SIADH in a patient with sensory ataxic neuropathy with anti-disialosyl antibodies (CANOMAD)

Abstract

Dear Sirs, CANOMAD (chronic ataxic neuropathy, opthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies) is a rare variant of IgM paraproteinaemic neuropathy in which the paraprotein fraction contains antibodies against specific disialylated gangliosides, including GD1B, GD3, GT1B and GQ1B [1]. This disorder has so far not been reported in association with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here we describe a patient who developed SIADH during the first relapse of CANOMAD. A 57-year-old woman was admitted to our department because of the progressive development of gait unsteadiness and distal paresthesias over the past 2 years. Neurological examination showed a mild sensory ataxia (Table 1) and a stable exotropia with ambliopia in her left eye due to infantile strabismus; nerve conduction studies documented the absence of SAPs, consistent with a sensory neuropathy (Table 1). A diagnostic screening ruled out malignancies, malabsorption or systemic autoimmune disorders. Serum immuno-fixation electrophoresis revealed an IgM monoclonal gammopathy with k light chain component. Serum testing for anti-gangliosides antibodies [1] showed high titers of anti-GD1b, -GT1b, -GQ1b of IgM type ([1:12,500, n.v. IgM \ 1:500), while anti-MAG antibodies were negative. Serum test for cold agglutinins also resulted positive. One week later, she subacutely manifested a severe neurological deterioration (Table 1) and also developed a hypertensive state treated by calcium-antagonists and clonidine. Arterial blood gas analysis was normal. Routine blood studies documented severe hyponatremia (120 mEq/l) and hypokalemia (2.9 mEq/l), low levels of uric acid (1.3 mg/ dl) and urea nitrogen (7 mg/dl); urinary osmolality (570 mOsm/kg) was increased despite a low plasmatic osmolality (274 mOsm/kg) in clinical conditions of euvolemia, and natriuresis increased ([40 mmol/l) with unaltered dietary salt intake. These parameters indicated the occurrence of SIADH, which was successfully treated according to reported protocols [2]. In order to define the etiology of SIADH, brain and spinal cord MRI with i.v. gadolinium, thyroid and adrenal functions, serum AVP levels and urinary excretions of porphobilinogen and aminolevulinic acid were performed, all with normal results. A lumbar puncture documented a mild hyperproteinorrachia (59 mg/dl, n.v 20–40) with normal cell count; search for infections and oligoclonal bands were negative. Neurophysiologic studies suggested the development of proximal demyelination associated with axonal degeneration (Table 1): in fact, we documented a mild reduction of the CMAP amplitude of the axillary nerve, and the R. Iorio F. Capone E. Iannaccone A. Modoni P. A. Tonali G. Silvestri Department of Neurosciences, Institute of Neurology, Catholic University, Rome, Italy