Understanding Autism – A Historical Perspective

This article was published in the Indian Journal of Pediatrics…

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Abstract:
The study of the evolution in the diagnosis and treatment of autism is a lesson in the dangers of medical beliefs or doctrines that are not grounded in medical science. The early descriptions of autism suggested that it was the result of childhood psychoses or psychodynamic disturbances of parent-child relationships. This flawed conceptualization of autism spectrum disorders (ASD) gave way to advances in medical science, which have established ASD as a neurobiological disorder of early brain development. There are many genetic, epigenetic, metabolic, hormonal, immunological, neuroanatomical and neurophysiological etiologies of ASD, as well as an array of gastrointestinal and other systemic co- morbid disorders. Thus, ASD are a biologically heterogeneous population with extensive neurodiversity. Early identification and understanding of ASD is crucial; interventions at younger ages are associated with improved outcomes. The advent of understanding the biological sub-phenotypes of ASD, along with targeted medical therapies, coupled with a multimodal therapeutic approach that encompasses behavioral, educational, social, speech, occupational, creative arts, and other forms of therapies has created a new and exciting era for individuals with ASD and their families: personalized and precision medical care based upon underlying biological sub-phenotypes and clinical profiles. For many individuals and their families dealing with the scourge of autism, their long and frustrating diagnostic journey is beginning to come to an end, with a hope for improved outcomes and quality of life.

By Mark Mintz

The Epilepsy – Autism Connection

Under certain conditions, anyone can experience a seizure. However, individuals with neurodevelopmental disabilities and brain disorders are more prone to developing recurrent seizures, or epilepsy. Why?

What is Epilepsy?
Epilepsy is diagnosed when there are recurrent, unprovoked seizure events. Seizures occur when there is a sudden change in the electrical activity of the brain that disrupts normal brain functions. Seizures can take many forms. The more widely recognized types produce observable events, such as “convulsive” shaking, loss of body control, involuntary movements, and/or loss of awareness or consciousness. However, seizures can also be very subtle, for example disrupting a person’s thought patterns or memory but without noticeable external symptoms. There can also be unexpected “subclinical” electrical changes of the brain (particularly “spikes”), detected by electroencephalography (EEG, a device that records the electrical activity of the brain) monitoring, that are neither noticeable to the individual experiencing this phenomenon nor to observers. Unrecognized and untreated, epilepsy carries a risk of injury from seizures, including trauma, drowning, aspiration, and rarely, sudden unexpected death (SUDEP), as well as unfavorably affecting behavior, development, memory or learning. In those individuals with Autism Spectrum Disorder (ASD), having an associated diagnosis of epilepsy can increase the risk of mortality seven-fold.1

Is There an Autism-Epilepsy Connection?
It has been observed for many years that individuals diagnosed with ASD are at high risk of developing epilepsy. Various studies have placed the risk between 6% to 26% of children and adolescents, with a cumulative risk into the adult years reaching as high as 67%.2 Overall, the risk of epilepsy is higher in ASD if there are associated intellectual disabilities or Cerebral Palsy.3 Why is there this connection? Generally, any brain disorder will increase the predisposition and lower the threshold for generating seizures. Additionally, ASD and epilepsies appear to share common biological and anatomical mechanisms. Advances in biotechnologies have revealed that there are many types of genetic variations causing or contributing to both ASD and the generation of seizures. Innovations in neuroimaging tools and neuropathological studies have revealed “disconnectivity” of various brain circuits leading to both autism and epilepsies. Various prenatal, neonatal and childhood metabolic, infectious and inflammatory disorders have been implicated in both ASD and epilepsy. Thus, understanding the epilepsy-autism connection is providing clues to the causes of ASD.

How is Epilepsy Diagnosed in ASD?
The behavioral and developmental complications of ASD can obscure or mimic the clinical manifestations of seizures; thus, the recognition of seizures is not always apparent in this population. Oftentimes children and adults with ASD do not have classical seizure manifestations. An EEG is necessary to determine if there are clinical or subclinical seizures, or abnormal electrical discharges that might be interfering with brain function or present a high risk for recurrent seizures. Language regression can signify a severe form of an “epileptic encephalopathy” (“Landau-Kleffner” and other related syndromes). Such individuals have very abnormal EEGs, with abnormal electrical patterns worsening with sleep but usually without observable clinical events. Infantile seizures associated with fever can sometimes evolve to autism, and, like other epilepsy syndromes, can be associated with genetic defects of “ion transport” (ions include sodium, calcium, potassium, magnesium). Some individuals with ASD and epilepsy will have “drop attacks” (a sudden loss of motor/body control causing a person to drop their head or fall to the ground) and their EEG will have a specific electrical pattern (“Lennox-Gastaut Syndrome”). Other individuals might only have a staring spell, have unwitnessed seizure events during sleep, or may have classic convulsions.

Overall, since epilepsy is a diagnosable condition with important “actionable” clinical implications, clinical evaluations of individuals with ASD should include screening and assessment of seizure risk and susceptibility. In addition to a comprehensive medical and neurological history and examination, there are other neurodiagnostic tests that a specialist may consider or recommend, including:

EEG: This device measures the activity of brain cells (“neurons”) in real-time. Conventional EEG can be difficult to obtain in ASD since the application of the approximately 20 electrodes with glues/pastes/scalp abrasion can be traumatic in those with behavioral challenges. Newer “dense-array” EEG technologies allow for application of many more electrodes (128 sponge electrodes) using a specially designed “sensor net” that is applied in minutes without discomfort or risk of infection.

Neuroimaging: Magnetic Resonance Imaging (MRI) is the study of choice to assess for significant structural abnormalities or malformations of the brain. Other neuroimaging technologies (positron emission tomography [PET], single-photon emission computerized tomography [SPECT], MR Spectroscopy [MRS], diffusion tensor imaging [DTI]) can be useful in select cases.

Laboratory Evaluations: There are wide arrays of relevant laboratory tests of the blood, urine, and on occasion cerebrospinal fluid (CSF) or skin/muscle tissue, which can help identify a biological cause of epilepsy and/or ASD.

Genetics: There has been an explosion of the availability of advanced genetic testing technologies, which are transforming the understanding, diagnosis and treatment of epilepsy and ASD. In many cases, the sequencing of thousands of “genes of interest” can be performed on a saliva sample. Genetic testing can also provide information concerning risk, susceptibility and prevention of complications of epilepsy and ASD, sometimes with implications for other family members.

Neuropsychological Evaluation: Both epilepsy and ASD can have profound effects on neuropsychological function. Neuropsychological evaluations include a series of empirically validated, norm-referenced, and evidence-based tests that quantitatively and qualitatively measure brain function, processing and output.

How is Epilepsy Treated?
Treatment must be individualized and personalized, and include programs to encourage healthy lifestyles (good sleep patterns, nutrition, physical activity, and stress reduction). Therapeutic strategies should target identifiable biological mechanisms and triggers of epilepsy, and simultaneously attempt to relieve seizure burden. Therapies should attend to medical and neurological/neuropsychological complications of epilepsy and/or medications, involve preventative strategies for risk reduction and SUDEP, and provide for a “rescue” plan in cases of acute seizure events. The mainstay for limiting seizure recurrence and promoting spike suppression are antiepileptic drugs (AEDs). In cases of identifiable metabolic and genetic disorders, nutritional supplements or dietary alterations may be indicated. Other options include specific diets such as the ketogenic and related diets (high protein and fat, and minimal carbohydrates), neurostimulation (devices that deliver periodic electrical currents, such as the vagal nerve stimulator [VNS] and other modalities) and “seizure surgery” (the localization and removal of brain tissue identified as the source of seizure generation). Research into the common biological sources of epilepsy and autism may lead to new and novel therapies that propose to alter the course of the disease.

In most cases, epilepsy is a treatable condition. Through proper screening and diagnosis, and the utilization of pragmatic therapies and interventions, the quality of life for children, adolescents and adults who may be suffering from epilepsy and ASD can be improved.

References

Pickett J, Xiu E, Tuchman R, et al. Mortality in Individuals with Autism, with and without Epilepsy. J Child Neurol 2011; 26:932-939.

Amiet C, Gourfinkel-An I, Bouzamondo A, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry 2008; 64:577-582.

McVicar KA, Ballaban-Gil K, Rapin I, et al. Epileptiform EEG abnormalities in children with language regression. Neurology 2005; 65:129-131.

Suren P, Bakken IJ, Aase H, et al. Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in Norwegian children. Pediatrics 2012; 130:e152-158.

Bolton PF, Carcani-Rathwell I, Hutton J, et al. Epilepsy in autism: features and correlates. Br J Psychiatry 2011; 198:289-294.

Viscidi EW, Triche EW, Pescosolido MF, et al. Clinical characteristics of children with autism spectrum disorder and co-occurring epilepsy. PLoS One 2013; 8(7):e67797.

Woolfenden S, Sarkozy V, Ridley G, et al. A systematic review of two outcomes in autism spectrum disorder – epilepsy and mortality. Dev Med Child Neurol 2012; 54:306-312.

By Mark Mintz

Expert Panel “Not Enough Evidence for Autism Screenings”

“And mandating autism screening will help clinicians intervene early”, said Dr. Mark Mintz, a pediatric neurologist who heads the Center for Neurological and Neurodevelopmental Health in New Jersey and Pennsylvania. “If this report causes primary care and other providers to stop specific autism screenings, the result is going to be that many infants and children will not be diagnosed between 0 and 3. They’ll miss that opportunity for early intervention,” Mintz said…

This article reprinted courtesy of NewsWorks

By Karen Shakeridge

Should clinicians screen every single child under 3 for autism? The U.S. Preventive Services Task Force has addressed that question in a recent statement and the answer has advocacy groups and clinicians speaking out.

The technically independent but government-backed panel concludes there’s not enough evidence to recommend for or against screening all children for autism spectrum disorder.

“We are concerned that people will then take this further and say well, if there’s no evidence that it’s helpful or that it’s scientifically valid or useful, why should we do it?” said Dr. Susan E. Levy, chairwoman of the American Academy of Pediatric subcommittee on autism.

And mandating autism screening will help clinicians intervene early, said Dr. Mark Mintz, a pediatric neurologist who heads the Center for Neurological and Neurodevelopmental Health in New Jersey.

“If this report causes primary care and other providers to stop specific autism screenings, the result is going to be that many infants and children will not be diagnosed between 0 and 3. They’ll miss that opportunity for early intervention,” Mintz said.

One in every 68 children has an autism spectrum disorder, according to the Centers for Disease Control and Prevention. And while many pediatricians already look for signs, screening without regulation screening can be spotty.

“The government is probably looking at this a little bit more from an ideal perspective, saying that pediatricians do developmental screenings anyway, why add to their burden of an extra mandatory test?

“And that would be correct if everybody was doing those basic developmental screens. But in the real world, it’s just not happening,” Mintz said.

The taskforce called for more research on universal screening and invites comments from the public until Aug. 31.

Adolescents with Special Needs: Better Transitioning to Adult Health Care

Here is an article I contributed to New Jersey Pediatrics, Volume 39, Issue 2, Summer 2014 (reprinted with permission from the American Academy of Pediatrics – New Jersey Chapter). 

 

The goal of any health system is to optimize health and minimize disease burden over the life span, for individuals, families and society.[1] Pediatric primary care providers play a pivotal role in this process. It is their responsibility to promote and maintain the health of individuals from birth through 21 years of age. By addressing the sources and mechanisms of chronic disease and disabilities, pediatricians can contribute to improving odds of lifelong health.

Children and adolescents with neurological, neurodevelopmental, neurobehavioral and intellectual disorders and diseases present special challenges. Conditions such as Autism Spectrum Disorders and ADHD are being diagnosed in epidemic proportions, and are rapidly becoming adult epidemics. However, most adult practitioners have little education, training or experience in dealing with chronic disorders that begin during infancy or childhood. After years of being nurtured by an array of medical, educational, government and other support services prior to age 21, families are jettisoned into a confusing and dysfunctional system ill-equipped to continue the substantial gains and stability of the pediatric years. Families become despondent as their special needs children–now suddenly considered adults despite lacking the usual maturational surrogate markers of such a transition, and often functioning at childhood developmental levels–sit at home and regress without school routines, vocational programs, social outlets, or community integration. Families subsequently encounter a dearth of adult primary and specialty care providers that are versed in the care and management of these challenging individuals, which often leads to one crisis after another, without therapeutic progress.

Yet, individuals with special needs have abilities, not just disabilities. Their success is dependent upon the same needs as their typical peers: healthy lifestyles, educational and vocational opportunities, proper housing, community involvement, social outlets, creative arts and physical activities, and adult independence/supported individuality.[2] It is morally and ethically unjust to only provide these pathways to the non-disabled community. Additionally, the Affordable Care Act (ACA) has impelled government and insurance companies to create innovative health care delivery models that provide cost effective care through promoting quality health outcomes. The lack of proper adolescent to adult health care transitioning programs is antithetical to the tenets of the ACA. Rather, the absence of attention to transitioning special needs patients has, and will, explode the costs and risks to third party and government payers, as well as physicians. Additionally, there are many “hidden” costs associated with this dilemma, including fragmentation of care, stress on caregivers, absence from work, family instability, and more. This emergent situation is complex, but pediatric primary care providers can play a pivotal role in preparing special needs patients and their families for a smooth and well-planned transition to adult life, resulting in better health outcomes.

How can pediatric primary care providers make a difference?

  1. Understand that disorders in this population have a biological basis, and should be assigned medical, not “mental health”, diagnoses. Physicians should assist and assure that the diagnostic odyssey and therapeutic interventions of their patients are pragmatic and evidence-based. Misdiagnosis or improper diagnoses that are carried over to adult life will lead to unnecessary and potentially toxic therapies and interventions.
  2. Proper biological phenotyping of special needs populations requires primary care providers to engage with multidisciplinary teams of specialists. Analyzing their underlying genetic risks and susceptibilities, neurophysiological manifestations, metabolic state, neuropsychological functioning, and functional behaviors will lead to therapies targeted at underlying disease processes rather than external symptoms.
  3. Prepare families well in advance for the adult transition so they are ready for the challenges of obtaining intensive adult services, such as residential placement or vocational training. Pediatricians can partner with specialty care health organizations well versed in navigating these complexities, or can direct families to an array of family support organizations.
  4. Many pediatricians, by default or choice, find themselves caring for their special needs patients beyond age 21. I would encourage this approach to ensure that patient transitioning is complete and flawless. Many innovative specialty care medical homes provide seamless services throughout the lifespan, and pediatricians should consider partnering with them.
  5. Pediatricians are crucial in assuring that specialized health maintenance protocols are followed, as occurs, for example, with disorders such as Down Syndrome and various metabolic disorders. Additionally, please advocate on behalf of your patients for proper educational accommodations and classroom placements.
  6. It has been well documented that children with special needs have higher aggregate health care costs than their typical peers. [3] One cost contributor is higher prescription drug use. Although medications are sometimes necessary to target behavioral manifestations or co-morbid disorders, such as epilepsy, there is a tendency to over-medicate this population. Pediatricians should monitor for excessive prescribing that can occur as a result of fragmentation of specialty care. Pediatricians should refer families to organizations that provide non-pharmacological therapeutic interventions integrated with medical expertise.

Overall, health care funding paradigms will be changing to systems based on health outcomes, the ability to manage and/or share risk, physician accountability, longitudinal integration of services, and lifespan care and management. Thus, health care reforms present not just challenges, but rather opportunities for pediatricians to play an active role in helping this deserving population.

 

REFERENCES

  1. Halfon N, Conway PH: The opportunities and challenges of a lifelong health system. N Engl J Med 2013; 368:1569-1571.
  2. Taylor JL, Smith LE, Mailick MR: Engagement in vocational activities promotes behavioral development for adults with Autism Spectrum Disorders. J Autism Dev Disord 2013; Nov 28. [Epub ahead of print]
  3. Lavelle TA, Weinstein MC, Newhouse JP, et al.: Economic burden of childhood autism spectrum disorders. Pediatrics 2014; published online February 10; doi: 10.1542/peds.2013-0763

 

By Mark Mintz