Meningitis
Content
Meningitis, and other infections Epidemiology: Bacterial meningitis 5-10/100 000/yr in UK. 40million HIV positive worldwide. Risk Factors: Overcrowding, Immunocompromise (eg HIV, post-splenectomy -vulnerable to malaria and encapsulated bacteria like H.influenza, N. meningitidis, s. pneumonia), meningococcus contacts, alcohol excess (pneumococcus), CSF shunts, poverty, extremes of age, sickle cell, Diabetes mellitus, head injury (especially basal skull fracture), septic locus- eg pneumonia Aetiology and pathogenesis: Causative bacteria:Adults: Neisseria meningitides (35%), H. influenza (28%), strep Pneumoniae (16%) , (TB 1%), other (20%-staph, E.Coli…) Children <14: H.influenzae, meningococcus, s. pneumoniae, TB Neonates: E.Coli, B-haemolytic strep, listeria monocytogenes, Immunocompromised: listeria, tuberculosis, staphylococcus, pneumococcus, gram-negative, crytococcus
Other bacteria: SpirochaeteSyphilis: (trepenoma pallidum) General paralysis of the insane: parenchymal disease of the brain. Causes upper motor neurone signs (syphilitic gumma compresses tissue) including upward plantars, frontal lobe features, spastic paraparesis, dementia, cranial nerve palsies- II atrophy, Argyll Robertson pupils, seizures, tremor, dysarthria, depression, mania. May appear 4-6 years after infection. Syphilis: Tabes dorsalis: affects dorsal columns of spine, dorsal roots, causes sensory loss to limbs& trunk, neuropathic joints, foot ulcers, ataxia, paraesthesia, Argyll Robertson pupils, lower motor neurone signs including footdrop absent knee & ankle jerks, downward plantars double incontinence, impotence,. Tends to appear 8-12 years after infection, though possibly as much as 30 years. Lyme disease (borrelia burgdorferi)- transmitted by tick bite. Causes meningism, rash, arthralgia, encephalitis, meningitis, CN palsies. Viruses: Epstein Barr, mumps, echovirus, Herpes zoster/ simplex, coxsackie, polio, CMV… Fungal- immunocompromised eg Cryptococcus. Cerebral malaria- plasmodium falciparum. Cerebral Toxoplasma gondii- AIDS defining protozoal infection. Transmitted congenitally, via raw meat, cat faeces. Viral encephalitis often presents in a similar way to meningitis. Herpes simplex is the most common cause, others include CMV, herpes zoster, EpsteinBarr, mumps and adenovirus. It causes necrosis of neurones and glia. Acute disseminated encephalomyelitis (ADEM) may be caused as a post-viral syndrome or after vaccination. It is an acute multifocal inflammatory demyelinating CNS disease. It can also be caused by glandular fever (EBV), scarlet fever, measles, mumps, pertussis, rubella, chickenpox.
Cause of recurrent meningitis- spina bifida occulta with sinus at base of spine opening to meninges, vasulitis, skull fracture, Mollaret’s syndrome. Clinical Features/ Presentation: Headache (can be thunderclap), decreased consciousness, fever (with possible seizures), nonblanching macular, petechial rash (if neisseria septicaemia), nausea and vomiting, weight loss (Tuberculosis, Ca, HIV), delirium, photophobia, DIC, meningism- stiff neck, Kernig +ve (pain and spasm when knee extended on flexed hip), Brudzinski +ve (hip flexes on attempted passive neck flexion), raised intracranial pressure features possible (headache worse on lying, straining, Cushing BP, papilloedema, Cheyne-Stokes breathing…), lymph nodes, splenomegaly, cough and respiratory tract infection. N.Meningitidis has a 2-3 day incubation and occurs in epidemics. In baby: neck held in retraction, bulging fontanelles, bulging eyes
Toxoplasmosis: focal signs like hemiparesis, dysphasia, cerebellar signs, EPS, cranial nerve palsies, seizures. Congenital toxoplasmosis: hydrocephalus, hepatosplenomegaly, retinochoroiditis, reduced platelet count, Cerebral malaria: fever, malaise, headache, delirium, seizures. Viral encephalitis- may have focal neurological features such as dyspasia, hemiparesis. Chronic meningoencephalitis- TB has a prolonged prodrome of evolving meningitis. Adhesive arachnoiditis causes cranial nerve palsy and hydrocephalus. Localized vasculitis and caseation produces focal neurological signs eg papilloedema.
Systemic inflammatory response syndrome, 2 or more of: pulse >90bpm; temperature >38 or <36, WCC > 12x10^9 or <4x10^9 or >10% immature forms; respiratory rate >20/min or PaCO2 <4.3kPa Possible Investigations: FBC, U&E (risk of SIADH hyponatremia), ESR, CRP, anti-streptocolysin-O titre (ASOT) blood culture, HIV test, syphilis serology, blood pressure, tuberculin test if suspected CT (exclude space occupying lesion, extradural bleed), lumbar puncture (possible ZN stain, India ink stain for Cryptococcus, PCR for viruses), midstream urine, throat swab chest x ray, EEG shows periodic complexes in the temporal region in herpes simplex infection. Contraindications to LP- suspected mass lesion, extradural haemorrhage, clotting problem, lumbar sepsis. Causes of aseptic meningitis (culture –ve meningitis): carcinoma/leukaemia, encephalitis, syphilis, subarachnoid haemorrhage, Mollaret’s meningitis (benign, recurrent fever, meningism, CSF lymphocytosis), protozoal eg malaria, viral, Tuberculosis, partially treated bacterial, autoimmune: sarcoidosis, SLE, polyarteritis nodosa etc, drug eg intrathecal methotrexate. Neutrophil countGlucose*Lymphocyte count Bacterial ++raised <0.5 normal TB normal <0.5 raised Viral normal >0.5 raised Fungal- may be completely normal. *as proportion of plasma levels Protein Appearance Cell count/mm3 1-5g/L turbid 90-1000 >1.5g/L filmy web 10-1000 <1g/L clear 50-1000
Management: Bacterial meningitis: ABC- maintain BP, start IV fluids. Vs raised intracranial pressure- sit patient up, oxygen therapeutic hyperventilation, mannitol, dexamethasone can reduce complications of bacterial meningitis in the <15’s. Empirical- if suspected, start treatment with IM benzylpenicillin, cefotaxime, (plus possible thiamine) do not delay for culture. Symptomatic: analgesia, antiemetics, nurse in dark, isolated room with nurse use of mark-gloves-apron. Contact tracing with rifampicin prophylaxis (caution: cytochrome p450 inducer, if interferes with OCP use ciprofloxacin instead) Strep. Pneumococcus: Cefotaxime and vancomycin Listeria: gentamicin, ampicillin Staphyloccus: flucloxacillin. MRSA: vancomycin or teicoplanin.
Syphilis treatment: procaine penicillin and prednisolone to prevent Jarisch-Heixheimer reaction (resistant strains developing esp in Thailand) TB meningoencephalitis treated with rifampicin, isoniazid, pyrazinamide, ethambutol (stop eth after 3 months) plus pyridoxine, 18 months, corticosteroids used initially vs oedema. Cryptococcal meningitis treated with amphotericin B or 5-Fluorocytosine, HIV treatment. Viral encephalitis- acyclovir + betamethasone vs herpes simplex, ganciclovir vs CMV, diploid vaccine vs rabies. Mannitol and anti-epileptics may also be needed. Toxoplasmosis- pyrimethamine, sulfadiazine, folinic acid HIV treatment Malaria- treated with quinine and tetracycline Acute Demyelinating EncephaloMyelitis responds well to steroids.
Post-splenectomy, it is recommended to take daily antibiotic eg penicillin V for prophylaxis, as well as vaccinations and wearing medicalert bracelet. Vaccination: meningitis C, Haemophilus influenzae B, MMR, Pertussis Prognosis: Bacterial: 70-100% mortality if untreated. Neisseria has ~15% mortality overall in UK. Viral meningitis tends to be selflimiting, however it can present in a similar way to viral encephalitis which is extremely dangerous- 20% mortality with treatment, 70% without. Chronic TB meningoencephalitis has 20-30% mortality in treated patients and long-term disability. Toxoplasma brain infection: 70% mortality. Cerebral malaria has 22% mortality. Complications: brain damage, obstructing hydrocephalus, syndrome of inappropriate ADH release (hyponatremia), endocarditis, septicaemia, deafness, seizures, disseminated intravascular coagulation, encephalitis, cerebral oedema, abscess (70-100% mortality without treatment), deafness, dural sinus thrombosis, DIC and adrenal haemorrhage causing hypofunction (Waterson-Friedrich’s syndrome), endocarditis, septic arthritis, death in 24-48 hours (bacterial). Differentials: Viral encephalitis, cerebral malaria, extradural haemorrhage, subarachnoid haemorrhage, brain tumour/abscess/haematoma (especially in posterior fossa), aseptic meningitis, brain aneurysm, migraine/cluster/tension headache, dural sinus thrombosis, flu, Wernicke-Korsakov’s encephalopathy. other HIV brain conditions: CNS lymphoma, toxoplasma, HIV encephalopathy, CMV encephalitis, histoplasma, PML- progressive myeloid leucoencephalopathy (related to JC virus), cryptococcal meningitis, TB meningitis…
Other bacteria: SpirochaeteSyphilis: (trepenoma pallidum) General paralysis of the insane: parenchymal disease of the brain. Causes upper motor neurone signs (syphilitic gumma compresses tissue) including upward plantars, frontal lobe features, spastic paraparesis, dementia, cranial nerve palsies- II atrophy, Argyll Robertson pupils, seizures, tremor, dysarthria, depression, mania. May appear 4-6 years after infection. Syphilis: Tabes dorsalis: affects dorsal columns of spine, dorsal roots, causes sensory loss to limbs& trunk, neuropathic joints, foot ulcers, ataxia, paraesthesia, Argyll Robertson pupils, lower motor neurone signs including footdrop absent knee & ankle jerks, downward plantars double incontinence, impotence,. Tends to appear 8-12 years after infection, though possibly as much as 30 years. Lyme disease (borrelia burgdorferi)- transmitted by tick bite. Causes meningism, rash, arthralgia, encephalitis, meningitis, CN palsies. Viruses: Epstein Barr, mumps, echovirus, Herpes zoster/ simplex, coxsackie, polio, CMV… Fungal- immunocompromised eg Cryptococcus. Cerebral malaria- plasmodium falciparum. Cerebral Toxoplasma gondii- AIDS defining protozoal infection. Transmitted congenitally, via raw meat, cat faeces. Viral encephalitis often presents in a similar way to meningitis. Herpes simplex is the most common cause, others include CMV, herpes zoster, EpsteinBarr, mumps and adenovirus. It causes necrosis of neurones and glia. Acute disseminated encephalomyelitis (ADEM) may be caused as a post-viral syndrome or after vaccination. It is an acute multifocal inflammatory demyelinating CNS disease. It can also be caused by glandular fever (EBV), scarlet fever, measles, mumps, pertussis, rubella, chickenpox.
Cause of recurrent meningitis- spina bifida occulta with sinus at base of spine opening to meninges, vasulitis, skull fracture, Mollaret’s syndrome. Clinical Features/ Presentation: Headache (can be thunderclap), decreased consciousness, fever (with possible seizures), nonblanching macular, petechial rash (if neisseria septicaemia), nausea and vomiting, weight loss (Tuberculosis, Ca, HIV), delirium, photophobia, DIC, meningism- stiff neck, Kernig +ve (pain and spasm when knee extended on flexed hip), Brudzinski +ve (hip flexes on attempted passive neck flexion), raised intracranial pressure features possible (headache worse on lying, straining, Cushing BP, papilloedema, Cheyne-Stokes breathing…), lymph nodes, splenomegaly, cough and respiratory tract infection. N.Meningitidis has a 2-3 day incubation and occurs in epidemics. In baby: neck held in retraction, bulging fontanelles, bulging eyes
Toxoplasmosis: focal signs like hemiparesis, dysphasia, cerebellar signs, EPS, cranial nerve palsies, seizures. Congenital toxoplasmosis: hydrocephalus, hepatosplenomegaly, retinochoroiditis, reduced platelet count, Cerebral malaria: fever, malaise, headache, delirium, seizures. Viral encephalitis- may have focal neurological features such as dyspasia, hemiparesis. Chronic meningoencephalitis- TB has a prolonged prodrome of evolving meningitis. Adhesive arachnoiditis causes cranial nerve palsy and hydrocephalus. Localized vasculitis and caseation produces focal neurological signs eg papilloedema.
Systemic inflammatory response syndrome, 2 or more of: pulse >90bpm; temperature >38 or <36, WCC > 12x10^9 or <4x10^9 or >10% immature forms; respiratory rate >20/min or PaCO2 <4.3kPa Possible Investigations: FBC, U&E (risk of SIADH hyponatremia), ESR, CRP, anti-streptocolysin-O titre (ASOT) blood culture, HIV test, syphilis serology, blood pressure, tuberculin test if suspected CT (exclude space occupying lesion, extradural bleed), lumbar puncture (possible ZN stain, India ink stain for Cryptococcus, PCR for viruses), midstream urine, throat swab chest x ray, EEG shows periodic complexes in the temporal region in herpes simplex infection. Contraindications to LP- suspected mass lesion, extradural haemorrhage, clotting problem, lumbar sepsis. Causes of aseptic meningitis (culture –ve meningitis): carcinoma/leukaemia, encephalitis, syphilis, subarachnoid haemorrhage, Mollaret’s meningitis (benign, recurrent fever, meningism, CSF lymphocytosis), protozoal eg malaria, viral, Tuberculosis, partially treated bacterial, autoimmune: sarcoidosis, SLE, polyarteritis nodosa etc, drug eg intrathecal methotrexate. Neutrophil countGlucose*Lymphocyte count Bacterial ++raised <0.5 normal TB normal <0.5 raised Viral normal >0.5 raised Fungal- may be completely normal. *as proportion of plasma levels Protein Appearance Cell count/mm3 1-5g/L turbid 90-1000 >1.5g/L filmy web 10-1000 <1g/L clear 50-1000
Management: Bacterial meningitis: ABC- maintain BP, start IV fluids. Vs raised intracranial pressure- sit patient up, oxygen therapeutic hyperventilation, mannitol, dexamethasone can reduce complications of bacterial meningitis in the <15’s. Empirical- if suspected, start treatment with IM benzylpenicillin, cefotaxime, (plus possible thiamine) do not delay for culture. Symptomatic: analgesia, antiemetics, nurse in dark, isolated room with nurse use of mark-gloves-apron. Contact tracing with rifampicin prophylaxis (caution: cytochrome p450 inducer, if interferes with OCP use ciprofloxacin instead) Strep. Pneumococcus: Cefotaxime and vancomycin Listeria: gentamicin, ampicillin Staphyloccus: flucloxacillin. MRSA: vancomycin or teicoplanin.
Syphilis treatment: procaine penicillin and prednisolone to prevent Jarisch-Heixheimer reaction (resistant strains developing esp in Thailand) TB meningoencephalitis treated with rifampicin, isoniazid, pyrazinamide, ethambutol (stop eth after 3 months) plus pyridoxine, 18 months, corticosteroids used initially vs oedema. Cryptococcal meningitis treated with amphotericin B or 5-Fluorocytosine, HIV treatment. Viral encephalitis- acyclovir + betamethasone vs herpes simplex, ganciclovir vs CMV, diploid vaccine vs rabies. Mannitol and anti-epileptics may also be needed. Toxoplasmosis- pyrimethamine, sulfadiazine, folinic acid HIV treatment Malaria- treated with quinine and tetracycline Acute Demyelinating EncephaloMyelitis responds well to steroids.
Post-splenectomy, it is recommended to take daily antibiotic eg penicillin V for prophylaxis, as well as vaccinations and wearing medicalert bracelet. Vaccination: meningitis C, Haemophilus influenzae B, MMR, Pertussis Prognosis: Bacterial: 70-100% mortality if untreated. Neisseria has ~15% mortality overall in UK. Viral meningitis tends to be selflimiting, however it can present in a similar way to viral encephalitis which is extremely dangerous- 20% mortality with treatment, 70% without. Chronic TB meningoencephalitis has 20-30% mortality in treated patients and long-term disability. Toxoplasma brain infection: 70% mortality. Cerebral malaria has 22% mortality. Complications: brain damage, obstructing hydrocephalus, syndrome of inappropriate ADH release (hyponatremia), endocarditis, septicaemia, deafness, seizures, disseminated intravascular coagulation, encephalitis, cerebral oedema, abscess (70-100% mortality without treatment), deafness, dural sinus thrombosis, DIC and adrenal haemorrhage causing hypofunction (Waterson-Friedrich’s syndrome), endocarditis, septic arthritis, death in 24-48 hours (bacterial). Differentials: Viral encephalitis, cerebral malaria, extradural haemorrhage, subarachnoid haemorrhage, brain tumour/abscess/haematoma (especially in posterior fossa), aseptic meningitis, brain aneurysm, migraine/cluster/tension headache, dural sinus thrombosis, flu, Wernicke-Korsakov’s encephalopathy. other HIV brain conditions: CNS lymphoma, toxoplasma, HIV encephalopathy, CMV encephalitis, histoplasma, PML- progressive myeloid leucoencephalopathy (related to JC virus), cryptococcal meningitis, TB meningitis…
