 4 years prior; bilateral carpal tunnel release 3 years prior; ipsilateral shoulder arthroscopy with rotator cuff repair, subacromial decompression and acromioplasty, and open distal clavicle excision 1 year prior to presentation. Medical history included prostate cancer in remission diagnosed 5 years prior, treated with local radiation therapy completed 4 years prior; controlled hypertension; hyperlipidemia; hearing loss; wet macular degeneration of both eyes; and polymyalgia rheumatica. Current medications included amitriptyline 30 mg daily, atorvastatin 20 mg daily, diclofenac 75 mg twice daily, as needed, pregabalin 100 mg twice daily, losartan 100 mg daily, prednisone 10 mg daily, tamsulosin 0.8 mg daily, and tramadol 25 mg three times daily, as needed. Family history of diabetes in his mother. Social history reported daily walking, well-balanced diet, married and independent with activities of daily living, never a smoker, and occasional alcohol use. Physically active in manual labor, mostly carpentry. Previous imaging included left shoulder magnetic resonance imaging (MRI) 5 months prior that revealed high-grade near full-thickness supraspinatus tear, infraspinatus tendinopathy, subscapularis tendinopathy and partial tear, and a degenerative glenohumeral joint. Cervical spine MRI 5 months prior revealed neural foraminal narrowing at C2-C7 with moderate severe spinal stenosis of C4–5. Brachial plexus MRI 4 months prior revealed diffuse increased signal throughout left brachial plexus along with muscular edema in rotator cuff (Fig. 1). Electromyography (EMG) and nerve conduction study (NCS) 4 months prior revealed incomplete left brachial plexopathy with active denervation without signs of reinnervation affecting upper and middle trunks and posterior cord without evidence of left cervical radiculopathy or distal polyneuropathy. Patient was seen by a neurologist 3 months prior for his symptoms and diagnosed with Parsonage-Turner Syndrome. Patient’s chronic prednisone was increased from 10 mg daily to 30 mg for 1 month, then weaned to 20 mg.Figure 1: T1 weighted MRI image of brachial plexus showing thickening of the left brachial plexus.Patient’s subjective concerns at initial exam were inability to use his left upper extremity, particularly grip. Patient had completed more than 10 sessions of physical therapy with modalities of neuromuscular electrical stimulation, passive range of motion, and strength exercises for 5 months. Patient’s symptoms would wax and wane, notably improved after an increase in prednisone to 50 mg from his baseline 10 mg daily. Progress was not sustained as his strength would subsequently decline. The patient was previously trialed on celecoxib, duloxetine, and narcotic pain medications without benefit. Physical examination revealed atrophy of left upper extremity. No visible muscle activity with attempted left humeral forward flexion, abduction, or extension; left wrist and forearm flexion, extension, pronation, or supination; left phalange flexion, extension, or apposition/opposition. Sensory examination revealed decreased sensation of left upper extremity. At the initial sports medicine visit, a repeat EMG/NCS was ordered and this revealed progression of left brachial pan-plexopathy without evidence of reinnervation. Shortly after initial visit, the patient began to display bulbar deficits and blurry vision, he presented to the emergency department and was admitted to a tertiary care center. During admission testing for autoimmune causes, metal toxicity, and infectious etiologies were negative. A cerebrospinal fluid study demonstrated atypical, large lymphocytes with flow cytometry showing B-cells exhibiting moderate cluster of differentiation (CD) 19+, CD20+ and CD10+ expression, consistent with diffuse large B-cell lymphoma. Repeat MRI of the brachial plexus revealed asymmetric enlargement, edema, and enhancement seen throughout the left brachial plexus, along with atrophy and edema of shoulder girdle muscles. A nuclear FDG-PET scan was obtained showing intense, linear FDG uptake within an enlarged left brachial plexus, without increased FDG uptake along spinal cord or nerve roots (Fig. 2). The neurology team made the diagnosis of neurolymphomatosis and consultation to medical and radiation oncology was obtained. The oncology team recommended intrathecal methotrexate. However, prior to treatment, the patient developed aspiration pneumonia. The patient and family elected for hospice and the patient subsequently passed.Figure 2: FDG-PET scan image showing increased uptake in left brachial plexus.Discussion The patient’s presenting symptoms were asymmetric, neuropathic pain with weakness. The patient’s surgical history gave concern for rotator cuff pathology. However, with the waxing and waning of this patient’s condition, sensory component, and MRI failing to demonstrate musculoskeletal pathology consistent with the pattern of sensorimotor impairment, rotator cuff or glenohumeral pathology were unlikely causes. A prior EMG/NCS revealed denervation without reinnervation making demyelinating conditions, such as chronic inflammatory demyelinating polyneuropathy and Guillain-Barre Syndrome, less likely and was more concerning for inflammatory neuropathy (2). This along with asymmetry on examination indicated a malignant or vasculitic process (1,3). Early brachial plexus MRI and nerve biopsy should be considered. In our case, only the MRI was performed, which supported the diagnosis of Parsonage-Turner syndrome. Imaging aids in the diagnosis of neurolymphomatosis as demonstrated in the case. Nerve plexus MRI in pathohistologically proven neurolympomatosis cases represent congruence with our findings, demonstrating thickening and enhancement (6,7). FDG uptake on FDG-PET scan is more sensitive than MRI and can identify cranial or meningeal involvement (8,9). Steroids have been used for neurolymphomatosis but provide only momentary improvement (3). Chemotherapy, particularly rituximab, can improve strength and pain though in our case intrathecal methotrexate was considered (6,10). Our patient with neurolymphomatosis secondary to diffuse large B-cell lymphoma waited months for a diagnosis. Nerve biopsy remains an important diagnostic tool and the sports medicine physician should consider a referral for this diagnostic study in complex cases of worsening sensorimotor dysfunction