Central Pontine Myelinosis (CPM) and Extra Pontine Myelinosis (EPM) are debilitating conditions, resulting from the rapid correction of hyponatremia. The outcome and prognosis of this medical condition are variable; mainly involving functional decline from neuro-musculoskeletal upset. An intensive, multidisciplinary rehabilitation has played an essential role in facilitating and hasten recovery, promoting a favorable outcome. We reported our experience in rehabilitating a patient with a rare condition of comorbid CPM and EPM. The reported patient presented with disabling Locked-in Syndrome (LIS) and Parkinsonism movement disorder. We highlighted the stepwise rehabilitation approach according to Patterson and Grabois Motor Recovery scale for LIS in preventing and reversing the complications and disabilities caused by CPM and EPM that may facilitate favorable therapeutic outcomes.