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http://www.healthres.com/herpes-simplexvirus-encephalitis/

Shedding Light on TORCH Diseases

Web-Based Continuing Education Pacific University College of Optometry James Kundart OD MEd FAAO

Focus Questions
1.

Which congenital infectious diseases can affect mental health, and can cause serious mental health disorders, like schizophrenia? What are six characteristics of autism? Which of the infectious disorders raise the risk of children acquiring it? How common is congenital cytomegalovirus? What are the effects of CMV, both ocular and systemic?

2.

3.

4.

Which of the infectious disorders cause encephalitis and affect mostly patients of presbyopic age?
Which can cause meningitis, affecting mostly children?

5.

What Are the TORCH Diseases?

TORCH diseases can cause birth defects in the unborn child if

the mother contracts them during pregnancy.

TORCH stands for: 1. Toxoplasmosis 2. Other 3. Rubella 4. Cytomegalovirus 5. Herpes Simplex

Ill cover Other last when we talk about Varicella

1. What You Dont Know About Toxoplasmosis

The most common form of posterior uveitis in children and adults is

toxoplasmosis

Long known to be congenital, Toxo- has increasing evidence for

acquired forms as well

According to the Wikipedia, Toxoplasma infection also causes

damage to astrocytes in the brain

There is evidence that the toxoplasmosis protzoan makes infected

rodents lose their fear of predators!

Typically, we worry about the effects in the eyes and brain of the

unborn child and can cause coordination, learning, and perceptual disabilities

Toxoplasmosis Life Cycle: Cats or Meat Consumption?

Did you know that its not

cats, but ingestion of undercooked meat that usually causes toxo-?

I have personally seen it

also effect the expectant mothers retina, as well as the unborn child
Toxo- is not harmless to

cats either, and can affect their eyes and cerebellum

http://www.healthtree.com/articles/childhooddiseases/rare/toxoplasmosis-symptoms/

Toxoplasmosis: Objective Symptoms

Blurred vision Photophobia Watering eyes Blind spots (?)

Except for transient

lymphadenopathy, even patients with acquired Toxomay be asymptomatic

http://emedicine.medscape.com/ article/1204441-media

Toxoplasmosis: Subjective Signs

These occur in 70-90% of congenital and up to 21% of acquired cases of Toxo Focal Necrotic Retinal

Lesions
Glaucoma Loss of vision The patient shown has BCVA http://emedicine.medscape.com/ article/1204441-media

20/400 OS secondary to congenital Toxoplasmosis retinochoroiditis

Effects of Congenital Toxoplasmosis

Approximately 10% of

Toxo- infected infants have clinical manifestations at birth

Hydrocephalus, jaundice,

hepatosphenomegaly, and papillitis are seen in severe cases treat immediately!

Look for elevated blood

titers of IgA, IgE, and IgM

http://emedicine.medscape.com/ar ticle/1204441-media

Treatment of Acute Toxoplasmosis

Controversially, reduction

in BCVA by 2 or more lines caused by maculitis would call for systemic (oral or IV) treatment:
Pyrimathamine Sulfanomides or other

antibiotics Folic Acid Pyri-methamine Steroids?

http://emedicine.medscape.com/ar ticle/1204441-media

Toxoplasmosis and Mental Health

Toxo- affects dopamine

levels, which are involved in mood, sociability, attention, motivation and sleep patterns (Wikipedia)
Schizophrenia has long been

linked to dopamine dysregulation

Toxo- antibodies were found

at significantly higher levels in blood tests of schizophrenics

http://emedicine.medscape.com/a rticle/1204441-media

Toxoplasmosis and Behavior

Controversial correlations

have been found between latent Toxoplasma infections and various characteristics: behavior

Decreased novelty-seeking Slower reaction time Lower rule-consciousness Promiscuity and greater http://emedicine.medscape.com/a rticle/1204441-media

and greater jealousy (in men) conscientiousness (in women)

2. What You Dont Know About Congenital Rubella Syndrome

The classic triad:
Eye abnormalities,

especially cataract (30% of patients)

Sensorineural deafness

(58% of patients)
Congenital heart

disease (50% of patients)

Other features: Retinopathy Growth retardation Developmental Delay Autism Spectrum Developmental Disorders Diabetes

Congenital Rubella and Cataracts

30% of patients have

them, and are bilateral, as seen here

These cataracts have been

described as pearly and dense, but may have a clear ring around them
Rubella causes liquefaction

of the lens cortex and may have live virus inside (!)

http://en.wikipedia.org/wiki/Co ngenital_rubella_syndrome

Congenital Rubella and Retinopathy

About 45% will be expected

to have this salt-andpepper fundus

Expect no foveal light reflex

because of RPE hyperplasia

Vision is usually not affected

A mild microphalmos may be

http://www.kellogg.umich.edu/theeyeshaveit/ congenital/retinopathy.html

evident in short axial length and hyperopic refractive error

Congenital Rubella and Stunted Growth

All these children from

Madhya Pradesh in India are the same age, but 6/10 suffer from malnutrition, but show similar growth retardation
This can include not reaching

proper milestones (sitting up at 6 months, walking at 1 year, talking at 2 years, etc.)

Sometimes, milestones like

talking are delayed by sensorineural hearing loss

http://www.flickr.com/ph otos/dfid/4420550101/

Congenital Rubella and Developmental Delays

One possible cause of these

delays is hearing loss, which is part of the triad sensorineural hearing loss, seen in over half of congenital rubella patients absent cristae (hair cells) in the inner ear often have trouble with learning, specifically speech-language development

Unilateral or bilateral

Those with underformed or

http://www.thedeafblog.co.uk/2009/04/ha ir_cells_could_restore_heari.html

Congenital Rubella and Autism

Autism is characterized by:
1.

Repetitive movements

2.
3. 4. 5. 6.

Compulsive behavior
Resistance to change Daily rituals Special interests Self-injury
http://en.wikipedia.org/wiki/Autism

Congenital Rubella, Autism and Developmental Disorders

Is it normal for a child to

compulsively stack cans?

If the child also has

restricted social interaction and communication, it may be

Look for restricted and

repetitive behavior in autism and other pervasive developmental disorders

http://en.wikipedia.org/wiki/Autism

Congenital Rubella and Heart Disease

Part of the congenital rubella

triad is patent ductus arteriosus, or PDA

Children with congenital

Rubella can later develop progressive endocrine complications, including: IDDM Hypothyroidism Hyperthyroidism
http://en.wikipedia.org/wiki/ Patent_ductus_arteriosus

Congenital Rubella and Schizophrenia

While family history is far

and away the most serious risk factor, others are (in order of likelihood):
1. 2. 3. 4. http://www.schizophrenia.com/n ewsletter/buckets/hypo.html 5.

CNS damage Bereavement Rubella CNS infection (meningitis) Birth hypoxia

3. What You Dont Know About Cytomegalovirus (CMV)

According to the NY Times:
Cytomegalovirus is a large

herpes-type virus most have

It can cause serious infections in

people with impaired immunity, including newborns

CMV infection may result in

pneumonia, gastroenteritis, retinitis or encephalitis

Antiviral medications may stop

the replication of the virus but will not destroy it

http://www.nytimes.com/imagepages/ 2007/08/01/health/adam/17110CMVcyt omegalovirus.html

Subjective Symptoms of CMV

Blurred Vision (decreased

BCVA)
Photophobia

Redness
Loss of peripheral vision

(blind spots)
Lots of floaters
Learning disabilities and
http://eyecaremanual.com/eye-diseases/cmvretinitis/cmv-retinitis-symptoms-causestreatment-surgery.html

perceptual problems

Objective Signs of CMV

Though >80% of adults

have antibodies to CMV, retinitis is rarely seen in healthy adult patients

Look for a brushfire

retinitis pattern in immunocompromised patients, as seen here

Dont forget that unborn

children are as vulnerable as those with HIV/AIDS

http://depts.washington.edu/hiva ids/oit/case7/fig4d.html

CMV in Immunocompromised Adults

36 year-old patient with

HIV/AIDS, not on the cocktail, low CD4 count of only 9 cells/mm3 patch of retinal necrosis OD only

Had a large subfoveal irregular

Appears as a white, fluffy lesion

with overlying retinal hemorrhages and scattered necrotic spots perifoveally

disappeared in the US, but congenital CMV has not

HIV retinopathy has all but

http://webeye.ophth.uiowa.edu/eyeforum/cases/61CMV-Cytomegalovirus-Retinitis-HIV.htm

Congenital CMV Awareness

According to the Centers

for Disease Control and Prevention, expectant mothers are less aware of CMV of all diseases, including:
Fetal Alcohol

Congenital Rubella
Toxoplasmosis, etc.

Yet CMV is more common than all of these!

http://www.cdc.gov/Features/ dsCytomegalovirus/

Congenital CMV Incidence

Take a look at how many

cases of congenital Rubella occur annually in the U.S.

Conditions for which

vaccines are given, like H flu, are also much less common than CMV
Unfortunately, there is no

vaccine, but natural immunity is the norm

http://www.cdc.gov/Features/dsCytomegalovirus/

Bottom Lines on Congenital CMV

About 3000 children are born

with congenital CMV infection each year (thats 1:150 live births)
About 1 in 750 children in the

U.S. is born with (or develops) permanent problems due to congenital CMV infection
In the U.S., more than 5,000

children each year suffer permanent problems caused by CMV infection

http://www.cdc.gov/cmv/trends-stats.html#affected

Congenital CMV Prevention

Since most adults have

immunity, the greatest concern is not to spread CMV from other children to pregnant women handwashing not sharing cups, plates, washcloths, even pacifiers should make a difference more serious reservoir for CMV than cats are for Toxo-!!!

Hygiene measures with

In a real sense, children are a

http://www.cdc.gov/Features/dsCytomegalovirus/

4. What You Dont Know About the Herpes Simplex Virus Encephalitis
This 33 year-old female patient

presented with agitation, confusion, mutism, and fever and the histology was consistent with HSV-I encephalitis

A brain biopsy was performed

HSV-1 causes 95% of all

(septic?) herpetic encephalitis

and treatment is with intravenous antivirals

Mortality ranges from 50-70%,

http://www.radpod.org/2007/03/24/herpes-simplex-encephalitis/

What HSV Encephalitis Affects

The most common cause of

fatal sporadic viral encephalitis is HSV

HSV encephalitis

characteristic imaging findings: Asymmetric temporal lobe involvement, and Involvement of the insular cortex
http://radiopaedia.org/images/546349

Profile of HSV Encephalitis Patients

According to Wikipedia:
2 in 3 cases occur in

seropositive persons, few of whom have history of recurrent orofacial herpes individuals that develop HSV encephalitis are over 50 least 1 in 500,000 individuals per year in the U.S. (thats about 6000 cases annually)

Approximately 50% of

It is estimated to affect at

http://www.healthres.com/herpes-simplex-virusencephalitis/

HSV Encephalitis and CN I

The olfactory nerve (CN I)

may also be involved in HSV encephalitis

This may explain its

predilection for the temporal lobes, as CN I sends branches there

The virus also lies dormant
http://www.healthres.com/herpes-simplex-virusencephalitis/

in the trigeminal nerve, which explains HSK

HSV Encephalitis Symptoms

Patients typically have a

fever, and may have seizures

Most individuals with HSE

show:
Decreased consciousness

An altered mental state

Changes in personality Confusion, or even

dementia
http://www.health-res.com/herpes-simplex-virus-encephalitis/

HSV Encephalitis and Alzheimer Disease

http://www.sciencedaily.com/releases/2 003/11/031107055048.htm Researchers at Brown

University and the Marine Biological Laboratory at Woods Hole, Mass., have found a connection between the herpes simplex virus and amyloid precursor protein
This protein that breaks down

http://trendsupdates.com/link-betweenthe-herpes-virus-and-alzheimer/

to form a major component of the amyloid plaques that are consistently present in the brains of people with Alzheimer disease

Occurrence of HSV
Without treatment, HSV

encephalitis results in rapid death in approximately 70% of cases

Survivors suffer severe

neurological damage
Treatment is with high-dose

intravenous Acyclovir
When treated, HSV

encephalitis is still fatal in one-third of cases

http://www.textmed.com/diseas e/herpes-simplex.htm

Treatment for HSV Encephalitis

There are serious long-term

neurological damage in over half of survivors, including visual-perceptual problems

A 20% minority of treated

patients recover HSV encephalitis with minor (but permanent) brain damage
Only a small population of

survivors (2.5%) regain completely normal brain function

http://www.health-res.com/herpes-simplex-virus-encephalitis/

5. What You Dont Know About Neonatal Varicella-Zoster

Infection late in gestation

or immediately following birth is referred to as "neonatal varicella

Maternal infection is

associated with premature delivery and miscarriage

Newborns who develop

symptoms are at a high risk of pneumonia

http://en.wikipedia.org/wiki/Varicella

Ocular Damage from Neonatal Varicella-Zoster

More severe than HZO, Varicella can congenitally cause:
Microphthalmia

Cataracts/ lens vesicles

Chorioretinitis Optic atrophy Anisocoria Horners Syndrome http://cid.oxfordjournals.org/content/35/5/625.full

CNS Damage from Neonatal Varicella-Zoster

Much like HSV, if Varicella crosses the blood-brain barrier in utero, it can cause the following:
Encephalitis Hydrocephaly Microcephaly Cerebral Aplasia
http://www.lookfordiagnosis.com/mesh_info.php?ter m=Encephalitis%2C+Varicella+Zoster&lang=1

Other Neurological Effects of Neonatal Varicella-Zoster

Besides encephalitis, viral infection of the CNS can also cause meningitis and affect spinal nerves thusly:
Spinal cord damage
Motor ataxia Absent deep tendon reflexes http://www.medscape.com/featur es/slideshow/varicella-zoster Compare HSV and Varicella-

Zoster Virus (VZV) in each case

Systemic Effects of Neonatal Varicella-Zoster

How do you know if a patient once had shingles, congenital or otherwise? Look for:
Scars and other skin lesions

following a dermatome (C8/T1 shown in this child)

Hypopigmentation where the

vessicles once appeared

In cases of congenital

exposure, you may see stunted growth (hypoplasia) of the arms and legs
http://en.wikipedia.org/wiki/Herpes_zoster

Otitis Media, Learning Disabilities and Neonatal Varicella-Zoster

Chicken pox can invade the

ear canal where it is extremely uncomfortable

More importantly, due to

scarring, Varicella can interfere with long-term function of the eardrum

There is a high (>50%)

correlation between recurrent otitis media and http://www.umm.edu/patiented/articles/who_ learning disabilities

gets_chickenpox_shingles_000082_3.htm

The Case for (and Against) the Varicella Vaccine

Available since 1995, the

Varicella vaccine aims to prevent severe infections children obtain natural immunity for life by contracting chicken pox

Why is this necessary? 80% of

In the U.S., there are 9300

hospitalizations annually due to severe infections

10% and localized rash in up to 5%, and immunity may not last

The vaccine doe cause fever in

http://www.justsharethis.com/wpcontent/uploads/2009/07/chickenpoxmain_Full.j pg

Bottom Lines on Neonatal Varicella-Zoster

For pregnant women,

antibodies produced as a result of previous infection or immunization are transferred via the placenta to the fetus
Women who are immune

http://www.justsharethis.com/wpcontent/uploads/2009/07/ChickenPoxBabyCar toon.jpg

to chickenpox cannot become infected, and do not need to be concerned about their unborn infant during pregnancy

Bottom Lines on Infectious Diseases and Visual-Perceptual Problems

Review Capsule
1. 2. 3.

Which neonatal infectious diseases can cause retinal scarring, leading to scotomas? Which can scar the middle ear, or cause sensorineural hearing loss, leading to learning disabilities? Which neonatal infectious diseases can cause dementia and mental confusion?

4.
5.

Which commonly leads to congenital cataracts?

Which can reside in CN V and cause anisocoria and Horners Syndrome?

Readings and References

For further information on infectious disorders and the eye,

see chapter 9 in Wrights Handbook of Eye and Systemic Disease

The author welcomes your questions or comments:
James Kundart OD MEd FAAO Pacific University College of Optometry

2043 College Way

Forest Grove, OR 97116 503-352-2759 kundart@pacificu.edu