| Fact | Explanation |
|---|---|
| Fever [2] | Encephalitis is an inflammation of the brain parenchyma. Herpes simplex is one of the fastest replicating viruses that accounts for encephalitis. [1] Once the person is exposed to infected saliva or respiratory secretions, virus ascends along the olfactory nerve into the limbic lobe, or it may be reactivation of virus from Trigeminal ganglion. Flavivirus infection, is also known to cause japanese encephalitis which has a fatality of 60%. [2] Varizella zoster, tuberculosis, mumps, measles are the other major causative agents. [4] Once entered into the brain, it causes axonal spread to newly infected regions in the brain, that damages the brain by direct lysis of cells or, later, virus-induced damage causing further destruction accompanied by host's immune responses. 90% of patients show evidence of temporal lobe involvement. Inflammation of the meninges, brain matter and endothelium releases pyrogens causing fever. |
| Headache [2] | Pathogens may cross the BBB transcellularly (through human brain microvascular endothelial cells), paracellularly(penetration between barrier cells with and/or without disruption of tight junctions) and “Trojan horse” mechanism(penetration of the barrier cells using transmigration within infected phagocyte) . [5] Once the organism entered through the blood brain barrier, immune system of the body gets activated to release various cytokines and chemikines. Further it releases reactive oxygen radicals to cause more endothelial and nearby tissue damage. These can cause meningeal irritation, increased intracranial pressure and cerebral edema. |
| Seizures | Altered cerebral perfusion pressure can cause reduction of the cerebral blood flow and ischaemia. This also might represent viral invasion and destruction of neuronal cells. [1] |
| Decreased alertness, drowsiness | There can be increased intracranial pressure which may be due to the increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways etc. Neuronal cell death and cerebral edema may also contribute to the drowsiness. [4] |
| Behavioural changes | Temporal lobe involvement is common in encephalitis. Behavioural abnormalitieS [6] are occurred due to this and odd behaviour may be an earliest symptom. |
| Sensitivity to light (photophobia), Pain during retraction of the neck | Inability to tolerate light due to the associated meningoencephalitis. [8] Neck stiffness is due to the meningeal irritation. |
| Vomiting | Vomiting is a common finding in meningoencephalitis. [8,9] |
| Excessive crying, refusing the feeds | Infants and young children present with nonspecific features. [9] |
| Hearing loss | Inflammation can extends to the cranial nerves, when the 8th nerve is involved that causes sensorineural type hearing loss.[7] |
| Visual problems [2] | Visual problems Involvement of the optic and other cranial nerves related to the vision can be the cause. [2] |
| History of immunodeficiency | People with immune deficiency like malignancy, patients on chemotherapy, long term steroid use, organ transplant and HIV AIDS are particularly vulnerable for the disease. [1] |
| History of malignancy | They can develop paraneoplastic encephalitis. [3] |
| Fact | Explanation |
|---|---|
| Febrile | Fever is one of the commonest presenting features. [3] |
| Mental status changes | Alteration in mental status is a poor prognostic indicator. [5] |
| Unconsciousness and coma | Coma is a severe form of altered level of consciousness. [4] State of unarousable unconsciousness with no response to external stimuli. Patient appears to be asleep. |
| Stiff neck | Due to the meningeal irritation. [5] |
| Kernig sign and brudzinki sign | Kernig sign a is a bedside diagnostic sign used to evaluate suspected cases of meningitis. Patient is kept in supine position, hip and knee are flexed, the knee is slowly extended by the examiner. It is positive if there is a resistance or pain during extension. [1] Another sign of meningeal irritation is Brudzinki sign . First one hand is kept behind the patient's head and the other on chest in order to prevent the patient from rising, passive flexion of the neck produces reflex flexion of the patient's hips and knees in a positive Brudzinski's sign. |
| Tachycardia | Tachycardia or a fast heart rate is observed in hypotensive, confused patients. [6] |
| Focal neurological signs | Mostly cerebral involvement affects the temporal lobe causing hemiparesis, speech disturbances and odd behaviour. Cerebral-space-occupying lesions such as abscess formation can also cause these symptoms. [3] |
| Buldging of fontanelle | Due to the increased intracranial pressure. [6] |
| Growth retardation | Ischaemia can cause neuronal cell death and tissue damage, if the developing brain is affected with permanent neuropsychiatric sequelae [5] child may ends up with poor growth. |
| Sensorineural hearing loss [2] | Braistem encephalitis may cause cranial nerve palsies specially VIII the nerve palsy is the cause for this hearing loss. [2] |
| Papilloedema | This is due to the increased intracranial pressure. [7] Increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways as in hydrocephalus are the possible causes for the raised intracranial pressure. |
| Diplopia [3] | Is seen as a visual probleM. [3] |
| Other manifestations of Herpes Simplex Virus | Genital herpes may cause vesicles, gingivostomatis,eczema herpeticum which is an eczematous skin lesion, redness, watering, discharge, itching, irritation, and lid swelling, lid vesicles and ulcers. [8] |
| Fact | Explanation |
|---|---|
| Meningitis | Meningitis will be present with the same clinical features [4] as in encephalitis, fever, headache, vomiting with more prominent features of meningeal irritation such as neck stiffness, positive kernig sign [3] and brudzinki sign. Cerebrospinal fluid analysis findings may differ according to the aetiology. Elevated neutrophil count,markedly elevated protein and reduced CSF sugar is seen in bacterial meningitis. Viral meningitis will show less marked elevation of protein, and reduction of sugar with prominent lymphocytosis in the CSF. |
| Encephalopathy due to non infectious causes | Same clinical features of encephalitis presents with a history of anoxic/ischaemic damage, nutritional deficiency, alcoholism, critical illness, malignant hypertension, traumatic brain injury or epileptic (non-convulsive status). [1] Fever, headache like features are uncommon in encephalopathy than in encephalitis/ meningitis. Depressed mental status is steadily deteriorating in encephalopathy rathe than that may be fluctuating in encephalitis/ meningitis. Focal neurologic signs are uncommon in encephalopathy. Types of seizures are usually generalised. |
| ADEM/postinfectious encephalomyelitis | This usually follows a vaccination or an infection like measles, rubella or chickenpox. [1] |
| Cerebral malaria | Some CSF findings may help to differentiate cerbral malaria from encephalitis. [2] CSF glucose level below 3.4 mmol/l is one of the the best discriminators of cerebral malaria from viral encephalitis. CSF lactate, is also characteristically elevated in cerebral malaria. |
| Fact | Explanation |
|---|---|
| Lumbar puncture | Opening pressure will be elevated. Predominantly mononuclear pleocytosis with elevated lymphocytes [3] an elevated CSF protein, reduced CSF glucose <40 mg/dL is seen. Fewer inflammatory cells are observed among AIDS patients due to the lack of a vigorous cellular immune response. Viral cultures of CSF, including HSV should be done. Polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) is the diagnostic method for herpes encephalitis. [2] |
| Blood culture | Blood culture [4] done if the patient seems to be septic or lumbar puncture can not be done safely due to the possibility of increased intracranial pressure before the specific treatment. |
| Computer tomography(CT) scan of the head and Magnetic Resonance Imaging (MRI) [1] | CT scan will be even better as the first investigation specially to rule out the possibility of increased intracranial pressure before doing lumbar puncture. CT will reveal several foci in medial temporal lobes and inferior frontal gray matter with increased T2 signal intensity in encephalitis. It is also helpful to evaluate the presence of any haemorrhages and infarctions. Thalamic hyperintensity in magnetic resonance imaging (MRI) is a specific finding which could be very useful in diagnosing Japanese encephalitis. [3] MRI will demonstrate the inflammatory dural meningeal process with enhanced uptake over the affected areas in associated meningoencephalitis. . This also show the complications like hydrocephalus. |
| Electroencephalogram | EEG is often abnormal [4] with diffuse slowing or uni or bilateral temporal periodic discharges or low wave complexes at 2-3/second interval. |
| Full blood count | There can be elevated lymphocytes, it is also important to exclude the other causes for the fever such as low platelets in viral infections, high white blood cells (leucocytosis) [5] in bacterial infections. |
| Fact | Explanation |
|---|---|
| Erythrocyte sedimentation rate(ESR) and C Reactive protein(CRP) | Is elevated due to the inflammation. [1] |
| Renal functions and serum electrolytes | Syndrome of inappropriate Antidiuretic Hormone secretion [2] is a complication of encephalitis. This can cause hyponatraemia. Reduced intake of fluids can cause electrolyte imbalances. Medications may alter the renal functions and therefore baseline value is also needed. |
| Liver function tests | Medications may alter the liver functions and therefore baseline value is needed before the treatment. [3] |
| Random blood sugar | Should be done immediately especially if the patient is drowsy, to rule out the hypoglycaemia [4] as cause for drowsiness. |
| Fact | Explanation |
|---|---|
| Polymerase chain reaction (PCR) | After completion of antiviral therapy, PCR of the CSF may be needed to confirm the elimination of replicating virus. [1] |
| Fact | Explanation |
|---|---|
| MRI/CT brain | Increased intracranial pressure is evident on MRI by severe sulcal effacement and midline shift on brain imaging. [1] |
| HIV screening | Those who accept HIV screening [3] should have the antibody check up as these infections are common in people infected with HIV. |
| Thick and thin blood films for malaria | Cerebral malaria needs to be excluded. [2] |
| Fact | Explanation |
|---|---|
| Immediate management | This is particularly important if the patient presents with confusion and drowsiness. Airway, breathing, circulation, disability and environment need to be attended. Random blood sugar is done to exclude hypoglycaemia. [3] Lumbar puncture needs to be done before the antivirals or any other treatment. ( if the possibility of increased intracranial pressure can be rule out) If it is not safe to do the LP blood culture is done and anti virals are started as soon as possible without delay. |
| Supportive management [1] | Antipyretics, (acetaminophen), and antiemetics, (promethazine) may be given. [1] Hydration should be checked due to the possibility of syndrome of inappropriate Antidiuretic hormone, and transient renal insufficiency caused by antiviral therapy, Provide of adequate hydration with 2/3 of maintenance is preferable. Monitoring of the vital parameters should be done during the initial period. |
| Management of the complications | If there are seizures, anticonvulsants should be continued and close follow-up should be done.[1] If there is of rapidly increasing intracranial pressure with clinical deterioration where medical treatment failed, surgical decompression has to be considered as a life saving measure. Ventriculoperitoneal (VP) shunt is placed for the symptomatic improvement in hydrocephalus. [1] |
| Follow up | As they are vulnerable for complications such as hearing loss, vision problems, growth retardation, learning disability they need to be followed up with hearing, vision and growth assessment. [4] |
| Vaccination | Acute encephalitis has declined substantially due to the introduction of vaccines. MMR vaccination programmes eradicated measles-, mumps- and rubella-associated encephalitides. JE vaccinations have been used to control JE associated encephalitis. [2] |
| Fact | Explanation |
|---|---|
| Acyclovir | If the features are suggestive of of encephalitis, acyclovir, 10 mg/kg three times daily, is added as soon as possible and once the diagnosis is confirmed acyclovir is continued for 14 days. [1] This has shown to reduce the mortality and morbidity significantly. |
| Steroids | Steroids [2] eg:- Dexamethasone (4 mg every six hours)is given to reduce the inflammatory response occur during the anti microbial treatment. |