Stiff Person Syndrome and Encephalitis with GAD Antibodies with Severe Anterograde Amnesia in an Adolescent: A Case Study and Literature Review.

Antiglutamic acid decarboxylase (GAD65) encephalitis is rare and few pediatric cases have been reported, with variable clinical presentations. A 14-year-old female adolescent was managed in our department. She had been treated for several months for drug-resistant temporal lobe epilepsy and gradually presented major anterograde amnesia with confusion. Upon her arrival at the University Hospital Centre, she showed a classical form of stiff person syndrome. The brain magnetic resonance imaging showed bitemporal hyperintensities and hypertrophy of the amygdala. The blood and cerebrospinal fluid were positive for GAD65 antibodies. At 2 years of immunosuppressive treatment and rehabilitation, the course showed partial improvement of the memory and neuropsychiatric impairment, and epilepsy that continued to be active. GAD65 antibodies are associated with various neurological syndromes, and this presentation combining limbic encephalitis and stiff person syndrome is the first pediatric form published to date; there are also few cases described in adults.

PENDAH program for parents with children with attention deficit hyperactivity disorder. French adaptation of a behavioral parent training group: pilot study.

Behavioral parent training (BPT) is recognized as an effective part of the care offered to children with attention deficit hyperactivity disorder (ADHD). The aim of this pilot study was to objectively examine the effect that this intervention may have on motor activity, in addition to the measures classically found in this type of study. Parents of 24 school-aged children (6-12 year) with ADHD who met eligibility criteria were enrolled in the study. Before, after and five months after the intervention, we used three-dimensional accelerometers over one-week periods to measure the children's motor activity, and questionnaires for parental stress, quality of life, ADHD symptoms, anxiety and sensory disorders. To measure motor activity, a control group of normotypic children matched for age, sex and socio-professional category was set up. The experimental group showed slight decreases in motor activity compared with the control group, particularly in the classroom. The intervention showed improvements for parents in average stress and quality of life, and for children in average intensity global ADHD symptom, inattention, opposition and aggression, in line with previous studies on the effectiveness of BPT. The trial is the first clinical study to assess the effects of BPT on motor activity in children with ADHD.

Reading Comprehension Impairment in Children With Neurofibromatosis Type 1 (NF1): The Need of Multimodal Assessment of Attention.

Attention span, which has been shown to have an impact on reading quality in many other conditions, is one of the main cognitive disorders of neurofibromatosis type 1 (NF1). The aim of this work is to observe the impact of attention on reading comprehension, in NF1 and non-NF1 children. A multicenter, cross-sectional study was conducted on 150 children (8-12 years old) with or without NF1 (75 NF1 vs 75 non-NF1; 72 female, 78 male), matched for age, sex, handedness, and reading level, thus forming a continuum from good to poor readers in both NF1 and non-NF1 groups. Children with intellectual deficiency or neurologic or psychiatric disorder were excluded. Attentional skills were assessed by combining a parent questionnaire (Child Behavior CheckList) and a performance-based assessment (Conner's Continuous Performance Test-Second Edition). Reading comprehension was assessed through a standardized reading comprehension test (ORLEC Lobrot). The performance-based attention scores were associated with text and sentence comprehension ability (P = .0235 and P = .0164, respectively), while indirect questionnaire attention scores were only associated with sentence comprehension (P = .0263). For both groups, the correlations between questionnaire and performance-based measures were low. We have shown that reading comprehension is greatly influenced by attention in NF1 and non-NF1, even if predictors of good reading comprehension also include IQ score and reading accuracy. Indirect observer-rated questionnaires and direct performance-based measures of attention do not assess the same variables, are linked to different components of reading skills, and are not interchangeable assessments of attention difficulties. Both assessments are complementary and must be used simultaneously, leading to recommendations that support multimodal assessment of attention.

Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype?

Background: Cognitive impairment is the most common neurological manifestation in NF1 and occurs in 30-70% of NF1 cases. The onset and severity of each specific cognitive deficit varies greatly from child to child, with no apparent external causes. The wide variability of phenotype is the most complex aspect in terms of management and care. Despite multiple research, the mechanism underlying the high heterogeneity in NF1 has not yet been elucidated. While many studies have focused on the effects of specific and precise genetic mutations on the NF1 phenotype, little has been done on the impact of NF1 transmission (sporadic vs. familial cases). We used a complete neuropsychological evaluation designed to assess five large cognitive areas: general cognitive functions (WISC-IV and EVIP); reading skills ("L'Alouette," ODEDYS-2 and Lobrot French reading tests); phonological process (ODEDYS-2 test); visual perceptual skills (JLO, Thurstone and Corsi block tests) and attention (CPT-II), as well as psychosocial adjustments (CBCL) to explore the impact of NF1 transmission on cognitive disease manifestation in 96 children affected by NF1 [55 sporadic cases (29♀, 26♂); 41 familial cases (24♀, 17♂)]. Results: Familial and Sporadic form of NF1 only differ in IQ expression. The families' socioeconomic status (SES) impacts IQ performance but not differently between sporadic and familial variants. However, SES is lower in familial variants than in the sporadic variant of NF1. No other cognitive differences emerge between sporadic and familial NF1. Conclusions: Inheritance in NF1 failed to explain the phenotype variability in its entirety. IQ differences between groups seems in part linked to the environment where the child grows up. Children with NF1, and especially those that have early diagnoses (most often in inherited cases), must obtain careful monitoring from their early childhood, at home to strengthen investment in education and in school to early detect emerging academic problems and to quickly place them into care. Trial Registration: IDRCB, IDRCB2008-A01444-51. Registered 19 January 2009.

Neural substrates of low-frequency repetitive transcranial magnetic stimulation during movement in healthy subjects and acute stroke patients. A PET study.

The aim of the study was to investigate, with an rTMS/PET protocol, the after-effects induced by 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the regional cerebral blood flow (rCBF) of the primary motor cortex (M1) contralateral to that stimulated during a movement. Eighteen healthy subjects underwent a baseline PET scan followed, in randomized order, by a session of Real/Sham low-frequency (1 Hz) subthreshold rTMS over the right M1 for 23 min. The site of stimulation was fMRI-guided. After each rTMS session (real or sham), subjects underwent behavioral hand motor tests and four PET scans. During the first two scans, ten subjects (RH group) moved the right hand ipsilateral to the stimulated site and eight subjects (LH group) moved the left contralateral hand. All remained still during the last two scans (rest). Two stroke patients underwent the same protocol with rTMS applied on contralesional M1. Compared with Sham-rTMS, Real-rTMS over the right M1 was followed by a significant increase of rCBF during right hand movement in left S1M1, without any significant change in motor performance. The effect lasted less than 1 h. The same rTMS-induced S1M1 overactivation was observed in the two stroke patients. Commissural connectivity between right dorsal premotor cortex and left M1 after real-rTMS was observed with a psychophysiological interaction analysis in healthy subjects. No major changes were found for the left hand. These results give further arguments in favor of a plastic commissural connectivity between M1 both in healthy subjects and in stroke patients, and reinforce the potential for therapeutic benefit of low-frequency rTMS in stroke rehabilitation.

Deficit in phonological processes: a characteristic of the neuropsychological profile of children with NF1.

Learning disabilities are one of the most frequent complications of neurofibromatosis type 1 (NF1) in children. Studies of the effects of the neurocognitive deficit on academic performance are relatively rare, owing to the small size of the populations concerned. However, research is needed to develop effective rehabilitation programs. In the present study, we explored the impact of a possible phonological deficit on the reading abilities of children with NF1. A multicenter, cross-sectional study was conducted in France on two groups of 75 children with or without NF1 aged 8-12 years, matched for age, sex, handedness, and reading level. All participants underwent a neuropsychological evaluation to assess their general cognitive level, reading skills, phonological processes, visuoperceptual abilities, and attentional capacity. Phonological skills were assessed by means of two phonological awareness tasks and one short-term memory task. In the group of children with NF1, 41% had reading difficulties. Phonological processes were impaired in this group, compared with the children without NF1. Similar differences were found for a phoneme deletion task after adjustment for reading difficulties, IQ level, and visuoperceptual abilities. Phonological awareness, but not phonological short-term memory, was impaired in children with NF1, and not just those whose reading was impaired. Results suggest that children with NF1 have a phonological awareness deficit, whatever their reading level. Identification of reduced phonological skills may warrant the implementation of a specific rehabilitation program before early reading difficulties emerge.

Motor impairment in children with Neurofibromatosis type 1: Effect of the comorbidity with language disorders.

BACKGROUND: There is a body of evidence demonstrating comorbidity of motor and cognitive deficit in «idiopathic¼ developmental disorders. These associations are also found in developmental disorders secondary to monogenic disorders as in Neurofibromatosis type 1 for which the principal complication during childhood is learning disabilities. The comparison of motor impairment between developmental disorders either idiopathic or secondary as in NF1 could help us to better understand the cause of the combined language/motor deficit in these populations. AIM: The aim of this current study was to investigate motor impairment in children with NF1 for which oral language had been specified and then to compare the motors skills of the NF1 group to motor performance of children with Specific Language Disorder (SLD). METHOD: Two groups of 49 children between 5 and 12years old were included and compared, the NF1 group and the SLD (Specific Language Disorder) group. Each child completed evaluation involving cognitive, language and motor assessment. RESULTS: In NF1 group, motor impairment was more frequent and more severe and concerned specifically balance rather than manual dexterity or ball skills, compared to a group of children with SLD. This motor impairment was independent of language status in the NF1 group. CONCLUSIONS: These results as well as other studies on the same topic could suggest that in NF1 children, fine motor skills impairment would be dependent on the existence of comorbidity with language disorders. Also, that gross motor skills impairment, and more precisely the balance deficit would be characteristic of NF1. This issue encourages studies of procedural learning that can involve the fronto-striatal or the fronto-cerebellar loops according to the type of motor tasks and the stage of learning.