Hemolytic Uremic Syndrome With Severe Neurologic Complications in an Adult

Hemolytic uremic syndrome (HUS) is a rare illness that can be acquired through the consumption of food products contaminated with strains of Shiga toxin-producing Escherichia coli (E coli; STEC).¹ Between 6% and 15% of individuals infected with STEC develop HUS, with children affected more frequently than adults.^2,3 This strain of E coli releases Shiga toxin into the systemic circulation, which causes a thrombotic microangiopathy resulting in the characteristic HUS triad of symptoms: acute renal insufficiency, thrombocytopenia, and hemolytic anemia.^4-6

Although neurologic features are common in HUS, they have not been extensively studied, particularly in adults. We report a case of STEC 0157:H7 subtype HUS in an adult with severe neurologic complications. This case highlights the neurological sequelae in an adult with typical STEC-HUS. The use of treatment modalities, such as plasmapheresis and eculizumab, and their use in adult typical STEC-HUS also is explored.

Case

A 53-year-old white woman with no pertinent past medical history presented to the Bay Pines Veterans Affairs Healthcare System Emergency Department with a 2-day history of abdominal pain, vomiting, nausea, diarrhea, and bright bloody stools. She returned from a cruise to the Bahamas 3 days prior, where she ate local foods, including salads. She reported no fever, shortness of breath, chest pain, headache, and cognitive difficulties. She presented with a normal mental status and neurologic exam. Apart from leukocytosis and elevated glucose level, her laboratory results at initial presentation were normal, (Table). A stool sample showed occult blood with white blood cell counts (WBCs) but was negative for Clostridium difficile. She was started on ciprofloxacin 400 mg and metronidazole 500 mg on the day of admission.

Hematuria was found on hospital day 2. On hospital day 4, the patient exhibited word finding difficulties. Blood studies revealed anemia, thrombocytopenia, leukocytosis, and increasing blood urea nitrogen (BUN) and creatinine. A computed tomography scan of the head was normal. Laboratory analysis showed schistocytes in the peripheral blood smear.

The patient’s cognitive functioning deteriorated on hospital day 5. She was not oriented to time or place. Her laboratory results showed complement level C3 at 70 mg/dL (ref: 83-193 mg/dL) complement C4 at 12 mg/dL (ref: 15-57mg/dL). The patient exhibited oliguria and hyponatremia, as well as both metabolic and respiratory acidosis; dialysis was then initiated. Results from the stool sample that was collected on hospital day 1 were received and tested positive for Shiga toxin.

At this point, the patient’s presentation of hemolytic anemia and thrombocytopenia in the setting of acute bloody diarrheal illness with known Shiga toxin, schistocytes on blood smear, and lack of pertinent medical history for other causes of this presentation made STEC-HUS the leading differential diagnosis. Plasmapheresis was ordered and performed on hospital day 6 and 7. Shiga toxin was no longer detected in the stool and antibiotics were stopped on hospital day 7.

The patient’s progressive deterioration in mental status continued on hospital day 8. She was not oriented to time or place, unable to perform simple calculations, and could not spell the word “hand” backwards. Physicians observed repetitive jerking motions of the upper extremities that were worse on the left side. An electroencephalogram (EEG) revealed right hemispheric sharp waves that were thought to be epileptiform (Figure 1). The patient began taking levetiracetam 1500 mg IV with 750 mg bid maintenance for seizure control. Plasmapheresis was discontinued due to her continued neurologic deterioration on this therapy. Consequently, eculizumab 900 mg IV was given along with the Neisseria meningitidis (N meningitidis) vaccine and a 19-day course of azithromycin 250 mg po as prophylaxis for encapsulated bacteria.

The patient continued to seize on hospital days 10 through 13. Oculocephalic maneuvers showed a tendency to keep her eyes deviated to the right. Her pupils continued to react to light. A repeat EEG showed diffuse slowing (5-6 Hz) with no epileptic activity seen (Figure 2). A second dose of eculizumab 900 mg IV was administered on hospital day 15. The patient experienced cardiac arrest on hospital day 16 and was successfully resuscitated. On hospital day 25 (10 days after receiving her second dose of eculizumab), the patient was able to speak and follow simple commands but exhibited difficulty concentrating and poor impulse control.

The patient was alert and oriented to person, place, time, and situation on hospital day 28 (6 days after the third and final dose of eculizumab). A neurologic exam was significant only for a slight intention tremor. She was continued on levetiracetam with a plan to be maintained on the medication for the next 6 months for seizure control. She was discharged on hospital day 30.

Twenty-eight days postdischarge (57 days postadmission), the patient showed marked recovery. She had returned to her previous employment as a business administrator on a part-time basis and exhibited no deficiencies in executive functioning or handling activities of daily living. Although she had been very active prior to this illness, she now experienced decreased physical and mental endurance; however, this gradually improved with physical therapy. She planned on returning to work on a full-time basis when she had regained her stamina. She also noticed difficulties in retaining short term memory since her discharge but believed that these symptoms were remitting. On examination her mental status and neurologic exam was significant for inability to continue serial 7s, left sided 4/5 muscle strength in quadriceps and thumb to 5th metacarpal adduction, bilateral 1+ reflexes in muscle groups tested (triceps, biceps, brachioradialis, patellar, and Achilles), loss of dull pinprick sensation bilaterally at web of hands, deficit in tandem gait while looking away, and slight intention tremor on finger to nose testing bilaterally (with left hand tremor more pronounced than right). Her complete blood count was normal. Her recovery continues to be monitored in an outpatient setting.