One hand, two hands, two people: Prospective sensorimotor control in children with autism.

Where grasps are made reveals how grasps are planned. The grasp height effect predicts that, when people take hold of an object to move it to a new position, the grasp height on the object is inversely related to the height of the target position. In the present study, we used this effect as a window into the prospective sensorimotor control of children with autism spectrum disorders without accompanying intellectual impairment. Participants were instructed to grasp a vertical cylinder and move it from a table (home position) to a shelf of varying height (target position). Depending on the conditions, they performed the task using only one hand (unimanual), two hands (bimanual), or with the help of a co-actor (joint). Comparison between the performance of typically developing children and children with autism revealed no group difference across tasks. We found, however, a significant influence of IQ on grasp height modulation in both groups. These results provide clear evidence against a general prospective sensorimotor planning deficit and suggest that at least some form of higher order planning is present in autism without accompanying intellectual impairment.

Anti-N-methyl-D-aspartate-receptor encephalitis: cognitive profile in two children.

BACKGROUND: Anti-N-Methyl D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder associated with antibodies against NMDAR resulting in a characteristic neuropsychiatric syndrome characterized by seizures, dyskinesias, and cognitive impairment. The extent and specific tasks associated with cognitive dysfunction in anti-NMDAR encephalitis have not been fully investigated. AIMS: To describe cognitive and neuropsychological profile in two children with anti-NMDAR encephalitis. METHODS: Clinical, laboratory, cognitive and neuropsychological assessments have been performed. Cognitive functions have been evaluated one year after the disease onset, at age 4 years and 10 months in one patient and at age 5 years and 5 months in the other subject. The first patient has been re-assessed one year after the first evaluation. RESULTS: Both children, who were reported to be normal before disease onset, showed a severe neurological impairment during the acute phase of disease with progressive substantial recovery following treatment. Selective and prolonged attention, activation and integration of semantic information and verbal fluency were particularly impaired. Significant improvements were observed at neuropsychological re-assessment. CONCLUSIONS: Executive dysfunction seems to be the "core" of the neuropsychological profile of children with anti-NMDAR encephalitis. Cognitive abilities may be, at least to some extent, recovered providing that immunomodulatory treatment and specific psychomotor and pedagogical therapy are started soon after disease onset.

Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency.

BACKGROUND: SLC6A8, an X-linked gene, encodes the creatine transporter (CRTR) and its mutations lead to cerebral creatine (Cr) deficiency which results in mental retardation, speech and language delay, autistic-like behaviour and epilepsy (CRTR-D, OMIM 300352). CRTR-D represents the most frequent Cr metabolism disorder but, differently from Cr synthesis defects, that are partially reversible by oral Cr supplementation, does not respond to Cr treatment even if precociously administrated. The precursors of Cr are the non-essential amino acids Glycine (Gly) and Arginine (Arg), which have their own transporters at the brain-blood barrier level and, therefore, their supplementation appears an attractive and feasible therapeutic option aimed at stimulating Cr endogenous synthesis and, in this way, at overcoming the block of Cr transport within the brain. However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial. METHODS: In this study five Italian male patients affected by CRTR-D were supplemented with oral L-Arg at a dosage of 300 mg/kg/day divided into 3 doses, for 24-36 months. Biochemical and plasmatic amino acids examinations and thyroid hormone dosages were periodically performed. Moreover, Proton and Phosphorus Magnetic Resonance Spectroscopy (MRS) was monitored during follow-up in concurrence with neuropsychological evaluations. RESULTS: During L-Arg treatment a clinical improvement in motor skills and to a lesser extent in communication and attention was observed. In addition, all patients had a reduction in the number and frequency of epileptic seizures. Daily living skills appeared also to be positively influenced by L-Arg treatment. Moreover, Total Cr and especially PhosphoCr, evaluated by proton and phosphorus spectroscopy, showed a mild increase, although well below the normal range. CONCLUSION: This study provides information to support the effectiveness of L-Arg supplement treatment in CTRT-D patients; in fact the syndromic pattern of cognitive and linguistic deficit presented by CRTR-D patients was partially altered by L-Arg supplementation especially at a qualitative clinical level. Oral L-Arg may represent not only a protective factor towards a further cognitive decline, but can lead to the acquisition of new skills.

Anti-glutamic acid decarboxylase limbic encephalitis without epilepsy evolving into dementia with cerebellar ataxia.

OBJECTIVES: To expand the spectrum of the clinical presentation of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis and to improve the recognition of this entity. DESIGN: Case study. SETTING: University hospital. PATIENT: An 11-year-old-girl with progressive mood and behavioral disorder, speech impairment, and short-term memory impairment who manifested cerebellar ataxia with nystagmus during the disease course. INTERVENTIONS: Blood and cerebrospinal fluid analysis including autoantibodies, electroencephalography, brain and spinal magnetic resonance imaging, and cognitive and neuropsychological assessment were performed. High-dose methylprednisolone sodium succinate pulses, cycles of intravenous immunoglobulins, mycophenolate mofetil, and rituximab as well as antipsychotics and benzodiazepine were administered. RESULTS: Diagnosis of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis was made. The clinical features during the first months of disease included only mood, behavioral, and memory impairment. After 5 months, despite immunotherapies, cerebellar ataxia with nystagmus appeared with brain magnetic resonance imaging evidence of cerebral atrophy. No clinical or infraclinical seizures were recorded during follow-up. CONCLUSIONS: Anti-glutamic acid decarboxylase antibodies-related limbic encephalitis can present with only behavioral or neuropsychological symptoms without any epileptic disorder. Moreover, cerebellar ataxia related to anti-glutamic acid decarboxylase antibodies can be observed in patients with limbic encephalitis during the disease course.

Neonatal diabetes mellitus due to pancreatic agenesis and pervasive developmental disorder.

Recent studies suggested a link between type 1 diabetes mellitus and pervasive developmental disorder. Moreover, permanent neonatal diabetes mellitus due to pancreatic agenesis can be associated with neurological deficit involving cerebellar functions, but no association with pervasive developmental disorder has been described so far. Clinical and neuropsychological evaluation of a child with pancreatic agenesis, mental retardation and pervasive developmental disorder is reported.

Severe epilepsy in X-linked creatine transporter defect (CRTR-D).

Disorders of creatine synthesis or its transporter resulting in neurological impairment with mental retardation and epilepsy have only been recognized in recent years. To date, the epileptic disorder observed in creatine transporter deficiency (CRTR-D) has been described as a mild phenotype with infrequent seizures and favorable response to common antiepileptic drugs. We report on a 5 year-old boy with known speech delay who presented with severe and refractory epilepsy. After extensive investigations, metabolite analysis and brain 1H-MRS suggested CRTR-D, which was confirmed by the detection of a known pathogenic mutation in the SLC6A8 gene (c.1631C>T; p.Pro544Leu).