Publications by authors named "Igor Braga Farias"

14 Publications

  • Page 1 of 1

Acute hepatic porphyrias for the neurologist: current concepts and perspectives.

Arq Neuropsiquiatr 2021 01;79(1):68-80

Universidade Federal de São Paulo, Department of Neurology and Neurosurgery, Division of Neuromuscular Diseases, São Paulo SP, Brazil.

Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis.

Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias.

Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias.

Results: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients.

Conclusions: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.
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http://dx.doi.org/10.1590/0004-282X20200096DOI Listing
January 2021

Cervical Spondylotic Myelopathy Secondary to Ochronotic Vertebral Arthropathy.

Neurology 2021 03 10;96(13):627-628. Epub 2021 Feb 10.

From the Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

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http://dx.doi.org/10.1212/WNL.0000000000011663DOI Listing
March 2021

Acute hepatic porphyrias for the neurologist: current concepts and perspectives.

Arq Neuropsiquiatr 2021 Jan 6. Epub 2021 Jan 6.

Universidade Federal de São Paulo, Department of Neurology and Neurosurgery, Division of Neuromuscular Diseases, São Paulo SP, Brazil.

Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis.

Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias.

Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias.

Results: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients.

Conclusions: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.
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http://dx.doi.org/10.1590/0004-282X20200096DOI Listing
January 2021

GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes.

J Inherit Metab Dis 2020 Nov 3. Epub 2020 Nov 3.

Department of Neurology, Columbia University Medical Center, New York, New York, USA.

Adult polyglucosan body disease (APBD) represents a complex autosomal recessive inherited neurometabolic disorder due to homozygous or compound heterozygous pathogenic variants in GBE1 gene, resulting in deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart, lung, kidney, and liver cells. The diversity of new clinical presentations regarding neuromuscular involvement is astonishing and transformed APBD in a key differential diagnosis of completely different clinical conditions, including axonal and demyelinating sensorimotor polyneuropathy, progressive spastic paraparesis, motor neuronopathy presentations, autonomic disturbances, leukodystrophies or even pure myopathic involvement with limb-girdle pattern of weakness. This review article aims to summarize the main clinical, biochemical, genetic, and diagnostic aspects regarding APBD with special focus on neuromuscular presentations.
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http://dx.doi.org/10.1002/jimd.12325DOI Listing
November 2020

Intragenic variants in the gene determine the clinical phenotype in 5q spinal muscular atrophy.

Neurol Genet 2020 Oct 1;6(5):e505. Epub 2020 Sep 1.

Department of Neurology (R.H.M., C.M., G.J.P., A.M.S.S., D.J.F.S., F.K., U.C.R., E.Z.); Department of Pathology (L.K., A.T.D., E.A.Z.), Faculdade de Medicina da Universidade de São Paulo (FMUSP); Departamento de Pediatria e Neuropediatria (J.G.-G., A.C.M.L.M., G.P.C.S.), Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte; Departamento de Neurologia - UNIFESP (A.S.B.O., P.V.S.S., W.B.V.R.P., E.A.G., I.B.F.), São Paulo; Departamento de Pediatria, Seção de Neurologia Infantil - UFRJ (F.N., A.P.Q.C.A.), Rio de Janeiro; Departamento de Neurologia (W.M., P.J.T.), FMUSP-RP, Ribeirao Preto; Mendelics Análise Genômica (M.D.O.R., J.P.K., F.P.M., F.K.), São Paulo; Serviço de Neurologia (J.A.M.S.), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre; Unidade de Neurologia Infantil (M.M.B.), Hospital de Clinicas de Porto Alegre; Serviço de Genética Médica (J.A.M.S., M.L.S.-P., A.C.B.-F.), Hospital de Clinicas de Porto Alegre; UFRGS, Porto Alegre; Departamento de Bioquímica - UFRGS (M.L.S.-P.), Porto Alegre; Hospital Maria Lucinda (V.L., R.N.F.), Recife; Hospital Infantil Joao Paulo II (A.V.S.B.), Fundação Hospitalar de Minas Gerais, Belo Horizonte; Escola Bahiana de Medicina e Saúde Pública (M.C.M.-C.), Salvador; Hospital Infantil Albert Sabin (A.L.S.P.), Universidade Estadual do Ceará, Fortaleza; and Departamento de Neurologia (L.S.S., M.C.F.), Unicamp, Campinas, Brazil.

Objective: The aim of the study was to report the proportion of homozygous and compound heterozygous variants in the survival motor neuron 1 () gene in a large population of patients with spinal muscular atrophy (SMA) and to correlate the severity of the disease with the presence of specific intragenic variants in and with the copy number.

Methods: Four hundred fifty Brazilian patients with SMA were included in a retrospective study, and clinical data were analyzed compared with genetic data; the copy number was obtained by multiplex ligation-dependent probe amplification and pathogenic variants in by next-generation sequencing.

Results: Four hundred two patients (89.3%) presented homozygous exon 7- deletion, and 48 (10.7%) were compound heterozygous for the common deletion in one allele and a point mutation in the other allele. Recurrent variants in exons 3 and 6 (c.460C>T, c.770_780dup and c.734_735insC) accounted for almost 80% of compound heterozygous patients. Another recurrent pathogenic variant was c.5C>G at exon 1. Patients with c.770_780dup and c.734_735insC had a clinical phenotype correlated with copy number, whereas the variants c.460C>T and c.5C>G determined a milder phenotype independently of the copies.

Conclusions: Patients with specific pathogenic variants (c.460C>T and c.5C>G) presented a milder phenotype, and the copy number did not correlate with disease severity in this group.
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http://dx.doi.org/10.1212/NXG.0000000000000505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524579PMC
October 2020

Teaching NeuroImages: Slowly progressive hypertrophic brachial plexopathy due to mutation.

Neurology 2020 07 10;95(1):e109-e110. Epub 2020 Jun 10.

From the Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), Brazil.

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http://dx.doi.org/10.1212/WNL.0000000000009739DOI Listing
July 2020

Teaching NeuroImages: Hopkins syndrome: A rare differential diagnosis of neurogenic monomelic amyotrophy.

Neurology 2020 03 10;94(9):e996-e997. Epub 2020 Feb 10.

From the Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.

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http://dx.doi.org/10.1212/WNL.0000000000009038DOI Listing
March 2020

Paraneoplastic motor neuronopathy and malignant acanthosis nigricans.

Arq Neuropsiquiatr 2019 07 29;77(7):527. Epub 2019 Jul 29.

Universidade Federal de São Paulo; Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brasil.

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http://dx.doi.org/10.1590/0004-282X20190076DOI Listing
July 2019

Leigh syndrome caused by mitochondrial DNA-maintenance defects revealed by whole exome sequencing.

Mitochondrion 2019 11 2;49:25-34. Epub 2019 Jul 2.

Department of Neurology, Columbia University Medical Center, New York, NY, USA.

Leigh syndrome represents a complex inherited neurometabolic and neurodegenerative disorder associated with different clinical, genetic and neuroimaging findings in the context of bilateral symmetrical lesions involving the brainstem and basal ganglia. Heterogeneous neurological manifestations such as spasticity, cerebellar ataxia, dystonia, choreoathetosis and parkinsonism are associated with multisystemic and ophthalmological abnormalities due to >75 different monogenic causes. Here, we describe the clinical and genetic features of a Brazilian cohort of patients with Leigh Syndrome in which muscle biopsy analysis showed mitochondrial DNA defects and determine the utility of whole exome sequencing for a final genetic diagnostic in this cohort.
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http://dx.doi.org/10.1016/j.mito.2019.06.008DOI Listing
November 2019

Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND).

Pract Neurol 2019 Oct 24;19(5):424-426. Epub 2019 Apr 24.

Neurology and Neurosurgery, UNIFESP - Federal University of São Paulo, Sao Paulo, Brazil.

Atypical motor neurone disease (MND) represents a challenging and expanding group of neurodegenerative disorders involving the upper or lower motor neurones, and rarely both. Neuro-ophthalmological disturbances such as gaze-evoked downbeat nystagmus are extremely rare in the context of typical and atypical MND. Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND) syndrome has been recently recognised as a distinct syndromic phenotype of MND, with a characteristic clinical picture. We describe a 63-year-old woman with long-standing lower motor neurone involvement of the upper limbs, who on examination had gaze-evoked downbeat nystagmus. After extensive negative investigation for secondary causes of MND and downbeat nystagmus, we diagnosed FEWDON-MND syndrome.
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http://dx.doi.org/10.1136/practneurol-2018-002188DOI Listing
October 2019

Leukodystrophy with disorders of sex development due to WT1 mutations.

J Neurol Sci 2018 07 13;390:94-98. Epub 2018 Apr 13.

Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

Background: Hypomyelinating leukodystrophies represent an expanding group of neurogenetic disorders characterized primarily by central nervous system hypomyelination and variable neurological and non-neurological involvement. Hypomyelinating disorders have been rarely associated with gonadal dysfunction, being mainly represented by hypogonadotrophic hypogonadism in 4H syndrome. WT1 gene-associated disorders are classically associated with complex phenotypes including early carcinogenic risk for gonadoblastoma and Wilms' tumor, chronic renal failure, nephrotic syndrome and sex developmental disorders in intersex disorders and ambiguous genitalia.

Methods: The authors describe three non-related Brazilian patients with hypomyelinating leukodystrophy associated with complex neurological and systemic dysfunction with WT1 gene mutations.

Results: All described patients presented with similar neuroimaging features including thin corpus callosum, mild to moderate cerebellar atrophy and diffuse periventricular and profound hypomyelinating leukodystrophy involving supratentorial white matter with classical compromise linked to inherited non-somatic WT1 gene mutations in a similar pattern to Denys-Drash syndrome, including nephrotic syndrome with different glomerular disease, chronic renal failure, intersex disorder with ambiguous genitalia, and early occurrence of specific tumors, such as Wilms' tumor and gonadoblastoma.

Conclusions: Clinicians must include WT1 gene mutations in the differential diagnosis of hypomyelinating leukodystrophy with nephrotic syndrome, chronic renal failure, ambiguous genitalia or sex developmental disorders.
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http://dx.doi.org/10.1016/j.jns.2018.04.020DOI Listing
July 2018