Case Presentation: A 32 year old male presented to the emergency department unresponsive. Three months prior he had developed urinary incontinence, cognitive impairments, paresthesias in his extremities and weakness requiring crutches. His symptoms progressed leaving him bed bound weeks prior to arrival. EMS was contacted when he became unresponsive to verbal-noxious stimuli and exhibited difficulty breathing. On arrival he was febrile, tachycardic with profound lethargy, areflexia and flaccid paralysis on exam. CBC displayed Hgb 7.7g/dL, Hct 21.8%, MCV 112.4fl with WBC and serum lactate within normal limits. ABG revealed a pH of 7.18 with pCO2 of 82mmHg. Beside ultrasound demonstrated impaired diaphragm motility while venous duplex revealed an extensive DVT in the left common femoral vein and PE in both right and left pulmonary arteries on CT Angio. He was promptly intubated and initiated on IV heparin with foley catheter placed. MRI showed hyperintensity of periventricular white matter concerning for inflammatory origin with no evidence of epidural abscess, yet LP was negative for infectious/inflammatory etiology. Contrast MRI showed hyperdensity in the cortical spinal tract indicating a demyelination process. Serum folic acid and antiparietal cell antibodies were normal, Cobalamin levels were undetectable (< 150pg/mL), while levels of ESR (61mm/hr), Methylmalonic Acid (MMA) (54,736 nmol/L), homocysteine (159.7 umol/L) and intrinsic factor antibodies (90.4 Au/mL) were elevated. Upper EGD revealed a metaplastic autoimmune atrophic gastritis pattern consistent with pernicious anemia confirming the diagnosis of subacute combined degeneration (SACD) of the spinal cord. He was initiated on daily IM Cobalamin and transition to BiPAP until diaphragmatic motility returned. His megaloblastic anemia resolved and he was discharged on weekly IM supplementation, eliquis and foley catheter. He regained motor function in his upper extremities with urinary symptoms and lower extremity weakness persisting rendering him wheelchair bound a year later

Discussion: MMA is a toxic byproduct of fatty acid oxidation; without cobalamin, it accumulates and targets peripheral myelin sheath for destruction. The lateral corticospinal tract, dorsal columns and dorsal spinocerebellar tract are most susceptible to damage. SACD of the spinal cord occurs when all three locations are affected, in which case adequate repletion may reverse this neurologic complication if identified promptly. Homocysteine has prothrombotic effects on the endothelium and vascular smooth muscle via mechanisms involving oxidative stress and indirectly inhibits Protein C of the clotting cascade resulting in increased thrombin formation. In this case study, the patient’s severe cobalamin deficiency led to demyelination and consequential paralysis. As a result of delayed treatment, his subsequent immobile state and hypercoagulability from hyperhomocysteinemia led to the multifactorial development of his extensive DVT and PE, with neurological deficits persisting despite adequate treatment and resolution of his hematologic disorder

Conclusions: Cobalamin’s a role in myelin production and DNA synthesis increases susceptibility to neurologic deficits and hypercoagulable complications when altered. We must fine-tune diagnostic strategies for timely diagnosis and execute accurate approaches to management to reduce risk of irreversible neurodegenerative complications and optimally minimize mortality and morbidity in such cases

IMAGE 1: Figure 1. MRI of Cervical Spine w/wo IV Contrast: (A.) Sagittal section of cervical spine displaying T2 hyperintensities along the dorsal columns . (B.) Coronal section of the cervical spine reflecting the same T2 hyperintensities along the dorsal spinal tract

IMAGE 2: Figure 2. CT Angiography of the Chest w/ IV Contrast: Red arrows depict a central pulmonary emboli noted in the distal right pulmonary artery extending into the RUL and bronchus intermedius as well as the distal left pulmonary artery extending into the LUL and LLL without right heart strain or infarct detected