Case

Presentaion

Khaled Alzahrani
Chief complain :
• 28 years old Saudi male unknown to have any chronic
illness presented with repeated vomiting and mental
changes that include less responsiveness and sleepy for
the last 3 days
History of prsenting ilness
• Patient was a usual state of health till 26/5/2023 after arrival from England, after 3
days started to have sudden continuous subjective fever, associated with generalized
tension like headache that continuous, moderate to sever in intensity not responding
to adol
• Vomiting of food content no blood or mucus, 3 times
• Patient gave history of night sweet, unintentional weight loss approximately 5 kg in
last six months, and loss of appetite , no lymphadenopathy
• No neck pain, focal neurological weakness, or deficit , no convulsion and, no loss of
consciousness
• There is history of photophobia and phonophobia started after 2 days of main complain
• Patient denies any sick contact or similar presentation previously or among family or
friends.
• There is animal contact of camel with no consuming any of raw product
• No Respiratory symptoms of cough, dyspnea, chest pain no recent URTI
• No skin rash, arthralgia, back pain, or genitalia or mouth ulcers
Cont.
• No over-the-counter medications or illicit drug usage or intravenous
drug usage.
• No sexual activity
• No history of blood transfusion
• PMH: patient admitted under medical at 8/6/2023 for same
presentation
• Pt is up to date of vaccinations
• PSH : no previous surgery before
• Social hx: Patient is a single, live with nine persons in the flat. With
three in one room sharing food and personal equipment including
towels with good ventilation of room
• No alcohol use or smoking
On examination
Conscious alret oreinted to person and place not the time
Vitally stable : 121/95 HR: 86 SPo2: 98% on room air T: 36.9
Neurological examination:
Pupil equal , reactive and no limitations of EOM
No fascial asymmetry
o Motor : move all limb freely with normal tone
o Sensory intact of pin sensation
o Reflexes are normal
o Coordination is normal
Negative for Kernig’s sign, Brudzinski’s sign
CVS: normal heart sound
Chest: EBAE with no added sound
Leg: no sign of DVT or edema
Laboratory:
URINE EXAMINATION
• Cbc:
BILIRUBIN Nil
WBC: 5.4 UROBILINOGEN Normal Trace E.U/D
Hgb: 14.5 BLOOD +
NITRITE Nil
PLT : 296
LEUCOCYTE ESTERASE Nil
Renal profile: SP GRAVITY 1.030
Urea: 2.8 COLOR Dark Yellow
APPEARANCE Turbid
Creatnin: 83 REACTION (PH) 5
Na: 131 ALBUMIN Nil
K: 4 GLUCOSE Nil MG/DL
KETONES Nil MG/DL
Normal liver function test including cogaulation
Normal VBG
ESR : 4
Ddx ?
Imaging
• At ER: CT brain of pervious admssion :
Ill define hypodensity noted in the right termpoal lobe involving the basal
ganglia as well needs further evulation by contrast MRI
• MRI of the brain: of pervious addmsion:
Radiological findings highly suggestive of HSV encephalitis for CSF PCR of HSV-
1
• Ct brain at ER 8/6/2023:
there is persistant hypodensity / increase hypodensities ( Gloisis /
encephalomalscia) at the medial right temproal lobe
+ diffuse mild effacemnt of the cerbral sulci biltarlly likley rlated to intracianl
hypertesnion VS slight edema
Cont.
• MRI brain at current addmison : incomplete as patient moving

• CXR: NAD
Course of hopitalization
• Lumber puncture done 8/6/2023 --12/7/2023:
• CSF C/S 8/6 --> No growth
Cont.
• Septic work up:
o Blood at 8/6 and 9/7  no growth
o Sputum: rejected
o Urine: no C/S
What further work up
would like to add?
Cont.
• PCR FOR TB  Negative By Genexpert ( PCR )

• 2 nd HIV I/II AgAb  NON REACTIVE

• HCV, AB  NON REACTIVE , HCV QUANTITATION & DETECTION BY PCR 

Rejected

• 2 nd HBs, Ag  NON REACTIVE

• BRUCELLA ABORTUS SCREENING  received

• HSV 1/2 QUANTIFICATION & DETECTION BY PCR  received

Cont.
• Patient received at ER ceftzideme 2 g IV stat
• Started by ID :
Acyclovir 750 mg IV TID for 21 days
Patient after 3 days show improvement regarding headache and
respnseviness
Patient now on day 9
 ID sign off with recomendation to complete the course and follow up
of pervios work up
 Viral
Encephalitis
Introduction:
• Def. : Inflammation of brain parenchyma , characterized
by impaired cerebral function (altered metal status ,
neurologic deficits) ,
• Causes of encephalitis include viruses such as herpes
simplex virus and as well as bacteria , Other causes
include autoimmune and certain medications.
• often due to primary viral infection or post-viral
inflammation
MENINGITIS VS ENCEPHALITIS
• The presence or absence of normal brain function is the
important distinguishing feature between encephalitis and
meningitis.
• Abnormalities in brain function: altered mental status, motor or
sensory deficits, altered behavior and personality changes, and
speech or movement disorders.
• Seizures and postictal states can be seen with meningitis alone
and should not be construed as definitive evidence of
encephalitis.
• However, the distinction between them is blurred since some
patients may have both a parenchymal and meningeal process
with clinical features of both.  meningoencephalitis is also a
VIRAL VERSUS POSTINFECTIOUS
ENCEPHALITIS
• Viral encephalitis can be either primary or postinfectious
• Primary infection is characterized by viral invasion of the
central nervous system. Neuronal involvement can be
identified on histologic examination, which may show
inclusion bodies on light microscopy or viral particles on
electron microscopy. The virus can often be cultured from
brain tissue.
• Postinfectious encephalitis (also called acute
disseminated encephalomyelitis, or ADEM), a virus cannot
be detected or recovered, and the neurons are spared , that
EPIDEMIOLOGY
• HSV-1 encephalitis is the most common cause of fatal sporadic
encephalitis
• The infection arises in all age groups, with one-third of all cases
occurring in children and adolescents.
• HSV-1 is also the most commonly identified pathogen among
hospitalized patients diagnosed with encephalitis
• In neonates, herpes encephalitis may be caused by either HSV-
1 or HSV-2
VIRAL PATHOGENS
• A wide variety of different viruses can infect the central nervous
system (CNS).
• A common cause of sporadic encephalitis is herpes simplex
virus (HSV) type 1
• Other viral pathogens may be suggested by:
- Geographic location: (eg, Eastern equine encephalitis in North
America and Japanese encephalitis in Asia)
- Epidemiologic clues, such as exposure history (eg, bat exposure or
dog bite and rabies),
- regional outbreaks
- clinical clues: such as profound weakness and rash with West
Nile.
• Uncommon causes include: varicella zoster virus, Epstein-Barr
virus, HIV, human herpes virus-6, parvovirus, and Zika virus
History clues
• The cause of viral encephalitis is apparent in some cases because of an unusual
exposure history or a characteristic clinical presentation.
• Arboviruses (eg, eastern equine, western equine, St. Louis, Venezuelan equine
encephalitis, and West Nile virus) cause disease when mosquitoes are active,
• Both geography and animal exposure can broaden the diagnostic considerations
of etiologic agents:
- West Nile virus has been by far the most common cause of proven viral
encephalitis in the United States. West Nile virus first appeared in the United
States
- Nipah virus encephalitis associated with exposure to pigs or bats
- Hendra virus infected horses
- Lymphocytic choriomeningitis virus (LCMV) is a human-acquired zoonosis caused
by a rodent-borne arenavirus,  exposure to secretions of mice, rats, and hamsters
• Prior history of an animal exposure or bite may also suggest the possibility of
rabies encephalitis; however the absence of such a history does not eliminate
the diagnostic possibility of rabies.
In the absence of these findings, epidemiologic information such as seasonal occurrence or
exposures may be helpful in establishing a specific diagnosis
CLINICAL MANIFESTATIONS

• Signs and symptoms — Altered mental status ranging

from subtle deficits to complete unresponsiveness.
• Symptoms and signs of meningeal irritation (photophobia
and nuchal rigidity) are usually absent with a pure
encephalitis, but often accompany a meningoencephalitis.
• Seizures are common with encephalitis, and focal neurologic
abnormalities can occur, including hemiparesis, cranial
nerve palsies, and exaggerated deep tendon and/or
pathologic reflexes. Patients may appear confused, agitated,
or obtunded.
CLINICAL MANIFESTATIONS
Clues on physical examination

• Although there are usually no pathognomonic findings on the initial

patient encounter, certain physical examination features may suggest a
particular diagnosis:
- Grouped vesicles in a dermatomal pattern may suggest varicella zoster
virus (VZV),
- Parotitis strongly suggests the diagnosis of mumps encephalitis
- Flaccid paralysis, a polio-like presentation, that evolves into an
encephalitis strongly suggests the possibility of West Nile virus infection
- Tremors of the eyelids, tongue, lips, and extremities may suggest the
possibility of St. Louis encephalitis or West Nile encephalitis in the
appropriate geographic location or travel history.
- Findings of hydrophobia, aerophobia, pharyngeal spasms, and
hyperactivity suggest encephalitic rabies.
Cont. regarding HSV encephalitis
• Other associated neurologic symptoms include urinary and
fecal incontinence, aseptic meningitis, localized dermatomal
rashes, and Guillain-Barré syndrome
• Various behavioral syndromes have been reported in
association with HSV-1 encephalitis including:
●Hypomania: may include an elevated mood, excessive
animation, decreased need for sleep, inflated self-esteem, and
hypersexuality
●Klüver-Bucy syndrome (KBS) psychic blindness," loss of
normal anger and fear responses, and increased sexual activity
●Varying states of amnesia
DIAGNOSIS
• The initial diagnostic step in patients with suspected viral encephalitis is
Analysis the cerebrospinal fluid (CSF).
• The gold standard for establishing the diagnosis is the detection of herpes
simplex virus DNA in the cerebrospinal fluid (CSF) by polymerase chain reaction
(PCR).
• The opening CSF pressure should be noted and CSF should be analyzed for cell
count, glucose, and protein.
• In addition to :
 CSF polymerase chain reaction (PCR) testing for herpes simplex virus (HSV)-1,
HSV-2, VZV, and enteroviruses.
Additional testing (eg, serology for arboviruses, HIV testing) should be
considered based on geographic considerations, the clinical presentation, and
the exposure history.
Diagnostic evaluation for nonviral infectious (eg, bacteria, fungi, and
mycobacteria) and noninfectious etiologies should also be considered.
 The most important viral etiology to rule out in a patient with encephalitis is HSV, since this clinical entity is usually
fatal if untreated.
Cerebrospinal fluid findings
• Examination of the cerebrospinal fluid (CSF), although not diagnostic, The
following findings are characteristic of viral CNS infections:
• Increased white blood cell (WBC) count, but usually less than 250/mm3.
The differential shows a predominance of lymphocytes, although early infection
may reveal a predominance of neutrophils. In the latter setting, a repeat CSF
cell count eight hours later will generally show a shift from neutrophils to
lymphocytes
• Elevated protein concentration, but usually less than 150 mg/dL.
• Usually normal glucose concentration (>50 percent of blood value), but
moderately reduced values are occasionally seen with HSV, mumps, or some
enteroviruses.
• Red cells are usually absent (in a nontraumatic tap); their presence in the
appropriate clinical setting suggests HSV-1 infection or other necrotizing
encephalitides.
Imaging
Results of imaging in patients with encephalitis may or may not demonstrate abnormal
radiographic findings on (CT) or (MRI).
MRI with or without contrast is the study of choice to evaluate HSV-1 encephalitis,
and in the majority of cases, is abnormal.
The location of abnormal signal can sometimes be suggestive of specific etiologies:
• Temporal lobe involvement is strongly suggestive of herpes simplex virus (HSV)
encephalitis, although other herpes viruses (eg, VZV, Epstein-Barr virus, human herpesvirus 6)
can also produce this clinical picture
• Involvement of the thalamus or basal ganglia may be observed in the setting of
encephalitis due to respiratory viral infection, Creutzfeldt-Jakob disease, arbovirus, and
tuberculosis
• In a study of 17 patients with confirmed West Nile infection, MRI imaging demonstrated a
variety of abnormalities in the basal ganglia, thalami, mesial temporal structures, brainstem,
and cerebellum in eight patients . Three patients with muscle weakness also had
abnormalities noted in the spinal cord and cauda equina.
• The presence of hydrocephalus may suggest nonviral etiologies such as bacteria, fungal,
or parasitic agents.
• MRI during postinfectious encephalitis may demonstrate multifocal lesions mainly involving
supratentorial white matter
Electroencephalograph — is often abnormal in acute encephalitis>80 % ,. Focality in
the temporal lobe region is suggestive of HSV encephalitis,
• Brain biopsy — As a last resort, brain biopsy can be considered
in the patient if the etiology of encephalitis is still unknown.
• CSF antigen and antibody determinations — CSF antigen and
antibody determinations are not helpful in the early diagnosis of
HSV encephalitis.The use of purified HSV glycoprotein B to detect
CSF antibodies has a sensitivity of 97 percent and a specificity of
100 percent. However, viral antibody titers, which rise fourfold
over the course of the illness, are first positive after 10 days to 2
weeks of illness and are thus only helpful retrospectively.
• Viral culture — Viral culture of CSF is rarely positive in the early
stages of infection and is only positive later in about 4 to 5 percent
of patients with brain biopsy-proven HSV encephalitis
DIFFERENTIAL DIAGNOSIS
• A number of noninfectious etiologies can mimic central nervous
system (CNS) infections. These include primary intracranial or
metastatic tumors, adverse effects of medications, and autoimmune
or paraneoplastic diseases, such as those associated with vasculitis
or the anti-NMDA receptor
• Nonviral infectious etiologies to consider in the patient with
suspected CNS infection include brain abscess, syphilis, tuberculous
meningitis, and fungal meningitis (eg, coccidioides), which can
affect the sensorium.
• Knowledge of the patient's underlying immune status is also
critical, since the differential diagnosis is even broader in
immunocompromised hosts (eg, toxoplasmic encephalitis and
cryptococcal meningitis)
EMPIRIC THERAPY
• There are no specific therapies for most central nervous system (CNS)
viral infections. However, some important exceptions apply:
• Empiric treatment for herpes simplex virus (HSV)-1
infection with acyclovir (10 mg/kg intravenously every eight hours)
should always be initiated as soon as possible if the patient has
encephalitis without apparent explanation
• Acyclovir should also be administered if varicella zoster virus
encephalitis is likely.
• A list of the major pathogens that produce the clinical syndrome of
encephalitis, along with suggested initial treatment, appears in the
next table
HSV encephalitis

• Empiric therapy – We recommend empiric therapy with IV

Acyclovir (10 mg/kg IV every 8 hours
• Oral antiviral therapy (eg, valacyclovir) should not be used
for the treatment of HSV encephalitis.
Acyclovir

• DOSE ADJUSTMENTS: Dose modification of Acyclovir is recommended

for patients with a reduced estimated glomerular filtration rate (eGFR)
• TOXICITY:
Acute renal failure — Acute renal failure, produced by the
precipitation of relatively insoluble Acyclovir crystals in the renal
tubules,
Neurologic toxicity — Rare reports of neurologic toxicity have
included agitation, tremors, delirium, hallucinations, and myoclonus
USE IN PREGNANCY: no controlled studies have been performed to
establish the safety of Acyclovir during pregnancy, However, exposure
to antiviral therapy was not associated with an increased risk of a
congenital anomaly.
Duration for those with HSV encephalitis

• in immunocompetent patients should be 14 to 21 days

• shorter time periods have been associated with occasional
relapse with acyclovir-sensitive HSV
INCREASED INTRACRANIAL PRESSURE
• Information on the incidence or management of raised cerebrospinal
fluid (CSF) pressure in patients with viral encephalitis is limited.
• All of the "standard" therapeutic interventions for lowering CSF
pressure (eg, steroids, mannitol) have been used in this setting, but
none have been shown to be of well-established benefit.
• Although Dexamethasone has been shown to reduce brain edema
and improve neurologic outcomes in patients with pneumococcal
meningitis, there are only limited retrospective data on the use of
steroids in viral encephalitis
• However, serial ICP monitoring should be part of the management of
a patient with encephalitis with documented elevated ICP, since this
parameter has been associated with a negative prognosis.
PROGNOSIS
• Most studies of viral encephalitis are focused on short-term
outcomes.
• As an example, one prospective study in France examined 167
surviving patients with a history of encephalitis three years after
enrollment .
 61% percent survived without sequelae,
while 18 % were mildly impaired,
14 % were severely impaired
1 % remained in a vegetative state.
• The most frequent sequelae included difficulties in concentration,
behavioral and speech disorders, and memory loss.
• One-quarter of those who were previously employed had not returned
to work.
OUTCOMES
• Untreated, the fatality in herpes encephalitis can approach
70 percent and most of the survivors have serious
neurologic deficits. Survivors can also have significant
neuropsychiatric and neurobehavioral issues
• Mortality – Even with appropriate diagnosis and treatment,
mortality may still be as high as 20 to 30 percent
Autoimmune encephalitis
• HSV encephalitis is also associated with an autoimmune
encephalitis mediated by autoantibodies against the N-
methyl-D-aspartate receptor (NMDAR) for the
neurotransmitter glutamate. The hallmark symptoms
include prominent neuropsychiatric changes, decreased
consciousness, seizures, dyskinesias including
choreoathetosis, and autonomic instability.
• Thus, recurrent neurological symptoms in patients with a
recent history of HSV encephalitis should prompt CSF
evaluation of viral DNA and anti-NMDAR antibodies.
Any questions ?
Thank you..