The patient is a 26-year-old right-handed high school educated African American female. Beginning the third week of April, she started to complain of headache, runny nose, and cough. Her other medical morbidities included uncontrolled type 1 diabetes mellitus (on insulin), obesity, chronic kidney disease stage III (diabetic nephropathy), recurrent yeast (monilial) vaginitis, and a serum test positive for herpes simplex type 2 in 2019. Her developmental history was significant for a left brachial plexus injury (Erb’s palsy) from a prolonged labor and a genu varum which were treated with orthoses and corrective surgery, respectively.
She was positive for SARS - COV 2 via nasopharyngeal swab PCR after being exposed to her mother who was subsequently hospitalized in an intensive care unit (ICU). Patient herself presented to emergency room with fever, diffuse headache, exertional dyspnea, myalgia, fatigue, nausea, abdominal pain, diarrhea, and loss of appetite soon after. There was no associated chest pain, palpitations, photophobia, phonophobia, weakness, dizziness, or other sensorimotor symptoms.
First examination revealed an awake, conversational, and oriented obese female with no focal neurological findings but, relative tachypnea, tachycardia, hypertension, and a temperature of 39.2⁰ C. She was saturating 98% on pulse oximetry at room air. Pertinent laboratory values [reference range] included a serum glucose of 212 mg/dl [70 mg/dl − 99 mg/dl], creatinine of 2.7 mg/dl [0.6 mg/dl – 1.0 mg/dl], blood urea nitrogen of 34 mg/dl [7 mg/dl – 19 mg/dl], magnesium 1.6 mg/dl [1.6 mg/dl – 2.6 mg/dl] and lipase 771 IU/L [8 IU/L – 78 IU/L]. Patient also had an elevated C-reactive protein at 66.9 mg/L [0 mg/dl – 5 mg/dl], normocytic anemia of 7.9 gm/dl [12 gm/dl – 16 gm/dl], ferritin 1784 ng/ml [5 ng/ml – 204 ng/ml], fibrinogen of 651 mg/dl [191 mg/dl – 491 mg/dl] and a peak D-dimer of 10,180 ng/ml [270 ng/ml – 490 ng/ml]. Blood and urine cultures were negative for an infection.
Chest x-ray was hypo-inflated with mild bibasilar airspace opacities. She was administered intravenous fluids and placed on isolation precautions. Overnight she became hypoxic and lethargic requiring supplemental oxygen. Care was escalated to a stepdown level, in view of worsening kidney injury, metabolic acidosis and alteration of consciousness. The patient was alert but, speech was now limited to "yes, no and hurts" responses. Cranial nerves were intact, strength was symmetric and sensory modalities were preserved. A non-contrast CT (NCCT) head was negative for acute pathology.
A stroke alert was later initiated for an acute onset of focal sensory deficits when she could not feel pain on her left arm during phlebotomy. On this assessment she was essentially without speech, responding only with nods of her head but, able to follow simple motor instructions. Cranial nerve and motor exam were normal except for her Erb’s palsy but, her sensation to light touch was diminished on the left arm and leg. NCCT head on this occasion revealed a hypodense corpus collosum along its entire length. (Fig. 2A)
The next morning, she remained alert and oriented to being in a hospital. Speech was mildly dysarthric. Comprehension was intact but, she could not name, repeat or write. Cranial nerves, strength and sensation were preserved. Toes were down and no gross ataxia was present on movements of limbs on her right. Her left arm was apractic. The development of a disconnection syndrome with putative etiologies being either vascular, inflammatory, or infectious was entertained. An acute hypoxic respiratory failure requiring intubation, with non-oliguric acute kidney injury, normocytic anemia, and encephalopathy delayed further neurologic investigation. She received tocilizumab, steroids, remdesivir and convalescent plasma exchange as treatment modalities for a severe COVID-19 infection. A dysexecutive syndrome was noted once the acute medical issues began to resolve. 9
4 weeks from onset, her exam became referable to the dominant parietal lobe. Now extubated, she was making a steady recovery from her COVID-19 infection and had recently tested negative. While no longer aphasic or agraphic, she scored 19/30 on Montreal Cognitive Assessment (MoCA), for impairments in visuospatial/executive tasking, and calculation. (Fig. 1) She had a hoarse voice from a vocal cord palsy, without other cranial nerve anomalies. There was no new weakness. Her sensation was preserved to all exteroceptive and interoceptive modalities symmetrically across gross dermatomes. She continued to exhibit an apraxia of her left upper extremity. Finally, she had developed a finger agnosia of the left hand with suggestions of left-right disorientation.
A contrast enhanced MRI brain 18 days after the initial CT scan confirmed an expansile T2 hyperintense signal along the complete length of corpus callosum associated with restriction of diffusion, and T1 prolongation. (Fig. 2B and C) There was no superimposed susceptibility or pathologic enhancement. While a CT angiogram was not feasible with her kidney injury, no large vessel occlusions were identifiable from gradient echo (GRE), turbo spin echo (TSE), susceptibility weighted imaging (SWI) and post contrast MR sequences.
A diagnosis of probable COVID-19 encephalitis manifesting as a disconnection syndrome 1 was made. Additional attempts to consolidate a cytokine mediated excitotoxic injury through the burden of interleukins in cerebrospinal fluid (CSF) 5 and exclusion of a direct viral or auto-immune mediated encephalitis were abandoned in view of the clinical propriety of discharge after a prolonged stay in the hospital.
She continued to recuperate in brain injury rehabilitation for dyspraxia of left upper extremity, speech, swallowing, ambulatory dysfunction, and neuropsychiatric derangements (left visuospatial neglect, insomnia, mood and adjustment disorders). 9 An MRI brain repeated since discharge demonstrated an improving encephalitis by virtue of normalizing ADC values.