Neuroinflammation Pavel Štourač Department of Neurology University Hospital Brno Bacterial infections of the Nervous System • acute bacterial meningitis • an hematogenous infections of leptomeninges • tissue invasion - paranasal infection, craniocerebral injury/tissue invasion • clinical pattern: headache, stiff- neck, fever, meningeal syndrome Bacterial infections • The most common pathogens in meningitis: • Gram-positive pathogens: • Pneumococci • Streptococci • Staphylococci • Listeria monocytogenes Bacterial infections • Gram - negative pathogens: • Meningococci (Neisseria meningitidis) • Haemophilus influenzae • Escherichia coli Bacterial infections • CSF findings in bacterial meningitis • cloudy appearance of CSF, granulocytic pleocytosis, high increase of protein content,decreased glucose, increased lactate, microscopic detection of bacteria Neutrophils in purulent CSF inflammation Chronic bacterial infections of the Nervous System • Pathogens • Treponema pallidum, Mycobacterium tuberculosis,Listeria monocytogenes,Borrelia • clinical features: headache, involvement of cranial nerves, vascular ischaemic lesion, hydrocephalus • brain abscess /antibiotics, neurosurgery • spinal epidural abscess/antibiotics,surgery Brain abscess - MRI scan Viral infections of the Nervous System • isolated meningitis Coxsackieviruses A and B, HSV, VZV,mumps, HIV • meningoencephalitis HSV,VZV,CEE virus,CMV,enteroviruses,HIV • cranial neuritis VZV,HSV,CMV,HIV,CEE virus • myelitis Coxsackieviruses A and B, echoviruses,VZV,CEE virus, HIV Viral infections of the Nervous system • CSF findings in viral infections • microbiological analysis • DNA - polymerase chain reaction • specific antibody synthesis - AI • CSF cells count / lymphocytic or mixed cell pleocytosis • total protein increased • normal lactate, normal glucose Viral infections of the Nervous system • HSV encephalitis (HSV-DNA) • VZV herpes zoster (VZV-DNA) • Tick - borne encephalitis (Central European encephalitis (CEE) - ELISA - antigen specific antibodies IgM and IgG + inflammatory CSF pattern • West Nile virus - mosquito transmitted flavivirus Structure of herpetic virus Viral infections of the Nervous system • Cytomegalovirus (CMV) - Herpesviridiae • Human Immunodeficiency Virus (HIV) RNA • Clinical pattern HIV: meningitis, myopathy,neuropathy,myelopathy and encephalopathy - laboratory test ELISA • PCR detection HIV and viral load HIV structure Infection of the Nervous System by Fungi and Other Opportunistic Pathogens • Toxoplasma gondii - intracellular parasite • Toxoplasmosis (cerebral toxoplasmosis) - AIDS, • Congenital toxoplasmosis • Cryptoccocosis - (Cryptoccocus neoformans) most common mycosis of CNS - AIDS microscopic detection by India ink staining • Candidiasis - (Candida albicans), long - term immunosupressive treatment Infection of the Nervous system by Fungi and Other Opportunistic Pathogens • Aspergillosis (Aspergillus fumigatus) immunocompromised patients (multiple brain abscesses),granuloma,meningitis • Neurosyphyllis - Treponema pallidum Spirochaetacea - 3 stages: • 2 st.: asymptomatic meningitis, paralysis of cranial nerves • 3 st.: parenchymatous neurosyphyllis Infection of the Nervous system by Fungi and Other Opportunistic Pathogens • Neuroborreliosis - Borrelia burgdorferi sensu stricto, B.garinii, B.afzelii - multisystemic disease • 2.st. meningopolyradiculoneuritis - Bannwarth syndrome, lymphocytic meningitis, dg.ELISA , specific antibody positive index (AI - Bb) Infection of the Nervous system by Fungi and Other Opportunistic Pathogens • Progressive Multifocal Leukoencephalopathy(PML) • JC virus (polyomavirus) • Immunocompromised and AIDS patients • Natalizumab (Tysabri) treated patients • JCV - AI ≥ 1.4, 20 % mortality, risk stratification • Subacute Sclerosing Panencephalitis (SSPE) • measles infection - persistent infection with incomplete measles virus • Progressive rubella panencephalitis Case report 1 • Man, 39- years old, chronic dialysis programme, renal transplantation 1/2017, arterial hypertension, hypothyreosis • 5/2017: 2 weeks fever, consciousness disturbance,epileptic seizure, cerebrospinal fluid - mixed cell inflammation • PCR herpetic viruses, enteroviruses negative Case report 1 • Antibodies against CEE (Central European encephalitis virus: • 1. withdrawal (25.5.2017): serum: IgG negative, IgM positive (IP 1,6) CSF: IgG negative, IgM positive (IP 2,3) • 2. withdrawal (13.6.2017): serum: IgG negative, IgM negative (IP 0,7) • coma, GCS 3, lesion in the brainstem,exitus letalis 16.6.2017 • Dg: brainstem lesion (inflammation )caused CEE virus in immunosupressed patient Case report 2 • woman 67 years old • 7/2017: patient was admitted to hospital with sudden visual lesion of both eyes, blindness on the left eye ,anisocoria, distorted shape of left iris, convergetion reaction lost billateraly • cognitive impairment, dementia, walking disturbance hypacusis , history of herpes zoster thoracis 5/2017 • CSF: lymphocytic inflammation (13,9 mono/ul), oligoclonal bands IgG 0/22, PCR herpetic viruses negative, anti- borrelia antibodies negative, CEE antibodies negative Case report 2 • screening tests for syphilis: serum RPR 1:32, anti-TP 342,0 positive • Confirmation tests for syphylis: serum: ELISA IgG positive, IgM borderline WB IgG positive, IgM equivocal CSF: ELISA IgG positive, IgM negative WB IgG positive, IgM negative intrathecal synthesis positive (AI=2,0) • MRI scan: moderate T2 hyperintense lesions of white matter periventricular and T2 hyperintense lesions juxtacortically, diffuse brain atrophy Case report 2 • tabes dorsalis – degenerative lesions in dorsal part of spinal cord in the late stage of neurosyphilis, sensory disturbances, spinal ataxia, walking disturbance • tabes dorsalis – pathognomic Argyll Robertson´s pupil • complications of tabes dorsalis – deafness, blindness, brain atrophy, dementia • Diagnosis – neurosyphillis