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Question
This is known as [...] due to the shape that this non-causal association flows along when the graph is drawn with children below their parents.
Answer
M-bias

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This is known as M-bias due to the M shape that this non-causal association flows along when the graph is drawn with children below their parents.

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#Aseptic #Aseptique #Diagnosis #Diagnostic #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The term aseptic meningitis refers to patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures. The most common causes are the enteroviruses [1]. Additional etiologies include other infections (mycobacteria, fungi, spirochetes), parameningeal infections, medications, and malignancies (table 1) [2]
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opics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Apr 2022. | This topic last updated: Sep 26, 2018. INTRODUCTION — <span>The term aseptic meningitis refers to patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures. The most common causes are the enteroviruses [1]. Additional etiologies include other infections (mycobacteria, fungi, spirochetes), parameningeal infections, medications, and malignancies (table 1) [2]. Aseptic meningitis often has a similar presentation to that of bacterial meningitis (ie, fever, headache, altered mental status, stiff neck, photophobia), which can be a life-threateni




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Aseptic meningitis often has a similar presentation to that of bacterial meningitis (ie, fever, headache, altered mental status, stiff neck, photophobia), which can be a life-threatening illness. However, in contrast to bacterial meningitis, many patients with aseptic meningitis (particularly those who have disease caused by viruses or medications) have a self-limited course that will resolve without specific therapy
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ommon causes are the enteroviruses [1]. Additional etiologies include other infections (mycobacteria, fungi, spirochetes), parameningeal infections, medications, and malignancies (table 1) [2]. <span>Aseptic meningitis often has a similar presentation to that of bacterial meningitis (ie, fever, headache, altered mental status, stiff neck, photophobia), which can be a life-threatening illness. However, in contrast to bacterial meningitis, many patients with aseptic meningitis (particularly those who have disease caused by viruses or medications) have a self-limited course that will resolve without specific therapy. The assessment of patients with probable aseptic meningitis is complicated by the large number of potential etiologic agents and the relatively limited diagnostic tools for identifying




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The assessment of patients with probable aseptic meningitis is complicated by the large number of potential etiologic agents and the relatively limited diagnostic tools for identifying specific pathogens. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Herpes simplex virus type 1 encephalitis".)
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l meningitis, many patients with aseptic meningitis (particularly those who have disease caused by viruses or medications) have a self-limited course that will resolve without specific therapy. <span>The assessment of patients with probable aseptic meningitis is complicated by the large number of potential etiologic agents and the relatively limited diagnostic tools for identifying specific pathogens. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Herpes simplex virus type 1 encephalitis".) The symptoms, signs, and cerebrospinal fluid (CSF) findings for various etiologies of aseptic meningitis will be reviewed here. Each diagnostic entity is discussed in detail separately




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Patients with meningitis may be lethargic or distracted by headache, but their cerebral function remains normal. In contrast, patients with encephalitis commonly present with abnormalities in brain function such as altered mental status, motor or sensory deficits, altered behavior and personality changes, and speech or movement disorders.
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on the appropriate topic reviews. MENINGITIS VERSUS ENCEPHALITIS — The presence or absence of normal brain function is the important distinguishing feature between encephalitis and meningitis. <span>Patients with meningitis may be lethargic or distracted by headache, but their cerebral function remains normal. In contrast, patients with encephalitis commonly present with abnormalities in brain function such as altered mental status, motor or sensory deficits, altered behavior and personality changes, and speech or movement disorders. Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis. Other neurologic manifestations include hemiparesis,




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Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis. Other neurologic manifestations include hemiparesis, flaccid paralysis, and paresthesias
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litis commonly present with abnormalities in brain function such as altered mental status, motor or sensory deficits, altered behavior and personality changes, and speech or movement disorders. <span>Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis. Other neurologic manifestations include hemiparesis, flaccid paralysis, and paresthesias. However, the distinction between the two entities is frequently blurred since some patients may have both a parenchymal and meningeal process with clinical features of both. The patien




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However, the distinction between the two entities is frequently blurred since some patients may have both a parenchymal and meningeal process with clinical features of both. The patient is usually labeled as having meningitis or encephalitis based upon which features predominate in the illness although meningoencephalitis is also a common term that recognizes the overlap.
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s can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis. Other neurologic manifestations include hemiparesis, flaccid paralysis, and paresthesias. <span>However, the distinction between the two entities is frequently blurred since some patients may have both a parenchymal and meningeal process with clinical features of both. The patient is usually labeled as having meningitis or encephalitis based upon which features predominate in the illness although meningoencephalitis is also a common term that recognizes the overlap. (See "Viral encephalitis in adults".) VIRAL MENINGITIS — A number of viruses produce aseptic meningitis including enteroviruses, herpes simplex virus (HSV), human immunodeficiency virus




#Aseptic #Aseptique #Diagnosis #Diagnostic #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
A number of viruses produce aseptic meningitis including enteroviruses, herpes simplex virus (HSV), human immunodeficiency virus (HIV), West Nile virus (WNV), varicella-zoster virus (VZV), mumps, and lymphocytic choriomeningitis virus (LCM)
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tis based upon which features predominate in the illness although meningoencephalitis is also a common term that recognizes the overlap. (See "Viral encephalitis in adults".) VIRAL MENINGITIS — <span>A number of viruses produce aseptic meningitis including enteroviruses, herpes simplex virus (HSV), human immunodeficiency virus (HIV), West Nile virus (WNV), varicella-zoster virus (VZV), mumps, and lymphocytic choriomeningitis virus (LCM) [3]. (See "Viral encephalitis in adults".) Enteroviruses — Aseptic meningitis occurring during the summer or fall is most likely to be caused by enteroviruses (eg, Coxsackievirus, echov




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Enteroviruses — Aseptic meningitis occurring during the summer or fall is most likely to be caused by enteroviruses (eg, Coxsackievirus, echovirus, other non-poliovirus enteroviruses), the most common causes of viral meningitis [3]. However, seasonal variation of certain CNS viral infections is relative and not absolute. Enteroviruses continue to cause 6 to 10 percent of cases of viral meningitis in the winter and spring despite their predilection for inciting illness in the late summer and fall [4]
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us (HSV), human immunodeficiency virus (HIV), West Nile virus (WNV), varicella-zoster virus (VZV), mumps, and lymphocytic choriomeningitis virus (LCM) [3]. (See "Viral encephalitis in adults".) <span>Enteroviruses — Aseptic meningitis occurring during the summer or fall is most likely to be caused by enteroviruses (eg, Coxsackievirus, echovirus, other non-poliovirus enteroviruses), the most common causes of viral meningitis [3]. However, seasonal variation of certain CNS viral infections is relative and not absolute. Enteroviruses continue to cause 6 to 10 percent of cases of viral meningitis in the winter and spring despite their predilection for inciting illness in the late summer and fall [4]. The presenting signs and symptoms of enteroviral meningitis are not distinctive. The onset of symptoms is characteristically abrupt and typically includes headache, fever, nausea or vo




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The presenting signs and symptoms of enteroviral meningitis are not distinctive. The onset of symptoms is characteristically abrupt and typically includes headache, fever, nausea or vomiting, malaise, photophobia, and meningismus. Rash, diarrhea, and upper respiratory symptoms may also be present
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absolute. Enteroviruses continue to cause 6 to 10 percent of cases of viral meningitis in the winter and spring despite their predilection for inciting illness in the late summer and fall [4]. <span>The presenting signs and symptoms of enteroviral meningitis are not distinctive. The onset of symptoms is characteristically abrupt and typically includes headache, fever, nausea or vomiting, malaise, photophobia, and meningismus. Rash, diarrhea, and upper respiratory symptoms may also be present. Cerebrospinal fluid (CSF) findings are typical of other viral meningitides and include a white blood cell (WBC) count that is generally less than 250 cells/microL, a modest elevation i




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Cerebrospinal fluid (CSF) findings are typical of other viral meningitides and include a white blood cell (WBC) count that is generally less than 250 cells/microL, a modest elevation in CSF protein concentration (generally less than 150 mg/dL), and a normal glucose concentration (table 2).
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characteristically abrupt and typically includes headache, fever, nausea or vomiting, malaise, photophobia, and meningismus. Rash, diarrhea, and upper respiratory symptoms may also be present. <span>Cerebrospinal fluid (CSF) findings are typical of other viral meningitides and include a white blood cell (WBC) count that is generally less than 250 cells/microL, a modest elevation in CSF protein concentration (generally less than 150 mg/dL), and a normal glucose concentration (table 2). (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states".) Up to two-thirds of patients with enteroviral meningitis have a polymorphonuclear predominance i




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Up to two-thirds of patients with enteroviral meningitis have a polymorphonuclear predominance in the CSF when examined early in the course of the illness. Repeat lumbar puncture after 12 to 24 hours, if performed, generally shows an evolution to a lymphocytic predominance
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CSF protein concentration (generally less than 150 mg/dL), and a normal glucose concentration (table 2). (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states".) <span>Up to two-thirds of patients with enteroviral meningitis have a polymorphonuclear predominance in the CSF when examined early in the course of the illness. Repeat lumbar puncture after 12 to 24 hours, if performed, generally shows an evolution to a lymphocytic predominance. Polymerase chain reaction (PCR) testing for enteroviruses can be considered if a definitive diagnosis is desired, or in the setting of an outbreak situation, but is not necessary in al




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Polymerase chain reaction (PCR) testing for enteroviruses can be considered if a definitive diagnosis is desired, or in the setting of an outbreak situation, but is not necessary in all patients.
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predominance in the CSF when examined early in the course of the illness. Repeat lumbar puncture after 12 to 24 hours, if performed, generally shows an evolution to a lymphocytic predominance. <span>Polymerase chain reaction (PCR) testing for enteroviruses can be considered if a definitive diagnosis is desired, or in the setting of an outbreak situation, but is not necessary in all patients. CSF nucleic acid amplification tests (NAATs) for enteroviruses yield sensitivities that range from 86 to 100 percent and specificities that range from 92 to 100 percent [5]. Among patie




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CSF nucleic acid amplification tests (NAATs) for enteroviruses yield sensitivities that range from 86 to 100 percent and specificities that range from 92 to 100 percent [ 5]. Among patients with CNS manifestations and a negative CSF NAAT, upper respiratory tract and gastrointestinal tract specimens for enterovirus may be useful to establish a diagnosis of enterovirus infection [6]. However, detection of enterovirus from the throat or stool of an individual with aseptic meningitis may represent an infection that occurred weeks previously and is unrelated to the present syndrome [5].

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lymerase chain reaction (PCR) testing for enteroviruses can be considered if a definitive diagnosis is desired, or in the setting of an outbreak situation, but is not necessary in all patients. <span>CSF nucleic acid amplification tests (NAATs) for enteroviruses yield sensitivities that range from 86 to 100 percent and specificities that range from 92 to 100 percent [5]. Among patients with CNS manifestations and a negative CSF NAAT, upper respiratory tract and gastrointestinal tract specimens for enterovirus may be useful to establish a diagnosis of enterovirus infection [6]. However, detection of enterovirus from the throat or stool of an individual with aseptic meningitis may represent an infection that occurred weeks previously and is unrelated to the present syndrome [5]. Additional discussions of enterovirus infections are found elsewhere. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention"




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HIV infection — Primary infection with HIV frequently presents as a mononucleosis-like syndrome manifested by fever, malaise, lymphadenopathy, rash, and pharyngitis. A subset of these patients will develop meningitis or meningoencephalitis, manifested by headache, confusion, seizures or cranial nerve palsies.
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(See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention" and "Enterovirus and parechovirus infections: Epidemiology and pathogenesis".) <span>HIV infection — Primary infection with HIV frequently presents as a mononucleosis-like syndrome manifested by fever, malaise, lymphadenopathy, rash, and pharyngitis. A subset of these patients will develop meningitis or meningoencephalitis, manifested by headache, confusion, seizures or cranial nerve palsies. (See "Acute and early HIV infection: Pathogenesis and epidemiology".) In most patients with HIV-1 meningitis, the clinical findings resolve without treatment, and patients may be errone




#Aseptic #Aseptique #Diagnosis #Diagnostic #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In most patients with HIV-1 meningitis, the clinical findings resolve without treatment, and patients may be erroneously assumed to have a benign cause of viral meningitis. Thus, clinicians should have a high index of suspicion for primary HIV infection in patients at increased risk for acquisition of this virus. The identification of the patient with acute HIV infection is also important from a public health viewpoint since the risk of transmission is facilitated by high levels of viremia
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ients will develop meningitis or meningoencephalitis, manifested by headache, confusion, seizures or cranial nerve palsies. (See "Acute and early HIV infection: Pathogenesis and epidemiology".) <span>In most patients with HIV-1 meningitis, the clinical findings resolve without treatment, and patients may be erroneously assumed to have a benign cause of viral meningitis. Thus, clinicians should have a high index of suspicion for primary HIV infection in patients at increased risk for acquisition of this virus. The identification of the patient with acute HIV infection is also important from a public health viewpoint since the risk of transmission is facilitated by high levels of viremia. The CSF profile characteristically has a lymphocytic pleocytosis, an elevated protein concentration, and normal glucose concentration (table 2). Documentation of primary HIV infection




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The CSF profile characteristically has a lymphocytic pleocytosis, an elevated protein concentration, and normal glucose concentration (table 2). Documentation of primary HIV infection is accomplished by demonstration of seroconversion or detection of HIV-1 viremia in the absence of HIV antibody.
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this virus. The identification of the patient with acute HIV infection is also important from a public health viewpoint since the risk of transmission is facilitated by high levels of viremia. <span>The CSF profile characteristically has a lymphocytic pleocytosis, an elevated protein concentration, and normal glucose concentration (table 2). Documentation of primary HIV infection is accomplished by demonstration of seroconversion or detection of HIV-1 viremia in the absence of HIV antibody. (See "Techniques and interpretation of HIV-1 RNA quantitation" and "Screening and diagnostic testing for HIV infection".) Herpes simplex meningitis — Primary HSV has been increasingly r




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Herpes simplex meningitis — Primary HSV has been increasingly recognized as a cause of viral meningitis in adults. In contrast to HSV encephalitis, which is almost exclusively due to HSV-1, viral meningitis in immunocompetent adults is generally caused by HSV-2 [3].
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onversion or detection of HIV-1 viremia in the absence of HIV antibody. (See "Techniques and interpretation of HIV-1 RNA quantitation" and "Screening and diagnostic testing for HIV infection".) <span>Herpes simplex meningitis — Primary HSV has been increasingly recognized as a cause of viral meningitis in adults. In contrast to HSV encephalitis, which is almost exclusively due to HSV-1, viral meningitis in immunocompetent adults is generally caused by HSV-2 [3]. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".) Between 13 and 36 percent of patients presenting with primary genital herpes have




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Between 13 and 36 percent of patients presenting with primary genital herpes have clinical findings consistent with meningeal involvement, including headache, photophobia and meningismus. On the other hand, genital lesions are present in approximately 85 percent of patients with primary HSV-2 meningitis and generally precede the onset of CNS symptoms by approximately seven days. The CSF profile includes a pleocytosis with a predominance of lymphocytes, and a normal CSF glucose concentration (table 2). HSV meningitis can also occur without evidence of genital lesions, although this is less common [3,7]. Thus, the absence of genital lesions should not deter the clinician from testing for HSV-2 infection in a patient with aseptic meningitis.
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ue to HSV-1, viral meningitis in immunocompetent adults is generally caused by HSV-2 [3]. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".) <span>Between 13 and 36 percent of patients presenting with primary genital herpes have clinical findings consistent with meningeal involvement, including headache, photophobia and meningismus. On the other hand, genital lesions are present in approximately 85 percent of patients with primary HSV-2 meningitis and generally precede the onset of CNS symptoms by approximately seven days. The CSF profile includes a pleocytosis with a predominance of lymphocytes, and a normal CSF glucose concentration (table 2). HSV meningitis can also occur without evidence of genital lesions, although this is less common [3,7]. Thus, the absence of genital lesions should not deter the clinician from testing for HSV-2 infection in a patient with aseptic meningitis. (See "PCR testing for the diagnosis of herpes simplex virus in patients with encephalitis or meningitis".) There is no standard approach to the treatment of HSV meningitis [8]. For hosp




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There is no standard approach to the treatment of HSV meningitis [8]. For hospitalized patients, intravenous acyclovir at 10 mg/kg administered every eight hours is reasonable. The dose should be adjusted for individuals with reduced kidney function, and recommendations are provided in the Lexicomp drug information topic within UpToDate. Patients can be switched to an oral agent on discharge for a total of 10 to 14 days of treatment.
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r the clinician from testing for HSV-2 infection in a patient with aseptic meningitis. (See "PCR testing for the diagnosis of herpes simplex virus in patients with encephalitis or meningitis".) <span>There is no standard approach to the treatment of HSV meningitis [8]. For hospitalized patients, intravenous acyclovir at 10 mg/kg administered every eight hours is reasonable. The dose should be adjusted for individuals with reduced kidney function, and recommendations are provided in the Lexicomp drug information topic within UpToDate. Patients can be switched to an oral agent on discharge for a total of 10 to 14 days of treatment. However, the role of antiviral therapy for HSV meningitis remains unclear, especially in immunocompetent hosts. As an example, a retrospective observational study that evaluated forty-t




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However, the role of antiviral therapy for HSV meningitis remains unclear, especially in immunocompetent hosts. As an example, a retrospective observational study that evaluated forty-two patient episodes of HSV meningitis found that immunocompromised patients had fewer neurologic sequelae when treated with a short course of antiviral therapy [9]. By contrast, this benefit was not seen in the 27 patient episodes that occurred in immunocompetent patients. More studies are needed to help guide management decisions.
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ction, and recommendations are provided in the Lexicomp drug information topic within UpToDate. Patients can be switched to an oral agent on discharge for a total of 10 to 14 days of treatment. <span>However, the role of antiviral therapy for HSV meningitis remains unclear, especially in immunocompetent hosts. As an example, a retrospective observational study that evaluated forty-two patient episodes of HSV meningitis found that immunocompromised patients had fewer neurologic sequelae when treated with a short course of antiviral therapy [9]. By contrast, this benefit was not seen in the 27 patient episodes that occurred in immunocompetent patients. More studies are needed to help guide management decisions. Recurrent (Mollaret's) meningitis — Mollaret's meningitis is a form of recurrent benign lymphocytic meningitis (RBLM), an uncommon illness characterized by greater than three episodes o




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Recurrent (Mollaret's) meningitis — Mollaret's meningitis is a form of recurrent benign lymphocytic meningitis (RBLM), an uncommon illness characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution [10]. There is a large patient-to-patient variation in the time course to recurrence that can vary from weeks to years. One-half of patients can also exhibit transient neurological manifestations, including seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness
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, this benefit was not seen in the 27 patient episodes that occurred in immunocompetent patients. More studies are needed to help guide management decisions. Recurrent (Mollaret's) meningitis — <span>Mollaret's meningitis is a form of recurrent benign lymphocytic meningitis (RBLM), an uncommon illness characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution [10]. There is a large patient-to-patient variation in the time course to recurrence that can vary from weeks to years. One-half of patients can also exhibit transient neurological manifestations, including seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness. The most common etiologic agent in Mollaret's meningitis is HSV-2, although some patients do not have evidence of genital lesions at the time of presentation [11]. Studies suggest that




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The most common etiologic agent in Mollaret's meningitis is HSV-2, although some patients do not have evidence of genital lesions at the time of presentation [11]. Studies suggest that recurrent meningitis occurs in approximately 20 percent of patients who present with primary HSV-2 infection with meningitis [12,13]. The diagnosis can be made by PCR testing for HSV DNA in the CSF.
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from weeks to years. One-half of patients can also exhibit transient neurological manifestations, including seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness. <span>The most common etiologic agent in Mollaret's meningitis is HSV-2, although some patients do not have evidence of genital lesions at the time of presentation [11]. Studies suggest that recurrent meningitis occurs in approximately 20 percent of patients who present with primary HSV-2 infection with meningitis [12,13]. The diagnosis can be made by PCR testing for HSV DNA in the CSF. A randomized controlled trial evaluated whether suppressive therapy with valacyclovir (500 mg twice daily for one year) was more effective than placebo in preventing recurrent HSV-2-rel




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Noninfectious etiologies for Mollaret's meningitis have also been proposed. As an example, patients with an intracranial epidermoid cyst or other cystic abnormalities in the brain can develop meningeal irritation due to intermittent leakage of irritating squamous material into the CSF [15,16]. This may be detected acutely by polarizing microscopy of CSF. Imaging studies should be performed subsequently when the patient is asymptomatic, since the epidermoid cyst is often collapsed immediately after leaking its contents
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by several factors, including: inclusion of patients without a clear etiologic diagnosis at study entry, use of symptoms alone for the diagnosis of recurrent meningitis, and small sample size. <span>Noninfectious etiologies for Mollaret's meningitis have also been proposed. As an example, patients with an intracranial epidermoid cyst or other cystic abnormalities in the brain can develop meningeal irritation due to intermittent leakage of irritating squamous material into the CSF [15,16]. This may be detected acutely by polarizing microscopy of CSF. Imaging studies should be performed subsequently when the patient is asymptomatic, since the epidermoid cyst is often collapsed immediately after leaking its contents. Lymphocytic choriomeningitis virus — Lymphocytic choriomeningitis virus (LCMV) is a human zoonosis caused by a rodent-borne arenavirus. LCMV is excreted in the urine and feces of roden




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Lymphocytic choriomeningitis virus — Lymphocytic choriomeningitis virus (LCMV) is a human zoonosis caused by a rodent-borne arenavirus. LCMV is excreted in the urine and feces of rodents, including mice, rats, and hamsters, and is transmitted to humans by exposure to secretions or excretions (by direct contact or aerosol) of infected animals or contaminated environmental surfaces [17-19]. Infection is more common during winter months.

Affected patients generally present with an influenza-like systemic illness accompanied by headache and meningismus. A minority of patients develop orchitis, parotitis, myopericarditis, or arthritis

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rizing microscopy of CSF. Imaging studies should be performed subsequently when the patient is asymptomatic, since the epidermoid cyst is often collapsed immediately after leaking its contents. <span>Lymphocytic choriomeningitis virus — Lymphocytic choriomeningitis virus (LCMV) is a human zoonosis caused by a rodent-borne arenavirus. LCMV is excreted in the urine and feces of rodents, including mice, rats, and hamsters, and is transmitted to humans by exposure to secretions or excretions (by direct contact or aerosol) of infected animals or contaminated environmental surfaces [17-19]. Infection is more common during winter months. Affected patients generally present with an influenza-like systemic illness accompanied by headache and meningismus. A minority of patients develop orchitis, parotitis, myopericarditis, or arthritis. CSF findings are typical of other causes of viral meningitis except that low glucose concentrations are observed in 20 to 30 percent of patients with LCMV meningitis and CSF WBC counts




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CSF findings are typical of other causes of viral meningitis except that low glucose concentrations are observed in 20 to 30 percent of patients with LCMV meningitis and CSF WBC counts of greater than 1000/microL are not unusual [20]. The diagnosis is established by documentation of seroconversion to the virus in paired serum samples; in addition, cell culture of CSF usually detects the presence of LCMV [5]. There is no specific antiviral therapy for LCMV
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ed patients generally present with an influenza-like systemic illness accompanied by headache and meningismus. A minority of patients develop orchitis, parotitis, myopericarditis, or arthritis. <span>CSF findings are typical of other causes of viral meningitis except that low glucose concentrations are observed in 20 to 30 percent of patients with LCMV meningitis and CSF WBC counts of greater than 1000/microL are not unusual [20]. The diagnosis is established by documentation of seroconversion to the virus in paired serum samples; in addition, cell culture of CSF usually detects the presence of LCMV [5]. There is no specific antiviral therapy for LCMV. Mumps — Aseptic meningitis is the most frequent extrasalivary complication of mumps virus infection. Prior to the introduction of the mumps vaccine in 1967, this paramyxovirus was a re




It is common to classify economic activity into two sectors: the public sector and the private sector.
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Flashcard 7091346083084

Question
It is common to classify economic activity into two sectors: [...]
Answer
the public sector and the private sector.

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It is common to classify economic activity into two sectors: the public sector and the private sector.

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It is com- monly assumed that all businesses in the private sector have profit maximisation as their prime objective
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Flashcard 7091348704524

Question
It is com- monly assumed that all businesses in the private sector have [...] as their prime objective
Answer
profit maximisation

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It is com- monly assumed that all businesses in the private sector have profit maximisation as their prime objective

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Objectives can change over time. A business trading in a period of reduced econ- omic activity (especially a recession) may focus on survival rather than profit maxi- misation
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Flashcard 7091351325964

Question
Objectives can change over time. A business trading in a period of reduced econ- omic activity (especially a recession) may focus on [...] rather than profit maxi- misation
Answer
survival

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Objectives can change over time. A business trading in a period of reduced econ- omic activity (especially a recession) may focus on survival rather than profit maxi- misation

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Assets Assets are the resources which are used by the business as part of the activities of the business (e.g. property, equipment and cash).
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Flashcard 7091355520268

Question
Assets
Answer
Assets are the resources which are used by the business as part of the activities of the business (e.g. property, equipment and cash).

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Assets Assets are the resources which are used by the business as part of the activities of the business (e.g. property, equipment and cash).

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Liabilities represent the debts of the business – i.e. what is owed by the business to others. These may be short-term debts which are to be repaid soon or long-term debts which may be outstanding and owing for many years (e.g. a mortgage)
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Flashcard 7091359190284

Question
Liabilities
Answer
Liabilities represent the debts of the business – i.e. what is owed by the business to others. These may be short-term debts which are to be repaid soon or long-term debts which may be outstanding and owing for many years (e.g. a mortgage)

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Liabilities represent the debts of the business – i.e. what is owed by the business to others. These may be short-term debts which are to be repaid soon or long-term debts which may be outstanding and owing for many years (e.g. a mortgage)

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Capital refers to the resources supplied to the business by the owner(s) of the (or equity) business. This capital could be in the form of money or as other assets.
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Flashcard 7091362598156

Question
Capital or Equity
Answer
Capital refers to the resources supplied to the business by the owner(s) of the business. This capital could be in the form of money or as other assets.

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Capital refers to the resources supplied to the business by the owner(s) of the (or equity) business. This capital could be in the form of money or as other assets.

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This relates to the idea that accounting transactions can be considered from two different perspectives
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Flashcard 7091366792460

Question
This relates to the idea that accounting transactions can be considered from two different perspectives
Answer
The principle of duality

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This relates to the idea that accounting transactions can be considered from two different perspectives

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Assets == Capital ++ Liabilities
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Flashcard 7091370200332

Question
Assets =[...]
Answer
Capital + Liabilities

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Assets == Capital ++ Liabilities

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Rules and regulations are not as important for the purpose of internal accounts as they are for those for external publication and external use.
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Flashcard 7091373608204

Question
Rules and regulations are not as important for the purpose of internal accounts as they are for those for [...].
Answer
external publication and external use

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Rules and regulations are not as important for the purpose of internal accounts as they are for those for external publication and external use.

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Accounting standards are a set of continually evolving documents which provide guidance on various aspects of financial accounting
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Flashcard 7091376229644

Question
Accounting standards are a [...]
Answer
set of continually evolving documents which provide guidance on various aspects of financial accounting

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Accounting standards are a set of continually evolving documents which provide guidance on various aspects of financial accounting

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Flashcard 7091378851084

Tags
#has-images





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Flashcard 7092440796428

Answer
The term “fermentation” is derived from the Latin verb fervere, to boil, thus describ- ing the appearance of the action of yeast on the extracts of fruit or malted grain. The boiling appearance is due to the production of carbon dioxide bubbles caused by the anaerobic catabolism of the sugar present in the extract.

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Flashcard 7092441845004

Question
[default - edit me]
Answer
Its biochemical meaning relates to the generation of energy by the catabo- lism of organic compounds, whereas its meaning in industrial microbiology tends to be much broader.

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Flashcard 7092442893580

Question
[default - edit me]
Answer
Thus, industrial microbiologists have ex- tended the term fermentation to describe any process for the production of product by the mass culture of a microorganism.

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Flashcard 7092443942156

Question
five major groups of commercially important fermentations
Answer
[default - edit me]

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Flashcard 7092456000780

Question
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Answer
1. The formulation of media to be used in culturing the process organism during the development of the inoculum and in the production fermenter. 2. The sterilization of the medium, fermenters, and ancillary equipment. 3. The production of an active, pure culture in sufficient quantity to inoculate the production vessel. 4. The growth of the organism in the production fermenter under optimum conditions for product formation. 5. The extraction of the product and its purification. 6. The disposal of effluents produced by the process.

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Flashcard 7092458622220

Tags
#has-images


Question

Scheme of a fermentation process




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Flashcard 7092459932940

Question
[default - edit me]
Answer
CULTURE Batch culture is a closed culture system that contains an initial, limited amount of nutrient. The inoculated culture will pass through a number of phases, as illustrated in Fig. 2.1. After inoculation there is a period during which it appears that no growth takes place; this period is referred to as the lag phase and may be considered as a time of adaptation. In a commercial process, the length of the lag phase should be reduced as much as possible and this may be achieved by using a suitable inoculum, and cultural conditions

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Flashcard 7092464913676

Question
[default - edit me]
Answer
Following a period during which the growth rate of the cells gradually increases, the cells grow at a constant, maximum rate and this period is known as the log, or exponential, phase and the increase in biomass concentration will be proportional to the initial biomass concentration. ∝ dx dt x where x is the concentration of microbial biomass (g dm −3 ), t is time (h), d is a small change. This proportional relationship can be transformed into an equation by introduc- ing a constant, the specific growth rate (µ), that is, the biomass produced per unit of biomass and takes the unit per hours. Thus: µ = dx dt

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Flashcard 7092466224396

Question
[default - edit me]
Answer
Thus, a plot of the natural logarithm of biomass concentration against time should yield a straight line, the slope of which would equal to µ. During the exponential phase nutrients are in excess and the organism is growing at its maximum specific growth rate, µ max . It is important to appreciate that the µ max value is the maximum growth rate under the prevailing conditions of the experiment, thus the value of µ max will be affected by, for example, the medium composition, pH, and temperature

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Flashcard 7092467272972

Question
[default - edit me]
Answer
kinetics On integration Eq. (2.1) gives: = µ xxe t t 0 (2.2) where x 0 is the original biomass concentration, x t is the biomass concentration after the time interval, t hours, e is the base of the natural logarithm. On taking natural logarithms, Eq. (2.2) becomes: µ =+ xxtln

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#DAG #causal #edx
When there is an association between A and Y, even if A has a null causal effect, a zero causal effect on Y, then we say that there is bias under the null.
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#DAG #causal #edx
We have seen that confounding is a systematic bias when we are conducting causal inference research.
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#DAG #causal #edx
Systematic bias is an association between the treatment A and the outcome Y that does not arise from the causal effect of A on Y.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
A typical adult patient with acute bacterial meningitis usually seeks medical attention within a few hours to several days after the onset of illness
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The most common etiologic agents of acute meningitis are unknown. When a cause is identified, viruses (most often enteroviruses; children > adults), West Nile virus (WNV), and herpes simplex virus (HSV) type 2 (adults), but also human immunodeficiency virus (HIV), varicella-zoster virus (VZV), less likely mumps virus, and bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, and Listeria monocytogenes). 2 Less commonly, parasites (e.g., Naegleria fowleri and Angiostrongylus can- tonensis) may cause acute meningitis
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In contrast, patients with subacute (>5 days but <30 days="" of="" symptoms)="" or="" chronic="" meningitis="" (="">30 days of symptoms) typically present over weeks to months, or even years (see Chapter 88). 1,2 These patients are more likely to be immunosuppressed, have abnormal neurologic findings, and to have hypoglycorrhachia with less pronounced CSF pleocytosis. 2
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Méningo-encéphalite subaiguë ou chronique
#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The most common etiology is idiopathic, but tuberculous meningitis and fungal meningitis (e.g., caused by Cryptococcus neoformans, His- toplasma spp., and Coccidioides spp.) are important considerations. 1,2
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The clinical presentation of cryptococcal meningitis is different in patients with and without acquired immunodeficiency syndrome (AIDS). In non-AIDS patients cryptococcal meningitis is typically a subacute process, in which patients have days to weeks of symptoms characterized by headache, fever, meningismus, and personality changes. In AIDS patients the presentation is subtler with minimal, if any, symptoms; these patients may present with only headache and lethargy, with meningeal findings seen in only a few cases.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
An international consortium recently defined encephalitis with a combination of major and minor criteria. The major criteria are altered mental status (defined as a decreased, altered level of consciousness, lethargy, or personality change) lasting ≥24 hours without an alternative diagnosis and is a requirement for the diagnosis. The six minor criteria are (1) documented fever ≥38°C (100.4°F) within 72 hours before or after presentation, (2) seizures not attributable to a preexisting seizure disorder, (3) new-onset focal neurologic findings, (4) CSF white blood cells (WBCs) ≥5/mm 3 , (5) new- or acute-onset neuroimaging abnormali- ties consistent with encephalitis, and (6) abnormalities on electroen - cephalography consistent with encephalitis and not secondary to other etiologies. The presence of two minor criteria indicate possible encephalitis, and greater than or equal to three indicate probable or confirmed encephalitis, if the etiologic agent is confirmed by brain biopsy, serologies, polymerase chain reaction (PCR), or antibodies in patients with autoimmune encephalitis.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
A clinical overlap between encephalitis and encephalopathy may exist, the latter referring to a clinical state of altered mental status that can manifest as confusion, disorientation, or other cognitive impairment, with or without evidence of brain tissue inflammation; encephalopathy can be triggered by a number of metabolic or toxic conditions but occasionally occurs in response to certain infectious agents, such as Bartonella henselae and influenza virus. 6
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Of all the pathogens reported to cause encephalitis, most are viruses that may be associated with specific clinical and neuroimaging findings that suggest their diagnosis. 4,5 Unilateral temporal lobe encephalitis is classically caused by HSV, leading to clinical manifestations characterized by personality changes, altered mentation, a decreasing level of conscious- ness, seizures, and focal neurologic findings (e.g., dysphasia, weakness, and paresthesias). Bilateral temporal lobe involvement or lesions outside the temporal lobe, insula, or cingulate are less likely caused by HSV. 7
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Other herpesviruses that cause encephalitis during any season include VZV, cytomegalovirus (CMV), and human herpesvirus 6 and are usually seen more frequently in immunosuppressed individuals. Arboviruses (e.g., West Nile, eastern equine, St. Louis, La Crosse, and Japanese encephalitis viruses) and respiratory viruses can present with a thalamic and basal ganglia encephalitis presenting with tremors, including Parkinsonism features. 8
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Patients with WNV infection typically present between June and October, whereas respiratory viruses are usually present in children during the winter season.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Rabies virus is still a frequent cause of encephalitis in Asia (India especially) and in Africa.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Nonviral causes of encephalitis include Mycobacterium tuberculosis, L. monocytogenes, Rickettsia, Ehrlichia spp., Bartonella spp., Mycoplasma pneumoniae, and Toxoplasma gondii (more often seen in transplant patients with Toxoplasma encephalitis). 4
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Several free-living amebae (i.e., N. fowleri, Acanthamoeba spp., and Balamuthia mandrillaris) may cause a fatal encephalitis, usually during the summer months. 4
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In many cases of encephalitis (32%–75%) the etiology remains unknown, however, despite extensive diagnostic testing. 4,5,10
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Anti–N-methyl-d-aspartate receptor (NMDAR) encephalitis 11,12 is the most common cause of antibody-associated encephalitis and is typically seen in young females with an associated ovarian teratoma. Anti- NMDAR encephalitis has now also been associated with both HSV and VZV infections. 13
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Lésions focales (abcès, etc...)
#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Although patients may be brought to medical attention after development of a seizure or alteration in consciousness, fever is usually seen in less than 50% of patients.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In patients with fungal brain abscess caused by Aspergillus spp. or the Mucorales, the clinical presentation may be that of a stroke syndrome because of the propensity of these organisms to invade blood vessels.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The most common complication after lumbar puncture is headache, which is generally observed in 10% to 25% of patients; the headache is characteristically absent when the patient is recumbent and appears rapidly when the patient stands
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
A recommendation from the American Academy of Neurology supports the use of atraumatic (Sprotte or Pajunk) needles, rather than the standard (Quincke) needle, to reduce the risk of postlumbar puncture headache. 15 Reinsertion of the stylet before needle removal has also been shown to decrease the risk of headache. 15
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Infection is a very rare complication after lumbar puncture (1/50,000 procedures), even in patients with concomitant bacteremia. 1,15
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Lumbar puncture should not be performed in patients with established local infection in the lumbar space (e.g., spinal epidural abscess, spinal subdural empyema, or superficial or deep paraspinal infection); in these cases, CSF analysis should be obtained under fluoroscopic guidance via high cervical or cisternal puncture. 15
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Bleeding may occur from inadvertent puncture of the venous plexuses located dorsally and ventrally to the spinal dura or secondary to injury to vessels that accompany the cauda equina. This local bleeding rarely does harm to the patient, although patients with coagulation disturbances or who are receiving anticoagulants may develop continued bleeding with the development of spinal subdural or epidural hematomas, which may compress the cauda equina and produce permanent neurologic injury. This complication is extremely rare, even in patients with coagulopathies, with only 35 cases described in the literature over the last 42 years. 18
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Local bleeding is a more common complication after lumbar puncture 1,15 ; up to 20% of patients have a so-called traumatic tap. 1,15
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The Infectious Diseases of America (IDSA) guidelines recommend that patients with suspected meningitis with the following characteristics should get a cranial imaging study before the lumbar puncture: immunocompromised state (HIV infection or AIDS, receiving immunosuppressive therapy, or after transplantation), history of CNS disease (mass lesion, stroke, or focal infection), new- onset seizure, abnormal level of consciousness, papilledema, or focal neurologic deficit (including dilated, nonreactive pupil; abnormalities of ocular motility; abnormal visual fields; gaze palsy; or arm or leg drift). 19
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
However, adherence to the IDSA guidelines is low (40%), with no clinical benefit in those patients undergoing cranial imaging without an indication. 20
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Other guidelines (from the United Kingdom [UK], Europe, and Sweden) are more restrictive, with some guidelines (UK and Sweden) not recommending cranial imaging in immunosup- pressed individuals but recommending cranial imaging only with focal neurologic deficits or finding a Glasgow Coma Scale score <3
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
It has been suggested, however, that a normal CT scan does not always mean performance of a lumbar puncture is safe. Certain clinical signs of impending herniation, such as a deteriorating level of consciousness (particularly a Glasgow Coma Scale score ≤11), brainstem signs (including pupillary changes, posturing, or irregular respirations), or a very recent seizure, may be predictive of patients in whom lumbar puncture should be delayed. 24
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
CSF opening pressure is measured with an air-water manometer; in adults placed in the lateral decubitus position, the normal CSF opening pressure ranges from 50 to 195 mm H 2 O; values <150 mm="" H="" 2="" O="" are="" clearly="" normal,="" and="" those="">200 mm H 2 O are abnormal.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The CSF is normally clear and colorless but may appear cloudy or turbid in patients with increased concentrations of WBCs (>200/mm 3 ), red blood cells (RBCs, >400/mm 3 ), bacteria (>10 5 colony- forming units/mL), or protein.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Xanthochromia, a yellow or yellow-orange supernatant of centrifuged CSF, is usually a result of RBC lysis and the presence of oxyhemoglobin, methemoglobin, and bilirubin; it characteristically appears 2 to 4 hours after RBCs have entered the subarachnoid space, although it has occasion- ally been seen for 12 hours. 1,15
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[unknown IMAGE 7092536478988]
[MENINGO-ENCEPHALITE] - Mandell - Méningo-encéphalites introduction
#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis #has-images
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The normal CSF WBC count in children and adults is 0 to 5/mm 3 . CSF WBC counts in term neonates may be 32/mm 3 (mean, 8–9/mm 3 ), although by 1 month of age normal CSF has less than 10 WBCs/mm 3 .
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Elevated CSF concentrations of WBCs are seen in patients with men- ingitis, encephalitis, and parameningeal foci of infection (e.g., space- occupying lesions). 1,15
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Generalized seizures may also induce a transient CSF pleocytosis that is primarily neutrophilic, although the total WBC count should not exceed 80/mm 3 . Pleocytosis should not be ascribed to seizure activity alone, however, unless the fluid is clear and colorless, the opening pressure and CSF glucose are normal, the CSF Gram stain is negative, and the patient has no clinical evidence of CNS infection. 1
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Although CSF pleocytosis is suggestive of inflammation of the brain and/or meninges, the absence of CSF pleocytosis does not exclude the diagnosis of encephalitis. 25,26
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#DAG #causal #edx

Two sources of bias:

- common cause (confounding)

- conditioning on common effect (selection bias)

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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In patients with CSF pleocytosis, differential counts should be performed; a neutrophilic, mononuclear, or eosinophilic predominance may be suggestive of certain etiologies in the right clinical setting (see Table 86.2 and Chapters 88 and 89).
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
CSF hypoglycorrhachia is seen in many CNS infections. The patho- genesis of CSF hypoglycorrhachia is multifactorial and may include an increased rate of macrovesicular glucose transport across arachnoid villi, increased glycolysis by leukocytes and bacteria, increased metabolic rate of the brain and spinal cord, or inhibition of glucose entry into the subarachnoid space caused by alterations in the membrane carrier system responsible for glucose transfer from blood to CSF. 15,27
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#DAG #causal #edx
Today we will focus on confounding in a setting with no selection bias, with no measurement error, and with such a large population that we do not need to worry about chance variability
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The CSF glucose should always be compared with a simultaneous serum glucose that is drawn before lumbar puncture; the normal lumbar CSF-to–serum glucose ratio is approximately 0.6, and ratios <5
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[unknown IMAGE 7092564790540] #DAG #causal #edx #has-images
Let's start by considering two extreme examples. In the first causal graph here you see that A and Y have no common causes. And therefore, any association between them will be causation. This is the setting that we expect to find in a randomized experiment.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
An absolute CSF glucose < 45 mg/dL can be used to define hypoglycorrhachia, as hypoglycemia and hyperglycemia are rarely seen in patients with meningitis. 27
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Unfortunately, only 13% of patients with community-acquired meningitis have a simultaneous serum and CSF glucose performed. 27
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The CSF protein concentration is also elevated in numerous CNS infections, presumably because of disruption of the blood-brain barrier, manifested morphologically by separation of intercellular tight junctions and increased numbers of pinocytotic vesicles in microvascular endo- thelial cells. 1
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Lumbar CSF protein concentrations >50 mg/dL and ventricular CSF concentrations >15 mg/dL are considered abnormal. A CSF protein >100 mg/dL is a risk factor for an urgent treatable cause of meningitis in adults, and a CSF protein <29
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In patients with a traumatic lumbar puncture the true CSF protein concentration is determined by subtracting 1 mg/dL of protein for every 1000 RBCs/mm 3 , although these determinations must be made in the same CSF tube. 15
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The CSF Gram stain is positive in 60% to 90% of patients with acute bacterial meningitis, although this sensitivity varies depending on the concentra- tion of microorganisms in the CSF and the specific causative bacteria
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In patients with tuberculous meningitis, less than 15% to 25% of specimens are smear-positive by acid-fast stain and 20% of patients with tuberculous meningitis have persistently negative CSF cultures
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In patients with spirochetal meningitis (i.e., caused by Treponema pallidum or Borrelia burgdorferi) and Tox o- plasma encephalitis, there are no effective specialized stains that identify these organisms in CSF; in these cases serum or CSF antibody studies are most often used to aid in the diagnosis (see Chapters 88 and 89)
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CSF India ink examination is positive in 50% to 75% of patients with cryptococcal meningitis, and the yield increases to 88% in patients with AIDS
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The presence of virus-specific immunoglobulin M (IgM) in CSF is usually indicative of CNS disease because IgM antibodies do not readily diffuse across the blood-brain barrier; detection of IgM antibodies from patients with presumed flavivirus encephalitis is considered diagnostic of neuroinvasive disease. 4
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[unknown IMAGE 7092578422028] #DAG #causal #edx #has-images
Today we will focus on confounding in a setting with no selection bias, with no measurement error, and with such a large population that we do not need to worry about chance variability Let's start by considering two extreme examples. In the first causal graph here you see that A and Y have no common causes. And therefore, any association between them will be causation. This is the setting that we expect to find in a randomized experiment. In the second graph here, you see that A and Y have a common cause, L. But there is no causal effect of A on Y. In this setting, all the association between A and Y is due to confounding.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In patients with herpes simplex encephalitis CSF PCR is 96% to 98% sensitive and 95% to 99% specific in adult patients 30 ; CSF PCR results are positive early in the disease course and remain positive during the first week of therapy, although false-negative results may occur if hemoglobin or other inhibitors are present in CSF.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
An initially negative CSF PCR result for HSV may become positive if the test is repeated 1 to 3 days after the initiation of treatment 4,31 ; in undiagnosed cases in which patients have clinical or neuroimaging features suggestive of HSV encephalitis, consideration should be given to repeating the PCR for HSV 3 to 7 days later on a second CSF specimen. 4
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Diagnosis of CMV encephalitis by PCR has a high sensitivity and specificity for the diagnosis of CNS involvement 32 ; the absence of CMV DNA by PCR has a high negative predictive value.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Nucleic acid amplification with reverse-transcriptase PCR has also been found to be highly sensitive (86%–100%) and specific (92%–100%) for the diagnosis of enteroviral infections of the CNS, 15 and it has high specificity for the diagnosis of other viral causes of CNS infections, such as VZV and JC virus. 15,29
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Use of PCR to detect the fragments of mycobacterial DNA in CSF has also been used for rapid diagnosis of tuberculous meningitis. 35 The sensitivity for the different Mycobacterium tuberculosis (MTB) PCR technologies ranges from 55.8% to 87.6%, with recent nested MTB PCR showing sensitivity and specificity up to 89% and 100%, respectively. 36
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#DAG #causal #edx

What is the backdoor path criterion?

This is a graphical rule that tells us whether we can identify the causal effect of interest if we know the causal DAG. And the rule is the following: we can identify the causal effect of A and Y if we have sufficient data to block all backdoor paths between A and Y. We sometimes refer to these variables that we use to eliminate the backdoor path as confounders.

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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The clinical utility of PCR in patients with bacterial meningitis has been investigated with the use of a broad range of bacterial primers (i.e., broad-based PCR). 15,33 In one study 33 the broad range was highly sensitive and was able to detect pathogens up to 1 week after antibiotic therapy. A rapid (<
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
At present, however, with the currently available MTB PCRs a negative CSF PCR result cannot be used to exclude the diagnosis of tuberculous meningitis.
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In addition to conventional MRI sequences, recent advances have added further sensitivity and specificity to the diagnosis of brain infection. 38 These include diffusion-weighted imaging (DWI), diffusion tensor imaging, susceptibility-weighted imaging (SWI), perfusion-weighted imaging (PWI), and 1 H magnetic resonance spectroscopy.
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Flashcard 7092596772108

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#DAG #causal #edx #has-images
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
DWI is superior to conventional MRI for the detection of early signal abnormalities in viral encephalitis caused by HSV, enterovirus 71, and WNV. 38,39,40
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Flashcard 7092601752844

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[unknown IMAGE 7092603849996]
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Neuroimaging studies are less important in the diagnosis of patients with bacterial meningitis but may be useful in patients who are not responding as expected, that is, have persistent or prolonged fever, clinical evidence of increased ICP, focal neurologic findings, new or recurrent seizures, enlarging head circumference (in neonates), persistent neurologic dysfunction, or persistently abnormal CSF parameters or cultures. 1
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Flashcard 7092606209292

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[unknown IMAGE 7092606733580]
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The key to distinguishing abscess from other cystic intracranial processes (e.g., necrotic tumors) is DWI 40 ; pus in the abscess has restricted diffusion and appears DWI hyperintense.
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Flashcard 7092612762892

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[unknown IMAGE 7092614073612]
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In AIDS patients with positive immu- noglobulin G (IgG) antibody titers to T. g ond ii, the detection of multiple ring-enhancing lesions by CT with contrast enhancement or MRI is enough evidence to initiate a trial of anti-Toxoplasma chemotherapy 38 (see Chapter 90); CT or MRI is repeated in 10 to 14 days to document a clinical response.
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Drug penetration into CSF depends on the status of the blood-brain barrier, which is disrupted in the presence of meningeal inflammation. Some agents (e.g., corticosteroids) may reduce meningeal inflammation and reduce blood-brain barrier penetration of antimicrobial agents even though appropriate CSF vancomycin concentrations were documented in patients treated with adjunctive dexamethasone in one study. 42
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Entry of antimicrobial agents into CSF is also enhanced by drugs that have a low molecular weight, low degree of ionization at physiologic pH, high lipid solubility, and low degree of protein binding. 1,41
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#DAG #causal #edx

Other (wrong definitions of confounder):

- change in estimate definition

- conventional definition

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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In addition, intraventricular or intrathecal therapy may be required for eradication of resistant pathogens in patients with health care–associated ventriculitis and meningitis. 43 These principles are reviewed in further detail in Chapters 87 and 92
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In the therapy of focal intracranial infections, clinicians often rely on agents that are known to have efficacy in experimental animal models, which includes extrapolating data from animal models of meningitis, and based on anecdotal case series or case reports. This approach is reasonable because these infections are uncommon, and randomized trials of specific agents are not likely to be performed
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Adjunctive dexamethasone, given concomitant with or just before the first antimicrobial dose, improves outcomes in infants and children with H. influenzae type b, and perhaps pneumococcal meningitis, and in adults with pneumococcal meningitis (see Chapter 87). 1,19,44
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Adjunctive corticosteroids may not be beneficial, however, in patients with bacterial meningitis in the developing world, most likely because of their delayed presentation. 45
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Corticosteroids may also be beneficial in patients with focal intracranial infections and cerebral edema associated with significant mass effect. 44
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Although it should be noted that randomized studies of various strategies to lower ICP in patients with CNS infections have not been performed, some maneuvers may be beneficial. 45,46 Head elevation of 30 degrees is considered standard, and other factors that might increase ICP, such as pain, bladder distention, and agitation, should be avoided. Hyperventilation (to maintain the partial pressure of carbon dioxide in arterial blood at 27–30 mm Hg), which causes vasoconstriction and reduction in intracerebral volume, may also be used to reduce ICP, although it should be used only as a short-term intervention to quickly reduce ICP when it is dangerously elevated because it may induce cerebral ischemia (see Chapter 87).
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Hyperosmolar agents decrease ICP by making the intravascular space hyperosmolar relative to the brain, permitting movement of water from the brain tissue to the intravascular compartment. However, a controlled trial from Malawi of adjunctive glycerol in adult patients with bacterial meningitis showed that it was harmful and increased mortality. 47 Similarly, a clinical trial of hypothermia (to reduce ICP) in bacterial meningitis showed a trend toward worse clinical outcomes. 48
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
There is some evidence to support the use of IV maintenance fluids in the first 48 hours in patients with bacterial meningitis 50 ; although there is insufficient evidence to guide this practice, adult patients with meningitis should be treated with the goal of attaining a normovolemic state. 1,50
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#Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Seizures may occur in patients with CNS infections and must be managed quickly and aggressively to avoid permanent anoxic ischemic changes. 1,45,46 Status epilepticus that is continuous for 90 minutes or more can lead to permanent neurologic injury. Short-acting anticon- vulsants with a rapid onset of action (e.g., lorazepam or diazepam) should be given, followed by a long-acting agent, such as phenytoin.
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Meningitis, or infl ammation of the meninges, is typically identified by means of a cerebrospinal fluid (CSF) pleocytosis of more than five white blood cells (WBCs) in the CSF, even though approximately up to 8% of patients with central nervous system (CNS) infections can present with absence of CSF pleocytosis. 1
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Acute meningitis (duration of symptoms of less than 5 days) accounts for 75% of all community-acquired meningitis cases and is most commonly caused by unknown pathogens, as well as viral and bacterial organisms. 2
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In contrast, patients with subacute meningitis (duration of 5 days or more) are more likely to have comorbidi- ties, be immunosuppressed, have fungal etiologies, or present with abnormal neurologic examination findings or with hypoglycorrhachia (CSF glucose < 45 mg/dL). 2
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Chronic meningitis (>4 weeks’ duration of symptoms and signs and CSF abnormalities) has a broad differential diagnosis that includes conditions such as fungal infection, mycobacterial infection, neurobrucellosis, neurosyphilis, sarcoidosis, autoimmune disorders, paraneoplastic disorders, and vasculitis. 3
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Encephalitis is a community-acquired illness with altered mental status for more than 24 hours with at least two (possible encephalitis) or three (probable encephalitis) of the following criteria: fever, new-onset seizure, new-onset focal neurologic finding, CSF pleocytosis, and abnormal findings at magnetic resonance imaging (MRI) of the brain or electro- encephalogram (EEG) consistent with encephalitis. 4
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Viruses are the most commonly identified cause of the aseptic meningitis syndrome, a term used for a community-acquired illness with CSF pleocytosis, a negative CSF or blood culture, normal neurologic examination findings, and a benign clinical outcome.5
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The most common viral etiologic agents that cause the acute aseptic meningitis syndrome are enteroviruses (EVs), herpesviruses, and arboviruses such as WNV. 5
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Enteroviruses EVs are currently the leading recognizable cause of aseptic meningitis syndrome, accounting for 48% to 95% of all cases in which a causative virus is identified. 5–7
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
in adults, in whom a CSF EV polymerase chain reaction (PCR) assay is performed in only 15%. 5–7
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
A total of 118 types of EVs and 16 types of human parechoviruses (HPeVs) (both small viruses of the Picornaviridae family) have been described as causes of viral meningitis in the United States. 7 In addition to aseptic meningitis, these viruses can sometimes also cause acute flaccid paralysis (AFP), encepha- litis, myocarditis, and sepsis, with worse clinical presentations most commonly seen in neonates or infants. 7
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EVs have a worldwide distribution and, in temperate climates, have a summer/fall seasonality, although in tropical and subtropical areas they can occur perenially. 6
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EV's (enterovirus)
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Transmission is mainly via the fecal-oral route, but it has also been documented via respiratory droplets. 6
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From 2009 to 2013, based on data from the CDC laboratory-based surveillance system (the National Enterovirus Surveil- lance System), the majority of cases occurred from April to November and the two most common viruses identified were coxsackievirus A6, and HPeV type 3, accounting for a total of 24.6% of total serotypes detected. 7
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In addition, EV 71 can also cause AFP, in addition to aseptic meningitis and a brainstem encephalitis, which may manifest with shock and pulmonary edema.
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Infants and young children are the primary victims of enteroviral meningitis because they are the most susceptible host population within the community.
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In a study of 156 enteroviral infections in children, risk factors for severe disease were absence of oral lesions, seizures, and lethargy, with the majority of the severe cases caused by EV 71 and coxsackievirus A16. 16
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Herpesviruses Herpesviruses include HSV types 1 and 2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus (HHV) types 6, 7, and 8. Although neurologic complications are known to occur with some of these viruses, complications associated with HSV are of the greatest significance.
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In patients beyond the neonatal period, it is critical to differentiate between HSV encephalitis (usually caused by HSV type 1), a potentially fatal infection, and HSV meningitis (most commonly caused by HSV type 2), a self-limited syndrome.
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The syndrome of HSV-2 aseptic meningitis is most commonly associated with primary genital infection and has a benign clinical outcome that does not appear to be impacted by antiviral therapy. 19
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A study in which a multiplex PCR assay was used documented that HHV-6 was more commonly detected than HSV-1 or HSV-2 in adults and children with meningitis and encephalitis. 22 The proportion of these HHV-6 cases that represent a true infection, versus reactivation or chromosomal integration, remains to be determined. 23
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CMV and EBV may cause aseptic meningitis in association with a mononucleosis syndrome, particularly in an immunocompetent host. 24
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HSV-2 is also the most common cause of Mollaret meningitis (now termed recurrent benign lymphocytic meningitis), although a few cases associated with HSV-1 and EBV have been reported. 20 The majority of patients are female, have no history of genital HSV, and have no active lesions at presentation. 20
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Arboviruses (arthropod-borne virus) include several families of viruses that are transmitted by mosquitos, ticks or sand flies. 25
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The most common arthropod-transmitted cause of aseptic meningitis in the United States is WNV, a flavivirus
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
WNV infection is most commonly asymptomatic, with approximately 20% of patients having a febrile illness and 1% presenting with neuroinvasive disease. 26 Neuroinvasive disease may present as an aseptic meningitis, encephalitis or an AFP/myelitis, but may be underdiagnosed because only approximately one-third of adults and children with meningitis or encephalitis are tested. 27
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There is no vaccine or therapy for WNV infection
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In Europe, tick-borne encephalitis can be associated with a complex syndrome of meningoencephaloradiculitis (MER), which is associated with a relatively high risk of severe disease (requirement for intensive care and mechanical ventilation). Age, male sex, and preexisting diabetes mellitus were predictive of the more severe MER. 29
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Toscana virus has emerged as one of the most common causes of meningitis or encephalitis during the summer in the Mediterranean countries 30 ; it is transmitted by sand flies and is a bunyavirus.
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Less common arboviruses in the United States that can cause aseptic meningitis are two mosquito-borne illnesses—St. Louis encephalitis (a flavivirus) and the California encephalitis group of viruses
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Lymphocytic choriomeningitis virus (LCMV) can cause aseptic men- ingitis 24 ; this virus is now rarely reported as an etiologic agent. 5 A seroprevalence of 5% for LCMV was seen in 400 patients with neurologic infections, but there were no documented cases by PCR assay. 31
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
LCMV is transmitted to humans by contact with rodents (e.g., hamsters, rats, mice) or their excreta 24 ; the greatest risk for infection is in laboratory workers, pet owners, and persons living in impoverished and unhygienic situations.
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LCMV
#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
No evidence of human-to-human transmission has been reported
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In an unimmunized population, mumps can cause aseptic meningitis and encephalitis. 24
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With the introduction of the measles-mumps-rubella (MMR) vaccine, the incidence of mumps-associated meningitis has dramatically decreased, now accounting for <% of all cases of meningitis and encephalitis in the United Kingdom and the United States. 34,35
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Human immunodeficiency virus (HIV) can cause aseptic meningitis during HIV seroconversion; the clinical presentation is a mononucleosis- like picture. 24
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
HIV may also cause an encephalitis presentation in those with acquired immunodeficiency syndrome (AIDS) who are not receiving antiretroviral therapy (ART) (known as AIDS encephalopathy or HIV encephalitis) or in those patients on ART with CSF viral escape (detectable viral load in the CSF with undetectable or low-level viremia). 36 This latter form is named CD8 encephalitis and can be treated with steroids and by optimizing ART.
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A recent large study of community-acquired meningitis in the United States showed that 25% of patients tested had HIV coinfection. 37
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Japanese encephalitis is a vaccine-preventable infection that continues to cause both meningitis and encephalitis in countries where routine vaccination is not available. 38
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Dengue, chikungunya, and Zika viruses are emerging causes of meningitis or encephalitis in several parts of the world. 39,40
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Other newly identified causes of meningitis include astrovirus MLB2, usually a gastrointestinal virus, and Cache Valley virus in an immunosuppressed individual. 42,43
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The Global Burden of Disease Study showed that meningitis caused 318,000 deaths each year worldwide (4.5 per 100,000 persons), resulting in 20,383 years of life lost in 2016. 46
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The incidence rates vary per country, with most recent rates varying from 0.7 to 0.9 per 100,000 per year in the United States and European countries, whereas studies from Africa describe incidence rates varying from 10 to 40 per 100,000 per year. 47
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
In another surveillance study among residents in eight surveillance areas representing 17.4 million persons from 1998 to 2007, the impact of the heptavalent pneumococcal conjugate vaccine was appreciated; the incidence of meningitis caused by vaccine serotypes decreased from 0.61 cases per 100,000 population in 1998 to 1999 to 0.05 cases per 100,000 population in 2006 to 2007, although the number of cases of bacterial meningitis caused by nonvaccine serotypes increased by 61%. 50
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The mean age of all patients with meningitis increased from 30.3 years in 1998 to 1999 to 41.9 years in 2006 to 2007.
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However, despite the declining incidence of bacterial meningitis in the United States, the overall case-fatality rates did not change significantly (15.7% in 1998 to 1999 compared with 14.3% in 2006 to 2007; P = .50)
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Epidemiology of bacterial meningitis differs according to age group, with higher incidences in the very young (neonates) and the elderly. 52
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In neonates, the majority of meningitis cases are caused by Streptococcus agalactiae (or group B streptococci) and Escherichia coli. 53
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In children beyond the neonatal age, S. pneumoniae and N. meningitidis cause up to 90% of cases (Table 87.3)
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In patients 16 years old or older, most cases are caused by S. pneu- moniae, N. meningitidis, and L. monocytogenes (see Tab le 8 7. 3). 47–51
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Risk factors for meningitis in adults consist of splenectomy or splenic dysfunc- tion, alcoholism, HIV, diabetes, cancer, use of immunosuppressive medications, solid organ transplantation, and bone marrow transplantation. 56–59
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Elderly patients and patients in an immunocompromised state are at higher risk of L. monocytogenes meningitis, which should therefore be covered in the empirical antibiotic treatment in anyone older than 50 years and in those in an immunocompromised state, irrespective of age. 52,53
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Risk factors for death on admission among adults with community-acquired meningitis include older age, absence of otitis or sinusitis, alcoholism, tachycardia, lower score on the Glasgow Coma Scale, cranial nerve palsy, a CSF WBC count of less than 1000 cells per microliter, a positive blood culture, and a high serum C-reactive protein (CRP) concentration.60
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Geographic differences in bacterial meningitis epidemiology are substantial (Table 87.4). 50–53 The majority of cases worldwide occur in sub-Saharan Africa, a region often referred to as the “meningitis belt.”
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A study from Burkina Faso showed that despite the epidemics of meningococcal disease, 53% of cases were caused by S. pneumoniae. 62
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In regions with high rates of HIV infection, bacterial meningitis due to nontyphoidal Salmonella species causes a substantial proportion of cases. 63,64
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In Southeast Asia, the most common pathogen is Streptococcus suis, which is found in 25% to 30% of cases 65 ; risk factors are close contact with pigs due to pig farming or the pork-processing industry, and alcoholism. 66
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Outcome also differs geographically, with mortality rates ranging from 54% in Malawi to 6% in Germany. 67,68
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Mortality from neonatal meningitis in developing countries is estimated to be 40% to 58%, compared with only 10% in the developed world. 69
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In a 2012 study from Korea of 91 adult patients with health care–associated meningitis, coagulase-negative staphylococci (41% of cases) and Acinetobacter species (33% of cases) were the most common pathogens, with 86% of patients having infection related to an external ventricular drain. 72
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In a review of 132 studies including 18,183 survivors of acute bacterial meningitis, the risk for a major sequela (cognitive deficit, bilateral hearing loss, motor deficit, seizures, visual impairment, hydrocephalus) was greatest in Africa (25.1%) and southeast Asia (21.6%) when compared with Europe (9.4%) 74 ; the risk for at least one major sequela was also pathogen dependent—24.7% in survivors of pneumococcal meningitis compared with 9.5% with H. influenzae type b meningitis and 7.2% with N. meningitidis meningitis
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[MENINGO-ENCEPHALITE] - Mandell - Méningo-encéphalites aiguës
#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis #has-images
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H. influenzae was isolated in 45% to 48% of all cases of bacterial meningitis in the United States before introduction of the H. influenzae type b vaccine 48,49 ; this organism is now isolated in only 3% to 7% of cases. 50,51,60 The overall mortality rate is 3% to 7%. 48–51,77
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Haemophilus
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Most episodes of meningitis previously occurred in infants and children younger than 6 years (peak incidence of 6 to 12 months), with 90% of cases caused by capsular type b strains.
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Haemophilus
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Isolation of this organism in older children and adults should suggest the presence of certain underlying conditions, including sinusitis, otitis media, epiglottitis, pneumonia, diabetes mellitus, alcoholism, splenectomy or asplenic states, head trauma with CSF leak, and immune deficiency (e.g., hypogammaglobulinemia). 77–80
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
N. meningitidis most commonly causes meningitis in children and young adults and is associated with an overall mortality rate of 3% to 13% in the United States. 48–51
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More than 98% of cases of invasive meningococcal disease are sporadic. 86
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Annual outbreaks of meningococcal meningitis occur in the sub-Saharan meningitis belt during the dry season (December to June); cases tend to peak in late April and early May, when the dry desert wind (harmattan) has ceased and temperatures are high throughout the day, and terminate abruptly with the onset of the rainy season.
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A 2017 study of surveillance data from 25 European countries assessed almost 50,000 cases of meningococcal disease from the period of 2004 to 2014 and showed a variable incidence, ranging from 0.3 to 2.9 cases per 100 000 per year. 96 Overall, 74% of cases were caused by serogroup B, and serogroup C was the second most common, identified in 14% of cases. 96
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Respiratory tract infections, with viruses such as influenza virus, may play a role in the pathogenesis of invasive meningococcal disease. 79
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Nasopharyngeal carriage of N. meningitidis is an important factor that leads to the development of invasive disease. 80
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
atients with deficiencies in the terminal complement components (C5, C6, C7, C8, and perhaps C9), the so-called membrane attack complex, have a markedly increased incidence of neisserial infection, 81–83 including that caused by N. meningitidis, although mortality rates in patients with meningococcal disease are lower than those in patients with an intact complement system (3% vs. 19% in the general population).
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
Because meningococcal meningitis occurs in approxi- mately 39% of persons with late complement component deficiencies and 6% of those with properdin deficiencies, it has been suggested that a screening test for complement function (i.e., CH 50 ) should be performed for patients who have invasive meningococcal infections, with consid- eration of direct assessment of terminal complement components and properdin proteins. 85 However, this is most appropriate for patients with recurrent neisserial infections.
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Meningocoque
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Most recently, there has been an increased risk in patients who are receiving eculizumab (1000- to 2000-fold increased risk). 99
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
S. pneumoniae, the most frequently observed etiologic agent of bacterial meningitis in the United States, now accounts for 58% of the total cases. 51
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#Acute #Aigue #Meningite #Meningitis #Meningo-encephalite #Meningoencephalitis
The incidence of pneumococcal meningitis decreased in children first, and later also in adults. The decrease was the result of a reduction of cases due to serotypes included in the vaccine, but at the same time an increased incidence in nonvaccine serotypes occurred, limiting the effect of the vaccine’s introduction. 104
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In invasive pneumococcal disease other than meningitis, the effect of vaccination was substantially better, which was explained by different tropism for the meninges of the serotypes. 107
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A 2016 study from France assessing 5166 pneumococcal isolates from meningitis cases showed that the effect of the introduction of PCV7 and PCV13 was modest. 47,105
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The mortality rate of pneumococcal meningitis ranges from 18% to 26% in the United States. 48–51 In one study of 352 episodes of community- acquired pneumococcal meningitis in adults, 245 (70%) were associated with an underlying disorder and the overall in-hospital mortality rate was 30% 108 ; independent predictors of unfavorable outcome were a low score on the Glasgow Coma Scale, cranial nerve palsies, elevated erythrocyte sedimentation rate, a CSF WBC count of less than 1000/ mm, 3 and a high CSF protein concentration on admission
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Of the more than 90 known pneumococcal serotypes, 18 are responsible for 82% of the cases of bacteremic pneumococcal pneumonia, with a close correlation between bacteremic subtypes and those implicated in meningitis.
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Patients often have contiguous or distant foci of pneumococcal infection, such as pneumonia, otitis media, mastoiditis, sinusitis, and endocarditis.
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Serious infection may be observed in patients with various underlying conditions (e.g., splenectomy or asplenic states, multiple myeloma, hypogammaglobulinemia, alcoholism, HIV chronic liver or renal disease, malignancy, and diabetes melli- tus). 109–112
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The pneumococcus is the most common etiologic agent of meningitis in patients who have sustained a basilar skull fracture with CSF leak. 114
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L. monocytogenes causes 2% to 8% of cases of bacterial meningitis in the United States and carries a mortality rate of 15% to 29%. 48–51 Serotypes 1/2b and 4b have been implicated in up to 80% of meningitis cases caused by this organism
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Epidemiologic data show that the incidence of L. monocytogenes meningitis is highest in neonates and elderly, with incidences up to 0.61 per 100,000 in neonates and 0.53 per 100,000 in the elderly. 54
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A study from the Netherlands showed that the incidence of neonatal Listeria meningitis had decreased in the previous 25 years, potentially because of increased awareness of food restrictions for pregnant women.
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The rate of unfavorable outcome among adults with Listeria meningitis was found to increase over a 14-year period from 27% to 61%, with the emerging L. monocytogenes sequence type 6 identified as the main factor leading to a poorer prognosis. 115
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A follow-up whole-genome sequencing study of these Listeria strains identified a plasmid containing the benzalkonium chloride tolerance gene that was associated with decreased susceptibility to disinfectants commonly used in the food-processing industry. Strains containing the plasmid had increased minimal inhibitory concentrations (MICs) to amoxicillin and gentamicin, which are commonly used in treatment of L. monocytogenes infections. 116
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Listeria has been isolated from dust, soil, water, sewage, and decaying vegetable matter (including animal feed and silage).
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Listerial infection is most common in infants younger than 1 month (up to 10% of cases), adults older than 60 years, alcoholics, cancer patients, those receiving corticosteroid therapy, and immunosuppressed adults (e.g., renal transplant recipients). 117–119 Other predisposing conditions include diabetes mellitus, liver disease, chronic renal disease, collagen vascular diseases, pregnancy, and conditions associated with iron overload.
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Although colonization rates are low, pregnant women (who account for 25% of all cases of listeriosis) may harbor the organism asymptomati- cally in their genital tract and rectum and transmit the infection to their infants.
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Adults younger than 50 years with Listeria meningitis should be screened for HIV infection. 120 Meningitis can also occur in immunocompetent children and adults. 121,122
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Outbreaks of Listeria infection have been associated with the consumption of contaminated coleslaw, raw vegetables, milk, and cheese, with sporadic cases traced to contaminated turkey franks, alfalfa tablets, cantaloupe, diced celery, hog head cheese (a meat jelly made from hog heads and feet), and processed meats, thus pointing to the intestinal tract as the usual portal of entry. 117–119,123–126
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In a review of 444 cases of neonatal bacterial meningitis over a 7-year period, group B streptococci were the most common cause in early-onset (occurring between birth and day 4 of life) and late-onset (occurring between days 5 and 28 of life) disease, responsible for 77% and 50% of cases, respectively. 128 In the United States, the overall mortality rate ranges from 7% to 27%. 48–51
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Group B streptococci have been isolated from vaginal or rectal cultures of 15% to 35% of asymptomatic pregnant women 130 ; colonization rates do not vary during pregnancy, and carriage may be chronic (40%), transient, or intermittent. The risk for transmission from mother to infant is increased when the inoculum of organisms and the number of sites of maternal colonization are increased; the route of delivery does not influence transmission
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A study of 848 cases in newborns and infants in France documented that antibiotic prophylaxis was associated with a decrease in early-onset cases (0–6 days old) but with a concomitant increase in late-onset cases (7–89 days). 131
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Group B streptococci can also cause meningitis in adults. 132–135 Risk factors in adults include age older than 60 years, diabetes mellitus, pregnancy or the postpartum state, cardiac disease, collagen vascular diseases, malignancy, alcoholism, hepatic failure, renal failure, previous stroke, neurogenic bladder, decubitus ulcers, and corticosteroid therapy; in one review of group B streptococcal meningitis in adults, no underlying illnesses were found in 43% of patients. 133
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Some cases have been associated with disseminated strongyloidiasis in hyperinfection syndrome, a condition in which meningitis caused by enteric bacteria occurs secondary to seeding of the meninges during persistent or recurrent bacteremias associated with the migration of infective larvae. 144
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Meningitis caused by Staphylococcus aureus is usually found in early postneurosurgical or posttrauma patients and in those with CSF shunts; other underlying conditions include endocarditis, diabetes mellitus, alcoholism, chronic renal failure requiring hemodialysis, injection drug use, and malignancies. 145–148
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Staphylococcus epidermidis is the most common cause of meningitis in patients with CSF shunts (see Chapter 92).
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T. pallidum disseminates to the CNS during early infection. 166 The organism can be isolated by animal inoculation from the CSF of patients with primary syphilis, and CSF laboratory abnormalities are detected in 5% to 9% of patients with seronegative primary syphilis
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Clinical neurosyphilis can be divided into four distinct syndromes 166–168 : syphilitic meningitis, meningovascular syphilis, parenchymatous neurosyphilis, and gummatous neurosyphilis. Some overlap may be seen in the clinical and laboratory findings of these syndromes.
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The incidence of syphilitic meningitis is greatest in the first 2 years after infection and is estimated to occur in only 0.3% to 2.4% of untreated syphilis cases. In contrast, meningovascular syphilis is found in 10% to 12% of individuals with CNS involvement 169 and occurs months to years after syphilis acquisition (peak incidence, approximately 7 years).
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Parenchymatous neurosyphilis has two variants: general paresis and tabes dorsalis. Both are relatively rare today and do not become apparent until 10 to 20 years after the acquisition of infection.
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Gummas are late manifestations of tertiary syphilis and may occur anywhere; gummatous neurosyphilis is rare.
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In one report, 90% of patients with HIV with early syphilis undergoing lumbar puncture had evidence of CNS infection. 168
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The nervous system is eventually involved clinically in at least 10% to 15% of patients with Lyme disease, either while erythema migrans is still present or 1 to 6 months later. 170–172
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A 1992 study used PCR assay to detect spirochetal DNA in CSF samples from 8 of 12 patients with acute (<.
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Despite the hundreds of species of free-living amoebas that are known, only a few have been reported to infect humans. 169–173 The most important are in the genera Naegleria, Acanthamoeba, and Balamuthia
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Naegleria fowleri, the main protozoan causing primary amebic meningoencephalitis (PAM) in humans, has been recovered from lakes, puddles, pools, ponds, rivers, sewage sludge, tap water, air conditioner drains, and soil.
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Sporadic cases of PAM occur when persons, usually children and young adults, swim or play in water containing the amebas or when swimming pools or water supplies have become contaminated, often through failure of chlorination.
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Activities that increase insertion of water into the nasal cavities (e.g., water skiing and wakeboarding) may increase the risk for developing PAM. 173
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Infection of humans by larvae of the nematode A. cantonensis can lead to the development of an eosinophilic meningitis, and it is the most common cause of eosinophilic meningitis outside Europe and North America. 175–181 Humans become infected by eating infected intermediate hosts (i.e., mollusks, such as snails and slugs) or paratenic (i.e., freshwater prawns, crabs, frogs, and planaria) hosts or by eating food such as leafy green vegetables contaminated by these hosts.
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A. cantonensis is widespread, and human infection is fairly common and reported from many parts of the world (e.g., Thailand, India, Malaysia, Vietnam, Indonesia, Papua New Guinea, Taiwan, China and the Pacific Islands, including Hawaii).
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