Arthropod Borne Viral Encephalitis

Slide 1 · Arthropod-Borne

Viral Encephalitis

Neuropathology | Transmission, pathogenesis, morphology and diagnosis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain why arboviral infections can cause epidemic meningoencephalitis.

Trace the West Nile virus transmission and neuroinvasion sequence.

Recognize the characteristic clinical, CSF, and neuropathologic findings.

Integrate morphology with etiologic testing and differential diagnosis.

Slide 3 · Arboviruses: A transmission-defined group

“Arbovirus” denotes an arthropod-borne virus; It is not a single viral family.

Animal hosts and arthropod vectors are central to the infectious cycle.

The encephalitides encompass multiple viruses with overlapping pathology.

The causative virus therefore cannot be established by morphology alone.

Slide 4 · Viral encephalitis is parenchymal infection

Meninges

Brain parenchyma

Spinal cord

Infection involves the brain parenchyma rather than the meninges alone.

Meningeal inflammation usually accompanies parenchymal involvement.

The resulting clinicopathologic pattern is meningoencephalitis.

Extension to the spinal cord produces encephalomyelitis.

Slide 5 · Meningitis, encephalitis and myelitis: Localization

Meninges

Inflammatory CSF

Meningeal irritation

Brain

Parenchymal neuronal injury

Encephalopathy, seizures

Spinal cord

Motor-system involvement

Paralysis

Meningeal disease explains meningitic manifestations and CSF inflammation.

Brain parenchymal disease produces impaired cognition or consciousness and seizures.

Slide 6 · Neural tropism is not uniform

Viruses differ in the neural cell types they can infect.

Other viruses preferentially involve specific brain regions.

The clinical syndrome reflects anatomic distribution as well as injury severity.

A shared histologic pattern does not imply identical tissue distribution.

Slide 7 · Direct viral encephalitis versus immune injury

Direct infection

Virus reaches CNS

Infectious encephalitis

Postinfectious response

Immune-mediated damage

Not proof of CNS invasion

Viral invasion of neural tissue directly produces a parenchymal infection.

Systemic infections can also be followed by immune-mediated CNS disease.

Slide 8 · Why arboviruses matter in neuropathology

Arboviruses are important causes of epidemic encephalitis.

The burden in tropical regions.

Infections can produce serious neurologic morbidity and high mortality.

Outbreak context is useful, but pathology and virology must establish the diagnosis.

Slide 9 · Transmission involves hosts, vectors and susceptible people

Reservoir animal

Arthropod vector

Susceptible human

Animal hosts maintain viral circulation in nature.

Arthropods transfer infection between susceptible hosts.

Humans can acquire infection when an infected vector feeds.

Slide 10 · Vector does not mean reservoir

Vector

Arthropod that transmits infection

Mosquito in the West Nile cycle

Reservoir

Host supporting persistence/circulation

Birds in the West Nile cycle

An arthropod vector transfers infection between hosts.

A reservoir sustains infection within an ecological cycle.

Slide 11 · Mosquito- and tick-borne encephalitis

Mosquito-associated

West Nile; Equine; St. Louis; La Crosse

Several named diseases

Tick-associated

Tick-borne encephalitis

Europe/Russia

Mosquito-associated arboviruses include the equine encephalitis viruses and West Nile.

Tick-borne encephalitis is a separate named arboviral syndrome.

Slide 12 · Western Hemisphere: Named encephalitis viruses

Eastern equine encephalitis virus.

Western equine and Venezuelan equine encephalitis viruses.

West Nile and St. Louis encephalitis viruses.

La Crosse encephalitis virus.

Slide 13 · Other regional arboviral encephalitides

Region

Representative viruses

Americas

Eastern / Western / Venezuelan equine; West Nile; St. Louis; La Crosse

East Asia

Japanese encephalitis

Australia / New Guinea

Murray Valley encephalitis

Russia / Eastern Europe

Tick-borne encephalitis

Slide 14 · Geographic framing is a diagnostic clue

Exposure location

Plausible arboviruses

CNS syndrome

Agent-specific evaluation

Compare residence, travel and arthropod exposure with the known regional viruses.

Geographic plausibility narrows which agents to test for.

Slide 15 · West Nile virus: A flavivirus example

West Nile virus belongs to the flavivirus group.

Robbins also places dengue and yellow fever viruses in that group.

Its clinical presentations range from mild illness to neuroinvasive disease.

It offers a concrete model for linking transmission to CNS pathology.

Slide 16 · West Nile virus has broad geographic distribution

Africa, the Middle East and Europe.

Its distribution also includes Southeast Asia and Australia.

West Nile virus entered the United States in the 1999 New York City outbreak.

Geography should be interpreted as a changing epidemiologic context.

Slide 17 · West Nile: Birds are central to the reservoir cycle

Reservoir animal

Arthropod vector

Susceptible human

Infected birds can develop prolonged viremia.

Birds serve as the major West Nile virus reservoir.

Mosquitoes transmit the virus among hosts.

Slide 18 · Humans are incidental West Nile hosts

Reservoir bird

Prolonged viremia

Maintains enzootic circulation

Human

Incidental infection

May develop systemic or CNS disease

West Nile virus is transmitted to both birds and mammals by mosquitoes.

Humans are incidental hosts, not the principal reservoir.

Slide 19 · West Nile: Non-mosquito transmission is possible

Transfusion-associated infection is described.

Organ transplantation is another reported route.

Vertical transmission and breastfeeding-associated transmission are noted.

These routes are less common than mosquito-borne acquisition.

Slide 20 · West Nile entry: Inoculation into skin

Mosquito inoculation

Skin dendritic cells

Regional lymph node

Further replication

An infected mosquito inoculates virus during feeding.

The virus initially replicates in skin dendritic cells.

Slide 21 · Lymph-node replication precedes viremia

Local replication

Lymphatic migration

Bloodstream entry

Potential organ dissemination

Virus undergoes additional replication in lymphoid tissue.

Virus then enters the bloodstream.

Slide 22 · Neuroinvasion is a distinct pathogenic step

Peripheral viremia

Blood–brain barrier

Neuronal infection

In some infected individuals West Nile virus crosses the blood–brain barrier.

It then infects neurons within the central nervous system.

Slide 23 · Integrated West Nile pathogenic sequence

Mosquito bite

Skin / lymph nodes

Viremia

CNS entry

Neuronal injury

Skin and regional lymph nodes represent early amplification sites.

Viremia provides access to distant tissues.

Slide 24 · The usual West Nile infection is asymptomatic

20%

Approximately symptomatic infections

Most infected individuals have no recognized illness.

Symptomatic infection in approximately 20%.

Clinical disease is therefore an incomplete measure of transmission.

Neuroinvasive illness is much less common than all infections.

Slide 25 · Systemic West Nile fever: Constitutional symptoms

Fever and headache are prominent features.

Myalgia, fatigue and anorexia may accompany illness.

Vomiting and diarrhea are also described.

These findings are nonspecific without exposure context or virology.

Slide 26 · The skin may contribute a diagnostic clue

~½

Symptomatic cases with maculopapular rash

A maculopapular rash may accompany symptomatic West Nile disease.

Rash in approximately half of symptomatic cases.

Absence of rash does not exclude infection.

Rash alone cannot distinguish encephalitis from systemic illness.

Slide 27 · Neuroinvasive West Nile disease is uncommon

1 in 150

Infections with CNS complications

CNS complications include meningitis, encephalitis and meningoencephalitis.

CNS complications in about 1 of 150 infections.

Affected patients may sustain major neurologic injury.

The denominator is all infections, not only symptomatic cases.

Slide 28 · Syndromic spectrum of neuroinvasive disease

Meningitis

Meningeal syndrome

Inflammatory CSF

Encephalitis

Brain dysfunction

Seizures / confusion

Myelitis

Spinal cord dysfunction

Weakness / paralysis

Meningitis describes predominant meningeal inflammation.

Encephalitis indicates brain parenchymal involvement.

Slide 29 · Generalized neurologic dysfunction

Seizures may result from brain parenchymal involvement.

Confusion and delirium indicate cerebral dysfunction.

Stupor or coma occurs with more severe encephalitis.

These are major manifestations described for arboviral encephalitides.

Slide 30 · Altered mental status establishes encephalitic severity

Confusion

Delirium

Stupor

Coma

Confusion indicates impaired cognition or awareness.

Delirium reflects more pronounced disturbance of cerebral function.

Stupor and coma identify profoundly impaired consciousness.

Slide 31 · Focal deficits may coexist with generalized disease

Reflex asymmetry indicates uneven involvement of neural motor pathways.

Ocular palsies demonstrate focal cranial motor dysfunction.

Focal signs do not exclude diffuse meningoencephalitis.

Clinical examination can reveal the distribution of neurologic injury.

Slide 32 · West Nile encephalitis may involve spinal cord

Meninges

Brain parenchyma

Spinal cord

Spinal cord involvement is explicitly.

The resulting syndrome may resemble poliomyelitis.

Paralysis can accompany a West Nile neuroinvasive infection.

This finding shifts localization beyond brain and meninges.

Slide 33 · Polio-like paralysis is a localization clue

West Nile neuroinvasion

May include spinal cord

Polio-like paralysis

Poliovirus infection

Anterior horn motor-neuron injury

Spinal poliomyelitis

A polio-like phenotype suggests injury to lower motor neuronal circuitry.

West Nile belongs in the differential of acute paralysis with encephalitis.

Slide 34 · Who is at greatest risk of severe West Nile disease?

Older age

Greater risk of severe disease

Interpret neurologic symptoms urgently

Immunosuppression

Greater risk of severe disease

Heightened concern for CNS complications

Older adults are more vulnerable to severe disease.

Immunosuppressed individuals are another high-risk group.

Slide 35 · West Nile meningoencephalitis can leave sequelae

~10%

Mortality in West Nile meningoencephalitis

Approximately 10% mortality in meningoencephalitis.

Long-term cognitive or neurologic deficits occur in many survivors.

Acute survival does not necessarily mean full neurologic recovery.

Prognosis differs considerably between mild and neuroinvasive infection.

Slide 36 · Linking the clinical findings to anatomy

Meninges

CSF inflammation

Meningeal syndrome

Brain

Neuronal injury

Seizures / delirium

Spinal cord

Motor-system injury

Paralysis

Meningeal inflammation corresponds to inflammatory CSF findings.

Brain parenchymal injury explains seizures and altered consciousness.

Slide 37 · CSF macroscopic appearance and pressure

The CSF is generally colorless in arboviral encephalitis.

Opening pressure may be mildly elevated.

Normal gross appearance does not exclude neuroinvasive viral disease.

The inflammatory profile is more informative than CSF color alone.

Slide 38 · CSF protein and glucose pattern

CSF protein

Increased

Reflects inflammatory involvement

CSF glucose

Usually normal

Not a virus-specific marker

CSF protein is typically elevated.

CSF glucose is generally normal.

Slide 39 · CSF cells change over the course of illness

Early CSF

Neutrophilic pleocytosis

Rapid transition

Lymphocytic predominance

An early neutrophilic pleocytosis may occur.

The cell differential rapidly shifts toward lymphocytes.

An early sample can therefore appear neutrophil-predominant.

Slide 40 · The CSF profile is supportive, not definitive

CNS symptoms

CSF inflammation

Compatible pattern

Etiologic testing

Cell count and protein indicate central nervous system inflammation.

Normal glucose and evolving lymphocytosis fit the textbook description.

Slide 41 · Arboviral encephalitides share a morphology

A common pattern is meningoencephalitis with mononuclear inflammation.

Histologic differences often concern severity and extent.

Parenchymal tissue injury accompanies perivascular inflammation.

Histology identifies encephalitis better than it identifies the individual arbovirus.

Slide 42 · Perivascular lymphocytic cuffing

Lymphocytes accumulate around CNS blood vessels.

This produces the characteristic perivascular cuff.

Cuffs are a morphologic signature of viral meningoencephalitis.

The finding should be interpreted with neuronal and microglial changes.

Lymphocytes surrounding a vessel

Schematic — not a tissue specimen

Slide 43 · Microglial nodules: Focal glial response

Microglial cells assemble into small aggregates in affected tissue.

These aggregates are termed microglial nodules.

They accompany focal tissue injury and inflammation.

The finding is characteristic but not specific to a single arbovirus.

Focal aggregation of microglial cells

Schematic — not a tissue specimen

Slide 44 · Neuronophagia indicates neuronal destruction

Individual neurons may undergo necrosis.

Phagocytic cells remove the resulting cellular debris.

This process is termed neuronophagia.

It provides microscopic evidence of destructive parenchymal infection.

Phagocytes around an injured neuron

Schematic — not a tissue specimen

Slide 45 · Necrosis can affect both gray and white matter

Gray matter

Foci of necrosis

Parenchymal damage

White matter

Foci of necrosis

Parenchymal damage

Multiple foci of necrosis are described across the CNS parenchyma.

Gray matter may be involved.

Slide 46 · Severe cases may develop necrotizing vasculitis

Vessel-wall injury becomes prominent in severe encephalitis.

Necrotizing vasculitis in severe cases.

Associated focal hemorrhages may occur.

This is not presented as an obligatory feature of every arbovirus infection.

Severe vessel-wall injury

Schematic — not a tissue specimen

Slide 47 · Histologic findings vary with severity

Perivascular cuffs

Microglial reaction

Neuronal loss / necrosis

Severe vascular injury

Perivascular lymphocytes signal a characteristic inflammatory response.

Microglial nodules and neuronophagia identify parenchymal cellular injury.

Focal necrosis documents tissue destruction.

Slide 48 · West Nile: Documented tissue distribution

Perivascular and leptomeningeal inflammation.

Microglial nodules and neuronophagia are reported.

Temporal lobes and brainstem are noted among affected regions in fatal cases.

This distribution is an observation, not a pathognomonic tissue map.

Slide 49 · What histology can and cannot establish

Can establish

Pattern of viral encephalitis

Severity and tissue injury

Cannot establish alone

Exact arbovirus

Transmission route or reservoir

Histology can confirm an inflammatory and destructive encephalitic pattern.

Cuffs, microglial nodules and neuronophagia are not unique to one virus.

Slide 50 · Tissue-based etiologic identification

Morphologic pattern

Targeted tissue assays

Virus identification

Clinicopathologic integration

Ultrastructural methods among approaches used in tissue.

Immunohistochemistry can detect relevant viral material.

Slide 51 · West Nile diagnosis: Virus-specific IgM

West Nile virus–specific IgM can be sought in serum.

Virus-specific IgM can also be detected in cerebrospinal fluid.

This as the usual diagnostic method.

Interpret the result alongside the clinical and epidemiologic setting.

Slide 52 · West Nile diagnosis: Additional virologic tests

Serologic route

Virus-specific IgM

Serum or CSF

Direct detection route

Culture or PCR

Use in selected settings

Viral culture is mentioned as a diagnostic method.

PCR-based tests are also used.

Slide 53 · Reasoning from exposure to diagnosis

Clinical localization

Exposure context

CSF findings

Virologic confirmation

Identify a compatible CNS syndrome and its anatomic localization.

Consider geographic and arthropod exposure information.

Slide 54 · Differential pathology: Herpes simplex encephalitis

Arboviral encephalitis

Shared perivascular cuffs and nodules

Confirm with agent-directed methods

HSV-1 encephalitis

Hemorrhagic necrosis; Temporal predilection

Possible Cowdry A inclusions

HSV-1 classically affects inferior frontal and anterior temporal regions.

A hemorrhagic necrotizing inflammatory process.

Slide 55 · An early neutrophilic CSF is not automatically bacterial

Robbins explicitly describes early CSF neutrophilia in arboviral infection.

The differential may evolve rapidly toward lymphocytosis.

CSF glucose generally remains normal in the described arboviral pattern.

Diagnostic reasoning must integrate course and microbiology, not one differential count.

Slide 56 · Interpret histology without overcalling an agent

Perivascular cuffing is an inflammatory pattern, not a species marker.

Neuronophagia and microglial nodules indicate neuronal and glial responses.

Focal hemorrhage or severe vasculitis may indicate greater injury.

Only appropriately validated etiologic methods can establish the responsible virus.

Slide 57 · Case 1: Acute encephalitis after mosquito exposure

An older adult develops fever, confusion and seizures.

CSF is colorless, with elevated protein and normal glucose.

Early neutrophils become lymphocyte-predominant in a subsequent sample.

Question: What diagnostic category and next line of testing are indicated?

Slide 58 · Case 1: Interpret the evidence

The brain dysfunction and CSF findings support meningoencephalitis.

The evolving cell differential is compatible with arboviral infection.

Exposure and host risk justify West Nile evaluation where epidemiologically plausible.

Use virus-specific IgM in serum or CSF rather than histology alone.

Slide 59 · Case 2: Acute paralysis with encephalitis

A patient develops febrile encephalopathy and new limb paralysis.

The motor syndrome suggests concurrent spinal cord involvement.

West Nile virus may produce a polio-like syndrome.

Question: Which additional anatomic compartment requires attention?

Slide 60 · Case 2: Localize before naming the virus

The spinal cord joins brain and meninges in the suspected disease distribution.

Paralysis does not by itself prove poliovirus infection.

Consider West Nile neuroinvasion within the relevant exposure context.

Confirm with appropriate virologic methods.

Slide 61 · Case 3: Tissue shows lymphocytic cuffs and nodules

Microscopy demonstrates perivascular lymphocytes and microglial nodules.

Additional sections show neuronophagia.

The findings support destructive viral meningoencephalitis.

Question: Can these findings alone distinguish La Crosse from West Nile?

Slide 62 · Case 3: Morphology has an etiologic limit

No: The shared injury pattern does not identify the exact arbovirus.

Assess regional exposure and clinical syndrome.

Use agent-directed tests in serum, CSF or tissue where applicable.

Report the histopathologic pattern separately from etiologic confirmation.

Slide 63 · Clinical and pathologic synthesis

Arboviral meningoencephalitis links animal–arthropod ecology to CNS infection.

West Nile illustrates the route from skin replication to viremia and neuronal injury.

CSF shows elevated protein, normal glucose and an evolving cell differential.

Perivascular cuffs, microglial nodules and neuronophagia form a shared tissue pattern.

Slide 64 · References

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th edition (2026).

Central nervous system: infections, viral meningoencephalitis and arthropod-borne encephalitis.

Infectious diseases: West Nile virus clinical features, pathogenesis and morphology.

Microscopic teaching diagrams in this presentation are original native PowerPoint schematics, not human tissue images.