Pediatric Case of the Week 21: "Ticks, Mosquitos, and Crows; Oh My!"

You find yourself working a weekend shift during a rare, temperate, Minnesota spring day.  You take a moment to ponder global warming, global cooling, globalization, and (of course) global navigation.  (Tickets to Australia remain far too expensive...flights to Prague aren't much better.  So much for Sailing with Shiraz or Hiking with Pilsner...)

Your next patient is an 11 year old male who had recently been seen at a well branded urgent care (named after a unit of time) for persistent headaches, fevers, and bodyaches over the past week.   His parents assumed that had "the flu" and had been treating him with acetaminophen and ibuprofen as directed.  An influenza swab performed at the well branded urgent care was reportedly negative.  His symptoms were well managed but over the past day he has developed worsening headache and irritability.  He also has had 2 episodes of vomiting since last night with decreased po intake.  His mother reports that he is "very sleepy/"

His parents report no known history of trauma.  Dad notes that he had recent "cold" symptoms 2 weeks ago.  No recent travel but he had been to the family cabin recently which is located in the "boon-docks" of western Wisconsin.  A territory also known as: "Kapsner Kountry."

VS: T 38.6, P 100, R 20, BP 118/75, oxygen saturation 98% ra, Wt 40kg. 

He is somnolent but arousable to voice. His head shows no signs of trauma. His pupils are equal at 3 mm and reactive to light. Photophobia  is present.  No papilledema on funduscopic exam noted. His oral mucosa is moist with no oral lesions. His neck is supple without adenopathy. Heart is regular. Lungs are clear with shallow aeration. His abdomen is normal. His pulses, color and perfusion are good.  You notice a small rash on his lower back area.  Which looks like this: 

Labs?

Imaging?

You return to your computer, order labs, and hope that flight prices have dramatically dropped over the past 30 minutes.  While the laboratory technologist is in the room drawing your requests you hear the faint sound of medical provider panic, "Can I get some help in here!!!"  

You re-enter the room to find the patient completing the last few tonic clonic motions of a seizure. 

What actions?

What meds?

You repeat a physical exam: His airway is patent, breathing has calmed and he is moving air.  You note normal pulses throughout. He has increased tone to the right side of his body and brisk reflexes R>L. He is non-responsive to voice commands, but he withdraws to pain. He exhibits no purposeful movements or signs of posturing. His breathing has calmed and he is moving air with normal pulses throughout. 

Repeat VS: T 38.6, P 123, R 14, BP 108/65, oxygen saturation 100% with mask. 

Is there a procedure you would like to perform, now that you've seen the light?

Is there place you would like him to spend the night?

There's gotta be a cheap flight to Vegas, right?

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WEEKEND UPDATE:

Disclaimer: This was an attempt at presenting a case of Lyme's encephalitis.  This would be a rare case and a rare presentation. In fact, this presentation is more consistent with HSV or one oth the Arthropod-borne viruses. Nonetheless it helps to illustrate encephalitis as a disease process. The reality is that encephalitis is not always a clear diagnosis, but should be considered in all patients with combinations of fever, headache, severe lethargy, personality changes, and/or SEIZURE. 

Encephalitis is an acute infection with focal or diffuse inflammation of brain parenchyma usually from viral etiologies, but it may also be associated with bacterial, fungal, protozoan, and autoimmune processes. 

The differential diagnosis for acute encephalitis includes: bacterial meningitis, Rocky Mountain spotted fever, brain abscesses, drug intoxication, lead encephalopathy, Reye's syndrome, hepatic coma, uremia, organic acidemias, amino acidemias, urea cycle defects, intracranial neoplasms, systemic lupus erythematosus, cerebrovascular accidents, pseudotumor cerebri, trauma, and post-infectious encephalopathies. The presence of fever is helpful in distinguishing encephalitis from encephalopathies due to toxins or inborn errors of metabolism.

The list of pathogens causing encephalitis is IMMENSELY long (here are some highlights):

HSV is the most common cause of severe encephalitis in children and accounts for approximately 10% of all cases of encephalitis in the United States. Neonatal HSV-2 encephalitis with treatment, has a mortality of 14% (compared to 85% without treatment) and severe neurological dysfunction is found in 50 to 70% of affected individuals. HSV-1 encephalitis in older children represents the commonest cause of nonepidemic fatal viral encephalitis with a mortality of 30 to 50% and major neurological sequelae in 40 to 50% (2,6). 

Arthropod-borne viruses (arboviruses) are agents of several virus families that can replicate in both invertebrate and vertebrate cells.   

 -La Cross (California) virus is the most common cause of endemic arboviral encephalitis. Most often  associated with rural areas and prevalent in Wisconsin and Ohio. 

-St. Louis encephalitis, in contrast, causes large urban epidemics among the elderly and occurs more frequently in the lower socioeconomic groups in the Midwestern and southeastern United States in late August and September following heavy spring rains and summer droughts. The virus is more common in urban environments where there is stagnant water with high organic content, particularly poorly draining sewage (6). 

 -Japanese encephalitis is the most common cause of arthropod-borne encephalitis worldwide with over 50,000 cases reported per year in China, Southeast Asia, and India (5). During epidemics, mortality ranges from 20 to 40%, with death usually occurring in the first week of illness (4). 

 -Eastern Equine encephalitis has peak activity from August to September and is geographically located along the eastern coast from Massachusetts to Florida. Compared to other arboviral encephalitides, Eastern Equine encephalitis symptoms are more severe and mortality is greatest at 50 to 75%. 

-West Nile Virus: Transmitted by mosquito bite. Incubation 1-6 days but could be up to 14 days. There are many WNV hosts but birds are one of the most common.  WNV is particularly deadly to crows.  In fact, Crow deaths is one way WNV is monitored.  Surprisingly, Only 26% of patients with WNV become symptomatic. Most people are asymptomatic or develop a mild "flu-like illness" only a small minority of people develop neurologic symptoms. J Infect Dis.  2010; 202(9):1354-61. 

Mosquito-borne viruses peak in late summer in temperate regions, whereas tick-borne diseases occur in spring and early summer.

Lyme Encephalitis: Initially presents with "flu-like symptoms", Lyme's can progress with multiple focal effects including hepatitis, myocardits, arthritis, and cranial neuritis (facial palsy).  It is a frequent cause of heart block.  It can occasionally cause both meningitis and encephalitis (not to be confused with Lyme's encephalopathy which is chronic condition.) 

Additional Causes of Encephalitis: Post-infectious encephalomyelitis, Mycoplasma pneumoniae, EBV, mumps, Rabies (rare in US), Measles (rare in US), and human herpes virus 6 (HHV-6) (2,6). 

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Clinical Manifestations:

ALWAYS CONSIDER HSV ENCEPHALITIS IN FEBRILE NEONATES REQUIRING A FULL SEPTIC WORK-UP.  

In older children, the clinical manifestations of the inflammatory response are initially subtle and diverse. Specific neurological findings vary according to which areas of brain parenchyma are affected and also the degree of increased intracranial pressure. Some features of acute encephalitis are similar to those found in aseptic meningitis and include headache, stiff neck, photophobia, fever, vomiting, and irritability; however, the hallmark of disease is alteration of higher cerebral function, characterized by change in level of consciousness, psychiatric and behavioral abnormalities, and/or seizure activity. 

Predominant cortical involvement may lead to disorientation and confusion. Basal ganglia involvement may lead to movement disorders and brainstem involvement may lead to cranial nerve dysfunction. Occasionally, spinal cord involvement (myelitis) may accompany the encephalitis with findings of flaccid paraplegia and abnormalities of the deep tendon reflexes.

Evaluation: 

Evaluation of an infant, child, or adolescent with signs of neurological dysfunction with or without fever requires a thorough neurodiagnostic assessment that may include: cerebrospinal fluid (CSF) examination, electroencephalogram (EEG), and imaging studies of the brain and/or spinal cord. The sequence of these studies will depend on severity of condition and concerns regarding possibility of CNS mass lesion, presence of increased intracranial pressure, or other acute neurological conditions requiring specific intervention.

In general, there is little correlation of CSF abnormalities with clinical or histologic severity of encephalitis. The CSF is usually clear and colorless, but may be xanthochromic when blood has been in the CSF for some time. The CSF cell count and protein are frequently normal or slightly elevated, and the glucose concentration remains normal. In the early phase of viral infection, there is often a mixed pleocytosis with both polymorphonuclear (PMN) and mononuclear cells that typically shifts to a lymphocytic pleocytosis over time (1,2). Subsequent lumbar punctures can be helpful in demonstrating pleocytosis. 

Polymerase chain reaction (PCR) is an inexpensive, rapid, molecular genetic assay that detects specific organism DNA sequences and provides confirmatory viral isolation and thus a specific etiologic diagnosis. PCR affords rapid diagnosis of infections with HSV, CMV, EBV, enterovirus, JC virus, HHV-6, varicella-zoster virus, B. burgdorferi (Lyme disease), Bartonella henselae (cat scratch disease), and HIV. The specificity of PCR in HSV encephalitis approaches 100% and the sensitivity ranges from 75 to 95% depending on the quality of the laboratory (1). PCR has become the gold standard for evaluation of infants and children with suspected HSV encephalitis.

Further EEG testing and MRI imaging would likely be performed by the admitting team or consulting neurologist. 

Treatment:

Since antiviral therapy has decreased the mortality for HSV infections by nearly 40% from the pre-antiviral era, acyclovir is the treatment of choice for herpes simplex encephalitis. Antivirals inhibit viral infection by binding with viral nucleic acid and prevent viral replication. The currently approved dose is 30 mg/kg/day IV divided every 8 hours for 14 to 21 days, but some experts recommend increasing the total daily dose to 45-60 mg/kg/day IV divided every 8 hours. Acyclovir has also been effective against varicella zoster virus, while other antiviral agents such as ganciclovir and foscarnet have been used for CMV infections. 

Encephalitis from arthropod-borne viruses cannot be treated with specific therapy and typically resolve with conservative management, antipyretics, intravenous fluids, and antiepileptic drugs. Seizures, a frequent complication of viral encephalitis, can be treated acutely with lorazepam and may need maintenance antiepileptic drug therapy with phenobarbital or phenytoin in standard doses.

I would consider doxycycline for Lyme's, but would consult infectious disease. 

Disposition: 

Pediatric Intensive Care Unit (PICU) for initial evaluation and supportive care. 

Thanks to: Jonathan K. Marr, MD,  Department of Pediatrics, University of Hawaii John A. Burns School of Medicine. 

References
1. Bale JF Jr. Chapter 64 - Viral Infections of the Nervous System. In: Swaiman KF, Ashwai S (eds). Pediatric Neurology Principles and Practice, third edition. 1999, St. Louis: Mosby, pp. 1001-1024
2. Berkowitz ID, et al. Chapter 32 - Meningitis, Infectious Encephalopathies, and Other Central Nervous System Infections. In: Rogers MC, et al (eds). Textbook of Pediatric Intensive Care, third edition. 1996, Baltimore: Williams & Wilkins, pp. 1062-1089.
3. Bingham AC, Saiman L. Short Course Viral Encephalitis. Office and Emerg Pediatr 2000;13(5/6):184-189.
4. Roos KL. Central Nervous System Infections. Neurol Clin 1999;17(4):813-833.
5. Whitley RJ, Kimberlin DW. Viral Encephalitis. Ped Rev 1999;20(6):192-198.
6. Johnson, R.T. Viral Infections of the nervous system, second edition. 1998, Philadelphia: Lippincott-Raven