Infections of the Nervous System PDF

Infections of Nervous System Meningitis and Encephalitis Prof Naga  Account for around 4% of infections in the ICU. Associated with significant morbidity and mortality. Early recognition and treatment improves outcomes...

Infections of Nervous System Meningitis and Encephalitis Prof Naga  Account for around 4% of infections in the ICU. Associated with significant morbidity and mortality. Early recognition and treatment improves outcomes Urgent brain imaging when clinical evidence of raised ICP before lumbar Key points puncture, but this should not delay treatment with antibiotics. Geographical location and immune status should be considered when determining the likely causative organism Autoimmune encephalitis is suspected CNS infection when microbiological tests are negative.  CNS can be infected by: Parasites (hydatid cysts, cysticercosis) Protozoa (toxoplasmosis) Rickettsiae ( Rocky Mountain spotted fever) Spirochetes (syphilis, leptospirosis, Lyme disease) Introducti Fungi (cryptococcus, candida) on Chronic mycobacteria (TB, leprosy) Pyogenic bacteria (meningococcus, haemophilus influenza) Chronic viruses (AIDS, SSPE) Acute viruses (HSV, H Zoster, polio virus) Prion disease ( Creutzfeldt-Jacob disease) Mycoplasma (M pneumonia)  Bacterial meningitis is defined as inflammation of the meninges, particularly the pia and arachnoid associated with invasion of bacteria into the subarachnoid space. It is thought that bacterial invasion into CNS is preceded by high-grade bacteraemia, invasion in highly Meningitis vascularized sites- choroid plexus and leptomeningeal vessels. Another source of entry is direct access to CNS via local access as in sinusitis, or via dural defects following trauma, surgery or base of skull fracture or spontaneous. Bacterial invasion leads to endothelial activation and leucocyte infiltration. Bacterial Infections Acute Bacterial Meningitis 2 classical signs: Kernig’s sign Medical emergency. and Brudzinski’s sign. Headache, fever and neck Kernig’s sign: pain upon stiffness. Confused, reduced passive extension at the knee consciousness, seizures and when the hip is flexed. other focal neurology Brudzinski’s sign: involuntary depending on the extent of involvement. flexion at the hips when the neck (meningoencephalitis). is flexed. Photophobia and vomiting A non-blanching petechial or are often present. purpuric rash- meningococcal infection. Aetiology Common organisms causing bacterial meningitis vary depending on the age of presentation. Streptococcus pneumoniae, Neisseria meningitides, Haemophilus influenza- vaccination against these have reduced the incidence among children. Spread: haematogenous from respiratory tract. Traumatic or mechanical invasion into the subarachnoid space such as after neurosurgery or open head injury. Sinuses-----parameningeal foci to subarachnoid space.  CSF analysis from lumbar puncture. CT scan must be performed prior to LP to avoid brain herniation if papilledema or focal neurology is present. CSF characteristics: elevated WBC count, predominance of Diagnosi polymorphonuclear leukocytes, elevated protein and low glucose. s CSF: gram stain, culture and sensitivity. Auramine stain (TB) and India ink stain (cryptococcal infection) in immunocompromised or at-risk individual. Empiric antibiotic therapy if potentially life threatening.  Appropriate antibiotic therapy promptly with specific drugs chosen on most likely organisms------Subsequently modified on Gram stain and culture results. IV Cefotaxime 2g 6-hourly for the initial treatment of acute bacterial meningitis Add IV Ampicillin 2g 4-hourly or co- Treatmen trimoxazole if risk of Listeria (elderly or immunocompromised) t Key points: a) medical emergency. b) Classic CSF profile: high WBC count, high protein and low glucose. c) Antibiotics can be tailored based upon the identification of responsible organisms and penetration into subarachnoid space.  Oral Rifampicin or Ciprofloxacin to eradicate nasopharyngeal carriage of the meningococcus. Meningoco Those who had prolonged contact in ccal a household setting during the 7 Prophylaxi days before the onset of the illness. s A vaccine for meningococcal group C and Haemophilus Influenza is now a part of the routine childhood immunization. Tuberculous infection. TB meningitis, intracranial tuberculoma, Pott disease of the spine. Affects basal meninges and thus can present with cranial nerve palsies. Basal meningitis leads to hydrocephalus or brain infarcts. Subacute or chronic insidious presentation- prolonged prodrome of malaise and non-specific symptoms. CSF: leucocytosis with lymphocyte dominance and CSF glucose is often very low. AFB staining, cultures and PCR testing for antigens. Anti-TB treatment for 9 months at least. Brain Abscess Presents like any other intracranial lesions: headache, focal neurological signs, seizures and signs of raised ICP. Fever +/- Most abscesses contain multiple organisms, often a mixture of aerobic and anaerobic pathogens. Routes of infection: sinuses, open trauma, mechanical instrumentation, infective endocarditis or immunocompromised states. Diagnosis: CT or MRI with iv contrast will show a mass lesion with ring enhancement. SPECT can distinguish a neoplasm from an abscess. Blood cultures and neurosurgical drainage for definite pathogen. Prolonged courses of iv antibiotics with broad spectrum coverage of aerobic and anaerobic organisms or specifically tailored. Spinal Epidural Abscess Typically present with a combination of neck or back pain and focal neurological signs of cord compression or cauda equina involvement. For thoracic and lumbar abscess, these signs include lower extremity weakness, sensory loss with a detectable sensory level, urinary and sexual dysfunction. For cervical involvement, upper extremities may be affected. Fever +/-. An acute presentation suggests associated spinal cord infarction. Cause: spinal and epidural anaesthesia, spinal surgery, vertebral osteomyelitis or diskitis. CT or MRI with contrast. LP contraindicated. Blood cultures/ radiologically guided biopsy or drainage for culture and sensitivity. Prolonged course of antibiotics. Viral Infections Viral Meningitis: commonly caused by enteroviruses such as Coxsackie virus or arboviruses such as West Nile virus.. Clinically very similar to acute bacterial meningitis. CSF profile: lymphocyte dominance, elevated protein and normal glucose levels. Gram stain and bacterial culture negative. Blood and CSF tests for virus specific serologies and PCR assays. Treatment supportive unless herpes simplex virus (HSV1) is suspected. Encephalitis Viral encephalitis affects brain parenchyma- headaches, fever, altered conscious level, seizures and focal neurological signs. HSV 1: predilection for base of the brain especially medial temporal lobes and orbitofrontal regions of cortex. Limbic dysfunction, complex partial seizures of mesial temporal lobe origin, hallucinations and memory disturbances. CSF: elevated RBC count in addition to leucocytosis. CSF PCR for HSV1. EEG periodic discharges over one or both temporal lobes. Prolonged iv acyclovir. Supportive care, analgesics and anticonvulsants are appropriate. IV Acyclovir- (10 mg/kg every 8 hours for 2 to 3 weeks) Fungal Infections Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, candida species. Cryptococcus is the most common. Immunocompromised as well as immunocompetent hosts rarely. Routes: inhalation of the fungus present in soil and pigeon droppings. Insidious- headache, neck pain, confusion and fever. CSF: lymphocyte dominance (except initially), elevated protein and low glucose. India ink stain, rapid agglutination assay. Treatment- amphotericin. Parasitic Infections Toxoplasmosis: Toxoplasma gondii an intracellular parasite. Congenital Toxoplasmosis is one of TORCH: Toxoplasma, Rubella, CMV, HSV. From cat faeces, under-cooked meat. Intracranial infection in AIDS patients. Imaging: multiple ring-enhancing lesions in basal ganglia or at the grey-white matter junction. Serologies and CSF PCR assays. Brain biopsy if no improvement with treatment. Neurocysticercosis. Pork tapeworm, Taenia solium is a common parasitic infection causing new-onset focal seizures. Endemic in Central and South America. Multiple cystic lesions which can be ring-enhancing or calcified. Treatment: albendazole and steroids. HIV Infection Late complications of direct HIV infection or prolonged immunosuppression. HIV-associated Dementia. Vacuolar myelopathy- posterior column signs (loss of vibration and position sense with sensory ataxia, spasticity and hyperreflexia. Progressive multifocal leukoencephalopathy- demyelinating disease of the CNS. JC virus infection of oligodendrocytes. MRI shows patchy, non-enhancing foci of T2 hyperintensity within subcortical white matter. Opportunistic infections like toxoplasmosis and cryptococcus Primary CNS lymphoma – EBV Neurosyphilis Rare now. Asymptomatic neurosyphilis: positive serology without symptoms and signs. Meningovascular syphilis (3-4 years): subacute meningitis with cranial nerve palsies, Gumma as a mass lesion, paraparesis. General paralysis of the insane (10-15 years): progressive dementia, brisk reflexes and upgoing plantars. Tabes Dorsalis: Argyll Robertson pupils, ptosis and optic atrophy, ataxia, sharp shooting neuropathic pain, neuropathic joints (Charcot joints. Treatment with benzyl penicillin 1 gm daily im for 10 days. Transmissible spongiform encephalopathy Creutzfeldt-Jakob Disease. Progressive dementia after 50 years of age. Spongiform changes in the brain. Caused by prions (proteinaceous infective particle) Sporadic or infected material like corneal grafts and human growth hormone. VCJD, a variant neuropsychiatric symptoms, ataxia and dementia. Younger age group. Diagnosis by tonsillar biopsy and CSG gel electrophoresis. Post-infective neurological syndromes A) Acute disseminated encephalomyelitis: Days or weeks after an infection or immunization, a multifocal perivascular allergic reaction in the CNS, associated with demyelination may occur. Clinical expression may range from mild features of an acute encephalomyelitis to a major focal or multifocal neurological deficits to a life-threatening syndrome with seizures, bilateral neurological signs, ataxia, brainstem signs and coma. Cont’d B) Guillain-Barre syndrome: Post-infectious immunological lesion affects the spinal roots, cranial and peripheral nerves. Damage to myelin. Progressive weakness and numbness over 1-4 weeks. The clinical state and pathological process stabilize with subsequent recovery. Recovery is usually complete, whereas persistent deficits are not uncommon. Schwann cells can reconstitute nerve myelin with greater efficiency than oligodendrocytes within CNS Cont’d C) Reye’s syndrome: Occurs in young children. Damage to brain and liver in the wake of a viral infection. Especially influenza and varicella. Treatment of child’s infection with aspirin seems to increase the chances of developing the syndrome. Vomiting, rapidly progressing to coma, seizures, raised ICP (cerebral oedema) and bilateral neurological signs. Abnormal LFTs, hypoglycaemia seen. Cont’d D) Myalgic encephalomyelitis: A small number of patients enters into a protracted clinical state following a viral infection. Extreme tiredness, reduced exercise tolerance, muscle aches and pains develop. May last for months or even years. Status of the illness not fully established. ? Psychosomatic or ? Immunological. ? Coxsackie B infection Cont’d Sydenham’s chorea (St Vitus’ dance): Group A streptococcal sore throats, were common in children. Chorea with altered mental and emotional state. 1-4 weeks after the infection. Lasts a few weeks, then settle with occasional relapses. Rheumatic fever and raised ASOT titres in the blood. Very rare now. Q1 A 40-year-old alcoholic presented with 4-week history of headache, lethargy and mental symptoms. On examination, he was conscious but confused with signs of mild meningeal irritation. Results of CSF examination: Pressure 32 cm H2O. White cells: 225/mm3 (70% lymphocytes and 30% polymorphs). Protein 1.3 g/L (0.1 to 0.45), Glucose 1.7 mmol/L (blood glucose 6.4 mmol/L. CSF glucose 50 to 70% of blood level Gram stain: negative 1) What further tests should be done on this CSF sample? 2) What is the most likely diagnosis? Answers Q 1. 1) Ziehl-Neilson stain, Culture for pyogenic organisms, mycobacterium and fungi 2) Tuberculous meningitis Q 2. A previously healthy 45-year-old man is admitted with 2-day history of headache, fever, increasing confusion and seizures. He was taking ampicillin for his sore throat. The first CSF sample on admission and second sample 10 days later because of failure to respond to antibiotics 1st and anti-TB 2nd drugs. sample sample WBC 67/mm3 150/mm3 Neutrophi 80% 10% ls Lymphocy 20% 90% te Red cells 1/mm3 10/mm3 Protein 0.47 g/L 1.2 g/L CSF 3.8 3 mmol/L glucose mmol/l Answer 2 Presentation and initial sample- probably viral encephalitis, partially treated bacterial meningitis or TB meningitis. However, seizures occurring early, increased lymphocytes in CSF, normal glucose level and lack of response to treatment favour encephalitis. Herpes simplex is likely. When in doubt, start IV acyclovir. Q 3. A 35-year-old male homosexual is seen for acute confusional state. CSF sample showed: Protein 0.46 g/L WBC < 5/mm3 Glucose 2.4 mmol/L (blood glucose 5.2 mmol/L) TPHA positive VDRL negative How would you interpret the results? Answer Q 3 Previously treated neurosyphilis. The presence of anti-treponemal antibodies in an otherwise normal CSF (protein, cells and negative VDRL) is evidence of previous, probably treated. Specific tests TPHA, FTA (FTA-Abs) are specific. VDRL non-specific but used to assess activity of disease. Clinical presentation is unrelated. Q4 A 28-year-old iv drug user was admitted with a 3-day history of headache. He was febrile 38 degrees C, mild neck stiffness; and CT Brain was normal. HIV screen positive. CSF: Protein 0.58 g/L, Red cell count < 5/mm3, WBC count 32/mm3, Glucose 3.5 (blood glucose 6.2), Gram stain-negative, Ziehl-Neilsen stain- negative, TPHA, VDRL- negative. What infective cause should be actively sought? Answer Q 4 Cryptococcus neoformans. Fungal complication of HIV infection. Meningeal irritation, CSF showing lymphocytic pleocytosis with normal glucose. Cryptococcal meningitis causes subacute granulomatous meningitis, severe meningoencephalitis, raised ICP, focal deficits and systemic upset. India ink staining is positive in 50-60% of cases. Latex agglutination test is definitive. IV amphotericin B