CNS Infections Siddiqui

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CNS Infections Siddiqui

  1. 1. CNS Infections Tahseen J. Siddiqui, M.D Infectious Disease Consultant Medical Director HIV/STD Care Program Jackson Park Hospital & Medical Center Chicago President The Chicago Society of Internal Medicine
  2. 2. Definitions <ul><li>Meningitis </li></ul><ul><li>􀂃 Inflammation of the leptomeninges </li></ul><ul><li>(the covering of the brain) </li></ul><ul><li>􀂃 Usually caused by bacteria </li></ul><ul><li>Meningitis is the 9th deadliest disease in the modern world </li></ul><ul><li>The incidence of bacterial meningitis declined from 1.9 to 1.5 cases per 100,000 from 1998 to 2003, in part, due to the introduction of the conjugate Haemophilus influenzae type b and pneumococcal conjugate vaccines </li></ul><ul><li> Encephalitis </li></ul><ul><li>􀂃 Inflammation of the brain itself </li></ul><ul><li>􀂃 Caused by many types of organisms </li></ul><ul><li>but mainly viruses </li></ul>Chronic meningitis is defined as meningeal inflammation that persists for more than 4 weeks, whereas acute meningitis lasts for less than 4 weeks.
  3. 3. Meningitis Mortality/Morbidity Morbidity and mortality depend on pathogen, patient's age and condition, and severity of acute illness Among bacterial pathogens, pneumococcal meningitis causes the highest rates of mortality (21%) and morbidity (15%). Mortality rate is 50-90% and morbidity even higher if severe neurologic impairment is evident at the time of presentation (or with extremely rapid onset of illness), even with immediate medical treatment. Race Blacks are at greater risk than other races, although race may not be an independent risk factor. Sex In neonates, male-to-female ratio is 3:1. No sex preference exists among adults. Age According to the Centers for Disease Control and Prevention (CDC),4 the median age is 39 years. In 1986, it was 15 months.
  4. 4. Microorganisms That Can Infect the Brain <ul><li>􀂄 Bacteria </li></ul><ul><li>􀂄 Viruses </li></ul><ul><li>􀂄 Fungi </li></ul><ul><li>􀂄 Parasites </li></ul><ul><li>􀂄 Prions </li></ul>Aseptic meningitis (CSF pleocytosis and normal CSF glucose, negative bacteria on Gram stain), is the most common CNS infection Most common microorganisms are enteroviruses ( primarily cause infection in the summer and early fall, account for up to 80% of all cases), human herpesvirus-2 ( HHV-2 ), lymphocytic choriomeningitis virus ( LCM ), HIV , and other viruses. Aseptic meningitis can also follow infection with Borrelia burgdorferi , the causative agent of Lyme disease, and neurosyphilis etc plus drug-induced (NSAIDs, metronidazole, IVIG)
  5. 5. Bacterial Meningitis <ul><ul><li>Streptococcus pneumoniae (50%) </li></ul></ul><ul><ul><li>Neisseria meningitis (25%) </li></ul></ul><ul><ul><li>Group B Streptococci (15%) </li></ul></ul><ul><ul><li>Listeria monocytogenes (10%) (malignancy) </li></ul></ul><ul><ul><li>Haemophilus influenzae (<10%) </li></ul></ul><ul><ul><li>M. tuberculosis, </li></ul></ul><ul><ul><li>T. pallidum, B. burgdorferi, </li></ul></ul><ul><ul><li>Leptospira (through exposure to animal fluids or infected water) </li></ul></ul><ul><ul><li>Brucella (through exposure to cattle or unpasteurized milk) </li></ul></ul><ul><ul><li>Nocardia asteroides (found in the soil; can cause infection in immunocompromised </li></ul></ul>
  6. 6. Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes CSF shunts S pneumoniae H influenzae Group A streptococci Basilar skull fracture Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa Intracranial manipulation, including neurosurgery S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli Immunocompromised state S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli Age older than 50 years S pneumoniae N meningitidis H influenzae Age 18-50 years N meningitidis S pneumoniae H influenzae Age 3 months to 18 years S agalactiae E coli H influenzae S pneumoniae N meningitidis Age 4-12 weeks S agalactiae (group B streptococci) E coli K1 L monocytogenes Age 0-4 weeks Bacterial Pathogen Risk and/or Predisposing Factor
  7. 7. Slide 2. Neisseria meningitidis meningitis This cerebrospinal fluid contains a high concentration of neutrophils and many gram-negative diplococci singly and in pairs. Although Neisseria meningitidis is the most likely organism, differentiation from N. gonorrhoeae , which can also cause meningitis, is not possible with Gram stain.  But with the PCR Slide 1. Streptococcus pneumoniae meningitis This cerebrospinal fluid from a child with meningitis contains many neutrophils and oval gram-positive cocci singly and in pairs. Because the number of organisms in infected cerebrospinal fluid is small, most laboratories centrifuge the specimen to increase the concentration and then use the sediment for both stains and cultures. The density of microbes per milliliter of fluid cannot be estimated from a specimen that has been centrifuged . Neisseria meningitides and Streptococcus pneumoniae account for 37% to 93% of acute bacterial meningitis
  8. 8. Slide 3. Haemophilus influenzae meningitis This cerebrospinal fluid contains many neutrophils and gram-negative coccobacilli, primarily in the cytoplasm of the white cells. Slide 4. Listeria monocytogenes meningitis This cerebrospinal fluid contains a few neutrophils and two slender gram-positive bacilli. Although Gram stains of cerebrospinal fluid are positive in specimens from about 80% of all patients with bacterial meningitis, organisms are detected in the cerebrospinal fluid of only about 40% of patients with Listeria meningitis. Even when specimens reveal bacteria, only a small number may be visible.
  9. 9. Signs & Symptoms of Meningitis <ul><li>􀂃 Headache > 90% </li></ul><ul><li>􀂃 Fever > 90% </li></ul><ul><li>􀂃 Neck Stiffness > 85% </li></ul><ul><li>􀂃 Vomiting 35% </li></ul><ul><li>􀂃 Seizures 30% </li></ul><ul><li>􀂃 Weakness 15% </li></ul><ul><li>Photophobia </li></ul><ul><li>Altered mental status ( irritability to somnolence, delirium, and coma ) </li></ul><ul><li>Kernigs and Brudzinski’s Sign </li></ul><ul><li>Papilledema </li></ul><ul><li>Focal neurologic signs-Isolated cranial nerve abnormalities (principally III, IV, VI, VII) in 10-20% …worse outcome (no LP) </li></ul><ul><li>Symptoms in infants </li></ul><ul><li>Fever </li></ul><ul><li>Lethargy and/or change in level of alertness </li></ul><ul><li>Poor feeding and/or vomiting </li></ul><ul><li>Respiratory distress, apnea, cyanosis </li></ul><ul><li>In partially treated meningitis (40%), seizures may be the sole presenting symptom </li></ul><ul><li>Low-grade ventriculitis associated with VP shunt: Patients may have a less dramatic presentation with headache, nausea, minimal fever, and malaise </li></ul><ul><li>Fungal meningitis: mild/fluctuating headache, low-grade fever, and lethargy are the primary symptoms </li></ul><ul><li>Tuberculous meningitis: Fever, weight loss, night sweats, and malaise, with or without headache and meningismus </li></ul>
  10. 10. Systemic findings <ul><li>Extracranial infection (eg, sinusitis, otitis media, mastoiditis, pneumonia, urinary tract infection) may be noted. </li></ul><ul><li>Arthritis is seen with N meningitidis, </li></ul><ul><li>Rash. Nonblanching petechiae and cutaneous hemorrhages are seen classically with N meningitidis; (can occur with other bacterial and viral infections) </li></ul><ul><li>Endotoxic shock with vascular collapse is characteristic of severe N meningitidis infection. </li></ul>
  11. 12. Laboratory Studies <ul><li>CBC with differential </li></ul><ul><li>Serum electrolytes and liver profile (dehydration or SIADH, to assess organ functioning and adjust antibiotic dosing) </li></ul><ul><li>Serum glucose as baseline for determining normal CSF glucose; </li></ul><ul><li>Coagulation profile and platelets in patients with chronic alcohol use, liver disease, or if DIC is suspected. (require platelets or FFP prior to LP.) </li></ul><ul><li>Urinary electrolytes (SIADH)) </li></ul><ul><li>Serum cryptococcal antigen, especially if baseline is known (less diagnostic than India ink and CSF cryptococcal antigen) </li></ul><ul><li>Cultures (prior to antibiotics) : blood (50% positive in meningitis caused by H influenzae, S pneumoniae, N meningitidis ); nasopharynx, respiratory secretions, urine, and skin lesions. </li></ul><ul><li>Latex agglutination or counter immunoelectrophoresis (CIE) of blood, urine, and CSF for specific bacterial antigens (partially treated meningitis) </li></ul><ul><li>Serum/CSF- RPR/VDRL if neurosyphilis is in differential diagnosis. (CSF VDRL may be negative) </li></ul>
  12. 13. Imaging Studies <ul><li>Head CT scan (contrast) or MRI (gadolinium) </li></ul><ul><li>In patients with evidence of head trauma, immunosuppression, altered mental status, or focal findings.  </li></ul><ul><li>Presence of papilledema and inability to fully assess fundi or neurologic status are indications for CT scan prior to LP. </li></ul><ul><li>Obtain blood cultures and initiate treatment before imaging studies and LP in patients with suspected bacterial meningitis. </li></ul><ul><li>Results may be normal or demonstrate small ventricles, effacement of sulci, and contrast enhancement over convexities. </li></ul><ul><li>Late findings include venous infarction and communicating hydrocephalus. </li></ul><ul><li>Rule out brain abscess, sinus or mastoid infection, skull fracture, and congenital anomalies. </li></ul><ul><li>Chest radiography- 50% of patients with pneumococcal meningitis also have evidence of pneumonia </li></ul>Non Contrast CT- mild ventriculomegaly and sulcal effacement. contrast-enhanced, axial T1-weighted magnetic resonance image shows leptomeningeal enhancement
  13. 14. Lumbar Puncture Procedure <ul><li>Elevated opening pressure correlates with increased risk of morbidity and mortality in bacterial and fungal meningitis. </li></ul><ul><li>Take tube #1 to chemistry lab for glucose and protein. </li></ul><ul><li>Take tube #2 to hematology lab for cell count with differential. </li></ul><ul><li>Take tube #3 to microbiology and immunology lab for Gram stain, bacterial culture, acid-fast bacillus (AFB) stain and tuberculosis (TB) cultures, India ink stain and fungal cultures, CIE, VDRL, and cryptococcal antigen, if indicated . </li></ul><ul><li>Hold tube #4 for repeat cell count with differential, if needed (or for other subsequent studies not initially ordered). </li></ul><ul><li>According to Seupaul, 3 diagnostic tests have clinically useful likelihood ratios for the diagnosis of bacterial meningitis in adults: CSF/blood glucose ratio less or equal to 0.4 , CSF WBC count greater or equal to 500/L , and CSF lactate level equal or greater than 31.53 . </li></ul>
  14. 15. Diagnosis <ul><li>CT Head (SOL/Increased ICP) </li></ul><ul><li>LP </li></ul><ul><li>Blood Cultures </li></ul><ul><li>CSF </li></ul><ul><ul><ul><li>↑ WBC (PMN), ↓ Glucose (<2.2mmol/L), ↓ CSF/Serum Glucose (<0.4), ↑ Protein (>0.45g/L), ↑ Opening Pressure (>180mm H 2 O) </li></ul></ul></ul><ul><ul><ul><li>CSF culture and gram stain </li></ul></ul></ul><ul><ul><ul><ul><li>Latex agglutination test-detects bacterial antigens </li></ul></ul></ul></ul><ul><ul><ul><ul><li>PCR-Can detect small numbers of bacteria </li></ul></ul></ul></ul><ul><ul><ul><ul><li>CIE-(Counter Immunoelectropheresis) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Able to detect small amounts of antigen </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Early detection (~24h) </li></ul></ul></ul></ul></ul>
  15. 16. Open P . AIDS patients with crypto meningitis have increased risk of blindness, death unless open pressure maintained at <30 cm In Bact mening- Lymphocytosis with normal CSF chemistries seen in 15-25%, especially when cell counts <1000 or if partially treated. In Viral mening Up to 48 hours, significant PMN pleocytosis may be indistinguishable from early bacterial meningitis After 8-12 hours, reexamine the CSF . If initial granulocytosis changes to mononuclear predominance, CSF glucose remains normal, and patient continues to look well, the infection is most likely nonbacterial. Nontraumatic RBCs in 80% of HSV meningoencephalitis, although 10% have normal CSF results ~90% of patients with VP shunts have CSF WBC count >100 cells/mm3 are infected; CSF glucose usually normal, and organisms are less pathogenic (Staph epi, Propionibacterium acnes, and diphtheroids) and S aureus, coliforms India ink 80-90% effective for fungi; AFB stain 40% effective for TB Prior antibiotics may cause gram-positive organisms to appear gram negative and decrease culture yield on average 20%. lowest levels of CSF glucose are seen in TB, primary amebic meningoencephalitis, neurocysticercosis An aseptic profile - bacterial (eg, Mycoplasma, Listeria, Leptospira species, Borrelia burgdorferi [Lyme], spirochetes), partially treated bacterial , HSV and arboviruses TB meningitis and parasites resemble the fungal profile more closely. 5-15 cm H2 O
  16. 17. <ul><li>In acutely ill patients, perform an LP (if appropriate) and administer first dose(s) of antibiotics +/- steroids within 30 minutes of presentation to ED. </li></ul><ul><li>Initiate empiric therapy if LP cannot be performed within 30 minutes. </li></ul><ul><li>Begin empiric therapy prior to head CT scan if a focal neurologic deficit is present. If no mass effect is present, perform LP </li></ul><ul><li>Treat systemic complications : hypotension and/or shock, hypoxemia, hyponatremia (SIADH), DIC,cardiac arrhythmias and ischemia, seizure and CVA </li></ul><ul><li>Seizure precautions in ED: Aggressively control seizures if present, since seizure activity increases ICP (ie, lorazepam 0.1 mg/kg IV and IV load with phenytoin 15 mg/kg or phenobarbital 5-10 mg/kg). </li></ul><ul><li>Dexamethasone may be beneficial in bacterial meningitis if given 15-20 mins before or with the first dose of antibacterial therapy, sepecially for H.Inf, S.pneumoniae or TB meningitis, raised ICP </li></ul><ul><li>Look for signs of hydrocephalus and increasing ICP. </li></ul><ul><li>Manage fever and pain, control straining and coughing, avoid seizures, and avoid systemic hypotension. </li></ul><ul><li>In stable patients, elevating head and monitoring neurologic status. </li></ul><ul><li>Diuresis (ie, furosemide 20 mg IV, mannitol 1 g/kg IV), provided circulatory volume is protected. </li></ul><ul><li>Hyperventilation in intubated patients, with a goal of PaCO2 25-30 mm Hg, may briefly lower ICP; hyperventilation with PaCO2 <25 mm Hg may decrease CBF disproportionately and lead to CNS ischemia. </li></ul><ul><li>Consider placing an ICP monitor in comatose patients or in those with signs of increased ICP. </li></ul><ul><li>With elevated ICP, remove CSF until pressure decreases by 50% and maintain at less than 300 mm water. </li></ul><ul><li>. </li></ul><ul><li>Meningococal meningitis/ H. flu needs droplet isolation </li></ul>
  17. 18. Prophylaxis For Close Contacts <ul><li>Close contact with patient with suspected N meningitidis for at least 4 hours during the week before onset (eg, house mates, daycare center, cell mates) or were exposed to patient's nasopharyngeal secretions (eg, kissing, mouth-to-mouth resuscitation, intubation, nasotracheal suctioning)., </li></ul><ul><li>Rifampin (pediatric dose: children <1 mo - 5 mg/kg q12h; children >1 mo - 10 mg/kg q12h; adult dose: 600 mg PO bid) for 4 doses </li></ul><ul><li>Alternative - Ciprofloxacin (adults) 500 mg PO single dose or ceftriaxone (<15 y: 125 mg; >15 y: 250 mg) IM single dose </li></ul><ul><li>Meningococcal vaccine only in established epidemics or in travelers to epidemic countries </li></ul><ul><li>Prophylaxis for H influenzae type b is controversial. Most authorities treat contacts to protect unvaccinated children, younger than 4 years </li></ul>
  18. 19. Adult doses: cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h) vancomycin (15-20 mg/kg IV q12h Ampicillin 50-100 mg/kg IV q6h Chloramphenicol (PCN allergic) 50-100 mg/kg/d PO/IV divided q6h AGE CAUSATIVE ORGANISM TREATMENT <1 MONTH GBS, E.COLI/GNRs, listeria Ampicillin + cefotaxime or gentamicin 1-3 months Pneumococci, meningococci, H influenzae Vancomycin IV + ceftriaxone or cefotaxime 3 months-adulthood Pneumococci, meningococci Vancomycin IV +ceftriaxone or cefotaxime >60 yrs/alcoholism/ chronic illness Pneumococci, gram – bacilli, listeria, meningococci Ampicillin + vancomycin+ cefotaxime or ceftriaxone
  19. 20. 21 Ceftazidime plus an aminoglycoside ... P aeruginosa 21 Ceftriaxone or cefotaxime plus an aminoglycoside ... Enterobacteriaceae 14-21 Penicillin G plus an aminoglycoside, if warranted ... S agalactiae 14-21 Ampicillin or penicillin G plus an aminoglycoside ... Listeria monocytogene 7 Penicillin G or ampicillin ... N meningitidis Ceftriaxone or cefotaxime Beta-lactamase-positive 7 Ampicillin Beta-lactamase-negative H influenzae Ceftriaxone or cefotaxime plus vancomycin or rifampin Ceftriaxone MIC >0.5 mg/L Ceftriaxone or cefotaxime MIC >2 mg/L Ceftriaxone or cefotaxime MIC 0.1-1 mg/L 10-14 Penicillin G Penicillin MIC <0.1 mg/L S pneumoniae Duratiin Days Antibiotic(s) Susceptibility Bacteria
  20. 21. Trauma/ Surgery <ul><li>Basilar skull Fracture </li></ul><ul><ul><li>S. pneumoniae, H. influenzae & group A beta hemolytic streptococci </li></ul></ul><ul><ul><ul><li>Treatment- Vancomycin and Rocephin </li></ul></ul></ul><ul><li>Penetrating Trauma and neurosurgery/VPS </li></ul><ul><ul><li>S. aureus, S. epidermidis, Pseudomonas </li></ul></ul><ul><ul><ul><li>Treatment- Vancomycin & Cefepime, or ceftazidim or meropenem </li></ul></ul></ul>
  21. 22. Tuberculous Meningitis-TBM <ul><li>Most common cause of chronic meningitis is Mycobacterium tuberculosis (40%-60%) </li></ul><ul><li>Mycobacterium tuberculosis may infect CNS by crossing the BBB or rupture of a Rich focus. </li></ul><ul><li>Following active primary pulm TB but may be absent </li></ul><ul><li>Travel Hx, HIV- Immunosuppressants, alcoholics, </li></ul><ul><li>Presentation is nonspecific , (headache, fever, malaise, lethargy, and confusion-over 1 to 2 weeks, ) </li></ul><ul><li>PPD may be negative </li></ul><ul><li>Diagnosis- CSF-AFB smear (higher-grade infection, PCR (expensive) & AFB cultures (weeks) </li></ul><ul><li>CSF findings include increased opening pressure, lymphocytosis, increased protein levels, decreased glucose levels </li></ul><ul><li>Treatment: longer than that for pulmonary TB (6m) extended to 1 to 2 years in neurologically compromised or immunosuppressed. </li></ul><ul><li>Tx: rifampin 10 mg/kg/day orally, isoniazid 5 mg/kg/day orally (with pyridoxine), pyrazinamide 15 to 30 mg/kg/day orally, and either ethambutol 15 to 20 mg/kg/day orally or streptomycin 15 mg/kg/day intramuscularly for 2 months , followed by 10 months of rifampin and isoniazid . </li></ul><ul><li>Most common side effects peripheral neuropathy ( isoniazid ), flulike illness, red discolor ( rifampin ), nausea/vomiting/malaise/hyperurecemia ( pyrazinamide ), and optic neuropathy-eye ( ethambutol ). All of the agents may cause rash and hepatotoxicity. </li></ul><ul><li>Moxifloxacin 400 mg/day orally if resistance </li></ul><ul><li>Steroids for the first 6 months </li></ul><ul><li>Household contacts should be tested and treated for latent TB </li></ul>
  22. 23. CEREBRAL MALARIA <ul><li>Plasmodium falciparum </li></ul><ul><li>mortality between 25-50%. If a person is not treated, CM is fatal in 24-72 hours. </li></ul><ul><li>risk factors include being a child under 10 years of age and living in malaria-endemic area </li></ul><ul><li>The histopathological hallmark of this encephalopathy is the sequestration of cerebral capillaries and venules with parasitized red blood cells (PRBCs) </li></ul><ul><li>key elements of Dx are: (1) unrousable coma--no localizing response to pain persisting for more than six hours if the patient has experienced a generalized convulsion; (2) asexual forms of P. falciparum found in blood; and (3) exclusion of other causes of encephalopathy, i.e. viral or bacterial </li></ul><ul><li>Tx is supportive, IV quinine and Exchange transfusion- when peripheral parasitemia exceeds 10% of circulating erythrocytes </li></ul>
  23. 24. Syphilitic meningitis (Neurosyphilis) <ul><li>Due to Treponema pallidum in the primary or secondary stage of infection </li></ul><ul><li>both immunocompetent and immunocompromised (especially HIV/AIDS ) individuals </li></ul><ul><li>evolves within months of inoculation, but frequently is asymptomatic . </li></ul><ul><li>Fever often is absent, but headache and confusion may be evident. </li></ul><ul><li>Typical CSF findings include (Aseptic profile) lymphocytosis, increased protein levels, normal glucose levels, and positive serologic tests for syphilis. (CSF) VDRL & FTA-Abs </li></ul><ul><li>Treatment- Penicillin G , Aggressive dosing (24 million units/day IV) x 14 days </li></ul><ul><li>allergy to penicillin, desensitization </li></ul><ul><li>With initiation of penicillin G, a release of endotoxin may occur, resulting in skin rash and an inflammatory response known as the Jarisch-Herxheimer reaction. </li></ul>
  24. 25. Lyme Meningitis (neuroborreliosis ) <ul><li>Due to Borrelia burgdorferi in stage 2 </li></ul><ul><li>exposure to an ixodid tick </li></ul><ul><li>presents after the characteristic Lyme disease rash disappears </li></ul><ul><li>main symptoms are peripheral and cranial neuropathies (71%) </li></ul><ul><li>CSF findings include (Aseptic profile) lymphocytosis, increased protein levels, normal glucose levels, and positive serologic tests for B burgdorferi . </li></ul><ul><li>treatment is ceftriaxone 2 g/day IV or penicillin G 20 million units/day IV for 10 to 14 days. </li></ul><ul><li>Doxycycline 100 mg/day IV may be used in patients who are allergic to penicillins or cephalosporins </li></ul><ul><li>Symptoms usually resolve slowly over weeks to months </li></ul>
  25. 26. Differentiating Lyme meningitis from enteroviral meningitis (Aseptic meningitis) The duration of symptoms before evaluation was longer for patients with Lyme meningitis (12 days) than with enteroviral meningitis (1 day). Cranial neuropathy , erythema migrans rash or papilledema occurred mostly in patients with Lyme meningitis; no patients with enteroviral meningitis Lyme meningitis was unlikely when cerebrospinal fluid neutrophils exceeded 10%
  26. 27. Meningitis: Complications 􀂃 Death 􀂃 Hearing loss 􀂃 Seizures 􀂃 Learning disorders
  27. 28. Brain Abscess <ul><li>The most common organisms are streptocooci, staphylococci and anaerobes </li></ul><ul><li>May develop from: </li></ul><ul><ul><li>Spread from a cranial infection </li></ul></ul><ul><ul><li>Sinusitis </li></ul></ul><ul><ul><li>Dental infection- anaerobes, frontal lobe </li></ul></ul><ul><ul><li>Otitis media, (temporal lobe and cerebellum-Strep, pseudomonas, haemophilus) </li></ul></ul><ul><ul><li>Head trauma </li></ul></ul><ul><ul><li>Neurosurgery </li></ul></ul><ul><ul><li>Hematogenous spread- MCA </li></ul></ul><ul><ul><li>Posterior frontal and parietal lobes- multiple abscess that are poorly encapsulated and located at the gray-white junction </li></ul></ul>
  28. 29. Brain Abscess <ul><li>Symptoms </li></ul><ul><ul><li>Headache, fever, focal/general neuro deficits </li></ul></ul><ul><ul><li>Mass effect, Cerebral edema </li></ul></ul><ul><ul><ul><li>Frontal lobe-hemiparesis </li></ul></ul></ul><ul><ul><ul><li>Temporal lobe-dysphasia </li></ul></ul></ul><ul><ul><ul><li>Cerebellum-ataxia </li></ul></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>MRI, CT </li></ul></ul><ul><ul><li>Gram stain and culture by needle aspiration </li></ul></ul><ul><ul><li>NO LP! </li></ul></ul>
  29. 30. Brain Abscess <ul><li>Treatment-Parenteral antibiotics-6-8wks </li></ul><ul><ul><li>Rocephin and Metronidazole </li></ul></ul><ul><ul><li>Trauma-Use cefepime or ceftazidime for pseudomonas and vancomycin for staphylococci </li></ul></ul><ul><ul><li>Neurosurgical Drainage </li></ul></ul>
  30. 31. Subdural Empyema & Epidural Abscess <ul><li>Diagnosis </li></ul><ul><ul><li>MRI, CT </li></ul></ul><ul><ul><li>NO LP! </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Emergency surgical evacuation of empyema </li></ul></ul><ul><ul><li>3 rd generation cephalosporin, vancomycin & metronidazole (Parenteral) </li></ul></ul><ul><ul><li>Fluid gram stain and culture </li></ul></ul>
  31. 32. Viral Meningitis <ul><ul><li>Enteroviruses (Poliovirus/Echovirus/ Coxsackievirus A/B) </li></ul></ul><ul><ul><li>Paramyxovirus (Mumps/Measles virus) </li></ul></ul><ul><ul><li>Herpesvirus (HSV-1 and HSV 2/Varicella-zoster virus/EBV/CMV/HHV*-6 HHV-7 </li></ul></ul><ul><ul><li>Rabies virus </li></ul></ul><ul><ul><li>HIV </li></ul></ul><ul><ul><li>LCM virus (Lymphocytic choriomeningitis) </li></ul></ul>Morbilliform rash with pharyngitis and adenopathy may suggest a viral etiology (eg, Epstein-Barr virus [EBV], cytomegalovirus [CMV], adenovirus, HIV). Varicella zoster virus ( VZV ), or HHV-3 , and CMV are causes of meningitis in immunocompromised hosts, especially patients with AIDS and transplant recipients. HIV encephalitis . Plain CT scan . Bilateral and symmetric diffuse hypodensity in the periventricular white matter without any mass effect
  32. 33. Lymphocytic Choriomeningitis (LCM) <ul><ul><li>Rodent-borne (common house mouse) viral (Arenaviridae-LCMV ) meningoencephalitis. </li></ul></ul><ul><ul><li>Infections from pet rodents(mice, hamsters, or guinea pig) fresh urine, droppings, saliva, or nesting materials. </li></ul></ul><ul><ul><li>Vertical transmission (Pregnancy)-congenital hydrocephalus, chorioretinitis, and mental retardation. </li></ul></ul><ul><ul><li>Transmission -directly introduced into broken skin, the nose, the eyes, or the mouth, or presumably, via the bite of an infected rodent, organ transplantation </li></ul></ul><ul><ul><li>Onset of symptoms usually occurs 8-13 days after exposure </li></ul></ul><ul><ul><li>A characteristic biphasic febrile illness then follows. </li></ul></ul><ul><ul><li>The initial phase, which may last as long as a week , typically begins with any or all of the following symptoms: fever, malaise, lack of appetite, muscle aches, headache, nausea, and vomiting. Other symptoms that appear less frequently include sore throat, cough, joint pain, chest pain, testicular pain, and parotid (salivary gland) pain. </li></ul></ul><ul><ul><li>Following a few days of recovery, the second phase of the disease occurs, consisting of symptoms of meningitis (for example, fever, headache, and a stiff neck) or characteristics of encephalitis (for example, drowsiness, confusion, sensory disturbances, and/or motor abnormalities, such as paralysis). </li></ul></ul><ul><ul><li>LCMV has also been known to cause acute hydrocephalus , which often requires surgical shunting to relieve increased intracranial pressure. </li></ul></ul><ul><ul><li>Rarely, myelitis (muscle weakness, paralysis, or changes in body sensation) </li></ul></ul><ul><ul><li>An association between LCMV infection and myocarditis </li></ul></ul>
  33. 34. Lymphocytic Choriomeningitis (LCM) Diagnosis <ul><ul><li>During the first phase: ( leukopenia/thrombocytopenia ). Liver enzymes in the serum may also be mildly elevated. </li></ul></ul><ul><ul><li>After the onset of neurological disease during the second phase, CSF- ( aseptic profile ) ↑ WBC (lymphocytes), normal or ~↑ protein, normal glucose, normal or ~↑ opening pressure </li></ul></ul><ul><li>Serology </li></ul><ul><li>Viral Cultures </li></ul><ul><li>PCR </li></ul><ul><li>CSF </li></ul><ul><ul><li>Supportive tx </li></ul></ul><ul><ul><li>Analgesics </li></ul></ul><ul><ul><li>Antipyretics </li></ul></ul><ul><ul><li>Antiemetics </li></ul></ul><ul><ul><li>mortality is less than 1%. </li></ul></ul><ul><ul><li>Exposure to rodents suggests infection with lymphocytic choriomeningitis (LCM) virus and Leptospira infection . </li></ul></ul>
  34. 35. Fungal Meningitis <ul><li>Most common fungal cause of chronic meningitis is Cryptococcus neoformans (an encapsulated yeast), most often in patients with HIV/AIDS </li></ul><ul><li>Other are Coccidioides immitis , Histoplasma capsulatum , Blastomyces dermatitidis , Aspergillus fumigatus , Candida albicans , and Sporothrix schenckii. </li></ul><ul><li>Immunocompromised individuals, and presentation depends on the fungus involved. </li></ul><ul><li>Cryptococcal meningitis usually presents as headache, fever, and lethargy . Other symptoms are visual impairment, cranial neuropathies, ataxia, seizures, and altered cognition. </li></ul><ul><li>Diagnosis- CSF (Aseptic profile) lymphocytosis, decreased glucose levels, increased protein levels, positive culture tests, and a greatly elevated opening pressure upon lumbar puncture </li></ul><ul><li>Cultures and serology. C. neoformans- India ink stain/Crypto antigen (may be neg in capsule-deficient C neoformans ) </li></ul><ul><li>Amphotericin B AMB deoxycholate (AMBD) 0.7 to 1 mg/kg/day with flucytosine 100 mg/kg/day for 2 weeks , followed by fluconazole 400 mg/day orally for at least 10 weeks . Long-term fluconazole (usually 400 mg/day orally) may be used for secondary prophylaxis </li></ul>
  35. 36. Cryptococcus neoformans & HIV Cryptococcal meningitis is the most common opportunistic infection of the CNS, affecting 5-7% of patients with AIDS . The second most common type of meningitis is aseptic meningitis, which may be caused by HIV-1 itself. HIV-associated meningitis develops within days to weeks after HIV infection. It appears as a mononucleosis-like illness and is rarely associated with encephalitis. Tx with HAART
  36. 37. Parasitic Meningitis <ul><li>Amoeba </li></ul><ul><li>primary amebic meningoencephalitis (PAM) </li></ul><ul><li>Naegleria fowleri </li></ul><ul><li>southern tier states (AR, AZ, CA, FL, GA, LA, MO, MS, NC, NM, NV, OK, SC, TX, and VA). </li></ul><ul><li>Bodies of warm freshwater, such as lakes, rivers </li></ul><ul><li>Geothermal (naturally hot) water such as hot springs </li></ul><ul><li>Geothermal (naturally hot) drinking water sources </li></ul><ul><li>Warm water discharge from industrial plants </li></ul><ul><li>Poorly maintained and minimally-chlorinated or unchlorinated swimming pools </li></ul><ul><li>Soil </li></ul><ul><ul><li>Diagnosis </li></ul></ul><ul><ul><ul><li>CSF wet prep </li></ul></ul></ul><ul><ul><li>Treatment </li></ul></ul><ul><ul><ul><li>Amp B and miconazole </li></ul></ul></ul><ul><li>Helminths </li></ul><ul><ul><li>Angiostrongylus cantonensis </li></ul></ul><ul><ul><ul><li>Rat lungworm </li></ul></ul></ul><ul><ul><li>G. spinigerum </li></ul></ul><ul><ul><ul><li>GI parasite </li></ul></ul></ul><ul><ul><li>Treatment </li></ul></ul><ul><ul><ul><li>Supportive </li></ul></ul></ul>􀂄 Chronic meningitis include Taenia solium (pork tapeworm- Neurocycticercosis , the most common parasitic infection of the CNS ), Angiostrongylus cantonensis ( Rat lungworm ), Toxoplasma gondii , and Acanthamoeba species. Echinococcus granulosus ( Hydated Disease )
  37. 38. Neurocycticercosis <ul><li>most common in Latin America , Asia, Africa, and parts of Europe </li></ul><ul><li>can affect subcutaneous, muscle, or CNS ( ~ 50% meningitis) </li></ul><ul><li>can be asymptomatic, but sometimes symptoms such as severe headache, seizures , vision changes, and ischemic cerebrovascular disease </li></ul><ul><li>CSF findings usually include elevated protein levels, normal glucose levels, and eosinophilia. </li></ul><ul><li>albendazole 400 mg twice daily orally for 15 days, then 400 mg/day orally for 15 days and prednisone 60 mg/day orally for 3 days </li></ul>
  38. 39. TOXOPLASMOSIS <ul><li>eating undercooked meat of animals harboring tissue cysts     . </li></ul><ul><li>consuming food or water contaminated with cat feces or by contaminated environmental samples (such as fecal-contaminated soil or changing the litter box of a pet cat)     . </li></ul><ul><li>blood transfusion or organ transplantation     . </li></ul><ul><li>transplacentally from mother to fetus </li></ul><ul><li>Laboratory Studies </li></ul><ul><li>Serology </li></ul><ul><ul><li>Anti- Toxoplasma immunoglobulin detection </li></ul></ul><ul><ul><li>Rising serum (IgG) titers </li></ul></ul><ul><ul><li>(IgM) antibody response in newly acquired toxoplasmosis or Toxoplasma encephalitis. </li></ul></ul><ul><li>may be unreliable in immunodeficient individuals especially in AIDS </li></ul><ul><li>Serologic testing can be falsely negative or noncontributory if levels do not rise from a baseline. </li></ul><ul><ul><li>In one study, 16% of patients with a clinical diagnosis and 22% of patients with a histologic diagnosis of toxoplasmosis had undetectable anti- T gondii IgG levels. </li></ul></ul><ul><ul><li>Causes of false-negative results include recent infection and insensitive assays. </li></ul></ul><ul><li>The detection of Toxoplasma gondii by PCR may facilitate the diagnosis and follow-up of toxoplasmosis in patients with AIDS (sensitivity of 83.3% and specificity of 95.7%.) </li></ul>Toxoplasma gondii abscesses
  39. 40. TOXOPLASMOSIS <ul><li>CT scan or MRI </li></ul><ul><li>Single or multiple hypodense or hypointense lesions in white matter and basal ganglia with mass effects may be observed. </li></ul><ul><li>Lesions may enhance in a homogeneous or ring pattern with contrast. </li></ul><ul><li>Imaging studies may be normal in diffuse toxoplasmosis. </li></ul><ul><li>MRI is more sensitive than CT scan in detecting multiple lesions. </li></ul><ul><li>Single lesions favor the diagnosis of lymphoma over that of toxoplasmosis. However, while multiple lesions are more common than single lesions in toxoplasmosis, in one study 27% of patients had a single lesion on CT scan. In the same study, 14% had a single lesion on MRI. </li></ul><ul><li>Thallium Th 201 brain single-photon emission computed tomography ( SPECT ) may be useful in distinguishing between lymphoma and toxoplasmosis. Lymphoma shows an increased uptake compared with toxoplasmosis. False-positive and false-negative results may occur if the lesion is smaller than 2 cm. </li></ul><ul><li>Procedures </li></ul><ul><li>Indications for brain biopsy include the following: </li></ul><ul><ul><li>Single mass lesion and negative serologic results </li></ul></ul><ul><ul><li>No response to 14 days of empiric therapy </li></ul></ul>tissue cyst and tachyzoites in the brain parenchyma Ring-enhanced lesions in the right basal ganglia and the left frontal lobe with a large mass effect and peripheral oedema. ring-enhanced parieto-occipital lesion with a large mass effect and peripheral oedema.
  40. 41. TOXOPLASMOSIS Prevention & Treatment <ul><li>Reduce Risk of Toxo from the Environment </li></ul><ul><li>Avoid drinking untreated drinking water, particularly when traveling in less developed countries. </li></ul><ul><li>Wear gloves when gardening and during any contact with soil or sand because it might be contaminated with cat feces that contain Toxoplasma . Wash hands thoroughly after gardening or contact with soil or sand. </li></ul><ul><li>Keep outdoor sandboxes covered. </li></ul><ul><li>Feed cats only canned or dried commercial food or well-cooked table food, not raw or undercooked meats. </li></ul><ul><li>Change the litter box daily if you own a cat. The Toxoplasma parasite does not become infectious until 1 to 5 days after it is shed in a cat's feces. </li></ul><ul><ul><li>Avoid changing cat litter if possible. If no one else can perform the task, wear disposable gloves and wash your hands thoroughly with soap and water afterwards. </li></ul></ul><ul><ul><li>Keep cats indoors. </li></ul></ul><ul><ul><li>Do not adopt or handle stray cats, especially kittens. Do not get a new cat while you are pregnant. </li></ul></ul><ul><li>Reduce Risk of Toxo from Food </li></ul><ul><li>Reduce the risk of acquiring toxoplasmosis and other infections from food by following these guidelines: </li></ul><ul><li>Cook food to safe temperatures. A food thermometer should be used to measure the internal temperature of cooked meat. Do not sample meat until it is cooked. </li></ul><ul><ul><li>Lamb, beef, pork, or venison should be cooked to an internal temperature of 165°F-170°F throughout.* </li></ul></ul><ul><ul><li>Whole poultry should be cooked to 180°F in the thigh. </li></ul></ul><ul><li>Peel or wash fruits and vegetables thoroughly before eating. </li></ul><ul><li>Wash cutting boards, dishes, counters, utensils, and hands with hot soapy water after contact with raw meat, poultry, seafood, or unwashed fruits or vegetables. </li></ul><ul><li>Freeze meat for several days before cooking to greatly reduce chance of infection. </li></ul>Most healthy people recover from toxoplasmosis without treatment. Persons who are ill can be treated with a combination of drugs such as pyrimethamine and sulfadiazine , plus folinic acid .
  41. 42. Viral Encephalitidis <ul><li>Arboviruses are the most common causes of episodic encephalitis with </li></ul><ul><li>The 2 most common arboviruses </li></ul><ul><li>St Louis encephalitis , found throughout the United States but principally in urban areas around the Mississippi River </li></ul><ul><li>Geographically misnamed California virus (in particular, the strain that causes LaCross encephalitis [LAC]), which affects children in rural areas in states of the northern Midwest and East.   Among the other arboviruses causing encephalitis, the deadliest and, fortunately, most uncommon, eastern equine encephalitis (EEE), is encountered in New England and surrounding areas; the milder western equine encephalitis (WEE) is most common in rural communities west of the Mississippi River. </li></ul>
  42. 43. Domestic Arboviral Encephalitidis <ul><li>Eastern equine encephalitis also infects birds that live in freshwater swamps of the eastern U.S. seaboard and along the Gulf Coast. In humans, symptoms are seen 4-10 days following transmission and include sudden fever, general flu-like muscle pains, and headache of increasing severity, followed by coma and death in severe cases. About half of infected patients die from the disorder. Fewer than 10 human cases are seen annually in the United States. </li></ul><ul><li>Western equine encephalitis is seen in farming areas in the western and central plains states. Symptoms begin 5-10 days following infection. Children, particularly those under 12 months of age, are affected more severely than adults and may have permanent neurologic damage. Death occurs in about 3 percent of cases. </li></ul><ul><li>LaCrosse encephalitis occurs most often in the upper midwestern states (Illinois, Wisconsin, Indiana, Ohio, Minnesota, and Iowa) but also has been reported in the southeastern and mid-Atlantic regions of the country. Most cases are seen in children under age 16. Symptoms such as vomiting, headache, fever, and lethargy appear 5-10 days following infection. Severe complications include seizure, coma, and permanent neurologic damage. About 100 cases of LaCrosse encephalitis are reported each year. </li></ul><ul><li>St. Louis encephalitis is most prevalent in temperate regions of the United States but can occur throughout most of the country. The disease is generally milder in children than in adults, with elderly adults at highest risk of severe disease or death. Symptoms typically appear 7-10 days following infection and include headache and fever. In more severe cases, confusion and disorientation, tremors, convulsions (especially in the very young), and coma may occur. </li></ul><ul><li>Among less common causes of viral encephalitis , </li></ul><ul><li>Varicella-zoster encephalitis has an incidence of 1 in 2000 infected persons. </li></ul><ul><li>Measles produces 2 devastating forms of encephalitis: postinfectious, which occurs in about 1 in 1000 infected persons, and SSPE, occurring in about 1 in 100,000 infected patients. </li></ul><ul><li>Typically, 0-3 unrelated cases of rabies encephalitis are identified yearly. </li></ul>
  43. 44. Cumulative Total Entire Country: 547 West Nile Virus Cumulative 2010 Data as of 3 am, Sep 28, 2010 1 Kentucky 6 Kansas 3 Iowa 5 Indiana 18 Illinois 1 Idaho 10 Georgia 7 Florida 7 Connecticut 38 Colorado 50 California 3 Arkansas 101 Arizona 3 Alabama 2 Ohio 8 North Dakota 89 New York 11 New Mexico 17 New Jersey 2 Nevada 36 Nebraska 4 Missouri 5 Mississippi 3 Minnesota 16 Michigan 3 Massachusetts 9 Maryland 18 Louisiana 4 Wyoming 1 Wisconsin 2 Virginia 31 Texas 1 Tennessee 20 South Dakota 12 Pennsylvania
  44. 45. Domestic Arboviral Diseases West Nile Virus <ul><li>Clinical description </li></ul><ul><li>may be asymptomatic </li></ul><ul><li>meningitis: fever, headache, stiff neck, and pleocytosis in CSF </li></ul><ul><li>Myelitis: fever and acute bulbar or limb paresis or flaccid paralysis </li></ul><ul><li>Encephalitis: fever, headache, and AMS-confusion to coma </li></ul><ul><li>cranial and peripheral neuritis or other neuropathies, including Guillain-Barré syndrome. </li></ul><ul><li>West Nile fever [WNF], febrile illnesses (non-localized, self-limited illnesses with headache, myalgias, arthralgias, skin rash or lymphadenopathy </li></ul>WNV : between the months of July and September . incubation period ranges from three to 14 days .
  45. 46. Clinical criteria for diagnosis <ul><li>Neuroinvasive disease requires the presence of fever and at least one of the following </li></ul><ul><li>Acutely altered mental status (e.g., disorientation, obtundation, stupor, or coma), or </li></ul><ul><li>Other acute signs of central or peripheral neurologic dysfunction (e.g., paresis or paralysis, nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions, or abnormal movements), or </li></ul><ul><li>Pleocytosis (increased white blood cell concentration in cerebrospinal fluid [ CSF ]) associated with illness clinically compatible with meningitis (e.g., headache or stiff neck). </li></ul><ul><li>Non-neuroinvasive disease requires, at minimum, the presence of documented fever , as measured by the patient or clinician, the absence of neuroinvasive disease (above), and the absence of a more likely clinical explanation for the illness. Involvement of non-neurological organs (e.g., heart, pancreas, liver) should be documented using standard clinical and laboratory criteria </li></ul>West Nile Virus
  46. 47. Laboratory criteria for diagnosis Four-fold or greater virus-specific serum antibody titer , OR Isolation of virus from or demonstration of specific viral antigen or genomic sequences in tissue, blood, cerebrospinal fluid (CSF), or other body fluid, OR Elevated virus-specific immunoglobulin (IgG) antibodies in the acute or convalescent serum specimen as measured by VN or HI, or IgG enzyme immunoassay (EIA), OR Virus-specific immunoglobulin M (IgM) antibodies demonstrated in serum by IgM antibody-capture enzyme immunoassay (EIA) Case classification A case must meet one or more of the above clinical criteria and one or more of the above laboratory criteria. Confirmed case : Four-fold or greater change in virus-specific serum antibody titer, OR Isolation of virus from or demonstration of specific viral antigen or genomic sequences in tissue, blood, CSF, or other body fluid, OR Virus-specific immunoglobulin M (IgM ) antibodies demonstrated in CSF by antibody capture enzyme immunoassay (EIA), OR Virus-specific IgM antibodies demonstrated in serum by antibody-capture EIA and confirmed by demonstration of virus-specific serum immunoglobulin G (IgG) antibodies in the same or a later specimen by another serologic assay (e.g., neutralization or hemagglutination inhibition) Probable case : Stable (less than or equal to a two-fold change) but elevated titer of virus-specific serum antibodies , OR Virus-specific serum IgM antibodies detected by antibody-capture EIA but with no available results of a confirmatory test for virus-specific serum IgG antibodies in the same or a later specimen West Nile Virus
  47. 48. Caveat in Diagnosis <ul><li>In some persons, West Nile virus-specific serum IgM antibody can wane slowly and be detectable for more than one year following infection. Therefore, in areas where West Nile virus has circulated in the recent past, the co-existence of West Nile virus-specific IgM antibody and illness in a given case may be coincidental and unrelated. </li></ul><ul><li>In those areas, the testing of serially collected serum specimens assumes added importance. </li></ul><ul><li>Dengue fever and West Nile fever can be clinically indistinguishable, the importance of a recent travel history and appropriate serologic testing </li></ul><ul><li>No specific treatment is available. </li></ul><ul><li>In severe cases treatment consists of supportive care </li></ul>West Nile Virus
  48. 49. CMV Encephlitis <ul><li>Cytomegaloviral (CMV) infection usually presents as an encephaloventriculitis with possible meningeal involvement. </li></ul>Proton density-weighted (SE, 2700/30) axial and coronal images disclose hyperintensity surrounding the frontal horns and trigones of the lateral ventricles and also involving the splenium of the corpus callosum (arrows) .
  49. 50. Herpes simplex encephalitis (HSE) <ul><li>10 percent of all cases, the overall incidence is 0.2 per 100,000 </li></ul><ul><li>More than half of untreated cases are fatal </li></ul><ul><li>30 percent of cases due to primary infection, majority due to reactication of virus lying dormant in the trigeminal ganglia </li></ul><ul><li>The mortality rate of herpes simplex encephalitis in untreated patients is 70%. Among treated patients, the mortality rate is 19%, and more than 50% of survivors are left with moderate or severe neurological deficits . </li></ul><ul><li>HSV-1 : most often seen in persons under age 20 or over age 40 , single most important cause of fatal sporadic encephalitis in the U.S. </li></ul><ul><li>transmitted through contact with an infected person </li></ul><ul><li>Symptoms include headache and fever for up to 5 days, followed by personality and behavioral changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness. Brain damage in adults and in children beyond the neonatal period is usually seen in the frontal and temporal lobes and can be severe. </li></ul>
  50. 51. Herpes simplex encephalitis <ul><li>Type 2 virus (genital herpes) is most often transmitted through sexual contact. An infected mother can transmit the disease to her child at birth , through contact with genital secretions, but this is uncommon. In newborns, symptoms such as lethargy, irritability, tremors, seizures, and poor feeding generally develop between 4 and 11 days after delivery. </li></ul>
  51. 52. Herpes simplex encephalitis <ul><li>Typical symptoms include the following: </li></ul><ul><li>Fever (90%) </li></ul><ul><li>Headache (81%) </li></ul><ul><li>Psychiatric symptoms (71%) </li></ul><ul><li>Seizures (67%) </li></ul><ul><li>Vomiting (46%) </li></ul><ul><li>Focal weakness (33%) </li></ul><ul><li>Memory loss (24%) </li></ul><ul><li>Typical findings on presentation include the following: </li></ul><ul><li>Alteration of consciousness (97%) </li></ul><ul><li>Fever (92%) </li></ul><ul><li>Dysphasia (76%) </li></ul><ul><li>Ataxia (40%) </li></ul><ul><li>Seizures (38%) </li></ul><ul><ul><li>Focal (28%) </li></ul></ul><ul><ul><li>Generalized (10%) </li></ul></ul><ul><li>Hemiparesis (38%) </li></ul><ul><li>Cranial nerve defects (32%) </li></ul><ul><li>Visual field loss (14%) </li></ul><ul><li>Papilledema (14%) </li></ul>
  52. 53. Herpes simplex encephalitis <ul><li>Laboratory Studies </li></ul><ul><li>Serologic analysis </li></ul><ul><ul><li>Serologic evaluation of blood or CSF may be useful for retrospective diagnosis, but it has no role in the acute diagnosis and treatment of patients. </li></ul></ul><ul><ul><li>Strategies based on increases in antibody levels and on the ratio of antibody levels in serum and CSF have not proven to be clinically useful. </li></ul></ul><ul><li>CSF analysis </li></ul><ul><ul><li>Patients with herpes simplex encephalitis (HSE) typically have mononuclear pleocytosis of 10-500 WBCs/µL (average, 100 WBCs/µL). </li></ul></ul><ul><ul><li>As a result of the hemorrhagic nature of the underlying pathologic process, the RBC count may be elevated (10-500 RBCs/µL). </li></ul></ul><ul><ul><li>Protein levels are elevated to the range 60-700 mg/dL (average, 100 mg/dL). </li></ul></ul><ul><ul><li>Glucose values may be normal or mildly decreased (30-40 mg/dL). </li></ul></ul><ul><ul><li>In about 5-10% of patients, especially children, initial CSF results may be normal. However, on serial examinations, the cell counts and protein values increase. </li></ul></ul><ul><ul><li>Viral cultures of CSF are rarely positive and should not be relied on to confirm the diagnosis. </li></ul></ul><ul><li>Polymerase chain reaction </li></ul><ul><ul><li>PCR analysis of CSF for the detection of HSV DNA has virtually replaced brain biopsy as the criterion standard for diagnosis. </li></ul></ul><ul><ul><li>PCR is highly sensitive (94-98%) and specific (98-100%). </li></ul></ul><ul><ul><li>Results become positive within 24 hours of the onset of symptoms and remain positive for at least 5-7 days after the start of antiviral therapy. </li></ul></ul><ul><ul><li>Clinical severity and outcome appear to correlate with viral load as assessed by quantitative PCR techniques,16 but not all investigators have confirmed this. </li></ul></ul><ul><ul><li>False-negative findings may occur early in the course of the disease when viral DNA levels are low ( within 72 h of the onset of symptoms ) or when blood is present in the CSF , as hemoglobin may interfere with PCR.18 </li></ul></ul><ul><ul><li>Pretest probability should be considered in interpretation of results. A negative result obtained less than 72 hours after the onset of symptoms in a patient with a high pretest probability (fever, focal neurological abnormalities, CSF pleocytosis) should be repeated . </li></ul></ul><ul><ul><li>False-positive test results are rare and usually reflect accidental contamination of the specimen in the laboratory. </li></ul></ul>
  53. 54. Herpes simplex encephalitis ) <ul><li>Imaging Studies </li></ul><ul><ul><li>MRI of the brain is the preferred imaging study. Abnormalities are found in 90% of patients with HSE; MRI may be normal early in the course of illness. </li></ul></ul><ul><ul><li>Findings of localized temporal abnormalities are highly suggestive of HSE, but confirmation of the diagnosis depends on the identification of HSV by means of PCR or brain biopsy. </li></ul></ul><ul><ul><li>Head CT may show changes in the temporal and/or frontal lobe, but CT is less sensitive than MRI. </li></ul></ul><ul><ul><li>Approximately one third of patients with HSE have normal CT findings on presentation. </li></ul></ul><ul><ul><li>Electroencephalography </li></ul></ul><ul><ul><li>Electroencephalography ( EEG ) shows focal abnormalities, such as spike and slow- or periodic sharp-wave patterns over the involved temporal lobes. </li></ul></ul><ul><ul><li>EEG is 84% sensitive to abnormal patterns in HSE but lacks specificity (32%) </li></ul></ul>Axial gadolinium-enhanced T1-weighted image reveals enhancement of the right anterior temporal lobe and parahippocampal gyrus. At the right anterior temporal tip is a hypointense, crescentic region surrounded by enhancement consistent with a small epidural abscess.
  54. 55. Herpes simplex encephalitis (HSE) <ul><li>The diagnosis of HSE should be considered in any patient with a progressively deteriorating level of consciousness, fever, abnormal CSF findings, and focal neurological abnormalities in the absence of any other causes. </li></ul><ul><li>Rapid initiation of acyclovir therapy is crucial to reduce mortality and morbidity risks. </li></ul><ul><li>Since most relapses occur within 3 months of completing an initial course of intravenous acyclovir, a prolonged course of an oral antiviral agent (eg, valacyclovir ) has been suggested following initial treatment. </li></ul><ul><li>Steroids have been used to reduce cerebral edema in patients with severe HSE. </li></ul>
  55. 56. RABIES Patients with rabies could present atypically with aseptic meningitis , and rabies should be suspected in a patient with a history of animal bite (eg, skunk, raccoon, dog, fox, bat).
  56. 57. Rabies: Major Vector Species in the U.S.
  57. 58. RABIES CONTROL IN ANIMALS <ul><li>􀂄 Stray animal control </li></ul><ul><li>􀂄 Vaccination </li></ul><ul><li>􀂄 Humans </li></ul><ul><li>􀂄 Those at risk </li></ul><ul><li>􀂄 Dogs and cats (horses, cattle, sheep) </li></ul><ul><li>􀂄 Given by veterinarian every 3 years </li></ul><ul><li>􀂄 Ferrets (approved vaccine only) </li></ul>
  58. 59. RABIES - IF A PERSON IS BITTEN... <ul><li>1. Wash with soap and water </li></ul><ul><li>2. Rabies immunoglobulin (RIG) </li></ul><ul><li>􀂄 Given immediately into the wound </li></ul><ul><li>3. Rabies vaccination </li></ul><ul><li>􀂄 Given at day 0, 3, 7, 14, and 28 </li></ul>
  59. 60. Diagnosis <ul><li>Signs and Symptoms </li></ul><ul><ul><li>Similar to meningitis-Correspond with area of infection </li></ul></ul><ul><ul><ul><li>hallucinations, seizures, personality changes, aphasia, ataxia, CN deficits, DI, SIADH </li></ul></ul></ul><ul><li>CSF-Similar to viral meningitis </li></ul><ul><ul><li>↑↑ Opening pressure </li></ul></ul>
  60. 61. Progressive Multifocal Leukoencephalopathy (PML) <ul><li>Due to JC virus </li></ul><ul><li>Most patients are immunocompromised </li></ul><ul><li>Diagnosis </li></ul><ul><ul><li>MRI-Periventricular white matter lesions </li></ul></ul><ul><ul><li>CSF typically normal </li></ul></ul><ul><ul><ul><li>PCR for JVC DNA </li></ul></ul></ul><ul><li>Treatment-No effective treatment </li></ul><ul><ul><li>Neither cytarabine and cidofovir showed any benefits </li></ul></ul><ul><li>slow virus infections, such as those implicated in the measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML), </li></ul>
  61. 62. Prions
  62. 63. Examples of Prion Disease That Affects the Brain <ul><li>􀂄 Kuru </li></ul><ul><li>􀂄 Variant Creutzfield-Jacob Disease </li></ul><ul><li>(Mad Cow Disease) </li></ul><ul><li>􀂄 Chronic Wasting Disease (CWD) </li></ul><ul><li>in deer and elk </li></ul>
  63. 64. Noninfectious Causes <ul><li>Neurosarcoidosis - noncaseating granulomas in the lungs, skin, joints, eyes, and—rarely CNS- acute aseptic meningitis or chronic meningitis, meningeal mass lesions , meningitis is usually is caused by opportunistic organisms, (cryptococc) </li></ul><ul><li>CSF lymphocytosis or monocytosis, decreased or normal glucose levels, and increased protein levels. </li></ul><ul><li>oral corticosteroids. Methotrexate may be added to shorten the time </li></ul><ul><li>Aseptic meningitis can occur in people with SLE as a result of the lupus, from the medications (i.e., nonsteroidal anti-inflammatory drugs [ NSAIDs], azathioprine ) used for specific symptoms, or from opportunistic infections that develop in individuals receiving chronic immunosuppressive therapy. CSF findings typically include lymphocytosis, increased protein levels, and variable glucose levels. </li></ul><ul><li>WG is a severe, necrotizing, granulomatous systemic vasculitis associated with the ANCA antibody. It mostly involves the respiratory tract and kidneys, but may also affect the eyes and CNS. Chronic meningitis, a rare complication of WG, is treated with high-dose corticosteroids and cyclophosphamide </li></ul>

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