Cns infections Lecture

9. The classic presentation of meningitis includes the triad fever, sever neck stiffness/rigidity, called meningismus, and change in mental status (eg, lethargy, confusion, irritability, delirium, and coma) Signs of meningeal irritation are observed in only approximately 50% of patients with bacterial meningitis, and their absence certainly does not rule out meningitis. • Kernig sign: flex patients hip to a 90° angle and then attempting passively straighten the leg at the knee produces pain in the hamstrings and resistance to further extension. Should present bilaterally to support the meningitis diagnosis. • Brudzinski sign: is positive if the patients hips and knees flex automatically when the examiner flexes the patients neck while the patient is supine. • Nuchal rigidity: Resistance to passive flexion of the neck is also a sign. • Headache-Exacerbation of existing headache by repeated horizontal movement of the head, at a rate of 2-3 times per second, may also suggest meningeal irritation. • Cranial nerve palsies may be observed as a result of increased ICP or the presence of exudates encasing the nerve roots. • Nuchal rigidity (generally not present in children <1 y or in patients with altered mental status) • Fever and chills • Photophobia • Vomiting • Prodromal upper respiratory infection (URI) symptoms (viral and bacterial) • Seizures (30-40% in children, 20-30% in adults) • Papilledema is present in only one third of meningitis patients with increased ICP; it takes at least several hours to develop.

10. Brudzinski Sign of Meningitis:

11. Kernig’s Sign of Meningitis:

12. Systemic findings upon physical examination may provide clues to the etiology. o Skin findings range from a nonspecific blanching, erythematous, maculopapular rash to a petechial or purpuric rash, most characteristic of meningococcal meningitis. Commonly affects the trunk and extremities. Symptoms in infants Cardinal signs of meningitis (eg, fever, vomiting, stiff neck) are rarely present. For neonatal meningitis, these signs are the exception, rather than the rule. • Lethargy and/or change in level of alertness • Poor feeding and/or vomiting • Respiratory distress • Bulging fontanelle • Paradoxic irritability (ie, quiet when stationary, cries when held) • High-pitched cry • Hypotonia • Approximately 6% of affected infants and children show signs of disseminated intravascular coagulopathy and endotoxic shock. These signs are indicative of a poor prognosis.

13. Meningitis is caused by the following pathogens in each age group: • Beyond the neonatal period, the 3 most common organisms that cause acute bacterial meningitis are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (Hib). • Neonates - Group B or D streptococci, nongroup B streptococci, Escherichia coli, and L monocytogenes • Infants and children -H influenzae (48%), S pneumoniae (13%), and N meningitidis • Adults -S pneumoniae, (30-50%), H influenzae (1-3%), N meningitidis (10-35%), gram-negative bacilli (1-10%), staphylococci (5-15%), streptococci (5%), and Listeria species (5%)

14. Etiology of neonatal meningitis oBacteria are often acquired from the maternal vaginal flora. oEarly onset group B streptococcal meningitis occurs during the first 7 days of life, a consequence of maternal colonization and the absence of protective antibody in the neonate; it is often associated with obstetric complications. The disease is seen most often in premature or low birth weight babies. Pathogens are acquired before or during the birth process. Etiology of meningitis in infants and children: In children older than 4 weeks, S pneumoniae and N meningitidis are the most common etiologic agents. H influenzae type b has essentially disappeared in countries where the conjugate vaccine is routinely used. oMost deaths occur within 24 hours of hospital admission in patients who have features associated with poor prognosis (eg, hypotension, shock, neutropenia, extremes of ages, petechiae and purpura of <12 h duration, disseminated intravascular coagulopathy, acidosis, presence of organism in WBC on peripheral smear, low erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP], serogroup C disease).

15. S pneumoniae meningitis oS pneumoniae are lancet-shaped, gram-positive diplococcic, 84 serotypes. oIt is a common colonizer of the human nasopharynx (5-10% of healthy adults and 20-40% of healthy children). oPresently, it is the most common bacterial cause of meningitis, accounting for 47% of cases. oChildren of any age may be affected, but incidence and severity are highest in very young and elderly persons.

16. N meningitidis meningitis oN meningitis is a gram-negative diplococcus that is carried in the nasopharynx of otherwise healthy individuals. It initiates invasion by penetrating the airway epithelial surface. oPresently, it is the leading cause of bacterial meningitis in children and young adults, accounting for 59% of cases. oMost cases occur in infants aged 6-12 months; a second lower peak occurs among adolescents. A petechial or purpuric rash frequently is seen. oMost deaths occur within 24 hours of hospital admission in patients who have features associated with poor prognosis (eg, hypotension, shock, neutropenia, extremes of ages, petechiae and purpura of <12 h duration, disseminated intravascular coagulopathy, acidosis, presence of organism in WBC on peripheral smear, low erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP], serogroup C disease).

17. H influenzae type b meningitis o H influenzae type b is a gram-negative rod frequently found as part of the normal flora in the upper respiratory tract. o H influenzae meningitis occurs primarily in children who have not been immunized with H influenzae type b vaccine, with 80-90% of the cases occurring in children aged 1 month to 3 years o Its isolation in adults suggests the presence of an underlying medical disorder, including paranasal sinusitis, otitis media, alcoholism, CSF leak following head trauma. o Since the implementation of the HIB vaccine, the carriage rates for the B strain have decreased from 2-4% to less than 1% o Current mortality rates are less than 5%. Most fatalities occur during the first few days of the illness. o It can spread from one individual to another by airborne droplets or direct contact with secretions.

18. General guidelines The cornerstone in the diagnosis of meningitis is examination of the CSF. Bacterial meningitis is a medical emergency. A firm diagnosis is usually made when bacteria are isolated from the cerebrospinal fluid (CSF) and evidence of meningeal inflammation is demonstrated by increased pleocytosis, elevated protein level, and low glucose level in the CSF. Measure the opening pressure and send the fluid for cell count (and differential count), chemistry (ie, CSF glucose and protein), and microbiology (ie, Gram stain and cultures).The opening pressure of CSF should be measured in older children. Similarly, the color of the CSF (eg, turbid, clear, bloody) should be recorded.

19. The bacterial meningitis score : Positive cerebrospinal fluid Gram stain CSF absolute neutrophil count greater than or equal to 1000 cells/mcL CSF protein greater than or equal to 80 mg/dL Peripheral blood absolute neutrophil count greater than or equal to 10000 cells/mcL History of seizure before or at the time of presentation

21. • Examination of the CSF in patients with acute bacterial meningitis reveals the characteristic neutrophilic pleocytosis (usually hundreds to a few thousand, with >80% PMN cells). In some cases of L monocytogenes meningitis (25-30%), a lymphocytic predominance may occur. Low CSF WBC count (<20 cells/µL) in the presence of a high bacterial load suggests a poor prognosis. • The opening pressure (reference range is 80-200 mm H2O) may be elevated, suggesting some form of increased ICP from cerebral edema. • The CSF glucose (reference range is 40-70 mg/dL) is less than 40 mg/dL in 60% of patients. Obtain a simultaneous blood glucose determination for comparison purposes. Some patients may have elevated blood sugar levels as a result of underlying diabetes mellitus, and the predictive value of the CSF and blood sugar ratio may not be accurate in these circumstances. • The CSF protein (reference range is 20-50 mg/dL) is usually elevated.

22. Table 1. Comparison of CSF Findings by Type of Organism Bacterial Meningitis Viral Meningitis* Fungal Meningitis** Pressure 5-15 cm H 2 O Increased Normal or mildly increased Normal or mildly increased in TB. May be increased in fungal. AIDS patients with cryptococcal meningitis have increased risk of blindness, death unless maintained at <30 cm. Cell count preterm: 0-25 term: 0-22 >6 months: 0-5 mononuclear cells/mm 3 No cell count result can exclude bacterial meningitis. Typically thousands of PMNs, but may be less dramatic or even normal (classically, in very early meningococcal meningitis and in extremely ill neonates). Lymphocytosis with normal CSF chemistries seen in 15-25%, especially when cell counts <1000 or if partially treated. Approximately 90% of patients with ventriculoperitoneal shunts have CSF WBC count >100 cells/mm 3 are infected; CSF glucose usually normal, and organisms are less pathogenic. Cell count and chemistries normalize slowly (over days) with antibiotics. Usually <500 cells, nearly 100% mononuclear. Up to 48 hours, significant PMN pleocytosis may be indistinguishable from early bacterial meningitis; this is particularly true with eastern equine encephalitis. Presence of nontraumatic RBCs in 80% of HSV meningoencephalitis, although 10% have normal CSF results Hundreds of mononuclear cells Micro no organisms Gram stain 80% effective. Inadequate decolorization may mistake H influenzae for gram-positive cocci. Pretreatment with antibiotics may affect stain uptake, causing gram-positive organisms to appear gram negative and decrease culture yield on average 20%. No organism India ink 80-90% effective for fungi; AFB stain 40% effective for TB (increase yield by staining supernate from at least 5 cc CSF) Glucose euglycemia: >50% serum hyperglycemia: >30% serum wait 4 h after glucose load Decreased Normal Sometimes decreased. Aside from fulminant bacterial meningitis, the lowest levels of CSF glucose are seen in TB, primary amebic meningoencephalitis, neurocysticercosis Protein preterm: 65-150 term: 20-170 >6 months: 15-45 mg/dL Usually >150, may be >1000 Mildly increased Increased; >1000 with relatively benign clinical presentation suggestive of fungal disease

23. • CSF Gram stain permits rapid identification of the bacterial cause in 60-90% of patients with bacterial meningitis. The presence of bacteria is 100% specific, but the sensitivity for detection is variable. The likelihood of detection is higher in the presence of a higher bacterial concentration and diminishes with prior antibiotic use. • CSF bacterial cultures yield the bacterial cause in 70-85% of cases. The yield diminishes significantly in patients who have received antimicrobial therapy. In these cases, some experts advocate the use of a CSF bacterial antigen assay. This is a latex agglutination technique that can detect the antigens of HIB, S pneumoniae, N meningitidis, E coli K1, and S agalactiae. Its theoretical advantage is the detection of the bacterial antigens even after microbial killing, as is observed following antibacterial therapy. Others, however, have shown that it may not be better than the Gram stain. It is specific (a positive result indicates a diagnosis of bacterial meningitis), but a negative finding on bacterial antigen test does not rule out meningitis (50-95% sensitivity). • Obtain blood cultures and appropriate cultures from possible sites of infection. Obtain these promptly and prior to the administration of an antibacterial agent. The utility of these cultures is most evident in cases when the performance of a lumbar puncture is delayed by the need for head imaging (risk for herniation in a patient with focal neurologic deficit or coma) and when antimicrobial therapy is rightfully initiated before the lumbar puncture and neuroimaging tests.

24. Acute viral meningitis • The CSF picture of acute viral meningitis is different from the CSF picture of bacterial meningitis. • The opening pressure is usually within the reference range. • The CSF cell count is usually in the few hundreds (100-1000 cells/µL) with a predominance of lymphocytes. Some cases of echovirus, mumps, and HSV meningitis may produce a neutrophilic picture early in the course of disease. • The CSF glucose level is usually within the reference range, but some cases of LCM, HSV, mumps, and polio may cause low CSF glucose levels. • CSF protein levels may be within the reference range but are usually elevated. • PCR assay Cryptococcal meningitis • The definitive diagnosis usually relies on the demonstration of the specific fungal pathogen in the CSF. • The CSF is characterized by a lymphocytic pleocytosis (10-200 lymphocytes), a reduced glucose level, and an elevated protein level. • The CSF opening pressure may be elevated at times, suggesting increased ICP. • The CSF picture of other fungal meningitis is similar to the CSF picture of cryptococcal meningitis, usually with lymphocytic pleocytosis.

25. Tuberculosis meningitis • The CSF of patients with tuberculosis meningitis is characterized by a predominantly lymphocytic pleocytosis, usually in the hundreds. • The opening CSF pressure is usually elevated. • A characteristic hypoglycorrhagia (glucose <40 mg/dL) is present, and the protein level is usually elevated, especially if a CSF block is present. • The demonstration of the acid-fast bacilli in the CSF is difficult and usually requires a large volume of CSF. • Meningeal biopsy, with the demonstration of caseating granulomas and acid-fast bacilli on the smear, may prove useful because it has a higher yield than the CSF acid-fast bacilli smear. • The culture for Mycobacterium usually takes several weeks and may delay definitive diagnosis. • PCR • The need for mycobacterial growth in cultures remains because this offers the advantage of performing drug susceptibility assays.

26. Lumbar puncture o Elevated opening pressure correlates with increased risk of morbidity and mortality in bacterial and fungal meningitis. o Take tube #1 to chemistry lab for glucose and protein. o Take tube #2 to hematology lab for cell count with differential. o 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. o Hold tube #4 for repeat cell count with differential, if needed (or for other subsequent studies not initially ordered). o Research correlates CSF cytokines in children with bacterial meningitis.

27. Neonatal Initiate treatment as soon as bacterial meningitis is suspected. Ideally, blood and cerebrospinal fluid (CSF) cultures should be obtained before antibiotics are administered. Fluid and electrolyte management By prescribing the correct type and volume of fluid, the risk of development of brain edema can be minimized. The child should receive fluids sufficient to maintain systolic blood pressure at around 80 mm Hg, urinary output of 500 mL/m2/d, and adequate tissue perfusion. Although care to avoid SIADH is important, underhydrating the patient and risk of decreased cerebral perfusion are equally concerning as well.

28. Traditionally, initial antimicrobial treatment consists of ampicillin and an aminoglycoside combination (ampicillin and cefotaxime also appropriate).As per the 2004 Infectious Diseases Society of America (IDSA) practice guidelines for bacterial meningitis, the combination of vancomycin and either ceftriaxone or cefotaxime is recommended for those with suspected bacterial meningitis, with targeted therapy based upon susceptibilities of isolated pathogens. This combination provides adequate coverage for most penicillin-resistant pneumococci and beta-lactamase resistant H influenzaetype b. Once the pathogen has been identified and antimicrobial susceptibilities determined, the antibiotics may be modified for optimal targetted treatment.

29. One of the major contributors to the morbidity associated with bacterial meningitis is the severity of inflammation. Decreased inflammation, reduction in cerebral edema and intracranial pressure, and lessening brain damage with use of dexamethasone.As a result, the IDSA guidelines recommend the use of adjunctive dexamethasone in cases of H influenzae type b meningitis to be initiated 10-20 minutes prior to or at least concomitant with the first antimicrobial dose at 0.15 mg/kg q6h for 2-4 days.

30. Table.Specific Antibiotics and Duration of Therapy for Patients With Acute Bacterial Meningitis Bacteria Susceptibility Antibiotic(s) Duration (Days) S pneumoniae Penicillin MIC <0.1 mg/L Penicillin G 10-14 MIC 0.1-1 mg/L Ceftriaxone or cefotaxime MIC >2 mg/L Ceftriaxone or cefotaxime Ceftriaxone MIC >0.5 mg/L Ceftriaxone or cefotaxime plus vancomycin or rifampin H influenzae Beta-lactamase-negative Ampicillin 7 Beta-lactamase-positive Ceftriaxone or cefotaxime N meningitidis ... Penicillin G or ampicillin 7 L monocytogenes ... Ampicillin or penicillin G plus an aminoglycoside 14-21 S agalactiae ... Penicillin G plus an aminoglycoside, if warranted 14-21 Enterobacteriaceae ... Ceftriaxone or cefotaxime plus an aminoglycoside 21 P aeruginosa ... Ceftazidime plus an aminoglycoside 21

47. T1-weighted MRI of brain demonstrates diffuse enhancement of the meninges in viral meningoencephalitis.

51. Destruction of inferior frontal and anterior temporal lobes – necrotizing inflammation

56. Top Image: Axial diffusion-weighted image reveals restricted diffusion in the left medial temporal lobe consistent with herpes encephalitis. This patient also had a positive result on polymerase chain reaction assay for herpes simplex virus, which is both sensitive and specific. In addition, the patient had periodic lateralized epileptiform discharges on electroencephalogram, which supports the diagnosis of herpes encephalitis. Bottom Image: Coronal T2-weighted image reveals hyperintensity in the left temporal lobe ( arrows ) in a distribution similar to the restricted diffusion abnormality seen in the previous image. This finding is typical for herpes encephalitis. In patients with HHV6 infection, one series noted that in addition to mesial temporal lobe abnormality, abnormal T2 hyperintensity has been seen in the insular and inferior frontal region, which may suggest the diagnosis. There are felt to be 2 typical imaging appearances: one seen in older adults involves T2 hyperintensity confined to the medial temporal lobe; in young adults, a more varied pattern has been described that includes foci of restricted diffusion with an otherwise normal magnetic resonance, diffuse cortical necrosis, or small focal regions of abnormal T2 hyperintensity.

61. Poliomyelitis Pathophysiology The virus enters via the oral route and multiplies in the intestinal mucosa lymphoid tissues in the pharynx, it is usually present in the throat and stool before clinical onset. Within 1 week of clinical onset little virus exists in the throat, but it continues to be excreted in the stool for several weeks. The virus invades the local lymphoid tissue, enters the blood stream and then infects the CNS. Viral replication in the anterior horn cells of the spinal cord and the brainstem motor neuron cells results in cell destruction and paralysis.

66. Rabies Virus (Rhabdovirus)-Treatment Treatment after exposure, known as post-exposure prophylaxis (PEP) , is highly successful in preventing the disease if administered promptly, generally within ten days of infection. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is very effective at reducing the number of viral particles. If available, a virucidal antiseptic such as povidone-iodine, iodine tincture, aqueous iodine solution or alcohol (ethanol) should be applied after washing. Exposed mucous membranes such as eyes, nose or mouth should be flushed well with water. One dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a fourteen day period . The immunoglobulin dose should not exceed 20 units per kilogram body weight. As much as possible of this dose should be infiltrated around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site. The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days three, seven and fourteen after the first. Patients who have previously received pre-exposure vaccination do not receive the immunoglobulin, only the post-exposure vaccinations on day 0 and 2.

75. Tuberculous meningitis-Pathophysiology T1 w MRI IMAGE Tuberculoma is the round gray mass in the left corpus callosum. The red meninges on the right are consistent with irritation and probable meningeal reaction to tuberculosis. Tuberculomas are conglomerate caseous foci within the substance of the brain. Under conditions of poor host resistance, this process may result in focal areas of cerebritis or frank abscess formation, but the usual course is coalescence of caseous foci and fibrous encapsulation (ie, tuberculoma).

77. Brain and spine Tuberculosis-Neuroimaging T2-weighted magnetic resonance image of the thoracic spinal cord of a patient with 2 hyperintense intramedullary tuberculomas.

81. Brain and spine Tuberculosis-Neuroimaging T2-weighted magnetic resonance image of a patient with a tuberculoma in the right parietal lobe.

86. Progressive multifocal leukoencephalopathy-Pathology-demyelinative foci

88. PML-Neuroimaging Contrast-enhanced T1-weighted MRI demonstrates a hypointense lesion predominantly in a subcortical, left frontoparietal location. Note the characteristic absence of enhancement and lack of mass effect.

89. PML-Neuroimaging Fluid-attenuated inversion recovery (FLAIR) MRI shows a PML lesion with improved contrast after the suppression of cerebrospinal fluid signal intensity.

90. PML-Neuroimaging Nonenhanced CT of the head shows a hypoattenuating lesion in the subcortical white matter. Note the characteristic scalloped lateral margin.

91. PML-Neuroimaging Fluid-attenuated inversion recovery (FLAIR) images in a patient with HIV infection presenting with visual defects, aphasia, and balance problems. Patchy, confluent, and hyperintense lesions are seen in the left occipitotemporoparietal lobes in the subcortical and periventricular white matter. The patient's clinical and radiologic features suggested progressive multifocal leukodystrophy, though cerebrospinal fluid results for the JC virus were negative.

96. Neuro-Cyptococcosis-Pathology Opaque thick fibrotic CSF obstruction - hydrocephalus. Gelatinous material within the subarachnoid space and small cysts within the parenchyma (&quot;soap bubbles“) Specially in the basal ganglia.

97. Neuro-Cyptococcosis-Treatment The nature and duration of treatment for cryptococcal infection is based on the immunity of the host and anatomic sites of involvement. For immunocompetent individuals with cryptococcal meningitis, the standard therapy consists of amphotericin B 0.7-1.0 mg/kg/day along with 5-flucytosine 100 mg/kg/day for 6-10 weeks. An alternative to this regimen is amphotericin B 0.7-1.0 mg/kg/day plus 5-flucytosine 100 mg/kg/day for two weeks, followed by fluconazole 400mg/day for a minimum of ten weeks. Fluconazole &quot;consolidation&quot; therapy may be continued for as long as 6-12 months, depending on the clinical status of the patient. For patients with HIV infection and cryptococcal meningitis, induction therapy with amphotericin B 0.7-1.0 mg/kg/day plus 5-flucytosine 100 mg/kg/day is given for two weeks, followed by fluconazole 400mg/day for a minimum of ten weeks. After ten weeks of therapy, the fluconazole dosage may be reduced to 200 mg/day, depending on the clinical status of the patient. Fluconazole should be continued for life or at least up to the time the CD4+ count reaches 350/cmm.

98. Neuro-Cyptococcosis-Treatment Elevated intracranial pressure occurs in up to 75% of the patients with cryptococcal meningitis and is an important contributor to mortality and morbidity. Treated aggressively-percutaneous lumbar drainage or ventriculoperitoneal shunting or acetazolamide. In patients with normal baseline opening pressure (< 200 mm H 2 O), a repeat lumbar puncture should be performed two weeks after the initiation of therapy to exclude elevated pressure and to evaluate culture status. Prognosis The majority of the patients with cryptococcal meningitis improve with adequate therapy. Mortality is seen in about 10% of the cases while morbidity is unusual. Mortality is more common in HIV-positive individuals.

99. Neuro-Cyptococcosis-Neuroimaging T2 MRI Multicystic form of cerebral cryptococcosis: lesions in basal ganglia and cerebellum

100. Neuro-Cyptococcosis-Neuroimaging T2 W MRI Small cystic lesions in basal ganglia

101. CNS cryptococcosis: brain MRI findings (A) Axial T2 sequence showing bilateral pseudocysts as hyperintensities (arrowheads) predominantly involving the basal ganglia. The pseudocysts are thick walled and septated with a proteinaceous content depicted by their relative hyperintensity compared to CSF. (B) Post-gadolinium MRI sequences showing little to no enhancement of the cysts or surrounding parenchyma. Neuro-Cyptococcosis-Neuroimaging

103. Nocardiosis Nocardiosis is an acute, subacute, or chronic infectious disease that occurs in cutaneous, pulmonary, and disseminated forms. Disseminated nocardiosis may involve the brain or meninges, usually from a pulmonary focus. Most persons with disseminated nocardiosis have underlying immunocompromising disease or are receiving immunosuppressive therapy. Pathophysiology Members of the genus Nocardia are aerobic actinomycetes that are ubiquitous saprophytes in soil, decaying organic matter, and water. Nocardia asteroides is responsible for most cases of Nocardia disease among humans. High-power microscopic appearance of Nocardia .

104. Nocardiosis Diagnosis Brain biopsy is the most reliable diagnostic technique if the diagnosis cannot be made by evaluation of pulmonary or skin lesion.

106. Nocardiosis-Treatment Sulfonamides have long been the first-line antimicrobial therapy for nocardiosis. Among the sulfonamides, sulfadiazine is generally preferred because of its CNS and CSF penetration. Alternative parenteral therapies include meropenem, third-generation cephalosporins (cefotaxime or ceftriaxone), and , alone or in combination. Meropenem plus amikacin (synthetic aminoglycoside) may be the preferred regimen. Surgery-Needle aspiration or surgical excision needed in most. Relapse common Mortality/Morbidity • Cure rates with appropriate therapy are approximately 100% in skin and soft-tissue infections. • Ninety percent of pleuropulmonary infections can be cured with appropriate therapy. • The cure rate in disseminated nocardiosis falls to 63%, while only half of patients with brain abscess can be cured with therapy. sulfadiazine meropenem amikacin

120. Neurocysticercosis-Neuroimaging CT scans showing different phases of neurocysticercosis.Top left: CT scan showing many calcifications and active cysts with scolices in both hemispheres.Top right: T1-weighted MRI showing 2 active cysts with the scolex in their interior (vesicular phase).Bottom left: Postcontrast CT scan showing a ring-enhancing cyst (colloidal phase) on left.Bottom right: Proton density-weighted MRI showing a thick capsule with adjacent scolex and perilesional edema (colloidal phase).

121. Neurocysticercosis-Neuroimaging Neuroimaging in neurocysticercosis. Cysticercotic encephalitis.Left: Contrast-enhanced CT scan showing multiple, small, nodular, and annular areas of abnormal enhancement in brain parenchyma.Right: Gadolinium-enhanced T1-weighted MRI showing hyperintense lesions.

124. Toxoplasmosis Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii . Up to one third of the world's human population is estimated to carry a Toxoplasma infection. Clinical manifestations Four major T. gondii clinical syndromes occur: congenital, ocular, lymphadenopathic, and severe neurologic or disseminated diseases. Acute toxoplasmosis During acute toxoplasmosis, symptoms are often influenza-like: swollen lymph nodes, or muscle aches and pains that last for a month or more. Rarely, a patient with a fully functioning immune system may develop eye damage or nasal lesions from toxoplasmosis. After the first few weeks of infection have passed, the parasite rarely causes any symptoms in otherwise healthy adults. However, subjects with HIV/.AIDS or those who are pregnant, may become seriously ill. Infants infected via placental transmission may be born with either of these problems, or with nasal malformations. Acute toxoplasma infection can leads to psychotic symptoms similar to schizophrenia. Latent toxoplasmosis In most immunocompetent patients, the infection enters a latent phase, during which only bradyzoites are present, forming cysts in nervous and muscle tissue. Occurs in 50% of immunocompromised patients. Diffuse encephalitis, meningoencephalitis, or focal cerebral mass lesions are common presentations in patients with AIDS or HIV with toxoplasmosis.

125. Toxoplasmosis-Transmission Toxoplasma eggs are shed in cat feces. After their release in the soil, these eggs require 24 hours to become infectious. Cats excrete the pathogen in their faeces for a number of weeks after contracting the disease, generally by eating an infected rodent. Intermediate hosts (dogs, rodents, food animals, and humans) become contaminated by ingesting Toxoplasma eggs. In the soil, the eggs can remain infectious for more than 1 year. Ingestion of raw or partly cooked meat, especially pork, lamb, or venison containing Toxoplasma cysts. Infection prevalence in countries where undercooked meat is traditionally eaten has been related to this transmission method. Oocysts may also be ingested during hand-to-mouth contact after handling undercooked meat, or from using knives, utensils, or cutting boards contaminated by raw meat. Pregnancy precautions Congenital toxoplasmosis is a special form in which an unborn child is infected via the placenta. A positive antibody titer indicates previous exposure and immunity and largely ensures the unborn baby's safety. A simple blood draw at the first pre-natal doctor visit can determine whether or not the woman has had previous exposure and therefore whether or not she is at risk.

126. Toxoplasmosis Diagnosis The indirect fluorescent Ab test measuring IgG Ab is the most widely used diagnostic tool. Detection of T. gondii in human blood samples may be also achieved by using the PCR. Treatment Acute • Pyrimethamine (antimalarial) 4-6 weeks • Sulfadiazine -in combination with pyrimethamine. • Clindamycin • Cotrimoxazole or spiramycin-used for pregnant women to prevent the infection of their child. Latent • In latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration. • Atovaquone - used to kill Toxoplasma cysts in AIDS patients. • Clindamycin - in combination with atovaquone Pyrimethamine spiramycin Atovaquone Clindamycin

127. Toxoplasmosis-Pathology CNS toxoplasmosis, which has a propensity for involvement of the basal ganglia.

133. Prion Related Diseases • The prion diseases are a large group of related neurodegenerative conditions, which affect both animals and humans. • Prion diseases are unique in that they can be inherited, they can occur sporadically, or they can be infectious. • These diseases all have long incubation periods but are typically rapidly progressive once clinical symptoms begin. Table. Prion-Related Diseases, Hosts, and Mechanism of Transmission Disease Host Mechanism Kuru Human Cannibalism Sporadic CJD Human Spontaneous PrP C to PrP Sc conversion or somatic mutation Iatrogenic CJD Human Infection from prion-containing material Familial CJD Human Mutations in the PrP gene vCJD Human Infection from BSE GSS Human Mutations in the PrP gene FFI Human D178N mutation in the PrP gene, with M129 polymorphism Sporadic fatal insomnia Human Spontaneous PrP C to PrP Sc conversion or somatic mutation Scrapie Sheep Infection in susceptible sheep BSE Cattle Infection from contaminated food

134. Prion Related Diseases-Pathophysiology The infectious agent in the prion disease is composed mainly or entirely of an abnormal conformation of a host-encoded glycoprotein called the prion protein. PrPC is a glycosylphosphatidylinositol-anchored cell-surface glycoprotein. PrP is found in most tissues of the body but is expressed at highest levels in the CNS, in particular in neurons. The replication of prions involves the recruitment of the normally expressed prion protein, which has mainly an alpha-helical structure, into a disease-specific conformation that is rich in beta-sheet, initiating a self-perpetuating vicious cycle. A unifying feature of all the prionoses is their neuropathology. These illnesses tend to affect the gray matter, producing neuronal loss affecting the cerebral hemispheres and cerebellum, gliosis, and characteristic spongiform change. In approximately 10% of patients with CJD, amyloid is present in the cerebellum or in the cerebral hemispheres. Prion-related diseases. Spongiform change in prion disease. This section shows mild parenchymal vacuolation and prominent reactive astrocytosis.