Meningitis and Encephalitis

YOUMANS Chapter 44

Meningitis

• Definition : inflammation of the leptomeninges• Symptom : headache, fever• Most common cause : operation on the CNS

Outline

• Bacterial meningitis• Tuberculous meningitis• Treponemal (syphilitic) meningitis• Meningitis from lyme disease• Fungal meningitis• Uncommon meningitides Rarely encountered• Viral meningitis and encephalitis• Aseptic meningitis

Bacterial meningitis

• Pathophysiology• Type of Bacterial Meningitis• Clinical Features• Clinical Testing• Radiologic Studies• Postcraniotomy meningitis• Recurrent meningitis• Treatment• Prevention & Prognosis

Pathophysiology

• Originate form– Hematogenous spread– infected thrombi– direct extension from bacterially colonized cranial

structures adjacent to the meninges : surgical or traumatic

• Parameningal foci of infection require physical breach in the arachnoid membranemeningitis

Pathophysiology

Pathophysiology

• Effect of the bacteria within the CSF– hyperemia of the meningeal vessels, followed rapidly

by migration of neutrophils into the subarachnoid space

– The exudates increase quickly and extend to the sheaths of cranial and spinal nerves and into the perivascular spaces of the cortex

– Exudation of fibrinogen and other proteins from blood continues

– Toward the end of the second week plasma cells appear, and thereafter they increase as well

Pathophysiology

• Infections controlled early may leave no trace on arachnoid structure, whereas those treated after the infection has become solidly established may leave behind a thickened, cloudy, and adherent arachnoid membrane

• Cellular immune reaction in CSF endothelial in small vessel swelling+adventitia infiltrates by neutrophil necrosis of arterial wall subarachnoid bleeding

Pathophysiology

• Vascular change can in ischemia and stroke• Dysfunction of cranial and spinal nerves occurs

as the purulent exudate surrounds the nerves• Spine : Chronic nerve root pain• Foramina of Magendie and Luschka or the basal

cisterns : Hydrocephalus • Brain : increase cortical microglia and astrocyte,

encephalopathy and seizure

Type of Bacterial Meningitis• Most common – 75%

– Haemophilus influenza– Neisseria meningitidis– Streptococcus pneumoniae

• Less frequent– Staphylococcus aureus– Staphylococcus epidermidis– Streptococcusgroup A, which usually occur after head

trauma neurosurgical procedures or with a brain or epidural abscess

Type of Bacterial Meningitis

• Less frequent– Streptococcusgroup B, which is seen in newborns;– Enterobacteriaceae (Klebsiella, Proteus, and

Pseudomonas spp.), which occur after lumbar puncture or shunt placement

– Meningococcal meningitis occurs most often in children and adolescents but can be seen in adulthood until the age 50

– Pneumococcal meningitis and Haemophilusmeningitis both predominate in the very young and in elderly adult

Clinical Features

• Adults and Older Children– Early manifestations : fever, headache (typically

severe), generalized seizures, and impaired sensorium

– Neck stiffness on flexion is common, Kernig sign and Brudzinski sign are sometimes seen but are less reliable

– if a petechial rash or ecchymosis accompanies the onset of symptoms, meningococcus should be suspected

Clinical Features

• Adults and Older Children– In patients with preexisting infection of the lungs,

sinuses, or ears or in those who have disorders of the heart valves, pneumococcus should be suspected

– The most common scenario for Haemophilus meningitis is after an upper respiratory or ear infection in a child

– In a young patient or in a comatose adult, signs of meningeal irritation may be absent

Clinical Features

• Infants– Infants have a greater incidence of meningitis than

adults do because of their less developed immune system

– signs are nonspecific : fever, irritability, drowsiness, vomiting, seizures, and a bulging fontanelle

– Risk factor : premature, prolong labour, UTI of mother

Clinical Testing

• Lumbar puncture– Before instituting ATB– Bleeding disorder : correct – Increase intracranial pressure : CT, MRI– Hydrocephalus : ventriculostomy with take CSF

• D• d

Clinical Testing

• CSF – C/S : positive 20 – 90 in untreated– G/S– ELISA, PCR if C/S negative– LDH (isozymes 4,5 )rise in patients with bacterial

meningitis– Lactic acid rise in bacterial or fungi but remain normal

in viral meningitis (higher than 35 mg/dL)• Blood cultures should always be done

Radiologic Studies

• Radiograph of chest, skull, and sinuses – in any patient suspected of having bacterial meningitis

without a known source• CT of the skull

– sinus infection – mastoiditis

• CT, MRI – Hydrocephalus– Infarction– brain abscess or subdural empyema (or effusion)

Postcraniotomy meningitis

• Most common organisms– S. Aureus– S. Epidermidis– Gram-negative organisms

• Signs and symptom– fever, neck stiffness– altered levels of consciousness– increased risk for stroke secondary to venous

infarction

Postcraniotomy meningitis

• Lumbar puncture and CSF for cell count, diff, glucose, protein

• Start ATB after LP– Vancomycin 1 gm v q 8 hrs + ceftazidime 1-2 gm v q

8 hrs (Greenberg)– For Pseudomonas add Gentamicin

• Role of prophylactic ATB remain controversial

Recurrent meningitis

• suspicion of an ongoing CSF leak through a previous basilar skull fracture or surgical procedure affecting the frontal, sphenoid, or ethmoid sinuses or the cribriform plate

• Absent trauma, a congenital fistula between the nasal sinuses and subarachnoid space may be suspected.

Recurrent meningitis• Difficult case to detect

– We have found the best method of detecting small leaks to be injection of radioactive tracer (typically 99Tc or 111In) into the lumbar subarachnoid space with placement of nasal pledgets.

– The patient is then imaged over the next 24 to 48 hours to observe gradual movement of the tracer to the head (and if leak is present, into the nose and stomach)

– The pledgets are removed after the first day and also scanned; if a very slow leak is present, they may be the only source of positive detection

Treatment

• ATB should be good penetration– low molecular weight– simple chemical structure of the drug– low degree of ionization at physiologic pH– high lipid solubility– low degree of protein binding

• Duration– bacterial meningitis : 10 – 14 days– gram-negative bacteria and Listeria : 21 days

Treatment

• If a shunt is present, it will typically require externalization or removal, or both, with reinsertion done only when the meningitis has been completely treated.

• Treatment is invariably by intravenous administration, and in refractory cases or in those with profound ventriculitis, intraventricular therapy may additionally be needed

Treatment

• It is not necessary to repeat lumbar puncture at intervals during therapy as long as progressive clinical improvement suggests that the disease is clearing

• Dexamethasone : 0.15 mg/kg every 6 hours during the first 4 days of antibiotic therapy

• Anticonvulsants should be given when seizures are present but need not be given prophylactically

Treatment

Prevention

• Strategies for prevention – active immunization : Haemophilus vaccine– passive immunization with immunoglobulins– chemoprophylaxis

• Rifampin (10 to 20 mg/kg per day orally for 4 days to a maximal dose of 600 mg daily) should be given to those who have had close contact with the patient in the 2 weeks before the diagnosis of meningococcal meningitis

Prognosis

• Mortality rate– Haemophilus and meningococcal meningitis : 5 – 15 – Pneumococcal meningitis : 15 – 30 % – Waterhouse-Friderichsen syndrome :

• Fulminant meningococcemia is possible with or without meningitis and has a very high mortality rate from vasomotor collapse associated with adrenocortical hemorrhage (Waterhouse-Friderichsen syndrome)

Prognosis

• Worse prognosis in– Bacteremia– Coma or Seizures– Concomitant disease as alcoholism and diabetes

mellitus• Those who recover from meningococcal

meningitis usually show no residual deficits, but neurological injury occurs in 25% or more of children with Haemophilusmeningitis and up to 30% of those with pneumococcal meningitis

Tuberculous meningitis• Inciden very low, 1 %• Organism

– Mycobacterium tuberculosis– Mycobacterium bovis

• Bacterial seeding to the brain formation tubercles rupture and seed mycobacteria to subarchnoid space

• Location : basal meninges, cerebral convexities• Spread to along pia vessel to invade adjacent brain

tissue

Tuberculous meningitis

• Active tuberculosis elsewhere• Alcholism is common• Serous meningitis

– self-limited meningitis develop in cerebral tuberculoma, mild symptom and tend to clear several week

– CSF : modest pleocytosis, normal or elevated protein levels, and normal glucose levels

Tuberculous meningitis

• Clinical feature : Headache, Stiff neck, lethargy, confusion, fever, CN involvement

• Diagnosis :– Lumbar puncture

• wbc 50-500, mononuclear cell predominate• pressure normal to high• glucose low but not usually very low levels seen in bacterial

meningitis

– CSF for Ziehl-Neelsen method(AFB), culture(1 month), PCR

Tuberculous meningitis

• Treatment– Combination, at least three– Isoniazid : side effect – neuropathy, hepatitis– Ethambutol : side effect - optic neuropathy– Corticosteroids are not generally used– Intracerebral tuberculoma requires resection : mass

effect or if it fails to shrink with drug therapy• Continues ATB for 18 – 24 Months

Treponemal (syphilitic) meningitis

• 25% of patient with syphilis• Asymptomatic, discover only by LP • Different form other : Afebrile• Rarely symptomatic : cranial nerve palsies,

seizures, and increased intracranial pressure• 2 year if no CNS invasion – 5 % will develop 5 year if no CNS invasion – 1 % will develop

Treponemal (syphilitic) meningitis

• CSF – pleocytosis of 200 to 300 cells/mm mainly

lymphocytes and other mononuclear cells– elevation of total protein to 40 to 200 mg/dL– normal glucose content– positive serologic tests

• VDRL : screen• FTA-ABS test : confirm

Treponemal (syphilitic) meningitis

• Meningovascular syphilis – more advanced form of the disease– occurs 6 to 8 years after the original infection– It should be considered when a relatively young

person has one or more cerebral infarcts– CSF will show positive serology and pleocytosis

Treponemal (syphilitic) meningitis

• Treatment– crystalline penicillin G : high doses intravenously for 2

weeks– At 6 Mo

• Pt symptom free,CSF normal : no further treatment• If CSF,pleocytosis or elevated glucose : penicillin

Meningitis from lyme disease

• Spirochetes of the genus Borrelia, • tick bite with rash week to month • asymptomatic meningitis, later neurological

abnormality : headache, stiff neck, nausea and vomiting, malaise, and chronic fatigue and fluctuates over a period of weeks to months

• CSF : pleocytosis 3000, lymphocyte, protein 300, glucose normal

• Treatment : high-dose penicillin or ceftriaxone

Fungal meningitis

• Less common than bacterial meningitis• Hematogenous, infected paranasal sinus• Occur in immunosuppression : diabetes

mellitus, hematopoietic malignancy, prolonged immunosuppression in transplant patients, or chronic steroid therapy

• Chronic meningitides : afebrile,cranial nerve involvement, arteritis with thrombosis, infarction, and hydrocephalus.

Fungal meningitis

• CSF– Mirror to tuberculos meningitis– Pressure elevate, moderate pleocytosis of

lymphocytic predominance,protein is elevated and glucose is low

– KOH, culture, PCR

Fungal meningitis

• Coccidioidomycosis – progresses from the typical influenza-like illness with

pulmonary infiltration to the disseminated form of the disease

• Candidiasis– Cause meningitis very rare– parenchymal abscesses and noncaseating

granulomas– Mortality rate very high

Fungal meningitis• Cryptococcosis

– Headache, fever, stiff neck, increase intracranial pressure, ataxia, confusion state

– CSF for india ink(60%), serumcryptcoccal Ag– RX : amphotericin B IV(0.7 mg/kg), voriconazole for 2 Wk– Positive culture after 2 Wks of Rx : predictive relapse– LP for sign of increase intracranial pressure

• Daily LP : drain enough CSF to release typically ICP by 50%• Daily LP may suspend when pressure are normal• Lumbar drain : occasionally need for extremely high Ops(. 40

mmHg)

Uncommon meningitides Rarely encountered

• Amebas of the genus Naegleria– Swimming in ponds colonized by the organism– Rapid characterized :severe headache, fever, nausea

and vomiting, and a stiff neck– CSF similar to bacterial meningitis– Treatment : amphotericin B

Uncommon meningitides Rarely encountered

• Toxoplasmosis, Toxoplasma gondii– HIV infection c rash, myocarditis, polymyositis,

seizures, confusion, coma– CSF : increased protein and lymphocytic pleocytosis– Treatment : sulfadiazine and pyrimethamine

Viral meningitis and encephalitis

• Route of entry– viruses is either through the respiratory passages

(mumps, measles, varicella)– through the gastrointestinal system (polioviruses and

other enteroviruses)– through the oral or genital mucosa (herpes simplex), – inoculation through the skin (arboviruses)

• Neurotropic infection is also thought possible through retrograde movement of virus up the axons of cranial or peripheral nerves, Rabies

Viral meningitis and encephalitis

• Virus attack leptomeninges aseptic meningitis• Virus attack cell of brain encephalitis• In herpes zoster and some cases of herpes

simplex, the virus stays latent within neurons for prolonged periods until the immune defenses falter as a result of either age or more active instances of immunosuppression

• The basic clinical syndromes – (1) aseptic meningitis – (2) acute encephalitis meningoencephalitis

Aseptic meningitis

• Clinical syndrome : fever, headache, and mild neck stiffness, photophobia

• CSF – mononuclear pleocytosis– slight rise in CSF protein– cultures are negative aseptic meningitis.– glucose is normal

• May be slight depression of CSF glucose – mumps, varicellazoster, lymphocytic choriomeningitis,

or herpes simplex type 2

Aseptic meningitis

• Viral infection,most common– entero virus family(echovirus, coxsackievirus, and

nonparalytic poliovirus) : children, fecal-oral route, august to september

– Mump : any time in the yeay, often winter– lymphocytic choriomeningitis : contact with infected

hamsters or food contaminated by mouse feces, most common in late fall and winter

– Herpes simplex typre virus, and adenovirus.• Leptospira : soil or water c contact urine mice

Aseptic meningitis

• Diagnosis of aseptic meningitis by exclusion• Treatment

– Most cases of viral meningitis are not treated with antiviral drugs but resolve on their own

– if herpesvirus or varicella-zoster is suspected, treatment with acyclovir is commonly recommended.

Aseptic meningitis

• Nonviral forms of aseptic meningitis that cause lymphocytic or mononuclear reaction in the leptomeninges with negative CSF cultures

• 1. Bacterial infection adjacent to the meninges, commonly referred to as a parameningeal focus of infection : mastoiditis or sinusitis.

Aseptic meningitis

• 2. the organism is difficult to isolate : syphilis, cryptococcosis, tuberculosis, brucellosis.

• The organism can rarely be cultured, and detection depends on antibody titers in serum and CSF ELISA.

Aseptic meningitis

• 3. leptomeningeal carcinomatosis : carcinomatous meningitis, leukemias and lymphomas

• CSF : pleocytosis of lymphocytic

Aseptic meningitis

• 4.autoimmune disease : Behçet’s disease• classic triad : relapsing iritis, ulcers of mouth

and genitalia, and meningitis• Neurological manifestations : recurrent

meningoencephalitis, recurring episodes of dysfunction of the brainstem and diencephalon mimicking vascular insufficiency

• CSF : pleocytosis, elevated protein, normal glucose

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