Abnormal vascular smooth muscle cell proliferation in sural nerve biopsy from a patient with sensorimotor axonal neuropathy

We report the case of a 75-year-old patient who was admitted to our department to investigate progressive weakness in his lower limbs associated with distal paraesthesias with a glove and stocking distribution. One year earlier he had been diagnosed with colon cancer with a liver metastasis and had undergone successful surgery followed by adjuvant chemotherapy (5-FU and oxaliplatin). Neurological examination revealed impaired strength in both lower limbs, graded 4 on the Medical Research Council scale in the proximal muscles and 3 in the distal ones; tendon reflexes at the knees and ankles were absent. There were no signs of upper motor neuron impairment. No abnormality was revealed on extensive laboratory studies, including complete blood count,erythrocyte sedimentation rate, immunofixation electrophoresis, concentrations of electrolytes, CRP, creatine kinase, FT3, FT4, thyroid-stimulating hormone, hepatic enzymes, creatinine, urine analysis and screening for infections, malignancies, malabsorption and systemic autoimmune disorders. Cranial and spinal gadolinium-enhanced MRI and a total body contrastenhanced CT scan detected no abnormalities. Nerve conduction studies showed reduced amplitude of sensory and compound motor action potentials in all four limbs with normal conduction velocities; needle electromyography performed in the proximal and distal muscles bilaterally revealed high-frequency large motor unit potentials, denervation (fibrillation potentials, positive waves) and fasciculations associated with spontaneous bursts of motor unit potentials (double, triple or multiple). An axonal sensorymotor polyneuropathy associated with neuromyotonia was diagnosed. Over the following 3 months the patient’s motor symptoms rapidly worsened despite trying different therapies (glucocorticoids, IVIg, plasma exchange, rituximab) and he ultimately required mechanical ventilation through a tracheostomy. Further investigations proved normal, including anti-gangliosides antibodies, anti-voltage-gated potassium channel antibodies,VEGF dosage, SOD1 sequencing and a new total body contrast-enhanced CT scan.After obtaining informed consent, a sural nerve biopsy was performed. Semithin sections stained with toluidine blue showed mild loss of myelinated fibres without active degenerations (Fig. 1a); HE staining revealed abundant smooth muscle cell proliferation around epineural vessels, with a characteristic perivascular concentric growth pattern (Fig. 1b). Elastin stain showed the typical vascular distribution of the elastic fibres (Fig. 1c). Immunostaining for desmin was negative (Fig. 1e); fluorescent phalloidin revealed diffuse presence of filamentous actin (Fig. 1e). Semithin sections (Fig. 1d) and ultrastructural analysis (Fig. 1f) confirmed the presence of smooth muscle cells. Atrophy and fasciculations of the tongue became evident 6 months later. Follow-up nerve conduction studies showed progressive reduction of compound motor action potentials in all limbs, while the amplitude of sensory action potentials did not significantly change. Electromyography of the tongue confirmed the presence of fibrillation potentials and positive sharp waves. The patient died 8 months after symptom onset as a result of a superimposed infection. An autopsy was not performed. Considering the rapid clinical deterioration, the possibility that a motor neuron disease (MND) complicated the peripheral neuropathy could not be excluded. Smooth muscle cell proliferation in sural nerve biopsy has been described as a manifestation of systemic or nonsystemic inflammatory or vascular disorders; there have also been reports of benign smooth muscle tumors involving single nerves or the peripheral nervous system diffusely, leading to a sensori-motor polyneuropathy. In our patient the proliferation of smooth muscle cells shows a concentric perivascular growth pattern and a desmin-negative, actin-positive immunohistochemical phenotype (Fig. 1e). These immunopathological findings have been described in myopericytoma, a rare benign tumor the cells of which show obvious differentiation toward myopericytes. The significance of our pathological findings is unclear. Considering the complex clinical phenotype of our patient configuring peripheral neuropathy, neuromyotonia and Disclosure: The authors report no conflicts of interest. Published online 6 December 2010. Neuropathology 2011; 31, 197–198 doi:10.1111/j.1440-1789.2010.01179.x