This Week in the Journal

August 1, 2002

Obesity and the Risk of Heart Failure

25
Extreme obesity is a risk factor for heart failure. This analysis from
Cumulative Incidence of

Women
20 the Framingham Heart Study assessed the risk associated with lesser
Heart Failure (%)

15 Obese degrees of obesity and overweight. There was a continuous increase

Over-
weight
in the risk of heart failure with increases in the body-mass index (an
10
increase in risk of 5 percent for men and 7 percent for women for each
5
Normal
increment of 1 in the body-mass index). Obesity accounts for about
0
11 percent of heart failure among men and 14 percent among women
0 3 6 9 12 15 18 21 in the Framingham population.
Years
Obesity may increase the risk of heart failure by virtue of its relation
to established risk factors, such as hypertension, diabetes, and hyper-
lipidemia, but obesity may also have a direct negative effect on myo-
cardial function.
see page 305 (editorial, page 358)

Risperidone in Children with Autism and Serious

30 Behavioral Problems
25
Serious behavioral problems in children with autism are common and
difficult to manage. Atypical antipsychotic medications are effective in
Mean Irritability Score

Placebo
20 treating adults with schizophrenia and have fewer side effects than
traditional antipsychotic medications. This randomized trial examined
15 Risperidone
whether risperidone improved behavior in children between the ages
10
of 5 and 17 years who had autistic disorder with severe tantrums, ag-
gression, or self-injurious behavior. At eight weeks, 69 percent of the
5 children treated with risperidone had substantial improvement in be-
havior, as compared with 12 percent of those who received placebo.
0
0 2 4 6 8 Fatigue, drowsiness, tremor, drooling, and increased appetite were mild
Week
but were more common among children taking risperidone.

This eight-week study suggests that atypical antipsychotic medications

improve moderate-to-severe behavioral problems in children with
autism. The long-term risks and benefits of treatment with risperidone
in children with autistic disorder are not yet known.
see page 314 (Perspective, page 302)

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 The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

PERSPECTIVE Characteristics of Pervasive Developmental Disorders

Disorder Characteristics
The Autistic- Presence of 6 of 12 potential deficits involving all
three behavioral domains that dene the autistic
Spectrum Disorders spectrum:
2 decits in sociability, empathy, and insight into
other persons feelings and agendas
Autistic disorder 1 deficit in communicative language and
(classic autism)

A
imagination
ny person, talented or
1 deficit in behavioral and cognitive flexibility
handicapped, whose social
Detectable before the age of 3 years
skills have been severely de- Diagnosis not excluded by the level of cognitive
ficient since very early childhood, competence or the existence of other handicaps
who started to talk late or whose Troublesome social ineptness, lack of insight
communicative use of language is Behavioral inflexibility with a narrow range of interests
inadequate, and who perseverates Asperger's disorder IQ 70 (affected children may be normally intelligent
and lacks cognitive and behavioral or gifted)
flexibility meets the diagnostic cri- No delay in the emergence of speech
Often clumsiness
teria for an autistic-spectrum disor-
der. The Diagnostic and Statistical Pervasive developmental Applies to less severely affected children who do not
Manual of Mental Disorders, 4th disorder not meet criteria for either autistic disorder or Asperger's
otherwise specied disorder
edition (DSM-IV), published by the
American Psychiatric Association, Early development entirely normal, including speech
and the International Classification Disintegrative disorder Severe regression between the ages of 2 and 10 years,
affecting language, sociability, cognition, and
of Diseases, 10th Revision (ICD-10), competence in skills of daily life
published by the World Health Or-
ganization, use the term pervasive Severe global regression in infant girls (rarely in boys),
resulting in lifelong severe mental retardation, lack of
developmental disorder to encom- Rett's syndrome
language and purposeful hand use, and other
pass the broad spectrum of devel- neurologic deficits
opmental disorders with these
characteristics (see Table). Pervasive
developmental disorders are more
common in boys than girls. Autistic for its stilted quality and unusual pected age have Aspergers disorder,
disorder is classic autism, one of the vocabulary and who had many au- and those who do not meet the cri-
more severe disorders on the spec- tistic characteristics despite average teria for either autistic disorder or
trum. Persons with autistic disorder or superior intelligence. Since then, Aspergers disorder have pervasive
have substantial impairment in so- widespread use of improved, stand- developmental disorder not other-
cial skills, verbal communication, ardized questionnaires and observa- wise specified.
and cognitive and behavioral flex- tional scales has resulted in the iden- DSM-IV and ICD-10 list two
ibility. About 70 percent of such tification of many persons with less other rare, very severe disorders
persons are mentally retarded, and severe disorders on the autistic spec- with a poor prognosis. The first,
a third have had at least two unpro- trum, some of whom have received disintegrative disorder, is diagnosed
voked epileptic seizures by the time a diagnosis such as developmental in previously normal children who
they reach late adolescence. About language disorder, attention-deficit do not have a degenerative disease
half are nonverbal or have grossly disorder, or obsessivecompulsive yet inexplicably undergo a cata-
impaired speech. Most persons with disorder. Their cognitive skills are strophic global regression, with or
autistic disorder are not able to live typically uneven. The least severely without epilepsy, and become au-
independently as adults. affected may not come to medical tistic, most often between the ages
As long as autistic disorder was attention at all or not until mid- of three and six years. Mutations of
the only recognized subtype on the childhood or adolescence, despite the MECP2 gene on Xq28, iden-
spectrum of autistic disorders, au- aberrant types of behavior that are tified in 1999, cause the second dis-
tism was considered to be rare (0.4 evident to family members, educa- order, Retts syndrome, which af-
case per 10,000 persons). In the tors, and peers. According to the fects girls almost exclusively. This
early 1940s, however, Kanner and DSM-IV and ICD-10 classifications, disorder is characterized by post-
Asperger independently described such children who are not retarded natal reduction in brain growth,
children whose speech was notable and who started to speak at the ex- with hand stereotypy, seizures, sen-

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 THIS WEEK IN THE JOURNAL

Inhaled Iloprost for Severe Pulmonary Hypertension

Mean Change in Distance Walked (m)

40 The number of effective, long-term treatments for pulmonary hyper-

Iloprost
tension is limited. In this double-blind, randomized trial, an aerosol-
20 ized form of iloprost, a stable analogue of the pulmonary vasodilator
prostacyclin, was assessed over a 12-week period. Iloprost had a ben-
P=0.004
0 eficial effect on the combined end point of the distance walked in six
minutes and an improvement in the New York Heart Association func-
20 Placebo tional class.

40
Base Line 4 Wk 8 Wk 12 Wk The advantage of iloprost is that it can be administered by inhalation,
thus avoiding the intravenous infusion required for the administra-
tion of prostacyclin and allowing delivery of the drug directly to the
lungs.
see page 322

sorimotor and autonomic deficits, epidemic of autism, and school disorders, tantrums, noncompli-
and curtailment of social, language, systems are hard put to address the ance, destructiveness, and self-injury
cognitive, and neurologic devel- problem. More active case ascer- impede integration into mainstream
opment. tainment and changes in diagnostic social and educational environ-
A puzzling feature reported by criteria probably account in large ments. Pharmacologic agents can-
about a third of the parents of chil- part for the increase. The role of not cure autism because, in most
dren with autism is stagnation or such environmental factors as peri- cases, the brain has undergone atyp-
regression of early language, usu- natal injury, vaccines (exposure to ical cellular development dating
ally between the ages of 18 and 24 minuscule amounts of mercury pre- from the earliest embryonic stages.
months, and regression of sociabil- servative or the persistence of mea- The goal is to alleviate troublesome
ity and play, with the appearance of sles in the enteric lymphatic system), symptoms that interfere with the
stereotypy. Some parents blame or food allergies is unsubstantiated. most effective intervention inten-
the problem on an intercurrent ill- In the case of both autism and a sive, targeted education. The results
ness or a traumatic environmental broad spectrum of developmental of a controlled study of the effec-
change, but in most cases, it is in- disorders in families, twin and fam- tiveness of risperidone, reported by
sidious and unexplained. Clinical or ily studies have implicated multigen- the Pediatric Psychopharmacology
subclinical epilepsy (the latter diag- ic influences in the families of many Autism Network in this issue of the
nosed on the basis of epileptiform affected persons. Because autism is Journal (see pages 314321), are
electroencephalographic features in a behavioral, not a biologic, diagno- therefore welcome and encourag-
the absence of clinical seizures) oc- sis, prenatal diagnosis is not possi- ing, despite the acknowledged lim-
curs in no more than 10 to 20 ble except in the rare case in which itations of the study. The search for
percent of children with autism, autism is associated with a single- safe and effective psychotropic med-
whether or not they have a history gene disorder, such as tuberous scle- ications has been frustrating so far.
of regression. The value of treat- rosis, Retts syndrome, the fragile May this study be followed by larg-
ment with antiepileptic medications X syndrome, or Angelmans syn- er, longer, and equally rigorous tri-
has not been determined. The nat- drome. Research requires brain im- als of interventions in children
ural course of autistic regression is aging and electrophysiological, bio- with autism. Such studies are sorely
an improvement, although full re- chemical, and genetic investigations, needed.
covery is rare. but the yield of these studies is min-
The dramatic increase in esti- imal in the clinic, barring specific ISABELLE RAPIN, M.D.
mates of the prevalence of autism indications. Albert Einstein College of Medicine
to 2 to 5 cases per 1000 children In a distressingly large proportion Bronx, NY 10461
has raised the possibility of an of children with autistic-spectrum

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 The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Diacetyl Bronchiolitis Obliterans in a Microwave-Popcorn Plant

Bronchiolitis obliterans results in irreversible obstruction of the small
(2,3 butanedione), airways and has known environmental and occupational causes. An
investigation was initiated at a plant that produces microwave popcorn
a ketone with butter- after signs and symptoms of bronchiolitis obliterans developed in eight
flavor characteristics, employees. Among current workers at the plant, those exposed to high
levels of diacetyl (2,3-butanedione), the principal additive that is used
was the predominant to give the popcorn its butter flavor, had more than three times the
expected rate of airway obstruction and more than twice the expected
compound isolated rate of cough. There were strong relations between the degree of air-
way obstruction and the level of exposure to diacetyl.
from air samples.
This study provides convincing evidence that occupational exposure
to a substance in microwave popcorn, presumably diacetyl, can lead
to severe and irreversible airway obstruction.
see page 330 (editorial, page 360)

Clinical Practice: Herpes Zoster

A 77-year-old man has a five-day history of burning and aching pain in
his right side and a two-day history of erythema and clusters of clear
vesicles, accompanied by headache and malaise. How should he be
evaluated and treated?
see page 340

Current Concepts: Bites of Venomous Snakes

At least 2000 persons are bitten by venomous snakes in the United
States each year. This article reviews the diagnosis and management
of bites from venomous snakes encountered in North America, but
the same principles apply to management of snakebites elsewhere in the
world. The review summarizes the complications of envenomation and
explains the current recommendations for the use of antivenoms. It
explains how to distinguish venomous from nonvenomous snakes.
see page 347

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