Childhood Disintegrative Disorder

Updated: Nov 20, 2018
Author: Bettina E Bernstein, DO; Chief Editor: Caroly Pataki, MD 

Overview

Background

Childhood disintegrative (or disintegration) disorder, also known as Heller syndrome, and now subsumed under the Autism Spectrum Disorders (ASDs) category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5), is characterized by a loss of previously acquired language and social skills and results in a persistent delay in these areas. For example, a child previously able to speak in 2- or 3-word phrases gradually or abruptly loses the ability to communicate using words or can use only fragments.

Social and emotional development also regress, resulting in an impaired ability to relate with others. For example, a child who was previously able to accept reassurance from his or her parent (eg, a hug) loses the ability to be consoled and may even withdraw from human (tactile) contact.

The disorder may be associated with lysosomal storage disorders such as late-onset Tay-Sachs disease(LOTS). A case report of a patient with symptoms of childhood disintegrative disorder at age 4 years determined that the patient had a sialylation deficiency and an increase of asialo-core fucosylated bisected N-glycans, aberrant N-glycan structures of CSF even though there were no changes of total plasma N-glycan strucutres of CSF proteins.[1]

Additional symptoms of childhood disintegrative disorder may include the onset of difficulty in the transition to waking from sleep. Social interactions become compromised (as manifested by aggressiveness, tantrums, or withdrawal from peers), as does motor function, resulting in poor coordination and possible awkwardness of gait.[2]

Overall, the social, communicative, and behavioral features of childhood disintegrative disorder resemble those of autistic disorder. Affected children have distinct qualitative impairments in social interaction and communication. In addition, restricted, repetitive, or stereotyped patterns of behavior, interests, and activities occur. Previously acquired motor skills are lost (eg, a child who was toilet-trained begins to soil during the day and night, or a child who was able to pedal a tricycle or draw shapes can no longer do so). Family home movies can be very helpful in early identification of ASDs.[3]

Illustrative case

A 3-year-old boy is referred for evaluation because his behavior has recently gotten him “expelled” from daycare. He screams, throws tantrums, and no longer accepts hugs from his daycare teacher, with whom he was previously familiar. He has lately become destructive to his toys and does not use them to interact with his peers. His parents report that he was doing “okay” up until the past 3 months. They do not report that he had had any language delays.

Pathophysiology

It was long held, erroneously, that “refrigerator mothers” (a term coined on the basis of the presumed emotional frigidity of such mothers toward their children) caused ASDs in their children. This flawed theory has caused unnecessary psychological pain in countless families. However, current research has yet to reveal a clear-cut pathophysiology for childhood disintegrative disorder, and there remains considerable debate within the developmental disabilities field regarding the long-term outcomes of children with this condition.

Some researchers hypothesize that genetic predispositions combined with environmental stressors (eg, virus exposure or birth trauma) result in brain deposition of amyloid and disruption of synaptic transmissions, possibly involving interleukin-1 (IL-1) or beta-endorphins. Provision of enriched environmental experiences during critical periods of development may restore brain plasticity and thus mitigate genetic predispositions. However, earlier disruption of psychosocial development can result in even more severe developmental consequences.

Several researchers have theorized that altered or inappropriate immune responses, potentially involving abnormal B-cell activation and neuronal function, may play a role in the pathophysiology. In this regard, some studies have found that lithium and hyperbaric oxygen[4] reduce oxidative stress and may increase blood flow to the brain, lending some support to the idea that a possible endophenotype leads to oxidative stress and neuronal injury.[5, 6, 7, 8] A much smaller subset of children with ASD who show onset of symptoms or behavioral deterioration after viral or infectious insults may have this response due to a specific polysaccharide antibody deficiency (SPAD) that may respond to treatment with IV immunoglobulin.[9]

Autoantibodies to myelin basic protein (MBP) in children with childhood disintegrative disorder appear to differ from those in children with nonregressive forms of autism; however, this finding has not yet been shown to correlate with disease severity or prognosis.[6]

No gene has yet been isolated as the cause of childhood disintegrative disorder; however, a gene that codes for elongator protein complex 4 (ELP4) has been identified on human chromosome 11 and appears to be associated with centrotemporal spikes (CTS), the electroencephalographic (EEG) feature typical of rolandic epilepsy (RE).

ELP4 is one component of the elongator complex, a group of 6 genes that function in transcription and modification of transfer RNA (including regulating the actin cytoskeleton, cell motility, and migration) and that seem to play a critical role in influencing genes important to neuronal migration, axon growth, motility of growth cones, and related activities.[10]

ELP4 may also play a critical role in the transcription and modification of transfer RNA. Interference with necessary migration, synaptogenesis, and division in the central nervous system (CNS) before adolescence may result from disruption of transcriptional regulatory and translational modification roles and may render dendrites unable to make the proper neuronal connections.[11]

ASDs, including PDD, are generally associated with an increased incidence of seizures. Other idiopathic focal epilepsies occur during sleep. In addition, other epilepsy syndromes are associated with impaired frontal lobe and language function, potentially leading to continuous epileptiform discharges during sleep.[12]

Etiology

No single causative factor for childhood disintegrative disorder (CDD) has been identified. Research suggests that a combination of genetic susceptibility, including possibly abnormal autoimmunity, and prenatal (or environmental) stress may explain the pathophysiologic findings of higher-than-expected brain deposition of amyloid and disruption of synaptic transmission.

As the child experiences developmental departure from normality, the diminished preferential attention to the eyes of others has cascading detrimental effects, decreasing further socialization. The child’s attention focuses on aspects (eg, point sounds, lights, and lip motions), leading to further impairment of appropriate social interaction (mediated by eye contact and facial expression).[13]

A study of 17 children with CDD compared them to children with low-functioning ASD, high-functioning ASD, and typically developing children and found that genetic changes found by whole exome sequencing, copy number variant, and gene expression analysis showed genetic differences were more highly expressed in non-neocortical regions; the thalamus, cerebellum, caudate, and hippocampus were abnormally hyperactive in those regions.[14]

Mutations in postsynaptic density genes are associated with higher likelihood of the development of regression and hence for CDD.[15]

Environmental risk factors for CDD include the following:

  • Viral exposure (and possibly bacterial infectious exposure for some vulnerable children; however, the more common pathway is usually intrauterine transmission) -Toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex (TORCH)

  • Birth trauma

  • Toxin exposure

  • Prematurity

  • Teratogenicity

  • Association of increased risk of ASD with in utero exposure to antiepileptic drugs: Meador and Loring in a recent review found up to an 8-fold increased risk of ASD associated with in utero exposure to valproate such that the American Association of Neurology has recommended avoidance of valproate during pregnancy whenever possible

Research directions include the possible association of ophthalmologic malformations with ASDs resulting from the teratogenicity of thalidomide and misoprostol.[16]

Genetic factors include the following:

  • Possible susceptibility to chromosomal breakage or disruption

  • Family history of autism or Asperger disorder

  • Family history of RE, with or without CTS – RE commonly affects prepubescent children aged 3–12 years, occurring in about 1 per 500 children (60% of whom are boys); seizures in RE typically begin as groaning noises (in the larynx) that interfere with speech and then may present as sensorimotor activity; seizures in benign RE (BRE) occur at night and during sleep, possibly because sleep is associated with a lowered seizure threshold[17, 18]

  • CTS are also associated with attention deficit/hyperactivity disorder (ADHD), speech disorders, and developmental coordination disorder; in many cases, CTS due to RE are missed because the child’s history of falls can be mistakenly attributed to poor coordination[18]

  • A specific polysaccharide antibody deficiency (SPAD)[9]

Disorders associated with childhood disintegrative disorder include the following:

  • Autoimmune disorders[19]

  • Allergies (eg, food sensitivity reactions) and gastrointestinal (GI) disorders, which may show differences in GI bacterial composition in individuals with autism (Recent work on the microbiology of autism subjects’ stool specimens show that the presence of Desulfovibrio species and the impact of penicillins and cephalosporins, including clindamycin, can predispose to the overgrowth of Clostridium difficile. This may eventually lead to a role of probiotics for those individuals with prominent GI symptoms.[20, 21] and which may include asthma[22]

  • Insomnia[23]

  • Vitamin B-12 deficiency[24]

  • Hyperhomocysteinemia[24]

  • Anti-NMDA–receptor encephalitis[25, 26]

  • Post-viral infection — a case report of CDD onset after chicken pox[27]

Epidemiology

In the United States, childhood disintegrative disorder (CDD) is very rare (affecting 2 per 100,000 children), much rarer than autistic disorder, which affects 20 per 10,000 children), or pervasive developmental disorder not otherwise specified (PDD-NOS), which occurs in 30 per 10,000 children.[5]  No current studies are large enough to determine the international frequency of CDD.

CDD occurs only after a period of at least 2 years of normal development, when the child is younger than 10 years.[28, 5] Onset generally occurs in children aged 3–4 years and may be insidious or abrupt. The average age at diagnosis is 3.9 years, comparable to that of autistic disorder (average age, 3.1 years; range, 4.1–5.5 years in some studies).[5]

CDD is slightly more common in males than in females.[5] No studies have shown the disorder to be any more or less common in any particular race or culture.

Prognosis

The prognosis of childhood disintegrative disorder (CDD) has been considered guarded; because the disorder is so rare, more data are needed.[2] Children with moderate-to-severe intellectual disability or lack of communicative language have a worse prognosis than those with usual intelligence and communicative language.[2, 29] The disorder is lifelong, and the social, communicative, and behavioral difficulties tend to impair function throughout life.[2, 30]

No mortality or morbidity is directly attributable to CDD. Indirectly, a comorbid medical condition, such as a neurodegenerative disorder, may increase the risk of mortality and morbidity. The clinician should be alert to the possibility of Landau-Kleffner syndrome (LKS).[31, 32]

LKS is a rare condition of unknown etiology that is more common in boys. LKS generally presents with more severe language impairment and later than childhood disintegrative disorder; LKS has a mean age of onset of 5.5 years. Excluding this syndrome is important because it is generally associated with seizure disorder and may respond to treatment with anticonvulsants such as valproic acid or steroids.[31, 32]

The risk of seizures increases with age and peaks at adolescence. Concomitant administration of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and low-dose high-potency neuroleptics such as haloperidol tends to lower the seizure threshold (as does alcohol), which may increase the likelihood of seizures.[33]

 

Presentation

History

Obtain a thorough history. If the family has home movies, this may help with early identification of a departure from normal development.[3]

Children with childhood disintegrative disorder (CDD) are developmentally normal before the age of onset. In this respect, they are similar to patients with Landau-Kleffner syndrome (LKS); however, the onset of LKS tends to be later (eg, age 5.5 years), whereas the onset of CDD usually occurs by age 3–4 years.[28] Developmental delays in language, social, emotional, cognitive, or motor areas may not have been previously apparent to either the parent or pediatrician.

Impaired social sensitivity and affect regulation (eg, inability to modulate anger and anxiety, resulting in rage and anxiety attacks) can occur with or without cognitive distortions (eg, vivid grandiose fantasies or idiosyncratic logic) and can result in cascading effects that further decrease adequate socialization and diminish the preferential attention to the eyes of other human beings that is necessary for adequate social interaction.[12, 2]

Children diagnosed with CDD tend to have more long-lasting abnormalities of auditory responsiveness and verbal communication than children with pervasive developmental disorder (PDD), but the abnormalities are not as severe as those in children with LKS. Although hyperlexia may be a feature of CDD it is not as likely as in LKS.[12, 34]

Physical Examination

Perform a thorough physical examination. Occasionally after diagnosis, mild neurologic abnormalities (eg, mild macrocephaly, microcephaly, motor incoordination, and impaired sleep-wake cycles) are detected on neurologic examination, necessitating a high index of suspicion for a seizure disorder.

No specific physical abnormalities are diagnostic of this disorder; however, some affected children may have a history of increased ear infections, reflecting possible decreased autoimmunity.[35, 19]

Special Concerns

Failure to document language and developmental dysfunction in the child with head trauma at the time of presentation is a medicolegal pitfall. For example, a 3-year-old child with a history of normal development may exhibit a regression of language usage and development after a documented head injury. Because it may be difficult to ascertain whether a loss of language and subsequent poor language development is directly related to the trauma, it is important to document the child’s condition at the time of presentation.

Such documentation may include a comprehensive neurologic examination, along with imaging studies. Through appropriate evaluation of the child’s current condition, potential sequelae (eg, seizures) can be excluded or diagnosed right after the trauma occurred. Documenting a reasonable cause for language dysfunction protects against potential liability.

Another potential medicolegal pitfall is failure to notify Child Protective Services (CPS) regarding suspected abuse or other safety issues affecting the presenting child. For example, a child may present with a history of regression in social relatedness that occurs simultaneously with possible physical abuse by a parent.

In such cases, the physician is legally required to involve the local CPS so that the agency can investigate the suspicion of abuse and make a judgment regarding the child’s safety. If this report is not made, the physician may be criminally liable. Therefore, it is important to call CPS regardless of whether the possible abuse is a likely cause of the child’s problems with social relatedness.

There have been case reports of a seasonal pattern to the speech loss (mutism).[36]

 

DDx

Diagnostic Considerations

In addition to the differential diagnosis (see below), other problems to be considered include the following:

  • Intellectual disability (idiopathic or due to a known cause, such as lead poisoning, aminoacidopathy, iodine deficiency, or hypothyroidism)

  • Brain tumor

  • Heavy metal intoxication

  • Insecticide overdose

  • Long-chain or medium-chain fatty acidopathy

  • Neurodegenerative disorders

  • Psychoactive substance poisoning

  • Seizure disorder

  • Unusual presentation of neurologic manifestation of

  • HIV/AIDS, Landau-Kleffner syndrome (LKS), or adrenoleukodystrophy

  • Rett syndrome

  • Schilder syndrome or other progressive central nervous system (CNS) storage or metabolic disorders

  • Aminoacidurias

  • MECP2 gene mutations

  • Semantic pragmatic syndrome

  • Multidimensional impairment

  • Hydrocephaly

  • Pathologic demand avoidance (PDA) syndrome

  • Nonverbal learning disorder

  • Teratogenicity[16]

  • Catatonia: In situations in which symptoms of catatonia are present (silence [mutism], tenseness and rigidity [holds back acts that are compelled by memories], refusal to obey commands, and displacing rising emotions and tension into motor acts that shut out reality [posturing, grimacing, staring, stereotypes]) and that appear to worsen or not respond to other medications, treatment with benzodiazepines should be considered. If a positive response occurs, the diagnosis of catatonia should be included in the differential diagnosis, especially because a state of extreme excitement can cause potentially fatal medical illness such as pneumonia, blood clotting problems (thrombosis), malnutrition or dehydration, concussion (due to head banging), or other cutaneous infection due to self-injurious behaviors while catatonic.[37]

Differential Diagnoses

 

Workup

Laboratory Studies

The following laboratory studies should be ordered:

  • Complete blood count (CBC)

  • Thyroid function testing – Triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH)

  • Glucose testing – Hemoglobin A1c (HbA1c), fasting glucose, and 2-hour postprandial glucose

  • Liver function tests – Gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)

  • Kidney function tests – Blood urea nitrogen (BUN) and serum or 24-hour creatinine

  • Heavy metal screening – Mercury and arsenic

  • HIV test

  • Urine for aminoacidopathy screening

Chromosome analysis may be done to exclude coexisting genetic syndromes.

Psychological, Occupational, and Educational Tests

Psychological tests that may be performed include the following:

  • Children’s Autism Rating Scale (CARS) – This test yields information on the probability that the child’s behavior pattern resembles that of children of commensurate developmental age who are autisticlike

  • Kaufman Assessment Battery for Children (KABC) – This test yields information on mental processing, sequential processing, and an intelligence quotient (IQ) equivalent composite score

  • Vineland Adaptive Behavior Scale – This test yields information regarding the child’s level of adaptive functioning; it has limitations, including the variable reliability of the informants (eg, parents and caregivers)

  • PDD Behavior Inventory – This assessment is a rating scale for evaluating the response to intervention in children with pervasive development disorder (PDD)[38]

  • Intelligence scales – These measures are not specifically helpful for diagnosing childhood disintegrative disorder but can be used to exclude other diagnoses

Occupational therapy evaluation may be helpful for determination of the presence of tactile sensitivity (eg, intolerance of hugs or discomfort with sensory input on skin) and for assessment of motor delays. A Grandin hug box is used by some occupational therapists.

Educational and achievement testing should be done to determine the patient’s academic level and appropriate educational setting. Such testing should include language testing and consideration of a nonverbal learning disability if the verbal intellectual capacity is much higher than shown by performance testing, especially in the setting of impaired gesture communication, decreased visual contact, abnormal facial expression, and prosody.[35]

MRI, PET, and CT

Magnetic resonance imaging (MRI), positron emission tomography (PET), or computed tomography (CT) may be used to exclude brain tumors or obstructive abnormalities in the brain parenchyma. Researchers have found functional MRIs to be helpful in localizing the areas of the brain experiencing audiovisual asynchrony.[12]

Avoid performing tests that may expose the developing brain to radiation or radioactive compounds if other tests (eg, neuropsychological tests) are available that can be diagnostically useful without imposing a risk of harm. The dye used for MRI and CT scanning also has the potential to impair kidney function.

Other Tests

Careful screening of the cranial nerves and a funduscopic examination are warranted.

Electroencephalography (EEG) may be performed as part of the neurologic workup to exclude seizure disorders such as Landau-Kleffner syndrome (LKS). Obtain both sleep (with nasopharyngeal leads) and awake EEGs. To exclude seizure disorder, a 24-hour EEG is the most sensitive test.

 

Treatment

Approach Considerations

The principles of therapy for childhood disintegrative disordere (CDD) are generally supportive in nature but do include specific behavioral interventions designed to halt behavioral deterioration and to improve communication, self-help, and social skills, thereby stabilizing the child’s reality testing scores and global functional level.[2]

No known medications address the core processes of CDD. No specific medications treat this disorder; generally, medications only address specific symptoms. Only haloperidol and risperidone have been approved by the US Food and Drug Administration (FDA) to treat autism in children. Children who present with markedly impaired attention may improve with very low-dose (and carefully monitored) treatment with stimulants or nonstimulants (eg, atomoxetine).

Generally, inpatient care is unnecessary for childhood disintegrative disorder in the absence of the following:

  • An associated medical condition (eg, seizures, head injury)

  • A severe psychiatric problem (eg, behavioral disturbances that warrant closer observation, supervision, and/or stabilization)

  • Neuroleptic malignant syndrome (NMS)

  • Alteration of electrolytes levels (such as hyponatremia related to treatment with selective serotonin reuptake inhibitors [SSRIs] or atypical antipsychotics), which may necessitate intravenous (IV) therapy

Pharmacologic Therapy

Medications in various classes, including atypical antipsychotics, stimulants, SSRIs, and nonselective serotonin reuptake inhibitors (NSRIs), have been used to treat a wide range of behavioral and mood problems that may occur in children with childhood disintegrative disorder (CDD).

Haloperidol and risperidone are the only medications that have been approved by the FDA for the treatment of irritability associated with childhood autism.[13, 29, 39, 40] These medications can be useful in treating associated symptoms of irritability, aggression, and hyperactivity. Citalopram has not been proved effective, and fluoxetine often causes undesirable gastrointestinal (GI) side effects in this population.[13, 29, 39, 40, 41]

Children who present with markedly impaired attention may improve when treated with very low doses of stimulants or nonstimulants (eg, methylphenidate or atomoxetine), and they should show signs of improvement within 4 weeks if these agents are tolerated and effective.[13, 42]

The dosages are much lower than those usually employed to treat attention deficit/hyperactivity disorder (ADHD), and close monitoring is required. During pharmacotherapy, the clinician must be vigilant for signs of adverse reactions, including insomnia, crying spells, anorexia, weight loss, and frank or worsening psychosis.[43]

If neuroleptic medications are used (eg, risperidone, haloperidol, or molindone), neuroleptic malignant syndrome (NMS) is a significant risk. NMS is a potentially irreversible and life-threatening syndrome that manifests with fever, rigidity, rhabdomyolysis, altered mental status, and lethargy. Laboratory studies used to diagnose NMS include creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, blood urea nitrogen (BUN), and creatinine levels.

If NMS is left untreated, it may progress to coma and respiratory depression. Appropriate treatment includes immediate cessation of the neuroleptic medication and immediate consultation with an anesthetist for respiratory support and possible treatment with dantrolene.[44, 45, 46, 47, 48, 49, 50]

Antipsychotic agents are also associated with a potential risk of QTc prolongation.

If seizure control is an issue and valproic acid or valproate is used along with an atypical antipsychotics (especially risperidone), the patient should be closely monitored for abnormal levels of ammonia, which are generally accompanied by alterations in mental status (often nonspecific slowing) and abnormalities of liver function.[51, 44, 48, 49, 50]

If an atypical antipsychotics (eg, risperidone, quetiapine, ziprasidone, or aripiprazole) is being given, ongoing monitoring should include screening for metabolic syndrome, new-onset diabetes, or diabetic ketoacidosis, both through physical examination (including waist circumference, blood pressure, and proportion of weight to height) and through laboratory studies (eg, serum glucose and, when indicated, hemoglobin A1c [HbA1c]).[13, 29]

Many children and (in particular) adolescents with childhood disintegrative disorder have difficulty maintaining a regular sleep-wake cycle. This chronic poor sleep may exacerbate aggressive behavior problems, especially intermittent assaultive behaviors in preteens and adolescents. Some individuals experience improvement in their sleep cycle with a short trial of a melatonin agonist such as agomelatine, provided that there is no contraindication (eg, seizures).[23, 29]

Some investigators have found memantine to be useful in childhood disintegrative disorder, but more studies, especially randomized placebo-controlled trials, are needed for confirmation.[13, 52]

Some children with childhood disintegrative disorder who were treated with corticosteroids have shown improvements in motor, language, and behavioral regression.[31]

More randomized placebo-controlled trials are needed to determine if other medications, such as antiepileptic mood stabilizers, are helpful in the management of childhood disintegrative disorder.[53]

Benzodiazepines (eg, diazepam, lorazapam, midazolam, clonazepam) are an alternative choice, but generally are not the first choice, owing to their addictive potential and the fact that they decrease alertness and impair attention, which couldd potentially interfere with a child’s ability to learn in school. However, for children with acutely disturbed behavior and psychotic symptoms, these medications should be considered for short-term use or to decrease the antipsychotic dose when used in combination. They do not cause malignant neuroleptic or metabolic syndrome or prolongation of the QT interval, which can occur with antipsychotics (eg, haloperidol) or atypical antipsychotics.[54]

In situations in which symptoms of catatonia are present (silence [mutism], tenseness and rigidity [holds back acts that are compelled by memories], refusal to obey commands, and displacing rising emotions and tension into motor acts that shut out reality [posturing, grimacing, staring, stereotypes]) and that appear to worsen or not respond to other medications, treatment with benzodiazepines should be considered. If a positive response occurs, the diagnosis of catatonia should be included in the differential diagnosis, especially because a state of extreme excitement can cause potentially fatal medical illness such as pneumonia, blood clotting problems (thrombosis), malnutrition or dehydration, concussion (due to head banging), or other cutaneous infection due to self-injurious behaviors while catatonic.[37]

Novel Therapies

Additional randomized placebo-controlled trials are necessary to determine whether novel interventions such as hyperbaric oxygen therapy are safe and effective in patients with childhood disintegrative disorder.[4] Other novel treatments, such as secretin, initially seemed to show promise but have not been proven to improve behavioral symptoms.[55]

Although several more novel treatments (eg, cranial manipulation, vitamin B-6 therapy, magnesium therapy, and dimethylglycine therapy) have been used in attempts to “quiet” the brain, there are no data supporting their efficacy in childhood disintegrative disorder or pervasive developmental disorder (PDD). In addition, they all involve some risk of harm (eg, fracture, subluxation, dislocation, or metabolic toxicity). Consequently, they are not recommended at present.[56, 57]

Diet and Activity

No special diet is known to improve the clinical course or prognosis of childhood disintegrative disorder.[58] Salicylate-free diets (ie, Feingold diets), diets low in yeast, and diets high in certain megavitamins or minerals (eg, zinc, magnesium, vitamin B-6, vitamin B-12, fatty acids) have not resulted in measurable and predictable improvements; however, some anecdotal reports have shown limited responses in individual cases.

If a parent wishes to try a special diet, it is advisable to obtain a nutrition consultation before and after the special diet is tried so that any undesirable diet-induced vitamin, mineral, or calorie changes can be prevented or reversed. Particular attention should be paid to ensuring adequate (but not excessive) caloric intake so as to prevent growth retardation.

No specific activity limitations are necessary unless the degree of motor deterioration is sufficient to suggest that activity restriction is warranted. This decision must be made on a case-by-case basis.

Consultations

A neurologic consultation should be obtained to exclude neurologic conditions, which, if present, may be reversible.[33] The neurology consult should include awake and sleep electroencephalography (EEG), magnetic resonance imaging (MRI), or positron emission tomography (PET). (See Workup.)

A child psychiatrist or a behavioral/developmental pediatrician should be consulted in conjunction with the pediatrician, family, or caregivers to assist with appropriate educational placement, therapeutic interventions, psychopharmacologic interventions, and psychotherapeutic interventions. Consider specific family support therapy for each individual with childhood disintegrative disorder.

Consultation with a speech pathologist should be sought, especially if language delay is significant (delay of 25% or more).

Collaboration of the primary clinician with an early childhood intervention specialist may facilitate appropriate educational placement.

 

Medication

Medication Summary

Medications in various classes, including atypical antipsychotics, stimulants, and anticonvulsants, have been used to treat a wide range of behavioral and mood problems that may occur in children with childhood disintegrative disorder.

Antipsychotics, Other

Class Summary

Risperidone and haloperidol have been approved by the US Food and Drug Administration for irritability associated with autistic disorders. If neuroleptic medications are used, neuroleptic malignant syndrome (NMS) is a significant risk. Patients should be monitored for NMS symptoms.

Monitoring for atypical antipsychotics should also include screening for metabolic syndrome, new-onset diabetes, or diabetic ketoacidosis, both through physical examination (including waist circumference, blood pressure, and proportion of weight to height) and through laboratory studies (eg, serum glucose and, when indicated, hemoglobin A1c [HbA1c]).

Risperidone (Risperdal, Risperdal M-Tab)

Risperidone is an atypical antipsychotic agent indicated for irritability associated with autistic disorder in children and adolescents aged 5-16 years. Risperidone binds to dopamine D1-receptor and has 20 times lower affinity than typical antipsychotics for the 5-HT2-receptor. Risperidone improves negative symptoms of psychoses. The incidence of extrapyramidal adverse effects is lower with risperidone than with conventional antipsychotics.

Haloperidol (Haldol)

Haloperidol blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain. It also decreases hypothalamic and hypophyseal hormones.

Aripiprazole (Abilify)

Aripiprazole is hypothesized to work differently from other antipsychotics; it is thought to be a partial dopamine (D2) and serotonin (5HT1A) agonist that antagonizes serotonin (5HT2A). Aripiprazole is available as a tablet, oral disintegrating tablet, oral solution, or intramuscular injection. Injection is indicated for agitation associated with schizophrenia or bipolar disorder, manic or mixed.

Quetiapine (Seroquel)

Quetiapine is a newer antipsychotic drug used for long-term management of schizophrenia and is indicated in adults for schizophrenia, depressive episodes associated with bipolar disorder, and acute manic episodes associated with bipolar I disorder as either monotherapy or adjunctive therapy to lithium or divalproex. This agent is available in tablet form and may act by antagonizing dopamine and serotonin effects. Quetiapine's improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.

Ziprasidone (Geodon)

Ziprasidone intramuscular (IM) injection is indicated for acute agitation in patients with schizophrenia in whom treatment with ziprasidone is appropriate and who need IM antipsychotic medication for rapid control of the agitation.

This agent antagonizes dopamine D2, D3, 5HT2A, 5HT2C, 5HT1A, 5HT1D, is alpha1-adrenergic, and has a moderate antagonistic effect for histamine H1. Ziprasidone moderately inhibits reuptake of serotonin and norepinephrine. This drug is available as a tablet and IM injection.

Stimulants

Class Summary

Children who present with markedly impaired attention may improve when treated with very low doses of stimulants or nonstimulants (eg, methylphenidate, atomoxetine), and they should show signs of improvement within 4 weeks if these agents are tolerated and effective. The dosages are much lower than those usually used to treat attention-deficit/hyperactivity disorder (ADHD). During pharmacotherapy, the clinician must monitor and be vigilant for signs of adverse reactions, including insomnia, crying spells, anorexia, weight loss, and frank or worsening psychosis.

Methylphenidate (Ritalin, Daytrana, Methylin, Concerta)

Atomoxetine (Strattera)

Atomoxetine inhibits the reuptake of norepinephrine with little to no activity at other receptor sites or neuronal reuptake pumps.

Anticonvulsant Agents

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. These agents are used when seizure control is an issue. Valproic acid or valproate is used along with an atypical antipsychotics (especially risperidone). The patient should be closely monitored for abnormal levels of ammonia, which are generally accompanied by alterations in mental status (often nonspecific slowing) and abnormalities of liver function.

Valproic acid (Depakote, Depakote ER, Depakene, Depacon, Stavzor)

Considered the drug of first choice for primary generalized epilepsy, valproate has a very wide spectrum and is effective in most seizure types, including myoclonic seizures. It has multiple mechanisms of anticonvulsant effects, including increasing gamma-aminobutyric acid (GABA) levels in brain, as well as T-type calcium channel activity. The extended-release (ER) formulation allows for once-a-day administration.