Abstract:
OBJECTIVE:Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments. METHODS:We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information. RESULTS:We identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI. CONCLUSION:Our patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.
journal_name
Brain Devjournal_title
Brain & developmentauthors
Kobayashi Y,Tohyama J,Takahashi Y,Goto T,Haginoya K,Inoue T,Kubota M,Fujita H,Honda R,Ito M,Kishimoto K,Nakamura K,Sakai Y,Takanashi JI,Tanaka M,Tanda K,Tominaga K,Yoshioka S,Kato M,Nakashima M,Saitsu H,Matsumotdoi
10.1016/j.braindev.2020.12.006subject
Has Abstractpub_date
2021-01-09 00:00:00eissn
0387-7604issn
1872-7131pii
S0387-7604(20)30330-2pub_type
杂志文章abstract::Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is caused by loss of the survival motor neuron gene, SMN1. SMA treatment strategies have focused on production of the SMN protein from the almost identical gene, SMN2. Valproic acid (VPA) is a histone deacetylase inhibitor that c...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2011.04.010
更新日期:2012-03-01 00:00:00
abstract::We report an 11-year-old girl with progressive hypopituitarism and visual loss of the right eye caused by trans-sphenoidal and sphenoethmoidal encephaloceles associated with morning glory syndrome. She was first seen at the age of 8 years, because of polydipsia and polyuria, and examination at that time revealed pitui...
journal_title:Brain & development
pub_type: 杂志文章,评审
doi:10.1016/0387-7604(95)00021-3
更新日期:1995-05-01 00:00:00
abstract::The common factor causing congenital arthrogryposis is lack of fetal movements. This can result from a large number of disorders. They may be neuropathic, affecting the brain, the spinal cord, or the peripheral nerves; they may be abnormalities of the muscles, such as myasthenia gravis, congenital muscular dystrophies...
journal_title:Brain & development
pub_type: 杂志文章,评审
doi:10.1016/s0387-7604(98)00037-0
更新日期:1998-10-01 00:00:00
abstract::This report describes a 60-year-old female patient with Krabbe disease who presented with slowly progressive gait disturbance due to mild spastic paraplegia. Brain magnetic resonance imaging showed high-intensity lesions along the upper parts of the bilateral pyramidal tracts in fluid-attenuated inversion recovery ima...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2012.08.004
更新日期:2013-06-01 00:00:00
abstract::Oral motor patterns during feeding were investigated in 58 patients with severe physical disability. Five patients showed a pattern resembling sucking. Twenty-nine exhibited an up-and-down movement of the jaw and protrusion of the tongue. Among these, the mouth opened when the food entered and the lips closed before s...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(97)00077-6
更新日期:1997-12-01 00:00:00
abstract:PURPOSE:We attempted to evaluate the ability of 125 preschool and school children with autism spectrum disorder (ASD children) to understand the intentions of those speaking to them using prosody of the voice, by comparing it with that of 119 typically developing children (TDC) and 51 development-age-matched children w...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2017.07.001
更新日期:2017-11-01 00:00:00
abstract::We evaluated the cyclic alternating pattern (CAP) during the first year of life in order to obtain information on the maturation of arousal mechanisms during NREM sleep and to provide normative data for CAP parameters in this age range (5-16months). Eleven healthy children (mean age 7.9±3.3months, seven boys) were stu...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2010.07.008
更新日期:2011-05-01 00:00:00
abstract::The number of large myelinated axons was markedly decreased in almost all the intramuscular nerve bundles included in 32 muscle biopsies from patients with Werdnig-Hoffmann disease compared to that in normals. The morphometric analysis of peripheral nerves in 5 epon-embedded sections also showed a selective loss of la...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(89)80040-3
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:This study investigated the efficacy and safety of zonisamide (ZNS) adjunctive therapy in children with intractable epilepsy to existing antiepileptic drugs (AEDs). METHODS:A clinical retrospective study was performed from 2003 to 2005 at two tertiary epilepsy centers. We reviewed the data from 163 children (1...
journal_title:Brain & development
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.braindev.2009.02.003
更新日期:2010-03-01 00:00:00
abstract::Blink reflex can be elicited by sudden strong auditory stimulation. Using a special transducer wer recorded this reflex which appears as a microvibration of the eyelid, and named it auditory-evoked eyelid microvibration (AMV). As the reflex pathway of AMV exists in the brainstem, AMV is an easy and useful way of knowi...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(84)80009-1
更新日期:1984-01-01 00:00:00
abstract::Doublecortin (DCX) and tubulin play critical roles in neuronal migration. DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females. We used whole-exome sequencing to investigate causative gene variants in a large family with late-childhood-onset focal epile...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2015.12.005
更新日期:2016-06-01 00:00:00
abstract::We recorded serially brainstem auditory evoked response (BAER) during the neonatal period in term infants who suffered perinatal asphyxia. The amplitudes of BAER components was analysed at 40 dB above BAER threshold of each subject who had a threshold journal_title:Brain & development pub_type: 杂志文章 doi:10.1016/j.braindev.2006.03.004 更新日期:2006-10-01 00:00:00
abstract::Self-induced seizures by somatosensory stimulation are rare. We describe two epileptic patients with self-induced seizures presumably by peri-orbital somatosensory stimulation. Two infants with severely delayed psychomotor development and poor visual acuity after acute subdural hemorrhage in early infancy had been dia...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2011.11.004
更新日期:2012-09-01 00:00:00
abstract::Factors useful to predict seizure frequency and duration of antiepileptic treatment of children with benign partial epilepsy and rolandic spikes were retrospectively evaluated in 72 patients seizure-free for at least 5 years and off antiepileptic drugs for at least 2 years. Three groups were considered: Group I, 11 pa...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(87)80049-9
更新日期:1987-01-01 00:00:00
abstract::Serial changes of MRI scanning of an 11-year-old boy with hemiparesis due to a germ cell tumor in the basal ganglia are presented. Initial brain MRI T1-weighted images revealed a subtle mixed signal intensity lesion at left anterior and posterior limbs of the internal capsule. This lesion was not enhanced with Gd-DTPA...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/0387-7604(93)90024-3
更新日期:1993-07-01 00:00:00
abstract::Eight patients who satisfied the following three criteria: 1) autistic behavior, 2) mental retardation and 3) stereotypic hand movements were evaluated. Four patients fulfilled the diagnostic criteria for the Rett syndrome developed by representatives of the International Rett Syndrome Association and the Center for D...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(12)80054-4
更新日期:1991-07-01 00:00:00
abstract::The sixth case of hydranencephaly in a twin is reported. The patient is an 11-year-old girl, and her twin was stillborn and macerated. Intrauterine disseminated intravascular coagulation may be the cause of hydranencephaly in this patient. ...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(80)80026-x
更新日期:1980-01-01 00:00:00
abstract::Oxidative stress resulting from increased free radical production and/or defects in antioxidant defences may be the cause of various neurodegenerative disorders. In this study, the roles of oxygen free radicals, nitric oxide, superoxide dismutase, vitamin E and vitamin C were investigated in pure and complicated hered...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2008.12.014
更新日期:2010-02-01 00:00:00
abstract::A case of precocious puberty due to postmeningitic hydrocephalus was presented. Concentrations of serum gonadotropins and estradiol were found to be elevated, and the response of LH to LHRH was also high, similar to that in the late pubertal stage. CT scanning demonstrated marked dilatation of the third ventricle. It ...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(83)80047-3
更新日期:1983-01-01 00:00:00
abstract::A 15-year-old boy presenting with epilepsy, optic atrophy and intracranial calcifications was diagnosed as having metaphyseal dysplasia by bone X-ray examinations. The patient had no laboratory data suggesting other metabolic or endocrinologic disorders. In addition, CT scans showed unique intracranial calcifications ...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/s0387-7604(97)00040-5
更新日期:1997-09-01 00:00:00
abstract:OBJECTIVES:To evaluate the outcome of ketogenic diets (KDs) in patients with glucose transport type 1 deficiency syndrome (GLUT1DS) in Japan. METHODS:A nationwide survey for GLUT1DS was conducted by sending questionnaires to board-certified pediatric neurologists nationwide to obtain clinical and laboratory data. RES...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2016.01.002
更新日期:2016-08-01 00:00:00
abstract::Congenital neuromuscular disease with uniform type 1 fibers is a rare form of congenital nonprogressive myopathy. We report a 3-year-old boy with this disease who showed delayed motor developmental milestones and recurrent acute respiratory failure. He obtained head control at 16 months, crawled at 17 months and sat a...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2005.06.008
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Cohen syndrome (CS) is a rare multi-system autosomal recessive disorder with a high prevalence in the Finnish population. Clinical features of Finnish-type CS are homogeneous, however, in non-Finnish populations, CS diagnosis is challenging due to broad phenotypic variability. METHODS:We studied a consangui...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2020.04.010
更新日期:2020-09-01 00:00:00
abstract::The future of human societies depends on children being able to achieve their optimal physical and psychological development. Developmental delay is failure to acquire age-appropriate functionality. It may involve one or more streams of development. Responsive parenting has potential to promote better development. Pri...
journal_title:Brain & development
pub_type: 杂志文章,评审
doi:10.1016/j.braindev.2009.06.004
更新日期:2010-02-01 00:00:00
abstract::A research committee supported by the Japanese government conducted a nationwide survey on the epidemiology of acute encephalopathy in Japan using a questionnaire. A total of 983 cases reportedly had acute encephalopathy during the past 3 years, 2007-2010. Among the pathogens of the preceding infection, influenza viru...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2011.07.012
更新日期:2012-05-01 00:00:00
abstract::We report sibling cases of aromatic L-amino acid decarboxylase (AADC) deficiency, which is a very rare congenital metabolic disorder. These patients were born to healthy and non-consanguineous parents, and presented oculogyric crises, paroxysmal dystonic attacks, and severe psychomotor retardation since early infancy....
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2009.05.004
更新日期:2010-06-01 00:00:00
abstract::Molecular background of neurogenetic disease is briefly reviewed. Importance and usefulness of genetic testing are emphasized. Molecular genetics is a powerful tool for investigation of epileptic syndromes. Diagnosis based on gene analysis will give a new insight for pathophysiology and clinical outcome of the patient...
journal_title:Brain & development
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.braindev.2011.01.007
更新日期:2011-10-01 00:00:00
abstract::Rett syndrome (RTT) is a neurodevelopmental disorder that is one of the most common causes of mental retardation in females. RTT diagnosis is based on distinct clinical criteria. We describe here a female patient with severe phenotype of congenital variant RTT. The patient originally presented with severe developmenta...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/j.braindev.2011.09.014
更新日期:2012-08-01 00:00:00
abstract::A 10-year-old male patient, who had suffered from intractable convulsions from the neonatal period, is presented. Serial brain images suggested slow, gradual destruction of neural elements. Human cytomegalovirus (HCMV) DNA was detected in his cerebrospinal fluid (CSF) by means of the polymerase chain reaction. Intrath...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/0387-7604(93)90086-n
更新日期:1993-11-01 00:00:00
abstract::A 2-year-old boy with herpes simplex encephalitis developed diffuse brain lesions involving the white matter of both cerebral hemispheres. These lesions in the white matter were clearly observed on magnetic resonance imaging (MRI) with the T2-weighted sequence, and were found to have spontaneously disappeared on subse...
journal_title:Brain & development
pub_type: 杂志文章
doi:10.1016/0387-7604(95)00141-7
更新日期:1996-03-01 00:00:00