Autistic Patient Research Articles

Idiopathic Autism: Cellular and Molecular Phenotypes in Pluripotent Stem Cell-Derived Neurons.

Autism spectrum disorder is a complex neurodevelopmental disorder whose pathophysiology remains elusive as a consequence of the unavailability for study of patient brain neurons; this deficit may potentially be circumvented by neural differentiation of induced pluripotent stem cells. Rare syndromes with single gene mutations and autistic symptoms have significantly advanced the molecular and cellular understanding of autism spectrum disorders; however, in aggregate, they only represent a fraction of all cases of autism. In an effort to define the cellular and molecular phenotypes in human neurons of non-syndromic autism, we generated induced pluripotent stem cells (iPSCs) from three male autism spectrum disorder patients who had no identifiable clinical syndromes, and their unaffected male siblings and subsequently differentiated these patient-specific stem cells into electrophysiologically active neurons. iPSC-derived neurons from these autistic patients displayed decreases in the frequency and kinetics of spontaneous excitatory postsynaptic currents relative to controls, as well as significant decreases in Na+ and inactivating K+ voltage-gated currents. Moreover, whole-genome microarray analysis of gene expression identified 161 unique genes that were significantly differentially expressed in autistic patient iPSC-derived neurons (>twofold, FDR < 0.05). These genes were significantly enriched for processes related to synaptic transmission, such as neuroactive ligand-receptor signaling and extracellular matrix interactions, and were enriched for genes previously associated with autism spectrum disorder. Our data demonstrate aberrant voltage-gated currents and underlying molecular changes related to synaptic function in iPSC-derived neurons from individuals with idiopathic autism as compared to unaffected siblings controls.

The impossible reparation

This article discusses the phantasy of returning to the past and symbiotically merging with the mother, which, in an autistic patient, constituted an attempt of impossible reparation. This mode of reparation resulted in a cycle in which any attempt to repair the inner experience by contact with an external object was destined to be disappointing because of the desire for an infantile connection without separateness. The author reviews the literature on reparation and emphasises recent developments resulting from work with Autism Spectrum Disorder children who are far from the depressive position and who have difficulty bearing separateness. The author recognises an essential positive aspect of reparation independent of the ability to perceive the object as separate and suggests that when working with very primitive emotional states, it seems suitable to use a wider definition for what can be considered essentially a primitive reparative act or a precursor for reparation. Next, the author discusses the significance of a phantasy of impossible reparation in an autistic girl with emphasis on the importance of considering the reparative aspects of this defensive phantasy to enable development. Finally, the author relates to the despair that occurs in both analyst and patient when the phantasy is not transformed.

De Novo Duplication of 7p21.1p22.2 in a Child with Autism Spectrum Disorder and Craniofacial Dysmorphism.

The duplication of the short arm of chromosome 7 as de novo is extremely rare. The phenotype spectrum varies depending on the region of duplication. We report a case of de novo duplication of chromosomal region 7p21.1p22.2 in a three-year-old male child with autism who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in January 2012. The patient was diagnosed with craniofacial dysmorphism, global developmental delay, hypotonia and bilateral cryptorchidism. The duplication was detected by conventional G-banded karyotype analysis/fluorescence in situ hybridisation and confirmed by array comparative genomic hybridisation. To the best of the authors' knowledge, this is the first report of chromosomal region 7p21.1 involvement in an autistic patient showing features of a 7p duplication phenotype. Identifying genes in the duplicated region using molecular techniques is recommended to promote characterisation of the phenotype and associated condition. It may also reveal the possible role of these genes in autism spectrum disorder.

Late-onset superior mesenteric artery syndrome four years following scoliosis surgery - a case report.

Background: Superior mesenteric artery (SMA) syndrome has been reported as an uncommon condition of external vascular compression of the SMA particularly after rapid weight loss, body casts, or after corrective surgery for spinal deformities, usually within the first few weeks after surgery. Methods: This is a retrospective report of a case of a non-verbal autistic female patient who started to develop SMA syndrome at the age of 16, 4 years after posterior spinal fusion surgery for scoliosis. She was treated conservatively by increasing oral caloric intake, which resulted in increased body weight and relief of symptoms. Results: Seen at 10 years’ follow up, the patient is doing well, and is functional within the limits of her suboptimal cognitive and verbal conditions. She maintains good trunk balance with solid spinal fusion and intact instrumentation at latest follow up. Conclusion: Spinal surgeons should maintain a high index of suspicion for diagnosis of SMA syndrome even years after scoliosis surgery, especially for patients with communication problems, like the case we present here. Appropriate conservative measures can succeed in relieving the symptoms, increasing body weight, and preventing complications including the risk of death.

Compound Heterozygous -30 (T&gt;C) and Cd 41/42 (-TTCT) Leading to β-Thalassemia Major in a Malay Autistic Patient

Cd 41/42 (-TTCT), IVS 1-5 (G-C), IVS 1-1 (G-T), and HbE are the most common β-globin defects among Malaysian Malays, and compound heterozygous states of the four mutations are commonly encountered. Here, we described the hematologic and DNA characterizations of our first-time encountered compound heterozygous state of β° Cd 41/42 (-TTCT) and a mild β+ TATA box mutation, -30 (T>C), in a Malay patient leading to β-thalassemia major. At the age of 2, she presented with symptomatic anemia, hepatosplenomegaly, and was put on a β- thalassemia major treatment regime. Now, at the age of 6, she was found to be autistic, a slow learner with social interaction problems, and she is under a psychiatric follow up for autism. Inevitably, the detection of β-globin defects among Malaysians must include comprehensive molecular analyses for an accurate assessment of emerging and rare mutations, as well as modifier genes affecting disease severity.

The relevance of autism in orthodontic management

Autism is a developmental disorder that can prove to be a barrier in providing orthodontic care due to a difficulty in developing language and communication. The purpose of legislation imposed in regards to mental capacity is to ensure that an individual has the right to autonomy. However, we must carefully balance an autistic patient and guardian's wishes with indications for orthodontic treatment. This article recognizes the difficulties in managing autistic patients and discusses methods to facilitate effective management. Clinical Relevance: Autistic patients may find difficulty in accessing orthodontic care owing to their inability to socialize and communicate. This article offers novel behaviour management techniques that may aid in tackling this barrier.

Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification

Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state.

Management of Pediatric Patients With Autistic Spectrum Disorders in the Emergency Department

Children and adolescents with autistic spectrum disorders present a special challenge in the emergency department setting due to highly individualized emotional-behavioral and communicative characteristics. When an autistic patient presents with agitated behavior, the emergency care provider must consider both emotional and somatic etiologies as well as which treatment modalities best serve the patient. Effective communication with parents, caretakers, and outpatient providers provides useful insights into likely etiologies of agitation as well as effective management strategies.

Cutaneous Rosai-Dorfmann Disease in Autistic Patient: Is there a Pathogenetic Correlation?

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a benign disorder of histiocyte proliferation that usually affects the lymph nodes. Purely Cutaneous Rosai-Dorfman Disease (CRDD) is a rare extranodal variant that is strictly limited to the skin. We report a patient with of cutaneous rosai-dorfman of the abdominal wall with a past medical history of autism spectrum disorders. Autism is surely a complex disease and the most prevailing opinion is that it is a neuro-immune disorder. Both the diseases are considered strictly correlated to the immune disorders and the immunodeficiency might play an important pathogenetic role. A brief review of the literature of CRDD is also provided.

Full mouth rehabilitation for a disabled patient: a case report

The spectrum of physically challenged patients who visit to a dental clinic for treatments are diverse: from ones of mild disabilities, who lead their lives in a similar way of ordinary people, to others who suffer from diseases that are difficult to be diagnosed, and need medical expertise due to systemic care or special techniques and instruments because of behavior management and difficulty of treatments. The patient in this case was 25-year-old autistic male patient who visited the clinic on account of overall treatment for multiple carious lesions. He could perform normal daily life to some degree under the care of a guardian. This case report describes predicaments of making a treatment plan resulted from lack of information about disabled patients, and difficulties of proceeding treatment procedures under general anesthesia. It is considered that sufficient consultation and history taking are needed before treatment for disabled patients. (J Korean Acad Prosthodont 2013;51:208-13)

Management of children with autism spectrum disorder in the dental setting: Concerns, behavioural approaches and recommendations

Objectives: This article reviews the present literature on the issues encountered while coping with children with autistic spectrum disorder from the dental perspective. The autistic patient profile and external factors affecting the oral health status of this patient population are discussed upon the existing body of evidence. Material and Methods: The MEDLINE database was searched using the terms ‘Autistic Disorder’, ‘Behaviour Control/methods’, ‘Child’, ‘Dental care for disabled’, ‘Education’, ‘Oral Health’, and ‘Pediatric Dentistry’ to locate related articles published up to January 2013. Results: Most of the relevant studies indicate poor oral hygiene whereas they are inconclusive regarding the caries incidence in autistic individuals. Undergraduate dental education appears to determine the competence of dental professionals to treat developmentally disabled children and account partly for compromised access to dental care. Dental management of an autistic child requires in-depth understanding of the background of the autism and available behavioural guidance theories. The dental professional should be flexible to modify the treatment approach according to the individual patient needs. Key words:Autism spectrum disorder, dental management, children.

Removable orthodontic appliance with nickel–titanium spring to reposition the upper incisors in an autistic patient

A newly designed removable appliance with a shape-memory wire was used for the orthodontic treatment of the anterior teeth in an 11-year-old child who had autism and intellectual disability. The device was designed to reduce the lateral incisor crossbite and the central incisors' labial rotation. The child was treated for 1 year with this removable appliance. Tooth movement was analyzed using cephalograms and surface data were derived from study models. This device proved to be very durable. The lateral incisor crossbite was corrected, and the inclination of the upper central incisors and the interincisal angle were improved. This appliance exerts light and continuous orthodontic force, without requiring any adjustments of the spring wire. The appliance also facilitated orthodontic treatment in a child with intellectual disability in whom treatment with a standard orthodontic device would be unsuitable.

Como se morde um pai? Estudo de caso de um jovem autista: uma abordagem psicanalítica

Através da abordagem de episódios de “passagem ao ato”, em que um paciente autista morde o pai, este trabalho debate as vicissitudes ocasionadas pela ausência do nome do pai como mediador das relações do sujeito com a alteridade, a dimensão objetal e a imagem. A discussão sobre o lugar que as “mordidas no pai” tiveram na economia libidinal deste sujeito aborda questões referentes à autoridade, a não diferenciação sexual e a construção da imagem de si. O trabalho tece considerações a propósito do apaziguamento possível de se acessar através da invenção de um corpo em suas relações com os registros Real, Simbólico e Imaginário, tal como concebido por Jacques Lacan. Palavras-chave: autismo; passagem ao ato; nome do pai; holófrase; corpo.

Tardive Tourette-Like Syndrome in a Patient Treated With Paliperidone

Tardive Tourette-Like Syndrome in a Patient Treated With Paliperidone

Increased secreted amyloid precursor protein-α (sAPPα) in severe autism: proposal of a specific, anabolic pathway and putative biomarker.

Autism is a neurodevelopmental disorder characterized by deficits in verbal communication, social interactions, and the presence of repetitive, stereotyped and compulsive behaviors. Excessive early brain growth is found commonly in some patients and may contribute to disease phenotype. Reports of increased levels of brain-derived neurotrophic factor (BDNF) and other neurotrophic-like factors in autistic neonates suggest that enhanced anabolic activity in CNS mediates this overgrowth effect. We have shown previously that in a subset of patients with severe autism and aggression, plasma levels of the secreted amyloid-β (Aβ) precursor protein-alpha form (sAPPα) were significantly elevated relative to controls and patients with mild-to-moderate autism. Here we further tested the hypothesis that levels of sAPPα and sAPPβ (proteolytic cleavage products of APP by α- and β-secretase, respectively) are deranged in autism and may contribute to an anabolic environment leading to brain overgrowth. We measured plasma levels of sAPPα, sAPPβ, Aβ peptides and BDNF by corresponding ELISA in a well characterized set of subjects. We included for analysis 18 control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We have observed that sAPPα levels are increased and BDNF levels decreased in the plasma of patients with severe autism as compared to controls. Further, we show that Aβ1-40, Aβ1-42, and sAPPβ levels are significantly decreased in the plasma of patients with severe autism. These findings do not extend to patients with mild-to-moderate autism, providing a biochemical correlate of phenotypic severity. Taken together, this study provides evidence that sAPPα levels are generally elevated in severe autism and suggests that these patients may have aberrant non-amyloidogenic processing of APP.

A de novo 1.5 Mb microdeletion on chromosome 14q23.2‐23.3 in a patient with autism and spherocytosis

Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5-7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk.

A dental look at the autistic patient through orofacial pain

Autism is a neurodevelopmental disorder characterized by impaired social interaction and restricted interests, compromised communication skills, and repetitive patterns of behavior. Both social and behavioral problems, which may include hyperactivity and quick frustration, may hinder the detection of other important pathologies such as orofacial pain. This is aggravated by the invasive nature of oral exploration, which may trigger violent and self-injurious responses, such as temper tantrums and/or head banging, which make the work of professionals extremely difficult during diagnoses, follow-up examinations, and dental treatments. In addition, mercury-containing amalgams used to treat dental caries (the most common form of acute orofacial pain) have been associated with higher rates of severe autism in children. The purpose of this review is to describe the current state of the art regarding the co-occurrence of orofacial pain and autism spectrum disorder, and how these conditions may interrelate clinically and neurobiologically.

Brief Report: Eosinophilic Esophagitis as a Cause of Feeding Problems in Autistic Boy. The First Reported Case

Unrecognized gastrointestinal disorders may contribute to the behavioral problems in non-verbal patients, but they are often overlooked since the clinical symptoms are nonspecific. Eosinophilic esophagitis (EE) is a chronic inflammatory disorder manifesting itself predominantly in reflux-type symptoms that do not respond to standard anti-reflux pharmacotherapy. Here we report the first case of EE in an autistic patient with feeding difficulties caused by exacerbated EE symptoms.

Intervention of a clinical psychologist in the treatment of an autistic patient with pancreatic cancer: a report on a surgical case

【症例】40歳代, 女性. 【臨床診断】軽度知的障害を伴う自閉症. 【症例報告】膵臓がんに対し, 膵頭十二指腸切除術を行った. 当初, 基礎疾患に自閉症を有することで医療者と患者・家族間の相互理解の困難さが予想されたため, 臨床心理士が介入した. 介入後, 障害が周術期にどのような影響を与えるか検討したところ, 医療者側に徐々に自閉症に対する認識が深まり, 患者の個別性に配慮したケアを行うことができた. 患者・家族に対しては, 臨床心理士が個別面接を繰り返し家族以外の理解者となるよう受容し, 共感的に支える関わりを継続したことで患者・家族の不安が軽減した. 【結語】臨床心理士の介入が, 患者・家族の精神的安定およびスタッフ教育に一定の効果をもたらした. Palliat Care Res 2010; 5(2): 323-326

Combination of Oral Clonidine and Midazolam as Premedication When Ketamine is not an Option in an Uncooperative Autistic Patient

Autism spectrum disorder is a neurodevelopmental disorder with qualitative abnormalities in reciprocal social interaction and patterns of communication. Patients with autism, or an autism spectrum disorder (ASD), are sometimes difficult to manage from an anesthetic perspective because they may become scared, or at least very inquisitive of what is, and what will be happening to them. In the pre-operative holding they may become agitated, self-destructive, or resistant because it is a change in their normal routine; sometimes leading them to refuse to cooperate during induction. If such behaviors are observed, or expected based on the preoperative evaluation and/or the conversation with the parent or caregiver, a premedication should be considered. Depending on the severity of the displayed or expected behavior, the premedication options at our institution often range from none, midazolam, or a combination of benzodiazepines and ketamine. However, there are cases where ketamine cannot be used (e.g., prior adverse event, allergy), thus alternative options are needed. We present a case report of a 22 yearold patient with severe autism who responded to a premedication combination of oral clonidine and midazolam, given due to a previous adverse reaction to ketamine.