Acute and chronic meningitis, encephalitis III Prof Dr Meral Sonmezoglu Yeditepe University Hospital

The two major divisions in the nervous system are the central nervous system (CNS), composed of the brain and the spinal cord, and the peripheral nervous system (PNS), composed of afferent (input to CNS) and efferent (output to periphery) neurons. Within the PNS, major divisions are the somatic nervous system (controls skeletal muscle) and in the autonomic nervous system, which has two branches: the parasympathetic (rest and digest) and the sympathetic (emergency) branches.

Protection of the Brain The brain is protected by bone, meninges, and cerebrospinal fluid (CSF)

The CSF circulates through the ventricular system CSF is produced by the choroid plexus inside the ventricles. It circulates through the ventricles. From the fourth ventricle, CSF enters the subarachnoid space, between the arachnoid mater and pia mater. Reabsorbed from subarachnoid space into venous blood via the arachnoid villi

Meninges (s. meninx) Three connective tissue membranes external to the CNS – dura mater, arachnoid mater, and pia mater Functions: Cover and protect the CNS Protect blood vessels and enclose venous sinuses Contain cerebrospinal fluid (CSF) Form partitions within the skull

Meninges

Dura Mater Tough meninx composed of two fibrous CT layers. Layers separate in certain areas and form dural sinuses. Dural sinuses collect venous blood from the brain. 3 dural septa limit excessive movement of the brain Falx cerebri – dural fold that dips into the longitudinal fissure Falx cerebelli – runs along the vermis of the cerebellum Tentorium cerebelli – horizontal fold extending into the transverse fissure

Dura Mater

Arachnoid Mater Separated from the dura mater by the subdural space (a narrow serous cavity) Beneath the arachnoid is a wide subarachnoid space filled with CSF and large blood vessels Arachnoid villi protrude superiorly and permit CSF to be absorbed into venous blood

Pia Mater Deepest meninx – delicate CT that clings tightly to the brain and follows convolutions

Cerebrospinal Fluid (CSF) Watery, similar in composition to blood plasma, but contains less protein and different ion concentrations than plasma Forms a liquid cushion that gives buoyancy to the CNS organs, prevents the brain from crushing under its own weight Protects the CNS from blows and other trauma Nourishes the brain and may carry chemical signals from one part of the brain to another

Choroid Plexuses Clusters of interwoven capillaries in each ventricle between the pia mater and a layer of ependymal cells. Ion pumps allow them to alter the ion concentrations of the CSF Help cleanse CSF by removing wastes

Circulation of CSF

Blood-Brain Barrier Protective mechanism that helps maintain a stable environment for the brain Bloodborne substances in brain capillaries are separated from neurons by: Continuous endothelium of capillary walls Relatively thick basal lamina Bulbous feet of astrocytes Least permeable capillaries in the body due the nature of the tight junctions between endothelial cells

Blood-Brain Barrier: Functions Selective barrier that allows nutrients to pass freely Is ineffective against substances that can diffuse through plasma membranes (fats, gasses, alcohol) Absent in some areas (vomiting center and the hypothalamus), allowing these areas to monitor the chemical composition of the blood

Meningitis Meningitis is a clinical syndrome characterized by inflammation of the meninges

Classification Depending on the duration of symptoms, meningitis may be classified as acute or chronic. Acute meningitis denotes the evolution of symptoms within hours to several days, while chronic meningitis has an onset and duration of weeks to months. The duration of symptoms of chronic meningitis is characteristically at least 4 weeks.

Classification Meningitis can also be classified according to its etiology.

Meningitis Bacterial Viral ( aseptic) TB Fungal Chemical Parasitic ? Carcinomatous

Classification of Meningitis Infectious Bacterial Viral Fungal Non-infectious Drug-Induced Neoplastic Autoimmune R1’s: What is the most common cause of bacterial meningitis in the developed world? R2’s: What is most common viral cause of meningitis? R3’s: Name a drug that is known to cause meningitis? Drugs: ibuprofen, erythromycin, amoxicillin, OKT3, azathiprine, INH Autoimmune – SLE; Behcets (sm vessel vasculitis)

Bacterial Meningitis in Adults Frequency of n. meningitidis is decreasing. Frequency of s. pneumoniae, group B streptococcal, h. influzena and listeria are constant. Frequency of staphylococcal meningitis increased (not significant) Staphylococcal meningitidis is caused by 2 species: S. auerus and s. epidermidis Streptococcal = GBS + group A strep – not separated in this study. Staphylococcal associated with instrumentation and hardware. Deeks SL. Bacterial meningitis in Canada (1994-2001). Canadian Communicable Disease Report. Dec 2005. 31:23.

Viral Meningitis Epidemiology less clear b/c the majority of cases are not reportable and the etiology is often not identified. Majority of cases occur in children < 1 yr. Enteroviruses: Strains of echovirus & coxsackie B are the two most common pathogens. HSV: HSV 2 causes the majority of cases. 30% of patients with primary genital herpes will develop septic meningitis. Arborviruses: Viruses which cause encephalitis in adults (Western Equine, Eastern Equine, Colardo tick fever, St. Louis encephalitis virus) may cause aseptic meningitis in children. Also includes West Nile virus Other: mumps (30% of cases will present w/ aseptic meningitis +/- parotitis), HIV PICNIC Study: Aseptic meningitis in Cdn children – 1998-1999 802 cases 233 had pathogen identified – all enteroviruses

Noninfectious.. Metabolic Mitochondrial (Reye’s, MELAS) NMS (Neuroleptic malignant syndrome) Nutritional deficiency (Wernicke’s) Paraneoplastic PRES or Malignant hypertension Seizures – (non-convulsive status) TBI Toxic Vascular

Meningitis Aseptic meningitis is a broad term that denotes a non-pyogenic cellular response, which may be caused by many different etiologic agents Many of these cases are found to have a viral etiology and can then be reclassified as acute viral meningitis (eg, enterovirus meningitis, herpes simplex virus [HSV] meningitis).

Bacterial Meningitis Definition Epidemiology Bacterial meningitis is an inflammatory response to bacterial infection of the pia-arachnoid and CSF of the subarachnoid space Epidemiology Incidence is between 3-5 per 100,000 More than 2,000 deaths annually in the U.S. Relative frequency of bacterial species varies with age.

Epidemiology Meningitis Neonates (< 1 Month) Gm (-) bacilli 50-60% Grp B Strep 20-40% Listeria sp. 2-10% H. influenza 0-3% S. pneumo 0-5%

Epidemiology Meningitis Children (1 month to 15 years) H. influenzae 40-60% Declining dramatically in many geographic regions N. meningitidis 25-40% S. pneumo 10-20%

Meningitis Epidemiology Adults (> 15 years) S. pneumo 30-50% N. Meningitidis 10-35% Major cause in epidemics Gm (-) Bacilli 1-10% Elderly S. aureus 5-15% H. influenzae 1-3% >60 include Listeria, E. coli, Pseudomonas

Pathogenesis Meningitis Majority of cases are hematogenous in origin Organisms have virulence factors that allow bypassing of normal defenses Proteases Polysaccharidases

Meningitis Pathology and Pathogenesis Sequential steps allow the pathogen into the CSF Nasopharyngeal colonization Nasopharyngeal epithelial cell invasion Bloodstream invasion Bacteremia with intravascular survival Crossing of the BBB and entry into the CSF Survival and replication in the subarachnoid space

Nasopharynx -> blood -> subarachnoid space

Pathophysiology of Bacterial Meningitis Bacterial colonization within the subarachnoid space Initiation of inflammatory response which leads to: Endothelial damage Disruption of the blood-brain barrier On a larger scale, this results in: Cerebral edema Cytotoxic Vasogenic Interstitial Increased ICP Cytotoxic: degradation of bacteria & neutrophils -> cell function disruption. Vasogenic: endothelial damage and BBB leakage Interstitial: increased CSF viscosity (due to protein leak) and decreased venous drainage

Meningitis Pathology and Pathogenesis Key advances in the pathophysiology of meningitis include the pivotal role of cytokines (eg, tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]–1), chemokines (IL-8), and other proinflammatory molecules in the pathogenesis of pleocytosis and neuronal damage during bacterial meningitis. Increased CSF concentrations of TNF-alpha, IL-1, IL-6, and IL-8 are characteristic findings in patients with bacterial meningitis

Meningitis Pathology Hallmark Exudate in the subarachnoid space Accumulation of exudate in the dependent areas of the brain Large numbers of PMN’s Within 2-3 days inflammation in the walls of the small and medium-sized blood vessels Blockage of normal CSF pathways and blockage of the normal absorption may lead to obstructive hydrocephalus

Meningitis Overall, the net result is vascular endothelial injury and increased BBB permeability leading to the entry of many blood components into the subarachnoid space. This contributes to vasogenic edema and elevated CSF protein levels. In response to the cytokines and chemotactic molecules, neutrophils migrate from the bloodstream and penetrate the damaged BBB, producing the profound neutrophilic pleocytosis characteristic of bacterial meningitis.

Pathophysiology of Bacterial Meningitis Complications: Seizures Hydrocephalus Infarction Herniation Seizures: cortical inflammation Hydrocephalus: basal obstruction of CSF flow Infarct: Inflammatory occulusion of basal arteries Herniation: generalized edema From van de Beek D Community-acquired bacterial meningitis in adults. 354:1. 44.

Clinical Presentation of Meningitis Classic signs ; fever, headache, neck stiffness, photophobia, nausea, vomiting, and signs of cerebral dysfunction (eg, lethargy, confusion, decreased level of consciousness coma). The triad of fever, nuchal rigidity, and change in mental status is found in only two thirds of patients Atypical presentation may be observed in certain groups (elderly, diabetic, neutropenic, immunocompromised hosts..).

Clinical Presentation of Meningitis Signs of cerebral dysfunction are common, including confusion, irritability, delirium, and coma. These are usually accompanied by fever and photophobia. Signs of meningeal irritation are observed in only approximately 50% of patients with bacterial meningitis, and their absence certainly does not rule out meningitis

Meningitis Clinical Manifestations – Nuchal rigidity Kernig’s Pt supine with flexed knee has increased pain with passive extension of the same leg Brudzinski’s Supine pt with neck flexed will raise knees to take pressure off of the meninges Present in 50% of acute bacterial meningitis cases Cranial Nerve Palsies IV, VI, VII Seizures

Brudzinski’s Sign Brudzinski’s sign: Passive flexion of the neck leads to hip & knee flexion Reported sensitivity much higher – 97% Specificity very low

Kernig’s Sign Kernig’s sign: Patient supine. Flex hip to 90°. Attempt to extend knee. Pain should not occur before 135°. Probably requires significant meningeal inflammation (as seen with bacterial meningitis), and is less likely to be positive in viral meningitis. Reported sensitvity of only 57%.

Trunk supported by arms Amos’s Sign Hips & knees flexed Back arched Neck in extension Trunk supported by arms Sign of significant meningismus.

Meningitis Focal neurologic signs may develop as a result of ischemia from vascular inflammation and thrombosis Papilledema and other signs of increased ICP may be present. Coma, increased blood pressure with bradycardia, and cranial nerve III palsy may be present. The presence of papilledema also suggests a possible alternate diagnosis (eg, brain abscess).

Meningitis Papilledema

Meningitis Clinical Manifestations - Meningococcemia Prominent rash Diffuse purpuric lesions principally involving the extremities Fever, hypotension, DIC History of terminal complement deficiency Classic findings often absent Neonates Elderly

Meningitis

Diagnosis of Meningitis Assess for increased ICP Papilledema Focal neurologic findings Defer LP until CT scan or MRI obtained if any of above present If suspect meningitis and awaiting neuroimaging Obtain BC’s and start empiric Abx

Diagnosis of Meningitis Obtain CT scan before lumbar puncture in patients with: Immunucompromised state History of CNS disease New onset seizures Papilledema Altered level of consciousness Focal neurologic signs

Diagnosis of Meningitis Obtain blood cultures and give empiric antibiotics if LP is delayed

Diagnosing Meningitis Spinal tap is performed needle is inserted into an area in the lower back Identification of the type of bacteria is important for selection of correct antibiotics.

Lumbar puncture

LP-CSF Tube # 1 Protein & Glucose Tube # 2 Gram stain & Culture Tube # 3 Cell count & differential Tube # 4 Store ( PCR, viral studies etc)

Diagnosis of Meningitis CSF Findings : Opening pressure Appearance Cell count & differential Glucose Protein Gram stain & culture

Bacterial Meningitis Opening pressure: high, > 200 mmH20 Cloudy 1000-5000 cells/mm3 with a neutrophil predominance of about 80-95% <40mg/dl and less than 2/3 of the serum glucose Protein elevated

Tuberculous meningitis 180-300 Agent Opening Pressure WBC count per µL Glucose (mg/dL) Protein (mg/dL) Microbiology Bacterial meningitis 200-300 100-5000; >80% PMNs* <40 >100 Specific pathogen demonstrated in 60% of Gram stains and 80% of cultures Viral meningitis 90-200 10-300; lymphocytes Normal, reduced in LCM and mumps Normal but may be slightly elevated Viral isolation, PCR† assays Tuberculous meningitis 180-300 100-500; lymphocytes Reduced, <40 Elevated, >100 Acid-fast bacillus stain, culture, PCR Cryptococcal meningitis 10-200; lymphocytes Reduced 50-200 India ink, cryptococcal antigen, culture Aseptic meningitis Normal Negative findings on workup Normal values 80-200 0-5; lymphocytes 50-75 15-40

Diagnosis Meningitis Rapid Tests CT/MRI CIE (Counter immunoelectrophoresis/ latex agglut.) PCR CT/MRI Little role in DIAGNOSIS of menigitis Obtain if suspect increased ICP

Diagnosis Additional Tests Meningitis CBC w/ diff Blood cultures CXR Electrolytes and renal function

Bacterial Cultures “Gold standard” Positive in 75-85% who have not been treated with antibiotics

Differential Diagnosis Meningitis Differential Diagnosis CNS infections (abscess, encephalitis) Viral/ Tb/ Lyme meningitis Ricketsial infections Cerebral vasculitis Subarachnoid hemorrhage Neurosyphilis

Risk and/or Predisposing Factor Bacterial Pathogen Age 0-4 weeks S agalactiae (group B streptococci) E coli K1 L monocytogenes Age 4-12 weeks S agalactiae E coli H influenzae S pneumoniae N meningitidis Age 3 months to 18 years N meningitidis S pneumoniae H influenzae Age 18-50 years S pneumoniae N meningitidis H influenzae Age older than 50 years S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli Immunocompromised state Intracranial manipulation, including neurosurgery Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa Basilar skull fracture S pneumoniae H influenzae Group A streptococci CSF shunts Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes

Fungi Cryptococcus neoformans C immitis B dermatitidis H capsulatum Candida species Aspergillus species Viruses Enterovirus PoliovirusEchovirusCoxsackievirus ACoxsackievirus BEnterovirus 68-71 Herpesvirus HSV-1 and HSV-2Varicella-zoster virusEBVCMVHHV*-6HHV-7 Paramyxovirus Mumps virusMeasles virus Togavirus Rubella virus Flavivirus Japanese encephalitis virusSt. Louis encephalitis virus Bunyavirus California encephalitis virusLa Crosse encephalitis virus Alphavirus Eastern equine encephalitis virusWestern equine encephalitis virusVenezuelan encephalitis virus Reovirus Colorado tick fever virus Arenavirus LCM virus Rhabdovirus Rabies virus Retrovirus HIV

Meningitis Treatment Neonates (<3 months) Emergent empirical antimicrobial therapy Based on age and underlying disease status Empiric antibiotic regimines Neonates (<3 months) Ampicillin plus a third generation cephalosporin Children Third generation cephalosporin ( alternative -ampicillin and chloramphenicol) Young adults Third generation cephalosporin (Ceftriaxone) + Vancomycin

Treatment Meningitis Empiric Antibiotic Regimines Older adults Ampicillin in combination with third generation ceph. Postneurosurgical Pt’s Vancomycin plus ceftazidime until cultures are available

Treatment Meningitis N. Meningitidis S. pneumoniae High dose Pen G Ceftriaxone For areas with high level resistance Vancomycin plus third generation cephalosporin or rifampin

Meningitis Treatment Gm (-) Enterics L. monocytogenes S. aureus Third generation cephalosporins L. monocytogenes Ampicillin S. aureus Vancomycin or Nafcillin S. epidermidis Vancomycin

Treatment Predisposing Feature Antibiotic(s) Age 0-4 weeks Ampicillin plus cefotaxime or an aminoglycoside Age 1-3 months Ampicillin plus cefotaxime plus vancomycin* Age 3 months to 50 years Ceftriaxone or cefotaxime plus vancomycin* Older than 50 years Ampicillin plus ceftriaxone or cefotaxime plus vancomycin* Impaired cellular immunity Ampicillin plus ceftazidime plus vancomycin* Neurosurgery, head trauma, or CSF shunt Vancomycin plus ceftazidime

Treatment Duration of Treatment Meningitis Dependent on infecting organism Average of 10-14 days Gm (-) bacilli for 3 weeks

Treatment Meningitis Steroids Shortly before or along with antibiotics. Do not give steroids after antibiotic treatment. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347:1549-56.

Corticosteroids in Children Despite the conclusion of the Cochrane review, use is still controversial CPS statement: No recommendations for routine use If used, should only be given to children > 6 wks and before or within 1 hr of antibiotics Current Capital Health practice is to limit the use of steroids to children presenting with severe sepsis Most evidence for benefit of dexamethasone in children is in those infected with h. influenzae – since this is now rarely a cause, feeling is that the evidence cannot be generalized to other types of meningitis. Canadian Paediatric Society Statement. Therapy of suspected bacterial meningitis in Canadian children six weeks of age and older. Ped & Child Health. 6:3. March 2001. 147-52. Reaffirmed February 2006.

Complications The long-term neurologic sequelae can be grouped into 3 categories as follows: Hearing impairment Obstructive hydrocephalus Brain parenchymal damage: Most important feared complication of bacterial meningitis. It could lead to sensory and motor deficits, cerebral palsy, learning disabilities, mental retardation, cortical blindness, and seizures.

Mortality of meningitis Overall mortality rate from bacterial meningitis has decreased but remains alarmingly high. It is reported to be approximately 25%. Among the common causes of acute bacterial meningitis, the highest mortality rate is observed with pneumococcus. 19-26% for S pneumoniae meningitis, 3-6% for H influenzae meningitis, 3-13% for N meningitidis meningitis, 15-29% for L monocytogenes meningitis.

Meningitis Pneumococcal Meningitis Prognosis Associated with the highest mortality rate 19-26% Permanent neurologic sequelae 1/3 of pts Hearing loss Mental retardation Seizures Cerebral Palsy

Vaccination The use of the HIB vaccination is strongly recommended in susceptible individuals. Vaccination against S pneumoniae is strongly encouraged in susceptible individuals, (older than 65 years and with chronic cardiopulmonary illnesses). Vaccinations against encapsulated bacterial organisms (eg, S pneumoniae, N meningitidis) are encouraged for those with functional or structural asplenia. Offer vaccination with quadrivalent meningococcal polysaccharide vaccine to all high-risk populations, including those with underlying immune deficiencies, those who travel to hyperendemic areas and epidemic areas, and those involved with laboratory work that deals with routine exposure to N meningitidis. College students who live in dormitories or residence halls are at modest risk; inform them about the risk and offer vaccination. Vaccination against N meningitidis is recommended for all adolescents aged 11-18 years.  Vaccination against measles and mumps effectively eliminates aseptic meningitis syndrome caused by these pathogens.

Vaccinations Meningitis Asplenic pts should have had a pneumoccocal vaccine prior to their splenectomy Vaccines available for H. influenza Prophylaxis for N. meningitidis contacts Rifampin

Prevention The widespread use of viral vaccines for polio, measles, mumps, rubella and varicella has almost eliminated CNS complications from these in the US. Domestic rabies vaccinations have reduced the frequency of rabies encephalitis.

Prevention II Control of encephalitis from arboviruses has been less successful without specific vaccines. Control of insect vectors by spraying methods and eradication of insect breeding sites hasreduced incidence of these infections.

Meningococcal vaccine

Chemoprophylaxis

Conclusion Meningitis Meningitis is an infectious disease emergency Mortality is often high but can be prevented with appropriate medical therapy If you consider meningitis in your differential, you are committed to an LP and empiric antibiotics

The characteristic skin rash (purpura) of meningococcal septicemia, caused by Neisseria meningitidis

Pneumococcal meningitis in a patient with alcoholism Pneumococcal meningitis in a patient with alcoholism. Courtesy of the CDC/Dr. Edwin P. Ewing, Jr.

Follow-up Close follow-up needed after hospital discharge: Hearing should be assessed 1-2 mo. after d/c using BEARS testing Neuromuscular assessment at the time of d/c should be documented and periodically assessed outpatient to detect any deficiencies Learning disabilities, behavior disorders and speech delay require close monitoring after d/c

An Approach to the Adult Patient with Suspected Bacterial Meningitis Summary: Shock: Sepsis Protocol From supplement to: Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354:44-53

Summary: An Approach to the Adult Patient with Suspected Bacterial Meningitis Indications Age > 60 Recent seizures Immunocompromised Prev CNS disease or hardware Focal neurological deficits Papilledema Altered LOC* Shock: Sepsis Protocol From supplement to: Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354:44-53

Give dexamethasone IV before or with 1st dose of antibiotics Summary: An Approach to the Adult Patient with Suspected Bacterial Meningitis Corticosteroids Give dexamethasone IV before or with 1st dose of antibiotics Contraindications Antibiotics w/in 48 hrs Shunt Head trauma Shock: Sepsis Protocol From supplement to: Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354:44-53

Contraindications to LP Summary: An Approach to the Adult Patient with Suspected Bacterial Meningitis Shock: Sepsis Protocol Contraindications to LP Recent seizure Signs of herniation at any time GCS < 11 or rapidly declining LOC Focal neurologic deficits Papilledema * SOL or brain shift on CT Coagulopathy From supplement to: Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354:44-53

Empiric Antibiotic Therapy Summary: An Approach to the Adult Patient with Suspected Bacterial Meningitis Shock: Sepsis Protocol Empiric Antibiotic Therapy Cefotaxime 2g IV or Ceftriaxone 2g IV +/- Ampicillin 3g IV +/- Vancomycin 1g IV From supplement to: Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354:44-53

CHRONIC MENINGITIS

Chronic meningitis is an inflammation of the meninges with subacute onset and persisting cerebrospinal fluid (CSF) abnormalities lasting for at least one month. Several non-infectious and infectious etiologies are known to be causative. The wide range of different etiologies renders the approach to patients with this syndrome particularly difficult

Chronic meningitis Bacteria Fungi Parasites Category Agent M tuberculosis B burgdorferi T pallidum Brucella species Francisella tularensis Nocardia species Actinomyces species Fungi C neoformans C immitis B dermatitidis H capsulatum Candida albicans Aspergillus species Sporothrix schenckii Parasites Acanthamoeba species N fowleri Angiostrongylus cantonensis G spinigerum B procyonis Schistosoma species S stercoralis Echinococcus granulosus

Common infectious causes of chronic meningitis and diagnostic approach

Any inflammatory process of the meninges and/or of the brain parenchyma leading to signs and symptoms for more than 4 weeks is termed chronic meningitis and meningoencephalitis, respectively Criteria of this diagnosis a pleocytosis in the cerebrospinal fluid is obligatory

Clinical Picture and Complications Neurologically, these patients present with an insidious onset of headache, mild neckstiffness, usually low grade fever, and – only as time goes by – with focal neurological signs. Only in case of vasculitis there may be a sudden onset of neurological focal signs. A potentially life-threatening complication is the development of hydrocephalus, be it obstructive or malresorptive, eventually leading to qualitative and quantitative impairment of consciousness. Rarely, a chronic inflammatory process may lead to epileptic seizures, according to the underlying pathology of focal or generalized pattern.

ENCEPHALITIS

Encephalitis Encephalitis, an inflammation of the brain parenchyma, presents as diffuse and/or focal neuropsychological dysfunction. Encephalitis is distinct from meningitis, though on clinical evaluation the 2 often coexist with signs and symptoms of meningeal inflammation, such as photophobia, headache, or a stiff neck.

Encephalitis Acute encephalitis is most commonly a viral infection with parenchymal damage varying from mild to profound Subacute and chronic encephalopathies, most likely toxoplasmosis in immunocompromised patients

Encephalitis Individuals at the extremes of age are at highest risk, particularly for HSE

Encephalitis The classic presentation is encephalopathy with diffuse or focal neurologic symptoms, including the following: Behavioral and personality changes, decreased level of consciousness Stiff neck, photophobia, and lethargy Generalized or localized seizures (60% of children with California encephalitis [CE]) Acute confusion or amnestic states Flaccid paralysis (10% with WNE)

Infectious etiologies of Encephalitis Viral agents, such as HSV type 1 and 2 (almost exclusively in neonates), VZV, EBV, Measles virus (PIE and SSPE), mumps, and rubella are spread through person-to-person contact. Human herpesvirus 6 may also be a causative agent. Bacterial pathogens, such as Mycoplasma species, rickettsial or catscratch disease, Toxoplasma gondii West Nile virus can be transmitted by means of an organ transplant and via blood transfusions. 

Physical Examination Altered mental status Personality changes are very common Focal findings, such as hemiparesis, focal seizures, and autonomic dysfunction Movement disorders (St Louis encephalitis, eastern equine encephalitis [EEE], western equine encephalitis [WEE]) Ataxia Cranial nerve defects Dysphagia, particularly in rabies Meningismus (less common and less pronounced than in meningitis) Unilateral sensorimotor dysfunction (postinfectious encephalomyelitis [PIE]) Physical Examination

Encephalitis Laboratory tests (biochemical). Viral serology CT scan EEE CSF analysis

Complications Seizures Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) Increased intracranial pressure (ICP) Coma

Encephalitis-treatment The goal of treatment for acutely ill patients is administration of the first dose or doses acyclovir with or without antibiotics or steroids as quickly as possible Look for and treat systemic complications, particularly in HSE, EEE, JE, such as hypotension or shock, hypoxemia, hyponatremia (SIADH), and exacerbation of chronic diseases