CNS Infections: A Clinical Approach
Pathogenesis cont…. Specific Pathogens Mince only if filamentous fungi expected. Room temperature.
Pus, irrigation fluid, and fluid aspirates Sterile container. Anaerobic culture request requires transport in oxygen-free container. Refrigeration for longer times. Do not refrigerate if anaerobic culture is ordered.
Study explores blood-brain barrier leakage in CNS infections
Tissue, debridement material Sterile container. Keep small specimen portions moist with sterile saline solution. As for pus above.
Which tube for microbiology? CSF Macroscopy Direct smear — Gram stain Emerging issues American Academy of Pediatrics recommended combination therapy, initially with vancomycin and either cefotaxime or ceftriaxone for all children 1 month of age or older with definite or probable bacterial meningitis. You just clipped your first slide!
Clipping is a handy way to collect important slides you want to go back to later. CNS Infections: A Clinical Approach is of value to the busy clinician; the neurological international community as well as all primary care doctors, internal medicine specialists and residents who take care of patients with suspected neurological infections. Help Centre. My Wishlist Sign In Join.
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Clinical data are limited to case reports; thus this approach cannot be recommended for routine use yet [ DIII ] [ ]. Any indwelling device such as a ventricular drain or a central venous line should be removed in invasive Candida infection [ BIII ] [ , ]. Mucormycosis is a rare opportunistic infection mainly caused by Rhizopus spp. The brain might be involved in a disseminated infection or by infiltration from adjacent rhino-sinu-orbital regions [ 8—10 , , ].
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Clinical symptoms such as facial pain or swelling may be nonspecific but are frequently present in patients with rhinocerebral mucormycosis [ ]. The CT scan frequently reveals characteristic bone destruction of the paranasal sinuses, the hard palate or adjacent structures [ ]. Histopathological examination of infected tissue typically shows the irregular fungal hyphae with wide-angle branching, in addition to tissue necrosis and fungal angioinvasion [ 53 ]. PCR assays using infected tissue specimens [ B ] or blood [ C ] have also been evaluated to diagnose mycormycosis [ 54 , 55 , 57 ]. However, these methods are not standardized yet.
Immediate surgical resection of necrotic tissue may be crucial in addition to antifungal treatment in invasive mucormycosis [ AII t,u ] [ 8 , 9 , , ]. Besides reduction of immunosuppressive drugs conditions associated with the occurrence of mucormycosis such as hyperglycemia, lactic acidosis and iron overload should be corrected whenever possible [ BIII ]. However, a placebo-controlled trial exploring L-AmB together with the iron chelating agent deferasirox was terminated prematurely due to inefficacy, despite the crucial role of iron in the pathogenesis of mucormycosis [ DII t ] [ ]. Hyperbaric oxygen has been investigated as primary or salvage treatment of mucormycosis [ — ].
This approach is available only in some centers and there are no larger trials confirming its benefit [ CIII ]. Reports from human immunodeficiency virus HIV -negative patients with hematological disorders and infection with Cryptococcus spp. Neuroimaging by MRI may show dilated Virchow-Robin spaces, cyst-like structures and granuloma of the choroid plexus [ ]. The diagnosis might further be confirmed by detection of capsular antigen using different techniques such as enzyme immune assays, latex agglutination or the lateral flow assay [ A ] [ 58 , 61 ].
Biopsy of infected tissues followed by culturing and histopathological investigation is required only in selected cases [ C ] [ 60 ].
Voriconazole or posaconazole may be used for salvage treatment [ CIII ] [ , , ]. Cryptococcus spp. Thus, these agents do not play a role in the treatment of cryptococcal meningitis [ DIII ]. Reducing the CSF opening pressure e. Viral CNS infections typically present as meningoencephalitis, but strokes—e. JC virus-associated PML might occur [ 18 ]. However, studies comparing viral isolation from autopsy samples or brain-biopsy specimens—the former reference standard—with PCR are available only for few viruses such as HSV or cytomegalovirus CMV [ 64 , 65 , 70 ].
CSF virus PCR might initially be false-negative and the probability of a positive PCR increases when there is a time frame of 3—14 days between onset of symptoms and lumbar puncture [ ]. The incidence of HSV encephalitis is relatively low in patients with hematological disorders and there have been few cases published which mainly include allo-HSCT recipients [ 2 , 73 , ]. Cerebral MRI typically shows abnormalities in the medial and inferior temporal lobe, the insula and the cingulate supplementary Figure S3, available at Annals of Oncology online [ ].
In rare cases of aciclovir resistance, foscarnet may be administered [ CIII ] [ ]. CMV CNS disease is typically characterized by ventriculo-encephalitis, retinitis and polyradiculopathy [ , , ]. Some authors recommend a combination of both agents [ BIII ] [ , — ]. Cidofovir as single agent or in combination with foscarnet or ganciclovir might be used for salvage treatment [ CIII ] [ , , ].
There are no systematic data showing a benefit of the routine administration of CMV hyperimmunoglobulin in patients with hematological disorders and CMV disease. The role of rituximab in EBV disease i. EBV reactivation only might reduce the incidence of post-transplant lymphoproliferative disorder [ ]. Likewise, it remains unclear whether antivirals are beneficial in EBV disease [ ]. Ganciclovir, valganciclovir or foscarnet might be used to treat EBV meningoencephalitis [ BIII ] and there are few case reports on the potential efficacy of aciclovir in this situation [ CIII ] [ , — ].
HHV-6 encephalitis typically affects allo-HSCT recipients with unrelated mainly cord blood donors and it frequently develops at the time of engraftment or shortly thereafter [ 2 , 7 ]. Common clinical symptoms include alteration of consciousness, short-term memory loss and seizures [ 2 , 7 , ]. CSF analysis might show elevated protein levels and, more rarely pleocytosis [ 2 , 77 ]. Imaging abnormalities which typically involve the temporal lobe are more likely visible in MRI than in CT scan supplementary Figure S4, available at Annals of Oncology online [ 2 , 77 ].
Cidofovir can be administered as second-line treatment [ CIII ] [ ]. Diagnosis of VZV meningoencephalitis may be confirmed by serological tests such as detection of intrathecal VZV glycoprotein E [ ]. However, aciclovir resistance could occur and there are case reports on fatal CNS meningoencephalitis in allo-HSCT recipients despite early therapy with high-dose aciclovir [ ]. These patients might benefit from a combination of aciclovir and foscarnet [ CIII ] [ ]. The typical triad demyelination, bizarre astrocytes and enlarged oligodendroglial nuclei can frequently be demonstrated by histopathological work-up in biopsies which might be combined with tissue and CSF JC virus dual qualitative-quantitative nested PCR [ A ] [ 86 , 88 , 89 ].
MRI typically shows abnormalities in the posterior white matter without contrast enhancement supplementary Figure S5, available at Annals of Oncology online [ ]. Treatment with cidofovir may be beneficial in some patients with PML [ 2 , , ]. Several experimental approaches such as adoptive T-cell therapy or administration of interleukin-2, mefloquine or mirtazapine have been tested as a treatment option for PML [ 12 , — ].
Since none of them has clearly shown to be effective in larger series of patients they are recommended within experimental protocols only [ DIII ]. Diagnosis of CNS infections remains a great challenge in patients with hematological disorders since symptoms might both be masked and be mimicked by other conditions such as metabolic disturbances or consequences from antineoplastic treatment.
Thus, awareness of this complication is crucial and any suspicion of a CNS infection should lead to timely and adequate diagnostics and treatment to improve the outcome in this population. All remaining authors have declared no conflicts of interest.
Healthcare-Associated Ventriculitis and Meningitis
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