Into the unknown: Diagnosing mysterious brain lesions.

In this inaugural clinicopathological conference, the invited experts discussed the diagnostic approach to central nervous system infections in immunocompromised hosts. The case presented involved a pancreas-kidney transplant recipient with multiple brain abscesses caused by Bartonella henselae. CSF metagenomic next-generation sequencing played a significant role in the diagnosis. Bartonella henselae is a gram-negative zoonotic pathogen that causes cat-scratch disease, which can be transmitted to humans through cat bites or scratches. Symptoms can vary in severity, correlating with the patient's immune status. Visceral organ involvement, ocular involvement, and neurological manifestations have been reported in immunocompromised patients, but brain abscesses are rare.

Acute infectious myelopathies.

PURPOSE OF REVIEW: The patient who presents with an acute spinal cord syndrome with weakness/paralysis of the limbs presents a diagnostic. Two important syndromes are acute transverse myelitis (ATM) and acute flaccid paralysis (AFP). Both can be caused by a number of infectious and noninfectious causes. Since 2014 there have been outbreaks of acute flaccid myelitis (a subgroup of AFP) in the United States, with a national surveillance program underway. In addition, there have been increasing reports of ATM from new and emerging pathogens, and opportunistic infections in immunocompromised hosts. RECENT FINDINGS: Infectious causes of ATM or AFP need to be ruled out first. There may be important clues to an infectious cause from epidemiologic risk factors, immune status, international travel, MRI, and laboratory findings. We summarize key features for the more common pathogens in this review. Advances in laboratory testing have improved the diagnostic yield from cerebrospinal fluid, including real-time polymerase chain reaction, metagenomic next-generation sequencing, and advanced antibody detection techniques. These tests still have limitations and require clinical correlation. SUMMARY: We present a syndromic approach to infectious myelopathies, focusing on clinical patterns that help narrow the diagnostic possibilities.

Rathke's cleft cyst presenting with recurrent aseptic meningitis and inflammatory apoplexy: illustrative case.

BACKGROUND: Rathke's cleft cyst (RCC) is a benign sellar/suprasellar lesion often discovered incidentally. Rarely, symptomatic cases can present with headache and may exhibit concomitant aseptic meningitis or apoplexy. The authors describe a patient with an RCC presenting with recurring episodes of aseptic meningitis and ultimately inflammatory-type apoplexy. OBSERVATIONS: A 30-year-old female presented with three episodes of intractable headaches over 2 months. Each episode's clinical picture was consistent with meningitis though cerebrospinal fluid cultures, and viral tests remained negative. Imaging demonstrated a sellar lesion, initially thought to be coincidental. On the third presentation, there was rapid interval growth of the lesion, adjacent cerebritis, and new endocrinopathy. Resection was then performed via an endoscopic endonasal approach. Pathology showed an RCC with acute and chronic inflammation and no evidence of hemorrhage. Cultures were negative for organisms. The patient received several weeks of antibiotic treatment with the resolution of all symptoms and no recurrence. LESSONS: Recurrent aseptic meningitis with apoplexy-like symptoms is a rare presentation of RCC. The authors propose the term inflammatory apoplexy to describe such a presentation without evidence of abscess, necrosis, or hemorrhage. The mechanism is unclear although may be due to intermittent microleakage of cyst contents into the subarachnoid space.

High-Dose Oral Posaconazole for the Treatment of Recalcitrant Fungal Keratitis.

PURPOSE: To report the successful treatment of 3 cases of recalcitrant fungal keratitis (FK) with high-dose oral posaconazole. METHODS: This is a series of 3 patients from a single academic center with a culture-positive FK who were treated with oral posaconazole after failing to respond to conventional treatments. RESULTS: All 3 patients had a history of contact lens wear. Two of the 3 cases were culture positive for Fusarium and the other for Paecilomyces . The infections of all 3 failed to respond to conventional antifungal therapies including varying combinations of topical, systemic, and intraocular antifungal therapies. All 3 cases rapidly responded to high-dose oral posaconazole ranging from 500 to 600 mg once daily. In 1 case, multiple courses of high-dose therapy were required to treat delayed recurrences of a latent infection. There were no significant adverse effects with the elevated dose, and treatment was administered with the guidance of an infectious disease specialist. CONCLUSIONS: In cases of recalcitrant FK failing to respond to conventional therapies, high-dose posaconazole, in the delayed-release tablet formulation, can be an effective treatment option.

Methicillin-resistant Staphyloccocus aureus heel abscess: an uncommon emergency department diagnosis.

Heel abscesses present as heel pain that progressively worsens, with associated tenderness and fullness at the heel pad. Radiological studies like computed tomography, magnetic resonance imaging, or ultrasound can help correctly diagnose a heel pad abscess. Generally, these patients require i.v. antibiotics and operative management to adequately drain the abscess. It is recommended to avoid incising the plantar aspect of the heel to minimize chronic post-drainage heel pain.

Real-time polymerase chain reaction (PCR) cycle threshold and Clostridioides difficile infection outcomes.

OBJECTIVE: Clostridioides difficile infection (CDI) causes significant morbidity and mortality; however, the diagnosis of CDI remains controversial. The primary aim of our study was to evaluate the association of polymerase chain reaction (PCR) cycle threshold (Ct) values with CDI disease severity, recurrence, and mortality among adult patients with CDI. DESIGN: Retrospective cohort study. SETTING: Single tertiary-care hospital. PATIENTS: Adult patients diagnosed with hospital-onset, healthcare facility-associated CDI from June 2014 to September 2015. METHODS: We performed a retrospective chart review of included patients. Univariate and multivariable logistic regression methods were used to evaluate the association between Ct values and CDI severity, 8-week recurrence, and 30-day mortality. RESULTS: Among 318 included patients, 51% were male and the mean age was 62 years; ~32% of the patients developed severe CDI and 11% developed severe-complicated CDI. The 30-day all-cause mortality rate was 11% and the 8-week recurrence rate was 9.5%. The overall mean Ct value was 32.9 (range, 23-40). Multivariable analyses showed that lower values of PCR Ct were associated with increased odds of 30-day morality (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.72-0.96) but were not independently associated with CDI severity (OR, 0.99; 95% CI, 0.90-1.09) or recurrence (OR, 0.88; 95% CI, 0.77-1.00). CONCLUSIONS: Our findings suggest that PCR Ct values at the time of diagnosis may have a limited predictive value and utility in clinical decision making for inpatients with CDI. Larger, prospective studies across different patient populations are needed to confirm our findings.

A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase.

OBJECTIVE: Daptomycin has been associated with increased creatine phosphokinase (CPK) due to muscle injury leading to myalgias and muscle weakness. Statins have been proven to cause the same effects and it is recommended to discontinue the use of statins while on daptomycin. Evidence regarding this drug interaction is mixed. This study evaluated the risk of CPK elevation in concomitant use of daptomycin and statins compared to daptomycin alone. METHOD: This is a multisite retrospective case-control study of patients who received daptomycin therapy with monitoring of CPK. Rates of CPK elevations were compared in patients receiving daptomycin with a statin versus daptomycin alone. To estimate the association between CPK elevation and daptomycin therapy controlling for other risk factors, logistic regression was used to analyze data. Statistical significance was determined at ɑ of 0.05. RESULTS: A total of 3658 patients were included in the study, with 2787 on daptomycin therapy alone and 871 with concurrent statin use. The incidence of CPK elevation was 90 events (3.2%) in the daptomycin group and 26 events (3.0%) in the concurrent statin group. Patients who received daptomycin therapy in addition to statins had no statistically significant difference from patients on daptomycin alone (hazard ratio, 1.05; P = .85; 95% confidence interval, 0.61-1.84). After adjusting for potential risk factors, the hazards ratio remained almost the same. CONCLUSIONS: Concomitant use of daptomycin and statin did not show an increase risk of CPK elevation. Clinicians may consider concomitant use of daptomycin and statin therapy with weekly CPK monitoring.

Progressive Multifocal Leukoencephalopathy in a Lung Transplant Recipient: Isolation of John Cunningham (JC) Virus from Bronchoalveolar Lavage.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by polyomavirus John Cunningham (JC) virus. We report the case of a 60-year-old woman who presented 16 months after right single lung transplant with worsening memory, behavioral problems, emotional lability, and progressive left upper extremity weakness. Magnetic resonance imaging revealed white matter changes suggestive of PML. JC virus infection was confirmed with polymerase chain reaction (PCR) from both the bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid. To our knowledge, this is the first report of PCR isolation of JC virus from a BAL specimen. We also review the two additional cases in the literature that describe PML after lung transplantation. JC virus infection should be considered in the differential diagnosis of lung transplant recipients who develop neurological symptoms. BAL may have a role in the etiologic diagnosis of PML after lung transplantation.

MRI findings in cryptococcal meningitis of the non-HIV population.

OBJECTIVES: Cryptococcal meningitis is an opportunistic infection which can afflict immunocompetent and immunocompromised individuals. Imaging findings in the HIV population are well described; however, few studies have focused on the non-HIV population.The purpose of this study is to characterize clinical and magnetic resonance imaging (MRI) findings in the non-HIV population. METHODS: We performed a retrospective chart review of patients with positive CSF cryptococcal antigen (between 1997 and 2009) who were not HIV positive. Only patients with MRIs of the brain were included. Data collected included CSF findings, blood and CSF cryptococcal titers, and information regarding the use of immunosuppressant drugs. RESULTS: Nineteen patients fulfilled study criteria, and 74% of the patients had abnormal imaging.Ten patients were on immunosuppressants due to cancer, organ transplantation, or presumed vasculitis. Four patients had no known risk factors and 2 patients had idiopathic low CD4 counts.MRI findings in cryptococcal meningitis included leptomeningeal enhancement with or without a micronodular pattern, microcystic prominence involving the temporal lobes or basal ganglia, ventriculomegaly, and a brain abscess. Two patients had posterior fossa cysts at the foramen of Luschka. Five patients had a normal MRI. CONCLUSIONS: MRI findings in cryptococcal meningitis of the non-HIV population were more common in our series than previously recognized. In this patient population, leptomeningeal enhancement and intraventricular cystic lesions were more common than intraparenchymal findings.

Endogenous endophthalmitis: an 18-year review of culture-positive cases at a tertiary care center.

A retrospective chart review of all patients seen at the Cleveland Clinic Foundation with infectious endogenous endophthalmitis between January 1982 and August 2000 revealed 34 affected eyes in 27 patients. During this time, the median incidence of endogenous endophthalmitis was 1.8 cases/year, and 48.1% of patients presented as outpatients. Twenty-six patients presented to an ophthalmologist, and the diagnosis was initially missed in almost half the cases. Eleven patients had an unremarkable physical exam except for eye findings. We found an equal incidence of bacterial and fungal endophthalmitis and a predominance of among the fungal etiologic agents. We did not, however, note a predominance of Gramnegative organisms seen mostly in reports from Asia. The microbiologic diagnosis was based on aqueous and vitreous cultures or positive eye histopathology stains in almost two-thirds of cases. The sensitivity of the Gram stain was poor, but its specificity and positive predictive value were excellent. The vitreous cultures obtained by vitrectomy instruments were more sensitive in making the diagnosis than the vitreous needle biopsy. Aside from blood cultures and eye specimen cultures, half the patients had an additional infectious focus, most frequently a urinary tract infection, whereas infectious endocarditis was seen in a small minority. Twelve patients had visual improvement with treatment with a final visual acuity better than 20/200 in 44% of the eyes. Good visual outcome was associated with visual acuity of 20/200 or better at diagnosis and with the absence of hypopyon.

Predictive value and cost-effectiveness analysis of a rapid polymerase chain reaction for preoperative detection of nasal carriage of Staphylococcus aureus.

OBJECTIVE: To determine the accuracy and cost-effectiveness of a polymerase chain reaction (PCR) for detecting nasal carriage of Staphylococcus aureus directly from clinical specimens. CROSS-SECTIONAL STUDY: This occurred in a tertiary-care hospital in Cleveland, Ohio, and included 239 consecutive patients who were scheduled for a cardiothoracic surgical procedure. Conventional cultures and a PCR for S. aureus from nasal swabs were used as measurements. COST-EFFECTIVENESS ANALYSIS: Data sources were market prices and Bureau of Labor Statistics. The time horizon was the maximum period for availability of culture results (3 days). Interventions included universal mupirocin therapy without testing; initial therapy, with termination if PCR negative (treat-PCR); initial therapy, with termination if culture negative (treat-culture); treat PCR-positive carriers (PCR-guided treatment); and treat culture-positive carriers (culture-guided treatment). The perspective was institutional and costs and the length of time to treatment were outcome measures. RESULTS: Sixty-seven (28%) of the 239 swabs grew S. aureus. Rapid PCR was 97.0% sensitive and 97.1% specific for the detection of S. aureus. For populations with prevalences of nasal S. aureus carriage of up to 50%, the PCR assay had negative predictive values of greater than 97%. PCR-guided treatment had the lowest incremental cost-effectiveness ratio (1.93 dollars per additional day compared with the culture strategy). Among immediate treatment strategies, treat-PCR was most cost-effective. The universal therapy strategy cost 38.19 dollars more per additional day gained with carrier identification compared with the PCR strategy. CONCLUSION: Rapid real-time PCR is an accurate, rapid, and cost-effective method for identifying S. aureus carriers for preoperative intervention.

The neuropathology of West Nile virus meningoencephalitis. A report of two cases and review of the literature.

West Nile virus (WNV) is an emerging mosquito-transmitted encephalitis virus first recognized in North America in 1999. The pathologic manifestations of WNV infection have not been well defined. This study documents the clinicopathologic features, including autopsy findings, of 2 cases: an 81-year-old man who contracted WNV infection with meningoencephalitis and a polio-like paralysis and a hospitalized 74-year-old woman with meningoencephalitis who acquired WNV through transfusion. The pathologic findings in both cases were marked by perivascular and leptomeningeal chronic inflammation, microglial nodules, and neuronophagia, predominantly involving the temporal lobes and brainstem. These findings also were present in the spinal cord, especially the lumbar region, of the patient with polio-like paralysis. In both cases, most of the inflammatory infiltrate was composed of CD3+ T lymphocytes (a predominance of CD8+ over CD4+ T cells), CD68+ macrophages, and rare CD20+ B lymphocytes. These cases further define the clinical and pathologic spectrum of central nervous system disease in WNV infection.

West Nile fever: lessons from the 2002 season.

West Nile fever has now spread to much of the United States. This disease can be diagnosed using one of several laboratory tests, notably an immunoglobulin M enzyme-linked immunosorbent assay. It can cause devastating neurologic damage, including an unusual polio-like syndrome. Magnetic resonance imaging is an important imaging tool in such patients. Treatment is largely supportive, although antiviral agents are under investigation.

Spinal tuberculosis deserves a place on the radar screen.

Spinal involvement may be the first manifestation of tuberculosis and the problem that drives the patient to seek medical care. Spinal tuberculosis (often called Pott's disease) is by definition advanced disease, requiring meticulous assessment and aggressive systemic therapy. Physicians should keep the diagnosis in mind, especially in a patient from a group with a high rate of tuberculosis infection.

Transitioning from a noon conference to an academic half-day curriculum model: effect on medical knowledge acquisition and learning satisfaction.

BACKGROUND: The academic half-day (AHD) curriculum is an alternative to the traditional noon conference in graduate medical education, yet little is known regarding its effect on knowledge acquisition and resident satisfaction. OBJECTIVE: We investigated the association between the 2 approaches for delivering the curriculum and knowledge acquisition, as reflected by the Internal Medicine In-Training Examination (IM-ITE) scores and assessed resident learning satisfaction under both curricula. METHODS: The Cleveland Clinic Internal Medicine Residency Program transitioned from the noon conference to the AHD curriculum in 2011. Covariates for residents enrolled from 2004 to 2011 were age; sex; type of medical degree; United States Medical Licensing Examination Step 1, 2 Clinical Knowledge; and IM-ITE-1 scores. We performed univariable and multivariable linear regressions to investigate the association between covariates and IM-ITE-2 and IM-ITE-3 scores. Residents also were surveyed about their learning satisfaction in both curricula. RESULTS: Of 364 residents, 112 (31%) and 252 (69%) were exposed to the AHD and the noon conference curriculum, respectively. In multivariable analyses, the AHD curriculum was associated with higher IM-ITE-3 (regression coefficient, 4.8; 95% confidence interval 2.9-6.6) scores, and residents in the AHD curriculum had greater learning satisfaction compared with the noon conference cohort (Likert, 3.4 versus 3.0; P  =  .003). CONCLUSIONS: The AHD curriculum was associated with improvement in resident medical knowledge acquisition and increased learner satisfaction.