01Approach to the Critical Patient/attcp64

Immediate priorities

›Airway and breathing

›GCS <= 8 as intubation threshold

›Rapid sequence intubation preparation

›Aspiration precautions in obtunded patient

›Oxygen saturation target

›SpO2 >= 94% on supplemental oxygen

›HFNC for hypoxemic respiratory failure

›If respiratory failure or airway compromise, airway before lumbar puncture

›Class I recommendation

›Neurocritical care team involvement

›Neurological status

›GCS trending

›Rapid decline as ICU trigger

›Serial assessments every 1 to 2 hours in moderate to severe disease

›Seizure activity

›Witnessed convulsions or subtle ictal movements

›Nonconvulsive status epilepticus concern in persistently altered patients

›Signs of elevated intracranial pressure

›Cushing response: hypertension with bradycardia

›Papilledema on fundoscopy

›Unilateral or fixed dilated pupil

Monitoring and targets

›Monitoring bundle

›Continuous cardiac monitoring

›Arrhythmia detection in autonomic instability

›QTc monitoring if QT-prolonging agents initiated

›Neurological monitoring

02History/hx80

Exposure and tick history

›Tick exposure context

›Geographic location of exposure

›Northeastern US

›Great Lakes region

›Upper Midwest

›Outdoor activities

›Hiking

›Hunting

›Gardening in wooded or brushy areas

›Tick bite details

›Known tick bite versus unrecognized attachment

›Duration of attachment may be very brief

›POWV can transmit in as little as 15 minutes unlike Lyme disease

›Seasonality

›Peak season May through September

›Most cases spring through fall

›Rare winter cases in hunters

Symptom progression

›Prodrome phase

›Fever

›Typically 38 to 40 degrees C

›Onset 1 to 4 weeks after tick exposure

›Headache

›Often severe

›Early and prominent feature

›Nausea and vomiting

›Common early symptoms

03Physical Exam/exam77

Vital signs and general appearance

›Vital sign assessment

›Temperature

›Fever often present

›Hypothermia in severe sepsis or late stage

›Heart rate and blood pressure

›Cushing response: hypertension plus bradycardia as ICP marker

›Tachycardia from fever or autonomic instability

›Respiratory rate

›Increased rate from central dysregulation or hypoxemia

›Apneic episodes in brainstem involvement

›Oxygen saturation

›Room air baseline

›Declining saturation as escalation trigger

›General appearance

›Level of alertness

›Somnolence to coma spectrum

›Agitation or restlessness from encephalitis

›Toxic vs nontoxic appearance

›Flushed or diaphoretic from fever

›Posturing in severe cases

Neurological exam

›Mental status assessment

›Glasgow Coma Scale

›Eye opening motor verbal scoring

›Trend over time more important than single value

›Orientation

›Person place time situation

04Differential Diagnosis/ddx55

Life-threatening encephalitis mimics

›Herpes simplex encephalitis

›ICD-10 B00.4 herpesviral encephalitis

›Temporal lobe predominance on MRI

›Must empirically treat with acyclovir until excluded

›HSV PCR in CSF with high sensitivity

›Bacterial meningitis

›ICD-10 G00.9 bacterial meningitis unspecified

›Neutrophilic CSF pleocytosis

›Low CSF glucose

›High CSF protein

›Blood cultures and CSF cultures essential

›Autoimmune encephalitis

›Anti-NMDA receptor encephalitis ICD-10 G04.81

›Psychiatric features prominent

›Antibody panel in CSF and serum

›Anti-LGI1 anti-CASPR2 anti-AMPA consider

Other arboviral encephalitides

›West Nile virus encephalitis

›ICD-10 A92.31 West Nile virus infection with encephalitis

›Mosquito-borne versus tick-borne

›Basal ganglia and thalamic involvement on MRI

›Similar CSF profile

›PRNT distinguishes from POWV cross-reactivity

›Eastern equine encephalitis

›Mosquito-borne with very high mortality

›Basal ganglia and thalamic involvement

›Fulminant course

05Laboratory Tests/lt84

CSF analysis

›Lumbar puncture timing and safety

›CT head before LP if papilledema or focal deficits

›Exclude mass lesion or obstructive hydrocephalus

›Do not delay empiric treatment for imaging

›Opening pressure documentation

›Elevated in many encephalitis cases

›Normal less than 20 cm H2O

›Standard CSF analysis

›Cell count with differential

›Lymphocytic pleocytosis typical 10 to 500 cells per cubic mm

›Neutrophilic predominance possible early in disease

›Shift to lymphocytes over first 24 to 48 hours

›CSF protein

›Mildly elevated 50 to 150 mg/dL typical

›Very high protein suggests bacterial or tuberculous etiology

›CSF glucose with simultaneous serum glucose

›Typically normal in viral encephalitis

›Low glucose points to bacterial or fungal etiology

›Gram stain and bacterial culture

›Essential to exclude bacterial meningitis

›Send before antibiotics if possible without delaying treatment

›Viral and arboviral CSF testing

›HSV PCR

›High sensitivity for HSV-1 and HSV-2 encephalitis

›Negative result allows acyclovir de-escalation

›POWV IgM antibodies in CSF

›Primary diagnostic method for confirmed cases

›May be negative early in illness

›POWV RT-PCR in CSF

›More useful in early disease or immunocompromised patients

›Viral RNA detectable before antibody response

›Arboviral encephalitis panel

›West Nile IgM and IgG

›Eastern equine encephalitis serology

›Sent to CDC or state reference laboratory

Serum diagnostic testing

›POWV serology

›POWV IgM in serum

›Positive within 1 to 2 weeks of symptom onset

›May be false negative in B-cell depleted patients

›Plaque reduction neutralization test

›Confirms POWV and distinguishes from cross-reactive flaviviruses

›West Nile dengue SLEV cross-reactivity can cause false-positive IgM

›Reference laboratory testing only

›Coinfection serology

›Lyme serology enzyme immunoassay with reflex Western blot

›Two-tier testing required for Lyme confirmation

›Negative in early acute Lyme disease

›Anaplasma PCR whole blood

›High sensitivity early in disease

›Leukopenia thrombocytopenia suggestive

›Babesia smear and PCR

›Intraerythrocytic parasites on thick and thin smear

›PCR more sensitive in low-level parasitemia

Routine and supportive labs

›Complete blood count

›Leukocyte count

›Leukopenia or leukocytosis with coinfection

›Thrombocytopenia with anaplasmosis or babesiosis

›Hemoglobin

›Hemolytic anemia with babesiosis

›Comprehensive metabolic panel

›Sodium

›SIADH causes hyponatremia in encephalitis

›Cerebral salt wasting differential

›Renal and hepatic function

›Antibiotic dosing adjustment

›Multiorgan involvement in severe sepsis

›Glucose

›Hypoglycemia as altered mental status confounder

›Coagulation studies

›Prothrombin time and INR

›DIC concern in severe infection

›Fibrinogen and D-dimer if DIC suspected

›Blood cultures

›Bacterial coinfection or secondary infection

›Obtain before antibiotics if feasible without delay

›Inflammatory markers

›C-reactive protein

›Elevated in infection and inflammation

›Not specific to POWV

›ESR

›Nonspecific elevation in viral encephalitis

›Procalcitonin

›Lower in viral versus bacterial infection

›Adjunct to distinguish etiology

06Diagnostic Tests/dt99

Scoring Systems

›Encephalitis severity assessment

›Glasgow Coma Scale

›Score 13 to 15 mild impairment

›Score 9 to 12 moderate impairment

›Score 3 to 8 severe impairment requiring airway intervention

›Modified Rankin Scale

›Functional outcome measure at discharge and follow-up

›Score 0 no symptoms

›Score 6 death

›POWV specific severity stratification

›Mild disease

›Febrile illness without CNS involvement

›Likely underdiagnosed

›Moderate disease

›Meningitis with preserved consciousness

›Lymphocytic CSF pleocytosis

›Severe disease

›Encephalitis with AMS seizures or focal deficits

›Neuroinvasive disease mortality 10 to 18.8%

›Rhombencephalitis mortality up to 60%

›Tick-borne disease risk assessment

›Geographic and seasonal risk factors

›Endemic area exposure

›Spring through fall peak season

›Host immunosuppression risk

›B-cell depletion therapy as severe disease predictor

›Antibody-based diagnostics may be unreliable in immunocompromised

MRI

›Brain MRI with gadolinium contrast

›First-line and gold standard imaging for POWV encephalitis

›T2 and FLAIR sequences most informative

›Diffusion weighted imaging for acute cytotoxic edema

›Classic POWV MRI findings

›T2/FLAIR hyperintensities in basal ganglia

›Thalamic signal abnormalities

›Brainstem and cerebellar involvement

›Cerebral cortical signal changes

›Cerebellar-dominant pattern

›Seen in approximately 50% of cases

›Associated with 60% fatality in one series

›7 of 8 patients in New England series had deep T2/FLAIR foci

›MRI timing considerations

›May be normal in early disease

›Normal MRI does not exclude POWV meningitis

›Repeat MRI if initial negative with clinical deterioration

›MRI for differential diagnosis

›Temporal lobe hyperintensity

›HSV encephalitis pattern

›Prompt acyclovir continuation if present

›Leptomeningeal enhancement

›Bacterial or fungal meningitis pattern

›Basilar predominance suggests TB meningitis

›Diffuse cortical signal changes

›Autoimmune encephalitis pattern

›Anti-NMDA receptor encephalitis overlap

›Spinal cord MRI

›Meningoencephalomyelitis presentations

›Cervical and thoracic cord signal changes

›Anterior horn involvement

›Indicated for myelopathy symptoms

›Paraparesis

›Bladder dysfunction

CT

›CT head indications

›Pre-lumbar puncture safety evaluation

›Exclude mass lesion or obstructive hydrocephalus

›Papilledema focal deficits or immunocompromised status

›Normal CT does not guarantee safe LP in all cases

›Exclusion of hemorrhage

›Subarachnoid hemorrhage as mimic of acute headache with meningismus

›Subdural or epidural hematoma

›Rapid initial imaging

›Faster than MRI in unstable patients

›Low sensitivity for early encephalitis

›CT limitations

›Often normal in viral encephalitis

›Cannot confirm POWV diagnosis

›Does not assess posterior fossa and brainstem as well as MRI

›CT for complications

›Cerebral edema pattern

›Midline shift as herniation warning

›Hydrocephalus progression

Ultrasound

›Bedside ultrasound role in POWV encephalitis

›Point of care cardiac POCUS

›Hemodynamic assessment in septic or obtunded patients

›LV function gross estimate

›Pericardial effusion screen

›IVC assessment

›Volume status and fluid responsiveness

›Collapsibility index limitations in mechanically ventilated patients

›Optic nerve sheath ultrasound

›Optic nerve sheath diameter > 5.7 mm suggests elevated ICP

›Rapid noninvasive screening tool

›Sensitivity approximately 74% for ICP > 20 mmHg

›Ultrasound limitations in POWV

›No direct diagnostic role

›Brain parenchyma not assessable in adults

›MRI required for encephalitis characterization

›Supportive hemodynamic role only

›Fluid management guidance

›Venous access assistance

07Disposition/dispo69

ICU admission criteria

›ICU indications

›Airway compromise

›GCS <= 8

›Aspiration risk

›Inability to protect airway

›Seizure management requirement

›Refractory or recurrent seizures

›Nonconvulsive status epilepticus

›Continuous EEG monitoring need

›Elevated ICP management

›Clinical signs of herniation

›Osmotic therapy requirement

›Invasive ICP monitoring consideration

›Hemodynamic instability

›Vasopressor requirement

›Autonomic instability

›Respiratory compromise

›Mechanical ventilation

›HFNC escalation

›Hospitalization rate

›Approximately 91% of reported POWV cases require hospitalization

›All neuroinvasive disease should be admitted

›Low-risk febrile illness without CNS signs may not require admission

General ward admission criteria

›Ward-level care indication

›Confirmed or suspected POWV with mild meningitis

›Preserved consciousness and no seizures

08Treatment/t122

Empiric encephalitis treatment

›Acyclovir IV empiric therapy

›Acyclovir 10 mg/kg IV every 8 hours

›Initiate immediately for suspected encephalitis

›Do not delay for MRI or LP results

›Covers HSV encephalitis until PCR result

›Duration

›Continue until HSV PCR negative and HSV excluded clinically

›Typically 14 to 21 days if HSV confirmed

›Renal dosing adjustment

›Dose reduce for GFR < 50 mL per minute

›Nephrotoxicity and crystalluria risk with inadequate hydration

›Empiric bacterial coverage

›Ceftriaxone 2 g IV every 12 hours

›Standard gram-positive and gram-negative meningitis coverage

›Adjust based on local resistance patterns

›Vancomycin IV for penicillin-resistant pneumococcus coverage

›15 to 20 mg/kg IV every 8 to 12 hours

›AUC-guided dosing preferred

›Target AUC/MIC 400 to 600

›Ampicillin 2 g IV every 4 hours for Listeria coverage

›Add for age > 50 years

›Add for immunocompromised patients

›Add for suspected Listeria risk

›Duration of bacterial coverage

›De-escalate when bacterial cultures negative and clinical picture consistent with viral etiology

Tick-borne coinfection treatment

›Doxycycline for Anaplasma and Lyme

›Doxycycline 100 mg PO or IV twice daily

›Initiate empirically if coinfection clinically suspected

›Continue pending coinfection results

›Anaplasmosis typically responds within 24 to 48 hours

›Duration

›Anaplasmosis 5 to 7 days

›Lyme neuroborreliosis 14 to 28 days

›Babesiosis treatment

›Atovaquone 750 mg PO twice daily plus azithromycin 500 mg PO day 1 then 250 mg daily

›Mild to moderate babesiosis

›Duration 7 to 10 days

›Clindamycin 600 mg IV every 8 hours plus quinine 650 mg PO every 8 hours

›Severe babesiosis

›Asplenic or immunocompromised patients

›Exchange transfusion consideration

›Parasitemia > 10%

›Severe hemolysis or organ failure

POWV-specific supportive management

›No approved antiviral therapy for POWV

›Supportive care is the mainstay of treatment

›Class I recommendation by expert consensus

›No controlled antiviral trials exist

›Investigational approaches

›Case reports of IV immunoglobulin

›Plasma exchange in severe refractory cases

›Fever management

›Acetaminophen 650 mg PO or PR every 4 to 6 hours

›First-line antipyretic

›Target normothermia to minimize neuronal injury

›Ibuprofen 400 to 600 mg PO every 6 to 8 hours

›Adjunct if acetaminophen insufficient

›Avoid with renal impairment

ICP management

›Head positioning

›Head of bed at 30 degrees

›Promotes venous drainage

›Avoid neck flexion that impairs jugular venous outflow

›Osmotic therapy

›Mannitol 0.25 to 1 g/kg IV over 20 to 30 minutes

›Acute herniation or ICP elevation

›Serum osmolality target less than 320 mOsm/kg

›Repeat every 6 hours as needed

›Hypertonic saline 3% 250 mL IV infused over 30 minutes

›Alternative to mannitol

›Target serum sodium 145 to 155 mmol/l

›Preferred if hypovolemia present

›Hyperventilation

›Target PaCO2 35 to 40 mmHg standard

›Reduce to 30 to 35 mmHg for acute herniation as bridge therapy

›Not for prolonged use due to cerebral vasoconstriction risk

Seizure management

›First-line anticonvulsants

›Levetiracetam 1000 to 3000 mg IV loading dose

›500 to 1500 mg IV every 12 hours maintenance

›Well-tolerated with minimal drug interactions

›Preferred agent in encephalitis setting

›Lacosamide 200 to 400 mg IV loading dose

›100 to 200 mg IV every 12 hours maintenance

›Sodium channel modulator alternative

›Benzodiazepines for acute seizures

›Lorazepam 0.1 mg/kg IV maximum 4 mg per dose

›First-line for active convulsive seizure

›Repeat once if no response at 5 minutes

›Diazepam 0.15 mg/kg IV if lorazepam unavailable

›Status epilepticus refractory management

›Valproate 40 mg/kg IV loading dose maximum 3000 mg

›Second-line for benzodiazepine failure

›Hepatotoxicity monitoring

›Phenobarbital 15 to 20 mg/kg IV at 50 mg per minute

›Second-line alternative

›Respiratory depression risk

›Continuous EEG monitoring for all status epilepticus

›Nonconvulsive status exclusion

›Treatment response monitoring

›Corticosteroids

›Dexamethasone consideration in rhombencephalitis

›Case reports suggest benefit in POWV rhombencephalitis

›No controlled trial data

›Risk of immunosuppression versus potential benefit

›Decision individualized with neurology and infectious disease

›Consider when significant cerebral edema present

›Avoid if bacterial meningitis not yet excluded

Fluid and electrolyte management

›SIADH management

›Fluid restriction 800 to 1000 mL per day

›First-line for mild to moderate hyponatremia

›Sodium target gradual correction

›Correction rate

›Do not correct more than 8 to 10 mmol/l per 24 hours

›Rapid correction risk of osmotic demyelination

›Hypertonic saline for severe hyponatremia or symptoms

›Sodium < 120 mmol/l or symptomatic

›3% NaCl 1 to 2 mL/kg IV over 20 minutes

›DVT prophylaxis

›Sequential compression devices for all immobilized patients

›Initiate on admission

›Low bleeding risk

›Pharmacological prophylaxis when appropriate

›Enoxaparin 40 mg SC daily

›Hold if thrombocytopenia or high hemorrhage risk

09Special Populations/sp112

Pregnancy

›Pregnancy considerations for POWV

›Epidemiological data

›POWV in pregnancy is extremely rare

›Theoretical risk of vertical transmission as with other flaviviruses

›Limited published case data

›Fetal risk

›Potential vertical transmission not well characterized

›Maternal neuroinvasive disease with hypoxia risks fetal compromise

›Fetal monitoring with viable gestation

›Imaging in pregnancy

›MRI preferred over CT

›No ionizing radiation

›Gadolinium contrast avoided unless essential

›Defer non-urgent gadolinium to second or third trimester

›CT head when MRI not available or patient unstable

›Fetal radiation dose from head CT is very low

›Clinical need outweighs radiation risk

›Treatment considerations in pregnancy

›Acyclovir empiric therapy

›Category B in pregnancy

›Benefits outweigh risks for encephalitis management

›No dose adjustment required

›Antibiotic empiric coverage

›Ceftriaxone safe in pregnancy

›Ampicillin safe in pregnancy for Listeria coverage

›Avoid doxycycline after first trimester

›Corticosteroids

›Betamethasone preferred if lung maturation indication

›Dexamethasone for ICP management as needed

›Obstetrics consultation mandatory

›Fetal monitoring when viable

›Delivery planning if maternal condition deteriorates

›Anticonvulsant selection

›Levetiracetam considered relatively safe in pregnancy

›Preferred over valproate and phenobarbital

›Fetal risk versus maternal seizure risk assessment

›Valproate teratogenic risk highest in first trimester

›Avoid unless no alternative

Geriatric

›Age-related risk

›Median age approximately 63 years in POWV case series

›Older adults disproportionately affected

›Age associated with higher severity and mortality

›Comorbidities

›Multiple comorbidities complicate management

›Medication interactions with anticonvulsants and antivirals

›Atypical presentation

›Baseline cognitive impairment

›Difficult to distinguish new delirium from baseline

›Collateral history from family or caregivers essential

›Blunted fever response

›Afebrile infection possible

›Lower threshold for encephalitis workup

›Falls and functional decline as presenting features

›Ataxia or weakness may manifest as falls

›Pharmacological considerations

›Renal dosing adjustment

›Acyclovir dose adjustment for CrCl < 50 mL per minute

›Levetiracetam dose adjustment for CrCl < 50 mL per minute

›Enoxaparin dose adjustment for CrCl < 30 mL per minute

›Sodium management

›Higher SIADH risk in older adults

›More sensitive to rapid sodium correction

›Sedation avoidance

›Benzodiazepines cause paradoxical agitation

›Prefer nonbenzodiazepine anticonvulsants

›Disposition considerations

›Lower threshold for ICU admission

›Limited physiologic reserve

›Rapid decompensation risk

›Rehabilitation needs

›High rate of residual deficits in older adults

›Inpatient rehabilitation often required

›Caregiver burden assessment

Pediatrics

›Epidemiology in children

›Less common than in adults

›Case reports and small series

›Potential for severe neurological outcomes

›La Crosse virus more common pediatric arboviral encephalitis

›POWV should be included in differential in endemic areas

›Pediatric clinical features

›Febrile seizures overlap

›Distinguish from complex febrile seizure

›Focal deficits or prolonged postictal period warrant evaluation

›Altered consciousness as presenting feature

›GCS scoring with age-adjusted criteria

›Pediatric early warning score assessment

›Pediatric dosing

›Acyclovir

›Neonate less than 3 months 20 mg/kg IV every 8 hours

›Children 3 months to 12 years 500 mg per m2 IV every 8 hours or 10 mg/kg every 8 hours

›Adolescents adult dosing 10 mg/kg IV every 8 hours

›Ceftriaxone

›100 mg/kg IV per day divided every 12 to 24 hours

›Maximum 4 g per day

›Levetiracetam

›20 to 60 mg/kg IV per day divided every 8 to 12 hours

›Maximum 3000 mg per day in children

›Doxycycline for coinfection in children

›No longer strictly contraindicated in children of any age for short course use

›Anaplasmosis indication 2.2 mg/kg per dose twice daily maximum 100 mg per dose

›Short course 5 to 7 days for anaplasmosis

›Pediatric airway

›Lower threshold for intubation

›Smaller airway and higher aspiration risk

›Uncuffed versus cuffed ETT based on age

›Ketamine for RSI

›1.5 to 2 mg/kg IV

›Maintains airway reflexes and blood pressure

›Child protective services

›Recurrent unexplained neurological illness

›Exclude non-accidental trauma

›Appropriate social work involvement

10Background/b117

Epidemiology

›Geographic distribution

›Endemic regions

›Northeastern United States

›Great Lakes region

›Upper Midwest

›Expanding range with climate change and tick distribution changes

›Tick vector

›Ixodes scapularis deer tick primary vector in eastern US

›Ixodes cookei groundhog tick maintains enzootic cycle

›Ixodes marxi squirrel tick also implicated

›Reservoir hosts

›Groundhogs Marmota monax primary reservoir for Ixodes cookei cycle

›Squirrels and small mammals enzootic reservoir

›White-tailed deer and humans are dead-end hosts

›Case frequency and trends

›Nationally notifiable disease since 2000

›Approximately 25 to 50 confirmed cases per year in US

›Likely significant underreporting given nonspecific presentation

›Seroprevalence studies suggest true incidence much higher

›Temporal trends

›Increasing tick populations and range expansion

›Growing recognition and improved diagnostics

›New York State most affected state in recent epidemiological analyses

›Mortality and morbidity

›Neuroinvasive disease case fatality rate 10 to 18.8%

›Rhombencephalitis associated with up to 60% fatality

›Immunocompromised patients at highest mortality risk

›Residual deficits

›50 to 73% of survivors develop permanent neurological sequelae

›Cognitive impairment

›Motor weakness

›Movement disorders

›Prolonged recovery in majority

›Hospitalization rate approximately 91% in case series

Pathophysiology

›Virus characteristics

›Flavivirus family member

›Single-stranded positive-sense RNA virus

›Related to West Nile virus dengue and Zika virus

›Only tick-borne encephalitis flavivirus endemic to North America

›Two lineages

›Lineage I prototype POWV maintained in groundhog-Ixodes cookei cycle

›Lineage II deer tick virus maintained in Ixodes scapularis cycle

›Lineage II accounts for most human cases in modern era

›Transmission and incubation

›Tick to human transmission

›Can occur within as little as 15 minutes of tick attachment

›Unlike Lyme disease requiring 36 to 72 hours for significant transmission

›Brief attachment significantly reduces prevention window

›Incubation period 1 to 4 weeks

›Median time from exposure to symptom onset approximately 1 to 3 weeks

›Longer incubation obscures tick exposure history

›Neurotropism and CNS injury

›Entry into CNS

›Viremia followed by hematogenous seeding of brain

›Blood-brain barrier disruption

›Possible retrograde axonal transport

›Target regions

›Basal ganglia thalami most commonly involved

›Brainstem and cerebellum in rhombencephalitis pattern

›Cerebral cortex and hippocampus

›Anterior horn cells causing myelitis

›Immune response

›Lymphocytic inflammatory infiltrate

›Neuronal apoptosis and necrosis

›Glial activation and inflammatory cytokine production

›Immune-mediated injury may exceed direct viral injury

Therapeutic Considerations

›No specific antiviral therapy approved

›Supportive care remains standard of treatment

›No controlled trials of antivirals for POWV

›Ribavirin and interferon lack efficacy data

›Investigational flavivirus inhibitors in preclinical stages

›Clinical trial participation

›Refer to ClinicalTrials.gov for active studies

›Compassionate use or expanded access protocols for novel agents

›Immunosuppression management

›B-cell depleting therapies as major risk factor

›Rituximab impairs antibody-mediated clearance

›Serological diagnosis unreliable in B-cell depleted patients

›RT-PCR preferred over serology in immunocompromised

›Hold or modify immunosuppression

›In consultation with rheumatology or transplant medicine

›Balance infection severity against underlying disease

›Corticosteroid evidence

›Case reports of benefit in rhombencephalitis

›Potential anti-inflammatory effect in severe edema

›No randomized controlled data

›Decision individualized based on clinical severity

›Contraindication consideration

›May impair viral clearance

›Avoid until bacterial meningitis excluded

›Diagnostic access challenges

›Limited commercial laboratory availability

›CDC and state reference laboratories primary testing sites

›Testing delays common due to referral requirement

›Metagenomic next-generation sequencing

›Emerging diagnostic tool for POWV and other rare pathogens

›Particularly useful in immunocompromised with negative standard testing

›Available at select academic centers and commercial labs

›Plaque reduction neutralization test

›Required to confirm and distinguish from cross-reactive flaviviruses

›Reference laboratory only

›Results may take days to weeks

›Prevention strategies

›No vaccine available for POWV

›Unlike European tick-borne encephalitis which has approved vaccines

›Tick-bite prevention is only effective strategy

›DEET and permethrin

›DEET 20 to 30% on skin for 8 hours of protection

›Permethrin on clothing and gear for tick repulsion

›CDC recommended preventive measures

›Daily tick checks

›Full body examination after outdoor activity

›Prompt tick removal reduces transmission risk for most tick diseases

›Very brief attachment window for POWV means prevention is critical

›No post-exposure prophylaxis available after tick bite

›Observation for symptom development

›Medical evaluation for fever or neurological symptoms after exposure

11Patient Discharge Instructions/pdi54

copy discharge instructions

›Diagnosis and recovery overview

›Powassan virus infection is a tick-borne brain infection

›Caused by a virus transmitted by deer ticks

›No specific antiviral medicine exists

›Recovery requires rest and time

›Recovery may be prolonged

›Most patients have some symptoms for weeks to months

›Memory difficulties weakness and fatigue are common

›Many patients benefit from rehabilitation programs

›Medications to continue at home

›Take all prescribed medications as directed

›Antiseizure medications must not be stopped abruptly

›Follow-up blood tests for medication levels as instructed

›Acetaminophen for fever or pain

›Maximum 4000 mg per day in healthy adults

›Less if liver problems

›Activity restrictions

›No driving until seizure-free for duration specified by physician and local law

›Confirm seizure-free period with neurologist

›Varies by jurisdiction

›Avoid working at heights or operating heavy machinery if unsteady

›Supervision at home if balance or coordination affected

›Graduated return to activity guided by symptoms

›Tick prevention going forward

›Wear long sleeves and pants in wooded or grassy areas

›Light-colored clothing makes ticks easier to spot

›Apply DEET 20 to 30% to exposed skin

12References/r35

Guidelines and key sources

›Primary references

›Mendoza MA et al. Powassan Virus Encephalitis: A Tertiary Center Experience. Clinical Infectious Diseases 2024

›Tertiary center experience with clinical features outcomes and imaging

›Neuroinvasive disease mortality 10 to 18.8% and high residual deficit rate

›Piantadosi A et al. Emerging Cases of Powassan Virus Encephalitis in New England. Clinical Infectious Diseases 2016

›Clinical presentation imaging findings and outcomes in New England series

›Kemenesi G Banyai K. Tick-Borne Flaviviruses With a Focus on Powassan Virus. Clinical Microbiology Reviews 2019

›Comprehensive virology epidemiology and clinical review

›Kaur M Adam M Mladinich MC. Pathogenicity and Virulence of Powassan Virus. Virulence 2025

›Recent pathogenesis and virulence mechanisms review

›Guideline references

›CDC Tickborne Diseases of the United States Reference Manual Sixth Edition 2022

›National guidelines for tick-borne disease diagnosis and management

›POWV specific clinical and laboratory guidance

›Ho BM et al. Wilderness Medical Society Clinical Practice Guidelines for Tick-Borne Illness. Wilderness Environmental Medicine 2021

›Prevention and management guideline

›Miller JM et al. IDSA ASM Guide to Microbiology Laboratory Utilization 2024 Update. Clinical Infectious Diseases 2024

›Arboviral testing recommendations and laboratory guidance

›Supporting references

›Solomon IH et al. Fatal Powassan Encephalitis in Patient Receiving Rituximab. JAMA Neurology 2018

›Immunosuppression as severe disease risk factor

›Feder HM et al. Powassan Virus Encephalitis Following Brief Tick Attachment. Clinical Infectious Diseases 2021

›Rapid transmission risk with brief tick attachment

›Finelli PF. MR Imaging Patterns and Prognosis in Powassan Virus Encephalitis. The Neurologist 2024

›MRI pattern characterization and prognostic correlation

›Varon AR et al. Epidemiology and Risk Analysis of Powassan Virus New York State 2013 to 2023. Epidemiology and Infection 2026

›Contemporary epidemiological analysis

Evidence & Review