Clinical Reasoning: A young woman with respiratory failure, hearing loss, and paraplegia

SECTION 1

A 35-year-old woman with bipolar disorder presented to the emergency room (ER) obtunded with hypercapnic respiratory failure. Neurology was consulted because the patient had acute hearing loss and paraparesis. She was last seen normal the prior night by her ex-husband. Paramedics found her on the couch, obtunded, bradypneic, and hypoxic to 82% SpO₂, blood pressure 116/79 mm Hg, heart rate 98 beats per minute, and normothermic. She awakened after 0.4 mg of naloxone administration. Home medications included oxycodone/acetaminophen for chronic pain and venlafaxine, alprazolam, and lamotrigine for bipolar disorder. Of note, 34 pills were missing from the oxycodone/acetaminophen bottle.

Examination revealed supple neck, nontender and atraumatic back, reduced tone, and no withdrawal to noxious stimuli in the legs. Strength was normal in the arms. Reflexes were 2+ throughout but crossed knee adduction was noted. Babinski and Hoffman signs were absent. Pinprick and temperature were decreased bilaterally to a T2-3 level. Vibration and proprioception were intact; rectal tone was normal. The patient reported that she could not hear finger rub in either ear.

Bloodwork was remarkable for mild leukocytosis and mild transaminitis. Salicylate and acetaminophen levels were unremarkable. Urine toxicology was positive for benzodiazepines but negative for opioids.

SECTION 2

The patient's paraplegia along with a T2-3 spinal cord level suggested an upper thoracic spinal cord lesion. Her hearing loss and tinnitus were difficult to colocalize with the paraplegia. Although a brainstem lesion could tie together both deficits, the absence of cranial nerve deficits and normal motor-sensory examination in the arms made this unlikely. Diffuse coagulopathy involving the anterior spinal artery and bilateral anterior inferior cerebellar arteries that supply the cochlea was also less likely given absence of cerebellar symptoms. A toxic/metabolic insult such as drug toxicity or hypoxic injury to cochlea was thought to be more likely.

The acute onset of symptoms together with the dissociated sensory loss between spinothalamic tracts and dorsal columns point towards an acute anterior spinal cord syndrome, which is typically caused by ischemia/infarction from a vascular or hypoxemic insult. Other etiologies for acute spinal cord dysfunction include epidural abscess or hematoma, vascular malformation, ischemia, vasculitis, infectious or autoimmune myelitis, spinal mass apoplexy, and cervical flexion myelopathy.

SECTION 3

An emergent CT spine excluded a fracture or epidural hematoma. Subsequent spine MRI showed increased T2 signal from C5 to T5 and was more prominent in the anterior portion of the spinal cord; this region also showed positive diffusion restriction. No spinal canal stenosis was identified (figure). MRI findings were compatible with an anterior spinal cord infarction in the watershed territory. Brain MRI showed symmetric T2 fluid-attenuated inversion recovery hyperintensities with diffusion restriction in the globus pallidae consistent with hypoxic ischemic injury (figure).

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Figure MRI of the brain and cervical spine

(A) Sagittal short tau inversion recovery image of the cervical spinal cord reveals T2 hyperintensity at C5 extending to the thoracic spine with diffusion restriction on sagittal focus diffusion-weighted imaging (DWI) (B). (C) Axial cervical spinal cord T2 sequence demonstrates the preferential involvement of the anterior cord. (D) Axial brain T2 fluid-attenuated inversion recovery sequence shows bilateral hyperintensities in globus pallidae. (E) Brain DWI sequence demonstrates diffusion restriction within the highly metabolic regions of the basal ganglia.

CT angiogram of the head, neck, and aortic arch did not reveal any vascular pathology or dissection that could predispose the patient to a spinal cord infarction. Conventional angiogram of the spine to look for a vascular malformation was considered; however, the patient declined the test. Spinal fluid analysis ruled out any potential infectious, autoimmune, or vasculitic process. Extensive serum workup was also unrevealing (table).

After this workup, it was concluded that prolonged global hypoxia caused an anterior spinal cord infarction in the watershed territory, as well as hypoxic infarctions in the highly metabolic regions of the basal ganglia. The hearing loss was also thought to be due to hypoxic cochlear injury. Given the improved respiratory status after naloxone administration, her hypercapnic respiratory failure was the cause and not the consequence of her spinal cord infarction.

SECTION 4

The initial screening urine toxicology assay was positive for benzodiazepines, but negative for opiates, which cannot explain the patient's missing oxycodone tablets. The screening assay for opioids in the ER measures the presence of morphine, which is a metabolite of both heroin and codeine. Substances such as fentanyl, which lacks metabolites, and oxycodone, which is not metabolized to a morphine derivative, are typically undetected by urine drug screening. A specialized opioid assay detected >4,000 ng/mL of oxycodone in the urine of our patient, thus confirming oxycodone overdose as the cause of hypoxemia and hypercapnic respiratory failure. This led to a global hypoxic state with end organ damage in highly susceptible neurologic tissues.

SECTION 5

Acute management was focused on reversing the hypoxemic respiratory failure. The patient was immediately placed on bilevel positive airway pressure in the ER and the effects of oxycodone were reversed with naloxone. Measures to increase spinal perfusion were considered but ultimately not done because the mechanism of spinal cord infarction was thought to be due to reduced blood oxygen content and not compromised blood flow. Furthermore, the patient's blood pressures were normotensive to slightly hypertensive.

Psychiatry was consulted to assess the patient's depression and determined that her overdose was recreational and not a suicide attempt. Within days, the patient exhibited improved hearing, but her neurologic examination was otherwise unchanged. After 2 months of rehabilitation, she was still paraplegic with impaired pinprick sensation below T3 but could produce some trace non-anti-gravity muscle movements on the left leg. She developed spasticity in her lower extremities requiring a baclofen pump insertion and a neurogenic bladder necessitating frequent self-catheterizations.