Lalitha Sivaswamy, MD

The term “autism” originates from the Greek word “autos,” implying the preoccupation with oneself. Autism spectrum disorders (ASDs) are recognized as a heterogeneous group of neurodevelopmental disorders characterized by certain behavioral features. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defines autism as a syndrome manifested by impairments in social relatedness and communication and by repetitive routines and restricted interests. The term “pervasive developmental disorders” (PDDs), according to DSM-IV, refers to 5 conditions: (1) autistic disorder, (2) Asperger disorder, (3) Rett disorder, (4) childhood disintegrative disorder, and (5) PDD not otherwise specified. For the purpose of this discussion, ASD is used synonymously with PDD.

The prevalence of ASDs is 1 in 100 children, and the prevalence in males is 3 times higher than in females.

 However, no predilection has been reported for children from specific ethnic or socioeconomic groups. As the term “spectrum disorder” implies, the condition has varying manifestations and severity. In your practice, you are likely to treat children with ASDs. The following 5 points are important to keep in mind when faced with the challenge of treating a child with ASD.


The American Academy of Pediatrics recommends screening with standardized tests at 9, 18, 24, and 30 months of age. Examples of such tests include the Checklist for Autism in Toddlers (CHAT), Social Communication Questionnaire (SCQ), and Social Responsiveness Scale (SRS).

 For formal tests of cognitive level (Wechsler Intelligence Scale for Children), assessment of adaptive functioning (Vineland Adaptive Behavior Scale), and evaluation of autism-related behaviors (Childhood Autism Rating Scale or Gilliam Autism Rating Scale), referral to a neuropsychologist is recommended.

 These tests are important for determining the child’s intellectual abilities and comorbid conditions. Test results will help guide school placement to maximize the child’s potential and will offer caregivers a realistic prognosis. Nonetheless, abilities can change over time and interim analysis may be helpful to guide the family.


Children with autism sometimes demonstrate disruptive and self-aggressive behaviors in addition to anxiety, hyperactivity, and irritability. In fact, 30% of children with autism exhibit moderate to severe irritability.

These behaviors not only may be distressing to parents and teachers but also may be disruptive to family activities and are often the reason parents seek medical intervention. Behavioral and pharmacologic treatments are helpful. Risperidone has FDA approval for targeted therapy for severe tantrums and aggression in children, and several rigorous studies support its use.

 Olanzapine, quetiapine, and aripiprazole are antipsychotics that have shown beneficial effects in small studies. Hyperactivity may be managed with stimulants or ?-agonists (eg, clonidine). In children with a comorbid condition such as epilepsy, an anticonvulsant with mood-stabilizing properties (eg, valproic acid) may also be used. Although serotonergic dysregulation is well documented in autism, large randomized controlled studies do not provide support for use of selective serotonin reuptake inhibitors in children with ASDs.


One-third of all children with autism have seizures. The age at onset of epilepsy usually shows a bimodal distribution, with the first peak before the age of 5 years and second after puberty. The presence of cognitive impairment increases the risk for seizures.

 Seizures of all types may be observed, including complex partial, generalized tonic-clonic, and myoclonic. The “staring spells” and repetitive body movements that many parents report are usually not seizure-related phenomena and are more likely to be stereotypic behavior. The workup may include brain MRI and electroencephalography, as for any child with new-onset seizures. However, one caveat that must be kept in mind is that the findings on an electroencephalogram (EEG) can be abnormal in a child with ASD without evidence of clinical seizures.

 Hence, abnormal EEG findings in a child with no clear-cut clinical events suggestive of seizures must be handled with circumspection. A prolonged EEG aimed at recording clinical events may help determine whether the events being reported by the family are truly epileptic. Treatment of seizures includes standard antiepileptic medications, such as valproic acid, lamotrigine, and levetiracetam. Most important, counseling about safety issues related to activities such as swimming, bathing, and climbing must be reviewed at every visit because morbidity and mortality related to such activities are higher for children with epilepsy.


More than half of all children with ASDs tend to have sleep problems, with insomnia being the most common.

 Parents may note difficulties with sleep initiation and maintenance as well as restless sleep and awakening at very early hours. The behavioral deficits associated with ASDs, such as inability to calm oneself, difficulty with transitioning, and excessive sensitivity to light and sound, compounded by communication deficits may make it difficult for children with ASDs to develop established sleep regimens that are compatible with those of the rest of the family. Behavior interventions such as consistent bedtimes and calming activities toward the end of the day are helpful. Some children may benefit from use of melatonin, which is relatively safe.

 Other treatment options include low doses of clonidine, anxiolytics, and mood stabilizers.


 Parents often want to know if there is a reason why their child has autism. Genetic testing is widely available, and many parents want their child to be tested. Most children with ASDs do not have specific features in the history or physical examination to suggest a genetic cause. The most appropriate genetic test to order is chromosomal microarray analysis, which has a higher diagnostic yield (more than 15%) than karyotype analysis.

 In patients with conditions in which autistic symptomatology is prominent-such as in Smith-Lemli-Opitz, fragile X, Cornelia de Lange, Williams, and Rett syndromes-a clear-cut genetic diagnosis can be established. Dysmorphic facial appearance, limb anomalies, microcephaly, macrocephaly, and cardiac defects may point to an underlying diagnosis. In patients with well-established genetic conditions, such as tuberous sclerosis, neurofibromatosis, Down syndrome, and phenylketonuria, prominent pervasive features may indicate that ASD exists as a comorbidity.


As advocates for child health, pediatricians are often called on to offer their opinions regarding alternative treatment approaches, such as the gluten-free, casein-free (GFCF) diet and use of probiotics, oral immune modulators, omega-3 fatty acids, and digestive enzymes. Very little scientific evidence exists regarding the use of probiotics and enzymes. In two pilot studies,

the use of fatty acids produced negative results. A randomized placebo-controlled study by Elder and colleagues

 concluded that the GFCF diet is essentially unhelpful. High-quality studies are not yet available to strongly support the use of these remedies, although studies of parental perception have indicated high degrees of satisfaction with the GFCF diet, with patients showing improvement in social interaction and ASD behaviors.



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Articles

Autism spectrum disorders affect 1 in 100 children and the prevalence is 3 times higher in females. One-third of all children with autism have seizures.

Autism Spectrum Disorders: 5 Things Pediatricians Should Know

Childhood absence epilepsy (CAE), a syndrome that occurs in 1 out of 1000 children, is one of the most common types of early childhood (first decade) seizures. A classic CAE scenario may be that of a little girl who has just started kindergarten and has periods of “blanking out” every day. Her teacher calls out her name, but she does not respond. She sometimes blinks her eyes a few times and is back to “normal” in about 20 seconds. The teacher alerts the parents, who then make an appointment to see the pediatrician. Typically, the parents report never noticing these episodes at home.

It is important to distinguish CAE from partial epilepsy. The terms “absence epilepsy” and “partial epilepsy” are erroneously used as synonyms for each other-not only by parents, but also by health care professionals. There are differences, however. Partial epilepsy is characterized by the presence of an aura. A spell lasts longer than one seen in CAE and  classically produces focal changes on electroencephalogram (EEG). Medications used most often to treat partial epilepsy (oxcarbazepine or tegretol, for instance) can worsen CAE and precipitate an episode of absence status epilepticus. Distinguishing between these conditions is vital in order to guide families appropriately regarding treatment and prognosis.

The purest form of CAE is easily recognized, responds well to treatment, and carries a good prognosis. Here are 5 pointers that are useful to keep in mind when managing a child who has CAE:

1. Many children with CAE are misdiagnosed as having attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD). 

This is based on their frequent bouts of inattention and staring. These spells, known as “simple typical absences,” usually begin when the child is age 5 to 9 years old and are frequently first noticed by a teacher.

 Other clinical features may include automatisms, which take the form of chewing movements of the mouth, eye fluttering, or picking at clothes or hair (“complex typical absences”). A child may have numerous episodes per day, which interferes with his or her learning and ability to process information.

The spells last for approximately 3 to 30 seconds.

 There is no post-ictal state, and the child resumes normal activity right away. An articulate child might describe a time loss. Because these spells are not dramatic, they tend to pass unnoticed by parents and other caregivers for a long time.

Typical absences can also occur in other epilepsy syndromes, such as juvenile myoclonic epilepsy. Therefore, the diagnosis of CAE is based not only the classic seizure type, but also on a specific electroencephalogram (EEG) abnormality.

2. EEG is crucial to establishing a diagnosis of CAE.

 The classic pattern is a generalized 3 Hz per second spike and wave tracing. There are no focal spikes on the recording.

When EEG is not readily available, ask the child to hyperventilate for 45 to 60 seconds and observe for seizure. No other type of epilepsy produces this type of predictable response to hyperventilation. Failure to induce a seizure after 2 to 4 minutes of hyperventilation puts the diagnosis of CAE in question.

3. The drug of choice for children with typical absence events is ethosuximide.

 The most common starting dose is 10 to 20 mg/kg of body weight, taken in 2 divided doses. For maintenance, the child can take up to 40 mg/kg/d, not to exceed 500 mg/d. Ethosuximide is available in liquid and pill forms. Common side effects include anorexia and drowsiness; liver toxicity and drug rash are less common.

Valproic acid and lamotrigine are options when seizures are refractory to ethosuximide and when CAE is associated with atypical absences or generalized convulsions. Valproate is available as a liquid, sprinkle, capsule, and pill. Starting and maintenance doses are 20 and 60 mg/kg/d, respectively. Common side effects of valproate include abdominal discomfort, nausea, and weight gain. Valproate causes neural tube defects, so teenage girls must be monitored especially closely.

Lamotrigine is available in chewable and pill form. It is usually started at 0.5 mg/kg/d, divided in 2 doses, increasing to a maximum of 5 to 10 mg/kg/d, depending on whether the child is also taking other antiepileptic medications. Stevens Johnson syndrome is a rare but dreaded complication of lamotrigine treatment. It occurs in 0.8% of children who are between the ages of 2 and 16 years.

Treatment with anti-epileptic medications should be continued until the EEG normalizes and there are no clinical events for at least 2 years.

4. CAE is not associated with structural abnormalities on magnetic resonance imaging (MRI). 

Because of this, imaging is unlikely to be helpful in typical cases of CAE. Nonetheless, recent technology using blood oxygen level dependent imaging and functional MRI techniques have documented altered connectivity between different regions of the brain.

 This helps us understand why CAE is not necessarily a “benign” epilepsy syndrome. In fact, aberrations in language, cognition, and behavior have been described in a subset of these children. Teachers and parents should be informed of these comorbid conditions and should also understand the benefits of early neuropsychological testing, followed by appropriate educational intervention.

5. Remission rates up to 90% have been reported in the literature.

 Many children grow out of their seizures by puberty. Prognosis is poorer in children who: require more than 1 drug to control their seizures; have generalized convulsions in addition to typical absences; and have atypical EEGs.


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, 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008. 
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 6. Salvatore G, Daniela G, Piero, et al. Childhood absence epilepsy:  evolution and prognostic factors. 

Childhood absence epilepsy is distinct from partial epilepsy and is often misdiagnosed as ADD/ADHD. It is one of the most common types of pediatric seizure.

Childhood Absence Epilepsy: 5 Things Pediatricians Need to Know

A 6-month-old presents with episodes of recurrent head deviation to one side followed by irritability. These episodes may last for days. Both mother and aunt have migraine headaches. Examination and imaging are normal. An electroencephalogram during the event is normal.

What could explain the child’s symptoms?

 
  
 Benign paroxysmal torticollis (BPT) is an under-recognized torticollis of infancy and often mistaken for “congenital” torticollis. The episodes of head tilt/deviation may last from 10 minutes to 10 days, occur as early as 1 week of life, and in most cases have their onset in the first 7 months.(1,2).  Resolution by 4 years of age is almost universal. Episodes rarely last for more than 2 weeks. 
 
 No gender association has been noted in most studies although some have found a slight female predominance.

 Associated symptoms may include irritability, vomiting, ataxia, pallor, and somnolence.
   
 BPT is widely accepted as a forerunner of migraine headaches-- more specifically a manifestation of basilar migraine.

A proposed association between BPT and a calcium channel mutation that is implicated in the etiology of other types of migraine further supports BPT’s role as a migraine precursor.

 Treatment options for the acute phase of BPT remain unsatisfactory but parental reassurance is paramount. A trial of cyproheptadine may be safe and possibly effective.

Differential diagnosis includes dystonic drug reactions; tumors of the posterior fossa or cervical spine; focal seizures; and local pathology, such as fibrosis or contracture of the sternocleidomastoid muscle.  A thorough history may elicit the episodic and reversible nature of the symptoms and is the most important diagnostic clue.  A family history of migraine also may guide the clinician. There are no biomarkers for BPT, thus in many situations it may be a diagnosis of exclusion. Other migraine “equivalents” in the first few years of life include benign paroxysmal vertigo, abdominal migraine, and cyclic vomiting.

1. Rosman NP, Douglass LM, Sharif UM, et al. The neurology of benign paroxysmal torticollis of infancy: report of 10 new cases and review of the literature. 

. 2009;24:155-160. 
 2. Bhatia KP. Paroxysmal dyskinesias. 

. 2011;26:1157-1165.
 3. Drigo P, Carli G, Laverda AM. Benign paroxysmal torticollis of  infancy. 

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 4. Deonna T, Martin D. Benign paroxysmal torticollis in infancy. 

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 5. Giffin NJ, Benton S, Goadsby PJ. Benign paroxysmal torticollis of infancy: four new cases and linkage to CACN1 mutation.

. 2002;44:490-493.
 6. Lewis DW, Gozzo Y, Avner M, et al. Primary headache disorders in children, adolescents, and young adults. In: Winner P, Lewis DW, eds.

 Young adult and pediatric headache management.

 Hamilton. Ontario, Canada: B.C. Decker, 2005:41-115.

Episodes of recurrent head deviation to one side followed by irritability affect this infant, lasting for days. Migraine headaches affect mother and aunt. Is there a clue in the history?

Recurrent Head Deviation in an Infant: Dystonic Drug Reaction? Torticollis? Focal Seizures?

A 14-year-old girl presents with near constant frontal headaches of a month’s duration. The pain is dull and worsens with Valsava’s maneuver. Her parents say she is she is irritable and moody. The patient says she has recently gained a significant amount of weight. Eye examination reveals papilledema. CT imaging of her brain is normal.

New onset continuous headache is an uncommon symptom in childhood and warrants thorough neurologic and ophthalmic examinations. It is notable that the patient’s headaches worsen with activities that raise intracranial pressure. The alteration in mood and personality and weight gain may suggest depression-a comorbidity commonly associated with migraine headaches and chronic pain syndromes. The presence of papilledema, however, makes this case a neurologic emergency.

What tests would you order to reach a diagnosis?

Alone, CT imaging of the brain may not provide sufficient information for a diagnosis because it does not allow good visualization of the posterior fossa. If a tumor is strongly suspected, contrast-enhanced CT is a reliable test, particularly if MRI testing is not conveniently available although MRI remains the preferred imaging modality.
  
A spinal tap was performed with the patient in the left lateral decubitus position with her legs extended.  Opening pressure was 45 cm H

O. MRI images and of the venous sinuses of her brain showed no abnormalities. A diagnosis of idiopathic intracranial hypertension (IIH; previously known as pseudotumor cerebri) was entertained. Modified Dandy criteria

• Symptoms of raised intracranial pressure in an awake and alert patient, with normal imaging
• Elevated opening pressure on a spinal tap
• Exclusion of other conditions that could explain the raised intracranial pressure

Unfortunately, normative values for cerebrospinal fluid opening pressure have not been clearly established in children.  Opening pressure may vary on the basis of body mass index (BMI): heavier children have higher values. Nonetheless, values greater than 25 cm H

O are considered elevated, regardless of BMI.
  
The cause of IIH may not always be clearly identified. In children, however, over half of cases may be associated with an identifiable condition,

a number of which are well recognized. These include hypoadrenalism, iron deficiency anemia, Guillain-Barre syndrome, use of oral birth control, steroid withdrawal, and replacement therapy with human growth hormone.

In adults, IIH is strongly associated with obesity;

 this association is tenuous in children, however, especially in prepubertal youngsters.

 Common symptoms besides headache, pulsatile tinnitus, and blurry vision include diplopia, neck stiffness, and symptoms referable to other cranial nerve palsies. The cardinal sign is papilledema.
 
It is important to document visual perimetry in every patient who can cooperate, because visual field loss may be asymptomatic initially, but it may worsen over time. Perimetry results can also guide treatment.

 Ocular coherence tomography has recently emerged as an objective method of assessing optic nerve involvement. 
 
There are few randomized double-blinded, placebo controlled trials of treatment options for children.  Medical management begins with lowering intracranial pressure with acetazolamide (doses of 250 mg twice daily to a maximum dose of 3000 mg/day) or topiramate (doses of 50 mg twice daily to a maximum of 200 mg/day). Headaches may not resolve as intracranial pressure decreases and prophylaxis with tricyclic antidepressants or beta blockers is often required. 

Surgical options include shunting of CSF either with a ventriculoperitoneal shunt or lumboperitoneal procedure. Optic nerve sheath fenestration is also an option and should be strongly considered if vision loss does not respond to conservative measures. 

The importance of weight loss for the child must be emphasized to the family. Prompt recognition and treatment of IIH leads to almost complete resolution of symptoms.

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Lalitha Sivaswamy, MD

Articles

Autism Spectrum Disorders: 5 Things Pediatricians Should Know

Childhood Absence Epilepsy: 5 Things Pediatricians Need to Know

Recurrent Head Deviation in an Infant: Dystonic Drug Reaction? Torticollis? Focal Seizures?

Teenager with Persistent Headache, Irritable Mood, and Weight Gain