Shannon Beres, MD

All Publications

• Cerebroventricular deformation and vector mapping, a topographic visualizer for surgical interventions in pediatric hydrocephalus. Journal of neurosurgery. Pediatrics Yeom, K. W., Zhang, M., Lee, E. H., Duh, A. K., Beres, S. J., Prolo, L. M., Lober, R. M., Moss, H. E., Moseley, M. E., Forkert, N. D., Wilms, M., Grant, G. A. 2024: 1-9

  Abstract

  Hydrocephalus is a challenging neurosurgical condition due to nonspecific symptoms and complex brain-fluid pressure dynamics. Typically, the assessment of hydrocephalus in children requires radiographic or invasive pressure monitoring. There is usually a qualitative focus on the ventricular spaces even though stress and shear forces extend across the brain. Here, the authors present an MRI-based vector approach for voxelwise brain and ventricular deformation visualization and analysis.Twenty pediatric patients (mean age 7.7 years, range 6 months-18 years; 14 males) with acute, newly diagnosed hydrocephalus requiring surgical intervention for symptomatic relief were randomly identified after retrospective chart review. Selection criteria included acquisition of both pre- and posttherapy paired 3D T1-weighted volumetric MRI (3D T1-MRI) performed on 3T MRI systems. Both pre- and posttherapy 3D T1-MRI pairs were aligned using image registration, and subsequently, voxelwise nonlinear transformations were performed to derive two exemplary visualizations of compliance: 1) a whole-brain vector map projecting the resulting deformation field on baseline axial imaging; and 2) a 3D heat map projecting the volumetric changes along ventricular boundaries and the brain periphery.The patients underwent the following interventions for treatment of hydrocephalus: endoscopic third ventriculostomy (n = 6); external ventricular drain placement and/or tumor resection (n = 10); or ventriculoperitoneal shunt placement (n = 4). The mean time between pre- and postoperative imaging was 36.5 days. Following intervention, the ventricular volumes decreased significantly (mean pre- and posttherapy volumes of 151.9 cm3 and 82.0 cm3, respectively; p < 0.001, paired t-test). The largest degree of deformation vector changes occurred along the lateral ventricular spaces, relative to the genu and splenium. There was a significant correlation between change in deformation vector magnitudes within the cortical layer and age (p = 0.011, Pearson), as well as between the ventricle size and age (p = 0.014, Pearson), suggesting higher compliance among infants and younger children.This study highlights an approach for deformation analysis and vector mapping that may serve as a topographic visualizer for therapeutic interventions in patients with hydrocephalus. A future study that correlates the degree of cerebroventricular deformation or compliance with intracranial pressures could clarify the potential role of this technique in noninvasive pressure monitoring or in cases of noncompliant ventricles.

  View details for DOI 10.3171/2024.6.PEDS24117

  View details for PubMedID 39178478

• Benign Ocular Flutter. The Journal of pediatrics Silverman, A., Maran, K., Lin, G. L., Johnson, A., Cheronis, C., Beres, S. 2024: 114229

  View details for DOI 10.1016/j.jpeds.2024.114229

  View details for PubMedID 39178940

• TUMOR VOLUME IN NEWLY DIAGNOSED OPTIC PATHWAY GLIOMAS ASSOCIATED WITH NF1 (NF1-OPG): PRELIMINARY RESULTS FROM THE INTERNATIONAL MULTICENTER NF1-OPG NATURAL HISTORY STUDY Avery, R., Jiang, Z., Parida, A., Listernick, R., Liu, G., Ferner, R., Gutmann, D., de Blank, P., Lasky-Zeid, J., Ullrich, N., Heidary, G., Bornhorst, M., Stasheff, S., Rosser, T., Borchert, M., Arden-Holmes, S., Flaherty, M., Hummel, T., Motley, W., Bielamowicz, K., Phillips, P., Bouffet, E., Reginald, A., Wolf, D., Peragallo, J., Van Mater, D., El-Diari, M., Sato, A., Tarczy-Hornoch, K., Klesse, L., Hogan, N., Foreman, N., Mccourt, E., Allen, J., Ranka, M., Campen, C., Beres, S., Moertel, C., Areaux, R., Stearns, D., Orge, F., Crawford, J., O'Halloran, H., Brodsky, M., Esbenshade, A., Donahue, S., Oattes, J., Reddy, A., Cutter, G., Linguraru, M., Fisher, M. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae064.582

  View details for Web of Science ID 001252720000219

• DEMOGRAPHIC, CLINICAL AND IMAGING CHARACTERISTICS OF NEWLY DIAGNOSED OPTIC PATHWAY GLIOMAS ASSOCIATED WITH NF1: RESULTS FROM THE INTERNATIONAL MULTICENTER NF1-OPG NATURAL HISTORY STUDY Fisher, M. J., de Blank, P., Listernick, R., Liu, G., Ferner, R., Gutmann, D., Lasky-Zeid, J., Ullrich, N., Heidary, G., Bornhorst, M., Stasheff, S., Rosser, T., Borcher, M., Arden-Holmes, S., Flaherty, M., Hummel, T., Motley, W., Bielamowicz, K., Phillips, P., Bouffet, E., Reginald, A., Wolf, D., Peragallo, J., El-Dairi, M., Van Mater, D., Sato, A., Tarczy-Hornoch, K., Klesse, L., Hogan, N., Foreman, N., Mccourt, E., Allen, J., Ranka, M., Campen, C., Beres, S., Moertel, C., Areaux, R., Stearns, D., Orge, F., Crawford, J., O'Halloran, H., Oattes, J., Reddy, A., Brodsky, M., Esbenshade, A., Donahue, S., Cutter, G., Avery, R. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae064.579

  View details for Web of Science ID 001252720000545

• Teaching Video NeuroImage: Infantile Upbeat Nystagmus as an Isolated Presentation of CACNA1F-Related Retinal Dystrophy. Neurology Silverman, A., Cheronis, C., Beres, S. 2024; 102 (9): e209416

  View details for DOI 10.1212/WNL.0000000000209416

  View details for PubMedID 38579184

• Ocular features of NGLY1 deficiency from a prospective longitudinal cohort. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus Frater, C. H., Ruzhnikov, M. R., Beres, S., Alcorn, D., Shue, A., Levy, R. J. 2024: 103925

  Abstract

  NGLY1 deficiency is a rare autosomal recessive disorder with core features of global developmental delay, liver enzyme abnormalities, movement disorder, polyneuropathy, and hypo- or alacrima. We characterized the full spectrum and evolution of the ocular phenotype in a prospective natural history of NGLY1 deficiency.We collected ophthalmological data on 29 individuals with NGLY1 deficiency in a natural history study. Medical records were reviewed to confirm caregiver-reported symptoms. Of the 29, 15 participants appeared for at least one ophthalmological examination.Caregivers reported at least one ocular sign or symptom in 90% of participants (26/29), most commonly decreased tears, refractive error, and chronic infection. Daily eye medication, including artificial tears, ophthalmic ointment, and topical antibiotics were used by 62%. Ophthalmological examination confirmed refractive errors in 93% (14/15) and corneal abnormalities in 73% (11/15).Given nearly universal hypolacrima and additional prominent ocular findings in NGLY1 deficiency, a targeted ocular history and ophthalmologic examination may facilitate prompt diagnosis and early initiation of preventive eye care, preserving vision and overall ocular health.

  View details for DOI 10.1016/j.jaapos.2024.103925

  View details for PubMedID 38697387

• Artificial Intelligence to Differentiate Pediatric Pseudopapilledema and True Papilledema on Fundus Photographs. Ophthalmology science Chang, M. Y., Heidary, G., Beres, S., Pineles, S. L., Gaier, E. D., Gise, R., Reid, M., Avramidis, K., Rostami, M., Narayanan, S. 2024; 4 (4): 100496

  Abstract

  To develop and test an artificial intelligence (AI) model to aid in differentiating pediatric pseudopapilledema from true papilledema on fundus photographs.Multicenter retrospective study.A total of 851 fundus photographs from 235 children (age < 18 years) with pseudopapilledema and true papilledema.Four pediatric neuro-ophthalmologists at 4 different institutions contributed fundus photographs of children with confirmed diagnoses of papilledema or pseudopapilledema. An AI model to classify fundus photographs as papilledema or pseudopapilledema was developed using a DenseNet backbone and a tribranch convolutional neural network. We performed 10-fold cross-validation and separately analyzed an external test set. The AI model's performance was compared with 2 masked human expert pediatric neuro-ophthalmologists, who performed the same classification task.Accuracy, sensitivity, and specificity of the AI model compared with human experts.The area under receiver operating curve of the AI model was 0.77 for the cross-validation set and 0.81 for the external test set. The accuracy of the AI model was 70.0% for the cross-validation set and 73.9% for the external test set. The sensitivity of the AI model was 73.4% for the cross-validation set and 90.4% for the external test set. The AI model's accuracy was significantly higher than human experts on the cross validation set (P < 0.002), and the model's sensitivity was significantly higher on the external test set (P = 0.0002). The specificity of the AI model and human experts was similar (56.4%-67.3%). Moreover, the AI model was significantly more sensitive at detecting mild papilledema than human experts, whereas AI and humans performed similarly on photographs of moderate-to-severe papilledema. On review of the external test set, only 1 child (with nearly resolved pseudotumor cerebri) had both eyes with papilledema incorrectly classified as pseudopapilledema.When classifying fundus photographs of pediatric papilledema and pseudopapilledema, our AI model achieved > 90% sensitivity at detecting papilledema, superior to human experts. Due to the high sensitivity and low false negative rate, AI may be useful to triage children with suspected papilledema requiring work-up to evaluate for serious underlying neurologic conditions.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  View details for DOI 10.1016/j.xops.2024.100496

  View details for PubMedID 38682028

  View details for PubMedCentralID PMC11046195

• Correction to: Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study. Neurology and therapy Chiriboga, C. A., Bruno, C., Duong, T., Fischer, D., Mercuri, E., Kirschner, J., Kostera-Pruszczyk, A., Jaber, B., Gorni, K., Kletzl, H., Carruthers, I., Martin, C., Warren, F., Scalco, R. S., Wagner, K. R., Muntoni, F., JEWELFISH Study Group, Deconinck, N., Balikova, I., Joniau, I., Tahon, V., Wittevrongel, S., Goemans, N., Cassiman, C., Prove, L., Vancampenhout, L., van den Hauwe, M., Van Impe, A., Cances, C., Soler, V., De La Morandais, L. M., Vovan, D., Cintas, P., Auriol, F., Mus, M., Alphonsa, G., Bellio, V., Gil Mato, O., Flamein, F., Evrard, C., Ziouche, A., Bouacha-Allou, I., Debruyne, P., Derlyn, G., Defoort, S., Leroy, F., Danjoux, L., Desguerre, I., Bremond-Gignac, D., Rateuax, M., Deladriere, E., Vuillerot, C., Veillerot, Q., Sibille-Dabadi, B., Barriere, A., Tinat, M., Saidi, M., Fontaine, S., De Montferrand, C., Le-Goff, L., Portefaix, A., Louvier, U. W., Duval, P., Caradec, P., Touati, S., Herranz, A. Z., Kirschner, J., Bollig, J., Molnar, F., Vogt, S., Pechmann, A., Schorling, D., Wider, S., Kolbel, H., Schara, U., Braun, F., Gangfuss, A., Hagenacker, T., Eckstein, A., Dekowski, D., Oeverhaus, M., Stoehr, M., Andres, B., Smuda, K., Bertini, E., D'Amico, A., Petroni, S., Valente, P., Bonetti, A. M., Carlesi, A., Mizzoni, I., Bruno, C., Pedemonte, M., Brolatti, N., Priolo, E., Rao, G., Sposetti, L., Morando, S., Comi, G., Osnaghi, S., Minorini, V., Abbati, F., Fassini, F., Foa, M., Lopopolo, M. A., Magri, F., Govoni, A., Meneri, M., Parente, V., Mercuri, E., Antonaci, L., Pera, M. C., Pane, M., Amorelli, G. M., Barresi, C., D'Amico, G., Orazi, L., Coratti, G., De Sanctis, R., Vita, G., Sframeli, M., Vita, G. L., Aragona, P., Inferrera, L., Postorino, E. I., Montanini, D., Di Bella, V., Donato, C., Cala, E., Van der Pol, L., Aalbers, J., de Boer, J., Imhof, S., Cooijmans, P., Ruyten, T., Van Der Woude, D., Kostera-Pruszczyk, A., Klimaszewska, B., Romanczak, D., Gierlak-Wojcicka, Z., Kepa, M., Sikorski, A., Sobieraj, M., Lusakowska, A., Kierdaszuk, B., Czeczko, K., Fischer, D., Henzi, B., Gugleta, K., Kusnyerik, A., Siems, P., Akos, S., Frei, N., Seppi, C., Haschke, C. W., Guglieri, M., Straub, V., Bell, R., Nassar, M., Page, S., Clarke, M. P., Regan, A., Mayhew, A., Lofra, R. M., Parasuraman, D., Bruschi, S., Ghauri, A., Castle, A., Naqvi, S., Patt, N., Scoto, M., Trucco, F., Henderson, R. H., Kukadia, R., Moore, W., Milev, E., Rye, C., Selby, V., Wolfe, A., Darras, B., Baglieri, A. M., Fulton, A., Lucken, C., Maczek, E., Pasternak, A., Chiriboga, C. A., Kane, S., Bautista, M. E., Frommer, E., Pensec, N., Salazar, R., Yochai, C., Rodrigues-Torres, R., Chawla, M., Day, J., Beres, S., Gee, R., Young, S. D., Finkel, R., Nazario, A. N., Fasiuddin, A., Wells, J. A., Wilson, J., Berry, D., Rizzo, V., Duke, J., Monduy, M., Collado, J. 2023

  View details for DOI 10.1007/s40120-023-00503-7

  View details for PubMedID 37395990

• Inter-rater reliability of Pediatric Papilledema Fundus Photograph Frisen Grading Sudharshan, R., Reid, M., Beres, S., Heidary, G., Pineles, S., Chang, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795604017

• Isolated Sixth Nerve Palsies in a Child With Familial Hemophagocytic Lymphohistiocytosis Type 2. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Chiang, H. H., Fernandez-Pol, S., Bae, G. H., Rieger, K. E., Dahmoush, H. M., Beres, S. J. 2023; 43 (1): 137-140

  Abstract

  A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.

  View details for DOI 10.1097/WNO.0000000000001807

  View details for PubMedID 36790062

• Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study. Neurology and therapy Chiriboga, C. A., Bruno, C., Duong, T., Fischer, D., Mercuri, E., Kirschner, J., Kostera-Pruszczyk, A., Jaber, B., Gorni, K., Kletzl, H., Carruthers, I., Martin, C., Warren, F., Scalco, R. S., Wagner, K. R., Muntoni, F. 2023

  Abstract

  Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1-3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam.Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment.A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1-60 years) and 39.1 kg (9.2-108.9 kg), respectively. About 63% of patients aged 2-60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale-Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles.The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients.

  View details for DOI 10.1007/s40120-023-00444-1

  View details for PubMedID 36780114

• Mimickers of Classical Urticaria: Cryopyrin-Associated Autoinflammatory Syndrome Presenting as Isolated Urticaria in an Infant. The journal of allergy and clinical immunology. In practice Solomon, B. D., Skaljic, M., Liu, L. Y., Yan, D., Sheahon, K. M., Broderick, L., Hoffman, H. M., Beres, S. J., Brown, R. A., Teng, J. M., Gernez, Y. 2023

  View details for DOI 10.1016/j.jaip.2022.12.037

  View details for PubMedID 36720659

• Bilateral Marcus Gunn jaw-Winking Syndrome in a Neonate with Congenital Neurosyphilis JOURNAL OF PEDIATRICS Johnson, A., Silverman, A., Segal, J., Beres, S. 2023; 252: 223-224

  View details for DOI 10.1018/j.jpeds.2022.09.023

  View details for Web of Science ID 000903976100005

• Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. The Lancet. Neurology Masson, R., Mazurkiewicz-Beldzinska, M., Rose, K., Servais, L., Xiong, H., Zanoteli, E., Baranello, G., Bruno, C., Day, J. W., Deconinck, N., Klein, A., Mercuri, E., Vlodavets, D., Wang, Y., Dodman, A., El-Khairi, M., Gorni, K., Jaber, B., Kletzl, H., Gaki, E., Fontoura, P., Darras, B. T., FIREFISH Study Group, Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Gerber, M., Khwaja, O., Scalco, R. S., Seabrook, T., Koch, A., Balikova, I., Joniau, I., Accou, G., Tahon, V., Wittevrongel, S., De Vos, E., de Holanda Mendonca, R., Matsui, C. J., Fornazieri Darcie, A. L., Machado, C., Kiyoko Oyamada, M., Martini, J., Polido, G., Rodrigues Iannicelli, J., Caires de Oliveira Achili Ferreira, J., Hu, C., Zhu, X., Qian, C., Shen, L., Li, H., Shi, Y., Zhou, S., Xiao, Y., Zhou, Z., Wang, S., Sang, T., Wei, C., Dong, H., Cao, Y., Wen, J., Li, W., Qin, L., Barisic, N., Celovec, I., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Tomas, J., Boespflug-Tanguy, O., De Lucia, S., Seferian, A., Barreau, E., Mnafek, N., Peche, H., Grange, A., Trang Nguyen, D., Milascevic, D., Tachibana, S., Pagliano, E., Bianchi Marzoli, S., Santarsiero, D., Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Dosi, C., Zanin, R., Schembri, V., Brolatti, N., Rao, G., Tassara, E., Morando, S., Tacchetti, P., Pedemonte, M., Priolo, E., Sposetti, L., Comi, G. P., Govoni, A., Osnaghi, S. G., Minorini, V., Abbati, F., Fassini, F., Foa, M., Lopopolo, A., Pane, M., Palermo, C., Pera, M. C., Amorelli, G. M., Barresi, C., D'Amico, G., Orazi, L., Coratti, G., Leone, D., Laura, A., De Sanctis, R., Berti, B., Kimura, N., Takeshima, Y., Shimomura, H., Lee, T., Gomi, F., Morimatsu, T., Furukawa, T., Stodolska-Koberda, U., Waskowska, A., Kolendo, J., Sobierajska-Rek, A., Modrzejewska, S., Lemska, A., Melnik, E., Artemyeva, S., Leppenen, N., Yupatova, N., Monakhova, A., Papina, Y., Shidlovsckaia, O., Litvinova, E., Enzmann, C., Galiart, E., Gugleta, K., Wondrusch Haschke, C., Topaloglu, H., Oncel, I., Ertugrul, N. E., Konuskan, B., Eldem, B., Kadayifcilar, S., Alemdaroglu, I., Sari, S., Bilgin, N., Karaduman, A. A., Sarikaya, F. G., Graham, R. J., Ghosh, P., Casavant, D., Levine, A., Titus, R., Engelbrekt, A., Ambrosio, L., Fulton, A., Baglieri, A. M., Dias, C., Maczek, E., Pasternak, A., Beres, S., Duong, T., Gee, R., Young, S. 2022

  Abstract

  BACKGROUND: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment.METHODS: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing.FINDINGS: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p<0·0001 compared with the performance criterion derived from the natural history of untreated infants with type 1 spinal muscular atrophy). No infants could stand alone (0 [90% CI 0-7]) or walk alone (0 [0-7]) after 24 months of treatment. The most frequently reported adverse event was upper respiratory tract infection, in 22 infants (54%); the most common serious adverse events were pneumonia in 16 infants (39%) and respiratory distress in three infants (7%).INTERPRETATION: Treatment with risdiplam over 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The FIREFISH open-label extension phase will provide additional evidence regarding long-term safety and efficacy of risdiplam.FUNDING: F Hoffmann-La Roche.

  View details for DOI 10.1016/S1474-4422(22)00339-8

  View details for PubMedID 36244364

• Novel treatments in optic pathway gliomas. Frontiers in ophthalmology Maheshwari, A., Pakravan, M., Charoenkijkajorn, C., Beres, S. J., Lee, A. G. 2022; 2: 992673

  Abstract

  Optic pathway gliomas (OPG) are primary tumors of the optic nerve, chiasm, and/or tract that can be associated with neurofibromatosis type 1 (NF1). OPG generally have a benign histopathology, but a variable clinical course. Observation is generally recommended at initial diagnosis if vision is stable or normal for age, however, treatment may include chemotherapy, radiotherapy, or surgery in select cases. This manuscript reviews the literature on OPG with an emphasis on recent developments in treatment.

  View details for DOI 10.3389/fopht.2022.992673

  View details for PubMedID 38983553

  View details for PubMedCentralID PMC11182137

• Child Neurology: Horner Syndrome in an Otherwise Well-Appearing Infant. Neurology Silverman, A., Beres, S. 2022

  Abstract

  We report an exemplary case of acquired Horner syndrome secondary to neuroblastoma in infancy. The patient presented with ptosis, miosis, and heterochromia. In reviewing the patient's laboratory and imaging workup, we highlight key etiologic differences between the pediatric and adult populations. Other important teaching points included in the discussion are a review of sympathetic neuroanatomy and oculosympathetic paresis, the appropriate and evidence-based diagnostic workup in infants and children, and a review of pharmacologic testing using cocaine and apraclonidine drops.

  View details for DOI 10.1212/WNL.0000000000201377

  View details for PubMedID 36130839

• Bilateral Marcus Gunn Jaw-Winking Syndrome in a Neonate with Congenital Neurosyphilis. The Journal of pediatrics Johnson, A., Silverman, A., Segal, J. B., Beres, S. 2022

  View details for DOI 10.1016/j.jpeds.2022.09.023

  View details for PubMedID 36152687

• High Altitude as a Risk Factor for the Development of Nonarteritic Anterior Ischemic Optic Neuropathy. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Liu, Y. A., Mesentier-Louro, L. A., Shariati, M. A., Moss, H. E., Beres, S. J., Liao, Y. J. 2022

  Abstract

  Episodic high-altitude exposure leads to optic disc edema and retinopathy. It is uncertain whether high-altitude exposure is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION).We performed a single-center, retrospective, cross-sectional case study of 5 patients with high-altitude-associated NAION (HA-NAION) from April 2014 to April 2019. Main study parameters included known vascular risk factors for NAION, evolution of visual acuity, visual field, optic disc, and macula measurements.We studied 5 eyes of 5 patients with HA-NAION that occurred at 7,000-9,000 ft above sea level, 28 patients with classic NAION that developed at sea level (normal altitude NAION or NA-NAION), and 40 controls. All 5 patients with HA-NAION had clinically confirmed NAION by a neuro-ophthalmologist within 3-21 days of onset and comprehensive follow-up evaluations (average follow-up of 23 months). Other than high-altitude exposure, 4 of 5 patients had undiagnosed obstructive sleep apnea (OSA, apnea-hypopnea index 5.4-22.2) and 1 had systemic vascular risk factors. All patients had disc-at-risk in the contralateral eye. The best-corrected distance visual acuity was 20/20 to 20/70 (median logMAR 0) at presentation and 20/70 to counting finger (median logMAR 0) at ≥6 months. Automated static perimetry revealed average mean deviation of -18.6 dB at presentation and -22.1 dB at ≥6 months. The average retinal nerve fiber layer was 244 µm (80-348 µm) at onset and 59 µm (55-80 µm) at ≥6 months. The average ganglion cell complex thickness was 50 µm (43-54 µm) at onset and 52 µm (50-55 µm) at ≥6 months. The patients with OSA were started on home continuous positive airway pressure treatment. Visual outcomes were similar in patients with HA-NAION and NA-NAION. - After addressing all NAION risk factors, no new events occurred in the HA-NAION group within 2-8 years with or without repeat high-altitude exposure.NAION can occur under high-altitude conditions. HA-NAION is associated with relatively younger age at onset, disc-at-risk, and OSA. These patients exhibit a relatively progressive course of vision loss after initial onset and severe thinning of optic nerves on optical coherence tomography. Treatment for OSA is recommended, especially with repeated high-altitude exposure.

  View details for DOI 10.1097/WNO.0000000000001629

  View details for PubMedID 36166787

• CRB1-associated retinal dystrophy presenting as self-resolving opsoclonus and posterior uveitis. American journal of ophthalmology case reports Li, A. S., Pasricha, M. V., Mishra, K., Nguyen, Q. D., Beres, S. J., Wood, E. H. 2022; 26: 101444

  Abstract

  Purpose: To describe the unusual case of inflammatory CRB1-associated retinal dystrophy that initially presented with self-resolving opsoclonus.Observations: We report the case of a now 2-year-old female who developed opsoclonus without myoclonus at the age of 4 months. An extensive workup for neuroblastoma and other systemic diseases was unremarkable, and all unusual eye movements self-resolved at age 10 months. Twenty-one months after initial presentation, she began having reduced visual behaviors, and comprehensive ophthalmic exam at that time revealed recurrent saccadic intrusions as well as severe, chronic retinal inflammation and dystrophic changes. An extensive infectious and inflammatory workup was negative. Genetic sequencing revealed two variants in CRB1: a heterozygous missense mutation and a heterozygous novel deletion involving exon 12. The patient was treated with monthly infliximab and methylprednisolone infusions with improvement in her optic disc and macular capillary leakage. The patient's 8-month-old sister also harbored the same variants in CRB1 and had early signs of retinal dystrophy and peripheral vascular leakage on exam.Conclusion: Saccadic intrusions may be the first sign of a retinal dystrophy, and infants and children with this presentation should undergo a complete eye exam. We further highlight the link between CRB1-associated retinal dystrophy and inflammation, and how systemic steroids and tumor necrosis factor alpha (TNF-alpha) inhibitors may be effective therapies. Finally, we report a novel deletion in CRB1 that is likely highly penetrant.

  View details for DOI 10.1016/j.ajoc.2022.101444

  View details for PubMedID 35243176

• Multicolor Imaging of Optic Disc Drusen. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Yan, Y., Pugazhendhi, S., Beres, S. J., Liao, Y. J. 2022

  Abstract

  ABSTRACT: Optic disc drusen (ODD) are calcified deposits at the anterior optic nerve that are often detectable by ophthalmic imaging, including optical coherence tomography and fundus autofluorescence imaging. Multicolor (MC) imaging is a novel modality that captures reflectance of blue, green, and near-infrared laser lights with confocal scanning laser ophthalmoscopy to rapidly acquire high-resolution reflectance images of the optic disc and retina. Here, we show an eye with 3 MC imaging features of ODD, including prominent green hyperreflectance of the optic disc, green sheathing of the papillary and peripapillary vasculature (arterioles > venules), and presence of orange superficial ODD. MC imaging can provide rapid high-resolution assessment of eyes with optic nerve head elevation to help distinguish pseudopapilledema vs papilledema in children and adults without dilation, and future large studies incorporating MC imaging will help determine its contribution in the diagnosis and monitoring of ODD and assessment of other causes of optic nerve head elevation.

  View details for DOI 10.1097/WNO.0000000000001470

  View details for PubMedID 35482433

• Reply to Letter to the Editor: Atypical Optic Neuritis After COVID-19 Vaccination: Response. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Tugizova, M., Siegel, D. T., Huang, S., Su, E., Subramanian, P. S., Beres, S., Vora, N. 2022

  View details for DOI 10.1097/WNO.0000000000001596

  View details for PubMedID 35439209

• Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. The Lancet. Neurology Mercuri, E., Deconinck, N., Mazzone, E. S., Nascimento, A., Oskoui, M., Saito, K., Vuillerot, C., Baranello, G., Boespflug-Tanguy, O., Goemans, N., Kirschner, J., Kostera-Pruszczyk, A., Servais, L., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Staunton, H., Yeung, W. Y., Martin, C., Fontoura, P., Day, J. W., SUNFISH Study Group, Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Fuerst-Recktenwald, S., Marquet, A., Mulhardt, N., Trundell, D., Daron, A., Delstanche, S., Romain, B., Dal Farra, F., Schneider, O., Deconinck, N., Balikova, I., Delbeke, P., Joniau, I., Tahon, V., Wittevrongel, S., De Vos, E., Goemans, N., Casteels, I., De Waele, L., Balikova, I., Cassiman, C., Prove, L., Kinoo, D., Vancampenhout, L., Van Den Hauwe, M., Van Impe, A., Prufer de Queiroz Campos Araujo, A., Chacon Pereira, A., Nardes, F., Haefeli, L., Rossetto, J., Almeida Pereira, J., Ferreira Rebel, M., Campbell, C., Sharan, S., McDonald, W., Scholtes, C., Mah, J., Sframeli, M., Chiu, A., Hagel, J., Oskoui, M., Beneish, R., Pham, C., Toffoli, D., Arpin, S., Turgeon Desilets, S., Wang, Y., Hu, C., Huang, J., Qian, C., Shen, L., Xiao, Y., Zhou, Z., Li, H., Wang, S., Xiong, H., Chang, X., Dong, H., Liu, Y., Sang, T., Wei, C., Wen, J., Cao, Y., Lv, X., Wen, J., Zhao, J., Li, W., Qin, L., Barisic, N., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Servais, L., Boespflug-Tanguy, O., Gidaro, T., Seferian, A., De Lucia, S., Barreau, E., Mnafek, N., Momtchilova, M. M., Peche, H., Valherie, C., Grange, A., Lilien, C., Milascevic, D., Tachibana, S., Ravelli, C., Cardas, R., Vanden Brande, L., Davion, J., Coopman, S., Bouacha, I., Debruyne, P., Defoort, S., Derlyn, G., Leroy, F., Danjoux, L., Guilbaud, J., Desguerre, I., Barnerias, C., Semeraro, M., Bremond-Gignac, D., Bruere, L., Rateaux, M., Deladriere, E., Germa, V., Pereon, Y., Magot, A., Mercie, S., Billaud, F., Le Goff, L., Letellier, G., Vuillerot, C., Portefaix, A., Fontaine, S., De-Montferrand, C., Le-Goff, L., Saidi, M., Bouzid, N., Barriere, A., Tinat, M., Saidi, M., Kirschner, J., Dreesbach, M., Lagreze, W., Michaelis, B., Molnar, F., Seger, D., Vogt, S., Bertini, E., D'Amico, A., Petroni, S., Bonetti, A. M., Carlesi, A., Mizzoni, I., Bruno, C., Priolo, E., Rao, G., Morando, S., Tacchetti, P., Zuffi, A., Comi, G. P., Brusa, R., Corti, S., Daniele, V., Govoni, A., Magri, F., Minorini, V., Osnaghi, S. G., Abbati, F., Fassini, F., Foa, M., Lopopolo, A., Meneri, M., Zoppas, F., Parente, V., Baranello, G., Masson, R., Bianchi Marzoli, S., Santarsiero, D., Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Zanin, R., Mercuri, E., Amorelli, G. M., Barresi, C., D'Amico, G., Orazi, L., Coratti, G., Haginoya, K., Kato, A., Morishita, Y., Kira, R., Akiyama, K., Goto, M., Mori, Y., Okamoto, M., Tsutsui, S., Takatsuji, Y., Tanaka, A., Komaki, H., Suzuki, I., Takeuchi, M., Todoroki, D., Watanabe, S., Omori, M., Matsubayashi, T., Inakazu, E., Nagura, H., Suzuki, A., Osaka, H., Ohashi, M., Ishikawa, N., Harada, Y., Fudeyasu, K., Hirata, K., Michiue, K., Ueda, K., Saito, K., Yashiro, S., Seki, M., Sano, N., Uemura, A., Fukuyama, K., Matsumoto, Y., Miyazaki, H., Shibata, M., Kobayashi, K., Nakamura, Y., Takeshima, Y., Kuma, M., Kostera-Pruszczyk, A., Fraczek, A., Jedrzejowska, M., Lusakowska, A., Czeszyk-Piotrowicz, A., Hautz, W., Rakusiewicz, K., Burlewicz, M., Gierlak-Wojcicka, Z., Kepa, M., Sikorski, A., Sobieraj, M., Mazurkiewicz-Beldzinska, M., Lemska, A., Modrzejewska, S., Koberda, M., Stodolska-Koberda, U., Waskowska, A., Kolendo, J., Sobierajska-Rek, A., Steinborn, B., Dalz, M., Grabowska, J., Hajduk, W., Janasiewicz-Karachitos, J., Klimas, M., Stopa, M., Gajewska, E., Pusz, B., Vlodavets, D., Melnik, E., Leppenen, N., Yupatova, N., Monakhova, A., Papina, Y., Shidlovsckaia, O., Milic Rasic, V., Brankovic, V., Kosac, A., Djokic, O., Jaksic, V., Pepic, A., Martinovic, J., Munell Casadesus, F., Tizzano, E., Martin Begue, N., Wolley Dod, C., Subira, O., Planas Pascual, B., Toro Tamargo, E., Madruga Garrido, M., Medina Romero, J. D., Salinas, M. P., Nascimento Osorio, A., Diaz Cortes, A., Jimenez Ganan, E., Suh, S. D., Medina Cantillo, J., Moya, O., Padros, N., Roca Urraca, S., Gonzalez Valdivia, H., Pascual Pascual, S., de Manuel, S., Noval Martin, S., Burnham, P., Espinosa Garcia, S., Martinez Moreno, M., Topaloglu, H., Oncel, I., Eroglu Ertugrul, N., Konuskan, B., Eldem, B., Kadayifcilar, S., Alemdaroglu, I., Ayse Karaduman, A., Tunca Yilmaz, O., Bilgin, N., Sari, S., Chiriboga, C., Kane, S., Lee, J., Rome-Martin, D., Day, J. W., Beres, S., Duong, T., Gee, R., Dunaway Young, S. 1800; 21 (1): 42-52

  Abstract

  BACKGROUND: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy.METHODS: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2-25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing ≥20 kg) or 0·25 mg/kg (for individuals weighing <20 kg), or daily oral placebo (matched to risdiplam in colour and taste). Randomisation was conducted by permutated block randomisation with a computerised system run by an external party. Patients, investigators, and all individuals in direct contact with patients were masked to treatment assignment. The primary endpoint was the change from baseline in the 32-item Motor Function Measure total score at month 12. All individuals who were randomly assigned to risdiplam or placebo, and who did not meet the prespecified missing item criteria for exclusion, were included in the primary efficacy analysis. Individuals who received at least one dose of risdiplam or placebo were included in the safety analysis. SUNFISH is registered with ClinicalTrials.gov, NCT02908685. Recruitment is closed; the study is ongoing.FINDINGS: Between Oct 9, 2017, and Sept 4, 2018, 180 patients were randomly assigned to receive risdiplam (n=120) or placebo (n=60). For analysis of the primary endpoint, 115 patients from the risdiplam group and 59 patients from the placebo group were included. At month 12, the least squares mean change from baseline in 32-item Motor Function Measure was 1·36 (95% CI 0·61 to 2·11) in the risdiplam group and -0·19 (-1·22 to 0·84) in the placebo group, with a treatment difference of 1·55 (0·30 to 2·81, p=0·016) in favour of risdiplam. 120 patients who received risdiplam and 60 who received placebo were included in safety analyses. Adverse events that were reported in at least 5% more patients who received risdiplam than those who received placebo were pyrexia (25 [21%] of 120 patients who received risdiplam vs ten [17%] of 60 patients who received placebo), diarrhoea (20 [17%] vs five [8%]), rash (20 [17%] vs one [2%]), mouth and aphthous ulcers (eight [7%] vs 0), urinary tract infection (eight [7%] vs 0), and arthralgias (six [5%] vs 0). The incidence of serious adverse events was similar between treatment groups (24 [20%] of 120 patients in the risdiplam group; 11 [18%] of 60 patients in the placebo group), with the exception of pneumonia (nine [8%] in the risdiplam group; one [2%] in the placebo group).INTERPRETATION: Risdiplam resulted in a significant improvement in motor function compared with placebo in patients aged 2-25 years with type 2 or non-ambulant type 3 spinal muscular atrophy. Our exploratory subgroup analyses showed that motor function was generally improved in younger individuals and stabilised in older individuals, which requires confirmation in further studies. SUNFISH part 2 is ongoing and will provide additional evidence regarding the long-term safety and efficacy of risdiplam.FUNDING: F Hoffmann-La Roche.

  View details for DOI 10.1016/S1474-4422(21)00367-7

  View details for PubMedID 34942136

• Case Series: Atypical Optic Neuritis After COVID-19 Vaccination. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Tugizova, M., Siegel, D. T., Huang, S., Su, E., Subramanian, P. S., Beres, S., Vora, N. 2022

  View details for DOI 10.1097/WNO.0000000000001519

  View details for PubMedID 35020705

• Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2) : a phase 3, double-blind, randomised, placebo-controlled trial LANCET NEUROLOGY Mercuri, E., Deconinck, N., Mazzone, E. S., Nascimento, A., Oskoui, M., Saito, K., Vuillerot, C., Baranello, G., Boespflug-Tanguy, O., Goemans, N., Kirschner, J., Kostera-Pruszczyk, A., Servais, L., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Staunton, H., Yeung, W., Martin, C., Fontoura, P., Day, J. W., SUNFISH Study Grp 2022; 21 (1): 42-52

  View details for Web of Science ID 000734663200021

• Optic chiasm involvement in AQP-4 antibody-positive NMO and MOG antibody-associated disorder. Multiple sclerosis (Houndmills, Basingstoke, England) Tajfirouz, D., Padungkiatsagul, T., Beres, S., Moss, H. E., Pittock, S., Flanagan, E., Kunchok, A., Shah, S., Bhatti, M. T., Chen, J. J. 2021: 13524585211011450

  Abstract

  BACKGROUND: Optic neuritis (ON) is often the presenting symptom in inflammatory central nervous system demyelinating disorders.OBJECTIVE: To compare the frequency and pattern of optic chiasm involvement in patients with aquaporin-4-immunoglobulin G (AQP4-IgG)-associated ON to patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated ON.METHODS: Retrospective review of all patients evaluated at Mayo Clinic, Stanford University and Ramathibodi Hospital who were found to have: (1) ON, (2) either MOG-IgG or AQP4-IgG by cell-based assay, and (3) magnetic resonance imaging (MRI) at the time of ON. MRI was reviewed for contrast enhancement of the optic chiasm and the pattern of involvement.RESULTS: One hundred and fifty-four patients (74 AQP4-IgG and 80 MOG-IgG) were included. Among patients with AQP4-IgG-ON, 20% had chiasmal involvement, compared with 16% of patients with MOG-IgG-ON (p = 0.66). In patients with chiasmal involvement, longitudinally extensive optic nerve enhancement (from orbit extending to chiasm) was identified in 54% of MOG-IgG-ON patients, compared with 7% of AQP4-IgG-ON patients (p = 0.01).CONCLUSION: Chiasmal involvement of MOG-IgG-ON and AQP4-IgG-ON occur at more similar frequencies than previously reported. Furthermore, MOG-IgG-ON chiasmal involvement is more likely to be part of a longitudinally extensive optic nerve lesion.

  View details for DOI 10.1177/13524585211011450

  View details for PubMedID 33975499

• Risdiplam in Type 1 Spinal Muscular Atrophy. The New England journal of medicine Baranello, G. n., Darras, B. T., Day, J. W., Deconinck, N. n., Klein, A. n., Masson, R. n., Mercuri, E. n., Rose, K. n., El-Khairi, M. n., Gerber, M. n., Gorni, K. n., Khwaja, O. n., Kletzl, H. n., Scalco, R. S., Seabrook, T. n., Fontoura, P. n., Servais, L. n. 2021

  Abstract

  Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein.We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds.A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study.In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).

  View details for DOI 10.1056/NEJMoa2009965

  View details for PubMedID 33626251

• Microphthalmia and orbital cysts in DiGeorge syndrome. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus Chandramohan, A., Sears, C. M., Huang, L. C., Beres, S., Fredrick, D., Kossler, A. L. 2021

  View details for DOI 10.1016/j.jaapos.2021.06.001

  View details for PubMedID 34597781

• Feasibility and acceptability of virtually coaching residents on communication skills: a pilot study. BMC medical education Sasnal, M., Miller-Kuhlmann, R., Merrell, S. B., Beres, S., Kipp, L., Lee, S., Threlkeld, Z., Nassar, A. K., Gold, C. A. 2021; 21 (1): 513

  Abstract

  Developing communication skills is a key competency for residents. Coaching, broadly accepted as a training modality in medical education, has been proven a successful tool for teaching communication skills. Little research is available thus far to investigate virtual coaching on communication skills for telemedicine encounters. The purpose of the study was to test the hypothesis that virtually coaching residents on communication skills is feasible and acceptable. We surveyed 21 resident-faculty pairs participating in a "fully virtual" coaching session (patient, coach, and resident were virtual).We asked 50 neurology resident-faculty coach pairs to complete one "fully virtual" coaching session between May 20 and August 31, 2020. After each session, the resident and coach completed a 15-item survey, including Likert-style scale and open-ended questions, assessing feasibility and acceptability. Descriptive statistics and qualitative content and thematic analyses were performed.Forty-two percent (21/50) of all eligible residents completed "fully virtual" coaching sessions. The overall survey response rate was 91 % (38/42). The majority of respondents agreed that the direct observation and debriefing conversation were easy to schedule and occurred without technical difficulties and that debriefing elements (self-reflection, feedback, takeaways) were useful for residents. Ninety-five percent of respondents rated the coach's virtual presence to be not at all disruptive to the resident-patient interaction. Virtual coaching alleviated resident stress associated with observation and was perceived as an opportunity for immediate feedback and a unique approach for resident education that will persist into the future.In this pilot study, residents and faculty coaches found virtual coaching on communication skills feasible and acceptable for telemedicine encounters. Many elements of our intervention may be adoptable by other residency programs. For example, residents may share their communication goals with clinic faculty supervisors and then invite them to directly observe virtual encounters what could facilitate targeted feedback related to the resident's goals. Moreover, virtual coaching on communication skills in both the in-person and telemedicine settings may particularly benefit residents in challenging encounters such as those with cognitively impaired patients or with surrogate decision-makers.

  View details for DOI 10.1186/s12909-021-02936-w

  View details for PubMedID 34583691

• ENROLLMENT AND CLINICAL CHARACTERISTICS OF NEWLY DIAGNOSED, NEUROFIBROMATOSIS TYPE 1 ASSOCIATED OPTIC PATHWAY GLIOMA (NF1-OPG): PRELIMINARY RESULTS FROM AN INTERNATIONAL MULTI-CENTER NATURAL HISTORY STUDY Fisher, M. J., Liu, G. T., Ferner, R. E., Gutmann, D. H., Listernick, R., de Blank, P., Zeid, J., Ullrich, N. J., Heidary, G., Bornhorst, M., Stasheff, S. F., Rosser, T., Borchert, M., Ardern-Holmes, S., Flaherty, M., Hummel, T. R., Motley, W., Bielamowicz, K., Phillips, P. H., Bouffet, E., Reginald, A., Wolf, D. S., Peragallo, J., Van Mater, D., El-Dairi, M., Sato, A., Tarczy-Hornoch, K., Klesse, L., Hogan, N., Foreman, N., McCourt, E., Allen, J., Ranka, M., Campen, C., Beres, S., Moertel, C., Areaux, R., Stearns, D., Orge, F., Crawford, J., O'Halloran, H., Brodsky, M., Esbenshade, A. J., Donahue, S., Cutter, G., Avery, R. A. OXFORD UNIV PRESS INC. 2020: 419

  View details for Web of Science ID 000606080100614

• Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy. Annals of clinical and translational neurology Sergott, R. C., Amorelli, G. M., Baranello, G., Barreau, E., Beres, S., Kane, S., Mercuri, E., Orazi, L., SantaMaria, M., Tremolada, G., Santarsiero, D., Waskowska, A., Yashiro, S., Denk, N., Furst-Recktenwald, S., Gerber, M., Gorni, K., Jaber, B., Jacobsen, B., Mueller, L., Nave, S., Scalco, R. S., Marzoli, S. B., FIREFISH, S. 2020

  Abstract

  OBJECTIVE: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged≥2months in the United States, and is currently under Health Authority review in the EU.METHODS: Subjects included patients with SMA aged 2months-60years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age-appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2-6months depending on study and assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study.RESULTS: A total of 245 patients receiving risdiplam were assessed. Comprehensive, high-quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD-OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam-induced toxicity and resolved with ongoing treatment.INTERPRETATION: Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.

  View details for DOI 10.1002/acn3.51239

  View details for PubMedID 33231373

• Video Teaching NeuroImages: Atypical abnormal eye movements in PNPO-related Epilepsy. Neurology Pavitt, S., Karamian, A. G., Chattree, G., Klotz, J., Beres, S. 2020

  View details for DOI 10.1212/WNL.0000000000010861

  View details for PubMedID 32913027

• Cryopyrin-Associated Periodic Syndrome in Neuro-Ophthalmology. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Harish Bindiganavile, S., Beres, S., Bhat, N., Lee, A. G. 2020

  View details for DOI 10.1097/WNO.0000000000001080

  View details for PubMedID 32868579

• 50 Years Ago in The Journal of Pediatrics: The Cause of Spasmus Nutans and Congenital Nystagmus: Frozen in Time. The Journal of pediatrics Beres, S. 2020; 223: 169

  View details for DOI 10.1016/j.jpeds.2020.02.042

  View details for PubMedID 32711744

• The Cause of Spasmus Nutans and Congenital Nystagmus: Frozen in Time JOURNAL OF PEDIATRICS Beres, S. 2020; 223: 169-+

  View details for Web of Science ID 000551283500036

• A Tearfully Painful Darkness. Survey of ophthalmology Leishangthem, L., Beres, S., Moss, H. E., Chen, J. 2020

  Abstract

  A 70-year-old woman presented with new onset of left eye and facial pain. Ophthalmic and neurological examinations, MRI brain, ESR and CRP were unrevealing. A few days later she developed vision loss in her left eye. Exam revealed decreased visual acuity with a relative afferent pupillary defect in the left eye, and a diffuse mild swelling of the left optic nerve head. Repeat MRI showed T2 hyperintensity and enhancement of the intraorbital optic nerve and surrounding tissues with no other intracranial abnormalities. Serum studies showed elevated myelin oligodendrocyte glycoprotein (MOG) IgG titer. She was treated with IV methylprednisolone 1000mg daily for 3 days and was discharged on prolonged prednisone taper with return of vision to baseline.

  View details for DOI 10.1016/j.survophthal.2020.06.002

  View details for PubMedID 32540257

• Update in Pediatric Pseudotumor Cerebri Syndrome. Seminars in neurology Beres, S. J. 2020

  Abstract

  Pseudotumor cerebri syndrome (PTCS) is a rare condition in children presenting with headache and papilledema from increased intracranial pressure that can cause significant morbidity. This can be idiopathic, also known as idiopathic intracranial hypertension or primary intracranial hypertension, or can be secondary to medications and associated medical conditions. Given the threat to vision, early detection and treatment is needed in all age groups. However, identifying papilledema or pseudopapilledema in children presents unique challenges sometimes as a result of differences between prepubertal and postpubertal children, further elucidating the complex pathophysiology. Management requires brain imaging, lumbar puncture, and frequent eye exams with medical and rarely surgical treatment. Visual outcomes in children are favorable if caught early and management can be prolonged over years. Pediatric PTCS is different from adult PTCS in many ways, and this review will focus on the most updated definitions of the disease, theories of pathophysiology, management, and treatment in the pediatric population.

  View details for DOI 10.1055/s-0040-1708847

  View details for PubMedID 32422670

• Atypical abnormal eye movements in PNPO-related epilepsy Pavitt, S., Karamian, A., Chattree, G., Klotz, J., Beres, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000536058002073

• Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder. Neurology Chen, J. J., Flanagan, E. P., Bhatti, M. T., Jitprapaikulsan, J. n., Dubey, D. n., Lopez Chiriboga, A. S., Fryer, J. P., Weinshenker, B. G., McKeon, A. n., Tillema, J. M., Lennon, V. A., Lucchinetti, C. F., Kunchok, A. n., McClelland, C. M., Lee, M. S., Bennett, J. L., Pelak, V. S., Van Stavern, G. n., Adesina, O. O., Eggenberger, E. R., Acierno, M. D., Wingerchuk, D. M., Lam, B. L., Moss, H. n., Beres, S. n., Gilbert, A. L., Shah, V. n., Armstrong, G. n., Heidary, G. n., Cestari, D. M., Stiebel-Kalish, H. n., Pittock, S. J. 2020

  Abstract

  Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments.We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy.Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5).This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

  View details for DOI 10.1212/WNL.0000000000009758

  View details for PubMedID 32554760

• Anatomic and Thermometric Analysis of Cranial Nerve Palsy after Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy. Operative neurosurgery (Hagerstown, Md.) Huang, Y., Leung, S. A., Parker, J. J., Ho, A. L., Wintermark, M., Patel, S. H., Pauly, K. B., Kakusa, B. W., Beres, S. J., Henderson, J. M., Grant, G. A., Halpern, C. H. 2019

  Abstract

  BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive therapy for treating medication-resistant mesial temporal lobe epilepsy. Cranial nerve (CN) palsy has been reported as a procedural complication, but the mechanism of this complication is not understood.OBJECTIVE: To identify the cause of postoperative CN palsy after LITT.METHODS: Four medial temporal lobe epilepsy patients with CN palsy after LITT were identified for comparison with 22 consecutive patients with no palsy. We evaluated individual variation in the distance between CN III and the uncus, and CN IV and the parahippocampal gyrus using preoperative T1- and T2-weighted magnetic resonance (MR) images. Intraoperative MR thermometry was used to estimate temperature changes.RESULTS: CN III (n=2) and CN IV palsies (n=2) were reported. On preoperative imaging, the majority of identified CN III (54%) and CN IV (43%) were located within 1 to 2 mm of the uncus and parahippocampal gyrus tissue border, respectively. Affected CN III and CN IV were more likely to be found<1 mm of the tissue border (PCNIII=.03, PCNIV<.01; chi-squared test). Retrospective assessment of thermal profile during ablation showed higher temperature rise along the mesial temporal lobe tissue border in affected CNs than unaffected CNs after controlling for distance (12.9°C vs 5.8°C; P=.03; 2-sample t-test).CONCLUSION: CN palsy after LITT likely results from direct heating of the respective CN running at extreme proximity to the mesial temporal lobe. Low-temperature thresholds set at the border of the mesial temporal lobe in patients whose CNs are at close proximity may reduce this risk.

  View details for DOI 10.1093/ons/opz279

  View details for PubMedID 31555820

• Unilateral retinitis pigmentosa in children JOURNAL OF AAPOS Mercado, C. L., Pham, B. H., Beres, S., Marmor, M. F., Lambert, S. R. 2018; 22 (6): 457–61

  View details for DOI 10.1016/j.jaapos.2018.08.003

  View details for Web of Science ID 000453638000013

• Pseudotumor Cerebri Syndrome is the Best Term for This Condition PEDIATRIC NEUROLOGY Beres, S. J., Digre, K. B., Friedman, D. I., Liu, G. T. 2018; 87: 9–10

  View details for DOI 10.1016/j.pediatrneurol.2018.08.018

  View details for Web of Science ID 000454972400004

• Pseudotumor Cerebri Syndrome is the Best Term for This Condition. Pediatric neurology Beres, S. J., Digre, K. B., Friedman, D. I., Liu, G. T. 2018; 87: 9–10

  View details for PubMedID 30501891

• Unilateral retinitis pigmentosa in children. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus Mercado, C. L., Pham, B. H., Beres, S., Marmor, M. F., Lambert, S. R. 2018

  Abstract

  BACKGROUND: Retinitis pigmentosa (RP) is a group of rare inherited retinal disorders characterized by diffuse progressive degeneration of the retina that typically presents bilaterally. Unilateral RP has not often been reported in children. We present a series of cases that illustrate discrimination between unilateral and asymmetric disease and between dystrophy and acquired degeneration.METHODS: Four patients (9-15 years of age; 3 females) were referred to our institution for possible unilateral RP based on fundus appearance and unilateral symptoms. All underwent full-field electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), widefield and color fundus photography, and fundus autofluorescence (FAF) imaging. Genetic testing and a vitamin and essential fatty acids panel were also conducted in 1 patient.RESULTS: Unilateral retinal degeneration was confirmed in 2 patients, whose fellow eyes showed no abnormalities on ERG or imaging. The other 2 patients were found to have highly asymmetric retinal degeneration based on ERG, wide-angle images, and repeated examinations (range, 0.3-9.8 years). Genetic testing and blood testing in 1 unilateral case were negative.CONCLUSIONS: Childhood-onset "unilateral RP" remains a difficult and uncertain diagnosis. ERG testing and longitudinal and widefield fundus examination are necessary to exclude asymmetrical disease. Although unilateral degeneration may exist in some children, its inherited or acquired etiology remains poorly understood.

  View details for PubMedID 30243749

• Optic Pathway Gliomas Secondary to Neurofibromatosis Type 1 SEMINARS IN PEDIATRIC NEUROLOGY Beres, S., Avery, R. A. 2017; 24 (2): 92–99

  Abstract

  Children with neurofibromatosis type 1 frequently manifest optic pathway gliomas-low-grade gliomas intrinsic to the visual pathway. This review describes the molecular and genetic mechanisms driving optic pathway gliomas as well as the clinical symptoms of this relatively common genetic condition. Recommendations for clinical management and descriptions of the newest imaging techniques are discussed.

  View details for PubMedID 28941532

• Pediatric Pseudotumor Cerebri Syndrome: Diagnosis, Classification, and Underlying Pathophysiology SEMINARS IN PEDIATRIC NEUROLOGY Sheldon, C. A., Paley, G. L., Beres, S. J., McCormack, S. E., Liu, G. T. 2017; 24 (2): 110–15

  Abstract

  Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure in the setting of normal brain parenchyma and cerebrospinal fluid. PTCS can occur in the pediatric and adult populations and, if untreated, may lead to permanent visual loss. In this review, discussion will focus on PTCS in the pediatric population and will outline its distinct epidemiology and key elements of diagnosis, evaluation and management. Finally, although the precise mechanisms are unclear, the underlying pathophysiology will be considered.

  View details for PubMedID 28941525

• Optic Pathway Gliomas JOURNAL OF PEDIATRIC NEUROLOGY Beres, S., Avery, R. A. 2017; 15 (1): 15–24

  View details for DOI 10.1055/s-0036-1593742

  View details for Web of Science ID 000395403100004