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Meningitis

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Meningitis ist der Name für eine Entzündung der schützenden äußeren Hüllen von Gehirn und Rückenmark.[1] Die Erkrankung wird durch Viren, Bakterien oder andere Mikroorganismen verursacht. In seltenen Fällen kann eine Entzündungsreaktion der Hirnhäute auch durch Medikamente verursacht werden.[2] Eine Meningitis kann aufgrund der unmittelbaren Nähe der Entzündung zu Gehirn und Rückenmark lebensbedrohlich sein, sie wird deshalb immer als medizinischer Notfall angesehen.[1][3] Die häufigsten Symptome einer Meningitis sind Kopfschmerzen und Nackensteifigkeit, verbunden mit Fieber, Verwirrheit oder Bewußtseinsminderung, Übelkeit und eine Überempfindlichkeit gegen Licht und laute Geräusche. Vor allem Kinder können unspezifische Symtome zeigen, wie Reizbarkeit und Benommenheit. Ein Hautausschlag kann ein Hinweis auf das Vorliegen einer Meningokokkenmeningitis sein.[1][4] Üblicherweise wird das Vorliegen der Krankheit durch eine Lumbalpunktion bestätigt oder ausgeschlossen. Dabei wird eine Injektionskanüle in den Lumbalkanal geschoben, um eine Liquorprobe zur Untersuchung zu entnehmen.[3] Eine Meningitits wird durch die rechtzeitige Gabe von Antibiotika und falls nötig antiviralen Substanzen behandelt. Kortikosteroide können zur Verhütung von Komplikationen hilfreich sein.[3][4] Eine Meningitis kann, vor allem, wenn sie nicht rechtzeitig erkannt und behandelt wird, zu schwerwiegenden Folgeschäden wie Taubheit, Epilepsie, einem Hydrozephalus oder kognitiven Beeinträchtigungen führen.[1][4] Für einige Formen der Meningitis (vor allem solche, die durch Meningococcen, Hemophilus influenzae Typ B, Pneumococcen und Mumpsviren verursacht werden) existiert eine Impfung.[1]

Klinische Zeichen und klinische Symptome

Bei Erwachsenen ist ein schwerer Kopfschmerz das häufigste Symptom der Erkrankung und tritt in über 90% aller Fälle einer bakteriellen Meningitis auf. Es wird meist von einer Nackensteifigkeit begleitet.[5] Die klassische Trias klinischer Zeichen einer Meningitis besteht aus Nackensteifigkeit, hohem Fieber und Bewußtseinsminderung. Man findet diese Trias jedoch nur in ca. 45% der Fälle einer bakteriellen Meningitis.[5][6] Wenn keines der drei klinischen Zeichen vorliegt ist eine Meningitis sehr unwahrscheinlich.[6] Andere klinische Zeichen, die häufig bei einer Meningitis vorkommen sind eine Photophobie und eine Geräuschempfindlichkeit. Kleine Kinder zeigen häufig keine charakteristischen Symptome, sie sind manchmal nur reizbar und kränklich.[1] Kleinkinder bis zu einem Alter von 6 Monaten zeigen manchmal eine Vorwölbung der Fontanelle, Schmerzen in den Beinen, kalte Extremitäten und eine Blässe.[7] Eine Nackensteifigkeit findet man bei 70% der erwachsenen Patienten mit einer bakteriellen Meningitis.[6] Weitere Hinweise für einen Meningismus sind positive Kernig- und Brudzinski-Zeichen. Dabei finden man die Patienten häufig im Bett mit angezogenen Beinen liegend, wobei sie die Knie nicht strecken können (Kernig-Zeichen). Wenn es beim Vorbeugen des Kopfes zu einem unwillkürlichen Anziehen der Beine kommt, spricht man vom Brudzinski-Zeichen. Obwohl diese Zeichen im klinischen Alltag häufig angewendet werden, ist ihre Sensitivität begrenzt.[6][8] Sie haben allerdings eine hohe Spezivität, das heißt, sie kommen selten bei anderen Erkrankungen vor.[6] Ein anderer Test, das "jolt accentuation maneuver" kann ebenfalls hilfreich sein. Wenn die Patienten den Kopf horizontal drehen und dies den Kopfschmerz nicht verschlimmert ist eine Meningitis unwahrscheinlich.[6] Wenn die Meningitis durch das Bakterium Neisseria meningitidis verursacht wird (Meningokokkenmeningitis), dann kann diese durch das Auftreten einer Purpura charakterisiert sein.[7] Der Ausschlag bsteht aus zahlreichen kleinen irregulären roten oder lilafarbenen Flecken (Petechien), am Körperstamm, den unteren Extermitäten, Schleimhäuten, Konjunktiven und gelegentlich den Handinnenflächen oder Fußsohlen. Petechien kann man nicht "wegdrücken", sie verschwinden nicht durch einen Druck auf die Haut mit dem Finder oder besser mit einem Glasspatel. Obwohl der Ausschlag bei einer Meningokokkenmeningitis nicht immer vorkommt, ist er doch recht spezifisch für die Erkrankung, kommt aber auch bei anderen Erregern vor.[1] Charakteristische Hautausschläge bei einer Meningitis gibt es auch bei solchen Formen die durch die Erreger der Hand-Fuß-Mund-Krankheit und bei der Herpes simplex-Meningoenzephalititden auftreten.[9]

Komplikationen im Frühverlauf

Das Foto zeigt ein Kind mit einem sehr schweren Verlauf einer Meningokokkenmeningitis. Die Petechien entwickelten sich schnell zu Gangränen und erforderten die Amputation aller Extremitäten. Die Patientin Charlotte Cleverley-Bisman, überlebte die Erkrankung und wurde als "Baby Charlotte" im Rahmen einer Meningitis-Impfkampagnie in Neuseeland bekannt.

Patienten mit einer Meningitis können im Frühverlauf der Erkrankung besondere Komplikationen erleiden. Diese Komplikationen erfordern eine besondere Behandlung und zeigen manchmal eine ungünstige Prognose an. Die Infektion kann eine Sepsis mit einem sog. systemischen inflammatorischen Response-Syndrom mit Blutdruck-Abfall, Tachykardie, Entgleisung der Körpertemperatur und Tachypnoe erzeugen. Der Blutdruckabfall kann früh im Verlauf der Erkrankung auftreten, vor allem bei einer Meningokokkenmeningitis und zu einer Durchblutungsstörung verschiedener Organe führen.[10]

Eine Verbrauchskoagulopathie ist das Resultat einer überschiessenden Gerinnungsaktivierung und kann einerseits die Blutversorgung ganzer Organe stören und andererseits das Blutungsrisiko erheblich vergrößern. Bei einer Meningokokkenmeningitis können Gangräne der Extremitäten entstehen.[1] Infektionen mit Meningokokken und Pneumokokken können Einblutungen der Nebenniere mit der Folge eines Waterhouse-Friderichsen-Syndrom verursachen, das nicht selten tödlich verläuft.[11] Ein weiteres Problem ist die Entwicklung eines Hirnödems, mit ansteigendem Hirndruck und dem Risiko einer Einklemmung durch die Hirnschwellung. Dies kann von einer Bewußtseinsminderung mit Aufhebung der Pupillenreflexe, Atemstörung und einer abnormen Körperhaltung begleitet sein.[12] Eine Infektion des Gehirngewebes kann auch zu einer Liquorabflussbehinderung mit der Folge eines Hydrocephalus führen. [13] Epileptische Anfälle können aus unterschiedlichen Gründen auftreten und sind bei Kindern eine häufige Komplikation im Frühverlauf (30% der Fälle) und geben keinen Hinweis auf die zugrundeliegend Störung. [14] Krampfanfälle nehmen manchmal ihren Ausgang von Hirnarealen, die komprimiert oder entzündet sind.[15] Partielle Anfälle (das sind Anfallsformen, die zu motorischen Entäußerungen in einer Extremität oder in Teilen des Körpers führen), ein Anfallsstatus, spät eintretende Anfälle und solche, die medikamentös nicht oder nur schwer beherrschbar sind, können ein Hinweis für eine ungünstige Langzeitprognose sein.[16] Eine Meningitis kann auch zu Beeinträchtigungen der Hirnnerven und somit zu Störungen der Kontrolle der Augen- Gesichts- und Kopfbewegungen, Schlucken und Hören führen.[17][18] Sehstörungen und Hörminderung können nach einer Meningitis anhaltend gestört sein. .[1] Eine Entzündung des Gehirngewebes (Enzephalitis) oder der Hirngefäße (eine sog. Zerebrale Vaskulitis), können ebenso wie die Entstehung einer Thrombose der Hirnvenen (Sinusvenenthrombose), zu einem fokalen neurologischen Defizit mit Lähmung, Sensibilitätsstörungen und Bewegungsstörungen in den von den betroffenen Hirnregionen versorgten Körperarealen führen.[19][20]

Ursachen

Eine Meningitis wird gewöhnlich durch die Infektion verursacht. In den meisten Fällen können Infektionen mit Viren,[6] Bakterien, Pilze, und Parasiten festgestellt werden.[2] Eine Meningitis kann auch durch verschiedene nicht-infektiöse Mechanismen verursacht werden.[2] Alle Formen bei denen kein bakterieller Erreger nachgewiesen werden kann werden allgemein als aseptische Meningitis bezeichnet. Das ist der Fall bei viraler Ursache, aber auch bei anbehandelten bakteriellen Meningitiden, bei denen sich keine Bakterien mehr in der Hirnhaut finden, oder aber auch bei hirnhautnahen Infektionen (beispielsweise einer Sinusitis). Eine Endokarditis (Infektion der Herzklappe mit Aussat von Bakterien in den Blutstrom) kann ebenfalls die Ursache einer aseptischen Meningitis sein.


Aseptic meningitis may also result from infection with Spirochäten, a type of bacteria that includes Treponema pallidum (the cause of Syphilis) and Borrelia burgdorferi (known for causing Lyme-Borreliose). Meningitis may be encountered in [[|Malaria|zerebrale Malaria]] (malaria infecting the brain). Meningitis durch Pilze, e.g. due to Cryptococcus neoformans, is typically seen in people with immune deficiency such as AIDS. Amoeben Meningitis, meningitis due to infection with amoebae such as Naegleria fowleri, is contracted from freshwater sources.

[2]

PAME = eitrige Meningoenzephalitis, nicht aseptisch![21]


Bakterien

Generell gilt, dass es vom Alter der Patienten abhängt, welche bakteriellen Erreger bevorzugt eine Meningitis verursachen. Bei Frühgeborenen und Säuglingen bis zu einem Alter von 3 Monaten , werden häufig Streptokokken gefunden, vor allem der Subtyp III der Serogruppe B (Gruppe B-Streptokokken (GBS)), der vor allem innerhalb der ersten Lebenswochen als Meningitisverursacher im Rahmen einer Neugeborenensepsis in Frage kommt. Sie haben ihr natürliches Reservoir im Magen-Darm-Trakt (Gastrointestinaltrakt). Allerdings kann auch die Scheide intermittierend, chronisch oder vorübergehend mit GBS besiedelt sein.[22][23] Außerdem findet man in dieser Altersgruppe Kolibakterien, die ebenfalls den Gastrointestinaltrakt besiedeln. Neugeborene können auch durch Listeria monocytogenes (vor allem Serotyp IVb), ein Erreger der auch epidemisch auftritt, erkranken. Ältere Kinder erkranken eher an Neisseria meningitidis (Meningokokken), Streptococcus pneumoniae (Serotypen 6, 9, 14, 18 und 23) und Kinder unter fünf Jahren an Haemophilus influenzae Typ B.[1][3] Bei Erwachsenen verursachen N. meningitidis und S. pneumoniae zusammen ca. 80% aller Fälle einer Meningitis. Mit steigendem Alter (nach dem 50. Lebensjahr) finden sich vermehrt L. monocytogenes.[3][4]


Recent Schädel-Hirn-Traumata to the skull gives bacteria in the nasal cavity the potential to enter the meningeal space. Similarly, individuals with a Cerebralshunt or related device (such as an extraventricular drain or Ommaya-Reservoir) are at increased risk of infection through those devices. In these cases, infections with Staphylokokken are more likely, as well as infections by Pseudomonas and other Gram-negative bacilli.[3] The same pathogens are also more common in those with Immundefekt.[1] In a small proportion of people, an infection in the head and neck area, such as Akute Mittelohrentzündung or Mastoiditis, can lead to meningitis.[3] Recipients of Cochleaimplantats for hearing loss are at an increased risk of pneumococcal meningitis.[24]

Tuberculöse Meningitis, meningitis due to infection with Mycobacterium tuberculosis, is more common in those from countries where Tuberkulose is common, but is also encountered in those with immune problems, such as AIDS.[25]

Recurrent bacterial meningitis may be caused by persisting anatomical defects, either Kongenital or acquired, or by disorders of the Immunsystem.[26] Anatomical defects allow continuity between the external environment and the Nervensystem. The most common cause of recurrent meningitis is Schädelfraktur,[26] particularly fractures that affect the base of the brain or extend towards the Nasennebenhöhlen and Felsenbein.[26] A literature review of 363 reported cases of recurrent meningitis showed that 59% of cases are due to such anatomical abnormalities, 36% due to immune deficiencies (such as [[|Gerinnungsstörung|complement deficiency]], which predisposes especially to recurrent meningococcal meningitis), and 5% due to ongoing infections in areas adjacent to the meninges.[26]

Viren

Obwohl neurotrope Viren überwiegend eine Enzephalitis hervorrufen, können manche Virusspezies auch Ursache einer Meningoenzephalitis, Enzephalomyelitis und Meningitis sein. Als Abgrenzung zur klassischen bakteriellen Meningitis werden die viralen Meningitiden auch als lymphozytäre Meningitis bezeichnet. Nur wenige Viren verursachen ausschließlich eine Meningitis wie das durch Nagetiere übertragene Virus der Lymphozytären Choriomeningitis (LCMV). Eine Meningitis als Mischform oder als fortgeschrittener Infektionsverlauf wird bei immunkompetenten Erwachsenen am häufigsten durch Enteroviren wie dem Coxsackie-Virus und den ECHO-Viren verursacht. Als Meningitis können sich auch Infektionen oder Reaktivierungen verschiedener Herpesviren manifestieren, so das Herpes-simplex-Virus 1, seltener das Herpes-simplex-Virus 2, Humane Herpesvirus 6 und Humane Herpesvirus 7. Die Herpes-simplex-Viren vermögen als einzige virale Erreger auch eine chronisch verlaufende Meningitis hervorzurufen. Bei schwerer zellulärer Immundefizienz (beispielsweise nach Knochenmarktransplantation oder bei AIDS im Stadium C3) vermögen auch das Cytomegalievirus und das Epstein-Barr-Virus eine Meningoenzephalitis oder Meningitis auszulösen. Als typische Komplikationen treten diese auch bei Infektionen mit dem Masernvirus, dem Mumpsvirus und dem Rötelnvirus auf. Bei Hantaviren und dem Parvovirus B19[27] ist eine meningitische Mitbeteiligung beschrieben. Im Rahmen einer frischen Infektion kann das Humane Immundefizienz-Virus neben einer Enzephalitis auch eine Meningitis hervorrufen (Akutes retrovirales Syndrom).

Verschiedene durch Gliederfüßer wie Stechmücken und Zecken übertragene Viren (Arboviren) können neben einer Enzephalitis auch eine Meningitis verursachen. Zu ihnen gehören das FSME-Virus, Japanische-Enzephalitis-Virus, West-Nil-Virus, Rifttal-Fieber-Virus, Denguevirus und verschiedene Subtypen des Sandmückenfiebervirus wie das Toskana-Virus.[28]

Parasitäre Ursachen

Eine parasitäre Ursache wird oft angenommen, wenn sich eine Eosinophilie im Liquor cerebrospinalis findet. Am häufigsten finden sich dabei Angiostrongylus cantonensis und Fadenwürmer (Gnathostoma spinigerum); eine dabei durchgeführte Behandelung mit Albendazol ist von fraglicher Wirksamkeit.[29]

Als seltene Ausschlußdiagnosen gelten Tuberkulose, Syphilis, Kryptokokkose und die Kokzidioidomykose.[30][31][32]

Non-infectious

Meningitis may occur as the result of several non-infectious causes: spread of cancer to the meninges (malignant meningitis)[33] and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins).[34] It may also be caused by several inflammatory conditions such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall) such as Behçet's disease.[2] Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space.[2][26] Mollaret's meningitis is a syndrome of recurring episodes of aseptic meningitis; it is now thought to be caused by herpes simplex virus type 2. Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated.[2]

Mechanism

The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a very delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes, and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull.

In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live upon mucous surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood-brain barrier is vulnerable—such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults.[1] Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the dura mater can be identified.[1]

The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entrance of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood-brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges, and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to a decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to an increased intracranial pressure; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain, and brain cells are deprived of oxygen and undergo apoptosis (automated cell death).[1]

It is recognized that administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune system's response to this phenomenon.[1][4]

Diagnosis

CSF findings in different forms of meningitis[35]
Type of meningitis   Glucose   Protein Cells
Acute bacterial low high PMNs,
often > 300/mm³
Acute viral normal normal or high mononuclear,
< 300/mm³
Tuberculous low high mononuclear and
PMNs, < 300/mm³
Fungal low high < 300/mm³
Malignant low high usually
mononuclear

Blood tests and imaging

In someone suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive protein, complete blood count), as well as blood cultures.[3][36]

The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid through lumbar puncture (LP, spinal tap).[37] However, lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure (ICP) is elevated, as it may lead to brain herniation. If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a CT or MRI scan is recommended prior to the lumbar puncture.[3][36][38] This applies in 45% of all adult cases.[4] If a CT or MRI is required before LP, or if LP proves difficult, professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment,[3] especially if this may be longer than 30 minutes.[36][38] Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.[1]

In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia is common in bacterial meningitis, due to a combination of factors including dehydration, the inappropriate excretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration.[4][39]

Lumbar puncture

A lumbar puncture is done by positioning the patient, usually lying on the side, applying local anesthetic, and inserting a needle into the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using a manometer. The pressure is normally between 6 and 18 cm water (cmH2O);[37] in bacterial meningitis the pressure is typically elevated.[3][36] The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis.[3]

Gram stain of meningococci from a culture showing Gram negative (pink) bacteria, often in pairs

The CSF sample is examined for presence and types of white blood cells, red blood cells, protein content and glucose level.[3] Gram staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken, and Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture of the sample is more sensitive (it identifies the organism in 70–85% of cases) but results can take up to 48 hours to become available.[3] The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant),[3] although in the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.[40]

The concentration of glucose in CSF is normally above 40% that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis;[37] in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal.[3] High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count.[37]

Various more specialized tests may be used to distinguish between various types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli and group B streptococci; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful.[3] Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus, herpes simplex virus 2 and mumps in those not vaccinated for this).[9] Serology (identification of antibodies to viruses) may be useful in viral meningitis.[9] If tuberculous meningitis is suspected, the sample is processed for Ziehl-Neelsen stain, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly.[25] Diagnosis of cryptococcal meningitis can be made at low cost using an India ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive, particularly in persons with AIDS.[41][42][43]

A diagnostic and therapeutic conundrum is the "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR).[9]

Postmortem

Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia mater and arachnoid layers of the meninges covering the brain and spinal cord. Neutrophil leucocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord, may be surrounded with pus—as may the meningeal vessels.[44]

Prevention

For some causes of meningitis, prophylaxis can be provided in the long term with vaccine, or in the short term with antibiotics.

Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries where the disease burden is highest, however, the vaccine is still too expensive.[45][46] Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps.[9]

Meningococcus vaccines exist against groups A, C, W135 and Y.[47] In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially.[45] A quadrivalent vaccine now exists, which combines all four vaccines. Immunization with the ACW135Y vaccine against four strains is now a visa requirement for taking part in the Hajj.[48] Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weak response from the immune system, or cross-react with normal human proteins.[45][47] Still, some countries (New Zealand, Cuba, Norway and Chile) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules.[47]

Routine vaccination against Streptococcus pneumoniae with the pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis.[45][49] The pneumococcal polysaccharide vaccine, which covers 23 strains, is only administered in certain groups (e.g. those who have had a splenectomy, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children.[49]

Childhood vaccination with Bacillus Calmette-Guérin has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine.[45]

Short-term antibiotic prophylaxis is also a method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, prophylactic treatment of close contacts with antibiotics (e.g. rifampicin, ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition, but does not protect against future infections.[36][50]

Treatment

Initial treatment

Meningitis is potentially life-threatening and has a high mortality rate if untreated;[3] delay in treatment has been associated with a poorer outcome.[4] Thus treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted.[38] If meningococcal disease is suspected in primary care, guidelines recommend that benzylpenicillin be administered before transfer to hospital.[7] Intravenous fluids should be administered if hypotension (low blood pressure) or shock are present.[38] Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early,[38] as well as admission to an intensive care unit if deemed necessary.[4]

Mechanical ventilation may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g. mannitol).[4] Seizures are treated with anticonvulsants.[4] Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral shunt.[4]

Bacterial meningitis

Antibiotics

Structural formula of ceftriaxone, one of the third-generation cefalosporin antibiotics recommended for the initial treatment of bacterial meningitis.

Empiric antibiotics (treatment without exact diagnosis) must be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place. For instance, in the United Kingdom empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone.[36][38] In the USA, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended.[3][4][36] Empirical therapy may be chosen on the basis of the age of the patient, whether the infection was preceded by head injury, whether the patient has undergone neurosurgery and whether or not a cerebral shunt is present.[3] For instance, in young children and those over 50 years of age, as well as those who are immunocompromised, addition of ampicillin is recommended to cover Listeria monocytogenes.[3][36] Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens.[3]

The results of the CSF culture generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics.[3] For an antibiotic to be effective in meningitis, it must not only be active against the pathogenic bacterium, but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on meningitis patients in clinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits.[3]

Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer.[25] In tuberculous meningitis there is a strong evidence base for treatment with corticosteroids, although this evidence is restricted to those without AIDS.[51]

Steroids

Adjuvant treatment with corticosteroids (usually dexamethasone) reduces rates of mortality, severe hearing loss and neurological damage in adolescents and adults from high income countries which have low rates of HIV.[52] The likely mechanism is suppression of overactive inflammation.[53] Professional guidelines therefore recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days.[36][38] Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified.[3][36]

Adjuvant corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income countries is not supported by evidence; the reason for this discrepancy is not clear.[54] Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis,[3][55] the incidence of which has decreased dramatically since the introduction of the Hib vaccine. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae and only if given prior to the first dose of antibiotics, whereas other uses are controversial.[3]

Viral and fungal meningitis

Viral meningitis typically requires supportive therapy only; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as aciclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective.[9] Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics.[56] Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of highly dosed antifungals, such as amphotericin B and flucytosine.[41][57]

Prognosis

Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortality (risk of death) from bacterial meningitis depends on the age of the patient and the underlying cause. Of the newborn patients, 20–30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19–37% in adults.[1][4] Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid,[1] the severity of the generalized illness, decreased level of consciousness or abnormally low count of white blood cells in the CSF.[4] Meningitis caused by H. influenza and meningococci has a better prognosis compared to cases caused by group B streptococci, coliforms and S. pneumoniae.[1] In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.[4]

In children there are several potential disabilities which result from damage to the nervous system. Sensorineural hearing loss, epilepsy, learning and behavioral difficulties, as well as decreased intelligence, occur in about 15% of survivors.[1] Some of the hearing loss may be reversible.[58] In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%).[4]

Epidemiology

Demography of meningococcal meningitis.
  • meningitis belt
  • epidemic zones
  • sporadic cases only
    • Disability-adjusted life year for meningitis per 100,000 inhabitants in 2002.[59]
  • no data
  • ≤ 10
  • 10-25
  • 25-50
  • 50-75
  • 75-100
  • 100-200
  • 200-300
  • 300-400
  • 400-500
  • 500-1000
  • 1000-1500
  • ≥ 1500

    • Although meningitis is a notifiable disease in many countries, the exact incidence rate is unknown.[9] Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually. In sub-Saharan Africa, large epidemics of meningococcal meningitis occur in the dry season, leading to it being labeled the "meningitis belt"; annual rates of 500 cases per 100,000 are encountered in this area, which is poorly served by medical care. These cases are predominantly caused by meningococci.[6] The most recent epidemic, affecting Nigeria, Niger, Mali and Burkina Faso, started in January 2009 and is ongoing.[60]

    Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, college campuses[1] and the annual Hajj pilgrimage.[48]

    There are significant differences in the local distribution of causes for bacterial meningitis. For instance, N. meningitides groups B and C cause most disease episodes in Europe, while group A meningococci are more common in China and amongst Hajj pilgrims. In the "meningitis belt" of Africa, group A and C meningococci cause most of the outbreaks. Group W135 meningococci have caused several recent epidemics in Africa and during the Hajj.[45] These differences are expected to change further as vaccines against common strains are introduced.[45]

    History

    Some suggest that Hippocrates may have realized the existence of meningitis,[6] and it seems that meningism was known to pre-Renaissance physicians such as Avicenna.[61] The description of tuberculous meningitis, then called "dropsy in the brain", is often attributed to Edinburgh physician Sir Robert Whytt in a posthumous report that appeared in 1768, although the link with tuberculosis and its pathogen was not made until the next century.[61][62] It appears that epidemic meningitis is a relatively recent phenomenon.[63] The first recorded major outbreak occurred in Geneva in 1805.[63][64] Several other epidemics in Europe and the United States were described shortly afterward, and the first report of an epidemic in Africa appeared in 1840. African epidemics became much more common in the 20th century, starting with a major epidemic sweeping Nigeria and Ghana in 1905–1908.[63]

    The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum, who in 1887 described the meningococcus.[65] Mortality from meningitis was very high (over 90%) in early reports. In 1906, antiserum was produced in horses; this was developed further by the American scientist Simon Flexner and markedly decreased mortality from meningococcal disease.[66][67] In 1944, penicillin was first reported to be effective in meningitis.[68] The introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of meningitis associated with this pathogen,[46] and in 2002 evidence emerged that treatment with steroids could improve the prognosis of bacterial meningitis.[53][54][67]

    Einzelnachweise

    1. ↑ a b c d e f g h i j k l m n o p q r s t u Sáez-Llorens X, McCracken GH: Bacterial meningitis in children. In: Lancet. 361. Jahrgang, Nr. 9375, Juni 2003, S. 2139–48, doi:10.1016/S0140-6736(03)13693-8, PMID 12826449.
    2. ↑ a b c d e f g Ginsberg L: Difficult and recurrent meningitis. In: Journal of Neurology, Neurosurgery, and Psychiatry. 75 Suppl 1. Jahrgang, März 2004, S. i16–21, doi:10.1136/jnnp.2003.034272, PMID 14978146, PMC 1765649 (freier Volltext) – (bmj.com).
    3. ↑ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Tunkel AR, Hartman BJ, Kaplan SL, et al.: Practice guidelines for the management of bacterial meningitis. In: Clinical Infectious Diseases. 39. Jahrgang, Nr. 9, November 2004, S. 1267–84, doi:10.1086/425368, PMID 15494903 (uchicago.edu).
    4. ↑ a b c d e f g h i j k l m n o p q van de Beek D, de Gans J, Tunkel AR, Wijdicks EF: Community-acquired bacterial meningitis in adults. In: The New England Journal of Medicine. 354. Jahrgang, Nr. 1, Januar 2006, S. 44–53, doi:10.1056/NEJMra052116, PMID 16394301.
    5. ↑ a b van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M: Clinical features and prognostic factors in adults with bacterial meningitis. In: The New England Journal of Medicine. 351. Jahrgang, Nr. 18, Oktober 2004, S. 1849–59, doi:10.1056/NEJMoa040845, PMID 15509818 (nejm.org).
    6. ↑ a b c d e f g h i Attia J, Hatala R, Cook DJ, Wong JG: The rational clinical examination. Does this adult patient have acute meningitis? In: JAMA. 282. Jahrgang, Nr. 2, Juli 1999, S. 175–81, doi:10.1001/jama.282.2.175, PMID 10411200.
    7. ↑ a b c Theilen U, Wilson L, Wilson G, Beattie JO, Qureshi S, Simpson D: Management of invasive meningococcal disease in children and young people: Summary of SIGN guidelines. In: BMJ (Clinical research ed.). 336. Jahrgang, Nr. 7657, Juni 2008, S. 1367–70, doi:10.1136/bmj.a129, PMID 18556318, PMC 2427067 (freier Volltext). Full guideline page
    8. ↑ Thomas KE, Hasbun R, Jekel J, Quagliarello VJ: The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningitis. In: Clinical Infectious Diseases. 35. Jahrgang, Nr. 1, Juli 2002, S. 46–52, doi:10.1086/340979, PMID 12060874 (uchicago.edu).
    9. ↑ a b c d e f g Logan SA, MacMahon E: Viral meningitis. In: BMJ (Clinical research ed.). 336. Jahrgang, Nr. 7634, Januar 2008, S. 36–40, doi:10.1136/bmj.39409.673657.AE, PMID 18174598, PMC 2174764 (freier Volltext).
    10. ↑ Sáez-Llorens X, McCracken GH: Bacterial meningitis in children. Lancet vol. 361/9375, S. 2139–48 2003 PMID 12826449
    11. ↑ Varon J, Chen K, Sternbach GL: Rupert Waterhouse and Carl Friderichsen: adrenal apoplexy. In: J Emerg Med vol. 16/4 S. 643–7, 1998 PMID 9696186
    12. ↑ van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. In: The New England Journal of Medicine vol. 354/1 S. 44–53, 2006, PMID 16394301
    13. ↑ van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. In: The New England Journal of Medicine vol. 354/1 S. 44–53, 2006, PMID 16394301
    14. ↑ Tunkel AR, Hartman BJ, Kaplan SL, et al.: Practice guidelines for the management of bacterial meningitis. In: Clinical Infectious Diseases, vol. 39/9 S. 1267–84, 2004, PMID 15494903
    15. ↑ van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. In: The New England Journal of Medicine vol. 354/1 S. 44–53, 2006, PMID 16394301
    16. ↑ Sáez-Llorens X, McCracken GH: Bacterial meningitis in children. Lancet vol. 361/9375, S. 2139–48 2003 PMID 12826449
    17. ↑ Sáez-Llorens X, McCracken GH: Bacterial meningitis in children. Lancet vol. 361/9375, S. 2139–48 2003 PMID 12826449
    18. ↑ Attia J, Hatala R, Cook DJ, Wong JG: The rational clinical examination. Does this adult patient have acute meningitis? In: JAMA vol. 282/2 S. 175–81, 1999 PMID 10411200
    19. ↑ Sáez-Llorens X, McCracken GH: Bacterial meningitis in children. Lancet vol. 361/9375, S. 2139–48 2003 PMID 12826449
    20. ↑ van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. In: The New England Journal of Medicine vol. 354/1 S. 44–53, 2006, PMID 16394301
    21. ↑ Wiwanitkit V. Review of clinical presentations in Thai patients with primary amoebic meningoencephalitis. MedGenMed. 2004 Mar 8;6(1):2. Review. PMID 15208515
    22. ↑ S1-Leitlinie Prophylaxe der Neugeborensepsis - frühe Form - durch Streptokokken der Gruppe B der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI), Deutschen Gesellschaft für Gynäkologie und Geburtshilfe, Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI), und Deutschen Gesellschaft für Perinatale Medizin (DGPM). In: AWMF online (Stand 7/2008)
    23. ↑ Anna Katharina Bürckstümmer: Streptococcus agalactiae bei Schwangeren und Neugeborenen: Prävalenz und Transmission sowie Serotypen und molekulargenetische Charakteristika. Dissertation, Albert-Ludwigs-Universität Freiburg 2004 online (PDF-Dokument; 1,3 MB)
    24. ↑ Wei BP, Robins-Browne RM, Shepherd RK, Clark GM, O'Leary SJ: Can we prevent cochlear implant recipients from developing pneumococcal meningitis? In: Clin. Infect. Dis. 46. Jahrgang, Nr. 1, Januar 2008, S. e1–7, doi:10.1086/524083, PMID 18171202 (uchicago.edu).
    25. ↑ a b c Thwaites G, Chau TT, Mai NT, Drobniewski F, McAdam K, Farrar J: Tuberculous meningitis. In: Journal of Neurology, Neurosurgery, and Psychiatry. 68. Jahrgang, Nr. 3, März 2000, S. 289–99, doi:10.1136/jnnp.68.3.289, PMID 10675209, PMC 1736815 (freier Volltext) – (bmj.com).
    26. ↑ a b c d e Tebruegge M, Curtis N: Epidemiology, etiology, pathogenesis, and diagnosis of recurrent bacterial meningitis. In: Clinical Microbiology Reviews. 21. Jahrgang, Nr. 3, Juli 2008, S. 519–37, doi:10.1128/CMR.00009-08, PMID 18625686, PMC 2493086 (freier Volltext).
    27. ↑ Douvoyiannis M, Litman N, Goldman DL: Neurologic manifestations associated with parvovirus B19 infection. Clin. Infect. Dis. (2009) 48(12): S. 1713-1723 PMID 19441978
    28. ↑ H. W. Doerr, W. H. Gerlich (Hg.): Medizinische Virologie, 2. Auflage Stuttgart 2010 ISBN 978-3-13-113962-7, S. 206ff
    29. ↑ {{Chotmongkol V.: Comparison of prednisolone plus albendazole with prednisolone alone for treatment of patients with eosinophilic meningitis.. In: Am J Trop Med Hyg, 2009 /81/3, S.443ff., PMID 19706911
    30. ↑ Panackel C., e.a.: Eosinophilic meningitis due to Angiostrongylus cantonensis. In: Ind J Med Microbio, 2006/24/3, S., 220ff.m PMID 16912445
    31. ↑ Weller P. F., e.a.: Eosinophilic meningitis. In: Semin Neurol, 1993/13/2, S.161–8, PMID 8356350
    32. ↑ Schermoly M. J., e.a.: Eosinophilia in coccidioidomycosis. In: Arch. Intern. Med., 1988/148/4, S.895–6, PMID 3355309
    33. ↑ Chamberlain MC: Neoplastic meningitis. In: Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology. 23. Jahrgang, Nr. 15, Mai 2005, S. 3605–13, doi:10.1200/JCO.2005.01.131, PMID 15908671.
    34. ↑ Moris G, Garcia-Monco JC: The Challenge of Drug-Induced Aseptic Meningitis. In: Archives of Internal Medicine. 159. Jahrgang, Nr. 11, Juni 1999, S. 1185–94, doi:10.1001/archinte.159.11.1185, PMID 10371226 (ama-assn.org).
    35. ↑ Drew Provan, Andrew Krentz: Oxford Handbook of Clinical and Laboratory Investigation. Oxford University Press, Oxford 2005, ISBN 0-19-856663-8.
    36. ↑ a b c d e f g h i j Chaudhuri A, Martinez-Martin P, Martin PM, et al.: EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults. In: European Journal of Neurolology. 15. Jahrgang, Nr. 7, Juli 2008, S. 649–59, doi:10.1111/j.1468-1331.2008.02193.x, PMID 18582342.
    37. ↑ a b c d Straus SE, Thorpe KE, Holroyd-Leduc J: How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis? In: JAMA : the journal of the American Medical Association. 296. Jahrgang, Nr. 16, Oktober 2006, S. 2012–22, doi:10.1001/jama.296.16.2012, PMID 17062865.
    38. ↑ a b c d e f g Heyderman RS, Lambert HP, O'Sullivan I, Stuart JM, Taylor BL, Wall RA: Early management of suspected bacterial meningitis and meningococcal septicaemia in adults. In: The Journal of infection. 46. Jahrgang, Nr. 2, Februar 2003, S. 75–7, doi:10.1053/jinf.2002.1110, PMID 12634067. – formal guideline at British Infection Society & UK Meningitis Research Trust: Early management of suspected meningitis and meningococcal septicaemia in immunocompetent adults. In: British Infection Society Guidelines. Dezember 2004, abgerufen am 19. Oktober 2008.
    39. ↑ Maconochie I, Baumer H, Stewart ME: Fluid therapy for acute bacterial meningitis. In: Cochrane Database Syst Rev. Nr. 1, 2008, S. CD004786, doi:10.1002/14651858.CD004786.pub3, PMID 18254060.
    40. ↑ Weller PF, Liu LX: Eosinophilic meningitis. In: Semin Neurol. 13. Jahrgang, Nr. 2, Juni 1993, S. 161–8, PMID 8356350.
    41. ↑ a b Bicanic T, Harrison TS: Cryptococcal meningitis. In: British Medical Bulletin. 72. Jahrgang, 2004, S. 99–118, doi:10.1093/bmb/ldh043, PMID 15838017 (oxfordjournals.org).
    42. ↑ Saag MS, Graybill RJ, Larsen RA, et al.: Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. In: Clin. Infect. Dis. 30. Jahrgang, Nr. 4, April 2000, S. 710–8, doi:10.1086/313757, PMID 10770733 (uchicago.edu).
    43. ↑ Sloan D, Dlamini S, Paul N, Dedicoat M: Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings. In: Cochrane Database Syst Rev. Nr. 4, 2008, S. CD005647, doi:10.1002/14651858.CD005647.pub2, PMID 18843697 (wiley.com).
    44. ↑ David A Warrell, et al.: Oxford Textbook of Medicine Volume One. Oxford, 2003, ISBN 0-19-852787-X, S. 1115–29.
    45. ↑ a b c d e f g Segal S, Pollard AJ: Vaccines against bacterial meningitis. In: British Medical Bulletin. 72. Jahrgang, 2004, S. 65–81, doi:10.1093/bmb/ldh041, PMID 15802609 (oxfordjournals.org).
    46. ↑ a b Peltola H: Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. In: Clinical Microbiology Reviews. 13. Jahrgang, Nr. 2, April 2000, S. 302–17, doi:10.1128/CMR.13.2.302-317.2000, PMID 10756001, PMC 100154 (freier Volltext) – (asm.org).
    47. ↑ a b c Harrison LH: Prospects for vaccine prevention of meningococcal infection. In: Clinical microbiology reviews. 19. Jahrgang, Nr. 1, Januar 2006, S. 142–64, doi:10.1128/CMR.19.1.142-164.2006, PMID 16418528, PMC 1360272 (freier Volltext) – (asm.org).
    48. ↑ a b Wilder-Smith A: Meningococcal vaccine in travelers. In: Current Opinion in Infectious Diseases. 20. Jahrgang, Nr. 5, Oktober 2007, S. 454–60, doi:10.1097/QCO.0b013e3282a64700, PMID 17762777.
    49. ↑ a b Weisfelt M, de Gans J, van der Poll T, van de Beek D: Pneumococcal meningitis in adults: new approaches to management and prevention. In: Lancet Neurol. 5. Jahrgang, Nr. 4, April 2006, S. 332–42, doi:10.1016/S1474-4422(06)70409-4, PMID 16545750.
    50. ↑ Fraser A, Gafter-Gvili A, Paul M, Leibovici L: Antibiotics for preventing meningococcal infections. In: Cochrane Database of Systematic Reviews (Online). Nr. 4, 2006, S. CD004785, doi:10.1002/14651858.CD004785.pub3, PMID 17054214 (wiley.com).
    51. ↑ Prasad K, Singh MB: Corticosteroids for managing tuberculous meningitis. In: Cochrane Database of Systematic Reviews (Online). Nr. 1, 2008, S. CD002244, doi:10.1002/14651858.CD002244.pub3, PMID 18254003 (wiley.com).
    52. ↑ Assiri AM, Alasmari FA, Zimmerman VA, Baddour LM, Erwin PJ, Tleyjeh IM: Corticosteroid administration and outcome of adolescents and adults with acute bacterial meningitis: a meta-analysis. In: Mayo Clin. Proc. 84. Jahrgang, Nr. 5, Mai 2009, S. 403–9, doi:10.4065/84.5.403, PMID 19411436, PMC 2676122 (freier Volltext).
    53. ↑ a b de Gans J, van de Beek D: Dexamethasone in adults with bacterial meningitis. In: The New England Journal of Medicine. 347. Jahrgang, Nr. 20, November 2002, S. 1549–56, doi:10.1056/NEJMoa021334, PMID 12432041 (nejm.org).
    54. ↑ a b van de Beek D, de Gans J, McIntyre P, Prasad K: Corticosteroids for acute bacterial meningitis. In: Cochrane Database of Systematic Reviews (Online). Nr. 1, 2007, S. CD004405, doi:10.1002/14651858.CD004405.pub2, PMID 17253505.
    55. ↑ McIntyre PB, Berkey CS, King SM, et al.: Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. In: JAMA. 278. Jahrgang, Nr. 11, September 1997, S. 925–31, doi:10.1001/jama.278.11.925, PMID 9302246.
    56. ↑ Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke (NINDS), 11. Dezember 2007, abgerufen am 27. April 2009.
    57. ↑ Gottfredsson M, Perfect JR: Fungal meningitis. In: Seminars in Neurology. 20. Jahrgang, Nr. 3, 2000, S. 307–22, doi:10.1055/s-2000-9394, PMID 11051295.
    58. ↑ Richardson MP, Reid A, Tarlow MJ, Rudd PT: Hearing loss during bacterial meningitis. In: Archives of Disease in Childhood. 76. Jahrgang, Nr. 2, Februar 1997, S. 134–38, doi:10.1136/adc.76.2.134, PMID 9068303, PMC 1717058 (freier Volltext) – (bmj.com).
    59. ↑ Mortality and Burden of Disease Estimates for WHO Member States in 2002. (xls) In: World Health Organization. 2002;.
    60. ↑ Meningococcal Disease: situation in the African Meningitis Belt. WHO, abgerufen am 29. März 2009.
    61. ↑ a b Arthur Earl Walker, Edward R. Laws, George B. Udvarhelyi: The Genesis of Neuroscience. Thieme, 1998, ISBN 1-879284-62-6, Infections and inflammatory involvement of the CNS, S. 219–21 (google.co.uk).
    62. ↑ Whytt R: Observations on the Dropsy in the Brain. J. Balfour, Edinburgh 1768.
    63. ↑ a b c Greenwood B: 100 years of epidemic meningitis in West Africa – has anything changed? In: Tropical Medicine & International health: TM & IH. 11. Jahrgang, Nr. 6, Juni 2006, S. 773–80, doi:10.1111/j.1365-3156.2006.01639.x, PMID 16771997 (wiley.com).
    64. ↑ Vieusseux G: Memoire sur la maladie qui regnéà Geneve au printemps de 1805. In: Journal de Médecine, de Chirurgie et de Pharmacologie (Bruxelles). 11. Jahrgang, 1806, S. 50–53.
    65. ↑ Weichselbaum A: Ueber die Aetiologie der akuten Meningitis cerebro-spinalis. In: Fortschrift der Medizin. 5. Jahrgang, 1887, S. 573–583.
    66. ↑ Flexner S: The results of the serum treatment in thirteen hundred cases of epidemic meningitis. In: J Exp Med. 17. Jahrgang, 1913, S. 553–76, doi:10.1084/jem.17.5.553 (rupress.org [PDF]).
    67. ↑ a b Swartz MN: Bacterial meningitis--a view of the past 90 years. In: The New England Journal of Medicine. 351. Jahrgang, Nr. 18, Oktober 2004, S. 1826–28, doi:10.1056/NEJMp048246, PMID 15509815.
    68. ↑ Rosenberg DH, Arling PA: Penicillin in the treatment of meningitis. In: JAMA. 125. Jahrgang, 1944, S. 1011–1017. reproduced in Rosenberg DH, Arling PA: Penicillin in the treatment of meningitis. In: JAMA. 251. Jahrgang, Nr. 14, April 1984, S. 1870–6, doi:10.1001/jama.251.14.1870, PMID 6366279.

    * [[Kategorie: Symptomatische Epilepsien]] * [[Kategorie: Infektionskrankheiten]] * [[Kategorie: Medizinische Notfälle]] * [[Kategorie: Krankheitsbild in der Neurologie]]

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