3207 Case series of multisystem proteinopathy due to valosin-containing protein (VCP) gene variants: an inconsistent phenotype

Cases The present case series describes five patients diagnosed with Mills syndrome.The patient cohort comprises four males and one female, with a mean age at onset of 61 years.Clinical follow up over eleven years established that all patients have disease, most prominently limb weakness, confined to one side of their body.Spasticity was a key feature in all patients, with asymmetric reflexes, brisk on the symptomatic side, and normal sensory examination.Magnetic resonance (MR) tractography established marked asymmetry of the white matter fiber density, corresponding with clinical presentation.Brain imaging with positron emission tomography (PET) scan identified hypometabolism involving the left lateral frontal cortex posteriorly corresponding to the symptomatic side.Transcranial magnetic stimulation (TMS) showed inexcitability of the motor cortex of the affected side, and motor cortex excitability within normal limits on the contralateral side, consistent with disease confined to one hemisphere.Discussion Mills syndrome represents a unique phenotype of ALS.Structural imaging, in particular MR tractography, combined with metabolic (PET imaging) and the assessment of cortical motor function promote an accurate diagnosis.Further understanding the pathophysiology of Mills syndrome will broaden understanding of motor neuron disorders, and perhaps expand knowledge of the ALS-PLS spectrum.