Occupational Exposures to Bloodborne Pathogens

Occupational Exposures to Bloodborne Pathogens
By:Arjun Srinivasan
Johns Hopkins Hospital

Outline
* What’s an exposure?
* 1st step in all exposures - Clean the site!!
* Specific pathogens
o Hepatitis C
o Hepatitis B
o HIV

Scope of the Problem
Impossible to measure the psychological stress that an exposure places on a health care worker
At Risk Exposures
1. Percutaneous injury
Hollow needle > Solid sharp
Visible blood
Deep injury
Device in patient’s artery or vein
2. Splash on non-intact skin
3. Splash on mucous membrane

Risks From Body Fluids
* Known to be infectious:
o Blood
o Any fluid visibly contaminated with blood
o Semen
o Vaginal secretions
o Concentrated virus (used in labs)
* Potentially infectious
o CSF
o Pleural fluid
o Pericardial fluid
o Peritoneal fluid
o Amniotic fluid
o Synovial fluid
o Tissue samples
* Not Infectious (if not visibly bloody)
o Tears
o Saliva
o Urine
o Feces
o Sweat
o Emesis

The Solution to Pollution . . .
* Exposure site should be cleaned IMMEDIATELY! This may be the most important part of PEP
* Skin wounds should be washed with soap and water
* No evidence that antiseptics are useful and caustic agents (bleach) may do more harm than good
* Mucous membranes should be flushed thoroughly with water
* Eyes should be irrigated with a liter of saline

A word from our lawyers . . .
* ALL exposures should be reported to the proper people (Occupational health, Employee health etc.)
* Disability claims can be denied if follow up reporting was not done right

Hepatitis C
Hepatitis C: Risk of Exposure
Hepatitis C: Risk of Disease
Post Exposure Recommendations
* Clean the site immediately
* Hepatitis B immune globulin has NOT been effective
* Interferon is NOT recommended at this time
Hepatitis C: Follow Up
* Enzyme linked immunoassay (EIA) is screening test of choice
* ALL exposed HCWs should have LFTs monitored
* Average interval between exposure and seroconversion with EIA is 8-10 weeks
* Follow up guidelines vary - CDC recommends follow up at 4-6 months
Hepatitis C: Follow up issues
* EIA is falsely positive in up to 50% of HCW and falsely negative in 5% - results must be confirmed by RIBA or VL
* PCR may catch infection earlier but detection is highly variable
* Immediate referral for treatment if HCW seroconverts
Hepatitis C: Counseling
* Risk of transmission to infants and partners is thought to be low
* Exposed HCW do not need to modify sexual practices, stop breast feeding or refrain from becoming pregnant
* Should not donate blood

Hepatitis B
Hepatitis B: Risk of Exposure
Hepatits B: Outcome of Infection
* In patients who are infected with Hep B:
o 25% get jaundice
o 5% require hospitilization
o 6-10% become chronically infected
o .125% die of fulminant hepatitis

Hepatitis B: Good News
* Most HCWs have been vaccinated and vaccine offers virtually complete protection to responders
Hepatitis B: Bad News
* Some employees are NOT vaccinated
* 6-10% of vaccinees do NOT develop antibody
* Really bad news:
CDC estimates that 50-75 HCW die from Hep B each year
Hepatitis B: Post Exposure
* Clean the site immediately
* Determine the vaccine status of the HCW
* Determine the surface antigen status of the source patient

Hep B: HCW Never Vaccinated
* HCW should receive vaccine ASAP
1. Source patient is sAg positive:
HCW should also receive one dose of Hep B immune globulin (HBIG) .06ml/kg (1 vial=5 ml) ASAP and absolutely within 7 days of exposure
2. Source patient sAg neg or unknown
Vaccine alone
Hep B: HCW Vaccinated (one or more doses)
* Source patient should be tested for sAg AND HCW should be tested for sAb
* If HCW has adequate Ab >10 IU/mL (now or at any time) then no additional treatment
* IF HCW has inadequate Ab:
1. If pt is sAg negative:
HCW should get booster dose of vaccine (or complete series)
2. If pt is sAg positive:
HCW should receive HBIG AND a booster dose of vaccine at different sites (complete series if necessary)
If HCW has inadequate Ab:
3. Unknown source:
Give vaccine booster or complete series
Vaccine non-responders
* If HCW has inadequate Ab after 3 dose series they should get another series: 30-50% chance of responding to 2nd series
* If no response to 2nd series HCW should be considered susceptible
* PEP for known non-responders exposed to Hep B positive or high risk unknown sources: 2 doses of HBIG- 1 at exposure then 4 weeks later
Hep B: Follow Up Testing
* Hepatitis B sAg is the test of choice as it rises in about 6 weeks
* LFTs should be monitored at regular intervals
Post Exposure Counseling
* Risk of transmission to infants and partners is thought to be low
* Exposed HCW do not need to modify sexual practices, stop breast feeding or refrain from becoming pregnant
* Should not donate blood
HIV
HIV: Risk of Exposure
* Risk of transmission from percutaneous expsosures involving HIV positive pts estimated at 0.3%
* Risk from mucous membrane exposure estimated at 0.1%
* As of 2000 there were 56 confirmed and 138 possible cases of occupational transmission in the US
Rationale for PEP
* HIV infects dendritic cells and then regional lymph nodes before becoming systemic
* AZT blocks infectivity of HIV infected dendritic cells
* Goal of PEP is to halt viral replication before systemic infection is established

Does It Work?
* Several animal studies showing efficacy
* Peri-natal prophylaxis has been effective
* Retrospective study showed that risk of seroconversion after exposure was 81% lower in HCWs who took AZT PEP.
Time is Virus
What To Use?
* Before: AZT+3TC +/- IDV or NFV
* Now: Becoming more difficult to answer!
* Regimens may need to be tailored based on the treatment history of the source patient -Surveillance study from 1998-1999 found that 39% of virus from source patients had some NRTI resistance and 10% had some PI resistance.

Nucleoside Reverse Transcriptase Inhibitors (NRTI)
* Still form the backbone of most regimens
* AZT has been formally studied thus it should be included if possible
* Addition of 3TC is recommended because:
1. It appears non-toxic
2. It has some synergistic effect with AZT with respect to mutations
* If source patient’s virus is felt to be resistant to AZT or 3TC alternatives include:
* d4T + 3TC
* d4T + ddI
* Role of abacavir?
* Role of tenofovir?
Protease Inhibitors (PI)
* Are very potent anti-virals and work very well in patients
* BUT they have significant side effects and can cause HCW to stop PEP altogether
* PI should be recommended primarily when the exposure is high risk
* Any PI can be used but indinavir and nelfinavir have been used the most
Non Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
* Not much experience using these for PEP
* Use should be reserved for situations when source patient’s virus is thought to be resistant to all PIs
* Nevirapine should probably be avoided as PEP: from 1997-2000 there were 22 reports of serious toxicity in HCW taking it for PEP

Toxicity of PEP
Side Effects of PEP
PEP Counseling
* Clean the site immediately
* Determine the HIV status of the source
* Determine the extent of the exposure
PEP management: Source Patient Testing
* Crucial 1st step as most exposures do NOT involve HIV positive patients
* Rapid test kit (SUDS) is available and yields an answer in about 30 minutes
* Rapid test is an EIA that is >99.9% sensitive
* Testing of blood on sharps is NOT recommended
* Patient consent is required in Maryland
HIV RNA Testing of Source
* No official recommendations and test is not approved for this indication
* Should be reserved for cases where there is a suspicion of acute retroviral conversion

Source Patient
1. Patient HIV negative - No PEP
2. Patient HIV positive
Low viral load / high CD4 = class 1
High viral load / low CD4 = class 2
3. Patient HIV positive, unknown CD4, VL
Use best judgement - err towards class 2
4. Unknown source
Exposure Types
1. Non-infectious fluids - No PEP
2. Mucous membrane, non-intact skin
Small volume
Large volume
3. Percutaneous injury
Less severe
More severe
HIV PEP Recommendations
Percutaneous injuries
Less severe
* Source pt HIV negative - No PEP
* Source pt class 1 - Recommend 2 drugs
* Source pt class 2 - Recommend 3 drugs
* Source of unknown status- Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors

HIV PEP
More severe injury
* Source pt HIV negative - No PEP
* Source pt HIV class 1 or 2 - Recommend expanded 3-drug regimen
* Source of unknown status - Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors
HIV PEP
Mucous membrane exposures
Small Volume
* Source pt HIV negative - No PEP
* Source pt class 1 - Consider 2 drugs
* Source pt class 2 - Recommend 2 drugs
* Source of unknown status- Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors
Large volume
* Source pt HIV negative - No PEP
* Source pt class 1 - Recommend 2 drugs
* Source pt class 2 - Recommend 3 drugs
* Source of unknown status- Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors
Duration of Treatment
* Current recommendation is 4 weeks but this is an arbitrary selection
* Animal studies suggest 10 days is too short but 28 days conferred protection
Resistance
* Becoming a significant problem now that so many patients are getting treated
* Treatment history can be helpful in the acute setting
* Recent history may be more important than remote
Resistance Issues
* Full medical history often not available when the exposure occurs - PEP should NOT be delayed
* Data from maternal transmission studies shows viral resistance does not preclude benefit
* Consultation with someone experienced in HIV treatment is recommended in cases where HIV resistance is possible
* PEP may need to be modified once more history is available
* Resistance testing is too slow to be of use right now

PEP and Pregnancy
* Women of child bearing age should be offered a pregnancy test before starting PEP
* BUT, recommendations on starting PEP should NOT change just because HCW is pregnant

HIV medications to avoid in Pregnant HCW
* d4T, ddI: have been associated with severe lactic acidosis in pregnant women
* Efavirenz: is teratogenic in primates
* Indinavir: causes hyperbilirubinemia in newborns if given near time of delivery

Post Exposure Testing
* Testing should be done at regular intervals (eg 6,12 weeks and 6 months)
* Testing should continue for 12 months if the HCW contracts HCV from the exposure
* Unclear if testing should be prolonged in exposures to pts with HIV and HCV or in HCW who have history of impaired Ab responses
* EIA is test of choice
* Viral loads and p24 assays should be reserved for suspected cases of acute seroconversion given high false pos rate
Counseling
* For 3 months following exposure HCW should avoid:
-unprotected sex
-donating blood
-sharing razors, toothbrushes
* HCW should consider stopping breast feeding (risk of perinatal transmission and drugs may get into breast milk)

Time to Seroconversion
* Most HCW seroconvert in 6-12 weeks with median time of 46 days
* 95% seroconvert within 6 months
* 100% seroconvert in one year
* Co-infection with HCV may delay HIV seroconversion

Acute Retroviral Conversion
* Symptomatic seroconversion develops in 50-90% of cases
* Average time from exposure to symptoms is 2-6 weeks
* ANY HCW who develops a flu-like illness in the follow up period should be encouraged to get HIV RNA testing

Resources
Conclusion

* People react very differently to exposures - be prepared for anything!
* The psychological impact of an exposure can be enormous
* Your patience and understanding may be the best PEP of all

Occupational Exposures to Bloodborne Pathogens.ppt

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Prenatal Testing And Screening

Prenatal Testing And Screening
By:Adel D. Gilbert, MS, CGC
Genetic Medicine Education Coordinator
Institute of Genetic Medicine
Johns Hopkins University

Genetics Board Review Lecture
Lecture Outline
* Definitions
* Age related risks
* Etiology and phenotype of chromosome anomalies
* Risks, phenotype and testing options of ONTD
* 1st and 2nd Trimester Prenatal Testing Options
* 1st and 2nd Trimester MS Screening Options
* New approaches to combining these tools
* Ultrasound as a screening tool

Testing Defined
Screening Defined
* Identify those at increased risk who are not be perceived to be at risk
* Does not dx definitively
* Follow-up options available for definitive information
* Sensitivity=True positives/all affected
* Specificity=True negatives/all unaffected
Baseline Risk for Having a Child With a Serious Birth Defect
Phenotype
* Moderate mental retardation
* Characteristic facies
o upslanting palpebral fissures
o epicanthic folds,
o midface hypoplasia,
o macroglossia
* Congenital malformations
o heart (30-40%), atrioventricular canal
o gastrointestinal tract, such as duodenal stenosis or atresia, imperforate anus, and Hirschsprung disease
o Leukemia (both ALL and AML) 10-20x
o acute megakaryocytic leukemia occurs 200 to 400 times more frequently in the Down syndrome
o 90% have significant hearing loss, usually of the conductive type
Facial
* microcephaly with prominent occiput
* narrow bifrontal diameter
* short palpabral fissures
* low-set malformed ears
* cleft lip +/- palate
* narrow palatal arch
* micrognathia

Skeletal
* neck
* webbed
* chest
* short sternum
* widely spaced nipples
* hips:
* small pelvis, congenital dislocation of the hips, limited hip abduction
* extremities:
* phocomelia
* rockerbottom feet or equinovarus short dorsiflexed big toes fixed flexion deformity of the fingers (overlapping of the 2nd and 5th fingers over the 3rd and 4th fingers)simple arch pattern of the fingers and toes

hypoplasia of fingernails single crease of 5th finger or all fingers (absence of interphalangeal flexion creases)
Trisomy 18
Kleinfelter syndrome
Miscarriage
Turner syndrome
Neural Tube Defects
* Second most common major congenital defect (1-2/1000)
* Not a chromosome anomaly
* Routinely tested and screened for in pregnancy
* Failure neural tube to close at 28 days gestation
* 20% are closed lesions and difficult to detect prenatally

Open Neural Tube Defects
Closed lesions
Open lesions
INDICATIONS FOR PRENATAL DIAGNOSIS
PRENATAL DIAGNOSTIC PROCEDURES
* AMNIOCENTESIS
* CHORIONIC VILLUS SAMPLING
* PERCUTANEOUS UMBILICAL CORD SAMPLING

AMNIOCENTESIS
ULTRASOUND GUIDED
AMNIOCENTESIS
Amniocentesis Testing
* Chromosome analysis
* AF-AFP levels
* Acetylcholinesterase
* Risk of miscarriage associated with procedure 1/100-1/400
Advantages
* Highly reliable results 99+%
* Familiar
* Long standing reputation
* NTD detection
Disadvantages
* Late in gestation
o Decision making
o Privacy
o Mom feels movement
* Fear of needles
* Needle invades the sac

Fetus: 12 weeks gestation
Transcervical
Chorionic Villus Sampling
Transabdominal
Performed >10 wks-13 weeks
Chromosome analysis
Risk 1/100-1/200
* trophoblastic shell cells
* Syncitiotrophoblasts – poly-proliferate tissue type=directs
* cytotrophoblasts
* Mesodermal core=tissue culture
* frorm finger-like extensions

Disadvantages
* Placental mosaicism 1% of CVS is confirmed in the fetus ~ 10-40%
* Second trimester amniocentesis mosaicism ~ 0.1-0.3% & confirmed in a fetus up to 70% of the time.
* ?LRD risk prior to 70 days gestation (10 weeks)
* Higher loss rate
* Less access to procedure
* Higher chance of insufficient sample
* Early test=risk of sampling a fetus potentially destined to miscarry
* No ONTD testing
* More risk of vaginal bleeding
* Speculum

Benefits
* Earlier in gestation
* rapidly growing cell cultures practically free of maternal cell contamination
* an efficient direct method to obtain high quality metaphases from the of the syncitiotrophoblasts tissue which the fetal karyotype is defined within a few hours of chorionic villi sampling (specialty cyto techinque)
* is suitable for a rapid, direct diagnosis of the related metabolic diseases.
* placental mosaicism (trisomic rescue in fetus) can increase the risks of genetic abnormalities such as uniparental disomy

Fetal Blood Sampling
Percutaneous Umbilical Cord Sampling
(PUBS) or Cordocentesis
* ~2% risk of loss
* Technically difficult prior to 20 weeks
* Blood disorders such as hemophilia and anemia
o Useful for detection of Rh isoimmunization of the fetus (blood cell count and oxygen level)→erythroblastosis fetalis (HDN)
* Chromosomal abnormalities Fetal karyotype in 48 hours
* Infections such as toxoplasmosis and rubella.
* The procedure is also used to perform blood transfusions to the fetus and to administer medication directly into the fetal blood supply.

Reproductive Decision Making
RISK Fetal Aneuploidy
Procedure Related RISK
TO TEST OR NOT TO TEST
* I want to know
* The benefits outweigh the risks
* Options are desirable
* Because my doctor says so…..
* Not sure I want to know
* Risks are a big worry
* Options stink
* Because my doctor says so….

SECOND TRIMESTER
MATERNAL ANALYTES FOR ANEUPLOID
SCREENING
FETAL
Alpha-fetoprotein- AFP
Estriol- uE3
PLACENTAL
Estriol- uE3
Human chorionic gonadotrophin- hCG
Inhibin-A

2nd Trimester MSS Overview
Used for detection of:
+ ONTD
+ Down syndrome
+ trisomy 18
+ Smith-Lemli-Opitz syndrome
Serum Marker
Smith Lemli Opitz Syndrome
* Defect enzyme in the conversion of 7-dehydrocholesterol to cholesterol.
* Affects 1 in 20,000 to 40,000 births
* Autosomal Recessive
* Mental Retardation
* Slow growth
* Heart defects
* Facial cleft
* Screen positive women have uE3 < 0.4 MoM
* ~2% baby affected
* Testing AF for 7-8- dehydrocholesterol (7/8-DHC) levels

Turner T13 Triploidy Pregnancy complications
ONTD screening
Detection Rates
MSAFP
Add Ultrasound
Screening for DS
2nd Trimester 1/270 Cut-off
First Trimester Integrated Screening For Trisomies =FIRST
Nuchal Translucency (NT)
First Trimester Screening
Down syndrome DR ~1:270 Cut-off
Nasal bone
Recommendations 1st Trimester Nuchal >3.5
* CVS
* Targeted ultrasound evaluation 18-20
* Echocardiogram
* Residual 5-6% risk neonate may have a yet undefined genetic syndrome…
Fetal Nasal Bone
* 65% DS have absent nasal bone
* General population 1%
o African Americans 8%-10%
* Secondary screen
* Difficult to obtain
* Higher false positive in 1st

Integrated Screening
PAPP-A and Nuchal
Quad Screen
Screen Positive
Screen Negative
Timeline weeks
Decision Making
Advantages
* Increases detection rate
* Decreases false positive rate (fewer tests and fewer procedure related losses)
Disadvantages
* Long wait time for result
* Unable to utilize CVS and early detection
* Late GA by the time amnio results final
Contingent

First Trimester Screening
High risk
Low Risk
Intermediate
Triple Screening Integration
Offer CVS
High risk
Low Risk
US and Amnio
Stop
Advantages
* Increase detection rate 90%
* Decrease FPR 2%
* Reduce the number of amnios performed in low risk pregnancies
Disadvantages
* New (limited data)
* Hard to determine uptake
* Offered at few institutions
RISK OF ANEUPLOIDY BASED ON GA AND ANOMALY

3D Ultrasound
Fetal Face
24 weeks Gestation
Fetal MRI
FETOSCOPY
Amnion (stuck twin)
Umbilical cord

Prenatal Testing And Screening.ppt

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Neurobiology of autism

Neurobiology of autism
By:Christopher Gillberg, MD, PhD
Professor of Child and Adolescent Psychiatry
University of Göteborg (Queen Silvia´s Hospital)
University of London (St George´s Hospital Medical School)


Autism spectrum disorders: neurobiology

* Overview
* Acquired brain lesions
* Genetics
* Where in the brain is autism?
* Psychosocial interactions
* Intervention implications
* Outcome implications
* The future

Overview
* At least four clinical presentations of autism (autism/autistic spectrum disorder)
* Autistic disorder (Kanner syndrome)
* Asperger’s disorder (Asperger syndrome)
* Childhood disintegrative disorder (Heller syndrome)
* PDD NOS (atypical autism, other autistic-like condition, other autism spectrum disorder)
* Prevalence much higher than believed in the past: ASD in 1% of population, AD in 0.2%
* Associated with learning disability 15% (80% in autistic disorder/AD)
* Associated with epilepsy 5-10% (35% in AD)
* Medical disorder in 5% (25% in AD)
* Skewed male:female ratio 2-4:1
* High rate of visual, hearing and motor impairments (including at birth)
* Sibling rate raised; identical twin conocordance rate much raised in classic autism

”Acquired” brain lesions
* Tuberous sclerosis, Fragile X syndrome, Partial tetrasomy 15, Down syndrome, XYY, XO, Hypomelanosis of Ito, Rett complex variants, Angelman syndrome, Williams syndrome, CHARGE association, Smith-Magenis syndrome, Smith-Lemli-Opitz syndrome, 22q11 deletion, Silver-Russell syndrome, Fetal alcohol syndrome, Retinopathy of prematurity, Thalidomide embryopathy, Moebius syndrome, Herpes and rubella infection
* Known medical disorders 25% in autistic disorder ”proper” (unselected samples) and 2-5% in Asperger syndrome
* These are either genetic in their own right, affect autism susceptibility gene areas, or cause brain lesions through direct/indirect insults
* High rate of pre- and perinatal risk factors
* Tuberous sclerosis
o 3-9% of all autism cases, more common in those with epilepsy
o chromosome 16p involved in one variant (autism susceptibility genetic area? ADHD susceptibility genetic area)
o dopamine genes on chromosome 9 affected in other TS variant
o autism likely if TS lesions in temporofrontal regions and if there are many lesions

* Herpes encephalitis
o affects temporofrontal areas more often than other brain structures
o can lead to classic symptoms of autism even in previously unaffected individuals who are 14 and 31 years of age
* Thalidomide embryopathy
o 5% of all have (classic) autism
o Brainstem lesions
o Day 20-24 postconceptionally

Genetics
* Sibs affected in 3%: core syndrome
* Sibs affected in 10-20%: spectrum disorder
* Identical twins affected in 60-90%
* Non-identical twins affected in 0-3%
* All of these findings refer to probands with autism proper, not spectrum disorders
* First-degree relatives increased rates of affective disorders (depression, bipolar), social phobia, obsessive-compulsive phenomena, and ”broader phenotype symptoms”, ADHD?, Tourette syndrome?
* First-degree relatives also show possibly increased rates of learning disorders including MR, dyslexia and SLI
* Genes on certain chromosomes (e.g. 2, 6, 7, 16, 18, 22, and X) may be important (genome scan studies of sib-pairs)
* Clinical findings in particular syndromes such as partial tetrasomy 15 (15q), Angelman (15q), tuberous sclerosis (9q, 16p), fragile X (X), Rett syndrome (X), Turner syndrome (X)

* Neuroligin genes on X-chromosome mutated in some cases
o (Jamain, Bourgeron, Gillberg et al 2003. Laumonnier et al 2004)
* Neuroligin genes on other chromosomes, including chromosome 17
o (Jamain et al 2003)
* Other neurodevelopmental genes according to microarray study
o (Larsson, Dahl, Gillberg et al 2003)

Where in the brain is autism?

* Clinical finding: macrocephalus common
o (Bayley et al 1997, Gillberg & deSouza 2002)
* Acquired brain lesions implicate temporal, frontal, fronto-temporal and bilateral dysfunction in core syndrome; right or left dysfunction in spectrum disorder
o (Gillberg & Coleman 2000)
* Autopsy data suggest: amygdala, pons and cerebellum
o (Bauman 1988)
* Brainstem damage suggested by
o Thalidomide
+ (Strömland, Gillberg et al 1994)
o Moebius syndrome association
+ (Gillberg & Steffenburg 1997)
o CHARGE association
+ Johansson et al 2004
o Auditory brainstem responses
+ (Rosenhall, Gillberg et al 2003)
o Decrease in/lack of postrotatory nystagmus
+ (Ornitz, Ritvo 1967)
o Aberrant muscle tone and concomitant squint
+ (Gillberg & Coleman 2000)
* Cerebellar dysfunction suggested by
o Autopsy studies
+ (Bauman et al 1992, Bayley et al 1999, Oldfors, Gillberg et al 2000, Weidenheim, Rapin, Gillberg et al 2001)
o Imaging studies
+ (Courchesne 1988)
o Relationship to ataxia
+ (Åhsgren, Gillberg et al 2003)
* Frontotemporal brain dysfunction suggested by
o Autopsy studies
o Functional imaging studies
o Neuropsychological studies
o Combined neuropsychological-neuroimaging studies
o Clinical picture
* Neuropsychological studies show
o Metarepresentation problems
o Central coherence problems
o Non-verbal learning disability in AS
o Verbal learning disability in AD
o Executive function deficits
o Procedural (complex) learning deficits
o Superior fact learning
o Aberrant reading of facial expression

* At least four biological variants of autism?
o Early brainstem/cerebellar associated with severe secondary problems
o Midtrimester bitemporal lobe damage
o Uni- or bilateral frontotemporal dysfunction in high-functioning cases
o Multi-damage autism

* Likely that several functional neural loops are implicated and that all impinge on neurocognitive/social cognitive functions that are crucially (but possibly not specifically) impaired in autism

Where in the brain is autism?
* Dopamine
o (Gillberg et al 1987)
* Serotonin (in LD also)
o (Coleman 1976)
* Noradrenaline dysfunction
o (Gillberg et al 1987)
* Neuroligins
o (Jamain et al 2003)
* GFA-protein
o (Ahlsén et al 1993)
* Gangliosides
o (Nordin et al 1998)
* Endorphines
o (Gillberg et al 1985)
* Immune system
o (Plioplys 1989)
* Glycine, GABA, Ach, glutamate?

Psychopharmacology of autism
* Only dopamine antagonists (neuroleptics) have been convincingly shown to affect core symptoms of autism
o (van Buitelaar 2000)
* SRIs?
* Antiepileptics??
* Peptides?? And peptide-targeted drugs

The pathogenetic chain
* Genetic or environmental insult
* Damage or neurochemical dysfunction
* Neurocognitive and social cognitive functions restricted (metarepresentations, central coherence, executive functions, procedural learning, )
* The ”syndrome” (or, sometimes, the ”arbitrary” symptom constellation) of autism
* The dyad of social impairment plus the monad of restricted behaviour pattern as a common comorbidity? (rather than the triad?)

Psychosocial interactions
* Not associated with social class
* Not associated with psychosocial disadvantage; however, “pseudoautism” described in children exposed to extreme psychosocial deprivation
* Temporally restricted major improvement in good psychoeducational setting
* Immigration links? Indirect link with genetic factors?
* Abnormal child triggers unusual interactions
* Some parents have autism spectrum disorders themselves
* Anxiety, violent behaviours, self-injury and hyperactivity reduced in autism-know-how-millieu

Implications for treatment
* All people are individuals first and foremost; at least as true in autism as in “neurotypicality”
* People WITH autism; not autistic people!
* Change attitudes
* Respect for people in the autism spectrum
* Focus on changing environment and
* Foster adaptive skills
* If known underlying disorder: treat this (and be aware of syndrome-specific symptoms such as gaze avoidance in fragile X)
* If epilepsy: treat this (however, there are major caveats here)
* If hearing, vision, or motor impaired: treat this
* Psychoeducational measures
* Symptomatic biological treatments
* No medication for majority
* Atypical neuroleptics, antiepileptics, SSRIs, stimulants, lithium (and other drugs) for some
* Diets??
* Physical exercise!!
* “Sensory awareness” environment (reduce noise, certain sounds, smell etc.)
* Concrete, visual (not always), straight-forward
* Minimize ambiguities and symbolic interpretation

Outcome
* Very variable
* Better with early diagnosis
* Majority probably live to be old, but increased mortality in subgroup
* Basic problems remain, albeit modified
* High rate of secondary psychiatric problems (personality disorder, affective, social, catatonia)

Outcome
* Better but also very restricted in Asperger syndrome
+ Cederlund et al 2004
* If autism and no language at age 7, classic autism in adulthood
* If autism and no language at age 3, some classic, some Asperger in adulthood
* If autism and some language at age 3, most will be Asperger in adulthood


The future
* Specific knowledge (including genetic) and treatment for subgroups (new diagnostic criteria)
* Symptomatic treatments
* Psychoeducation
* Acceptance and attitude change!
* People with autism, not autists or autistic people! Cannot be stressed enough
* Respect!

Neurobiology of autism .ppt

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