A previously healthy 42-year-old man is brought to the ED by his wife who noticed that he was stumbling and almost fell down on two occasions over the past few hours. He had been having nausea and vomiting for the last few days followed by global headaches and subjective fevers. This morning he woke up complaining of double vision, and his wife noticed that he was limping when he got up from his bed. In the ED, his vital signs are:
On examination, he was alert and oriented. Cardiovascular, respiratory, and abdominal examination were normal. He did not have nuchal rigidity, but lateral gaze of the right eye was restricted; he had mild left-sided hemiparesis and decreased sensation on the left side of the body. Laboratory data included a hemoglobin of 12.3 g/dL, WBC count 16 000/dL (90% neutrophils), platelets 235 000/dL, sodium 126 mmol/L, creatinine 1.5 mg/dL (no prior data available), aspartate aminotransferase 37 U/L, alanine aminotransferase 26 U/L, and total bilirubin 1.0 mg/dL. A CT head without contrast was obtained, which did not show any acute abnormality. He was empirically started on vancomycin and ceftriaxone for community-acquired bacterial meningitis and transferred to the floor. Overnight, his level of consciousness decreased and respiratory status deteriorated resulting in the need for intubation before being transferred to the medical ICU. Bedside electroencephalography did not show any seizure activity. He continued to spike high-grade fevers and eventually underwent an LP, which showed mild neutrophilic pleocytosis and mildly elevated protein, suggestive of aseptic meningitis but was otherwise normal. A brain MRI with contrast was planned; however, before this could happen, the patient’s neurological status worsened with loss of cranial nerve reflexes and the family decided to withdraw care. Blood cultures from admission showed growth of gram-positive bacteria in two of two bottles at 48 hours, about 24 hours after the patient’s death. Final pathology from autopsy reported severe inflammation of the brainstem, which led to herniation.
Which of the following is true regarding the management of this patient?
A. Empiric therapy with acyclovir should have been started pending diagnostic workupCorrect Answer: B
Listeria monocytogenes can cause invasive CNS disease in otherwise healthy individuals requiring a very high level of suspicion for diagnosis. Early administration of ampicillin, which is the treatment of choice, significantly alters morbidity and mortality.
Inflammation of the brainstem, also known as rhomboencephalitis, is a well-described syndrome that can result from a variety of infectious and noninfectious insults. In immunocompromised individuals such as those with HIV and slowly progressing infections such as Cryptococcus and tuberculosis are seen more commonly, but HSV-1 and Listeria monocytogenes can affect immunocompentent individuals as well. In contrast to its other manifestations, Listeria monocytogenes rhomboencephalitis typically occurs in young healthy individuals. This syndrome is distinct from the more commonly seen Listeria meningitis in neonates, in the immunosuppressed and elderly. It classically presents as a biphasic illness with 72 to 96 hours of prodromal symptoms consisting most commonly of fevers, headaches, nausea, and vomiting, which are followed by rather rapid progression of focal neurological deficits involving the brainstem. Meningeal signs may be completely absent in these patients, and CSF analysis may or may not be suggestive of meningoencephalitis. Blood cultures are positive in up to half of these cases, and CSF PCR for Listeria monocytogenes (as part of multiplex panels) may aid in diagnosis. The treatment of choice is ampicillin, with trimethoprim-sulfamethoxazole as an alternative in the setting of penicillin allergy. Mortality without early initiation of adequate therapy is up to 50%. Even with treatment, high mortality and morbidity from persistent neurological deficits have been reported. As this syndrome occurs in young, otherwise healthy individuals in whom Listeria is not usually considered a causative organism of meningitis and for whom Listeria coverage is not usually included in empiric antimicrobial regimen for CNS infections, the diagnosis requires high index of suspicion and early initiation of empiric treatment while awaiting diagnostic studies.
Consideration should also be given to noninfectious etiologies of rhomboencephalitis including multiple sclerosis and autoimmune or paraneoplastic syndromes; however, antimicrobial therapy should be started early while workup is in process for other noninfectious etiologies. Although HSV can cause rhomboencephalitis, the presence of bacteremia with Listeria argues against this being the etiological agent. The addition of dexamethasone during treatment of invasive Listeriosis was associated with a trend toward worsened outcomes in a large French study and is therefore discouraged.
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