神经病学教学ppt课件：Meningitis and encephalitis.ppt

Meningitis and encephalitis,Contrast MRI,Meningitis,Enhanced CT of a patient with tuberculous meningitis showing perivascular inflammatory changes and temporal infarction due to vasculitis.,Axial post-gadolinium T11WI showing ring-enhancing lesion with mass effect in a patient with pyogenic brain abscess.,In acute meningeal inflammation:Pure pia-arachnoiditis: headache, stiff neck, Kernig and Brudzinski signs. B. Subpial encephalopathy: confusion, stupor, coma, and convulsions are related to this lesion. C. Inflammatory or vascular involvement of cranial nerve roots: ocular palsies, facial weakness, and deafness are the main clinical signs. D. Thrombosis of meningeal veins: focal seizures, focal cerebral defects such as hemiparesis, aphasia (rarely prominent), E. Cerebellar or cerebral hemisphere herniation: due to swelling (as in B), causing upper cervical cord compression with quadriplegia or signs of midbrainthird nerve compression.,Pathologic-clinical correlations in meningeal reactions,II. In more subacute and chronic forms of meningitis:Tension hydrocephalus, due at first to purulent exudate around the base of the brain, later to meningeal fibrosisB. Subdural effusion: impaired alertness, refusal to eat, vomiting, immobility, bulging fontanels, and persistence of fever despite clearing of CSF. C. Extensive venous or arterial infarction: unilateral or bilateral hemiplegia, decorticate or decerebrate rigidity, cortical blindness, stupor or coma with or without seizures.,III. Late effects or sequelae:Meningeal fibrosis around optic nerves or around spinal cord and roots: blindness and optic atrophy, spastic paraparesis with sensory loss in the lower segments of the body (opticochiasmatic arachnoiditis and meningomyelitis, respectively).B. Chronic meningoencephalitis with hydrocephalus: dementia, stupor or coma, and paralysis (e.g., general paralysis of the insane).,Bacterial infections of CNS bacterial meningitis, septic thrombophlebitis, brain abscess, epidural abscess, and subdural empyemaViral infections of CNS Viral meningitis, Herpes simplex virus (HSV) encephalitis Retrovirus: human immunodeficiency virus (HIV)Fungal infections Cryptococcal meningoencephalitis Aspergillosis and candidiasisThe granulomatous infections of the CNS Tuberculosis, syphilis and other spirochetal infectionsParasitic,Infections of the central nervous system (CNS),Meningitis - fever, headaches- Signs of meningeal irritation: stiff neck; Kernig sign, Brudzinski sign - except in neonates, which may present with irritability, in elderly, presenting with changes in the mental state.Encephalitis - considered when the patient presents with alteration of mental state, personality changes, confusion, and memory deficit, as well as focal and lateralizing neurological signs such as paresis, aphasia, visual field defect, or focal seizures.,Definition, Perform a quick neurological examination; look particularly for meningealsigns, mental status abnormalities, focal neurological deficits, or papilledema. Obtain a set of blood cultures and routine admission labs. Do lumbar puncture (LP) as soon as possible. If the patient has focal neurological signs or signs of increased intracranialpressure, obtain head computed tomography scan or magnetic resonanceimaging before LP. Spinal fluid analysis will differentiate bacterial from viral meningitis, and thelaboratory will define the antibiotic sensitivities of the infecting organism.,The general approach to suspected cases of acute meningitis,HSV-1 is a highly successful human pathogen: 39% of individuals 1419 years of age are already infected, prevalence rates increase to 65.3% by middle adulthoodTransmission: the vast majority is through saliva, genital transmission (less)The yearly incidence of HSV-1 encephalitis: 24 cases /1million individualsIt is the most common cause of sporadic viral encephalitis responsible for 75% of hospitalizations for viral encephalitis in USIndividuals risk for HSV-1 encephalitis: mutations in UNC-93B and in TLR3 that impair host defenses, IFN-R-deficiency, STAT 1 deficiency.,Herpes Simplex Virus (HSV)-1 infection,Pathogenesis: Is an immune response a good thing?,Herpes simplex virus type 1 (HSV-1),activation of pattern recognition receptors,type I interferon production,robust immune response,quell virus replication,drive the pathogen into a “latent” state, and likely hinder viral reactivation,release of inflammatory mediators including reactive oxygen species,demonstrable cell death and foci of tissue pathology in the central nervous system (CNS),Mechanisms of HSV-1-mediated antagonism of TLR-dependent, anti-viral pathways,toll-like receptors,protein kinase,Clinical presentations,Fever, signs of meningeal irritation such as headache, altered consciousness, and seizures.Nuchal rigidity or other meningeal irritation is often found. Mental deficits include confusion and personality change (temporal lobe involvement)Cerebrospinal fluid (CSF) : pressure increased (moderately or greatly); pleocytosis (10 to 200 cells/mm3); lymphocytes may be predominant; Red cells are frequently seen. The electroencephalogram (EEG): diffuse slowing or focal changes over temporal areas; periodic lateralized epileptiform discharges(PLEDs) against a slow-wave background.,Imaging,unilateral abnormal signal lesions in the left hippocampi and amygdala (arrows).,30 HSV infection,Clinical features: fever, altered consciousness, seizure, meningeal signs;CSF findings: pleocytosis, protein increase, but normal glucose;EEG, CT MRI reveal asymmetrical fronto-temporal lesions;Brain abscess, tuberculous, fungal meningitis should be excluded;CSF HSV ELISA positive.,Diagnosis of HSV,Anti-herpes virus drugs: should be started when two criteria are satisfied 10-14-day course of acyclovir 30 mg/kg.day is recommendedThe use of adjunctive corticosteroids: Possible mechanisms: modulate of the immune response, reduce viral replication reduce severe brain edema Clinical trial: a multi-center, randomized, placebo-controlled GACHE trial (German trial of Acyclovir and Corticosteroids in Herpes simplex- virus Encephalitis) Dexamethasone + acyclovir ? An option,Treatment of HSV,Fungal infections of the central nervous system (CNS),Rare in the general population , invariably secondary to primary focus elsewhere, usually in the lung or intestine.Most frequently encountered in immunocompromised patients such as those with acquired immunodeficiency syndrome or after organ transplantation, or with longstanding diabetes.Cryptococcal meningoencephalitis is most frequently seen, followed by aspergillosis and candidiasis.,Cryptococcosis,A ubiquitous organism found in mammal and bird feces, particularly in pigeon droppings. It causes disease primarily in patients with impaired immunity, particularly in those with AIDS. However, up to 30% of the patients have been reported with no predisposing condition. The most common mycotic agent to affect the CNS: The central nervous system is the preferred site because soluble anticryptococcal factors present in serum are absent in CSF and the polysaccharide capsule of the fungus protects it from host inflammatory response.,Pathogenesis of cryptococcosis,Meningitis: - the primary manifestation- most pronounced at the base of the brain. Parenchymal involvement (cryptococcomas ):- The commonest sites are the midbrain and the basal ganglia.- dilated Virchow-Robin spaces - enhancing cortical nodules. - chronic granuloma: composed of macrophages, lymphocytes and foreign body giant cells. - pseudocysts: due to dilatation of the Virchow-Robin spaces with mucoid gelatinous material produced by the capsule of the organism,Clinical presentation and diagnosis,Symptoms and signs of subacute meningitis or meningoencephalitis:- Headache is the most common and sometimes the sole symptom. - Meningeal features like photophobia and neck stiffness are uncommon.- 20-40% patients have no fever when first examinedSymptoms and signs related to increased intracranial pressure - Headache, vomiting, papilledema is present in half such patients- With high morbidity and mortalityCSF- ICP extremely high- usually less than 50 cells/mm3, glucose is reduced in 3/4 of cases- India-ink preparations showing a thick, refractile capsule are diagnostic- A latex agglutination test for the cryptococcal polysaccharide antigen in the CSF: about a 90% reliability for diagnosis,Radiographic characteristics,Protean and frequently minimal.The spectrum of MR and CT abnormalities ranges from no abnormality to meningeal enhancement, abscesses, intraventricular or intraparenchymal cryptococcomas, gelatinous pseudocysts and/or hydrocephalus. On DWI, cryptococcoma shows hypointensity in the central cavity and mimics a necrotic brain tumor, rather than a pyogenic brain abscess. MRS shows marked increase in lactate along with decrease in NAA, choline and creatine,Cryptococcosis with dilated Virchow-Robin spaces in an immunocompromised patient. T2WI (A) shows multiple bilateral basal ganglia hyperintensities, which do not reveal any enhancement on postcontrast T1WI (B). Lesions show no restriction on DWI (C). CSF culture showed Cryptococcus neoformans,Cryptococcal meningoencephalitis in an immunocompetent patient. A: Axial T2WI shows hyperintensity in the left parietal region. B: Lesion is hypointense on T1WIC: Lesion is isointense on DWI.D: Postcontrast image shows meningeal enhancement in the region of abnormality. CSF showed India ink positive yeast and culture confirmed it to be Cryptococcus neoformans,Cryptococcoma: isointense on T1WI (B) and hypointense on DWI (C).,contrast image,MRS,Treatment,Intravenous administration of amphotericin B - A dose of 0.5 to 0.7 mg/kg/day. - Renal tubular acidosis also frequently complicatesThe addition of flucytosine (150 mg/kg/day) - permits the reduction of the amphotericin dose to 0.3 to 0.5 mg/kg/day.Mortality from cryptococcal meningoencephalitis, even in the absence of AIDS or other disease, is about 40 percent.,Etiology and Pathogenesis,The treponeme (Treponema pallidum) usually invades the CNS within 3 to 18 months of inoculation with the organism.The initial event in the neurosyphilitic infection is a meningitis,which occurs in about 25% of all cases of syphilis, leading to parenchymal damage .All forms of neurosyphilis begin as a meningitis, and a more or less active meningeal inflammation is the invariable accompaniment of all forms of neurosyphilis.The CSF is a sensitive indicator of the presence of active neurosyphilitic infection.,Neurosyphilis,Diagram of the evolution of neurosyphilis.,Neurological involvement in syphilis; the estimates reflect the probability of progressing to each stage, and the brackets on the right provide the average time to progression. Note, the figure assumes no therapeutic intervention (i.e. natural progression).,Principal Types of Neurosyphilis,Asymptomatic NeurosyphilisEarly Symptomatic Neurosyphilis (Acute Syphilitic Meningitis or “Neurorecurrence”)Meningovascular SyphilisGeneral ParesisTabetic Neurosyphilis (Tabes Dorsalis),Asymptomatic Neurosyphilis (ANS),13.5% had ANS: in a series of 5293 patients with all stages of syphilis from the preantibiotic era;The peak incidence of ANS occurred 1218 months after infectionand declined thereafter;Persons with any stage of syphilis and evidence of ANS had a significantly higher probability of developing late neurological complications;The presence and extent of CSF abnormalities, irrespective of syphilis stage, significantly impact long-term prognosis. (i.e.WBC count 50 cells/mL, elevated protein concentration),Early Symptomatic Neurosyphilis (Acute Syphilitic Meningitis or “Neurorecurrence”),Diffuse inflammation of the meninges: - headache, photophobia, nausea, vomiting, - cranial nerve palsies - occasionally seizuresIt was infrequently diagnosed The majority of cases reportedly occurred after the inadequatetreatment of early syphilis,Meningovascular Syphilis,Endarteritis of vessels in the CNS resulting in thrombosis and infarction.Tends to occur 512 years after initial infection with T. pallidumClinical presentation: - Early symptoms included headache, vertigo, and insomnia. - In over 75% of persons, the onset was sudden ( “syphilitic apoplexy”). - The symptoms depended on the site of thrombosis - the majority involving the middle cerebral artery or its branches; - spinal cord vessels involved is common, syphilitic meningomyelitisIn the antibiotic era, the rates of meningovascular syphilis have declined.,General Paresis,Pathologically, there is atrophy of the frontal and temporal lobe, leading to dilatation of the lateral ventricles.Up to 100% of autopsy specimens were found to harbor spirochetes by tissue stainingThe clinical manifestations of general paresis are protean - Early symptoms: irritability, forgetfulness, personality changes, headaches, and changes in sleep habits. - Late symptoms: emotional lability, impaired memory and judgment, disorientation, confusion, delusions, and occasionally seizures. - Psychiatric manifestations range from depression, to delirium hallucinations), mania, and psychosis,Tabetic Neurosyphilis (Tabes Dorsalis),Tabes dorsalis affected 39% of persons infected with syphilisPathologically, there is degeneration of the posterior roots andcolumn of the spinal cord. Clinical presentation: - the ataxic gait, lightning pains, paresthesias, bladder dysfunction, and failing vision (optic atrophy) - Signs include pupillary abnormalities (Argyll Robertson pupils being the most common), diminished reflexes, impaired vibratory sense and proprioreception, ocular palsies.,Serologic and CSF Testing,Serologic test:- nonspecific lipoidal tests : the RPR and VDRL, as the screening test, followed after therapy to document response:For early syphilis, a 4-fold decline in titers is expected 612 m after therapy. For late stage disease, a decline is expected 1224 m after therapy- treponemal-specific tests: as confirmatory tests serum fluorescent treponemal antibody (FTA) testCSF examination:- Pleocytosis: lymphocyte predominant up to 10% of patients with tabes, cell count may be normal.- a positive VDRL establishes a diagnosis of neurosyphilis, but a negative VDRL does not exclude it. RPR was less specific.- A positive CSF-FTA Abs may not reflect neurosyphilis. A negative CSF- FTA Abs may be reasonable to rule out neurosyphilis.,An 18 year old patient presented with dementia had generalised cerebral atrophy with ventricular dilatation,A 43 year old HIV positive patient who presented with hemiparesis had stroke,There are no pathognomonic radiographic findings,Treatment of Neurosyphilis,Since its introduction in the 1940s, penicillin remains the mainstay of therapy to treat neurosyphilis. - The recommended treatment regimen for neurosyphilis is 1824 MU of intravenous aqueous penicillin G daily, either as a continuous infusion, or divided 3 to 4 MU every 4 h, for 1014 days - Herxheimer reaction, which is a matter o