Immune-mediated chorea in a patient with kappa light-chain monoclonal gammopathy
Amrita J Gotur1, Roopa Rajan1, Rishi Dhawan2, Ajay Garg3 1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India 2 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India 3 Department of Neuroradiology, All India Institute of Medical Sciences, New Delhi, India
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Correspondence Address: Dr. Roopa Rajan Department of Neurology, Neurosciences Center, All India Institute of Medical Sciences, New Delhi. India
Source of Support: None, Conflict of Interest: None
The objective of this paper was to report on a case of steroid-responsive chorea in a patient with κ light-chain monoclonal gammopathy. In addition to subacute-onset generalized chorea, evidence of peripheral neuropathy in this elderly gentleman led us to investigate for paraproteinemia. We treated the patient with intravenous steroids in view of elevated κ light-chain assay and bone marrow biopsy, suggestive of monoclonal gammopathy of undetermined significance. There was a remarkable improvement of paresthesias and chorea at 6 months follow-up with no evidence of evolution to malignancy at 1 year. Autoimmune chorea is a treatable condition if identified and treated timely.
Keywords: Chorea, immune-mediated, monoclonal gammopathy of undetermined significance, peripheral neuropathy
How to cite this article: Gotur AJ, Rajan R, Dhawan R, Garg A. Immune-mediated chorea in a patient with kappa light-chain monoclonal gammopathy. Ann Mov Disord 2020;3:112-4
How to cite this URL: Gotur AJ, Rajan R, Dhawan R, Garg A. Immune-mediated chorea in a patient with kappa light-chain monoclonal gammopathy. Ann Mov Disord [serial online] 2020 [cited 2022 Sep 28];3:112-4. Available from: https://www.aomd.in/text.asp?2020/3/2/112/291076
Consider autoimmune etiology in a subacute presentation of chorea in an adult.
Light-chain monoclonal gammopathy maybe associated with central nervous system manifestations such as chorea.
Chorea (derived from the Greek word “khoros” meaning dance) is a hyperkinetic movement disorder, characterized by brief, abrupt involuntary movements, resulting from a continuous flow of random muscle contractions. Chorea can be classified into neurodegenerative (Huntington’s disease—most common), drug induced, immune-mediated, infectious, metabolic, vascular, and miscellaneous etiologies.
Immune-mediated chorea may be paraneoplastic or idiopathic in origin. An autoimmune basis is usually supported by clinical or serologic evidence of cancer and inflammatory markers in the cerebrospinal fluid (CSF). Here, we report on a novel association of steroid-responsive chorea with κ light-chain monoclonal gammopathy in an elderly gentleman. Light-chain monoclonal gammopathy of undetermined significance (LC-MGUS) is considered a precursor of light-chain multiple myeloma (20% of all multiple myeloma) and of amyloid light-chain (AL) amyloidosis. It has a prevalence of 0.8% among individuals aged ≥50 years and a rate of malignant transformation of 0.3% per year. Although peripheral neuropathy is a common accompaniment of LC-MGUS, central nervous system (CNS) involvement is exceedingly rare.
A 68-year-old gentleman presented with abnormal involuntary movements, involving the left upper and lower limbs for the past 6 months. These fidgety, astereotypical movements, fleeting from one body part to another, spread to the right upper limb and perioral region, involving the tongue for the past 1 month. He also reported burning sensations over both feet for the past 2 months. He had no significant comorbid illnesses, and he was not on any regular medications. He consumed oral tobacco occasionally and had no other addictions. He had no history of exposure to neuroleptics, levosulpiride, other dopamine receptor blocking agents, or toxins. He had no history of dry eyes, dry mouth, parotid enlargement, abdominal pain, diarrhea, or breathlessness.
General physical examination was unremarkable with no pallor, lymphadenopathy, or organomegaly. There was no orthostatic hypotension (supine: 130/84 mm Hg, standing 3 min: 139/87 mm Hg). Nervous system examination revealed generalized chorea, involving the left-sided limbs more than right, with prominent perioral and lingual movements and motor impersistence in the tongue [Video 1] . Rest of the neurological examination, including higher mental functions, motor and sensory examination, and coordination were normal. Deep tendon reflexes were elicited normally.
Etiologies for subacute-onset chorea in the elderly were considered, including structural lesions in the caudate or subthalamic regions, metabolic causes such as hyperthyroidism, hypoparathyroidism, polycythemia, drug-induced chorea, Huntington’s disease, neuroacanthocytosis, and neuroferritinopathy. Investigations revealed plasma hemoglobin of 12.4 (range, 12–18 × 103/µL), hematocrit of 36.54% (range, 37%–52%), total leukocyte count of 11.6 (range, 5.2–12.4/µL), platelets of 171 × 103/µL (range, 130–400 × 103/µL), erythrocyte sedimentation rate of 30 mm/h (range, 0–20 mm/h), and C-reactive protein of 1.3 mg/L (range, 0–6 mg/L). Rest of the blood and CSF investigations was unremarkable, as shown in [Supplementary Table 1]. Serum and urine protein electrophoresis carried out by immunofixation method was negative for monoclonal proteins. Brain magnetic resonance imaging (MRI) [Figure 1] revealed nonspecific T2 hyperintensities in the frontal and parietal white matter and bilateral anterior putamen. No contrast enhancement was noted. Nerve conduction studies revealed a mixed axonal and demyelinating symmetrical peripheral neuropathy [Supplementary Table 2].
Supplementary Table 1: Blood and CSF investigations
Figure 1: MRI reveals multiple discrete T2 hyperintensities in bilateral frontal and parietal lobe white matter, anterior part of both putamen and bilateral medial lemnisci-rest, nonspecific in nature. Rest of the brain parenchyma is normal in signal intensity
A paraneoplastic etiology was strongly considered, and the patient underwent whole body fluorodeoxy glucose positron emission tomography (FDG-PET), which revealed no metabolically active focus. Individual paraneoplastic antibody testing could not be performed. As a part of workup for demyelinating peripheral neuropathy in the elderly, serum-free light-chain assay was ordered, which revealed markedly elevated free κ light chains: 118.36 mg/L (range, 3.3–19.4 mg/L), slightly elevated λ light chains: 30.92 mg/L (range, 5.71–26.3 mg/L), and an abnormal serum-free κ/λ ratio: 3.82 (range, 0.26–1.65). Bone marrow aspirate revealed hematopoietic cells of myeloid and erythroid lineage with approximately 2% plasma cells. Flow cytometric immunophenotyping of bone marrow aspirate showed 0.03% plasma cells that were polyclonal. No aberrant plasma cells were detected. Skeletal survey revealed no evidence of multiple myeloma. An abdominal fat pad biopsy ruled out amyloidosis; the patient did not consent for a nerve biopsy. A diagnosis of LC-MGUS with peripheral neuropathy and possible immune-mediated chorea was made, and the patient was started on intravenous methylprednisolone 1g/day for 5 days, followed by oral prednisolone. Both the neuropathy and chorea symptoms improved significantly by 6 weeks with complete resolution at 6 months. No recurrence of either symptom on tapering steroids was observed, and the patient continues to do well at follow-up 1 year after the initial presentation [Video 2] . Repeat free light-chain assay after treatment and resolution of symptoms (1 year) revealed normal serum-free κ light chains (4.86 mg/L, range, 3.3–19.4 mg/L) and serum-free λ light chains (1.69 mg/L, range, 5.71–26.3 mg/L) with reducing κ/λ ratio (2.87, range, 0.26–1.65).
Peripheral neuropathy is a common accompaniment of both κ and λ light-chain LC-MGUS. Symptomatic CNS involvement in the form of chorea has not been reported previously with LC-MGUS. LC-MGUS has a prevalence of 0.8% of general population and is considered a premalignant plasma cell disorder. In our patient, the co-occurrence of steroid-responsive chorea with LC-MGUS may be a chance association. However, free light chains are being increasingly recognized in CNS autoimmunity. κ-free light chains in the CSF were recently implicated in CNS autoimmunity, specifically multiple sclerosis. They are being investigated as diagnostic biomarkers and to predict disease progression in multiple sclerosis. Hyperviscosity, as seen in other hematological conditions such as polycythemia rubra vera and heavy-chain MGUS, may also be a contributory mechanism for the manifestation of chorea.
A large proportion of adults with immune-mediated chorea are labeled idiopathic when paraneoplastic antibodies and active cancer are not detected.
In the largest case series of autoimmune chorea, 36 patients were identified between 1996 and 2013. The paraneoplastic group had 14 patients with the evidence of cancer. Among them, six patients had cancer predictive paraneoplastic antibodies, CRMP5 and ANNA1 being the most common. The idiopathic group had 19 patients; lupus and antiphospholipid antibodies were the most common etiologies in this group. There was no evidence systemic autoimmune disease or active malignancy in our patient. In the 2-year follow-up under hematology and neurology, our patient had no evidence of myeloma, lymphoma, or renal disease. He continues to be under close follow-up.
Other known associations of LC-MGUS are shown in [Table 1]. In the absence of paraneoplastic antibody testing, elevated κ-free light chains and the presence of peripheral neuropathy were considered as evidence for an immune-mediated etiology in our patient. We report a novel association of LC-MGUS with chorea and postulate that serum or CSF light-chain assay may be a promising biomarker or surrogate marker in this population.
Table 1: Systemic manifestations of Light Chain - Monoclonal Gammopathy of Undetermined significance
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We would like to thank Prof. Kameshwar Prasad, former Head of Department and Chief, Neurosciences Center, and Prof. Ritu Gupta, professor and Head of Laboratory Oncology for technical support in preparing this case report.
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