Pain is common in people living with HIV (HIV+ people). The early prescription of antiviral drugs, within the first 72 hours, is effective in the reduction of acute pain and occurrence of late complications. It is estimated that one out of three people in the U.S. It is also distinct from cerebritis. But each individual person is different. Post-herpetic neuralgia may persist for months or even years; this is why it is substantial to be careful in the prescription of advised medications. People with risk factors such as HIV and cancer have compromised immune systems and are susceptible to herpes zoster.
Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. Pictures can also describe pain. Furthermore, herpes zoster vaccine seems to have an important role in the management of herpes zoster and associated pain in the elderly population. It starts as red spots, which turn into groups of clear and painful blisters. However, attempts to distinguish these acute arboviral encephalitides from the treatable acute viral encephalitides due to herpes simplex or varicella are important. Where is it located? Varicella-zoster virus encephalitis (VZVE) is life threatening in immune-compromised patients.
Antiviral medication and pain medications will shorten the duration if initiated within 72 hours of the appearance of the rash. From a risk-benefit standpoint, most authorities recommend initiating ED treatment with acyclovir in any patient whose central nervous system (CNS) presentation is suggestive of viral encephalitis, especially in the presence of fever, encephalopathy, or focal findings, and in all neonates who appear ill for whom a CNS infection is being considered. Talking to your health care provider about how you feel is not complaining – it is the best thing you can do to find out what is wrong and get the right treatment. By late summer 2002, West Nile virus had been identified throughout the eastern and southeastern United States. The blisters help the skin heal. For more information, see the CDC fact sheet on West Nile virus, links to state and local government web sites on West Nile virus, and the Environmental Protection Agency (EPA)/CDC article on mosquito control. Endorphins are brain chemicals that act similarly to drugs like morphine and codeine.
Many viruses are transmitted by humans, though most cases of HSE are thought to be reactivation of HSV lying dormant in the trigeminal ganglia. The lesions are infectious until they dry and crust over. With some viruses, such as varicella-zoster virus (VZV) and cytomegalovirus (CMV), an immune-compromised state is usually necessary to develop clinically apparent encephalitis. Examples include prednisone and hydrocortisone. The etiology of slow virus infections, such as those implicated in the measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML), is poorly understood. Once across the blood-brain barrier, the virus enters neural cells, with resultant disruption in cell functioning, perivascular congestion, hemorrhage, and a diffuse inflammatory response that disproportionately affects gray matter over white matter. Regional tropism associated with certain viruses is due to neuron cell membrane receptors found only in specific portions of the brain, with more intense focal pathology in these areas.
Opiates can lead to dependence or addiction and may be a problem for people with a history of substance use. In contrast to viruses that invade gray matter directly, acute disseminated encephalitis and postinfectious encephalomyelitis (PIE), most commonly due to measles infection and associated with Epstein-Barr virus (EBV) and CMV infections, are immune-mediated processes that result in multifocal demyelination of perivenous white matter. The cause of encephalitis is usually infectious in nature. Viral agents, such as HSV types 1 and 2 (the latter much more common in neonates than adults), VZV, EBV, measles virus (PIE and SSPE), mumps virus, and rubella virus, are spread through person-to-person contact. Ignoring pain often makes matters worse and can cause more damage in the long run. Bacterial pathogens, such as Mycoplasma species and those causing rickettsial disease or catscratch disease, are rare and invariably involve inflammation of the meninges out of proportion to their encephalitic components. Encephalitis due to parasites and fungi other than Toxoplasma gondii are covered elsewhere.
Determining the true incidence of encephalitis is impossible, because reporting policies are neither standardized nor rigorously enforced. What makes the pain worse? These figures probably represent a fraction of the actual number of cases. HSE, the most common cause of sporadic encephalitis in Western countries, is relatively rare; the overall incidence is 0.2 per 100,000, with neonatal HSV infection occurring in 2-3 per 10,000 live births. The arbovirus group is the most common cause of episodic encephalitis, with a reported incidence similar to that of HSV. Tell your health care provider – Report pain to your provider without delay. Arboviruses require an insect vector, which is generally present between June and October.
The 2 most common arboviruses result in (1) St Louis encephalitis, found throughout the United States but principally in urban areas around the Mississippi River, and (2) the geographically misnamed California virus encephalitis (CE)—in particular, LaCross encephalitis (LAC)—which affects children in rural areas in states of the upper Midwest and North East. Among the other arbovirus-caused encephalitides, the deadliest (and, fortunately, rarest) is eastern equine encephalitis (EEE), which is encountered in New England and surrounding areas; western equine encephalitis (WEE), a milder disease, is most common in rural communities west of the Mississippi River. In fact, waiting almost always results in your needing to take more pain medication than if you had begun taking it at the first sign of pain. Less common causes of viral encephalitis include VZV encephalitis, with an incidence of roughly 1 in 2000 infected persons. Measles produces 2 devastating forms of encephalitis: PIE, which occurs in about 1 in 1000 infected persons, and SSPE, occurring in about 1 in 100,000 infected patients. Rarest in the United States are the 0-3 unrelated annual cases of rabies encephalitis, typically a consequence of the immigration of an infected person from Mexico or Central America during the long incubation period of the rabies virus but prior to the onset of clinically apparent disease. High doses can cause breathing problems.
Neonatal HSE is a manifestation of disseminated infection type 1 or 2, whereas older infants, children, and adults are much more likely to have localizing CNS infection almost exclusively due to type 1, in a bimodal distribution of patients aged 5-30 years or older than 50 years. St Louis encephalitis and WNE are more common and are most severe in patients older than 60 years; conversely, LAC is more common and is most severe in children younger than 16 years. EEE and WEE disproportionately affect infants while EEE disproportionately affects children and elderly persons. Tell your health care provider if your pain is still present while taking medication. Extremes of age (< 1 y or >55 y), immune-compromised status, and preexisting neurologic conditions are associated with poorer outcomes. Untreated HSE has a mortality of 50-75%, and virtually all untreated or late-treatment survivors have long-term motor and mental disabilities. The mortality in treated HSE averages 20%, and the neurologic outcome correlates with the neurological disability present at the time of the first dose of acyclovir or comparable antiviral agents.
However, it can be managed using a variety of methods. Outcomes in arboviral JE and EEE are catastrophic, similar to untreated HSE, with high mortality and severe morbidity, including mental retardation, hemiplegia, and seizures. Other arboviruses cause substantially less morbidity and mortality. For example, St Louis encephalitis and WNE have a mortality rate of 2-20%, the higher rates found in patients older than 60 years. Long-term sequelae with St Louis encephalitis include behavioral disorders, memory loss, and seizures. WEE is associated with few deaths and much less morbidity, although developmental delay, seizure disorder, and paralysis occasionally occur in children, and postencephalitic parkinsonism may occur in adults. CE is typically associated with mild illness, and most patients make a full recovery; however, the minority of patients with severe disease have a 25% chance of focal neurologic dysfunction.
Death rates from WEE and LAC are less than 5%. PIE secondary to measles is associated with a mortality rate approaching 40% of cases, with a high rate of neurologic sequelae in survivors. SSPE is uniformly fatal, although the disease course may last anywhere from several weeks to 10 years. VZVE has a mortality of 15% in immune-competent patients and virtually 100% in immune-suppressed patients. The mortality for EBV encephalitis is 8%, with substantial morbidity found in approximately 12% of survivors. The clinical presentation and course can be markedly variable. The acuity and severity of the presentation correlate with the prognosis.
A history of mosquito or tick bites or exposure to mouse/rat droppings should be sought. Recognizing certain mammalian animal bite(s) associated with rabies or exposure to a bat in an enclosed space for which antirabies treatment was not obtained is very important. The viral prodrome is typically several days and consists of fever, headache, nausea and vomiting, lethargy, and myalgias. The specific prodrome in encephalitis caused by varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles virus, or mumps virus includes rash, lymphadenopathy, hepatosplenomegaly, and parotid enlargement. Dysuria and pyuria are reported with St Louis encephalitis. Extreme lethargy has been noted with West Nile encephalitis (WNE). Symptoms of herpes simplex virus (HSV) infection in neonates (aged 1-45 d) may include localized skin, eye, or mouth lesions in the early phase of illness with encephalitis.
Diminished alertness, irritability, seizures, and poor feeding develop later in the course of illness, and disseminated disease and shock are late findings. Herpes simplex encephalitis (HSE) in older children and adults is not typically associated with active herpetic eruptions and is characterized by the acute onset of more severe symptoms of encephalitis early in the course of illness. Toxoplasma encephalopathy accounts for as many as 40% of HIV-positive patients with neurologic disease who present with a subacute headache, findings of subtle to remarkable encephalopathy, and, often, focal neurological complaints/findings. Rarely, this may be the presenting symptom complex of profound immune suppression due to HIV infection. Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. Accordingly, in addition to standard blood and urine tests, studies may be performed to identify the infectious agent causing the encephalitis. It is important, when possible, to distinguish acute arboviral encephalitides from potentially treatable acute viral encephalitides, especially herpes simplex encephalitis (HSE) and varicella-zoster encephalitis, as a high suspicion for these disorders and prompt treatment can reduce the severity of neurological sequelae and can be lifesaving. The serum glucose level should be determined to rule out confusion due to treatable hypoglycemia and to compare with the cerebrospinal fluid (CSF) glucose value.
Low serum results are found in nutritionally deprived patients, while diabetic patients may present with elevated glucose levels compatible with complicating hyperosmolar state or diabetic ketoacidosis. Blood urea nitrogen (BUN) and creatinine levels are helpful to assess hydration status, and liver function tests should be performed to assess for end-organ dysfunction or the need to adjust antimicrobial therapy dosing regimens. A lumbar puncture (LP) should be performed on all patients suspected of having a viral encephalitis. A platelet count and coagulation profile are indicated in patients who are chronic alcohol users, have liver disease, and those in whom disseminated intravascular coagulation (DIC) is suspected. The patient may require platelets or fresh frozen plasma (FFP) before LP. A urinary electrolyte test should be performed if SIADH is suspected. Urine or serum toxicology screening may be indicated in selected patients presenting with a toxic delirium or confusional state.
Herpes simplex virus (HSV) cultures of suspicious lesions and a Tzanck smear should be obtained. Viral cultures of CSF, including HSV, should be performed, although the incidence of the latter being positive is rare. Blood cultures for bacterial pathogens should be obtained. Complement fixation antibodies are useful in identifying arbovirus. Cross-reactivity exists among a subgroup of arboviruses, the flaviviruses (eg, viruses that cause St Louis encephalitis, Japanese virus encephalitis [JE], and West Nile encephalitis [WNE]), and the antibodies found in persons inoculated with yellow fever vaccine. Serologic tests for toxoplasmosis can be helpful in light of an abnormal computed tomography (CT) scan, particularly in the case of single lesions. However, the overlap in titer levels between exposed but currently uninfected and reactivated groups may complicate interpretation.
Performance of a head CT scan with and without contrast agent should be performed in virtually all patients with encephalitis. This should be done prior to LP if there are focal complaints or findings, signs to search for evidence of elevated intracranial pressure (ICP), obstructive hydrocephalus, or mass effect due to focal brain infection. Head CT scanning also helps exclude brain hemorrhage or infarction as a cause of an encephalopathic state. Magnetic resonance imaging (MRI) is more sensitive than CT scanning in demonstrating brain abnormalities earlier in the disease course. In HSE, MRI may show several foci of increased T2 signal intensity in medial temporal lobes and inferior frontal gray matter. Head CT commonly shows areas of edema or petechial hemorrhage in the same areas. EEE and tick-borne encephalitis may show similar increased MRI signal intensity in the basal ganglia and thalamus.
In toxoplasmosis, contrast-enhanced head CT typically reveals several nodular or ring-enhancing lesions. Because lesions may be missed without contrast, MRI should be performed in patients for whom use of contrast material is contraindicated. In HSE, electroencephalography (EEG) often documents characteristic paroxysmal lateral epileptiform discharges (PLEDs), even before neuroradiography changes. Eventually, PLEDs are positive in 80% of cases; however, the presence of PLEDs is not pathognomonic for HSE. CSF analysis is essential. Typical patterns of findings in the CSF pressure and CSF analysis follow in the Table 1 regarding bacterial versus viral versus fungal (including cryptococcal) meningitis or encephalitis. The most important diagnostic test in the emergency department (ED) to rule out bacterial meningitis is prompt Gram staining and, if available, polymerase chain reaction (PCR) of the CSF in patients with suspected HSV encephalitis.
PCR for HSV DNA 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. Arguably, a series of quantitative PCRs documenting the decline of viral load with acyclovir treatment is strongly supportive of the diagnosis of HSV, and selected patients my avoid need for brain biopsy. The presence of Negri bodies in the hippocampus and cerebellum are pathognomonic of rabies, as are HSV Cowdry type A inclusions with hemorrhagic necrosis in the temporal and orbitofrontal lobes. With the important exceptions of HSE and varicella-zoster encephalitis, the viral encephalitides are not treatable beyond supportive care. Treatments for T gondii and cytomegalovirus (CMV) encephalitis are available but generally not initiated in the ED. The goal of treatment for acutely ill patients is administration of the first dose or doses of acyclovir, with or without antibiotics or steroids, as quickly as possible.
The standard for acute bacterial meningitis is the initiation of treatment within 30 minutes of arrival. Consider instituting an ED triage protocol to identify patients at risk for HSE. Collect laboratory samples and blood cultures before the start of IV therapy. Even in uncomplicated cases of encephalitis, most authorities recommend a neuroimaging study (eg, magnetic resonance imaging [MRI] or, if that is not available, a contrast-enhanced head computed tomography [CT] scan) before lumbar puncture (LP). In otherwise stable patients, elevating the head and monitoring neurologic status usually are sufficient. When more aggressive maneuvers are indicated, early use of diuresis (eg, furosemide 20 mg IV, mannitol 1 g/kg IV) may be helpful, provided that circulatory volume is protected. Dexamethasone 10 mg IV q6h helps in managing edema surrounding space-occupying lesions.
Hyperventilation (arterial CO2 tension [PaCO2] 30 mm Hg) may cause a disproportional decrease in cerebral blood flow (CBF), but it is used to control increasing ICP on an emergency basis. Intraventricular ICP monitoring is controversial. Some authorities believe that dangerous focal edema with a pressure gradient between the temporal lobe and the subtentorial space usually is not detected by the monitor and that this failure of detection can lead to a false sense of security. In fact, monitor placement may potentially aggravate a pressure gradient. Look for and treat systemic complications (eg, hypotension or shock, hypoxemia, hyponatremia, and exacerbation of chronic diseases), particularly in herpes simplex encephalitis (HSE), eastern equine encephalitis (EEE), Japanese virus encephalitis (JE). Empiric adult emergency treatment for herpes simplex virus (HSV) meningoencephalitis and varicella-zoster virus (VZV) encephalitis consists of acyclovir 10 mg/kg (infused over 1 h) q8h for 14-21 days. Give acyclovir 10-15 mg/kg IV q8h for neonatal HSV; for HSV encephalitis in the pediatric population, give acyclovir 10 mg/kg IV q8h.
Clinical Context: Foscarnet is an organic analogue of inorganic pyrophosphate. It inhibits replication of known herpes viruses, including cytomegalovirus, CMV, HSV-1, and HSV-2. It exerts antiviral activity by inhibiting viral replication at pyrophosphate-binding sites on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Patients who have poor clinical response or experience persistent viral excretion during therapy, especially HIV-positive patients, may be resistant to acyclovir. Patients who tolerate foscarnet may benefit from maintenance-level administration of 120 mg/kg/d early in treatment. Dosing should be individualized on the basis of the patient’s renal function. The goal of the use of antivirals for herpes simplex encephalitis (HSE) and varicella-zoster encephalitis is to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency.
Clinical Context: Furosemide is a loop diuretic that increases excretion of water by interfering with the chloride-binding co-transport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. It increases renal blood flow without increasing the filtration rate. The onset of action generally is within 1 hour. It increases potassium, sodium, calcium, and magnesium excretion. The proposed mechanism for furosemide in lowering intracranial pressure include (1) lowering cerebral sodium uptake, (2) affecting water transport into astroglial cells by inhibiting the cellular membrane cation-chloride pump, and (3) decreasing cerebrospinal fluid production by inhibiting carbonic anhydrase. The dose must be individualized to the patient. Depending on the response, administer at increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until desired diuresis occurs.
When treating infants, titrate with 1-mg/kg/dose increments until a satisfactory effect is achieved. Clinical Context: Mannitol may reduce pressure in the subarachnoid space by creating an osmotic gradient between cerebrospinal fluid in the arachnoid space and plasma. This agent is not intended for long-term use. Initially assess for adequate renal function in adults by administering a test dose of 200 mg/kg, given IV over 3-5 minutes. This should produce a urine flow of at least 30-50 ml/h of urine over 2-3 hours. In children, assess for adequate renal function by administering a test dose of 200 mg/kg, given IV over 3-5 minutes. This should produce a urine flow of at least 1 mL/kg over 1-3 hours.
By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including limbic and reticular formation. *Some bacteria (eg, Mycoplasma, Listeria, Leptospira, Borrelia burgdorferi [Lyme disease]) cause alterations in spinal fluid that resemble the viral profile. An aseptic profile is also typical of partially treated bacterial infections (>33%, especially those in children, are treated with antimicrobials) and of the 2 most common causes of encephalitis—the arboviruses and the potentially curable HSV. † Wait 4 hours after glucose load.