Ali Fatemi - Academia.edu (original) (raw)
Papers by Ali Fatemi
International Journal of Developmental Neuroscience, 2019
Developmental Neuroscience, 2013
Wiener Klinische Wochenschrift, Oct 1, 2002
Sudden infant death (SID) is the most common cause of death among infants aged 2 to 12 months in ... more Sudden infant death (SID) is the most common cause of death among infants aged 2 to 12 months in Austria. The complete autopsy required in order to diagnose SID, including the additional investigations, and the comprehensive autopsies needed for epidemiological studies are not common practice because of the different statutory regulations in the provinces and the absence of a uniform federal law in this regard. According to statistics, in the last four years only 83% (1997) to 70% (1999) of the reported SID cases in Austria were autopsied. Our survey in the forensic medicine and pathological institutes of Austria also revealed markedly different practices in regard of the manner in which autopsies are performed and parents are interviewed and followed up. For this reason, the SIDS Consensus Work Group of Austrian centers for the prevention of sudden infant death recommends the following: a) a comprehensive autopsy by a trained specialist to be established as a prerequisite for diagnosing "SIDS"; b) performing autopsies on a centralized basis in those forensic or pathological institutes that have agreed to adhere to protocol-based autopsy standards; c) the introduction of quality control in terms of a regional clinical-pathological conference; and d) standardizing the elements of the interview with parents of SID victims. Implementing these measures and entering the collected information into a data base in which the master data are encoded by the individual institutions, will help to evaluate the role of major epidemiological risk factors that information campaigns are focused upon, namely sleeping in prone position, the role of nicotine, etc. In addition, it will be necessary to formulate federal laws that standardize the divergent provincial regulations.
Data Revues 00029378 V208i1ss S0002937812017395, Dec 28, 2012
Wiener Klinische Wochenschrift, 2004
The prevalence of snoring was evaluated in school children between 11 and 15 years of age. In add... more The prevalence of snoring was evaluated in school children between 11 and 15 years of age. In addition to items reported by parents, children were asked to answer a questionnaire in order to receive information about the children's potential complaints, life style and school performance. The study was performed in 21 randomly selected schools in the Vienna area. 1434 school children were interviewed by a questionnaire (mean age 12.5 years, median 13 years, 676 girls vs. 699 boys). The questionnaire consisted of 45 multiple-choice questions about the socioeconomic status, possible sleep disorders and signs or symptoms of obstructive sleep apneas (OSA). The questionnaire completed by parents was also used to calculate the Brouillette-Score from the items snoring, obstructed breaths and apneas. 5.2% (74/1434) of children and 6.9% (86/1259) of parents or caregivers reported about snoring (frequently or very frequently). There were no sex differences for the children's and the parents' questionnaire. None of the children had a clearly positive result (hint of OSA) from the Brouillette-Score whereas "suspicious OSA" was observed in 3.2% (40/1259). When frequent and very frequent snorers were compared with the other children, more mouth breathing during sleep (p < 0.00001), mouth dryness (p < 0.00005), headache (p < 0.0005), cigarette exposition at home (p < 0.001), smoking (p < 0.005), daytime naps (p < 0.005), crying out of sleep (p < 0.01), daytime tiredness (p < 0.05) und a higher body mass index (p < 0.05) could be observed in this group, in addition to the items reported by the parents. The prevalence of snoring is lower in our study than in other studies. No statistically significant sex differences were observed, both in the parents' and the children's questionnaire. In our study snoring seems to be a sign or symptom of different sleep disorders, and not only of OSA. A statistically significant correlation between snoring and anamnestic hints of sleep disorders underlines the need to ask concerned children themselves for observations potentially associated with sleep disorders. Results of the Brouillette-Score could not be used to identify sleep disorders in our study.
Wien Klin Wochenschr, 2003
Journal of controlled release : official journal of the Controlled Release Society, Jan 13, 2015
Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead ... more Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and mig...
American journal of medical genetics. Part A, Jan 2, 2015
Elongator is a multi-subunit protein complex essential to transcription elongation, histone acety... more Elongator is a multi-subunit protein complex essential to transcription elongation, histone acetylation, and tRNA modification. The complex consists of six highly conserved protein subunits, called Elongator Proteins (ELP) 1-6. Apart from an association with intellectual disability (ID), there is limited clinical information about patients with ELP2 variants. Here we report on two brothers with severe ID, spastic diplegia, and self-injury whose presentation eluded a diagnosis for over 20 years. In both brothers, whole exome sequencing revealed a likely pathogenic, compound heterozygous missense variant in ELP2. We describe the phenotype and natural history of the ELP2-related disorder in these brothers. © 2015 Wiley Periodicals, Inc.
American journal of obstetrics and gynecology, Jan 30, 2014
Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammat... more Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammation induces preterm birth and perinatal brain injury. Mesenchymal stem cells (MSCs) have been shown to exhibit immunomodulatory effects in many inflammatory conditions. We hypothesized that treatment with human adipose tissue-derived MSCs may decrease the rate of preterm birth and perinatal brain injury through changes in antiinflammatory and regulatory milieu. A mouse model of intrauterine inflammation was used with the following groups: (1) control; (2) intrauterine inflammation (lipopolysaccharide); and (3) intrauterine lipopolysaccharide + intraperitoneal (MSCs). Preterm birth was investigated. Luminex multiplex enzyme-linked immunosorbent assays were performed for protein levels of cytokines in maternal and fetal compartments. Immunofluorescent staining was used to identify and localize MSCs and to examine microglial morphologic condition and neurotoxicity in perinatal brain. Behavi...
Annals of Neurology, 2014
Whole exome sequencing (WES) represents a significant breakthrough in clinical genetics as a powe... more Whole exome sequencing (WES) represents a significant breakthrough in clinical genetics as a powerful tool for etiological discovery in neurodevelopmental disorders. To better characterize the genetic landscape of neurodevelopmental disorders, we analyzed patients in our pediatric neurogenetics clinic who underwent WES. We performed a retrospective cohort study on 78 patients with various neurodevelopmental disabilities and unrevealing workup prior to WES. We characterized their molecular diagnoses, clinical features, and whether their previous treatment plan changed due to WES results. The overall presumptive diagnostic rate for our cohort was 41% (n = 32 of 78 patients). Nineteen patients had a single autosomal dominant (AD) disorder, 11 had a single autosomal recessive (AR) disorder, 1 had an X-linked dominant disorder, and 1 had both an AD and an AR disorder. The 32 patients with pathogenic or likely pathogenic variants exhibited various neurobehavioral and neuroimaging abnormalities, including intellectual disability/developmental delay (n = 28), cerebral palsy-like encephalopathy (n = 11), autism spectrum disorder (n = 5), delayed/hypomyelination (n = 7), and cerebellar abnormalities (n = 9). The results of WES affected management for all patients with a presumptive diagnosis, triggering reproductive planning (n = 27), disease monitoring initiation (n = 4), investigation of systemic involvement of the disorder(s) (n = 6), alteration of presumed disease inheritance pattern (n = 7), changing of prognosis (n = 10), medication discontinuation (n = 5) or initiation (n = 2), and clinical trial education (n = 3). The high diagnostic yield of WES supports its use in pediatric neurology practices. It may also lead to earlier diagnosis, impacting medical management, prognostication, and family planning. WES therefore serves as a critical tool for the child neurologist.
Wiener Klinische Wochenschrift, 2003
Pediatric Neurology, 2013
Perinatal hypoxic-ischemic brain injury and stroke in the developing brain remain important cause... more Perinatal hypoxic-ischemic brain injury and stroke in the developing brain remain important causes of chronic neurologic morbidity. Emerging data suggest that transplantation of umbilical cord blood-derived stem cells may have therapeutic potential for neuroregeneration and improved functional outcome. The pluripotent capacity of stem cells from the human umbilical cord blood provides simultaneous targeting of multiple neuropathologic events initiated by a hypoxic-ischemic insult. Their high regenerative potential and naïve immunologic phenotype makes them a preferable choice for transplantation. A multiplicity of transplantation protocols have been studied with a variety of brain injury models; however, only a few have been conducted on immature animals. Biological recipient characteristics, such as age and sex, appear to differentially modulate responses of the animals to the transplanted cord blood stem cells. Survival, migration, and function of the transplanted cells have also been studied and reveal insights into the mechanisms of cord blood stem cell effects. Data from preclinical studies have informed current clinical safety trials of human cord blood in neonates, and further work is needed to continue progress in this field.
Neurochemical Research, 2000
* Special issue dedicated to Dr. Nicole A. Baumann. This article is dedicated to Dr. Nicole Bauma... more * Special issue dedicated to Dr. Nicole A. Baumann. This article is dedicated to Dr. Nicole Baumann, who has made such major contributions to further understanding of the basic biology of metabolic and genetic disorders of the nervous system. One aspect that is particularly ...
Magnetic Resonance in Medicine, 2005
The magnetization transfer ratio (MTR) is a reliable measure of MT effects because it employs an ... more The magnetization transfer ratio (MTR) is a reliable measure of MT effects because it employs an internal standard that allows quantitative comparison between subjects, independent of other contrasts, coil loading, and coil sensitivity profiles. However, at very high spatial resolution in the spinal cord at 1.5 T, the use of MTR quantification has been hampered by low signal-to-noise ratio (SNR) and acute sensitivity to motion. Here, the suitability of cerebrospinal fluid (CSF) as an alternative inter-subject MT signal intensity reference for the spine is evaluated. Contrary to MTR, this so-called MTCSF internal standard does not remove interfering T(1), T(2), and spin density contrast and is not expected to be able to discriminate between myelination and inflammation effects. However, it can detect initial changes in myelination when signal alterations are not yet detectable by conventional MRI. As a first example, this is demonstrated for the noninflammatory spinal cord white matter disease adrenomyeloneuropathy.
Magnetic Resonance in Medicine, 2009
The Lancet Neurology, 2011
International Journal of Developmental Neuroscience, 2019
Developmental Neuroscience, 2013
Wiener Klinische Wochenschrift, Oct 1, 2002
Sudden infant death (SID) is the most common cause of death among infants aged 2 to 12 months in ... more Sudden infant death (SID) is the most common cause of death among infants aged 2 to 12 months in Austria. The complete autopsy required in order to diagnose SID, including the additional investigations, and the comprehensive autopsies needed for epidemiological studies are not common practice because of the different statutory regulations in the provinces and the absence of a uniform federal law in this regard. According to statistics, in the last four years only 83% (1997) to 70% (1999) of the reported SID cases in Austria were autopsied. Our survey in the forensic medicine and pathological institutes of Austria also revealed markedly different practices in regard of the manner in which autopsies are performed and parents are interviewed and followed up. For this reason, the SIDS Consensus Work Group of Austrian centers for the prevention of sudden infant death recommends the following: a) a comprehensive autopsy by a trained specialist to be established as a prerequisite for diagnosing "SIDS"; b) performing autopsies on a centralized basis in those forensic or pathological institutes that have agreed to adhere to protocol-based autopsy standards; c) the introduction of quality control in terms of a regional clinical-pathological conference; and d) standardizing the elements of the interview with parents of SID victims. Implementing these measures and entering the collected information into a data base in which the master data are encoded by the individual institutions, will help to evaluate the role of major epidemiological risk factors that information campaigns are focused upon, namely sleeping in prone position, the role of nicotine, etc. In addition, it will be necessary to formulate federal laws that standardize the divergent provincial regulations.
Data Revues 00029378 V208i1ss S0002937812017395, Dec 28, 2012
Wiener Klinische Wochenschrift, 2004
The prevalence of snoring was evaluated in school children between 11 and 15 years of age. In add... more The prevalence of snoring was evaluated in school children between 11 and 15 years of age. In addition to items reported by parents, children were asked to answer a questionnaire in order to receive information about the children's potential complaints, life style and school performance. The study was performed in 21 randomly selected schools in the Vienna area. 1434 school children were interviewed by a questionnaire (mean age 12.5 years, median 13 years, 676 girls vs. 699 boys). The questionnaire consisted of 45 multiple-choice questions about the socioeconomic status, possible sleep disorders and signs or symptoms of obstructive sleep apneas (OSA). The questionnaire completed by parents was also used to calculate the Brouillette-Score from the items snoring, obstructed breaths and apneas. 5.2% (74/1434) of children and 6.9% (86/1259) of parents or caregivers reported about snoring (frequently or very frequently). There were no sex differences for the children's and the parents' questionnaire. None of the children had a clearly positive result (hint of OSA) from the Brouillette-Score whereas "suspicious OSA" was observed in 3.2% (40/1259). When frequent and very frequent snorers were compared with the other children, more mouth breathing during sleep (p < 0.00001), mouth dryness (p < 0.00005), headache (p < 0.0005), cigarette exposition at home (p < 0.001), smoking (p < 0.005), daytime naps (p < 0.005), crying out of sleep (p < 0.01), daytime tiredness (p < 0.05) und a higher body mass index (p < 0.05) could be observed in this group, in addition to the items reported by the parents. The prevalence of snoring is lower in our study than in other studies. No statistically significant sex differences were observed, both in the parents' and the children's questionnaire. In our study snoring seems to be a sign or symptom of different sleep disorders, and not only of OSA. A statistically significant correlation between snoring and anamnestic hints of sleep disorders underlines the need to ask concerned children themselves for observations potentially associated with sleep disorders. Results of the Brouillette-Score could not be used to identify sleep disorders in our study.
Wien Klin Wochenschr, 2003
Journal of controlled release : official journal of the Controlled Release Society, Jan 13, 2015
Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead ... more Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and mig...
American journal of medical genetics. Part A, Jan 2, 2015
Elongator is a multi-subunit protein complex essential to transcription elongation, histone acety... more Elongator is a multi-subunit protein complex essential to transcription elongation, histone acetylation, and tRNA modification. The complex consists of six highly conserved protein subunits, called Elongator Proteins (ELP) 1-6. Apart from an association with intellectual disability (ID), there is limited clinical information about patients with ELP2 variants. Here we report on two brothers with severe ID, spastic diplegia, and self-injury whose presentation eluded a diagnosis for over 20 years. In both brothers, whole exome sequencing revealed a likely pathogenic, compound heterozygous missense variant in ELP2. We describe the phenotype and natural history of the ELP2-related disorder in these brothers. © 2015 Wiley Periodicals, Inc.
American journal of obstetrics and gynecology, Jan 30, 2014
Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammat... more Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammation induces preterm birth and perinatal brain injury. Mesenchymal stem cells (MSCs) have been shown to exhibit immunomodulatory effects in many inflammatory conditions. We hypothesized that treatment with human adipose tissue-derived MSCs may decrease the rate of preterm birth and perinatal brain injury through changes in antiinflammatory and regulatory milieu. A mouse model of intrauterine inflammation was used with the following groups: (1) control; (2) intrauterine inflammation (lipopolysaccharide); and (3) intrauterine lipopolysaccharide + intraperitoneal (MSCs). Preterm birth was investigated. Luminex multiplex enzyme-linked immunosorbent assays were performed for protein levels of cytokines in maternal and fetal compartments. Immunofluorescent staining was used to identify and localize MSCs and to examine microglial morphologic condition and neurotoxicity in perinatal brain. Behavi...
Annals of Neurology, 2014
Whole exome sequencing (WES) represents a significant breakthrough in clinical genetics as a powe... more Whole exome sequencing (WES) represents a significant breakthrough in clinical genetics as a powerful tool for etiological discovery in neurodevelopmental disorders. To better characterize the genetic landscape of neurodevelopmental disorders, we analyzed patients in our pediatric neurogenetics clinic who underwent WES. We performed a retrospective cohort study on 78 patients with various neurodevelopmental disabilities and unrevealing workup prior to WES. We characterized their molecular diagnoses, clinical features, and whether their previous treatment plan changed due to WES results. The overall presumptive diagnostic rate for our cohort was 41% (n = 32 of 78 patients). Nineteen patients had a single autosomal dominant (AD) disorder, 11 had a single autosomal recessive (AR) disorder, 1 had an X-linked dominant disorder, and 1 had both an AD and an AR disorder. The 32 patients with pathogenic or likely pathogenic variants exhibited various neurobehavioral and neuroimaging abnormalities, including intellectual disability/developmental delay (n = 28), cerebral palsy-like encephalopathy (n = 11), autism spectrum disorder (n = 5), delayed/hypomyelination (n = 7), and cerebellar abnormalities (n = 9). The results of WES affected management for all patients with a presumptive diagnosis, triggering reproductive planning (n = 27), disease monitoring initiation (n = 4), investigation of systemic involvement of the disorder(s) (n = 6), alteration of presumed disease inheritance pattern (n = 7), changing of prognosis (n = 10), medication discontinuation (n = 5) or initiation (n = 2), and clinical trial education (n = 3). The high diagnostic yield of WES supports its use in pediatric neurology practices. It may also lead to earlier diagnosis, impacting medical management, prognostication, and family planning. WES therefore serves as a critical tool for the child neurologist.
Wiener Klinische Wochenschrift, 2003
Pediatric Neurology, 2013
Perinatal hypoxic-ischemic brain injury and stroke in the developing brain remain important cause... more Perinatal hypoxic-ischemic brain injury and stroke in the developing brain remain important causes of chronic neurologic morbidity. Emerging data suggest that transplantation of umbilical cord blood-derived stem cells may have therapeutic potential for neuroregeneration and improved functional outcome. The pluripotent capacity of stem cells from the human umbilical cord blood provides simultaneous targeting of multiple neuropathologic events initiated by a hypoxic-ischemic insult. Their high regenerative potential and naïve immunologic phenotype makes them a preferable choice for transplantation. A multiplicity of transplantation protocols have been studied with a variety of brain injury models; however, only a few have been conducted on immature animals. Biological recipient characteristics, such as age and sex, appear to differentially modulate responses of the animals to the transplanted cord blood stem cells. Survival, migration, and function of the transplanted cells have also been studied and reveal insights into the mechanisms of cord blood stem cell effects. Data from preclinical studies have informed current clinical safety trials of human cord blood in neonates, and further work is needed to continue progress in this field.
Neurochemical Research, 2000
* Special issue dedicated to Dr. Nicole A. Baumann. This article is dedicated to Dr. Nicole Bauma... more * Special issue dedicated to Dr. Nicole A. Baumann. This article is dedicated to Dr. Nicole Baumann, who has made such major contributions to further understanding of the basic biology of metabolic and genetic disorders of the nervous system. One aspect that is particularly ...
Magnetic Resonance in Medicine, 2005
The magnetization transfer ratio (MTR) is a reliable measure of MT effects because it employs an ... more The magnetization transfer ratio (MTR) is a reliable measure of MT effects because it employs an internal standard that allows quantitative comparison between subjects, independent of other contrasts, coil loading, and coil sensitivity profiles. However, at very high spatial resolution in the spinal cord at 1.5 T, the use of MTR quantification has been hampered by low signal-to-noise ratio (SNR) and acute sensitivity to motion. Here, the suitability of cerebrospinal fluid (CSF) as an alternative inter-subject MT signal intensity reference for the spine is evaluated. Contrary to MTR, this so-called MTCSF internal standard does not remove interfering T(1), T(2), and spin density contrast and is not expected to be able to discriminate between myelination and inflammation effects. However, it can detect initial changes in myelination when signal alterations are not yet detectable by conventional MRI. As a first example, this is demonstrated for the noninflammatory spinal cord white matter disease adrenomyeloneuropathy.
Magnetic Resonance in Medicine, 2009
The Lancet Neurology, 2011