Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia))

M.E. Ivanova1, V.V. Kadyshev2, D.S. Atarshchikov3, I.V. Zolnikova4, N.P. Akchurina4, N.K. Serova5, F.A. Konovalov6, E.R. Lozier6, E.A. Pomerantseva7, N.V. Vetrova7, D. Barh8, L.M. Balashova9,&nbsp;J.M. Salmasi10 1 LLC “Oftalmic”, Moscow, Russian Federation 2 Research Centre for Medical Genetics, Moscow, Russian Federation 3 Central Clinical Hospital under Presidential Affairs, Moscow, Russian Federation 4 Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russian Federation 5 N.N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation 6 Independent Clinical Bioinformatics Laboratory, Moscow, Russian Federation 7 Center for Genetics and Reproductive Medicine “Genetiko”, Moscow, Russian Federation 8 Institute of Integrative Omics and Applied Biotechnology (IIOAB), Bangalore, India 9 Non-profit partnership International Scientific and Practical Center for the Proliferation of Tissues of Russia, Moscow, Russian Federation 10Pirogov Russian National Research Medical University, Moscow, Russian Federation The article describes the clinical case of optic atrophy due to a homozygous mutation in exon 3 of the C19orf12 gene (chr19: 30193863AACAGCCCCCCG&gt; A, rs515726204), the frequency of which in the ExAC control sample is 0.0074. With this mutation, a frameshift occurs at 69-th position (p.Gly69fs, NM_001031726.3), which usually leads to neurodegeneration with the brain iron accumulation (NBIA), type 4 (OMIM: 614298). In described clinical case the main complaint of patient was visual impairment, with magnetic resonance imaging patient revealed only the expansion of the sellar fossa. The vision of 7-year-old boy decreased significantly for 2 years without any apparent reasons, spectacle correction did not give an improvement in vision to 100%. During the examination partial atrophy of the optic nerves was revealed, consultations were conducted with a neurologist, neurophthalmologist. Hyperreflexia, gait changes, and a slight delay in speech development were also revealed. No other clinical neurological symptoms were observed. The article describes a detailed ophthalmic clinical picture, discusses diagnostic and therapeutic tactics. Keywords: optic nerve atrophy, neurodegeneration with the brain iron accumulation, NBIA, mutation, gene, C19orf12. For citation: Ivanova M.E., Kadyshev V.V., Atarshchikov D.S. et al. Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia)). Russian Journal of Clinical Ophthalmology. 2020;20(1):–36. DOI: 10.32364/2311-7729-2020-20-1-33-36. </p

Транскраниальная декомпрессия каналов зрительных нервов при менингиомах хиазмально-селлярной области: эффективность, риски и осложнения

The study objective is evaluate the effectiveness and risks of using intradural and extradural decompression of the optic nerve channels during standard transcranial removal of meningiomas of the chiasmal-cellar region region. Materials and methods. The results of 161 decompression of channel of optic nerve in 129 patients are analyzed. In most patients (n = 122), an intradural decompression (resection) of the canal roof was performed. In 7 patients, an extradural decompression of the upper and lateral walls of the canal was performed. Results. In assessing the risks of visual impairment as a result of channel decompression, we found that decompression itself, without attempts to separate the tumor from the nerve, causes vision impairment in 8.6 % of cases. Attempts to separate the tumor from the optic nerves increase the risk of vision impairment from 16.7 to 26.9 %, depending on the radicality. Conclusion. A small number of complications (iatrogenic amaurosis and nasal liquorrhea) make it possible to recommend the described technique as an effective and safe addition to standard transcranial operations to remove the meningiomas of the chiasmal-cellar region.Цель исследования - определить эффективность и безопасность интрадуральной и экстрадуральной декомпрессии канала зрительного нерва в ходе стандартной транскраниальной операции по удалению менингиомы хиазмально-селлярной области. Материалы и методы. Проанализированы результаты 161 декомпрессии канала зрительного нерва у 129 пациентов. У большинства пациентов (n = 122) выполняли интрадуральную декомпрессию (резекцию) крыши канала. У 7 пациентов провели экстрадуральную декомпрессию верхней и боковой стенки канала. Результаты. Оценивая риски ухудшения зрения в результате декомпрессии канала, мы установили, что сама декомпрессия без попыток отделения опухоли от нерва вызывает ухудшение зрения в 8,6 % случаев. Попытки отделения опухоли от зрительного нерва повышают риск ухудшения зрения до 16,7-26,9 % в зависимости от радикальности. Заключение. Небольшая частота осложнений (ятрогенного амавроза и назальной ликвореи) позволяет рекомендовать описанную методику как эффективное и безопасное дополнение к стандартным транскраниальным операциям по удалению менингиом хиазмально-селлярной области

Transcranial microsurgical decompression of the optic canal in surgical treatment of meningiomas of the sellar region

Rationale. When removing the meningiomas of the sellar region, there is always a risk of visual impairment for various reasons, in particular, as a result of traction damage to the optic nerve. Decompression of the optic canal increases nerve mobility during tumor manipulation. In cases of meningioma growing into the canal, its decompression often seems necessary. Aim. Evaluation of the effectiveness and risks of performing decompression of the optic canal. Materials and methods. The study included patients with meningiomas of the parasellar location, who underwent surgical treatment at the Burdenko Neurosurgical Center for the period from 2001 to 2017. They were divided into two groups — main and control. The main group consisted of 129 patients who underwent decompression of the optic nerve canals when the tumor was removed. The tumor matrix in this group was most often located in the region of the tuberum sellae, supradiaphragmally, in the region of the anterior clinoid process and the optic canal. In 31 cases, decompression was bilateral — during one operation and using one access in 27 patients; in 4 cases, the decompression of the second canal was delayed for 1.5—3 months after the first operation. 160 decompressions were performed by the intradural and 7 — by extradural methods. During intradural decompression, the roof of the optic canal was resected, and during extradural decompression, the lateral wall of the canal was trephined. The control group consisted of 308 patients who did not undergo canal decompression when the tumor was removed. It included meningiomas with a predominant location of the matrix in the area of the tuberclum and diaphragm of the sella. Tumors in both groups were removed according to the same principles (matrix coagulation, mainly the gradual removal of the tumor, the use of ultrasonic aspirator, a situational decision on the radicality of the operation, etc.). The main difference between operations in these two groups was only canal related algorithms (with or without its trepanation), as well as the probable prevalence of significant lateral tumor growth in cases with canal trepanation. Visual functions in the «primary» group were evaluated before and after operations with trepanation of the canal depending on various factors — the initial state of vision and the radicality of the tumor excision, including removal from the canal. The differences in the postoperative dynamics of vision in the main and control groups were studied. The primary data processing was carried out using the program MSExcel. Secondary statistical processing was carried out using the program Statistica. To assess the statistical significance of differences in the results obtained in the compared patient groups, the Chi-square test was used, and in the case of small groups — the exact Fisher test was applied. Results. In the main group postoperative vision improvement of varying degrees on the side of trepanation was registered in 36.9% (59 out of 160) cases, no vision changes were found in 36.9% (59 out of 160), and in 26,2% (42 out of 160) the eyesight deteriorated. If preserving vision is attributed to a satisfactory result, then in general the results of these operations should be considered good. A comparative study of the results of removal of meningiomas with trepanation of the canals (main group) or without it (control group) was carried out among patients with the most critical vision situation (visual acuity 0.1 and below, up to only light perception). These groups are comparable in the number of observations — 62 and 73 respectively. The predominance of cases with improved vision in the main group compared with the control group (50.0% versus 38.36%) and a lower incidence of vision impairment (22.58% versus 34.25%) were found. However, the revealed differences are statistically unreliable and make it possible for us to talk only about the trend. The complications associated with trepanation of the canal include mechanical damage to the nerve by the drill. In our series of observations, there was only 1 case of abrasion of the nerve surface with the burr, which did not lead to a significant visual impairment. With the intradural method of trepanation in the area of the medial wall of the canal, the sphenoid sinus may open (in our series, in 34 cases out of 160 trepanations). Immediately closure of these defects was performed by various auto-and allomaterials in various combinations (pericranium, fascia, muscle fragment, hemostatic materials, and fibrinthrombin glue). A true complication — CSF rhinorrhea liquorrhea developed in only one case, which required transnasal plastic surgery of the CSF fistula using a mucoperiostal flap. Conclusions. 1. Trepanation of the optic canal in cases of meningiomas of parasellar localization is a relatively safe procedure in the hands of a trained neurosurgeon and does not worsen the results of operations compared with the excision of the same tumors without trepanation of the canal. 2. The literature data and the results of our study make it possible to consider the decompression of the optic canal as an optional, but in many cases, useful option that facilitates the transcranial removal of some meningiomas of the sellar region. © 2020, Media Sphera Publishing Group. All rights reserved