Encephalopathy

Encephalitis an inflammation of the brain parenchyma and presents as an alteration in consciousness, fever, headache, seizures, and/or focal neurologic signs without the identification of a neurotropic agent or confirmation by brain tissue analysis, the diagnosis of encephalitis is presumptive and is based on clinical characteristics

Encephalitis depressed or altered level of consciousness lasting 24 h, lethargy, or a personality change with 1 of the following characteristics: – Fever – Seizure – focal neurological findings – Pleocytosis – or electroencephalography or neuroimaging findings consistent with encephalitis

Source: Beyond Viruses: Clinical Profile and Etiologies Associated with Encephalitis C. A. Glaser,1 S. Honarmand,1 L. J. Anderson,3 D. P. Schnurr,1 B. Forghani,1 C. K. Cossen,1 F. L. Schuster,1 L. J. Christie,1 and J. H. Tureen2 1Viral and Rickettsial Disease Laboratory, California Department of Health Services, Richmond, and 2Department of Pediatrics, University of California, San Francisco, California; and 3Respiratory and Enteric Viruses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia

Infectious Causes 69% of agents were viral 20% bacterial 7% prion 3% parasitic 1%, fungal Other probable agents: M. pneumoniae (n=96), influenza virus (n=22), adenovirus (n=14), Chlamydia species (n=10), and human metapneumovirus (n=4)

Confirmed or probable viral etiology EV (25% of cases) and HSV-1 (24% of cases) Median age of individuals: – HSV- 1 (54.0 years) – VZV (44.0 years) – WNV (66.0 years) encephalitis – EV (12.0 years) – EBV (11.0 years) – measles causing subacute sclerosing panencephalitis (12.0 years) WNV and EV encephalitis occurred more commonly in the summer 75% of the patients presented with fever exceptions included individuals with measles causing subacute sclerosing panencephalitis, VZV infection, and hepatitis C

No consistent prodromes were seen except influenza virus (respiratory prodromes) and rotavirus (gastrointestinal prodrome) Seizures ~38% of patients with viral encephalitis – measles causing subacute sclerosing panencephalitis (83%), human herpesvirus 6 infection (75%), and HSV-1 infection (59%) The initial MRI findings were abnormal for 87 patients (60%) and were most frequently abnormal for patients with HSV-1 (93%).

Non viral etiology Bacterial agents – Diverse – Mycobacterium tuberculosis (n=19),Bartonella species (n=13), M. pneumoniae (n=2), and Tropheryma whippelii (n=1) – cases of pyogenic bacteria

Non viral etiology Parasitic etiology – Balamuthia mandrillaris and Baylisascaris procyonis – Pleocytosis (median CSF WBC count, 126 cells/mm3) – elevated protein level (median, 945 mg/dL) – abnormal neuroimaging findings – B. procyonis in children whose age ranged from 11 months to 17 years  CSF and peripheral eosinophilia

Non viral etiology Fungal – C. immitis, C. neoformans – elevated CSF WBC count (median, 117 cells/mm3) – elevated CSF protein level (median, 176 mg/dL) – depressed CSF glucose level (median, 25 mg/dL)

Possible causes serological evidence and/or PCR evidence of an acute infection but organism was not detected from a CNS site possible EV infection were identified by detection of EV in respiratory samples and by serum EV IgM assay

Non-infectious causes 52 cases of autoimmune disease and/or vasculitis (43%) 33 neoplastic cases (27%) 7 metabolic cases (6%) 30 cases due to other disorders (25%)

Figure 1. Number of patients with confirmed or probable etiologic agents of encephalitis identified, by CSF WBC count and type of etiologic agent.

CSF laboratory values infectious agent  higher CSF WBC than patients who had a noninfectious agent diagnosed median CSF WBC count, 53.5 vs. 9.5 cells/mm3; P <0.001) – Difference in CSF protein levels was not significant (median level, 71.0 vs mg/dL)

Clinical Profiles 4 Focal – Temporal lobe involvement – Movement and/or extrapyramidal disorders – Cerebellar disorders – Hydrocephalus 6 Generalized – Diffuse cerebral edema – Intractable seizure – Seizure with rapid recovery – Psychosis presentation – Recurrent or Chronic inflammatory CNS disease – Multifocal white matter disease

Focal group encephalitides Temporal lobe involvement – encephalitis with temporal lobe enhancement noted on MRI or CT – Most common agent HSV-1 Some patients showed temporal lobe activity noted on electroencephalography but had n enhancement noted on CT or MRI

Focal group encephalitides Movement and/or extrapyramidal disorders – Observed in 47 patients These patients were younger (median age, 11 years <23) The length of hospitalization was prolonged (median duration, 39 days > 11) mortality rate for this group (9%) was comparable to the overall morality rate noted in the CEP study (11%)

Focal group encephalitides Cerebellar disorders – 87 patients presented with a predominance of cerebellar signs (i.e., ataxia and dysmetria) and/or focal cerebellar lesions noted on MRI The median age is 15 yrs <23yrs The mortality rate for this group is 2% <11% No single infectious agent found to be predominant Relatively high percentage (16%) of noninfectious etiologies

Focal group encephalitides Hydrocephalus – Thirty-two patients have new-onset hydrocephalus Relatively high percentage of nonviral organisms (47%) organisms included bacterial (11 cases), fungal (2 cases), and parasitic (2 cases) agents

Generalized group Encephalitides Diffuse cerebral edema – Forty-seven patients presented with or developed diffuse generalized cerebral edema within 7 days of admission, as evidenced by CT, MRI, or autopsy findings Evidence of inflammation was minimal (median CSF WBC count, 8 cells/mm3) CNS findings similar to Reye syndrome none of the patients had significant elevation of transaminase levels, hypoglycemia, or hyperammonemia 34 patients (72%) died within 7 days after hospitalization sec to tentorial herniation

Generalized group encephalitides Intractable seizures – Sixty-two patients either presented with or developed intractable seizures requiring general anesthesia or a barbiturate-induced coma to interrupt status epilepticus. Most patients were <18 years of age (median age, 10 years) Prolonged hospital stays (median duration, 46 days > 11days) had no causative agents identified Twenty percent died before discharge from the hospital, and of the patients who survived, most required extensive rehabilitation.

Generalized group encephalitides Seizures with rapid recovery – 25 patients presented with seizures but had a rapid recovery discharged from the hospital within 7 days after hospital admission

Generalized group encephalitides Psychosis presentation – Fifty-one patients presented with new-onset psychosis Noninfectious causes (20% of cases), infectious causes (12%) 59% of the cases had no etiology identified

Generalized group encephalitides Recurrent or chronic inflammatory CNS disease – Twenty-nine patients had experienced at least 1 previous hospitalization for CNS symptoms median age was 41 years single case of Creutzfeldt-Jakob disease a number of autoimmune and other noninfectious entities were identified

Generalized group encephalitides Multifocal white matter disease – 120 patients had multifocal white-matter lesions noted on neuroimaging. reported viral prodromal symptoms (34% upper respiratory tract infection, 41% gastrointestinal symptoms) possible agents were identified: M. pneumoniae and respiratory viruses consistent with a postinfectious disease process