Infectious Diseases of the Brain and Meninges

Overview


Meningitis and encephalitis can also appear in mixed forms: a meningeal infection can spread to the brain (and/or spinal cord), or vice versa, causing meningo(myelo)encephalitis. The latter term is only used if the patient unequivocally manifests clinical signs of both meningeal and cerebral involvement.


Localization and Nomenclature


The sites and nomenclature of infectious diseases of the CNS are summarized in ▶ Fig. 6.43.



9783131364524_c006_f043.eps


Fig. 6.43 Sites and nomenclature of intracranial (a) and spinal (b) infections.


The Meningitic Syndrome


The general features of the meningitic syndrome are as follows:




  • Headache.



  • Fever (though elderly and immune-deficient patients are often afebrile).



  • Nausea and vomiting due to intracranial hypertension.



  • Meningismus, which, in severe cases, may be evident as a spontaneous extended posture of the neck, or opisthotonus.



  • Positive meningeal signs, with the patient examined in the supine position:




    • Lasègue sign: passive elevation of an extended leg to 45 degrees (at most) induces shooting pain into the leg.



    • Brudzinski sign: passive neck flexion induces reflexive knee flexion.



    • Kernig sign: passive elevation of the extended legs induces reflexive knee flexion.


The clinical aspects of individual types of meningitis depend on the pathogen and the immune state of the host.


Meningitis can be classified as shown in ▶ Table 6.19.



































Table 6.19 Meningitic syndromes

Syndrome


Leukocyte count


Protein


Glucose


Lactate


Acute bacterial meningitis


100 to 1,000, mainly multinucleated


High


Low or very low


High


Acute viral meningitis


100, more mono- than multinucleated


Normal or mildly elevated


Normal or mildly diminished


Normal


Chronic meningitis


100, mainly mononuclear


High or very high


Low or very low


Normal or high


The Encephalitic Syndrome


The encephalitic, rather than meningitic, syndrome is characterized by focal neurologic and neuropsychological deficits as well as a variably severe impairment of consciousness. Encephalitis, like meningitis, can be of viral, bacterial, fungal, protozoal, or parasitic origin. Prion diseases are a special category of encephalitis. Encephalitis can also arise on an autoimmune or paraneoplastic basis; in such cases, it mainly affects the limbic system (see section ▶ 6.8.8).


The infectious processes that cause encephalitis often also involve other structures in the nervous system besides the brain (e.g., the peripheral nerves and plexuses, nerve roots, spinal cord, and meninges). In particular, the three important clinical varieties of spirochetal infection (syphilis, borreliosis, and leptospirosis) often present initially with meningitic or polyradiculitic/polyneuritic manifestations.


The general features of an encephalitic syndrome are as follows:




  • Fever.



  • Headache.



  • Impairment of consciousness.



  • Personality changes and neuropsychological abnormalities.



  • Epileptic seizures.



  • Focal neurologic deficits.


The diseases covered in this section are listed in ▶ Table 6.20.
















Table 6.20 Diseases presenting with a mainly meningitic or encephalitic syndrome

Meninigitic syndrome


Encephalitic syndrome


Acute meningitis




  • Acute bacterial meningitis



  • Acute viral meningitis


Chronic meningitis




  • Tuberculous meningitis



  • Fungal, protozoal, and parasitic meningitis



  • Meningitis due to sarcoidosis



  • Meningitis due to meningeal seeding with carcinoma or sarcoma (carcinomatous meningitis)



  • Extradural (parameningeal) chronic infection


Viral encephalitis




  • Herpes simplex encephalitis



  • ESME



  • HIV encephalitis



  • Zoster encephalitis


Fungal, protozoal, and parasitic encephalitis


(Meningo)encephalitis due to spirochetal infection




  • Neurosyphilis



  • Neuroborreliosis (Lyme disease)



  • leptospirosis


Encephalitis in prion disease




  • Creutzfeldt–Jakob disease


Encephalitis in slow viral disease


Noninfectious encephalitis




  • Autoimmune encephalitis



  • Paraneoplastic encephalitis


Abbreviations: ESME, early summer meningoencephalitis; HIV, human immunodeficiency virus.


General Diagnostic and Therapeutic Measures in Cases of Suspected CNS Infection


History The following should be specifically asked about:




  • Contact with animals (e.g., certain viruses, leptospira, Coxiella burnetii).



  • Tick bites, fleas, mites (borreliosis, early summer meningoencephalitis, rickettsiae).



  • Swimming in ponds (amebiasis).



  • Consumption of unpasteurized dairy products (listeriosis, brucellosis).



  • Past medical history (immune deficiency, diabetes, surgery, endocarditis, or recent pneumonia, mumps, or measles). The patient’s past illnesses may predispose to CNS infection with certain types of pathogen.


Physical examination




  • Meningismus (abnormal response to passive movement of the neck), neurologic examination.



  • Inspection: skin (petechiae, e.g., in meningococcal sepsis), oral cavity and throat (pharyngitis, tonsillitis, teeth, and gums).



  • Palpation: lymph nodes, trigeminal exit points (sinusitis as the source of CNS infection).



  • Auscultation of the heart and lungs.


Further procedure If the clinical signs warrant, blood cultures should be drawn.




  • No intracranial hypertension or focal deficit: CSF is obtained by LP and treatment is begun with antibiotics (directed against the most likely pathogen) and glucocorticoids (dexamethasone). The antibiotic treatment is tailored later based on the specific pathogen detected.



  • Presence of intracranial hypertension and/or focal deficits: immediate initiation of treatment with antibiotics and glucocorticoids (dexamethasone), then head MRI. An LP should not be performed until the signs of intracranial hypertension have subsided.


6.7.2 Acute Bacterial Meningitis


Pathogens and routes of infection The bacteria that cause bacterial meningitis can reach the meninges by any of three routes:




  • Hematogenous spread (e.g., from a focus of infection in the nasopharynx).



  • Continuous extension (e.g., from the middle ear or paranasal sinuses).



  • Direct contamination (through an open wound or CSF fistula).


The organisms that most commonly cause acute, purulent meningitis are:




  • In neonates, Escherichia coli, group B streptococci, and Listeria monocytogenes.



  • In children, Haemophilus influenzae (HIB), pneumococci, and meningococci (Neisseria meningitidis).



  • In adults, pneumococci, meningococci, and, less commonly, staphylococci and Gram-negative enterobacteria.




Practical Tip



If meningitis is suspected, the patient’s vaccination status should be determined: infants have usually been vaccinated against HIB. The Centers for Disease Control and Prevention (CDC) in the United States and the Standing Committee on Vaccination (STIKO) in Germany recommend vaccination of all small children and high-risk adults against pneumococci and group C meningococci.


Clinical features




Note



The clinical onset of purulent meningitis is usually acute or hyperacute, and patients very quickly become severely ill, usually with high fever and vomiting. The initiation of antibiotic therapy as rapidly as possible is essential for a good outcome.


The course of purulent meningitis is characterized by the meningitic signs and symptoms listed earlier, as well as by:




  • Myalgia, back pain.



  • Photophobia.



  • Epileptic seizures (40%; these may occur if the infection is mainly located over the cerebral convexity with irritation of the underlying brain parenchyma).



  • Cranial nerve deficits (10–20%, sometimes permanent deafness, particularly after pneumococcal infection).



  • Variably severe impairment of consciousness.



  • In infection with N. meningitidis, there may be petechial cutaneous hemorrhages and hemorrhagic necrosis of the adrenal cortex due to endotoxic shock (Waterhouse–Friderichsen syndrome).


Diagnostic evaluation The most important and most urgent components of the diagnostic evaluation are blood culture (at least two sets of aerobic and anaerobic cultures from two different veins) and CSF culture after the CSF has been obtained by LP. Whenever acute meningitis is suspected, an LP should be performed at once, unless there is clinical evidence of intracranial hypertension.


Laboratory findings: the CRP and ESR are elevated, and the differential white blood count may reveal leukocytosis (with mainly segmented granulocytes).


CSF examination enables confirmation of the diagnosis of meningitis and, in two-thirds of patients, demonstration of bacteria by Gram stain and identification of the pathogen by CSF culture.




Note



Typical CSF findings in bacterial meningitis:




  • Turbid CSF.



  • Florid granulocytic pleocytosis with 1,000 to several thousand cells/mm3.



  • High protein concentration (>2,000 mg/L).



  • Low glucose concentration (ratio of CSF to serum glucose concentration < 0.5).



  • High lactate concentration (>3.5 mval/L).


Treatment The treatment begins with antibiotic therapy, with a single drug or multiple drugs, chosen for their effectiveness against the most likely causative organism(s) in the given clinical setting (= empiric treatment).




  • Previously well children and adults with community-acquired meningitis are treated empirically at first with a third-generation cephalosporin (e.g., ceftriaxone) and ampicillin (which also covers Listeria).



  • Nosocomial infections and infections in parts of the world where penicillin-resistant pneumococci are common are treated, for example, with a combination of ceftriaxone and vancomycin.


Corticosteroids (dexamethasone) are given as well, as they have been shown to improve the clinical course. Once the pathogen has been identified in the blood or CSF culture (with antibiogram), the empirically chosen antibiotics can be replaced with specifically tailored ones.




Note



The antibiotic treatment of bacterial meningitis must be started immediately after the blood draw for culture and the LP—sometimes even before these are done and before the CT or MRI. The elapsed time up to the initiation of treatment is the most important prognostic factor.


Course and Prognosis Bacterial meningitis can have severe neurologic and general medical complications, including the following:




  • Malresorptive hydrocephalus.



  • Brain infarction and sinus vein thrombosis.



  • Cerebral edema.



  • Brain abscess.



  • Cochlear damage resulting in hearing loss.



  • Cranial nerve deficits.



  • General medical complications: pneumonia, septic shock, consumption coagulopathy.


The prognosis depends on the pathogenic organism. The mortality in meningitis due to Streptococcus pneumoniae is over 50%. Survivors often suffer from neurologic deficits including deafness.


Pneumococcal Meningitis


Pneumococci (S. pneumoniae) are Gram-positive diplococci; they are the commonest cause of bacterial meningitis in adults. The diagnosis is established by Gram stain, blood or CSF culture, or demonstration of the antigen in the blood or CSF. Vaccination is possible for infants as well as adults; it is recommended for persons with immune deficiency or chronic disease and for persons older than 60 years.


Meningococcal Meningitis


Meningococci (N. meningitidis) are Gram-negative diplococci; they are the commonest cause of bacterial meningitis in children and adolescents. The meningococcal antigen can be detected in the CSF or blood. In Germany, group B meningococci are the most common type (65–70%).




Note



The course of meningococcal infection can be complicated by the following:




  • Sepsis (35%).



  • Waterhouse–Friderichsen syndrome (15%), also known as adrenal apoplexy: fulminant meningococcal sepsis leading to adrenal dysfunction, petechiae (also called purpura), extensive skin necrosis, and disseminated intravascular coagulation. If untreated, patients with this condition die within hours.


Patients must be isolated for 24 hours after the beginning of antibiotic treatment, and their contacts should be given antibiotics prophylactically (e.g., rifampicin). Vaccination against group C meningococci is recommended for all infants, and vaccination against groups A and C is recommended for travelers to Africa (recommendations of the German vaccination authority [STIKO]). There is as yet no vaccine against group B. Meningococcal meningitis is a reportable illness: all cases (even suspected ones) and fatalities must be reported. Nasopharyngeal colonization with meningococci without any sign of illness is not reportable.


6.7.3 Acute Viral Meningitis: Aseptic or Lymphocytic Meningitis


Pathogens and routes of entry Several viruses can cause so-called aseptic or lymphocytic meningitis. The more common ones are enteroviruses (polio- and Coxsackie viruses), arboviruses, and HIV; other, rarer ones include lymphocytic choriomeningitis virus, CMV, type II herpesvirus, and the mumps, Epstein–Barr, and influenza viruses.


Clinical features The illness begins acutely (less commonly, subacutely) after a nonspecific prodromal stage with flulike or gastrointestinal symptoms. The main clinical manifestations are headache, fever, meningismus (often mild), and general symptoms such as fatigue and myalgia.


Diagnostic evaluation The causative virus is identified by serologic testing.


Treatment and course The natural course of aseptic meningitis is usually favorable, provided the brain is not involved (i.e., provided there is no encephalitic component). Antiviral treatment is given if the causative virus is one for which an effective treatment exists (a virustatic agent, e.g., acyclovir for herpes simplex virus or varicella zoster virus). Residual neurologic deficits, such as deafness, are rare.


6.7.4 Chronic Meningitis


Chronic meningitis is caused by different organisms from the pus-forming bacteria that cause acute meningitis, and therefore takes a less acute and dramatic course, at least initially: the meningitic symptoms arise gradually, often fluctuate, and, depending on the causative organism, may progressively worsen over a long period of time. Fever and other clinical and laboratory signs of infection (elevated ESR and CRP, blood count abnormalities, general symptoms such as fatigue and myalgia) are common but may be absent. There may be variably severe neurologic deficits. The spectrum of causative organisms is very wide. By definition, chronic meningitis lasts longer than 4 months. Fortunately, it is a rare condition.


Tuberculous Meningitis


Etiology and route of infection Mycobacterium tuberculosis bacilli reach the meninges by hematogenous spread, either directly from a primary complex (early generalization) or from a focus of tuberculosis in an internal organ (late generalization). The site of origin may be clinically silent.


Clinical features and pathogenesis Meningitic symptoms usually develop gradually. Febrile bouts and general symptoms are often but not always present. Because the infectious process typically centers on the base of the brain (so-called basal meningitis; ▶ Fig. 6.44), in contrast to bacterial meningitis, which is typically located around the cerebral convexities), cranial nerve palsies are common, particularly of the nerves of eye movement and the facial nerve. Moreover, arteritis of the cerebral vasculature may result in focal brain infarction. The protein concentration in CSF is typically markedly elevated, and gelatinous exudates in the subarachnoid space, including the basal cisterns, cause progressive fibrinous coating of the meninges and malresorptive hydrocephalus.



9783131364524_c006_f044.eps


Fig. 6.44 Tuberculous meningitis. (a) This T1-weighted MR image shows the typical meningeal contrast enhancement along the course of the middle cerebral artery (→). (b) Typical contrast enhancement surrounding the brainstem (→).


Diagnostic evaluation The most important part of the evaluation is the detection of the pathogen in the CSF or other bodily fluids (sputum, tracheal secretions, gastric juice, urine). In the past, the detection of mycobacteria in the CSF often required weeks of culture; it can now be done relatively quickly with PCR (polymerase chain reaction). Occasionally, a Ziehl–Neelsen stain of the CSF will directly and immediately reveal acid-fast bacilli (mycobacteria).




Note



CSF findings in tuberculous meningitis:




  • Initially granulocytic, then lymphocytic pleocytosis.



  • High CSF protein (1,000–5,000 mg/L), low glucose, high lactate.


Neuroimaging (CT, MRI) reveals pathologic lesions of multiple types (e.g., tuberculomas, infarcts, hydrocephalus, coated basal meninges).


Treatment and prognosis The treatment generally begins with a combination of four tuberculostatic drugs (isoniazid, rifampicin, pyrazinamide, and myambutol), followed by a combination of three drugs, and then of two, for at least 12 months. Untreated tuberculous meningitis is lethal.


Tuberculosis (confirmed or suspected) is a reportable illness.


Other Causes


Several other organisms can rarely cause chronic meningitis, usually accompanied by variably severe encephalitis. These include:




  • Fungi, mainly but not exclusively in immunodeficient patients; the causative species include Cryptococcus neoformans, Candida albicans, and Aspergillus.



  • Protozoa: T. gondii.



  • Parasites: Cysticercus, Echinococcus.


The noninfectious causes of the chronic meningitic syndrome include sarcoidosis, which, like tuberculous meningitis, is mainly found around the base of the brain ( ▶ Fig. 6.45), and seeding of the meninges with metastatic carcinoma or sarcoma (carcinomatous or sarcomatous meningitis).


6.7.5 Bacterial (Meningo)encephalitis: Spirochetal Infections


Neuroborreliosis (Lyme Disease)




































Table 6.21 The three stages of Lyme borreliosis

Stage


Manifestations


Local infection


Erythema chronicum migrans: a red, annular rash that expands centrifugally around the site of the tick bite, clearing in the central area as it grows outward


General symptoms (headache, fever, pain in the limbs, exhaustion)


Dissemination


General symptoms (fever, headache, diaphoresis)


Bannwarth syndrome (= acute neuroborreliosis: meningopolyradiculitis, facial palsy)


Lymphadenosis benigna cutis (hyperplasia of lymphatic cells, often visible as a reddish swelling of the earlobes)


“Migratory” arthritis and myalgia (affecting different joints one after another)


Late stagea


Acrodermatitis chronica atrophicans of Herxheimer (ACA)


Chronic, recurrent Lyme arthritis


Chronic neuroborreliosis: polyneuropathy, meningitis, encephalitis or encephalomyelitis, vasculitis of the cerebral vessels


Further inflammatory manifestations (e.g., heart, liver, sensory organs)


aIf untreated; rare after antibiotic treatment.


Etiology Borreliosis is called “Lyme disease” in North America (after the town of Lyme, Connecticut, in which an outbreak was described) and is caused there by Borrelia burgdorferi, a spirochete transmitted by bites of the tick Ixodes ricinus. Borrelia afzelii and Borrelia garinii cause borreliosis in Europe.


Clinical manifestations Borreliosis can involve the nervous system, joints, cardiovascular system, liver, and skin. Its clinical manifestations are equally varied and run through three stages ( ▶ Table 6.21). After transfer of the organism by a tick bite, some patients locally develop erythema chronicum migrans, a red, annular rash that expands centrifugally around the site of the tick bite, clearing in the central area as it grows outward. If the spirochetes are then disseminated systemically, headache, fever, arthralgia, and sometimes generalized lymphadenopathy will follow.



9783131364524_c006_f045.tif


Fig. 6.45 Sarcoidosis. This MR image of a 31-year-old woman with sarcoidosis shows infiltration of the basal meninges. There is marked signal abnormality in the basal ambient cistern.

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Dec 28, 2017 | Posted by in NEUROLOGY | Comments Off on Infectious Diseases of the Brain and Meninges
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