Post varicella angiopathy (PVA) is an underdiagnosed but potentially severe disease in both pediatric and adult settings. No guidelines are available for the medical and neurosurgical management of ...this condition. We report the first pediatric case with headache and PVA who was treated with surgical revascularization before the onset of ischemic events.
This case report was conducted via retrospective chart review. A literature review was also completed, in order to identify previously described PVA undergone to revascularization.
We report on a 9-year-old boy presenting with a long history of headache and PVA involving the distal left middle cerebral artery. The arterial lesion rapidly worsened over a 10 months’ period with formation of focal moyamoya-like collaterals, despite an adequate intravenous antiviral treatment. The pattern of headaches significantly changed with a clear left-side lateralization and a “re-build-up” phenomenon on EEG. The patient was treated with left superficial temporal artery - middle cerebral artery (STA-MCA) bypass and encephalo-duro-arterio-myo-pericranial-synangiosis. This combined treatment resulted in an immediate and persistent improvement of brain perfusion, accompanied by prompt resolution of neurological symptoms.
Two cases who presented with Suzuki stage III (unilateral or bilateral) moyamoya PVA and recurrent strokes or transient ischemic attacks despite adequate pharmacological prophylaxis have been surgically treated using both indirect and direct revascularization technique. The outcome was good in both cases.
Surgical revascularization may have a role in the treatment of PVA and may prevent stroke. Given the lack of standardized treatment algorithms, individualized regimens should be formulated on a case-specific basis.
Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its ...rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.
In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.
All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.
Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.
Abstract Introduction ADCY5 mutations have been recently identified as an important cause of early-onset hyperkinetic movement disorders. The phenotypic spectrum associated with mutations in this ...gene is expanding. However, the ADCY5 mutational frequency in cohorts of paediatric patients with hyperkinetic movement disorders has not been evaluated. Methods We performed a screening of the entire ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed childhood-onset hyperkinetic movement disorders, featuring chorea alone or in combination with myoclonus and dystonia. All patients had normal CSF analysis and brain imaging and were regularly followed-up in tertiary centers for paediatric movement disorders. Results We identified five unrelated subjects with ADCY5 mutations (11% of the cohort). Three carried the p. R418W mutation, one the p. R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while one patient inherited the mutation from his similarly affected father. All patients had delayed motor and/or language milestones with or without axial hypotonia and showed generalized chorea and dystonia, with prominent myoclonic jerks in one case. Episodic exacerbations of the baseline movement disorder were observed in most cases, being the first disease manifestation in two patients. The disease course was variable, from stability to spontaneous improvement during adolescence. Conclusion Mutations in ADCY5 are responsible for a hyperkinetic movement disorder that can be preceded by episodic attacks before the movement disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance are frequently observed in patients with ADCY5 mutations.
•GRID2 homozygous deletions or pathogenic variants cause SCAR18.•Severity depends on heterozygous/ homozygous state, onset age, variant position.•We report on the oldest (31-year-old) patient with ...congenital-onset SCAR18.•Association of deletion and loss of function variant can lead to early-onset SCAR18.•Stable cerebellar atrophy was documented between 14 and 30 years.
Autosomal recessive spinocerebellar ataxia type 18 (SCAR18) is caused by pathogenic variants in the Glutamate Receptor, Ionotropic, Delta-2 (GRID2) gene. We describe the long-term follow-up from 1 to 31 years of an Italian patient with congenital SCAR18 who is compound heterozygous for a maternally-inherited nonsense variant and a de novo microdeletion. To date, this is the longest follow-up in congenital SCAR18.
Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung ...disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined.
Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations.
Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis.
This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.
Abstract Background Mutations in the gene PRRT2 have been identified in a variety of early-onset paroxysmal disorders. To date associations between PRRT2 mutations and benign myoclonus of early ...infancy have not been reported. Clinical report We describe a baby affected by PRRT2 mutation and benign infantile epilepsy, with an episode of focal status epilepticus. During follow-up he developed benign myoclonus of early infancy. Discussion We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia. Conclusions Currently the function of PRRT2 is poorly understood, even if a marked pleiotropy and variable penetrance of its mutations are well known. Our case concurs in expanding the broad clinical spectrum of PRRT2-related disorders.
Abstract Background Guillain–Barré syndrome is the most frequent cause of flaccid paresis in Western countries. Moreover, CMV infection is the most common antecedent viral infection in adult patients ...and the presence of specific IGM antiganglioside antibodies is often identified. Instead, Guillain–Barré syndrome following CMV infections is rarely reported in childhood and often presents severe symptoms at onset and longer recovery times. Material and methods One year of clinical, electrophysiological and serological follow-up of a 9-year old child with axonal sensory-motor Guillain–Barré syndrome following CMV infection is reported. Moreover, the literature data on paediatric sensory-motor axonal GBS and GBS secondary to CMV infection and antiganglioside antibodies are reviewed. Results Our patient presented with paraesthesias and a pattern of weakness showing proximal predominance and affecting the upper limbs more than the lower limbs. At nadir, unilateral facial palsy was also present and he was unable to walk. Electroneurography showed motor-sensory axonal damage. Both anti-CMV and anti-GM2 IgM were positive. After early treatment with IVIG and IV methylprednisolone the patient recovered deambulation. Six months later, his neurological examination was normal and electroneurography showed normal data. Conclusion The sensory-motor axonal form of Guillain–Barré syndrome following CMV infection may present a good prognosis and a prompt full recovery also in children, if adequate treatment is started in time.
“Minimal” holoprosencephaly in a 14q deletion syndrome patient Della Giustina, Elvio; Iodice, Alessandro; Spagnoli, Carlotta ...
American journal of medical genetics. Part A,
December 2017, 2017-Dec, 2017-12-00, 20171201, Letnik:
173, Številka:
12
Journal Article
Recenzirano
We report on a patient with terminal deletion of the long arm of chromosome 14 displaying brain interhemispheric fusion limited to the midline anterior frontal cortex associated with hypoplastic ...corpus callosum and incomplete rotation of the left hippocampus in a clinical setting of motor and intellectual disability with poor language, and social behavior abnormalities with aggressiveness. Some possible correlations between clinical signs and symptoms and various aspects of the complex brain malformation are briefly discussed and compared with other known abnormalities of chromosome 14. The different neuropathology of the most common forms and the new forms of holoprosencephaly recently described is also discussed and leads us to suggest classifying the interhemispheric fusion of this case as a “minimal” form of holoprosencephaly. This appears to be the first description in a 14q deletion patient.
Summary
Objective
To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at ...time of recruitment and through the first month. The selected population will be followed for 2–5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance.
Methods
In this observational, multicenter, nationwide study, children (age 1 month–12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and <13 years; and (3) written informed consent. Children were subdivided into three groups: ≤3 years, >3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses.
Results
Two hundred fifty‐nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month–12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy.
Significance
In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone.
PDF
