Papers by Aviva Fattal-valevski
Pediatric Pulmonology, Jan 3, 2022
BackgroundEmergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramat... more BackgroundEmergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramatic improvements in respiratory failure and survival. However, these “treated” patients sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function. We observed three main nonrespiratory manifestations in these patients comprised of facial deformities, feeding problems, and spinal deformities.ObjectiveTo investigate these three main sequelae in nusinersen‐treated SMA1 patients.MethodsData on nusinersen‐treated SMA1 patients were prospectively collected throughout a 3‐year period, with special focus upon nonrespiratory features of the disease.ResultsTwenty nusinersen‐treated SMA1 patients were included (eight males, median age 13.5 months, interquartile range: 4–56.2 months), among whom 17 survived after 3 years of follow‐up. At follow‐up, 15 (88%) patients were diagnosed with facial weakness, hypoplasia, or deformity. All but one patient (94%) were fed invasively by percutaneous endoscopic gastrostomy or nasogastric tube feeding. Four patients (25%) had maintained oral feeding in parallel to gastrostomy feeding and had clinical and radiologic evidence of aspirations. Fifteen (88%) patients were diagnosed with scoliosis, of whom seven had undergone or were scheduled to undergo corrective surgery.ConclusionsNusinersen‐treated SMA1 patients may sustain facial deformities, feeding problems, and severe scoliosis, all of which affect their respiratory system. Strict surveillance of these complications is essential to avoid further respiratory morbidity.
Journal of Neuro-ophthalmology, Dec 1, 2017
Background: Pseudotumor cerebri syndrome (PTCS) is a disorder defined by increased intracranial p... more Background: Pseudotumor cerebri syndrome (PTCS) is a disorder defined by increased intracranial pressure in the absence of an intracranial space-occupying lesion. This retrospective study aimed to examine the outcomes in children with PTCS. Methods: Data was collected retrospectively from the charts of consecutive pediatric patients treated for PTCS at our hospital between 2000 and 2007 (60 patients; 36 females, 24 males). Results: Forty-six patients (76.6%) responded well to acetazolamide therapy, with full resolution of symptoms, including papilledema (average treatment duration 1 year; range: 1 month-5 years). Of the 14 patients with no response to treatment, 9 (23.4%) required surgical intervention. Nonresponders tended to be younger at presentation (8.7 vs 11.5 years, P = 0.04). Twelve patients (26%) experienced relapse after acetazolamide was discontinued. The group that experienced relapse was significantly younger than the nonrelapsers (8.9 vs 12.1 years, P , 0.05). Conclusions: Younger age at presentation with PTCS was found to be a risk factor for treatment failure or relapse.
Neuromuscular Disorders, Oct 1, 2021
Final Diagnoses Brain MRI Indications Total Number n=331 (100%) SOL n=51 (15%)* Epilepsy 27 (8%)*... more Final Diagnoses Brain MRI Indications Total Number n=331 (100%) SOL n=51 (15%)* Epilepsy 27 (8%)* West Syndrome 11 (3%)* Focal Cortical Dysplasia 8 (2%)* Infectious Process 51 (15%)* Cerebrovascular Disease 24 (7.3%)* Psychogenic Condition 10 (3%)* ADEM 8 (2%)* Other Demyelinating Condition 11 (3%)* Migraine 10 (3%)* IIH 12 (4%)* Hydrocephalus 6 (2%)* Other 21 (6%)* No Specific Diagnosis 81 (24%)* Cerebral SOL suspicion + Neurological signs + Papilledema
Frontiers in Neurology, Oct 13, 2021
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by deletion ... more Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by deletion or mutation of the SMN1 gene. It is characterized by a progressive loss of motor neurons resulting in muscle weakness. The disease affects 1 in 11,000 live births and before the era of treatment SMA was a leading genetic cause of mortality in infants. Recently, disease modifying therapies have been introduced in clinical practice. They include intrathecal and oral antisense oligonucleotides binding to pre-mRNA of SMN2 gene and increasing the translation of fully functional SMN protein as well as SMN1 gene replacement therapy. Onasemnogene abeparvovec uses the adeno-associated virus 9 (AAV9) vector to deliver the SMN1 gene. Phase 1 and phase 3 clinical trials showed that a single administration of onasemnogene abeparvovec resulted in improvement of motor functions in the majority of infants with SMA. Currently, phase 3 trials in SMA1 and SMA2 patients, as well as presymptomatic infants diagnosed with SMA, are ongoing. The drug was approved for medical use in the US in 2019, and in Japan and the European Union in 2020. Thus, first real-world data on efficacy and safety of onasemnogene abeparvovec in SMA patients are available.
Journal of Child Neurology, Feb 28, 2012
Journal of Child Neurology, Jun 10, 2020
The clinical applicability and yield of brain magnetic resonance imaging (MRI) in the setting of ... more The clinical applicability and yield of brain magnetic resonance imaging (MRI) in the setting of an inpatient pediatric department has not been investigated. The authors performed a retrospective chart review of nontraumatic/nonneurosurgical children who underwent brain MRI during their hospitalization in a general pediatric department over a 5-year period. Of the 331 children who underwent brain MRI, 148 (45%) had abnormal findings. High-risk headaches and focal seizures were significantly correlated with findings on brain MRI. Diagnostic and therapeutic yields were most significant in acute demyelinating events, acute cerebrovascular disorders, high-risk headaches when supported by neurologic and ophthalmologic findings, focal seizures with evidence of multifocal epileptic activity on an electroencephalogram and ophthalmic complaints when accompanied by cranial nerve palsy and optic nerve impairment. Since the contributions of a brain MRI in hospitalized children is pivotal in specific clinical situations, a judicious decisionmaking process should be done before its scheduling, in order to optimize clinical care.
Journal of Neuro-ophthalmology, Dec 1, 2011
We present a rare case of a diffuse anaplastic astrocytoma (gliomatosis configuration) in a child... more We present a rare case of a diffuse anaplastic astrocytoma (gliomatosis configuration) in a child, which was misdiagnosed as pseudotumor cerebri following initially normal CT of the brain and elevated opening pressure on lumbar puncture with normal cerebrospinal composition.
International journal of gynaecology and obstetrics, Feb 22, 2005
Pediatric Neurology, Jul 1, 2023
Children (Basel), Mar 9, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Neuropediatrics, Feb 12, 2021
Pompe's disease occurs due to an autosomal recessive trait resulting from numerou... more Pompe's disease occurs due to an autosomal recessive trait resulting from numerous distinctive mutations in the GAA gene. It manifests as a broad spectrum of clinical phenotypes with progressive weakness that impairs motor and respiratory functions being common for all its forms. Cardiac hypertrophy is a prominent feature of its classic infantile form. To date, the pathogenic variant c.2015G > A (p.Arg672Gln) in exon 14 of the GAA gene has been described in 10 children of different ethnic groups, with variable phenotypic presentations. This work describes three children from two unrelated families of Arab ethnicity who presented with infantile-onset Pompe's disease as a result of a c.2015G > A (p.Arg672Gln) mutation. The clinical course of the children we report was more severe than previous reports. This further emphasizes the lack of a strict genotype–phenotype correlation in regard to the unique c.2015G > A (p.R672Q) mutation that causes Pompe's disease. This information contributes to the knowledge of the phenotypic expression of the specific mutation c.2015G > A (p.Arg672Gln) that causes Pompe's disease.
Archives of Disease in Childhood, Oct 1, 2014
Kidney function tests were investigated in both 1-day and 7-days DMTU-treated (500 mg/kg ip initi... more Kidney function tests were investigated in both 1-day and 7-days DMTU-treated (500 mg/kg ip initially, then 125 mg/kg ip every 12h) rats. The effect of DMTU on maximum urine concentrating function was investigated in low (6%) and normal (20%) protein-fed rats. Results DMTU non-competitively inhibited UT-A and UT-B with IC 50 of~3 mM. Following 500 mg/kg ip injection, plasma DMTU concentration was initially 10 mM (plasma elimination t 1/2~1 0 h) and urine DMTU concentration was >20 mM for 12 h. DMTUtreated rats showed reversible, sustained reduction in urine osmolality (>60%) and 3-fold increased daily urine output. DMTU increased renal electrolyte-free water excretion without altering solute excretion. DMTU impaired maximum urinary concentrating function only in normal protein-fed rats. Methylurea, a non-UT inhibitor urea analogue, had no effect on either urine volume or osmolality. DMTU-treated rats had greater diuresis and much reduced urinary salt loss compared to that of furosemide-treated rats. Conclusions These results establish a rat model of sustained UT inhibition and demonstrate remarkable diuretic efficacy of UT inhibition. Prominent effect of UT inhibitors on net renal water excretion implies a novel therapeutic strategy for treatment of oedema in hypervolemic diseases.
Nutrition and Health, Jul 1, 2001
The neurodevelopmental and cognitive outcome of long-term Intrauterine Growth Restriction (IUGR) ... more The neurodevelopmental and cognitive outcome of long-term Intrauterine Growth Restriction (IUGR) has been followed up from pregnancy to school age at the Tel Aviv Child Development Centre.
Journal of Medical Genetics, Nov 6, 2015
Leukodystrophies are genetic white matter disorders affecting the formation or maintenance of mye... more Leukodystrophies are genetic white matter disorders affecting the formation or maintenance of myelin. Among the recently discovered genetic defects associated with leukodystrophies, several genes converge on a common mechanism involving protein transcription/translation and ER stress response. The genetic basis of a novel congenital leukodystrophy, associated with early onset spastic paraparesis, acquired microcephaly and optic atrophy was studied in six patients from three unrelated Ashkenazi-Jewish families. To this end we used homozygosity mapping, exome analysis, western blot (Hikeshi, HSF1-pS326 and b-actin) in patient fibroblasts, indirect immunofluorescence (HSP70 and HSF1) in patient fibroblasts undergoing heat shock stress, nuclear injection of plasmids expressing Hikeshi or EGFP in patient fibroblasts, in situ hybridization and Immunoblot analysis of Hikeshi in newborn and adult mouse brain. All the patients were homozygous for a missense mutation, p.Val54Leu, in C11ORF73 encoding HSP70 nuclear transporter protein, Hikeshi. The mutation segregated with the disease in the families and was carried by 1:200 Ashkenazi-Jewish individuals. The mutation was associated with undetectable level of Hikeshi in the patients' fibroblasts and with lack of nuclear HSP70 during heat shock stress, a phenomenon which was reversed upon the introduction of normal human Hikeshi to the patients cells. Hikeshi was found to be expressed in central white matter of mouse brain. These data underscore the importance of Hikeshi for HSP70 relocation into the nucleus. It is likely that in the absence of Hikeshi, HSP70 cannot attenuate the multiple heat shock induced nuclear phenotypes, leaving the cells unprotected during heat shock stress. We speculate that the sudden death of three of the six patients following a short febrile illness and the life-threatening myo-pericarditis in the fourth are the result of excess extra-nuclear HSP70 level which initiates cytokine release or provide target for natural killer cells. Alternatively, nuclear HSP70 might play an active role in stressed cells protection.
European Journal of Human Genetics, Mar 27, 2023
European Journal of Human Genetics, Oct 1, 2019
Epilepsia, Jun 21, 2011
Purpose: Benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most common epilept... more Purpose: Benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most common epileptic syndrome in childhood. The outcome is usually excellent, but there are some atypical forms of BCECTS with less favorable outcomes. The aim of this study was to delineate the frequency of these atypical features among patients with BCECTS. Methods: We conducted a retrospective chart study by retrieving the medical records of all consecutive patients with BCECTS who were evaluated in four pediatric neurology outpatient clinics in Israel between the years 1991 and 2008. Key Findings: A total of 196 patients with BCECTS were identified (78 female and 118 male; mean age at time of diagnosis 7.64 years, range 1.5-14). The mean duration of follow-up was 4.43 years (range 2-11). Nine patients (4.6%) developed electrical status epilepticus in slow waves sleep (ESES) during follow-up, four (2%) had Landau-Kleffner syndrome, three (1.5%) had BCECTS with frequent refractory seizures, two (1%) had BCECTS with falls at presentation, one (0.5%) had a ''classic'' atypical variant, and one (0.5%) had oromotor dysfunction. None had rolandic status epilepticus. Sixty-one patients (31%) had attention deficit hyperactivity disorder (ADHD), 43 (21.9%) had specific cognitive deficits, and 23 (11.7%) had behavioral abnormalities, including aggressiveness, anxiety disorders, depression, and pervasive developmental disorder (PDD). Significance: The prevalence of most atypical forms of BCECTS other than ESES is low. There is, however, a high prevalence of ADHD and specific cognitive deficits among patients with BCECTS.
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Papers by Aviva Fattal-valevski