BackgroundAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a pr... more BackgroundAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a primary microgliopathy caused by pathogenic variants in the colony-stimulating factor 1 receptor (CSF1R) gene. Since CSF1R signaling is crucial for microglia development, survival and function, induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial defects caused by ALSP patient-specificCSF1Rvariants.MethodsSerial modifications to an existing iMGL protocol were made, including but not limited to changes in growth factor combination to drive microglial differentiation, until successful derivation of microglia-like cells from an ALSP patient carrying a c.2350G > A (p.V784M)CSF1Rvariant. Using healthy control lines, the quality of the new iMGL protocol was validated through cell yield assessment, measurement of microglia marker expression, transcriptomic comparison to primary microglia, and evaluation of inflammatory and phagocytic activit...
Introduction The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world.... more Introduction The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world. This pandemic has had a significant impact on patients with chronic diseases. Among patients with demyelinating diseases of the central nervous system (CNS), such as Multiple Sclerosis (MS) or Neuromyelitis Optica Spectrum Disorder (NMOSD), concerns remain about the potential impact of COVID-19 on these patients given their treatment with immunosuppressive or immunomodulatory therapies. In this study, we review the existing literature investigating the impact of disease-modifying therapies(DMT) on COVID-19 risks in this group of patients. Method For this systematic review, we searched PubMed from January 1, 2020, to December 3, 2020. The following keywords were used: COVID-19” AND “Multiple Sclerosis” OR “Neuromyelitis Optica.” Articles evaluating COVID-19 in patients with demyelinating diseases of CNS were included. This study evaluates the different aspects of the DMTs in these patients during the COVID-19 era. Results and conclusion A total of 262 articles were found. After eliminating duplicates and unrelated research papers, a total of 84 articles met the final inclusion criteria in our study. Overall, the experiences of 2493 MS patients and 37 NMOSD patients with COVID-19 were included in this review. Among them, 46(1.8%) MS patients died(the global death-to-case ratio of Covid-19 was reported about 2.1%). Among DMTs, Rituximab had the highest mortality rate (4%). Despite controversies, especially concerning anti-CD20 monoclonal antibody therapies, a relation between DMT-use and COVID-19 disease- course was not found in many studies. This observation reinforces the recommendation of not stopping current DMTs. Other variables such as age, higher expanded disability status scale (EDSS) scores, cardiac comorbidities, and obesity were independent risk factors for severe COVID-19. Despite the risks of infection, most patients were willing to continue their DMT during the pandemic because of more significant concern about the risk of relapse or worsening MS symptoms. After the infection, an immune response's attenuation was seen in the patients on Fingolimod and anti-CD20 monoclonal antibodies. This may be a critical finding in future vaccinations.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
Background: Wolfram syndrome (WFS) is a genetic disorder clinically characterized by optic atroph... more Background: Wolfram syndrome (WFS) is a genetic disorder clinically characterized by optic atrophy (OA), diabetes mellitus, sensorineural deafness, and diabetes insipidus. It is caused by mutations in WFS1 (mono- or biallelic) or CISD2 (biallelic) genes. Neuroradiological features include cerebellar and/or brainstem atrophy with visual pathway and white matter involvement. We report two subjects with WFS in which multifocal, progressive, and contrast-enhancing white matter abnormalities (WMA) led to the consideration of multiple sclerosis (MS). Methods: We retrospectively analyzed the clinical, genetic, and radiological data from two unrelated subjects with genetically confirmed WFS and multifocal WMA. Results: Subject I: a 43-year-old woman, heterozygous for a known WFS1 variant, had a history of congenital deafness and OA. The brain MRI documented progressive multifocal WMA including pericallosal lesions. Subject II: a 28-year-old woman, compound heterozygous for two WFS1 variants...
BackgroundDominantly inherited GAA repeat expansions inFGF14are a common cause of spinocerebellar... more BackgroundDominantly inherited GAA repeat expansions inFGF14are a common cause of spinocerebellar ataxia (GAA-FGF14ataxia; SCA27B, late-onset). Molecular confirmation ofFGF14GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories.MethodsWe developed and validated a strategy to detectFGF14GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia.ResultsDiagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. Method comparison showed that capillary electrophoresis of long-range PCR products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, -2.48 to 31....
IntroductionAdult genetic leukoencephalopathies are rare neurological disorders that present uniq... more IntroductionAdult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders. We aim to present the experience of the WM Rounds Network and demonstrate the value of collaborative multidisciplinary international case discussion meetings in differentiating and preventing misdiagnoses between genetic white matter diseases and atypical MS.MethodsWe retrospectively reviewed the demographic, clinical and radiological data...
Introduction Existing stroke literature demonstrates that rapid recanalization of vessels improve... more Introduction Existing stroke literature demonstrates that rapid recanalization of vessels improves long-term prognosis after acute ischemic stroke. However, further optimization of the speed of the thrombectomy procedure, used to recanalize a blocked vessel, is limited by our minimal knowledge of the clot dimensions pre-procedure. Knowing the clot dimensions would allow planning of the thrombectomy procedure with the appropriate size and length of stent retriever, and determination of the correct site of the stent deployment ensuring total coverage of the clot by the stent retriever. Methods We performed a feasibility study to assess if multiphase computed tomography angiography (mCTA) can be used to estimate clot length by comparing CTA imaging data with imaging data obtained from conventional digital subtraction angiography (DSA). A retrospective chart review was performed of patients with clots in the proximal middle cerebral artery and adequate collateral circulation, who underw...
Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD)-are primarily autosomal re... more Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD)-are primarily autosomal recessive disorders caused by mutations in any of 13 PEX genes involved in peroxisome assembly. Compared to other PEX-related disorders, some PEX16 defects are associated with an atypical phenotype consisting of spasticity, cerebellar dysfunction, preserved cognition, and prolonged survival. In this case series, medical records and brain MRIs from 7 patients with this PEX16 presentation were reviewed to further characterize this phenotype. Classic PBD features such as sensory deficits and amelogenesis imperfecta were absent in all 7 patients, while all patients had hypertonia. Five patients were noted to have dystonia and received a treatment trial of levodopa/carbidopa. Four treated patients had partial but significant improvements in their dystonia and tremors, and 1 patient had only minimal response. Brain MRI studies commonly showed T2/FLAIR hyperintensities in the brainstem, superior and middle cerebellar peduncles, corticospinal tracts, and splenium of the corpus callosum. Genetic analysis revealed novel biallelic variants in 3 probands (c.683C > T/372delG; c.692A > G homozygous; c.865C > G/451C > T) and 1 novel variant (c.956_958delCGC) in another proband. We demonstrated residual PEX16 protein amounts by immunoblotting in fibroblasts available from 5 patients with this atypical PEX16 disease (3 from this series, 2 previously reported), in contrast to the absence of PEX16 protein in fibroblasts from a patient with the severe ZSD presentation. This study further characterizes the phenotype of PEX16 defects by highlighting novel and distinctive clinical, neuroradiological, and molecular features of the disease and proposes a potential treatment for the dystonia. ClinicalTrials.gov Identifier: NCT01668186. Date of registration: January 2012.
In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger g... more In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger gene sequencing in a proband with suspected but not confirmed CADASIL and her apparently asymptomatic father. The 35-year-old proband presented with migraine with visual aura. Brain MRI showed diffuse leukoencephalopathy, suggesting CADASIL. NOTCH3 gene sequencing (exons 3-6) was negative. Family history was unclear. The MRI study of the father documented severe, diffuse leukoencephalopathy, with involvement of the temporal poles and external capsules (not observed in the proband), and lacunar infarcts in the absence of cardiac disease or risk factors. The MRI findings were in favour of an autosomal dominant mode of transmission and reinforced the hypothesis of CADASIL. Full NOTCH3 gene sequencing uncovered a novel exon 8 mutation (c.1337G>A; p.Cys446Tyr) outside the most commonly mutated region of NOTCH3. The novel mutation leads to a typical MRI pattern but a variable overall phenotype. The study underlines the usefulness of combining full gene sequencing with familial MRI studies.
Intracerebral arteriovenous malformations (AVMs) are defined as the direct communication of arter... more Intracerebral arteriovenous malformations (AVMs) are defined as the direct communication of arteries to abnormal veins without interposing capillaries. Although AVMs can have various clinical presentations due to their dynamic nature, the most common presenting sign is intracerebral hemorrhage. Whenever an AVM is discovered, the therapeutic choice is often not obvious and it is influenced not only by the hemodynamic features of the AVM, but also by considerations of the extent of intervention-related morbidity and mortality. A patient with a left frontal AVM is described. He bled three years after gamma knife radiosurgery and developed aphasia. The complete obliteration of the AVM was later achieved by embolization. Functional compensatory brain reorganization and plasticity is discussed, since our patient presented with a fast recovery from aphasia and unexpected contralateral redistribution of the speech function and with preference for his second spoken language.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2015
Objective: Case report of NMDA receptor encephalitis in a young man with early refractory status ... more Objective: Case report of NMDA receptor encephalitis in a young man with early refractory status epilepticus and atypical radiological findings.Background:Anti-NMDA receptor encephalitis is an autoimmune disorder due to antibodies to the NR1-NR2B heterodimer of NMDA receptor. On imaging, it typically presents with T2 hyperintensities in mesio-temporal lobes, cerebral cortex and basal ganglia. We present a case with a dramatic clinical evolution and novel imaging findings. Design/Methods:Case report and review of imaging.Results:29-year-old male presented with mood disturbance followed by partial-complex seizures, facial dyskinesia and choreo-athetotic movements. Initial MRI showed subtle T2-hyperintensities in mesio-temporal lobes. Diagnosis of NMDA-receptor encephalitis was confirmed after CSF antibody detection. Prior to diagnostic confirmation, he developed refractory status epilepticus, and concomitant signs of herniation. A repeated MRI showed increased T2-hyperintensities of t...
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2011
Intracellular RNAses are involved in various functions, including microRNA maturation and turnove... more Intracellular RNAses are involved in various functions, including microRNA maturation and turnover. Mutations occurring in genes encoding RNAses cause Aicardi-Goutiéres syndrome (AGS). AGS mutations silence RNAse activity, thus inducing accumulation of endogenous RNAs, mainly consisting of short RNAs and microRNAs. Overload of intracellular RNA triggers Toll like receptor-dependent interferon-alpha production in the brain, which in turn activates neurotoxic lymphocytes and inhibits angiogenesis thus inducing the typical clinical phenotype of AGS. However, these pathogenic mechanisms are attenuated after three years of age by the endogenous production of DNAJP58IPK and Cystatin F, which arrest AGS progression. Because RNAses are involved in microRNA turnover, we evaluated the expression of 957 microRNAs in lymphocytes from AGS patients and control patients. Our results indicate that microRNA overload occurs in AGS patients. This upregulation inhibits microRNA turnover impeding the synthesis of the novel microRNAs required for the differentiation and myelination of the brain during the initial period of postnatal life. These pathogenic mechanisms result in AGS, a neurological syndrome characterized by irritability, mild hyperpyrexia, pyramidal and extrapyramidal signs, and spastic-dystonic tetraplegia. Typical cerebrospinal fluid alterations include lymphocytosis and elevated interferon-alpha levels. Brain imaging demonstrates cerebral calcifications, white matter abnormalities, and progressive cerebral atrophy.Thus, evidence exists that mutations silencing intracellular RNases affect microRNA turnover resulting in the severe clinical consequences in the brain characterizing the clinical feature of AGS.
We describe a case of brain cortical reorganization after embolization of a large right temporal ... more We describe a case of brain cortical reorganization after embolization of a large right temporal arteriovenous malformation. A comprehensive imaging protocol, including functional magnetic resonance imaging (fMRI), cortical thickness analysis and 320-row computed tomography (CT) perfusion was used to provide information on brain plasticity and potential steal phenomenon. A 25-year-old man known for a right temporal grade V Spetzler-Martin classification arteriovenous malformation (AVM) presented with left progressive hemiparesis. He underwent functional 3T magnetic resonance imaging (fMRI), cortical thickness analysis, and CT perfusion (CT 320 row, Aquilion ONE, Toshiba, Tokyo, Japan) before and after endovascular treatment. The results were compared to look for modifications in brain perfusion and organization. An improvement in the left hemiparesis and a reorganization of motor function were observed after endovascular treatment. Modifications in the angioarchitecture and perfusio...
Pol III-related leukodystrophies are caused by mutations in POLR3A and POLR3B genes and all share... more Pol III-related leukodystrophies are caused by mutations in POLR3A and POLR3B genes and all share peculiar imaging and clinical features. The objectives of this study are (1) to define the neuroradiologic pattern in a cohort of POLR3A and POLR3B subjects and (2) to compare the neuroradiologic pattern of Pol III-related leukodystrophies with other hypomyelinating disorders. The magnetic resonance imaging (MRI) examinations of 13 patients with POLR3A and POLR3B mutations and of 14 patients with other hypomyelinating disorders were analyzed. All the subjects with Pol III-related leukodystrophies presented hypomyelination associated with T2 hypointensity of the thalami and/or the pallida. Twelve subjects (92%) presented T2 hypointensity of the optic radiations. Cerebellar atrophy was observed in most patients (92%). The combination of the analyzed criteria identified patients with Pol III-related leukodystrophies with a sensitivity of 84.6 % and a specificity of 92.9%.
BackgroundAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a pr... more BackgroundAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a primary microgliopathy caused by pathogenic variants in the colony-stimulating factor 1 receptor (CSF1R) gene. Since CSF1R signaling is crucial for microglia development, survival and function, induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial defects caused by ALSP patient-specificCSF1Rvariants.MethodsSerial modifications to an existing iMGL protocol were made, including but not limited to changes in growth factor combination to drive microglial differentiation, until successful derivation of microglia-like cells from an ALSP patient carrying a c.2350G > A (p.V784M)CSF1Rvariant. Using healthy control lines, the quality of the new iMGL protocol was validated through cell yield assessment, measurement of microglia marker expression, transcriptomic comparison to primary microglia, and evaluation of inflammatory and phagocytic activit...
Introduction The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world.... more Introduction The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world. This pandemic has had a significant impact on patients with chronic diseases. Among patients with demyelinating diseases of the central nervous system (CNS), such as Multiple Sclerosis (MS) or Neuromyelitis Optica Spectrum Disorder (NMOSD), concerns remain about the potential impact of COVID-19 on these patients given their treatment with immunosuppressive or immunomodulatory therapies. In this study, we review the existing literature investigating the impact of disease-modifying therapies(DMT) on COVID-19 risks in this group of patients. Method For this systematic review, we searched PubMed from January 1, 2020, to December 3, 2020. The following keywords were used: COVID-19” AND “Multiple Sclerosis” OR “Neuromyelitis Optica.” Articles evaluating COVID-19 in patients with demyelinating diseases of CNS were included. This study evaluates the different aspects of the DMTs in these patients during the COVID-19 era. Results and conclusion A total of 262 articles were found. After eliminating duplicates and unrelated research papers, a total of 84 articles met the final inclusion criteria in our study. Overall, the experiences of 2493 MS patients and 37 NMOSD patients with COVID-19 were included in this review. Among them, 46(1.8%) MS patients died(the global death-to-case ratio of Covid-19 was reported about 2.1%). Among DMTs, Rituximab had the highest mortality rate (4%). Despite controversies, especially concerning anti-CD20 monoclonal antibody therapies, a relation between DMT-use and COVID-19 disease- course was not found in many studies. This observation reinforces the recommendation of not stopping current DMTs. Other variables such as age, higher expanded disability status scale (EDSS) scores, cardiac comorbidities, and obesity were independent risk factors for severe COVID-19. Despite the risks of infection, most patients were willing to continue their DMT during the pandemic because of more significant concern about the risk of relapse or worsening MS symptoms. After the infection, an immune response's attenuation was seen in the patients on Fingolimod and anti-CD20 monoclonal antibodies. This may be a critical finding in future vaccinations.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
Background: Wolfram syndrome (WFS) is a genetic disorder clinically characterized by optic atroph... more Background: Wolfram syndrome (WFS) is a genetic disorder clinically characterized by optic atrophy (OA), diabetes mellitus, sensorineural deafness, and diabetes insipidus. It is caused by mutations in WFS1 (mono- or biallelic) or CISD2 (biallelic) genes. Neuroradiological features include cerebellar and/or brainstem atrophy with visual pathway and white matter involvement. We report two subjects with WFS in which multifocal, progressive, and contrast-enhancing white matter abnormalities (WMA) led to the consideration of multiple sclerosis (MS). Methods: We retrospectively analyzed the clinical, genetic, and radiological data from two unrelated subjects with genetically confirmed WFS and multifocal WMA. Results: Subject I: a 43-year-old woman, heterozygous for a known WFS1 variant, had a history of congenital deafness and OA. The brain MRI documented progressive multifocal WMA including pericallosal lesions. Subject II: a 28-year-old woman, compound heterozygous for two WFS1 variants...
BackgroundDominantly inherited GAA repeat expansions inFGF14are a common cause of spinocerebellar... more BackgroundDominantly inherited GAA repeat expansions inFGF14are a common cause of spinocerebellar ataxia (GAA-FGF14ataxia; SCA27B, late-onset). Molecular confirmation ofFGF14GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories.MethodsWe developed and validated a strategy to detectFGF14GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia.ResultsDiagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. Method comparison showed that capillary electrophoresis of long-range PCR products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, -2.48 to 31....
IntroductionAdult genetic leukoencephalopathies are rare neurological disorders that present uniq... more IntroductionAdult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders. We aim to present the experience of the WM Rounds Network and demonstrate the value of collaborative multidisciplinary international case discussion meetings in differentiating and preventing misdiagnoses between genetic white matter diseases and atypical MS.MethodsWe retrospectively reviewed the demographic, clinical and radiological data...
Introduction Existing stroke literature demonstrates that rapid recanalization of vessels improve... more Introduction Existing stroke literature demonstrates that rapid recanalization of vessels improves long-term prognosis after acute ischemic stroke. However, further optimization of the speed of the thrombectomy procedure, used to recanalize a blocked vessel, is limited by our minimal knowledge of the clot dimensions pre-procedure. Knowing the clot dimensions would allow planning of the thrombectomy procedure with the appropriate size and length of stent retriever, and determination of the correct site of the stent deployment ensuring total coverage of the clot by the stent retriever. Methods We performed a feasibility study to assess if multiphase computed tomography angiography (mCTA) can be used to estimate clot length by comparing CTA imaging data with imaging data obtained from conventional digital subtraction angiography (DSA). A retrospective chart review was performed of patients with clots in the proximal middle cerebral artery and adequate collateral circulation, who underw...
Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD)-are primarily autosomal re... more Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD)-are primarily autosomal recessive disorders caused by mutations in any of 13 PEX genes involved in peroxisome assembly. Compared to other PEX-related disorders, some PEX16 defects are associated with an atypical phenotype consisting of spasticity, cerebellar dysfunction, preserved cognition, and prolonged survival. In this case series, medical records and brain MRIs from 7 patients with this PEX16 presentation were reviewed to further characterize this phenotype. Classic PBD features such as sensory deficits and amelogenesis imperfecta were absent in all 7 patients, while all patients had hypertonia. Five patients were noted to have dystonia and received a treatment trial of levodopa/carbidopa. Four treated patients had partial but significant improvements in their dystonia and tremors, and 1 patient had only minimal response. Brain MRI studies commonly showed T2/FLAIR hyperintensities in the brainstem, superior and middle cerebellar peduncles, corticospinal tracts, and splenium of the corpus callosum. Genetic analysis revealed novel biallelic variants in 3 probands (c.683C > T/372delG; c.692A > G homozygous; c.865C > G/451C > T) and 1 novel variant (c.956_958delCGC) in another proband. We demonstrated residual PEX16 protein amounts by immunoblotting in fibroblasts available from 5 patients with this atypical PEX16 disease (3 from this series, 2 previously reported), in contrast to the absence of PEX16 protein in fibroblasts from a patient with the severe ZSD presentation. This study further characterizes the phenotype of PEX16 defects by highlighting novel and distinctive clinical, neuroradiological, and molecular features of the disease and proposes a potential treatment for the dystonia. ClinicalTrials.gov Identifier: NCT01668186. Date of registration: January 2012.
In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger g... more In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger gene sequencing in a proband with suspected but not confirmed CADASIL and her apparently asymptomatic father. The 35-year-old proband presented with migraine with visual aura. Brain MRI showed diffuse leukoencephalopathy, suggesting CADASIL. NOTCH3 gene sequencing (exons 3-6) was negative. Family history was unclear. The MRI study of the father documented severe, diffuse leukoencephalopathy, with involvement of the temporal poles and external capsules (not observed in the proband), and lacunar infarcts in the absence of cardiac disease or risk factors. The MRI findings were in favour of an autosomal dominant mode of transmission and reinforced the hypothesis of CADASIL. Full NOTCH3 gene sequencing uncovered a novel exon 8 mutation (c.1337G>A; p.Cys446Tyr) outside the most commonly mutated region of NOTCH3. The novel mutation leads to a typical MRI pattern but a variable overall phenotype. The study underlines the usefulness of combining full gene sequencing with familial MRI studies.
Intracerebral arteriovenous malformations (AVMs) are defined as the direct communication of arter... more Intracerebral arteriovenous malformations (AVMs) are defined as the direct communication of arteries to abnormal veins without interposing capillaries. Although AVMs can have various clinical presentations due to their dynamic nature, the most common presenting sign is intracerebral hemorrhage. Whenever an AVM is discovered, the therapeutic choice is often not obvious and it is influenced not only by the hemodynamic features of the AVM, but also by considerations of the extent of intervention-related morbidity and mortality. A patient with a left frontal AVM is described. He bled three years after gamma knife radiosurgery and developed aphasia. The complete obliteration of the AVM was later achieved by embolization. Functional compensatory brain reorganization and plasticity is discussed, since our patient presented with a fast recovery from aphasia and unexpected contralateral redistribution of the speech function and with preference for his second spoken language.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2015
Objective: Case report of NMDA receptor encephalitis in a young man with early refractory status ... more Objective: Case report of NMDA receptor encephalitis in a young man with early refractory status epilepticus and atypical radiological findings.Background:Anti-NMDA receptor encephalitis is an autoimmune disorder due to antibodies to the NR1-NR2B heterodimer of NMDA receptor. On imaging, it typically presents with T2 hyperintensities in mesio-temporal lobes, cerebral cortex and basal ganglia. We present a case with a dramatic clinical evolution and novel imaging findings. Design/Methods:Case report and review of imaging.Results:29-year-old male presented with mood disturbance followed by partial-complex seizures, facial dyskinesia and choreo-athetotic movements. Initial MRI showed subtle T2-hyperintensities in mesio-temporal lobes. Diagnosis of NMDA-receptor encephalitis was confirmed after CSF antibody detection. Prior to diagnostic confirmation, he developed refractory status epilepticus, and concomitant signs of herniation. A repeated MRI showed increased T2-hyperintensities of t...
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2011
Intracellular RNAses are involved in various functions, including microRNA maturation and turnove... more Intracellular RNAses are involved in various functions, including microRNA maturation and turnover. Mutations occurring in genes encoding RNAses cause Aicardi-Goutiéres syndrome (AGS). AGS mutations silence RNAse activity, thus inducing accumulation of endogenous RNAs, mainly consisting of short RNAs and microRNAs. Overload of intracellular RNA triggers Toll like receptor-dependent interferon-alpha production in the brain, which in turn activates neurotoxic lymphocytes and inhibits angiogenesis thus inducing the typical clinical phenotype of AGS. However, these pathogenic mechanisms are attenuated after three years of age by the endogenous production of DNAJP58IPK and Cystatin F, which arrest AGS progression. Because RNAses are involved in microRNA turnover, we evaluated the expression of 957 microRNAs in lymphocytes from AGS patients and control patients. Our results indicate that microRNA overload occurs in AGS patients. This upregulation inhibits microRNA turnover impeding the synthesis of the novel microRNAs required for the differentiation and myelination of the brain during the initial period of postnatal life. These pathogenic mechanisms result in AGS, a neurological syndrome characterized by irritability, mild hyperpyrexia, pyramidal and extrapyramidal signs, and spastic-dystonic tetraplegia. Typical cerebrospinal fluid alterations include lymphocytosis and elevated interferon-alpha levels. Brain imaging demonstrates cerebral calcifications, white matter abnormalities, and progressive cerebral atrophy.Thus, evidence exists that mutations silencing intracellular RNases affect microRNA turnover resulting in the severe clinical consequences in the brain characterizing the clinical feature of AGS.
We describe a case of brain cortical reorganization after embolization of a large right temporal ... more We describe a case of brain cortical reorganization after embolization of a large right temporal arteriovenous malformation. A comprehensive imaging protocol, including functional magnetic resonance imaging (fMRI), cortical thickness analysis and 320-row computed tomography (CT) perfusion was used to provide information on brain plasticity and potential steal phenomenon. A 25-year-old man known for a right temporal grade V Spetzler-Martin classification arteriovenous malformation (AVM) presented with left progressive hemiparesis. He underwent functional 3T magnetic resonance imaging (fMRI), cortical thickness analysis, and CT perfusion (CT 320 row, Aquilion ONE, Toshiba, Tokyo, Japan) before and after endovascular treatment. The results were compared to look for modifications in brain perfusion and organization. An improvement in the left hemiparesis and a reorganization of motor function were observed after endovascular treatment. Modifications in the angioarchitecture and perfusio...
Pol III-related leukodystrophies are caused by mutations in POLR3A and POLR3B genes and all share... more Pol III-related leukodystrophies are caused by mutations in POLR3A and POLR3B genes and all share peculiar imaging and clinical features. The objectives of this study are (1) to define the neuroradiologic pattern in a cohort of POLR3A and POLR3B subjects and (2) to compare the neuroradiologic pattern of Pol III-related leukodystrophies with other hypomyelinating disorders. The magnetic resonance imaging (MRI) examinations of 13 patients with POLR3A and POLR3B mutations and of 14 patients with other hypomyelinating disorders were analyzed. All the subjects with Pol III-related leukodystrophies presented hypomyelination associated with T2 hypointensity of the thalami and/or the pallida. Twelve subjects (92%) presented T2 hypointensity of the optic radiations. Cerebellar atrophy was observed in most patients (92%). The combination of the analyzed criteria identified patients with Pol III-related leukodystrophies with a sensitivity of 84.6 % and a specificity of 92.9%.
Uploads
Papers by Roberta La Piana