Fig. 20.1
A general approach to suspected CNS infection in a patient immunocompromised by cancer and its therapies involves basic blood tests and an urgent imaging procedure, preferably MRI, before directed testing with lumbar puncture and additional serologies. For patients with normal MRI scans but impaired level of alertness, continuous EEG is advised
Given the inherent variability in CNS infection presentations, it is hazardous to place too much emphasis on the specific tropisms of pathogens, most of which can infect multiple sites simultaneously or sequentially. However, the presence of an exclusively brainstem, cerebellar, or spinal cord syndrome at times helps to narrow infectious possibilities.
Brainstem
Infectious conditions that preferentially affect the brainstem include Listeria (rhombencephalitis) and JCV-associated PML. However, noninfectious brainstem disorders including osmotic demyelination, Wernicke encephalopathy, lymphoma, and chronic lymphocytic inflammation with peripontine enhancement responsive to steroids (CLIPPERS) enter into the differential as well.
Cerebellum
Infectious pathogens that frequently or preferentially affect the cerebellum include Listeria, VZV, JCV and Creutzfeldt–Jakob disease. All but the last on this list are of relevance to potentially infected cancer patients. Acute postinfectious cerebellitis, more common in children and young adults, follows infections with EBV, influenza A and B, VZV, and other viruses, but is not a problem particular to the cancer population considered here. Some fungi such as Aspergillus have a tropism for the posterior circulation [9]. In JCV-associated granule cell neuronopathy, the affected cerebellar neurons produce a pure cerebellar syndrome of ataxia, tremor, and nystagmus [10].
Spinal Cord Infections
Infectious processes with a predilection for spinal cord involvement can be divided into those that produce a compressive myelopathy versus those that have root or parenchymal involvement that may occur in the course of a meningoencephalitis [11]; epidural cord compression is usually bacterial or occasionally fungal. The herpes family including herpes simplex virus types 1 and 2, Varicella zoster virus, cytomegalovirus, and human herpesvirus 7 causes spinal cord dysfunction both by direct infiltration after reactivation in the dorsal root ganglia with detectable CSF viral DNA and by inciting a vigorous, damaging inflammatory response. Enteroviruses (EV) , most recently EV 71 and EV D68, generally produce a self-limited illness in noncompromised hosts but can produce paralytic disease whose severity is worse in immunocompromised patients. West Nile Virus with an ascending acute poliomyelitis or ventral root infection can present as acute flaccid paralysis, and such infection is usually more severe in immunocompromised patients. Human T cell leukemia virus-1 (HTLV1)-associated myelopathy transmitted after living donor liver transplant has been described [12]. JCV-associated PML isolated to the spinal cord has been reported [13] as has paraneoplastic-isolated myelopathy resulting in some instances in a lateral spinothalamic tract “tractopathy” [14].
Noninfectious processes that produce a longitudinally extensive transverse myelitis include PRES and paraneoplastic disorders such as neuromyelitis optica (NMO) , occasionally reported as a paraneoplastic phenomenon in patients with metastatic cancer. Underlying neoplasms have included metastatic carcinoid and lung cancer [15]. Paraneoplastic NMO usually occurs at an older age than does the idiopathic variety (55 years vs. 39 years) [16].
Extra-CNS Sites
General physical examination may disclose abnormalities outside the CNS that can help with diagnosis. This discussion is necessarily incomplete, but examination of eyes, skin, and lungs should be the main focus of consultants’ attention. Ocular examination can be useful in diagnosing Varicella zoster and Aspergillus. Skin examination may disclose a rash or other lesion that when biopsied could confirm the presence of Cryptococcosis, Aspergillosis, VZV, or HSV. Since the lungs are the portal of entry for many fungal and bacterial pathogens, chest X-ray or chest computed tomography is additional valuable modalities.
Step Three: Investigations
Because of the numerous possibilities for mass lesions and frequent paucity of specific signs and symptoms, all immunocompromised patients should have at least a screening head CT before lumbar puncture and many will benefit from MRI investigation [17, 18].
Neuroimaging
As indicated in Fig. 20.1, an initial triage strategy begins with neuroimaging, preferably MRI scanning, and then considers possible pathogens by sites, recognize that there are always exceptions. While MRI is an invaluable addition to the diagnostic process, there are many pitfalls:
- 1.
The use of corticosteroids reduces contrast enhancement on both CT and MRI.
- 2.
Renal insufficiency or contrast allergy may preclude contrast use.
- 3.
Diffuse dural or meningeal enhancement can be seen after repetitive seizures as can parenchymal signal abnormalities on fluid-attenuated inversion recovery (FLAIR) sequences in affected areas. Additionally, a recent lumbar puncture with low intracranial pressure can cause dural enhancement as can neoplastic or chemical meningitis.
- 4.
Increased fluid-attenuated inversion recovery (FLAIR) signal intensity in the subarachnoid space could suggest proteinaceous fluid such as blood or pus, but is also frequently seen in patients ventilated with high partial pressure of oxygen.
- 5.
Ring-enhancing lesions are nonspecific and can represent abscesses or tumor recurrence, or pseudoprogression in patients treated with radiation and concurrent temozolomide [19]. They can also be seen days to weeks after a hemorrhage or can represent demyelinating lesions in the appropriate situation.
- 6.
Because gadolinium-enhanced sequences may be nonspecific, diffusion-weighted imaging (DWI) has been invoked to improve distinction between infections and other processes, though increased cellularity as seen with CNS lymphoma also can produce significant diffusion restriction. Restricted water diffusion is seen in fungal and bacterial abscesses, and purulent ventricular fluid is similarly hyperintense (Fig. 20.2a–f). Magnetic resonance angiography (MRA) would be most useful in evaluating potential aneurysms in suspected Aspergillus, arteritis associated with VZV or Mucormycosis.
Fig. 20.2
MRI diffusion-weighted (DWI) imaging sequences are most frequently used in stroke evaluation, but DWI is useful for diverse infections as well. a shows gadolinium-enhanced T1 sequence of two mass lesions that were found to be Nocardia asteroides. These infections are hyperintense on DWI (b), as is the large right temporal abscess in a patient with colon cancer whose operation was complicated by endocarditis with E. coli (c). The possibility of VZV-related stroke was raised by the MRI sequence in d and led to appropriate testing for VZV vasculopathy. e shows diffusion positive CSF in a patient with S. aureus meningitis, and f shows the characteristic cortical hyperintensity of a prion disease, Creutzfeldt–Jakob disease
Electroencephalography
Seizures are very common during CNS infections, so EEG may be useful in explaining altered mental status and long-term monitoring should be encouraged in any unresponsive patient with CNS infection. In one study, seizures or paroxysmal epileptic discharges occurred in nearly half of patients and were independently associated with poor prognoses. Half of the patients with seizures had no obvious clinical correlation on bedside examination [20].
Cerebrospinal Fluid
If there is no intracerebral lesion that contraindicates lumbar puncture and if clotting factor or platelet support is provided for cytopenic patients, this procedure can be useful when employed properly. Absolute CSF white blood cell count and differential are less useful than in the noncancer population. Not only can bacterial processes evoke very little inflammation in the heavily immunosuppressed cytopenic patient, but lymphocytic pleocytosis can have many noninfectious etiologies including drug reactions to nonsteroidal anti-inflammatory drugs, valacyclovir, azathioprine, isoniazid, intravenous immunoglobulin (IVIG) intrathecal chemotherapy, and lamotrigine. Disease states that can evoke a CSF pleocytosis include prolonged status epilepticus, arachnoiditis, and neoplastic meningitis.
Expeditious discovery of an infectious etiology for meningoencephalitis in this population can be challenging. Polymerase chain reaction (PCR) testing is expensive and time-consuming, and cultures may require prolonged incubation. Metagenomic deep sequencing (MDS) approaches, still investigational and not readily clinically available, are beginning to yield specific etiologies as this powerful diagnostic tool demonstrates potential for rapid and unbiased pathogen identification [21, 22].
Appropriate Use of Polymerase Chain (PCR) Reaction Testing
It is important to note that the confirmation of a viral infection by PCR can be done when the patient is seen early in the course of an infection due to a herpesvirus or other pathogen, but that if the patient is seen more than 7–10 days after onset of symptoms, the better test is a comparison of intrathecal pathogen-specific antibody level with concurrent serum antibody. This is particularly true for herpesvirus infections in which a negative PCR could lead to discontinuation of acyclovir in the presence of an active infection [23].
Brain or Leptomeningeal Biopsy
This procedure ideally should be reserved for situations in which an invasive procedure might lead to both specific antimicrobial diagnosis and therapeutic advantage such as debridement of a suspected fungal sinus infection or brain or spinal abscess drainage. As a procedure of last resort, sampling of an area of meningeal or parenchymal enhancement is likely of higher yield than targeting areas without contrast enhancement. Subcubic centimeter stereotactically biopsied lesions have a lower yield than larger lesions for which diagnostic yield exceeds 90%, though the former still succeeds in providing a diagnosis in 76.2% of procedures [24].
High-Risk Patient Groups
Neurosurgery-Related Infections
Patients with primary and secondary brain tumors account for up to one-quarter of CNS infections that occur among cancer patients. Bacterial meningitis due to a combination of barrier disruption, T cell immunity deficits due to corticosteroids, and poor wound healing after radiation therapy or multiple craniotomies predispose to this serious infection. Bacterial abscesses with or without subdural empyema usually occur within one month of craniotomy, but indolent skin-derived organisms can produce symptomatic infection many months to years after the surgery [25].
Three clinically important, yet often hard to recognize syndromes should be recognized among patients with brain tumors:
- 1.
Tumor cavity-implantable carmustine-containing wafers are approved for treatment of high-grade astrocytic tumors both at initial diagnosis and at recurrence. These induce a significant cerebritis with accompanying vasogenic edema. A characteristic “Swiss cheese-like” appearance in addition to a more typical ring-enhancing abscess has been described [26].
- 2.
Radiation therapy exacerbates wound-healing problems, a risk further compounded with the advent of bevacizumab, and other vascular endothelial growth factor (VEGF) inhibitors. These agents should not be used within one month before or after surgery as they lead to an incidence of wound-healing problems that is 3.5-fold greater than that seen without VEGF therapies [27].
- 3.
Radiation therapy with or without concomitant chemotherapy with temozolomide can predispose patients to reactivation of herpes simplex virus or, less commonly cytomegalovirus (CMV) with resultant encephalitis. HSV reactivation also has been related to anti-epileptic hypersensitivity reactions [28, 29].
Hematopoietic Cell Transplantation (HCT)
Approach to the diagnosis of potential CNS infections in transplantation patients involves consideration of the disease for which the procedure was performed, the specific pre-transplant conditioning regimen or other therapies, and, most importantly, the interval from the transplant to the presenting clinical syndrome. In one large retrospective study of allogeneic HCT, almost 70% of clinically significant neurologic complications and 86% of all episodes of posterior reversible encephalopathy syndrome (PRES) occurred within the first 100 days after the procedure [30]. Table 20.1 presents a summary of neurologic complications whose main point can be reduced to the fact that that transplantation patients present a remarkable array of diagnostic possibilities and that, while the specific complications vary with indication for and type of procedure, many infections and their mimics are common to all types of transplantation and associated medications and it is the time out from transplantation that helps to weight diagnostic priorities [31, 32]. Here the focus will be on infections associated with commonly used immunosuppressive regimens, including corticosteroids, mycophenolate, cyclosporine, tacrolimus, rituximab, and alemtuzumab. Other complications of HCT are covered in Chap. 18.
Table 20.1
Time course of neurologic complications of hematopoietic cell transplantation
Time from transplant | Infectious conditions | Noninfectious conditions |
|---|---|---|
Conditioning and infusion | Drug-related encephalopathy (busulfan, etoposide, ifosfamide, methotrexate, cytosine arabinoside), DMSO-related stroke, PRES, seizures, intracranial hypotension post-LP | |
<1 month, neutropenic period | CMV HHV-6 Aspergillus Toxoplasmosis Infections acquired from donor tissue: LCMV, WNV, rabies, adenovirus, Coxsackie B4 From IV lines: Candida | Engraftment syndrome Delirium due to organ failure Seizures: cefepime, imipenem PRES: cyclosporine, tacrolimus > sirolimus Parkinsonism: Amphotericin B, valproate SDH or SAH due to coagulopathy Intraparenchymal brain hemorrhage |
1–6 months | Aspergillus HHV-6 HSV PML PTLD Toxoplasmosis VZV | ADEM Osmotic demyelination syndrome IRIS GVHD |
>6 months | VZV CMV PML EBV-associated PTLD Aspergillus Mucoraceae | Autoimmune: graves, sarcoidosis, demyelinating IRIS GVHD (polymyositis, myasthenia, CIDP) Secondary malignancy Disease relapse |
Early Period Infections (Less Than 30 Days After Transplantation)
During this period of neutropenia, major concerns are bacterial, viral or fungal infections, donor or nosocomially acquired infections, and reactivation of preexisting infections (such as neurocysticercosis or toxoplasmosis). Emerging viruses and new patterns of infections that should be considered include donor-derived West Nile Virus, lymphocytic choriomeningitis virus, HTLV 1-associated myelitis, and rabies [33, 34]. This last pathogen usually surfaces within a month of transplantation, but recently it has been recognized that rabies can strike the recipient many months after infection by donor tissue [35–37].
A clinical problem specific to HCT is engraftment syndrome characterized by rash, fever, and headache 2–4 weeks following transplantation as the absolute neutrophil count begins to rise. The major differential entity here is post-transplant acute limbic encephalitis (PALE) caused by human herpesvirus 6 (HHV6) and accompanied by amnesia, hyponatremia, CSF pleocytosis, and abnormal EEG [38]. HHV6 is discussed in greater detail in the specific pathogens section of this chapter.
Middle Period Infections (1–6 Months After Transplantation)
Patients more than one month post-HCT remain at risk of invasive fungal infections. Toxoplasma gondii may resurface as encephalitis or as multiple ring-enhancing lesions, often deep in corona radiata and basal ganglia. VZV may emerge during this period despite valacyclovir prophylaxis, and PML begins to become a risk several months after HCT. EBV infection can occur at any point post-transplantation.
Late Period (>6 Months Post-transplantation)
Late complications of transplantation include secondary neoplasms such as melanoma and lymphomas as well as astrocytoma or meningioma in patients who have received cranial irradiation as part of their conditioning regimen. VZV, PTLD, and PML remain possibilities. The CNS is rarely the site of graft-versus-host disease (GVHD) , but when this question arises biopsy is necessary and in the few patients so investigated there have been mature lymphohistiocytic inflammatory infiltrates with perivascular cuffing and without viral cytopathic changes [39].
Hematologic Malignancies Treated Intensively but Without Transplant
As intensive chemotherapy regimens for hematologic malignancies have produced long-term survivors of hematologic malignancies, the risk of CNS infection has risen in patients who do not undergo transplantation. Such patients are often in hospital for extended periods and are at risk of sepsis from intravenous lines and Candida bacteremia. Necessary transfusion support for chemotherapy-induced cytopenias carries attendant risk of transfusion-transmitted disease caused by protozoa, prions, hepatitis virus, HIV CMV, EBV, HHV8, Cryptococcus, and Trypanosoma cruzi (Chagas disease ) [40].
Several drugs used in these situations such as fludarabine, cyclophosphamide, methotrexate, mycophenolate, alemtuzumab, and rituximab carry defined increased risk of specific infections. Fludarabine and mycophenolate are particularly associated with PML because they deplete T lymphocytes. Rituximab-associated infectious complications are discussed elsewhere in this chapter. Alemtuzumab , recently approved for therapy of multiple sclerosis, has long been used as induction therapy for solid organ and HCT, for treatment of rejection after HCT, and for chronic lymphocytic leukemia. Patients receiving the drug for rejection as opposed to as induction therapy have increased risk of developing an opportunistic infection including invasive fungal infections, HHV6, Listeria meningitis, CMV viremia, and Guillain Barre syndrome or myelitis due to VZV or HHV7 [41, 42].
Clinical Manifestations and Management of Specific Infections
In this section, common clinical variants and therapeutic strategies for several commonly encountered infections are summarized. Specific antibiotic recommendations are not offered as institutional variability in antibiotic resistance, and nosocomial trends must be respected. Neurologic consultants should work with their own institutional infectious disease departments to assure appropriate coverage for pathogens based on institutional antibiotic resistance and nosocomial trends.
General Medical Management Issues
Two major medical management issues present opportunities for effective neurologic consultative advice:
- 1.
Corticosteroid supplementation may be necessary, as many cancer patients may have been treated with large doses of corticosteroids as part of their cytotoxic regimens in the recent past. When stressed with an acute infection, some will have insufficient adrenal reserve that can present as hypotension unresponsive to volume repletion requiring urgent intravenous hydrocortisone [43, 44].
- 2.
Seizures complicate treatment of many patients with meningoencephalitis or infectious mass lesions. Some may be isolated events due to toxic drug reactions (Table 20.2), metabolic or electrolyte abnormalities, or posterior reversible encephalopathy syndrome (PRES) and therefore will not require long-term anti-seizure medicine. However, other pathologies in the cancer population such as bland or hemorrhagic cerebrovascular disease, venous sinus thrombosis, or abscess may carry longer-term seizure risks. Choice of anti-epileptic drug (AED) should weigh interactions between seizure treatment and ongoing cancer or transplant immunosuppressive therapy [45]. Phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, and phenobarbital are potent hepatic enzyme inducers that can reduce blood levels of many chemotherapeutic agents, including corticosteroids and immunosuppressives such as tacrolimus and cyclosporine. Phenytoin and valproate are heavily protein-bound and so in patients with low serum albumin levels, free level drug measurements are indicated. Levetiracetam, available orally and parenterally, has the advantage of rapid onset of activity and absence of significant protein-binding or hepatic enzyme induction. However, up to 5% of levetiracetam-treated patients may experience adverse neuropsychiatric effects including psychosis that can mimic behaviors associated more commonly with corticosteroid-induced psychiatric problems. Lacosamide shares similar advantages with levetiracetam over the older AEDs and does not carry the psychiatric adverse effect risk. Renal failure may reduce clearance of both of these AEDs, and, as hemodialysis removes small nonprotein-bound drugs, dosing must be adjusted for renal failure and supplementation after dialysis should conform to manufacturers’ recommendations.
Table 20.2
Neurologic toxicities of antimicrobial and immunosuppressive agents
Neurologic problem
Potential causative agentsa
Seizures
Penicillin G, imipenem, aztreonam, gentamicin ciprofloxacin, ofloxacin, cefepime, ceftazidime metronidazole, amphotericin B, acyclovir, foscarnet, meropenem, praziquantel, tacrolimus, cyclosporine
Potentiation of neuromuscular junction transmission blockade
Aminoglycosides, cephalosporins
Pseudotumor cerebri
Minocycline, tetracycline, tacrolimus
Ototoxicity/vestibular toxicity
Vancomycin, aminoglycosides, erythromycin, tacrolimus
Delirium
Cefepime, ceftazidime, ciprofloxacin, ofloxacin, metronidazole, foscarnet, praziquantel, amphotericin B
Visual hallucinations
Voriconazole
Extrapyramidal signs
Amphotericin B
Headache
Ciprofloxacin, ofloxacin, fluconazole, itraconazole, foscarnet, praziquantel, trimethoprim/sulfamethoxazole
Dizziness/Cerebellar signs
Metronidazoleb, aminoglycosides, minocycline, isoniazid, fluconazole, itraconazole, varicella vaccine
Lymphocytic meningitis
Trimethoprim/sulfamethoxazole, cephalosporins, IV immunoglobulin, valacyclovir
Optic neuropathy
Ethambutol, linezolid
PRES
Linezolid, roxithromycin, tacrolimus, cyclosporine
Serotonin syndrome
Linezolid (with selective serotonin reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors)
Tremor
Acyclovir, cephalosporins, tacrolimus, cyclosporine
Bacterial Meningitis
Streptococcus pneumoniae (S. pneumo) meningitis remains the most common community-acquired meningitis, and a quarter of such patients have an immunocompromising condition [46]. Nosocomially acquired meningitis includes a larger percentage of patients with gram-negative and MRSA infections [47]. Patients with active cancer have a several fold increased risk of bacterial meningitis compared to patients without cancer and may have lower peripheral blood and CSF leukocyte cell counts. Coverage of immunocompromised patients with bacterial meningitis must include Listeria, and, for patients recently in the hospital, gram-negative aerobic organisms. Based on Dutch studies demonstrating decreased mortality for gram-positive meningitis patients receiving corticosteroids, current recommendations for dexamethasone use prior the first dose antibiotics (10 mg every 6 h for 4 days) [48].
Although the overall incidence of neurosurgical infections appears to be decreasing in most centers, cancer patients undergo the procedures most likely to be complicated by infections. Patients having spinal tumor biopsy or CSF shunting remain a group at highest risk of infection. In one series, half of all infections were associated with shunt or Ommaya reservoir placement [49]. In these situations, removal of drains and intrathecal instillation of antibiotics can be considered in addition to recommended antibiotics appropriate to institutional resistance patterns.
Other Nosocomial Bacterial Infections
Brain Abscess
Risk factors for postoperative bacterial brain abscess are similar to those associated with meningitis: postoperative bone infections, septicemia, dental caries, and ear and pharyngeal infections. S. aureus is the most common postoperative pathogen, but other organisms more likely in cancer patients than in the general neurosurgical population require consideration: These include T. gondii, Taenia solium, Aspergillus, Mucoraceae, Histoplasma capsulatum, and Nocardia asteroides. Surgical intervention may be necessary for diagnosis or therapy in abscesses greater than 2 cm in maximal diameter. Some critical care specialists use steroids for short-term vasogenic edema management. Most consultants agree that no AEDs need be given prophylactically.
Infective Endocarditis
Twenty-five percent of patients with infective endocarditis (IE) have had recent health care contact. S. aureus, the most common causative organism, is associated with the highest mortality among bacterial endocarditis pathogens and is also associated with the highest risk of stroke. In-hospital mortality from all-cause IE is 14–20% [50].
Invasive Fungal Infections
Invasive fungal infections are among the most feared complications of chronic immunosuppression. The most common infections are Aspergillosis, Cryptococcosis, Mucormycosis, and Candidiasis. Prophylactic, empiric, and targeted strategies remain incompletely successful often because of delayed diagnosis. Invasive fungal infections can present with abscess or infarction due to hematogenous dissemination from extracranial, particularly pulmonary, sites. Extension from adjacent sinuses can produce an optic neuropathy sometimes mistaken for steroid-responsive giant cell arteritis [51].
Fungal infection can be suspected based on clinical presentation. An important and common syndromic constellation is persistent headache, visual changes, and cranial neuropathies in neutropenic patients with sinus disease. All neurologic consultants should recognize and pursue such symptoms vigorously with MRI, MRA, CSF sampling, and, when necessary, sinus debridement for diagnosis.
Neuroimaging of fungal infections provides valuable clues. Hyperintensity on FLAIR sequences in the basal cisterns and subarachnoid space, sometimes with contrast enhancement, suggests infection. High viscosity and cellularity of fungal pus lead to early reduced diffusion that can precede enhancement [52]. Aspergillosis, an angioinvasive organism, can produce hemorrhagic infarction (Fig. 20.3a–f). Cryptococcosis tends to produce pseudocysts in the basal ganglia. Mucormycosis, like Aspergillosis, can spread from the sinuses, producing frontal lobe abscesses and infarction. Candidiasis more often produces multiple microabscesses.
Fig. 20.3
Aspergillus fumigatus. MRI findings can be nonspecific, though often in the posterior circulation as seen in the fluid-attenuated inversion recovery (FLAIR) (a, c) and gadolinium-enhanced T1-weighted sequences (b). Diffusion-weighted imaging (d) suggestive of infarction by this angiotropic fungus and FLAIR images show increased signal in the subarachnoid space consistent with infection or blood (e). f shows a catastrophic hemorrhage form an infectious aneurysm due to Aspergillus
Aspergillosis
Cancer patients at most risk of rapidly fatal Aspergillus-related infections are those with acute myeloid leukemia, myelodysplastic syndromes, allogeneic HCT recipients [especially those with active graft-versus-host disease (GVHD) ], patients with longstanding intravenous lines, and those receiving long-term corticosteroids or conditioning regimens that include fludarabine or alemtuzumab [53]. Neutropenia lasting longer than 10 days with a neutrophil count less than 500/μL is the most important risk factor. High-risk patients should be monitored with daily serum galactomannan antigen that can be detected in serum up to a week before abnormal chest radiographic or clinical symptoms. Aspergillus species invade the internal elastic lamina of arteries leading to focal microhemorrhage or mycotic aneurysm formation. Fungal components also can occlude vessels leading to infarction with hemorrhagic transformation with a predilection for small perforating arteries of the basal ganglia, thalamus, and corpus callosum. Since infarction of the corpus callosum is rarely seen in noninfectious thromboembolic infarction or pyogenic infection, its presence should suggest Aspergillosis [54]. In a series of 14 cases from a single institution with an additional 123 literature-based cases, lung was the primary focus with paranasal sinuses nearly as common. Mortality with medial treatment alone was 60–100%, whereas those able to have surgical procedures that ranged from orbital exenteration to dural biopsies and abscess drainage had about a 25% mortality. Selection bias in favor of healthier patients undergoing surgery was a confounding factor in this retrospective study [55]. The treatment of choice is voriconazole [56].
Cryptococcus Neoformans
Cryptococcus is the most frequent cause of lymphocyte-predominant meningitis in HIV patients. In patients immunocompromised by cancer or its treatment, particularly when corticosteroids are used, meningitis can be either acute or quite indolent. Markedly elevated intracranial pressure or direct optic nerve invasion can lead to visual compromise. Gradually developing hydrocephalus, at times requiring repetitive lumbar punctures or ultimately ventriculoperitoneal shunting, occurs frequently. Cell counts may be misleading in significantly immunocompromised patients, whereas cryptococcal polysaccharide antigen in CSF is a sensitive and specific diagnostic modality. Treatment requires both acute combination therapy (amphotericin B and flucytosine) and lifelong prophylaxis in immunocompromised patients. Immune reconstitution-related exacerbation of symptoms has been observed after successful cryptococcal treatment.
Viral Infections
Table 20.3 summarizes many viruses and associated clinical parameters to be considered by clinicians consulting on oncology or transplantation services. The most important of these is Varicella zoster virus (VZV) whose diversity of clinical manifestations makes diagnosis difficult.
Table 20.3
The Prevalence and Impact of Neurological Disease in Cancer
Neurologic Complications of Gastrointestinal Cancer
Neurologic Complications of Genitourinary Cancer
Neurologic Complications of Head and Neck Cancer
Neurologic Complications of Hematopoietic Stem Cell Transplantation
Neurological Complications of Chemotherapy
Overview of viral infections in cancer patients
Related posts:
The Prevalence and Impact of Neurological Disease in Cancer
Neurologic Complications of Gastrointestinal Cancer
Neurologic Complications of Genitourinary Cancer
Neurologic Complications of Head and Neck Cancer
Neurologic Complications of Hematopoietic Stem Cell Transplantation
Neurological Complications of Chemotherapy
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