Anna Presicci

GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak

Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1.

Mental retardation and epilepsy in patients with isolated cerebellar hypoplasia

Congenital nonprogressive cerebellar ataxia includes a complex group of disorders with heterogeneous phenotypic and etiopathogenetic characteristics. Despite recent advances in the understanding of the role of the cerebellum in cognition and behavior, the opinion that the clinical presentation of congenital cerebellar diseases is principally linked to motor dysfunction is common. This is largely due to the lack of well-organized epidemiologic studies on the prevalence of nonmotor disturbances in cerebellar disease. The association between congenital cerebellar disease and epilepsy has rarely been described. We report clinical, neurophysiologic, neuroimaging, and neuropsychologic features in a group of 14 patients with congenital nonprogressive cerebellar ataxia associated with cerebellar hypoplasia, 5 of whom have familial disease, aiming to further a better knowledge of the prevalence of cognitive and/or emotional impairment and epilepsy. The results confirm that cerebellar hypoplasia predisposes individuals to psychomotor delay (71.4%) and cognitive impairment (85.7%). Moreover, the tendency toward abnormal electroencephalographic (EEG) findings (78.5%), associated in a minor percentage of cases with epilepsy (28.5%), is also evident in our study. (J Child Neurol 2006;21:776—781; DOI 10.2310/7010.2006.00181).

Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study.

Although schizophrenia has been diagnosed in children, this group of disorders has received too little attention in the clinical and research literature. Preliminary data suggest that early onset schizophrenia (EOS) and very early onset schizophrenia (VEOS) tend to have a worse outcome than adult onset schizophrenia, and seem to be related to a greater familial vulnerability, due to genetic, psychosocial, and environmental factors. Recently, advanced neuroimaging techniques have revealed structural and functional brain abnormalities in some cerebral areas. This paper reports on a case diagnosed as VEOS, with premorbid year-long psychopathological history. The patient showed atypical proton magnetic resonance spectroscopy findings, and normal brain and spine computer tomography and brain magnetic resonance images.

Cerebral venous thrombosis after lumbar puncture and intravenous high dose corticosteroids: a case report of a childhood multiple sclerosis.

The association between cerebral venous thrombosis (CVT) and multiple sclerosis (MS) has already been reported in several adult patients with clinically definite MS, in a suspected relation to i.v. corticosteroids or previously performed lumbar puncture (LP). We are reporting a case, which is, to our knowledge, the first one concerning a child patient with a MS, who developed multiple CVT after LP and during high-dose i.v. corticosteroid. Our conclusions are that the sequence LP followed by high dose corticosteroids may be a contributory factor for the development of CVT when associated with other risk factors.

Electrophysiological Study in 2 Children With Transient Hypohidrosis Induced by Topiramate

Objective: Hypohidrosis, often associated with hyperthermia, has been reported, mostly in children, as a rare and reversible adverse effect of topiramate, an anticonvulsant drug with a broad spectrum of antiepileptic activity. The aim of our study is to detect a possible skin innervation involvement asthe mechanism underlying hypohidrosis in children treated with topiramate. Methods: A neurophysiological study has been performed on 2 children who have developed hypohidrosis under topiramate treatment. Electrophysiologicaldata have been recorded during topiramate treatment and compared with a control group. Sympathetic skin responses have been recorded during topiramate assumption and after its discontinuation. Results: In our 2 cases with hypohidrosis related to topiramate, electrophysiological study showed normal function of both beta and delta sensory fibers and absent sympathetic skin responses that recovered to normal after topiramate discontinuation. Conclusions: Our findings confirm that topiramate might induce a transitory specific carbonic anhydrase block at the level of sweat glands, without involvement of peripheral nervous system.

Neuropsychiatric impairment in children with continuous spikes and waves during slow sleep: a long-term follow-up study.

A long-term follow-up study was conducted in patients affected by Continuous Spikes and Waves during slow Sleep (CSWS) to evaluate the long-term outcomes. Twenty-five patients (19 males, 6 females), from 2 to 16 years of age (mean age 6 years±3 SD), affected by CSWS syndrome, as defined by the International League Against Epilepsy (ILAE, 1989), were enrolled and followed for 11 years (mean duration of follow-up: 3.9 years). At the time of the appearance of CSWS, one or more neuropsychiatric disorders were present in 96% of the patients, such as behavioral problems in 54%, mental retardation in 37.5%, learning disabilities in 33%, developmental coordination disorder in 17%, language disorder in 12.5%, and pervasive developmental disorder in 8%. During the follow-up, neuropsychiatric dysfunctions remained unaltered in 52% of the patients, worsened in 24%, and improved in only 24%. Our data confirm that CSWS may be associated with a broad spectrum of neuropsychiatric disorders and may promote their worsening over time. Moreover, the findings cannot be generalized to all cases of children with CSWS because most of the children in the subgroups with no change in outcome and worse outcome had symptomatic CSWS.

Clinical and instrumental (magnetic resonance imaging [MRI] and multimodal evoked potentials) follow-up of brain lesions in three young patients with neurofibromatosis 1.

Diagnosis of neurofibromatosis 1 is based on clinical criteria. In a large number of children with neurofibromatosis 1, magnetic resonance imaging (MRI) reveals high-signal T2-weighted intensities in different brain regions, defined as unidentified bright objects. These lesions are asymptomatic; most of them regress spontaneously with age, but the presence of contrast enhancement or mass effect in them usually strongly suggests an increased risk of proliferative changes. To date, few studies have focused on evoked potentials in patients with neurofibromatosis 1, and the reported abnormalities did not have significant clinical correlations. We describe the clinical and instrumental (MRI and evoked potentials) follow-up of three patients with neurofibromatosis 1. MRI and evoked potentials showed subclinical involvement of the central nervous system. Some MRI T2-weighted hyperintensities showed enhancement and mass effect of uncertain significance. During follow-up, the MRI lesions spontaneously decreased in size or enhancement, allowing us to exclude the hypothesis of proliferative lesions; in the same way, some asymptomatic evoked potential abnormalities disappeared. These findings suggest that both MRI and evoked potentials could be useful in the detection and monitoring of cerebral complications of neurofibromatosis 1.

Depressive and adjustment disorders - some questions about the differential diagnosis: case studies.

Background Diagnosis and treatment of mood disorders in youth are still problematic because in this age the clinical presentation is atypical, and the diagnostic tools and the therapies are the same as that used for the adults. Mood disorders are categorically divided into unipolar disorders (major depressive disorder and dysthymic disorder) and bipolar disorder in Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision), but mood symptoms are also comprised in the diagnostic criteria of the adjustment disorder (AD), which occur in many different psychiatric disorders, and may also be found in some physical conditions. The differential diagnosis is not much addressed in the midst of clinical investigation and so remains the major problem in the clinical practice. Aims The associations between some variables and the depressive disorder and AD were analyzed to make considerations about differential diagnosis. Patients and methods We reported a retrospective study of 60 patients affected by depressive disorder and AD. The analysis has evaluated the association between some variables and the single diagnostic categories. We have considered 10 variables, of which 6 are specific to the disorders, and 4 have been considered related problems. Results The statistical analysis showed significant results for the associations of 3 variables (prevalent symptoms, treatment, and family history) with the single diagnostic categories. Conclusion The discriminate analysis resulted in statistically significant differences between patients with depressive disorders and those with AD on 3 variables, of which 2 are specific to the disorders, and 1 is included in the related problems. The other variables were weakly associated with the single diagnostic categories without any statistically significant differences. The 3 variables that were associated with the single diagnostic categories support the distinct construct validity of the 2 diagnostic categories, but, to date, it is difficult to establish if these variables can be considered diagnostic predictors. On the other hand, the other variables did not support the distinct construct validity of the 2 diagnostic categories, which suggest an overlapping and dimensional concept. The spectrum approach could unify categorical classification that is essential with a dimensional view. Combination of dimensional and categorical principles for classifying mood disorders may help to reduce the problems of underdiagnosis and undertreatment.

Megalocornea and mental retardation syndrome: clinical and instrumental follow-up of a case.

Megalocornea—mental retardation syndrome, otherwise known as Neuhauser syndrome, is a rare autosomal recessive disorder. Only 36 cases have been reported in the literature. We describe the clinical and instrumental follow-up, lasting 5 years, of a case showing the typical features of the syndrome, associated with transient hypothyroidism, epilepsy, cerebral palsy with choreoathetotic movements, and brain malformation. Our report might help better delineate the phenotype and natural history of the syndrome. (J Child Neurol 2006;21:893—896; DOI 10.2310/ 7010.2006.00202).

Costello syndrome: cognitive and proton magnetic resonance spectroscopy findings--a case report.

The authors describe a girl with Costello syndrome who showed cerebral palsy and neurosensorial deafness. Brain computer tomography and magnetic resonance findings were normal. Multivoxel proton magnetic resonance spectroscopy showed a lowering of the peak of choline with a reduced choline/creatine ratio at the level of the centrum semiovale. These findings might be due to a congenital dysmyelinating or hypomyelinating condition. A complete neuroimaging study can play a relevant role to better clarify the pathogenesis of brain involvement in Costello syndrome.