A 21-year-old female with an unremarkable medical history, initially presented to an outside hospital with fever and influenza-like symptoms. She was admitted for possible tonsillitis. Later that day, she became confused. Computed tomographic (CT) scan of brain was performed and it was found to be normal. The patient was transferred to another facility, where she was intubated for a worsening mental status. Brain magnetic resonance imaging (MRI) was suggestive of ADEM or vasculitis for which she received five days of intravenous methylprednisolone and intravenous immunoglobulin (IVIG). She was also treated for possible encephalitis or meningitis with acyclovir, ceftriaxone and vancomycin. Her cerebrospinal fluid (CSF) cultures did not grow any microorganisms and the patient did not show clinical improvement following antimicrobial therapy. The patient did not have any history of recent vaccinations. After a week from the initial presentation, she was transferred to our hospital where plasma exchange therapy was started due to failure of pulse dose steroids and IVIG for possible ADEM or vasculitis.
On admission to the intensive care unit (ICU), the patient had stable vital signs not requiring any vasopressors, she was afebrile, and was intubated from the outside hospital with a Glasgow coma scale (GCS) of 8/15. The rest of her physical examination was within normal limits. On laboratory examination, complete metabolic panel were within normal limits, toxicological screening was negative, and complete blood counts were normal except for leucocytosis [15.3 x 109/L white blood cells (WBC)] and elevated C-reactive protein [CRP 41.7 mg/L (normal value < 5 mg/L)]. Thyroid function tests were normal. Brain MRI demonstrated multifocal ill-defined patchy hyperintense lesions on T2-weighted images involving cerebral white matter and left posterior thalamus (Fig. 1, Fig. 2). These changes were thought to be non- specific and suggestive of possible ADEM, vasculitis, or autoimmune encephalitis. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis (70 nucleated cells/uL, 98% lymphocytes) with normal protein [0.27 g/L (normal value 0.15-0.45 g/L)] and elevated glucose concentration [5.9 mmol/L (normal value 2.22-3.89 mmol/L)]. Results of extensive encephalitis and meningitis polymerase chain reaction (PCR) testing of CSF including Cytomegalovirus, Herpes simplex virus 1 and 2, Human herpesvirus 6, Enterovirus, Parechovirus, Varicella zoster virus, Cryptococcus, Escherichia coli, Hemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae were all negative. CSF Mycoplasma pneumoniae PCR was negative. CSF Mycobacterium tuberculosis PCR testing, CSF acid fast bacilli (AFB) smear and culture were negative. CSF fungal smear and culture were also negative. All cultures including blood, urine, sputum and CSF were sterile.
Antinuclear antibody panel was within normal limits ruling out any autoimmune disorders and her CT angiography of the brain showed no stenosis or aneurysm of the intracranial arteries. Electroencephalogram (EEG) revealed changes consistent with encephalopathy and ruled out any subclinical seizure activity. Additionally, echocardiography and CT scans of both the thorax and abdomen were normal. Chest radiography was clear.
Results of extensive virological and bacteriological PCR testing of respiratory samples including Influenza (A, B, A-H1 and A-H1 Pandemic 2009), Respiratory syncytial virus A and B, Parainfluenza (1-4), Coronavirus (OC43, NL63, and 229E), Rhinovirus (A-C), Enterovirus, Adenovirus, Human metapneumovirus, Bocavius (1-4), Chlamydophila pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Bordetella pertussis, Bordetella parapertussis, Hemophilus influenzae and Streptococcus pneumoniae were all negative except for Mycoplasma pneumoniae. Serology test results for Epstein-Barr virus, Hepatitis B and C, Cytomegalovirus, Human immunodeficiency virus, Cryptococcus, Lyme, Brucella, Bartonella henselae, Bartonella quintana, Treponema pallidum and Legionella were all negative but Mycoplasma pneumoniae IgM antibody [patient value: 27 (normal value: <=8.99 NovaTec units)] was high.
A diagnosis of ADEM secondary to Mycoplasma pneumoniae (positive respiratory PCR and elevated IgM antibody) was made. Intravenous azithromycin 500 mg was started every 24 h and planned to complete a course of 14 days. Daily plasma exchange therapy was initiated and planned to continue for seven consecutive days. Intravenous acyclovir 500 mg every eight hours was continued for two more days until herpes simplex virus (HSV) PCR was negative, after which it was discontinued.
On the third day of ICU admission, the patient was normotensive, tachycardic (122 beats/min), tachypneic (23 breaths/min), febrile (100.4  F) with leukocytosis (19.1 x 109/L WBC). Femoral central venous catheter placed in outside hospital was removed and foley catheter was re-inserted. Primary report of sputum culture showed gram negative bacteria (GNB). The patient was empirically initiated on piperacillin/tazobactam to treat ventilator-associated pneumonia. She had persistent diarrhea. Clostridium difficile PCR was negative and her diarrhea was believed to be due to treatment with laxatives. Sedation was eventually weaned and stopped. The patient had generalized weakness and was not able to move her extremities. On the fourth day of the ICU admission, her Mycoplasma pneumoniae IgM antibody went down [patient value: 6.32 (normal value: <=8.99 NovaTec units)].
On day 5 of the ICU admission, she was more awake, responsive, well oriented and was extubated. She was afebrile, all cultures were negative and piperacillin/tazobactam was stopped. The patient showed marked improvement with physical therapy and she was mobilized using a walker. She passed a bedside swallow evaluation and was initiated on oral diet. Day eight of ICU admission, patient was discharged against medical advice to continue treatment outside the country. On the day of discharge, patient completed six sessions of plasma exchange therapy on daily basis. It was planned to continue azithromycin to complete the full course of treatment and to wean oral prednisolone over four to six weeks.