<ul><li>Bacteria can grow in the cerebrospinal fluid in the subarachnoid space of the CNS. </li></ul><ul><li>Meningitis: Inflammation of meninges. Bacterial infection involving the leptomeninges within the subarachnoid space. </li></ul><ul><li>Infection of leptomeninges </li></ul><ul><li>Skull or backbone fractures </li></ul><ul><li>Medical procedures </li></ul><ul><li>Along peripheral nerves </li></ul><ul><li>Blood or lymph </li></ul><ul><li>Encephalitis: Inflammation of the brain. </li></ul>
<ul><li>Depending on the duration of symptoms, meningitis may be classified as acute or chronic: </li></ul><ul><li>Acute meningitis evolution of symptoms within hours to several days, Acute meningitis (<1 d) is almost always a bacterial infection. Expedient diagnosis is essential-Medical emergency </li></ul><ul><li>Patients with acute bacterial meningitis may decompensate very quickly and so they require emergency care, including antimicrobial therapy, ideally within 30 minutes of emergency department (ED) presentation. </li></ul><ul><li>Most bacterial meningitis is not acute. Approximately 75% of patients with bacterial meningitis present subacutely with symptoms beginning several days prior. </li></ul>
• 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%)
<ul><li>Mortality/Morbidity </li></ul><ul><li>Bacterial meningitis was uniformly fatal before the antimicrobial era. With the advent of antimicrobial therapy, the overall mortality rate from bacterial meningitis has decreased but remains alarmingly high approximately 25%. </li></ul><ul><li>Sex </li></ul><ul><li>male-to-female ratio is 3:1. </li></ul><ul><li>Age </li></ul><ul><li>Very young individuals (infants and young children) and elderly individuals (>60 y) are more predisposed to the infection. </li></ul><ul><li>Newborns are at highest risk for acute bacterial meningitis. After the first month of life, the peak incidence is in infants aged 3-8 months. </li></ul>
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.
Brudzinski Sign of Meningitis: • Brudzinski sign: is positive if the patients hips and knees flex automatically when the examiner flexes the patients neck while the patient is supine.
Kernig’s Sign of 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.
<ul><li>Headache -Exacerbation of existing headache by repeated horizontal movement of the head, at a rate of 2-3 times per second, indicates meningeal irritation. </li></ul><ul><li>• Papilledema & Cranial nerve palsies may be observed as a result of increased ICP or the presence of exudates encasing the nerve roots. </li></ul><ul><li>• Fever and chills </li></ul><ul><li>• Photophobia </li></ul><ul><li>• Vomiting </li></ul><ul><li>• Seizures (30-40% in children, 20-30% in adults) </li></ul>
Systemic findings upon physical examination may provide clues to the etiology. 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.
General guidelines The cornerstone in the diagnosis of meningitis is examination of 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.
<ul><li>If the spinal fluid is not crystal clear, administer treatment immediately without waiting for the results of CSF tests. </li></ul><ul><li>CT scan of the brain may be performed prior to lumbar puncture in some patient groups with a higher risk of herniation. </li></ul><ul><li>A lumbar puncture (LP) may be contraindicated in some of the following conditions brain abscess, brain tumors or other cause of raised intracranial pressure, and occasionally infection at the lumbar puncture site- </li></ul><ul><li>Risk of cerebral herniation complicating lumbar puncture performed to diagnose acute bacterial meningitis. perform CT examinations performed before a lumbar puncture. An LP “removes the stopper from below, thus adding to the effects of the compression from above.” </li></ul><ul><li>Infants and children </li></ul><ul><li>Many children receive antibiotics before definitive diagnosis is made. As a rule, a few doses of oral antimicrobial agents, or even a single injection of an antibiotic, do not significantly alter CSF findings. </li></ul>
Meningitis: CSF findings <ul><li>Increased white blood cells </li></ul><ul><ul><li>Neutrophils with bacterial meningitis </li></ul></ul><ul><ul><li>Mononuclear cells (lymphocytes and macrophages) with TB and fungal infections </li></ul></ul><ul><ul><li>Lymphocytes with viral infection </li></ul></ul><ul><li>Increased protein (mild with viral) </li></ul><ul><li>Reduced glucose with bacterial meningitis </li></ul>
CSF Characteristics Bacterial Viral Fungal TB Opening Pressure Elevated Slightly elevated Normal or High Ususally high Glucose Low Normal Low Low Protein Very high Normal High High Rbcs Few None None None Wbcs (c/mm3) >200 <200 <50 20-30 Diff PMNs Mono Mono Mono Appearance Turbid Clear Turbid Cob-web
LP <ul><li>Tube #1 – glucose and protein </li></ul><ul><li>Tube #2 – cell count and differential </li></ul><ul><li>Tube #3 – gram stain and routine culture, cyrptococcal antigen, AFB stain and culture </li></ul><ul><li>Tube #4 – VDRL, or viral studies (PCR) </li></ul>
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 Ampicillin and an aminoglycoside combination (ampicillin and cefotaxime Resistant bugs- Vancomycin and either ceftriaxone or cefotaxime Dexamethasone-Decreased inflammation, reduction in cerebral edema
<ul><li>Caused by the bacteria spirochaete Treponema pallidum . </li></ul><ul><li>Occurs in persons with untreated syphilis 10 - 20 years after they are first infected </li></ul><ul><li>Incidence </li></ul><ul><li>Before the advent of antibiotics, typically 25-35% </li></ul><ul><li>Neurosyphilis in HIV </li></ul><ul><li>Neurosyphilis is now most common in patients with HIV infection. </li></ul><ul><li>In the AIDS population up to 1-3% of patients are. Without therapy, 5-10% of patients develop clinical evidence of neurosyphilis. </li></ul><ul><li>The classically described time intervals from infection to symptom onset of 20 and 25-30 years, shorter in HIV </li></ul>
<ul><li>Neurosyphilis-DIAGNOSIS </li></ul><ul><li>CSF and serum Veneral Disease Research Laboratory (VDRL) tests are highly specific for active neurosyphilis </li></ul><ul><li>Serum fluorescent treponemal antibody absorption test (FTA) </li></ul><ul><li>Treponema pallidum particle agglutination assay </li></ul><ul><li>Head CT or MRI scan </li></ul>Meningovascular syphilis. Imaging findings include meningeal enhancement and small infarcts or foci of ischaemia with a predilection for the basal ganglia and the middle cerebral artery regions , revealed in the subacute phase by areas of contrast enhancement. Cerebral atrophy is a frequent accompaniment.
<ul><li>There are 5 clinical types of neurosyphilis: </li></ul><ul><li>Syphilitic meningitis. headache, stiff neck, nausea, and vomiting, meningeal irritation, and cranial nerve abnormalities, Argyll Robertson pupil (bilateral small pupils that constrict when the patient focuses on a near object (they “accommodate”), but do not constrict when exposed to bright light (they do not “react” to light). They were formerly known as " Prostitute's Pupils " because of their association with tertiary syphilis, “ like a prostitute, they accommodate but do not react .” </li></ul><ul><li>Meningovascular syphilis. The focal deficits- seizures, paraplegia. Can also present as an infectious arteritis and cause an ischemic stroke . </li></ul>Argyll Robertson pupil
<ul><li>There are five clinical types of neurosyphilis: </li></ul><ul><li>General paresis (dementia paralytica) A chronic dementia that ultimately results in death in as little as 2–3 years. General paresis can occur between 3 – 30 years after infection. </li></ul>
<ul><li>There are five clinical types of neurosyphilis: </li></ul><ul><li>Tabes dorsalis- vision loss, loss of reflexes and loss of sense of vibration, spastic gait, and impaired balance, pains in the limbs or abdomen, failure of muscle coordination, and bladder disturbances. </li></ul><ul><li>Gumma A soft growth resulting from the tertiary stage of syphilis. It is a form of granuloma. </li></ul>
<ul><li>TREATMENT </li></ul><ul><li>Meningovascular syphilis responds promptly to treatment with penicillin G . Treatment of general paresis and tabes dorsalis is far less successful. iv or sc for 10 - 14 days. Combined with Oral Probenecid x4/day. </li></ul><ul><li>Non-pregnant individuals who have severe allergic reactions to penicillin may be effectively treated with oral tetracycline or doxycycline. </li></ul><ul><li>Prognosis </li></ul><ul><li>Meningovascular syphilis, general paresis, or tabes dorsalis usually do not return to normal health, although may improve . </li></ul>
Viral Meningitis <ul><li>Viral meningitis syn. aseptic meningitis. </li></ul><ul><li>Uncomplicated viral meningitis, usually self-limited, with complete recovery in 7-10 days. </li></ul><ul><li>Partially untreated bacterial meningitis in particular can present similarly to viral meningitis-devastating outcomes if misdiagnosed. </li></ul><ul><li>Causes </li></ul><ul><li>Enteroviruses account for more than 85% of all cases of viral meningitis. </li></ul><ul><li>Herpes family viruses. </li></ul><ul><li>Lymphocytic choriomeningitis virus </li></ul><ul><li>Adenovirus </li></ul><ul><li>Measles </li></ul><ul><li>Mumps </li></ul>
Viral Meningitis-Clinical Manifestations <ul><li>Upon presentation, most patients report fever, headache, irritability, nausea, vomiting, stiff neck, rash, or fatigue within the past 18-36 hours. </li></ul><ul><li>Nuchal rigidity or other signs of meningeal irritation (Brudzinski or Kernig sign) may be seen in more than half of patients but is generally less severe than in bacterial meningitis. Pediatric patients, especially neonates , tend not to exhibit nuchal rigidity on examination. </li></ul><ul><li>Other signs of specific viral infection can also aid in diagnosis: </li></ul><ul><li>e.g Skin manifestations, such as, vesicular eruption by herpes simplex. </li></ul><ul><li>Diagnosis </li></ul><ul><li>CT scan usually is performed prior to LP to rule out intracranial hematoma, mass effect, or obstructive hydrocephalus. </li></ul><ul><li>PCR testing for viral DNA. </li></ul><ul><li>CSF characteristics </li></ul>
Viral Meningitis-Treatment <ul><li>Mostly supportive-Rest, hydration, antipyretics, and pain or anti-inflammatory medications . The most important decision is whether to initiate antimicrobial therapy empirically for bacterial meningitis while waiting for the cause to be identified. Patients with signs and symptoms of meningoencephalitis should receive acyclovir early to possibly curtail HSV encephalitis. </li></ul><ul><li>Enteroviruses and HSV are both capable of causing viral septic shock in newborns and infants. In these young patients, broad-spectrum antibacterial coverage and acyclovir should be instituted as soon as the diagnosis is suspected . </li></ul>
Herpes Simplex Encephalitis <ul><li>Herpes simplex encephalitis (HSE) occurs as 2 distinct entities: </li></ul><ul><li>In children older than 3 months and adults, oral herpes, HSV-1 is responsible for virtually all cases. </li></ul><ul><li>In neonates herpes simplex virus type 2 (HSV-2), genital herpes which is acquired at the time of delivery. </li></ul><ul><li>Frequency </li></ul><ul><li>Herpes simplex encephalitis is the most common cause of sporadic lethal encephalitis , occurring in about 1 person per 250,000-500,000 population per year. </li></ul><ul><li>Mortality/Morbidity </li></ul><ul><li>Before the availability of IV acyclovir the mortality rate of herpes simplex encephalitis in untreated patients is 70%. </li></ul>
Herpes Simplex Encephalitis-Pathophysiology <ul><li>Brain infection is thought to occur by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve. The herpes virus preferentially involves the temporal lobe and orbital surfaces of the frontal lobes . Herpes viruses cause a hemorrhagic necrosis and inflammatory infiltrates. </li></ul>
Axial FLAIR MRI in herpes simplex encephalitis shows extensive signal change in the right temporal lobe (arrow). Destruction of inferior frontal and anterior temporal lobes – necrotizing inflammation
Herpes Simplex Encephalitis <ul><li>Diagnosis </li></ul><ul><li>LB CSF-Identification of HSV in the CSF by PCR or in brain tissue by brain biopsy. </li></ul><ul><li>Treatment </li></ul><ul><li>Acyclovir. In vivo converted to acyclovir triphosphate, a potent inhibitor of HSV DNA polymerase, without which viral replication cannot occur. Human cells are not affected. Start course as soon as HSE suspected. </li></ul><ul><li>Acyclovir has relatively few serious adverse effects. The drug is excreted by the kidney, and the dose should be reduced in patients with renal dysfunction.- high dose may crystallize out </li></ul><ul><li>Acyclovir considered appropriate for serious infections during pregnancy. </li></ul>
Poliomyelitis <ul><li>Humans are the only know reservoir for poliovirus, a member of the Picoviridae, enterovirus group. </li></ul><ul><li>Person-to-person spread occurs predominantly via the fecal-oral route. </li></ul><ul><li>Enhanced potency trivalent oral poliovirus vaccine containing attenuated strains of all 3 serotypes of poliovirus. Effective immunity (99% after 3 doses). </li></ul>
Poliomyelitis-clinical manifestations <ul><li>Three types of paralytic polio are described: </li></ul><ul><li>Spinal polio (79%) asymmetric paralysis usually involving the legs </li></ul><ul><li>Bulbar polio (2%) weakness of the muscles innervated by cranial nerves </li></ul><ul><li>Bulbospinal polio (19%) combination </li></ul>
Poliomyelitis-clinical manifestations <ul><li>Diagnosis </li></ul><ul><li>Poliovirus isolation from the pharynx or stool. Neutralizing Ab present early at high levels. </li></ul><ul><li>Treatment </li></ul><ul><li>Physical therapy is the most important part of treatment of paralytic polio during convalescence. The ideal strategy with polio is clearly to prevent it by immunization against poliovirus . </li></ul>
Rabies Virus (Rhabdovirus) <ul><li>Introduction </li></ul><ul><li>Rabies is a viral disease that causes acute encephalitis. It is zoonotic, most commonly by a bite from an infected animal. The rabies virus travels to the brain by following the peripheral nerves . The incubation period of the disease is usually a few months in humans , depending on the distance the virus must travel to reach the central nervous system . </li></ul>
<ul><li>Diagnosis </li></ul><ul><li>Demonstration of anti-rabies glycoprotein Ab in serum or CSF. </li></ul><ul><li>Prognosis </li></ul><ul><li>In unvaccinated humans, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms . Death ordinarily occurs within three to five days after the onset of symptoms due to cardiac or respiratory failure . </li></ul><ul><li>Incidence </li></ul><ul><li>Rabies is common in Asia, especially in India, where up to 50,000 die each year. Some parts of America and Africa, have it. Greenland and many countries in Europe have rabies in their animal populations. Scandinavia, as well as Japan, Australia and New Zealand are practically Rabies-Free! </li></ul>Rabies Virus (Rhabdovirus)
<ul><li>Signs and symptoms </li></ul><ul><li>In the unvaccinated individual rabies evolves in three stages: </li></ul><ul><li>The Neurological Stage or Paralytic Stage- 2-10 days after the prodrome, the encephalitic form presents with agitation, delirium, seizures, nuchal rigidity, severe pharynx spasms, stridor and hydrophobia and aerophobia. The paralytic (20%) form presents with progressive paralysis until death. </li></ul>Rabies Virus (Rhabdovirus) Patient with rabies, 1959
Rabies Virus (Rhabdovirus)-Treatment Post-exposure prophylaxis (PEP) , One dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a fourteen day period . 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.
Brain and spine Tuberculosis <ul><li>Tuberculous meningitis: tuberculosis infection of the meninges. It is the most common form of CNS tuberculosis. </li></ul><ul><li>Causative agent: Mycobacterium tuberculosis is an aerobic gram-positive rod. </li></ul><ul><li>CNS tuberculosis most commonly occurs in those infected with HIV and those from South East Asia where TB is still endemic </li></ul><ul><li>Frequency </li></ul><ul><li>The World Health Organization (WHO) estimates that one third of the world's population is infected by M. tuberculosis . </li></ul><ul><li>Clinical Manifestations </li></ul><ul><li>Tuberculous meningitis progresses rapidly with headache, fever, tremor, and cranial nerve deficts (esp CN-IV palsy). Focal neurological deficits may include monoplegia, hemiplegia, aphasia, and tetraparesis. Vasculitis with resultant thrombosis and hemorrhagic infarction may develop in vessels . Visual findings-Papilledema is the most common visual effect of TBM. </li></ul><ul><li>The clinical picture in primary spinal meningitis is often characterized by myelopathy, with radicular pain and progressive paraplegia or tetraplegia. </li></ul>
Brain and spine Tuberculosis-Pathophysiology <ul><li>Diagnosis </li></ul><ul><li>Diagnosis of TB meningitis is made by analysing cerebrospinal fluid collected by lumbar puncture. A spider-web clot in the collected CSF is characteristic of TB meningitis, but is a rare finding. </li></ul><ul><li>Culture for M. tuberculosis takes 2 weeks. More than half of cases of TB meningitis cannot be confirmed microbiologically, and these patients are treated on the basis of clinical suspicion only before the diagnosis is confirmed. </li></ul><ul><li>PCR </li></ul>
Brain and spine Tuberculosis-Treatment <ul><li>The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. </li></ul><ul><li>Treatment must be started as soon as there is a reasonable suspicion of the diagnosis. Treatment must not be delayed while waiting for confirmation of the diagnosis. </li></ul>
TUBERCULOMA 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).
Progressive multifocal leukoencephalopathy <ul><li>PML is caused by reactivation of the endemic JC papovavirus. </li></ul><ul><li>Progressive multifocal leukoencephalopathy (PML) occurs almost exclusively in AIDS patients. </li></ul><ul><li>As many as 90% of healthy individuals have serum antibodies to this virus, but less than 10% show any evidence of ongoing viral replication. </li></ul><ul><li>At present, PML develops in as many as 5% of all patients with AIDS- PML is an AIDS-defining illness . </li></ul>
Progressive multifocal leukoencephalopathy <ul><li>Pathophysiology </li></ul><ul><li>Multiple demyelinative lesions are generally located in the cerebral white matter. Spinal cord involvement is rare. </li></ul>This sliced fixed brain shows multiple isolated or confluent gray demyelinative foci. Atrophy may be present.
Progressive multifocal leukoencephalopathy <ul><li>Mortality/Morbidity </li></ul><ul><li>In the pre-HAART (Highly Active Antiretroviral therapy- three to four anti-virals taken in combination) era, the prognosis of PML was dismal, with death occurring within 4-6 months after diagnosis. </li></ul><ul><li>Clinical Manifestations </li></ul><ul><li>Present with rapidly progressive focal symptoms including behavioral, speech, cognitive impairment, hemiparesis, and visual impairment . Focal signs tend to be related to posterior brain (eg, occipital lobes). </li></ul><ul><li>Late in the course abnormalities may progress to quadriparesis, cortical blindness, profound dementia and coma . </li></ul><ul><li>Diagnosis </li></ul><ul><li>PCR </li></ul><ul><li>Brain biopsy has a sensitivity of 74-92% and a specificity of 92-100%. </li></ul><ul><li>CSF cell count and chemistry usually normal </li></ul><ul><li>Treatment </li></ul><ul><li>No specific antiviral therapy effective for PML. </li></ul>
Neuro-Cyptococcosis <ul><li>Cryptococcal meningitis -a leading cause of infectious morbidity and mortality in patients with AIDS. Among the human immunodeficiency virus (HIV)-seropositive subjects, cryptococcal meningitis is the second (1 st tuberculous meningitis) most common cause of opportunistic neuro-infection and usually occurs in advanced HIV disease. </li></ul><ul><li>Cryptococcal meningitis is the most common form of fungal meningitis and is caused by Cryptococcus neoformans . C. neoformans is Soil fungus (yeast) associated with bird droppings (primary infection via respiratory route). </li></ul>Cryptococcus neoformans
Neuro-Cyptococcosis-Clinical manifestations <ul><li>Cryptococcal meningitis commonly presents as chronic or subacute meningitis. Associated with papilloedema, hydrocephalus, focal deficits, seizures and cryptococcomas. Cranial neuropathies, especially of the lower cranial nerves, affecting one or more cranial nerves . </li></ul>
Neuro-Cyptococcosis-Pathophysiology Multicystic form of cerebral cryptococcosis: lesions in basal ganglia and cerebellum The fungus enters the human body through inhalation into the lungs. The cerebrospinal fluid is an ideal site for infection as it lacks complements and immunoglobulins.
Opaque thick fibrotic CSF obstruction - hydrocephalus. Gelatinous material within the subarachnoid space and small cysts within the parenchyma ("soap bubbles“) Specially in the basal ganglia. Neuro-Cyptococcosis-Pathology
Neuro-Cyptococcosis-Treatment Amphotericin B 0.7-1.0 mg/kg/day + 5-flucytosine 100 mg/kg/day for 6-10 weeks. + fluconozole consolidation 6-12 months . Prognosis The majority of the patients improve with adequate therapy. Mortality is seen in about 10% and more common in HIV-positive individuals.
<ul><li>Cysticercosis results from the ingestion of the eggs of the pork tapeworm, Taenia solium . The eggs are usually found in fecally-contaminated water or food. The incubation period ranges from months to over ten years. </li></ul><ul><li>Neurocysticercosis, is when the brain or spinal cord is affected by the larval stage of T. solium , neurocysticercosis is the most common helminthic (tapeworm) infestation to affect the CNS worldwide and is the prime cause of acquired epilepsy . </li></ul>Neurocysticercosis
<ul><li>Morbidity </li></ul><ul><li>The racemose form of NCC, which appears macroscopically as groups of cysticerci, often in clusters that resemble bunches of grapes, located in the subarachnoid space, is associated with poor prognosis and elevated mortality rate (over 20%). </li></ul><ul><li>Clinical manifestations </li></ul><ul><li>NCC is a pleomorphic disease, although it sometimes produces no clinical manifestation. This pleomorphism is due to variations in the locations of the lesions, the number of parasites, and the host's immune response. </li></ul><ul><li>Epilepsy </li></ul><ul><li>Headache </li></ul><ul><li>Strokes </li></ul><ul><li>Neuropsychiatric disturbances </li></ul><ul><li>Diplopia </li></ul><ul><li>Hydrocephalus </li></ul>Neurocysticercosis
<ul><li>Because the larvae are relatively large, they may lodge in the subarachnoid space, ventricles, or brain tissue. Cysts in the subarachnoid space may result in chronic meningitis, cysts in the ventricular system may lead to obstruction hydrocephalus. </li></ul>Neurocysticercosis-Pathophysiology
Neurocysticercosis Viable cysticercus cellulosae LIVING ( viable ) Stage : CT - appears as hypodense lesion that doesn’t show ring enhancement or perilesional oedema “ HOLE with DOT appearance ” Similar findings in T1w Images.
Neurocysticercosis Multiple parenchymal calcifications CALCIFIED Stage : Not visualised in MRI CT- hyperdense nodules with no edema or enhancement. Old nonviable cysts eventually calcify simplifying detection.
<ul><li>Antihelminthic drugs ( Albendazole or praziquantel ) and corticosteroids or surgery . Surgical treatment includes direct excision of ventricular cysts, shunting procedures, and removal of cysts via endoscopy . No antihelminthic treatment is administered in dead calcified cysts stage (stage 4). </li></ul>Neurocysticercosis-Management and Therapy
Toxoplasmosis <ul><li>Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii . </li></ul><ul><li>Up to one third of the world's human population is estimated to carry a Toxoplasma infection. </li></ul><ul><li>Clinical manifestations </li></ul><ul><li>Four major T. gondii clinical syndromes occur: congenital, ocular, lymphadenopathic, and severe neurologic or disseminated diseases . </li></ul><ul><li>Latent toxoplasmosis </li></ul><ul><li>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 advanced AIDS or HIV with toxoplasmosis. </li></ul>
<ul><li>T1-weighted axial gadolinium-enhanced magnetic resonance images at 2 levels through the basal ganglia (same patient as in the previous image). These images show 2 complex, ring-enhancing lesions in the basal ganglia on the right, with surrounding notable white matter edema. This appearance is typical of central nervous system toxoplasmosis, which has the propensity for involvement of the basal ganglia. </li></ul>Toxoplasmosis T1-MRI multiple contrast enhancing necrotic focal lesions with predispostion to the basal ganglia and subcortical region.
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 people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration. • Atovaquone+Clindamycin Pyrimethamine spiramycin Atovaquone Clindamycin
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
Prion Related Diseases <ul><li> </li></ul><ul><li> </li></ul><ul><li>Pathophysiology </li></ul><ul><li>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. </li></ul><ul><li>Prionoses tend to affect the gray matter of the CNS, producing neuronal loss affecting the cerebral hemispheres and cerebellum , gliosis, and characteristic spongiform change. </li></ul>Prion-related diseases. Spongiform change in prion disease. This section shows mild parenchymal vacuolation and prominent reactive astrocytosis (abnormal increase in the number of astrocytes due to the destruction of nearby neurons).
Prion Related Diseases-Clinical Manifestations <ul><li> </li></ul><ul><li> </li></ul><ul><li>CJD </li></ul><ul><li>By far the most common human prion disease is CJD, accounting for about 85% of all human prion disease. Clinically, CJD is characterized by a rapidly progressive dementia associated with myoclonic jerks . </li></ul><ul><li> </li></ul><ul><li>Treatment </li></ul><ul><li>All prion diseases are fatal; no effective treatment is available. Patients are currently provided symptomatic treatment . Hence, some patients with CJD who develop seizures should be administered antiepileptic drugs , while those with extrapyramidal symptoms should be administered anti-Parkinson drugs . </li></ul>
Prion Related Diseases -Diagnosis Imaging Studies MRI is an important imaging test. MRI may show hyperintense signals in the cortical ribbon, basal ganglia, and the thalamus Two characteristic radiological signs have been described. The "hockey stick" sign , which refers to increased signal in the putamen and head of the caudate nucleus resembling a hockey stick, and the "pulvinar" sign, which corresponds to a usually bilaterally increased signal in the pulvinar thalamic nuclei. Shows characteristic signal changes of an MRI taken from a patient with sporadic CJD, using diffusion-weighted imaging (DWI). An abnormal signal is shown in both the basal ganglia (red arrows) and the cortical ribbon (yellow arrow).
Tetanus Tetanus, -characterized by a prolonged contraction of skeletal muscle. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani. Infection generally occurs through wound contamination and often involves a cut or deep puncture wound. Risus sardonicus is a highly characteristic, abnormal, sustained spasm of the facial muscles that appears to produce grinning. The name of the condition derives from the appearance of raised eyebrows and an open "grin" - which can appear malevolent to the lay observer - displayed by those suffering from these muscle spasms. Opisthotonos ( o-pis-to-ton-is )
Tetanus-Pathophysiology <ul><li>Puncture skin rusty metal- C. tetani endospore </li></ul><ul><li>The spores transform into bacteria and produce the neurotoxin tetanospasmin (aka tetanus toxin). </li></ul><ul><li>Binds to the neuromuscular junction and then attaches to peripheral motor neuron nerve endings. It travels centrally up the nerve in by retrograde axonal transport to the anterior horn cells, where it enters adjacent spinal inhibitory interneurons, blocking inhibitory neurotransmitter release to the anterior horn cell . </li></ul><ul><li>Damaged upper motor neurons can no longer inhibit lower motor neurons. This leads to the classic muscular hypertonia and muscle spasms. </li></ul>
Tetanus-Treatment <ul><li>Tetanus immunoglobulin IV or IM, </li></ul><ul><li>metronidazole IV for 10 days, antibiotic that decreases the number of bacteria but has no effect on the bacterial toxin. </li></ul><ul><li>diazepam, </li></ul><ul><li>tetanus vaccination </li></ul><ul><li>Diagnosis </li></ul><ul><li>There are no blood tests that can be used to diagnose tetanus. The diagnosis is based on the presentation of tetanus symptoms. The "spatula test" is a clinical test for tetanus that involves touching the posterior pharyngeal wall with a sterile, soft-tipped instrument, and observing the effect. A positive test result is the involuntary contraction of the jaw (biting down on the "spatula"), and a negative test result would normally be a gag reflex attempting to expel the foreign object. </li></ul>
Botulism <ul><li>Botulism is a serious illness that causes flaccid paralysis of muscles . It is caused by a neurotoxin, generically called botulinum toxin, produced by the bacterium Clostridium botulinum . Food-borne and wound botulism. </li></ul><ul><li>Pathophysiology </li></ul><ul><li>Botulinum toxin paralyzes the nerves so that the muscles cannot contract. This neurotoxin enters nerve cells and interferes with the release of acetylcholine. </li></ul>
Botulism <ul><li>Diagnosis </li></ul><ul><li>The most direct way to confirm the diagnosis is to identify the botulinum neurotoxin in the patient's blood, serum, or stool. This is done by injecting the patient's serum or stool into the peritoneal cavity of mice. An equal amount of serum or stool from the patient is treated with multivalent antitoxin and injected in other mice. If the antitoxin-treated serum- or stool-injected mice live while those injected with untreated serum or stool die, then this is a positive test for botulism and is called the mouse inoculation test. </li></ul><ul><li>Treatment </li></ul><ul><li>The trivalent antitoxin (effective against three neurotoxins: A, B, and E). </li></ul>