Viral encephalitis

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VIRAL ENCEPHALITIS DR . Rabie Zahran. Tropical M . Consultant. Damietta Fever Hospital. Egypt. rabiezahran@gawab.com

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Inflammation of brain tissue caused by viral infection leading to either : Acute viral encephalitis caused by direct viral infection of neural cells. Post-infectious encephalomyelitis follows infection with various viral agents. Viral Encephalitis rabiezahran@gawab.com

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Arboviruses are the most common causes of viral encephalitis. Arbovirus stands for arthropod-borne viruses. There are 3 virus families associated with encephalitis. Togaviridae ( Alphavirus ) – most common Flaviviridae ( Flavavirus ) Bunyaviridae ( Bunyavirus ) Primary Cause rabiezahran@gawab.com

Alphavirus Surface:

Alphavirus Surface Spike-like structures on surface used to attach to susceptible animal cells. RNA- viruses. rabiezahran@gawab.com

Flavivirus:

Flavivirus Japanese Encephalitis Virus Saint Louis encephalitis virus West Nile Virus rabiezahran@gawab.com

Transmission of Arbovirus:

Transmission of Arbovirus Most encephalitides are transmitted by mosquitoes Other types are transmitted by ticks rabiezahran@gawab.com

Transmission cont..:

Transmission cont.. Infection occurs when the infected arthropod takes a blood meal Most cases of arboviral encephalitis occur from June – September, when arthropods are most active In warmer parts of the country, cases can occur year-round rabiezahran@gawab.com

Other Causes:

Other Causes Herpes simplex, type 1 (HSV-1) and type 2 (HSV-2 ). Entero -viruses . Colti -virus. Measles. Mumps. Rabies. Rubella. Lymphatic chorio -meningitis virus. rabiezahran@gawab.com

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Cytomegalo virus. Epstein-Barr virus (EBV ). Human immunodeficiency virus (HIV ). Varicella -zoster virus (VZV ). Influenza A and B. * Viruses are not the only cause of encephalitis; bacteria, fungus, parasites, toxins, and allergic reactions can also cause it. Other Cause cont... rabiezahran@gawab.com

Most Common Types of Arboviral Encephalitis in the US:

Most Common Types of Arboviral Encephalitis in the US Eastern equine encephalitis. Western equine encephalitis. La Crosse encephalitis. St. Louis encephalitis. West Nile encephalitis (most common in Africa). rabiezahran@gawab.com

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rabiezahran@gawab.com

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Flavavirus . First isolated in the West Nile Province of Uganda in 1937 First epidemic occurred in Israel in the 1950s Primarily affects individuals in Africa, the Middle East, western Asia, and Europe In late August and September 1999, there was an outbreak in New York City and neighboring counties Outbreak was initially attributed to St. Louis Encephalitis Most likely introduced to North America through international travel of infected persons to New York or by imported infected birds. West Nile Virus rabiezahran@gawab.com

Scanned images of West Nile virus isolated from brain tissue from a crow found in New York.:

Scanned images of West Nile virus isolated from brain tissue from a crow found in New York. rabiezahran@gawab.com

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The virus can infect people, horses, many birds, and some other animals. Infection usually occurs in the late summer or early fall. Most people who become infected with West Nile Virus have either no symptoms or only mild ones. A small percentage (<1%) of patients will develop more severe diseases from infection, including West Nile Encephalitis . Infections are most common in children and the elderly and as many as 10% of infected individuals will die. West Nile Virus (cont..) rabiezahran@gawab.com

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rabiezahran@gawab.com

Mosquito Breeding Grounds:

Mosquito Breeding Grounds rabiezahran@gawab.com

Discarded Tires:

Discarded Tires rabiezahran@gawab.com

Lakes and Ponds:

Lakes and Ponds rabiezahran@gawab.com

Trash:

Trash rabiezahran@gawab.com

Plants are natural incubators:

Plants are natural incubators rabiezahran@gawab.com

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Pathogenesis rabiezahran@gawab.com

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* Damage to brain parenchyma is induced by a wide variety of infective agents especially viruses as munched before. Many patients also have meningeal involvement (meningo-encephalitis ). Some patients may have brain and spinal cord involvement (encephalomyelitis ). Pathogenesis rabiezahran@gawab.com

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Pathogenesis Encephalitis may occur during the acute phase of a viral illness, or several days, weeks or months later . In the latter case, the pathogenesis is thought to be immunological . Meningo-encephalitis is, in most instances, self-limiting and benign. rabiezahran@gawab.com

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Diagnostic criteria rabiezahran@gawab.com

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Season Japanese encephalitis is more common during the rainy season. Arbovirus infections are more frequent during summer and fall. Predisposing factors: Immunosuppression caused by disease and/or drug treatment. Organ transplant → Opportunistic infections HIV → CNS infections HSV-2 encephalitis and Cytomegalovirus infection (CMV) Drug ingestion and/or abuse . Trauma. History rabiezahran@gawab.com

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Diagnostic criteria Clinical: • Severe headache, fever, nausea, vomiting , lethargy , and abnormal behavior . • Alteration in level of consciousness (drowsiness, confusion, stupor, coma). • Generalized and/or focal convulsions. Focal neurological deficits . * Clinical signs cannot distinguish different viral encephalitides . rabiezahran@gawab.com

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Level what is meaning ? Conscious Normal Confused Disoriented; impaired thinking and responses Delirious Disoriented; restlessness, hallucinations, sometimes delusions Somnolent Sleepy Obtunded Decreased alertness; slowed psychomotor responses Stuporous Sleep-like state (not unconscious); little/no spontaneous activity Comatose Cannot be aroused; no response to stimuli rabiezahran@gawab.com

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Glasgow Coma Scale rabiezahran@gawab.com

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Glasgow Coma Scale Score Response Test 1 2 3 4 None To pain To verbal stimuli Spontaneously Eye Opening 1 2 3 4 5 None Incomprehensible words Inappropriate words Disoriented conversation Oriented conversation Best Verbal Response 1 2 3 4 5 6 None Abnormal extension Abnormal flexion Flexion withdrawal Localizes pain Obeys commands Best Motor Response 3= deep coma or death -15= (fully awake person). commands rabiezahran@gawab.com

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Site of involvement clinically basal ganglia Abnormal movements Brain stem Cranial nerve palsies paresis of limbs loss of sphincter control spinal cord segmental sensory loss Meninges signs of meningeal irritation. Clinical: rabiezahran@gawab.com

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rabiezahran@gawab.com Function of basal ganglia Regulating voluntary motor activities. Abnormal movement. when affected

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rabiezahran@gawab.com Brain Stem involvement = cranial ns palsies

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rabiezahran@gawab.com paresis of limbs = loss of sphincter control

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Worsening neurologic symptoms. Vascular collapse and shock due to: Adrenal insufficiency . or Loss of tissue fluid. Homeostatic failure. Decreased respiratory drive. Disease Progression rabiezahran@gawab.com

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rabiezahran@gawab.com Differential Diagnosis

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rabiezahran@gawab.com Differential Diagnosis Brain Abscess Cat scratch Disease Herpes Simplex Herpes Simplex Encephalitis Hypoglycemia Leptospirosis in Humans Meningitis Status Epilepticus Subarachnoid Hemorrhage Systemic Lupus Erythematosus Tick-Borne Diseases, Lyme Tick-Borne Diseases, Rocky Mountain Spotted Fever Toxoplasmosis Tuberculosis

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rabiezahran@gawab.com Other Problems to be Considered Acute CNS events, such as hemorrhagic stroke Acute confusional states secondary to drugs, toxins, psychosis Amoeba ( Naegleria , Acanthamoeba ) Head trauma CNS syphilis Ehrlichiosis Intracranial hemorrhage Intracranial tumor Trauma

Encephalitis & Encephalopathy:

Encephalitis & Encephalopathy rabiezahran@gawab.com Encephalopathy = a syndrome of global brain dysfunction caused by many different illnesses.

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Encephalopathy Encephalitis Fever Uncommon Common Headache Uncommon Common AMS Steady deterioration May fluctuate Focal Neurologic Signs Uncommon Common Types of seizures Generalized Both Blood: Leukocytosis Uncommon Common CSF: Pleocytosis Uncommon Common EEG: Diffuse slowing Common +Focal MRI Often normal Focal Abnormal . ===================== AMS (Altered Mental Status ) Differential Diagnosis (). rabiezahran@gawab.com

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Anoxic/Ischemic conditions. Metabolic disorders. Nutritional deficiency. Toxic (Accidental & Intentional ). Systemic infections. Critical illness. Malignant hypertension. Causes of Encephalopathy rabiezahran@gawab.com

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rabiezahran@gawab.com Mitochondrial cytopathy (Reye’s and MELAS syndromes). Hashimoto’s encephalopathy. Traumatic brain injury. * Epileptic (non-convulsive status) * CJD (Mad Cow): Classic CJD is a human prion disease. It is a neurodegenerative disorder with characteristic clinical and diagnostic features. Causes of Encephalopathy

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Distinguish Etiology : (1) Bacterial infection and other infectious conditions. (2) Para-meningeal infections or partially treated bacterial meningitis (3) Non-viral infectious meningitides where cultures may be negative (e.g., fungal, TB, parasitic, or syphilitic disease) (5) Meningitis secondary to non-infectious inflammatory diseases Differential Diagnosis rabiezahran@gawab.com

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Complications rabiezahran@gawab.com

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Complications increased intracranial pressure, cerebral edema, inappropriate anti-diuretic hormone ( ADH) secretion , permanent neurological deficits, seizures , deafness and blindness. rabiezahran@gawab.com

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Investigations: rabiezahran@gawab.com

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Investigations: Laboratory tests are mostly not helpful . • Examination of CSF may reveals: * slightly raised protein. * normal glucose level . * mild pleocytosis , mostly lymphocytes. * A specific virus is sometimes isolated. * In some instances, the CSF may be completely normal . rabiezahran@gawab.com

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rabiezahran@gawab.com CSF polymerase chain reaction ( PCR ): A PCR for DNA HSV is 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs. Investigations:

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• Brain CT is often done and may reveal only brain edema. • EEG is often severely abnormal. • EEG may demonstrate changes suggestive of herpes encephalitis. Investigations: rabiezahran@gawab.com

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rabiezahran@gawab.com MRI : Can exclude: subdural bleeds, tumor, sinus thrombosis Biopsy : Reserved for patients who are worsening, have an un-diagnosed lesion after scan, or a poor response to acyclovir. Investigations:

Case Definition:

Case Definition 1) Suspected case. 2)Probable case. 3)Confirmed case. rabiezahran@gawab.com

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rabiezahran@gawab.com (1) Suspected case Fever + one of the following : Altered consciousness up to coma. +ve symptoms and signs of meningeal irritation. Systemic manifestations of causative disease if present. Positive history of prevailing disease, seasonal disease, or contact with animals

2)Probable case:

2)Probable case Suspected case + CSF findings : CSF findings : 1: Clear and may be slightly hazy. 2: Under tension. 3: Moderate increase in protein. 4:Slight increase in cells(mainly lymphocytes) rabiezahran@gawab.com

3)Confirmed case :

3)Confirmed case Not applicable. There is no specific confirmatory test for encephalitis. Diagnosis is often by exclusion . CT ., MRI,or serological study may confirm some cases rabiezahran@gawab.com

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Treatment objectives rabiezahran@gawab.com

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• Symptomatic and supportive treatment . • Prevention or early ttt . of complications . • Supportive and rehabilitative measures after recovery. rabiezahran@gawab.com

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Non-drug treatment (1) Maintain adequate nutrition & hydration. (2) Monitor: * level of consciousness, * heart rate, * respiration, * blood pressure, * Body temperature, * electrolytes, * serum and urine osmolality. rabiezahran@gawab.com

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Convulsions: Diazepam, slow IV, 0.25 – 1 mg/kg (maximum 10 mg) to control seizures. Titrate dose according to response. If no response, give a loading dose of phenobarbital , IV, 20 mg/kg. Maintenance therapy: Phenobarbital, oral, 5 – 10 mg/kg/24 hours in 2 divided doses, until convulsion-free for at least 2 weeks. rabiezahran@gawab.com

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Fever: Paracetamol 10 mg/kg orally 6 hourly until fever subsides . rabiezahran@gawab.com

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When HSE cannot be ruled out, Acyclovir must be started promptly (before the patient lapses into coma) and continued at least 10 days for maximal therapeutic benefit. Herpes encephalitis : rabiezahran@gawab.com

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Herpes encephalitis : Dose : Acyclovir , IV, 10 mg/kg 8 hourly for 14-21 days . Administer each dose slowly over 1 hour . rabiezahran@gawab.com

Suspected HSE Treatment Plan:

Suspected HSE Treatment Plan rabiezahran@gawab.com

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Raised intracranial pressure or cerebral edema: Elevate head of bed + 15 degrees. Maintain PaCO2 at 28 – 30 mmHg; (arterial partial pressure of carbon dioxide in the blood). intubate and ventilate if necessary. Mannitol , IV, 1g/kg over 1 hour. (Do not repeat.) Frusemide , IV,1 mg/kg. (Do not repeat.) Avoid fluid overload. Limit total daily fluid intake (IV+ oral), not to Exceed maintenance Requirements for age. rabiezahran@gawab.com

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Thank you rabiezahran@gawab.com

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