Autism Spectrum Disorder

Etiology

The cause is still not known. The onset is variable. The development is insidious without a clearly demarcated onset. Children that have an autism spectrum disorder have an increased risk of having epilepsy, however, a causal correlation has not yet been identified.

One subtype of ASD, Childhood disintegrative disorder, is associated with the following diseases, particularly if it is late-onset:

• Subacute sclerosing panencephalitis: A chronic infection of the brain by a form of the measles virus. This disease leads to the inflammation of the brain and the death of nerve cells.
• Tuberous sclerosis (TSC): A genetic disorder. Tumors formation in the brain, which is benign. It also affects other organs of the body like eyes, kidneys, heart, skin, and lungs.
• Leukodystrophy: In this condition, there is maldevelopment of the myelin sheath, causing white matter in the brain to disintegrate.
• Lipid storage diseases: Toxic accumulation of excessive fats (lipids) in the brain and nervous system

Epidemiology

According to some studies, ASD is becoming more prevalent. Whether this trend can be attributed to increased awareness, overdiagnosis, or overinclusive diagnostic criteria is yet to be identified. Its prevalence is reported to be 1 in 68. Childhood disintegrative disorder is a rare disease, with only 1.7 in 100,000 cases, and the prevalence of this disease is estimated to be 1 to 2 in 100,000.[2] Childhood disintegrative disorder is an uncommon disorder with a prevalence of 60 times less than that of autistic disorder.[3]

Pathophysiology

There is no clear-cut pathology of ASD however different populations have been suggested for different subtypes of ASD. For example, CDD occurs in children who have achieved normal developmental milestones, and this regression sometimes occurs very rapidly. This condition often develops abruptly and is most commonly seen in the fourth year of life, but there can be variation. Some consider it to be childhood dementia, indicating that the deposition of amyloid in the brain can be the possible cause of the disease, but this needs to be proven.[3][4]

History and Physical

The symptoms of ASD are usually identified by two years of age (specifically for CDD one-third of children experience regression of skills at the same time). Children with childhood disintegrative disorder generally have the worst outcome among individuals with ASD. Their cognitive and communication skills are affected. Most children with childhood disintegrative disorder experience a distinct prodrome characterized by bouts of anxiety and terror with no consistent medical, environmental, or psychosocial triggers.

A child affected with childhood disintegrative disorder shows normal development, and they normally develop age-appropriate verbal and nonverbal communication, as well as social relationships, motor, play, and self-care skills as compared to other same-aged children. However, by 2 to 10 years of age, they almost completely lose their acquired skills in 2 of the following 6 functional areas:

• Receptive language skills (comprehension of language: listening and understanding what is communicated)
• Expressive language skills (being able to produce speech and communicate a message)
• Social skills and self-care skills
• Bowel and bladder control
• Motor skills
• Play skills

Impairment of function also occurs in social interactions and communications.

The 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) Criteria for Childhood Disintegrative Disorder Diagnosis (WHO)

• Normal development up to the age of at least two years; the presence of normal age-appropriate milestones are achieved in the areas of communication, social relationships, play, and adaptive behavior at age two years or later are required for this diagnosis.
• A definite loss of previously acquired skills at the onset of the disorder. The diagnosis requires a clinically significant loss of skills (and not just a failure to use them in certain situations) in at least 2 of the following areas:
  • Expressive or receptive language
  • Play
  • Social skills or adaptive behavior
  • Bowel or bladder control
  • Motor skills
• Qualitatively abnormal social functioning, manifests in at least 2 of the following areas:
  • Qualitative abnormalities in reciprocal social interaction (of the type defined for autism)
  • Qualitative abnormalities in communication (of the type defined for autism)
  • Restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, including motor stereotypies and mannerisms
  • General loss of interest in objects and the environment
• The disorder is not attributable to the other varieties of pervasive developmental disorder acquired aphasia with epilepsy, elective mutism, schizophrenia, and Rett syndrome.

Evaluation

Children diagnosed with childhood disintegrative disorder rarely reveal an underlying neurological or medical cause. Complete medical and neurological examinations are done, and tests to exclude reversible  causes of the condition:

• Complete blood count
• Urea and electrolytes/glucose
• Liver function test
• Thyroid function test
• Heavy metal levels
• HIV testing
• Urine screening for aminoaciduria
• Neuroimaging studies (MRI or CT scan)
• Electroencephalogram (EEG)

These tests are usually done during the initial assessment in secondary care. Electroencephalogram (EEG) and neuroimaging studies are done to exclude the alternative diagnosis.

DSM V Criteria

1. Deficits in social interaction and communication
2. Restricted interests, repetitive behavior, and activities
3. These symptoms impair everyday functioning

Treatment / Management

Treatment for childhood disintegrative disorder is similar to the treatment of autism. The stress falls on early and excessive educational interventions. Most of the treatment plan is behavior-based and highly structured. Family counseling, including educating the parents so that they can follow the child's treatments at home, is usually part of the overall treatment plan. Therapies in the areas of language, speech, social skills development, occupational, and sensory integration may all be used according to the needs of the individual child. Loss of language, skills related to social interaction, and self-care are delirious, and the affected children face ongoing problems in certain areas and require long-term care. Treatment of childhood disintegrative disorder requires behavior therapy, environmental therapy, and medications.

Behavior Therapy

The applied behavioral analysis mainly focuses on methodically training the patient to re-learn self-care, language, and social skills. These treatment programs are designed in such a way that they use a reward system to reinforce acceptable behaviors and discourage trouble behavior. These programs are usually devised by certified professionals in behavior analysis, which is then can be used by other healthcare personnel. People from different domains like speech therapists, physical therapists, psychologists, and occupational therapists with differing levels of competence can benefit from this. Teachers, parents, and caretakers are advised to use these behavior models at all times.

Environmental Therapy

In the form of sensory enrichment applies augmentation of the sensory experience to improve symptoms in autism, many of which are also present in childhood disintegrative disorder.

Medications

Medications are used to treat the symptoms as they develop during the disease as there is no drug available to cure this disease directly. Antipsychotic medications are used for repetitive behavior patterns and aggression. To control problematic behavior, particularly aggression, experts use selective serotonin reuptake inhibitors (SSRIs), stimulants, and other antipsychotics. There is a significant risk of neuroleptic malignant syndrome with the use of neuroleptic medication. If seizures develop, anticonvulsants are used.

Differential Diagnosis

The differential diagnosis includes any of the other pervasive developmental disorders or causes of learning disability. Other specific diseases that need to be excluded are:

• Heavy metal poisoning (mercury and lead)
• Aminoacidurias
• Hypothyroidism
• Brain tumor
• Organophosphate exposure
• Seizure disorder (atypical)
• HIV infection
• Childhood schizophrenia
• Other rare  conditions (glycogen storage disorders)
• Subacute sclerosing panencephalitis
• Tuberous sclerosis
• Creutz-Jacob disease/new variant CJD

Prognosis

The prognosis of CDD is very poor, and the outcome is worse as compared with other subtypes of ASD. Once skills are lost, they usually do not return to normal. Only about 20% of children diagnosed with CDD can speak in sentences again. As adults, most patients with CDD remain dependent on full-time caregivers or are institutionalized. Around ten years of age, most of the skills are lost. There can be some but very restricted improvement seen in a few of the cases. Over the longitudinal course of the disease, children develop lifelong impairments of behavioral and intellectual functioning. The intellectual function, independence, and adaptive/adjusting skills are extremely affected, with most cases deteriorating to serious mental disability. Kids with this disease are dependent on caregivers for their entire life.[4]

Complications

Epilepsy commonly develops with the risk of seizures that increases throughout childhood with the highest seizure diathesis occurring during adolescence. SSRIs and neuroleptics can also the seizure threshold and thus must be used with caution. It has been previously reported that the life expectancy is normal, but mainly due to complications of epilepsy, the mortality of people with autistic spectrum disorders is two times that of the general population.