Bing–Neel Syndrome Mimicking Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis

Waldenström macroglobulinemia (WM) is a rare hematological malignancy, defined as a lymphoplasmacytic lymphoma (LPL) with immunoglobulin M (IgM) paraprotein. Rarely, LPL will infiltrate the central nervous system (CNS), an entity termed Bing–Neel syndrome (BNS). We describe an atypical BNS case, with a lower motor neuron-predominant presentation mimicking amyotrophic lateral sclerosis (ALS). A 74-year-old male with WM and type I cryoglobulinemia, in remission following bendamustine chemotherapy 4 years prior, and type 2 diabetes mellitus complicated by retinopathy and nephropathy was referred to our center with 24 weeks of slowly progressive, painless lower greater than upper extremity weakness, with subsequent diffuse muscle atrophy and fasciculation, without bulbar involvement. On examination (week 24), facial, palatal, and tongue musculature was preserved, and jaw jerk absent. Atrophy and fasciculations were present throughout all extremities and thoracic and lumbar paraspinals. Tone was reduced in lower extremities. Upper extremities were symmetrically weak proximally and distally (4−/5), as were lower extremities (3/5), save for left iliopsoas (2/5). He was areflexic, with downgoing plantars. There was unchanged, long-standing sensory loss to pinprick to mid-shin bilaterally and reduced vibratory sensation to the ankles, attributed to diabetic polyneuropathy. Prior investigations by the primary care physician (week 16), including complete blood count and differential, electrolytes, magnesium, calcium, creatinine, urea, creatine kinase, C-reactive protein, liver enzymes, and bilirubin, were normal. Serum protein electrophoresis (SPEP) was normal but had previously identified an IgM kappa peak (7 g/L) with the initial WM presentation that resolved with treatment. Contrast computed tomography (CT) of the head, chest, abdomen, and pelvis was unremarkable. Prereferral, outpatient nerve conduction studies (week 20, where clinical findings and pattern of weakness were similar to week 24, save for increased strength in the upper and lower extremities at 4+/5 and 4−/5, respectively) demonstrated axonal sensorimotor polyneuropathy. F-response was tested only in left tibial nerve and showed mildly prolonged latency. Electromyography demonstrated active denervation potentials (predominantly fibrillation potentials and/or positive sharp waves with fewer fasciculations) and chronic neurogenic changes in bilateral tibialis anterior, right gastrocnemius, bilateral vastus medialis, and left first dorsal interosseous. Active denervation potentials only without chronic neurogenic changes were observed in left gastrocnemius, deltoid, and triceps. Electromyography of tongue was normal, while thoracic paraspinal muscles demonstrated pervasive motor unit action potentials from incomplete relaxation. The rapidly progressive weakness, physical examination, and electrodiagnostic findings gave consideration to the diagnosis of lower motor neuron-predominant ALS, among other important mimics. Multifocal motor neuropathy progresses more slowly, motor-predominant chronic inflammatory demyelinating polyradiculoneuropathy typically has a relapsing-remitting course, and both have demyelinating features on electrophysiology not seen in our patient. The axonal sensorimotor polyneuropathy demonstrated on nerve conduction studies was attributed to diabetes based on a 20-year history of disease; however, the relatively equivalent proximal and distal weakness and presence of active denervation in proximal muscles would argue against a length-dependent axonal polyneuropathy as the sole cause of this presentation. Electromyography of abdominals and other paraspinal levels may have been helpful to distinguish an axonal polyneuropathy or motor neuropathy from a more proximal process, such as diffuse polyradiculopathy or motor neuronopathy, with active denervation being expected in these regions in the latter. However, abdominal or paraspinal studies might not be able to differentiate between polyradiculopathy from leptomeningeal disease and motor neuron disease. Symptomatically, the patient did not report radicular pain. Therefore, in view of the extensively normal pre-referral systemic workup, anterior horn cell disease was initially considered more likely than infiltrative or paraneoplastic polyradicular disease. Repeat SPEP (week 24) demonstrated recurrence of a monoclonal IgM kappa peak (2 g/L). Type I cryoglobulinemia was detected. Cerebrospinal fluid (CSF) analysis revealed 260white blood cells/ mm, protein 172mg/dL, and glucose 4.7 mmol/L. Fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT demonstrated hypermetabolism in biparietotemporal cerebral cortex (considered nonspecific, but compatible with CNS lymphoma [Figure 1(A)]), along the right parotid gland corresponding to right facial nerve perineural thickening and enhancement on magnetic resonance imaging (MRI) [Figure 1(B)], and along the brachial and lumbosacral plexi and sciatic nerves bilaterally [Figure 1(C–D)]. Contrast-enhanced MRI of brain and cervical, thoracic, and lumbosacral spine revealed enhancement along the conus medullaris with thickening and enhancement of the cauda equina [Figure 1(D)]. CSF flow cytometry subsequently demonstrated a monoclonal population of small lymphoid cells with plasmacytoid features and kappa restriction, confirming relapsed LPL in CSF and a diagnosis of BNS. While awaiting chemotherapy, the patient developed acute hypoxemic respiratory failure and digital ischemia secondary to hyperviscosity and cryoglobulinemia. Palliative measures were pursued and he passed away 2 days later. BNS is a rare complication of WM and likely underrecognized, owing to protean clinical manifestations dependent on site of tumoral infiltration. Diagnostic delay of several months was common in cohort studies. Epidemiological data are lacking, and prevalence is unknown; however, a retrospective study of patients withWM, which has an ageand sex-adjusted incidence of 0.57 per 100,000 person-years, demonstrated only 0.8% progressed to BNS. Up to one-third of BNS patients present without preceding WM diagnosis. Two disease forms are recognized: a diffuse form defined by leptomeningeal infiltration and a tumoral form whereby lymphomatous cells form clusters within CNS parenchyma. Diagnostic criteria were recently defined: biopsy of the CNS parenchyma or meninges demonstrating LPL is the gold standard; however, where biopsy is unattainable, CSF evidence of LPL by flow cytometry is accepted as evidence of leptomeningeal disease. Contrast-enhanced MRI of brain and spinal cord is recommended for supportive evidence of leptomeningeal disease, LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES