MATEUS MISTIERI SIMABUKURO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
5 resultados
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- Clinical manifestations of the anti-IgLON5 disease(2017) GAIG, Carles; GRAUS, Francesc; COMPTA, Yarko; HOGL, Birgit; BATALLER, Luis; BRUGGEMANN, Norbert; GIORDANA, Caroline; HEIDBREDER, Anna; KOTSCHET, Katya; LEWERENZ, Jan; MACHER, Stefan; MARTI, Maria J.; MONTOJO, Teresa; PEREZ-PEREZ, Jesus; PUERTAS, Inmaculada; SEITZ, Caspar; SIMABUKURO, Mateus; TELLEZ, Nieves; WANDINGER, Klaus-Peter; IRANZO, Alex; ERCILLA, Guadalupe; SABATER, Lidia; SANTAMARIA, Joan; DALMAU, JosepObjective: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. Methods: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. Results: Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. Conclusions: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.
- Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease(2021) GAIG, Carles; COMPTA, Yaroslau; HEIDBREDER, Anna; MARTI, Maria J.; TITULAER, Maarten J.; CRIJNEN, Yvette; HOEGL, Birgit; LEWERENZ, Jan; ERRO, Maria Elena; GARCIA-MONCO, Juan Carlos; NIGRO, Pasquale; TAMBASCO, Nicola; PATALONG-OGIEWA, Maja; ERDLER, Marcus; MACHER, Stefan; BERGER-SIECZKOWSKI, Evelyn; HOEFTBERGER, Romana; GEIS, Christian; HUTTERER, Markus; MILAN-TOMAS, Angela; MARTIN-BASTIDA, Antonio; MANZANARES, Lydia Lopez; QUINTAS, Sonia; HOEGLINGER, Guenter U.; MOEHN, Nora; SCHOEBERL, Florian; THALER, Franziska S.; ASIOLI, Gian Maria; PROVINI, Federica; PLAZZI, Giuseppe; BERGANZO, Koldo; BLAABJERG, Morten; BRUEGGEMANN, Norbert; FARIAS, Tarsis; NG, Chen Fei; GIORDANA, Caroline; MARTIN, Alejandro Herrero-San; HUEBRA, Lucio; KOTSCHET, Katya; LIENDL, Herburg; MONTOJO, Teresa; MORATA, Carlos; PEREZ, Jesus Perez; PUERTAS, Inmaculada; SEIFERT-HELD, Thomas; SEITZ, Caspar; SIMABUKURO, Mateus Mistieri; TELLEZ, Nieves; VILLACIEROS-ALVAREZ, Javier; WILLEKENS, Barbara; SABATER, Lidia; IRANZO, Alex; CANO, Joan Santamaria; DALMAU, Josep; GRAUS, FrancescBackground and Objectives Anti-IgLON5 disease is a recently described neurologic disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are underreported. We describe the frequency and types of movement disorders in a series of consecutive patients with this disease. Methods In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by 3 experts in movement disorders. Results Seventy-two patients were included. In 41 (57%), the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases. Discussion Movement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.
- Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis(2020) SPATOLA, Marianna; PEDROL, Mar Petit; MAUDES, Estibaliz; SIMABUKURO, Mateus; MUNIZ-CASTRILLO, Sergio; PINTO, Anne-Laurie; WANDINGER, Klaus-Peter; SPIEGLER, Juliane; SCHRAMM, Peter; DUTRA, Livia Almeida; IORIO, Raffaele; KORNBLUM, Cornelia; BIEN, Christian G.; HOEFTBERGER, Romana; LEYPOLDT, Frank; TITULAER, Maarten J.; SMITT, Peter Sillevis; HONNORAT, Jerome; ROSENFELD, Myrna R.; GRAUS, Francesc; DALMAU, JosepObjective To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters. Methods Clinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons. Results Eleven new patients were identified (10 adults, 1 child);4 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons. Conclusions Anti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in longterm disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons.
- Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2(2021) LANDA, Jon; GUASP, Mar; MIGUEZ-CABELLO, Federico; GUIMARAES, Joana; MISHIMA, Takayasu; ODA, Fumiko; ZIPP, Frauke; KRAJINOVIC, Vladimir; FUHR, Peter; HONNORAT, Jerome; TITULAER, Maarten; SIMABUKURO, Mateus; PLANAGUMA, Jesus; MARTINEZ-HERNANDEZ, Eugenia; ARMANGUE, Thais; SAIZ, Albert; GASULL, Xavier; SOTO, David; GRAUS, Francesc; SABATER, Lidia; DALMAU, JosepObjective The objective of this study was to report the identification of antibodies against the glutamate kainate receptor subunit 2 (GluK2-abs) in patients with autoimmune encephalitis, and describe the clinical-immunological features and antibody effects. Methods Two sera from 8 patients with similar rat brain immunostaining were used to precipitate the antigen from neuronal cultures. A cell-based assay (CBA) with GluK2-expressing HEK293 cells was used to assess 596 patients with different neurological disorders, and 23 healthy controls. GluK2-ab effects were determined by confocal microscopy in cultured neurons and electrophysiology in GluK2-expressing HEK293 cells. Results Patients' antibodies precipitated GluK2. GluK2 antibody-specificity was confirmed by CBA, immunoprecipitation, GluK2-immunoabsorption, and GluK2 knockout brain immunohistochemistry. In 2 of 8 samples, antibodies reacted with additional GluK2 epitopes present in GluK1 or GluK3; in both, the reactivity was abrogated after GluK2 immuno-absorption. Six of 8 patients developed acute encephalitis and clinical or magnetic resonance imaging (MRI) features of predominant cerebellar involvement (4 presenting as cerebellitis, which in 2 patients caused obstructive hydrocephalus), and 2 patients had other syndromes (1 with cerebellar symptoms). One of the samples showed mild reactivity with non-kainate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPAR] and N-methyl-D-aspartate receptors [NMDAR]) leading to identify 6 additional cases with GluK2-abs among patients with anti-AMPAR (5/71) or anti-NMDAR encephalitis (1/73). GluK2-abs internalized GluK2 in HEK293 cells and neurons; these antibody-effects were reversible in neurons. A significant reduction of GluK2-mediated currents was observed in cells treated with patients' GluK2 serum following the time frame of antibody-mediated GluK2 internalization. Interpretation GluK2-abs associate with an encephalitis with prominent clinicoradiological cerebellar involvement. The antibody effects are predominantly mediated by internalization of GluK2. ANN NEUROL 2021
conferenceObject Encephalitis with Autoantibodies against the Glutamate Kainate Receptor (GluK2)(2022) GUASP, M.; LANDA, J.; MIGUEZ-CABELLO, F.; GUIMARAES, J.; MISHIMA, T.; ODA, F.; ZIPP, F.; KRAJINOVIC, V.; FUHR, P.; HONNORAT, J.; TITULAER, M.; SIMABUKURO, M.; PLANAGUMA, J.; MARTINEZ-HERNANDEZ, E.; ARMANGUE, T.; SAIZ, A.; GASULL, X.; SOTO, D.; GRAUS, F.; SABATER, L.; DALMAU, J.