Unfamiliar and unpredictable situations which generally have no effect on children with normal development typically cause increased anxiety and fear in children with autism spectrum disorder (ASD). Children with ASD may feel a sudden visit to a hospital to be a disturbing event and may react with panic, tantrums, self-injuring behavior, and aggression due to extreme anxiety and fear prompted by medical procedures and examinations. Although sedation management is often performed even in older children prior to various examinations (CT, MRI, electroencephalogram, etc.) to reduce anxiety, suppress or minimize body movements, and ensure safety, many children with ASD suffer further distress if sedation is performed in the same way as with normal children, turning a procedure aimed at alleviating distress into a painful and negative experience for both patients and caregivers. To perform sedation in children with ASD appropriately, it is essential to recognize that these patients require special consideration ; the procedures or examinations should be explained to the patients in advance with the help of the caregivers, who have their trust, so as to minimize the anxiety arising from novel circumstances. In addition to building a trusting relationship with the children and the caregivers beforehand, a detailed assessment of each patient's characteristics is crucial for allowing the physician to respond in a manner more considerate of, and appropriate to, the specific characteristics of the patient.
Objective: Reading and writing difficulties in children with a multilingual background are often considered to be a consequence of limited language proficiency rather than developmental dyslexia (DD) or intellectual disabilities. However, since these latter conditions are also prevalent in a multilingual population, the present study explored the assessment and diagnosis of DD, through a case-series study of Japanese-English bilingual children. Methods: The participants were four school-aged Japanese-English bilingual children (Cases 1-4) with reading and writing difficulties as a major complaint. They were tested for cognitive abilities (IQ) and both oral language and basic literacy skills in Japanese and English, and we made a diagnosis of a specific learning disorder based on DSM-5. Results: Full-scale IQ and oral language abilities in both Japanese and English were within the normal range for all cases. Regarding basic literacy skills, three of them (Cases 1, 3, 4) showed difficulties from the level of Hiragana reading while one (Case 2) showed difficulties in kanji. Two children who used English at school also showed severe difficulties in alphabet naming (Case 3) and oral text reading (Cases 3, 4). Based on these results, Cases 1, 3, and 4 were diagnosed as having a specific learning disorder in both reading and writing, while Case 2 was diagnosed as having a disorder mainly in writing. Conclusions: The evaluation of basic literacy skills (e. g., letter, word, and simple text reading) were shown to be particularly useful for assessing DD in multilingual children. While assessment and diagnosis in similar cases that involve multiple languages pose many challenges in practice, approaches that can be used to identify innate specific learning disorders despite the complex environmental and linguistic background are needed.
Objective: It is imperative to sufficiently manage the daily life of pediatric patients with immune-mediated neuromuscular diseases, such as myasthenia gravis (MG) and chronic inflammatory demyelinating polyneuropathy (CIDP), for proper growth and development. However, current evidence on management practice is unclear and many pediatric neurologists have unresolved questions. We therefore conducted a multi-center questionnaire survey to establish a more standardized management plan. Methods: In February 2017, we distributed a written questionnaire to members of the Pediatric Immune-mediated Neuromuscular Diseases Study Group (82 members in 67 facilities at the time of survey). Results: Completed questionnaires were obtained from 15 respondents in 15 facilities. Each facility treated an average of 5.5 patients with MG and 0.3 patients with CIDP. We observed differences among the facilities in terms of immunization schedules, ophthalmological examinations, and prophylactic medication for the adverse effects of corticosteroids, which included infections, peptic ulcers, and osteoporosis. It was particularly evident that pediatricians were uncertain about the usage of anticonvulsants and sedatives, with prescribed benzodiazepine agents in fact being contraindicated for MG patients in Japan. Conclusions: The daily life management plan of pediatric patients with immune-mediated neuromuscular diseases varied considerably among institutions, possibly due to the limited number of patients with MG and CIDP treated at each facility. We therefore propose a guide for the daily life management of children with such diseases. Further investigation of cases and institutions is needed for more useful and effective guidelines.
Objective: To evaluate the efficacy of tacrolimus therapy for patients with childhood-onset myasthenia gravis (MG). Methods: We retrospectively evaluated tacrolimus therapy in 5 patients with childhood-onset MG from the Saitama Children's Medical Center between January 2012 and May 2020. We collected patients' background characteristics and clinical manifestations. We also evaluated changes in MG activity of daily living score, MG composite score, and anti-acetylcholine receptor antibody every 1 to 3 months for 1 year after tacrolimus commencement. Results: Five patients (1 male) were treated with tacrolimus : ocular type (n=2) and generalized type (n=3). The median age at tacrolimus commencement was 3.8 (2.3-9.0) years. The initial tacrolimus doses were 0.05 (0.04-0.05) mg/kg/day. The duration between tacrolimus commencement and response was 30 (9-67) days. In all patients, MG activity of daily living score and MG composite score decreased at 3 months after tacrolimus commencement. Two patients had pharmacologic remission, two had minimal manifestations, and one had improved at the last visit. Patients who had pharmacological remission and minimal manifestations were treated with tacrolimus within 10 months of onset. One patient with improvement was treated with tacrolimus at 55 months after onset. Conclusions: Our findings suggest we should evaluate the tacrolimus efficacy for patients with childhood-onset MG at 3 months after commencement. Patients with a short treatment lag may have better outcomes.
The IQSEC2 gene on chromosome Xp11.22 encodes a guanine nucleotide exchange factor (GEF), which is enriched at the postsynaptic density of excitatory synapses where it controls excitatory synaptic transmission. Since 2010, when IQSEC2 variants were discovered in families with X-linked intellectual disabilities, the spectrum of clinical features has expanded with early-onset seizures, as a frequent comorbidity in both affected male and female patients. Herein, we describe a boy with a pathogenic variant in exon 1 of IQSEC2, NM_001111125.2 : c.693del [p. (Thr232Profs＊25)], leading to a loss of all functional domains on the longest IQSEC2 isoform. Our patient has shown hypotonia and strabismus since infancy, later presenting with severe intellectual disabilities, including autism. Brain MRI showed brain atrophy, a thin corpus callosum, and periventricular T2 hyperintensities. He developed myoclonic seizures since 2 years of age in addition to tonic-clonic seizures and atypical absence seizures. An interictal EEG showed generalized polyspikes and wave discharges ; the epilepsy was refractory to antiepileptic drugs, and he underwent corpus callosotomy at 4 years of age, which led to disappearance of the drop attacks and improvement of facial expression ; however, his psychomotor development remained to be severely impaired. Overall, his clinical course matches that of developmental and epileptic encephalopathy (DEE). These clinical manifestations such as DEE with the characteristic MRI findings are considered to be the most severe form of the IQSEC2-related disorders.
Superior oblique palsy causes deviation, diplopia, and abnormal head posture. The Parks-Bielschowsky three-step test is used for diagnosis ; however, we experience cases that do not meet these 3 steps, or whose findings are difficult to evaluate. We were unable to detect findings in cases where deviation and abnormal head posture were mild. As we have to consider differential diagnoses, including systemic disorders causing diplopia, diagnosis is occasionally difficult. Here, we report the usefulness of the change of head tilt with monocular vision in the objective diagnosis of superior oblique palsy associated with diplopia. A 13-year-old Japanese girl experienced diplopia 2 years ago and presented to our hospital with exacerbated diplopia. She showed subtle right exotropic hypertropia and omnidirectional diplopia while her eye movements were preserved in 9 directions. She did not present with ptosis, but complained about circadian changes in diplopia that worsened in the evening. Blood examination, brain magnetic resonance imaging, a nerve conduction test, and a Tensilon test yielded normal results. Diagnosis of Myasthenia gravis, brain tumor, and Fisher syndrome was excluded. While comparing head tilt with the patient's right monocular vision to her left, we identified that head posture with left monocular vision, or the unaffected side was vertical. Alternatively, head posture with the patient's right monocular vision and the affected side revealed a compensating head posture. In this regard, the patient was diagnosed with superior oblique palsy. Diplopia was responsive to ophthalmic surgery. We conclude that the change of head tilt with monocular vision highlights the Bielschowsky sign and can be useful for objective diagnosis.
We present a case of early infantile epileptic encephalopathy type 7 (EIEE7) that partially responded to pyridoxal phosphate (PLP). On the first day, the patient presented with multiple generalized tonic-clonic seizures with eye deviation. Abnormal electroencephalogram (EEG) findings were recorded during the episodes. The patient improved with phenobarbital (PB), but frequent tonic-clonic seizures recurred on day 50. PLP was then introduced, and the seizures ceased within 3 days with EEG results returning to within normal limits. We clinically diagnosed pyridoxine-dependent epilepsy (PDE) in the patient. However, the seizures recurred at 10 months of age. Upon investigation at age 4, plasma and cerebrospinal fluid alpha-aminoadipic semialdehyde (α-AASA) and pipecolic acid levels were not elevated. Furthermore, ALDH7A1 sequencing was normal. PDE was therefore an unlikely diagnosis, and PLP was subsequently stopped. Whole exome sequencing identified a novel heterozygous KCNQ2 frameshift mutation (NM_172107.2 : c.2032dup ; p. (Glu678Glyfs＊187)) when she was 5 years of age, and we then diagnosed EIEE7. Recent reports show that PLP is effective for the treatment of EIEE7, emphasizing that EIEE7 and PDE should be carefully differentiated. It is important to control seizures early for improving the neurodevelopmental prognosis of EIEE7, and it is worth considering early administration of PLP as a second-line drug or treatment concomitant with a voltage-dependent sodium channel inhibitor.
Nusinersen, an antisense oligonucleotide that targets survival motor neuron (SMN) 2, was approved as a new therapeutic approach for spinal muscular atrophy (SMA). Although early intervention is recommended in patients with infantile-onset SMA, there are limited data about the efficacy of nusinersen for the very severe fetal-onset form of SMA (type 0). We report the case of a 2-year and 3-month-old boy with SMA type 0, who was treated with nusinersen. The patient presented with severe muscle weakness, marked hypotonia, respiratory distress, and joint contracture at birth. At 9 weeks of age, a genetic analysis revealed homozygous deletion of the SMN1 gene and two copies of the SMN2 gene. Based on these findings and presumed intrauterine-onset-related symptoms, a diagnosis of SMA type 0 was made. The intrathecal injection of nusinersen was started at 10 weeks of age. One week later, the patient exhibited improvements in spontaneous movement, starting in his left forearm. However, at 4 months of age he underwent tracheotomy due to worsening pharyngomalacia and required mechanical ventilation. After surgery, his respiratory condition stabilized and his motor function improved steadily. At discharge (at 9 months of age), he required sustained ventilator support, tube-feeding and frequent tracheal suctioning. After discharge, he continued receiving nusinersen treatment. No obvious adverse events were noted. At his last visit, he was unable to speak, but was able to sit independently for a minute. Although the ventilator could be removed for one hour, he remained ventilator-dependent. The patient's CHOP-INTEND score increased from 3 points at treatment initiation to 47 points. This case suggests that early diagnosis and treatment with nusinersen may improve the motor function of SMA patients, even those with SMA type 0. However, the long-term effects of nusinersen on motor function and other multi-organ symptoms in SMA type 0 should be examined further.
We report the results of a questionnaire survey conducted among six patients registered in the patients' association of ring chromosome 14 syndrome- “Paper Airplane,” with their families' consent. All patients had developmental delay and intractable epilepsy requiring multidrug therapy. The severity varied between cases, and the most common complications in half of the cases were otitis media, short stature, and microcephaly. It is advised to perform chromosomal examinations even if only infancy onset intractable epilepsy, and the other nonspecific symptoms are present.