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Currents in Diagnosis and Th erapy of Autism spectrum disorder

Autor: Viorel Lupu Andra Isac Izabela Ramona Lupu Lavinia Hogea Laura Nussbaum
Distribuie pe:

The latest data on the prevalence of autism in the US indicates 1 case among 68 children (1 out of 42 boys and 1 out of 189 girls) with TSA. According to DSM-5, patients with autism diagnosis, Asperger’s syndrome, pervasive developmental disorder will be factured in autistic spectrum disorders, and those with marked defi cits in social communication but whose symptoms do not meet the criteria of a diagnosis of autistic spectrum disorder autistic, will be assessed for a social communication disorder. Th e key points of DSM-5 changes: Uniting Disturbances in DSM IV TR – a single category of Autism Spectrum Disorder (ASD) / Autism Spectrum Disorder (TSA) Rett syndrome is removed from the TSA category Combines the areas of communication and social interaction (inseparable and considered as a single set of symptoms); Number of criteria for diagnosis (6/12 – 3/2); Early childhood; Includes diff erent levels of language; Symptoms: Appreciated as a continuum from mild to severe. Th ere is currently no treatment to heal autism, therapies reduce symptomatology and improve the quality of life. People with TSA and their families have the right to acces correct and complete information on existing therapeutic services. No treatment is eff ective for all children or for treating all the traits of the disorder. Th e programs – tailored to individual needs, fl exible and regularly re-evaluated to be improved.
Key words: TSA, DSM-5, diagnosis, therapy

In recent decades autistic spectrum disorders have become increasingly recognized as developmental disabilities, affecting thousands of children, adults and their families.
The evolution of the incidence and prevalence of autism is impressive. According to data provided by the US Disease Control Center in 2008, about one in 88 children was diagnosed with TSA – the fastest growing developmental disorder, three to four times more common in boys. According to January 2010, 1% (1 out of 110 children, of which 1 in 70 boys) has TSA. There has been an increase of 57% between 2002-2006 and 600% over the last 20 years, especially for TSA with a normal IQ.
Newer data provided on 27 March 2014 by the CDC (US Disease Control Center) on the prevalence of autism in the US indicates 1 case out of 68 children (1 out of 42 boys and one out of 189 girls) with TSA.
Some TSA data for the Transylvania area indicate that there were 43 cases admitted to TSA between 1986-1997, in one year – 2008, respectively – there were 408 admissions with the same disorder! Growth is real and may be due to the improvement of assessment scales, but also to environmental conditions, genetic mutations and epigenetics.
Historically, terminology has evolved in the following way:
– 1938-1943: Asperger syndrome / early childhood autism
– 1943-1968: child schizophrenia, borderline psychosis, symbiotic psychosis, infantile psychosis
– 1968: Rutter – four major diagnostic criteria (lack of social response, language impairment, bizarre motor behaviors, early onset)
– 1978: National Society for Children and Adults with Autism (Professional Advisory Board) – Autistic Syndrome
– 1980-1987: DSM-III / DSM-III-R Infantile Autism / Autistic Disorder (a group of early-onset disorders in childhood characterized by disruptions in social skills, cognition, and communication)
ICD-9-CM subtype of psychoses with specific origin in childhood
– 1983: Autistic Spectrum Disorders
– 1992/1994/2000: ICD 10 / DSM IV / DSM IVTR Pervasive Development Disorders [1]:
1) Autistic Disorder
2) Rett syndrome
3) Disintegrative disorder of childhood
4) Asperger Syndrome
5) Pervasive developmental disorder not otherwise specified / PDD-NOS (which includes atypical autism)
– The total number of diagnostic criteria has dropped from 16 to 12 and the minimum number of diagnostic criteria from 8 to 6 symptoms.
– 2005: Wing and Baron-Cohen Spectrum Autism Disorders (TSA)
– specific disorders of social development with a high heterogeneity of the clinical picture
– the concept of “autistic spectrum”
– autistic disorders would not qualitatively differ, but only quantitatively between them (depending on the degree of severity of the disorder)
– 2013: DSM-5 Autistic Spectrum Disorders: More Disorders or One with a Varying Spectrum of Variation [2]?
The diagnostic criteria offered by DSM-5 are persistent deficits in social communication and interaction, such as deficits in social-emotional reciprocity (abnormal social approach and inability to maintain proper conversation, reduced concerns for sharing interests, emotions or affection and failure to initiate or respond to social interactions); deficits in nonverbal communication (poorly integrated verbal and nonverbal communication, abnormalities in visual contact and body language, lack of understanding and use of gestures, lack of facial expressions and non-verbal communication); deficits in developing, maintaining and understanding reactions (difficulties in shaping behavior in different social contexts, difficulties in imaginative play and friendship, disinterest in relationships with other children).
They are also part of diagnostic criteria and repetitive patterns of behavior, interests, or activities, manifested by at least two of the following: stereotypes or rehearsals found in movements, use of objects or language (simple motor stereotypes, toy alignment or waving, echolalia and idiosyncratic phrases); adherence to routine or ritual patterns of verbal-nonverbal behavior (distress increased at small changes, difficulty in transition, rigid thinking patterns, greetings, the need to follow the same route, or to eat the same daily food); very restrictive interests that are abnormal in intensity or focus (increased attachment or concern to unusual objects); hyperactivity or hyporesponsiveness to sensory stimuli or unusual interests for the sensory aspects of the environment (apparent pain / temperature indifference, adverse response to specific sounds or textures, smell or excessive touch of objects, a visual fascination for light or movement).
All these symptoms must be present in the early development period, but they may not manifest until social requirements exceed limited capacities or may be masked by strategies learned later in life. They cause a significant deficit in daily social or occupational functioning and are not better explained by an intellectual disruption or a global delay in procurement. Intellectual disturbance and autistic spectrum disorders may coexist, and for their diagnosis, a lower level of social communication than that expected for a general level of development is needed.
According to DSM-5, patients with autism diagnosis, Asperger’s syndrome, pervasive developmental disorder will be factured in autistic spectrum disorders, and those with marked deficits in social communication but whose symptoms do not meet the criteria of a diagnosis of spectrum disorder autistic, will be assessed for a social communication disorder.
DSM-V-Key Changing Points:
z union of disorders in DSM IV TR – a single category of Autism Spectrum Disorder (ASD) / Autism Spectrum Disorders (TSA) z Rett’s syndrome is removed from the TSA category
z combines the fields of communication and social interaction (inseparable and considered as a single set of symptoms) z number of diagnostic criteria (6/12 – 3/2)
z early age: young childhood (early childhood)
z Includes different levels of language
z Symptoms: Appreciated as a continuum from mild to severe
z Increases the clarity and specificity of the diagnosis
z improve the stability of the diagnosis over time
Severity level 1
– No support
– Social communication: in the absence of support, deficits in social communication cause notable difficulties. It has difficulties in initiating social interactions and clearly presents atypical responses or failure to the social initiative of others. It may seem to have a low interest in social interactions. Restrictive attitudes and behavioral stereotypes: fixed concerns, fixed rituals and / or repetitive behaviors cause a significant impairment in one or more contexts. Resistance to attempts by others to interrupt repetitive behaviors, rituals, or distraction from fixed interests.
Level of severity 2
– Needs substantial support
– Social Communication: Significant deficits of verbal and non-verbal communication skills; social deficits are obvious, even if they receive support; limited initiation of social interactions and reduced or abnormal response to the social initiative of others
– Restrictive attitudes and behavioral stereotypes: concerns, fixed rituals and / or repetitive behaviors that occur frequently enough to be apparent to the ordinary observer and interfere with functioning in different contexts. Suffering or frustration is obvious when interrupting repetitive behaviors; difficult to distract from fixed interests.
Severity level 3
– It requires very substantial support
– Social communication: severe deficits of verbal and non-verbal communication skills that cause severe impairment of functioning; very limited initiation of social interactions and minimal response to the social initiative of others.
– Restrictive attitudes and behavioral stereotypes: concerns, fixed rituals and / or repetitive behaviors that interfere with marked functioning in all areas. Substantial suffering when rituals or routines are interrupted; very difficult to distract from fixed interests or quick return to them.
Neuropathology of Autistic Spectrum Disorders involves alterations in specific regions of the brain, as well as in connectivity patterns between many brain networks. Magnetic Resonance Imaging of Sleep Functional Connectivity detects spontaneous low frequency changes in neuronal activity that are synchronized between regions of the brain that belong to a functional network. Amygdala was frequently involved in the pathology of autistic spectrum disorders, volumetric studies showing that it is increased in volume in pre-school children diagnosed with TSA. Shen et al. (2016) shown that there is lower connectivity between tonsil and bilateral prefrontal cortex, temporal and striatal lobes, areas that are involved in social communication and repetitive behavior, as well as between the tonsil and temporal and frontal lobes involved in severity Autistic Spectrum Disorders. A weaker connectivity between the visual cortex and the sensory-motor regions was correlated with increased sensory hypersensitivity in the visual and auditory area.
D’Mello et al. (2015) has found that autistic spectrum disorders are associated with structural differences in the cerebellum, these differences being: increased functional relevance, so that the reduction of grey matter in discrete regions of the cerebellum was correlated with the severity of social behavior, communication and repetitive behavior scales used in the diagnosis of autism [3]. Epileptiform activity during sleep was also described in the absence of seizures in 43-68% of patients diagnosed with TSA. Top complexes differ in children diagnosed with TSA than those present in children with normal development. Chez et al. (2004) has demonstrated for the 12 children enrolled in the study that they exhibited peripheral or temporal, rare or occasional sleep-activated complexes or peaks, while their brethren, without TSA diagnosis, exhibited rolandal, benign epilepsy, or a generalized epileptic pattern on the EEG [4]. Autistic Spectrum Disorders may also be diagnosed at the age of two years, but the mean age of diagnosis is four years. There is evidence that parents may be concerned about the development of their child before the child has reached 12 months. There are many factors involved in the two-year difference between early symptoms and diagnosis: long-term assessments, cost of care, lack of service providers, lack of comfort of primary service providers in diagnostics, each requiring a different approach in narrowing this gap. It is necessary to identify early and to initiate specific therapy as quickly as there is evidence that the initiation of these therapies at the age of 18 months results in better long-term results.

The National Institute for Health and Clinical Excellence (NICE), September 2011 [5] Laboratory investigations
– Testing of fatty acids in the blood
– Urinary amino acids z IgG / E / A
– Extensive microbiological examination of faeces
– Testing intestinal permeability
– Hepatic functional profile z Serum homocysteine
– Urinary cryptopirals
– Serum test for Zn, Cu, Folic Acid, B12, B6, Mg
– Mineral hair analysis for nutrition and heavy metals tracking
– The activity of glutathione red cell peroxidase
– RAST test for IgG and IgA mediated food allergies
– Celiac serology
– Streptococcal serology for anti-streptococcal autoantibodies
Screening and early diagnosis  Between 2 and 3 years:
1) Communication:
– Inability to develop language, especially receptive;
– unusual use of language;
– low name response;
– bad non-verbal communication;
– can not show with his finger;
– does not smile socially to share joy;
– does not react to the smiles of others
2) Social Injury:
– limitations or lack of imitation of actions (e.g., applaud);
– does not show toys or other objects;
– is not interested in other children or has strange approaches to other children;
– does not recognize or has minimal reactions to emotions expressed by others;
– the game is a little varied, the limitation of imaginary roles, especially in terms of social imagination, is “in his world”
– Do not initiate games with others or participate in early social games; prefers solitary play activities Social Communication Questionnaire (SCQ) Modified Checklist for Autism in Toddlers (M-CHAT) Autism Behavior Checklist (ABC) Developmental Behavior Checklist – Early Screen (DBC) Autism Spectrum Screening Questionnaire (ASCQ) Absolute indicators to lead to specialized consultation:
– he does not babble, does not show with his finger or make any other gestures until 12 months;
– Does not speak a single word for up to 18 months;
– not spontaneous phrases in two words (which are not an echo) up to 24 months;
– Any loss of linguistic or social skills at any age

Differential diagnosis
It is the difference between autism and other psychiatric and developmental conditions that cause anomalies of language, play and social development, between pervasive developmental disorders (autism, Asperger’s Syndrome, Rett syndrome, childhood disintegration disorder), with other disorders: mental retardation, language acquisition, attention deficit hyperkinetic disorder, obsessive compulsive disorder, Tourette’s syndrome, schizophrenia, elective mutism, congenital hearing and vision abnormalities, LandauKleffner’s syndrome, tuberous sclerosis, fragile X syndrome, psychosocial deprivation
If there has been a period of at least 2 years in which development was normal, elective mutism, disintegrative childhood disorder and early onset schizophrenia should be considered. Comorbidities Approximately 40-80% of people diagnosed with TSA have low sleep quality, but the etiology of sleep disorders is unknown. Several theories suggest that sleep disorders are a direct result of autistic spectrum disorders or associated comorbidities, suggesting that the neurophysiology and neurochemistry underlying the individual may predispose them to chronic disturbances of nictemeral rhythm. Other studies have found variability in melatonin production, with some participants having normal melatonin profiles. It is important to know that melatonin abnormalities have been identified in other intellectual disabilities, raising the issue of non-specificity of TSA findings in melatonin production. At the same time, Krakowiak et al (2008), in the group of children with TSA, determined that cognitive and adaptive function did not predict the severity of sleep disturbances or sleep duration [6].
Malow et al. (2012) found that melatonin is useful in the treatment of sleeping insomnia in children diagnosed with TSA, responding at a dose of 1-3 mg of melatonin given 30 minutes before bed, having a favorable response in the first week of administration [7]. Rossignol and Frye (2011) in the meta-analysis carried out have found that melatonin improves sleep parameters and behavior throughout the day [8].
Poor sleeping leads to behavioral problems over the day, low tolerance to frustration, which can be manifested by self and heterogression. Soke et al (2016) reported a 27.7% prevalence of autoaggressive behavior in TSA-diagnosed children over a 3-year period [9]. This type of behavior is diverse, often repetitive and rhythmic, with no apparent intention of harming or resulting in physical damage. Self-aggressive behavior usually involves head injury, hair haemorrhaging, hand-bruising, and scratching. Children with TSA and autoaggressive behavior experienced developmental regression and cognitive and adaptive delay, so for them self-aggression behavior becomes a form of communication or a consequence of frustration due to inability to communicate.
Children’s distress and anxiety improve if the ability to communicate improves even slightly. Many children diagnosed with autism have a remarkable need for things to be done as they wish, often being valued due to lack of co-operation and oppositional behavior, and may have severe behavioral and emotional outcomes when things are not done as they wish. In addition to heterogeneity and self-aggression, they may also have other psychiatric comorbidities.
These include ADHD, attentional deficiency and hyperactivity being a common feature of children diagnosed with TSA (21 – 72%), the latter decreasing as the baby grows.
Obsessive Compulsive Disorder (OCD) can be a comorbid, Dr. Leo Kanner (1943), in the first case of autism described, notes that some repetitive elements have obsessive-compulsive quality. It is difficult to determine which of the repetitive thoughts and behaviors of children with TSA are similar to those in TOC, some of which are of undisturbed form and content from TOC.
Children diagnosed with autism have a variety of repetitive, stereotypical and vocalizing movements. These repetitive behaviors can be tics, intentional behavior that likes the child, motor stereotypes associated with expressing emotional states, rituals, myoclonus, dyskinesia or motor manifestations of partial seizures. Compared to stereotypes, tics tend to be sudden, fast and short-lived, of involuntary quality. Ticles interrupt language and behavior and are inappropriate for the child in the context in which they are.
Diarrheal disorders are often found in this category of patients, but tend to have a favorable progression with age. Some children prefer only one type of food, the food cooked in one way, or they eat until they vomit if an adult does not regulate the intake.
These children are often delayed using the toilet, Rutter et al. (1967) mentioning that 69.8% of 63 children aged over 4 years had enuresis and 58.7% had encopresis. These problems usually go away until puberty, but they can persist even in adult life in those with severe intellectual impairment. They may recur or worsen in stressful situations, convulsive disorders or in the event of a new psychiatric disorder, especially affective disorders.
7-84% of children have anxiety disorders, social anxiety, and panic disorder being the most rare. The most common are general anxiety disorder, simple phobias, separation anxiety, and agoraphobia. These occur in children undergoing a psychiatric consultation, adding a degree of significant impairment to those produced by the underlying symptoms of autistic spectrum disorders and are often the target of pharmacological treatment.
In addition to anxiety, they may also have a depressive disorder associated with the disorder, but the mood swings due to the latter are difficult to highlight by the basic features of the TSA child. This occurs frequently in those who are non-verbal or those with low IQ. The doctor’s experience in understanding autism and affective disorders is important, as are the observations of the parent or person who knows best the child.
z facilitating social development and language
z diminishing behavioral problems
z developing skills for independent functioning
z intervention at family level
z increasing the quality of child and family life

Counseling and psychotherapy
The most popular intervention programs:
ABA – Applied Behavioral Analysis;
TEACCH – Treatment and Education of Autistic and Communication Handicapped Children;
PECS – Picture Exchange Communication System; Social stories
Complementary: play therapy, music or art; hearing integration therapy; animal therapy; occupational therapy; language therapy and communication; behavior therapy with the inclusion of virtual reality techniques, computerized games or cartoons
Educational intervention
-secure appropriate services,
– trying to integrate into normal school curricula, with diverse, tailor-made, non-discriminatory and socially-oriented schooling options, especially for young children
– Providing short-term solutions (for children aged 3-5 years) with diminishing the long-term risk that accompanies their neglect
Pharmacological therapy
– there is no specific TSA medication, it is used only to control symptoms such as auto and heterogression, obsessions, stereotypes, hyperactivity, attention deficit, anxiety, depression
– correct assessment of symptoms (especially for institutionalized children), short time, reassessment of the need to continue
-FDA-approved medication for behavioral disorders: risperidone and aripiprazole
– selective serotonin reuptake inhibitors (sertraline, fluoxetine), other atypical antipsychotics, neuroleptics, timostabilizers, anxiolytics, ADHD-specific medication
Monitoring of pharmacological therapy
z ambulatory, community psychiatric services
z weight, height, BMI, waist circumference (baseline / monthly)
z pulse, TA (baseline / monthly)
z Involuntary Involuntary Movement AIMS Scale (baseline / monthly)
z Laboratory specimens: hemoleucogram, TS, TSH, FT3/4, TGO/TGP, glycemia, lipid profile, ex. urine summary, ex. toxicological (baseline / 3 months/ 1 year)
z prolactin (baseline)
z ECG (QT interval) (baseline / 1 year)
z EEG (baseline / 1 year)
z menstrual cycle (monthly)
Early intervention, a newly introduced concept, refers to a service plan in which the child is pursued from birth until reaching the age of about six years. There is a general agreement on the purpose of the intervention programs and their effectiveness: to be adapted to the child’s chronological age, level of development, family needs, talents and specific deficits. Improved assessment methods, the use of appropriate screening tools, broad availability of services, TSA specialists, schools offering tailor-made programs in less restrictive environments are also needed.
Key element – parent involvement in the therapeutic and educational process.
Characteristics of effective interventions:
– early specialized intervention;
– Implication of parents and carers;
– program focused on communication and language;
– program that involves social interactions and game skills;
– Access to academic curricula in a way that does not depend on social or communication skills;
– a proper management of behavior-the acquisition of positive and acceptable behaviors to obtain the same result.
There is currently no treatment to heal autism, therapies reduce symptomatology and improve the quality of life.
Persons with TSA and their families have the right to acces correct and complete information about existing therapeutic services.
No treatment is effective for all children or for treating all the traits of the disorder.
Programs – tailored to individual needs, flexible and regularly reassessed to be improved.
Many programs have important limitations and continue to evolve and change.

1. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision. Washington (DC). American Psychiatric Association, 2000.
2. Diagnostic and Statistical Manual of Mental Disorders, Washington DC (Fifth Edition). American Psychiatric Association, 2013.
3. D’Mello A.M, Crocettib D., Mostofsky S.H., Stoodley C.J (2015) Cerebellar gray matter and lobular volumes correlate with core autism symptoms, NeuroImage: Clinical 7 (2015) 631-639
4. Chez M.G., Buchanan T., Aimonovitch M., Mrazek S., Krasne V., Langburt W., Memon S. (2003) Frequency of EEG abnormalities in age-matched siblings of autistic children with abnormal sleep patterns. Epilepsy & Behavior 5 (2004) 159-162
6. Paul Ashwood, Paula Krakowiak, Irva Hertz-Picciotto, RobinHansen, Isaac N. Pessah, Judy Van de Water, Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders, Journal of Neuroimmunology, Volume 232, Issues 1–2, March 2011, Pages 196-199
7. Malow B.A., Adkins K.W, McGrew S.G., Wang L., Goldman S.E., Fawkes D., Burnette C. (2012) Melatonin for Sleep in Children with Autism: A Controlled Trial. Examining Dose, Tolerability, and Outcomes, Autism Dev Disord. 2012 August; 42 (8): 1729-1737.
8. Rossignol DA, et al., Melatonin in autism spectrum disorders: a systematic review and meta-analysis, Dev Med Child Neurol. 2011.
9. Soke GN, et al., Brief Report: Prevalence of Self-injurious Behaviors among Children with Autism Spectrum Disorder-A Population-Based Study., J Autism Dev Disord. 2016.