Application of a wearable switch to perform a mouse left click for a child with mix type of cerebral palsy: a single case study.

Purpose: Children with cerebral palsy may face difficulties using handheld pointing devices, due to involuntary muscle movements. This study aimed at describing the idea of the new wearable sensor switch and assessing its feasibility as an access solution in a case of mixed-type cerebral palsy.Methods: The study participant was a 17-year-old male with mixed-type cerebral palsy characterized by chorea-athetotic movements and bilateral spasticity with gross motor function classification system level V. He exhibited sudden and irregular involuntary upper limb movements when sitting. Because spastic finger movements limited his ability to use a handheld mouse, he used a trackball near his neck as a pointing device (previous input method). The wearable switch system using a stretchable strain sensor was introduced; the sensor was attached to a groove worn on the dorsal regions of the right hand crossing the proximal interphalangeal and metacarpophalangeal joints of the middle finger (new input method). The switch turned on when the subject flexed his middle finger.Results: The user successfully turned the switch on and typed almost the same numbers of characters per trial compared with the previous input method. The speed of his head movements during typing reduced (p < .01), and his sitting posture was nearly upright during computer operation (p < .01). No involuntary movement, requiring physical assistance, was observed when using the wearable switch.Conclusion: The new switch system can be a new option for people with difficulty using standard handheld input devices due to paralysis and involuntary muscle movements.Implications for rehabilitationCerebral palsy is a major cause of motor dysfunction and spasticity and dyskinesia in the fingers and upper limbs may prevent children with cerebral palsy from using handheld input devices.Wearable devices may be useful for children with cerebral palsy who have limited access to handheld pointing devices.We developed a new wearable switch to control devices using a flexible stretchable sensor.The wearable switch contributed to the improvement of sitting posture and reduction of neck burden during the typing task at the speed equivalent to that using the previous method in a child with mixed type of cerebral palsy exhibiting choreoathetotic movements and bilateral spasticity.

Genotype-phenotype correlations in alternating hemiplegia of childhood.

OBJECTIVE: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype-phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. METHODS: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. RESULTS: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. CONCLUSIONS: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.

Effect of CPS14217C>A genotype on valproic-acid-induced hyperammonemia.

BACKGROUND: In order to clarify the factors causing hyperammonemia and to predict occurrences during treatment with valproic acid (VPA), we investigated the effect of the genetic polymorphism of carbamoyl-phosphate synthase 1 (CPS14217C>A) on susceptibility of hyperammonemia, together with the effect of coadministration of other anticonvulsants. METHODS: Seventy-nine patients with epilepsy were enrolled, and five of them had hyperammonemia. Univariate and multivariate logistic regression analyses were performed. RESULTS: The aspartate aminotransferase level in the patients with hyperammonemia was significantly higher than that in those without hyperammonemia. The risk of hyperammonemia was significantly influenced by the number of anticonvulsants concomitantly administered with VPA. Also, the distribution of the CPS14217C>A genotype differed depending on whether the patients had hyperammonemia or not. No significant effects of CPS14217 genotypes and the number of anticonvulsants coadministered with VPA on the serum concentrations of VPA were observed. The multivariate logistic regression analysis showed that the concomitant administration of two or more anticonvulsants with VPA and the heterozygous or homozygous carrier state of the A allele of the CPS14217C>A polymorphism were independent risk factors for developing hyperammonemia. CONCLUSIONS: These findings suggested that in epileptic patients undergoing VPA therapy, CPS14217A polymorphism and the number of coadministered anticonvulsants would be considered as risk factors for hyperammonemia, even if the serum VPA concentrations were controlled.

Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation.

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle. Although a combination of molecular methods have been used including DNA sequencing of all 10 exons and exon-intron boundaries of OTC gene, only approximately 80% of patients with OTC deficiency are found to have mutations. We report two known and three novel mutations of the OTC gene in five Japanese patients including two neonatal-onset, one late-onset, and two symptomatic female patients. Known nonsense mutations (c.578G>A and c.421C>T) were detected in a neonatal-onset male and a symptomatic female patient, respectively. Mutation analysis revealed two novel mutations including one splice site mutation (c.386+1G>C) in a symptomatic female patient and one missense mutation (c.515T>A) in a late-onset male patient. In the remaining case, which was a neonatal-onset male patient, no mutation was disclosed by direct sequencing of all 10 exons and their flanking intron sequences. Therefore, OTC mRNA in the liver was analyzed by RT-PCR, and remarkably, a 135-nt insertion was detected between exons 5 and 6. Genomic DNA analysis of intron sequences revealed a single nucleotide change at 265 bp downstream from the 3' end of exon 5, which created the novel splice acceptor site. Thereby, a 135-nt exon was created from the central part of an intron sequence. This is the first report of mutation deep in the intronic sequence in the OTC gene. Molecular analysis using genomic DNA and mRNA will increase the mutation detection ratio in the OTC gene.

Pallister-Mosaic syndrome and neuronal migration disorder.

We diagnosed Pallister-Mosaic syndrome (PMS) in a 4-month-old female infant. In addition to the presence of non-specific anomalies, involving anorectal, finger and ear anomalies, characteristic cranio-facial features and irregular skin lesions that appeared after age 2 months suggested the possibility of genetic mosaicism, PMS in particular. Fluorescence in situ hybridization technique revealed an extra copy of chromosome 12p; i (12p) in 30% of cultured skin fibroblasts. When focal skin lesions accompany neurodevelopmental disabilities in early infancy, genetic analysis for mosaicism should be considered for differential diagnosis. Significantly, we describe several phenotypic features and neuroimaging findings of the PMS in the present case, which have not been described in previous reports. The neuroimaging abnormalities we encountered, such as polymicrogyria, speculating congenital brain anomaly, may explain the severe motor and intellectual disabilities of PMS.