Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.

Variants in CIB2 cause DFNB48 and not USH1J.

The genetic, mutational and phenotypic spectrum of deafness-causing genes shows great diversity and pleiotropy. The best examples are the group of genes, which when mutated can either cause non-syndromic hearing loss (NSHL) or the most common dual sensory impairment, Usher syndrome (USH). Variants in the CIB2 gene have been previously reported to cause hearing loss at the DFNB48 locus and deaf-blindness at the USH1J locus. In this study, we characterize the phenotypic spectrum in a multiethnic cohort with autosomal recessive non-syndromic hearing loss (ARNSHL) due to variants in the CIB2 gene. Of the 6 families we ascertained, 3 segregated novel loss-of-function (LOF) variants, 2 families segregated missense variants (1 novel) and 1 family segregated a previously reported pathogenic variant in trans with a frameshift variant. This report is the first to show that biallelic LOF variants in CIB2 cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients. Here, we provide evidence disqualifying CIB2 as an USH-causing gene.

Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss.

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.

A Mayan founder mutation is a common cause of deafness in Guatemala.

Over 5% of the world's population has varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (ARNHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a ARNHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared with those of Native American, European, and African populations shows a close match with the Mayan population.

Exploring the relationship between the severity of oligozoospermia and the frequencies of sperm chromosome aneuploidies.

The study was aimed to investigate the association between the degree of oligozoospermia and sperm chromosome aneuploidy frequencies in male infertility and to determine whether chromosomal profiles of sperm nuclei would be used for a supportive test before additive reproduction technics. The meiotic segregation profiles of chromosomes X, Y, 13, 18 and 21 were compared by fluorescent in-situ hybridisation (FISH) on the spermatozoa of 30 normally karyotyped oligozoospermic (10 mild, 11 moderate, nine severe) cases without Y-microdeletions, and 10 normozoospermic cases. The results showed significantly higher frequencies of chromosomes 13, 18, 21 disomies (P < 0.001) in the group of patients with moderate and severe oligozoospermia compared with the disomy frequencies of normozoospermic group. The statistically significant differences were also determined in disomy frequencies of sex chromosomes (XY, XX and YY) in between oligozoospermic and normozoospermic groups (P < 0.001, P < 0.001, P < 0.040, respectively). Because oligozoospermic patients are the ones consulted the most for assisted reproductive techniques, identification of sperm aneuploidy rates in men could be considered as an appropriate supportive test before the reproductive implementations. Furthermore, the patients should be counselled with respect to genetic screening results for the potential risk of aneuploid embryo and pre-implantation genetic diagnosis or prenatal diagnosis.

Extremely delayed renal cell carcinoma metastasis mimicking convexity meningioma.

Cerebral extra-axial metastasis mimicking meningioma which satisfy several criteria for a diagnosis of meningioma, but which have proved instead to be metastatic carcinoma and extremely delayed cerebral metastasis from renal cell carcinoma, form the focus of the presentation. 68-year-old-woman who had been operated for renal cell carcinoma 20 years previously is presented with new symptoms of intracranial mass. A large extra-axial mass of the convexity which destroyed calvarium and dura was excised with Simpson Grade I removal, revealed metastatic carcinoma. Imaging characteristics can not always discern between meningioma and metastatic tumours. A meticulous clinical evaluation and histopathological diagnosis is essential in patients with intracranial mass even when they resemble both primary and metastatic tumours.

Extremely delayed renal cell carcinoma metastasis mimicking convexitymeningioma

Cerebral extra-axial metastasis mimicking meningiomawhich satisfy several criteria for a diagnosisof meningioma, but which have proved instead to bemetastatic carcinoma and extremely delayed cerebralmetastasis from renal cell carcinoma form the focus ofthe presentation.68-year-old-woman who had been operated forrenal cell carcinoma 20 years previously is presentedwith new symptoms of intracranial mass. A large extraaxialmass of the convexity which destroyed calvariumand dura was excised with Simpson Grade I removal,revealed metastatic carcinoma.Imaging characteristics can not always discern betweenmeningioma and metastatic tumours. A meticulousclinical evaluation and histopathological diagnosisis essential in patients with intracranial mass even theyresemble both primary and metastatic tumours (AU)

Se presenta un caso de metástasis craneal extra-axial,que satisface varios criterios para el diagnóstico de meningioma,en el cual se demostró que se trataba de lametástasis tardía de un carcinoma renal.Una paciente de 61 años, que había sido operada deun carcinoma renal 20 años antes, se presentó con síntomasde un tumor cerebral. Se extirpó un gran tumorextra-axial de la convexidad, que destruía la bóvedacraneal y la duramadre, (Simpson grado I), pero quereveló se trataba de una metástasis.Las imágenes de estas característica no siempre pueden discernir entre un meningioma y una metástasis.Es esencial realizar una meticulosa valoraciónclínica y un diagnóstico histopatológico en pacientescon tumores intracraneales, aunque parezcan tumoresmetastáticos (AU)

Can facet joint infiltrative analgesia reduce postoperative pain in degenerative lumbar disc surgery?

OBJECTIVE: Perioperative analgesia effects the postoperative course of pain. The purpose of this study was to evaluate its possible relation with the consumption of dolantine and analgesics and the facet-induced pain and postoperative pain score in degenerative disc surgery. METHODS: We employed perioperative intra- and perifacet bupivacaine infiltration technique to reduce the postoperative pain after lumbar disc surgery. The study was randomized and observer blinded enrolling 40 American Society of Anesthesiologists physical status class I-II patients scheduled for elective degenerative lumbar disc surgery. The patients were divided into two groups of 20 of which Group 1 underwent injection of bupivacaine into the subcutaneous and muscular layers around the incision site, while Group 2 underwent additional intra- and perifacetal joint infiltration. Postoperatively, the patients were provided with a programmed patient-controlled pump which was only activated on demand to infuse dolantine for the next 24 hours. In the postanesthesia care unit the delay for analgesia and the dose of dolantine used were recorded. RESULTS: There was no statistical significance between these two groups regarding postoperative visual analoque scale scores. The time before the first analgesic request was significantly longer in facet group (p= 0,006). The cumulative dolantine dose was also significantly lower in the facet group (p= 0,001). CONCLUSION: The results indicate that facet joint infiltrative analgesia may have an effect on the postoperative analgesic requirement and reduce the dolantine consumption.

The morphometric and cephalometric study of anterior cranial landmarks for surgery.

OBJECTIVE: The aim of this work was to determine reliable bony landmarks for the anterior skull base and to standardize some specific dimensions among the frontal sinus and neighboring structures for safe anterior cranial surgery. METHODS: The study consisted of a topographical anatomic examination and cephalometric analysis of the skull. Thirty adult skulls (60 sides) were studied regarding the localization and dimensions of the supraorbital foramen (SOF), frontal sinus (FS), frontozygomatic fissure, infraorbital foramen, anterior nasal spine, and nasion. Differences between the measurement of skulls and cephalograms were analyzed by Student's t test. The Pearson correlation test was used for statistical analysis of the cephalogram. RESULTS: Examination of the 60 sides of the bony heads revealed that the shape of the SOF was a foramen in 25 sides (41%), a notch in 29 sides (49%), and a groove in 6 sides (10%). A total of 20 (33%) SOFs were inside the FS and the mean distance was 6.3+1.34 mm from the lateral border of the sinus, 27 (45%) of SOFs were outside of the FS and the mean distance was 8.8+2.01 mm, and 13 (22%) of SOFs were at the border of the FS. According to our measurements the medial border of the craniotomy should be placed approximately 43 mm lateral to the nasion to avoid entering into the frontal sinus. CONCLUSION: To plan and to decide the convenient and safe anterior midline skull base approach and to avoid postoperative complications, bony landmarks and anatomic measurements around the SOF and FS will be helpful for the surgeon to constitute a simplification of topographic anatomy.

Can facet joint infiltrative analgesia reduce postoperative pain in degenerative lumbar disc surgery?

Objetivo. La analgesia peroperatoria influye en el curso del dolor postquirúrgico. El propósito del estudio reside en la evaluación de la posible relación entre el consumo de dolantina y otros analgésicos en el control del dolor postquirúrgico de origen facetario lumbar en la enfermedad discal degenerativa. Métodos. Empleamos peroperatoriamente infiltraciones percutáneas de bupivacaína intra y perifacetariapara reducir el dolor postoperartorio tras cirugía discal lumbar. El estudio fue randomizado y oculto al observador y se realizó sobre 40 pacientes operados de cirugía electiva por enfermedad degenerativa lumbar, con una situación general Clase I-II de la clasificación de la American Society of Anesthesiologist. Los pacientes se dividieron en dos grupos de 20 .El Grupo1 se le administró bupivacaína en el tejido subcutáneoy capas musculares. El grupo 2 recibió una inyección adicional de bupivacaína intra y perifacetaria. Durante el postoperatorio, los pacientes, dispusieron de una bomba programable de analgesia controlada, que se activó exclusivamente a demanda para infundir dolantina en las 24 horas siguientes a la operación. En la Unidad de Reanimación postquirúrgicas se recogieron las necesidades de dolantina de los distintos pacientes. Resultados. No se encontraron diferencias estadísticamente significativas entre ambos grupos en relación a los valores de la escala analógica visual. El tiempo de demanda del primer bolo analgésico fue significativamente mayor en el grupo de facetas infiltradas (p=0,006). La acumulación de las dosis de dolantina fue también significativamente inferior en el grupo de facetas infiltradas (p=0.001) Conclusión. Los resultados indican que la infiltración de la faceta articular con anestésico local puede tener un efecto positivo reduciendo las necesidades analgésicas postoperatorias de dolantina

Objective. Perioperative analgesia effects the postoperative course of pain. The purpose of this study was to evaluate its possible relation with the consumption of dolantine and analgesics and the facet-induced pain and postoperative pain score in degenerative disc surgery. Methods. We employed perioperative intra- and perifacet bupivacaine infiltration technique to reduce the postoperative pain after lumbar disc surgery. The study was randomized and observer blinded enrolling40 American Society of Anesthesiologists physical status class I-II patients scheduled for elective degenerative lumbar disc surgery. The patients were divided into two groups of 20 of which Group 1 underwent injection of bupivacaine into the subcutaneous and muscular layers around the incision site, while Group 2 underwent additional intra- and perifacetal joint infiltration. Postoperatively, the patients were provided with a programmed patient-controlled pump which was only activated on demand to infuse dolantine for the next 24 hours. In the postanesthesia care unit the delay for analgesia and the dose of dolantine used were recorded. Results. There was no statistical significance between these two groups regarding postoperative visual analoque scale scores. The time before the first analgesic request was significantly longer in facet group (p=0,006). The cumulative dolantine dose was also significantly lower in the facet group (p= 0,001). Conclusion. The results indicate that facet joint infiltrative analgesia may have an effect on the postoperative analgesic requirement and reduce the dolantine consumption

VACTERL-H associated with central hypothyroidism: a case report.

The VACTERL-H syndrome is a rare combination of vertebral anomalies, anal atresia, congenital heart defects, tracheo-esophageal fistula, abnormalities of kidneys and limb anomalies together with hydrocephalus. This condition is recognized as a hereditary entity with poor prognosis. We present a newborn weighing 3400 g, born by cesarean section to a 27 years old mother who had had an irregular antenatal follow-up. The patient had severe hydrocephalus, proximal esophageal atresia and distal tracheoesophageal fistula, gastric outlet obstruction, imperforated anus and recto-urethral fistula, patent ductus arterious, a bifid scrotum, a vertebral defect, sacral dimple and central hypothyroidism. The patient had no limb defects. The association of central hypothyroidism and VACTERL-H has previously not been reported.

Late dissemination of ependymoma: case report.

Spinal cord dissemination over 10 years after surgical removal of the fourth ventricle ependymoma without local recurrence is extremely rare. A 49-year-old male underwent a macroscopically gross total removal of the fourth ventricle ependymoma and postoperative radiotherapy to the posterior fossa. Twelve years after the initial operation, the patient complained from uncontrolled fever attacks, low back pain and numbness of the legs. Spinal Magnetic Resonance Imaging revealed intradural extramedullary mass lesions located at the thoracic 2-3 and lumbar 5 vertebrae levels. Cerebrospinal fluid examination showed no tumour cells. He underwent total excision of these spinal lesions. Although the majority of the recurrences take place within a few years after surgery, we experienced a case with multiple spinal disseminations 12 years after the resection of the fourth ventricle ependymoma and administration of the radiation therapy to the posterior fossa. Up to our knowledge, this case represents the second unusual late recurrence reported in the literature. We conclude that low grade ependymomas should be followed neurologically and radiologically for more than 10 years after the initial treatment.

Critically located cavernous malformations.

INTRODUCTION: The aim of this study was to evaluate the clinical results of patients who underwent resection with the aid of microsurgical techniques and stereotactic and image-guided surgery for critically located cavernous malformations which still represent a considerable surgical challenge due to the close proximity of vital and eloquent structures. METHODS: Between 1997 and 2003, 12 patients with critically located cavernous malformations (CMs) underwent surgical resections at Ankara University Hospital. CMs of the pons (n=3), medulla oblongata (n=1), cavernous sinus (n=3), motor cortex (n=4) and the newly defined superior cerebellar peduncle (n=1) were treated using image-guidance and advanced microsurgical principles. Preoperative assessment was done with CT, MRI and angiography. Lesion locations, clinical presentations and outcome were analyzed. The surgical approach was chosen as lateral suboccipital (n=4), parietal (n=4), cranio-orbitozygomatic (n=3) and retrosigmoid (n=1). RESULTS: All CMs were readily identified and completely removed with no permanent morbidity and mortality. The immediate outcome after surgery was improved for 8 patients (66.6%). Long-term outcome was unchanged for one patient and a proved good surgical outcome for three patients, during the mean follow-up period. DISCUSSION: Stereotactic methods together with image-guidance and microsurgical techniques allow the creation of most effective and safe corridors to access the CMs in eloquent regions with a minimization of tissue manipulation and low risk of permanent neurological deficit.

Late dissemination of ependymoma: case report

Spinal cord dissemination over 10 years after surgical removal of the fourth ventricle ependymoma without local recurrence is extremely rare. A 49-year-old maleunderwent a macroscopically gross total removal of the fourth ventricle ependymoma and postoperative radiotherapy to the posterior fossa. Twelve years after the initial operation, the patient complained from uncontrolled fever attacks, low back pain and numbness of the legs. Spinal Magnetic Resonance Imaging revealed intradural extramedullary mass lesions located at the thoracic 2-3 and lumbar 5 vertebrae levels. Cerebrospinal fluid examination showed no tumour cells. He underwent total excision of these spinal lesions. Although the majority of there currences take place within a few years after surgery, we experienced a case with multiple spinal disseminations12 years after the resection of the fourth ventricle ependymoma and administration of the radiation therapy to the posterior fossa. Up to our knowledge, this case represents the second unusual late recurrence reported in the literature. We conclude that low grade ependymomas should be followed neurologically and radiologically for more than10 years after the initial treatment

La diseminación raquídea, después de la extirpaciónquirúrgica de un ependimoma del cuarto ventrículo, sin recurrencia local, es muy rara. Un varón de 49 años fue intervenido de un ependimoma del IV ventrículo, con resección total y radioterapia postoperatoria de la fosa posterior. Doce años después de esta intervención, el paciente comenzó a quejarse de episodios febriles incontrolables, dolor lumbar y adormecimiento en las piernas. La resonancia magnética mostraba lesiones localizadas a la altura de la 2-3ª vértebra dorsal y de la L5. El líquido cefalorraquídeo no mostraba células tumorales. Fue operado de ambos tumores raquídeos, con resección total. Aunque la mayoría de las recurrencias tienen lugar en los primeros años después de la operación, hemos observado un caso con diseminación raquídea múltiple, después de la resección de un ependimoma del IV ventrículo y radioterapia de la fosa posterior. Que sepamos, este caso es el segundo de recurrencia tardía, publicado en la literatura. En conclusión, los ependimomas de bajo grado deben ser vigilados neurológica y radiológicamente durante más de diez años después del tratamiento inicial

Persistent metopic suture can mimic the skull fractures in the emergency setting?

Metopism is partially or totally persisting suture extending from the nasion to the anterior angle of the bregma. The time of physiological closure of the metopic suture varies from birth to 8 years of age. Widely accepted closuring time is approximated at 2 years of age. Although formerly reported skull studies mentioned the persistent metopic suture, it is extremely rare in clinical practice. We presented a trauma case of 43 years of age who was demonstrated radiologically to have a persisting suture. Persistent metopic suture may be misdiagnosed as a vertical traumatic skull fracture extending in the mid-line in head trauma patients. Therefore the surgeon should be aware of this anatomical condition in the primary and secondary surveillance of the traumatized patient and during surgical intervention including especially frontal craniotomy. Reconstructed tomography scan demonstrating sutural closuring status may provide additional informative value in the diagnostic sequence superior to plain X-ray in the emergency setting.

Persistent metopic suture can mimic the skull fractures in the emergency setting?

El cuadro denominado metopismo consiste en lapersistencia parcial o total de la sutura que se extiendedesde el nasion hasta el ángulo anterior del bregma. Eltiempo de cierre de la sutura metópica oscila desde elmomento del nacimiento hasta los ocho años. El criteriomás aceptado es que el cierre suele terminar a losdos años. Algunos estudios mencionaban la posibilidadde la persistencia de dicha sutura a lo largo de toda lavida, pero es excepcional en la práctica clínica. Se presentaun caso de traumatismo de 43 años de edad, quemostraba en la radiología la falta de cierre de dichasutura metópica. Aunque puede considerarse comouna anomalía rara, también puede con una fracturavertical frontal, cercana a la línea media, en pacientescon traumatismos. Por lo tanto, el cirujano debe percatarsede este hecho anatómico en la atención inicialdel paciente y en la planificación de una craneotomíabifrontal. En este trabajo se señala que la reconstruccióntridimensional de la TAC añade una informaciónvaliosa al estudio radiológico convencional en la unidadde urgencias

Metopism is partially or totally persisting sutureextending from the nasion to the anterior angle of thebregma. The time of physiological closure of the metopicsuture varies from birth to 8 years of age. Widelyaccepted closuring time is approximated at 2 years ofage. Although formerly reported skull studies mentionedthe persistent metopic suture, it is extremely rarein clinical practice. We presented a trauma case of 43years of age who was demonstrated radiologically tohave a persisting suture. Persistent metopic suture maybe misdiagnosed as a vertical traumatic skull fractureextending in the mid-line in head trauma patients.Therefore the surgeon should be aware of this anatomicalcondition in the primary and secondary surveillanceof the traumatized patient and during surgicalintervention including especially frontal craniotomy.Reconstructed tomography scan demonstrating suturalclosuring status may provide additional informativevalue in the diagnostic sequence superior to plain X-rayin the emergency setting

"Triple cross" of the hypoglossal nerve and its microsurgical impact to entrapment disorders.

OBJECTIVE: Cadaveric dissections were performed to review the intracranial and extracranial course of the hypoglossal nerve. The neurological significance of a newly defined "triple cross" of the hypoglossal nerve is discussed. MATERIALS AND METHODS: 10 cadaveric heads (left and right; 20 sides) were dissected using microsurgical techniques. RESULTS: In the cisternal segment of hypoglossal nerve, the diameter of the rostral trunk amounted to 155-680 microm (mean 435 microm), and the caudal trunk to 210-820 microm (mean 482 microm). The roots formed three trunks in 20% of the hypoglossal nerves and two trunks in the rest. As a first cross, the anterior medullary segment of the vertebral artery crossed the hypoglossal nerve roots in 14 of 20 sides (70%). As a rare variation, the vertebral artery extended medial to the nerve (25%) or between its roots (5%). The second cross was found between the descendens hypoglossus and the occipital artery (75%), sternocleidomastoid artery and vein complex (15%) and external carotid artery (10%). The third cross was shown in the submandibular triangle between the lingual hypoglossus and its drainage vein; vena committans nervus hypoglossus. CONCLUSION: Throughout its way, the hypoglossal nerve passes over vascular structures in three crossing points which may serve as a probable cause of hypoglossal nerve entrapment disorders.

First illustrations of female "Neurosurgeons" in the fifteenth century by Serefeddin Sabuncuoglu.

Males have dominated medicine for many centuries. Females could not appear in the medical history equally till the end of the 18th century; although they always have been in medicine as healers. It is worth mentioning that first illustrations indicating female surgeons were found in the book written in Turkish by Serefeddin Sabuncuoglu in the 15th century; while Europe was newly waking up from its dark ages and Middle East was under the influence of strict rules of Arabic and Islamic culture. Serefeddin Sabuncuoglu (1385-1470) was the author of the first illustrated surgical textbook Cerrahiyyetu'l-Haniyye (Imperial surgery) in Turkish Literature. Inside miniatures drawn by Serefeddin Sabuncuoglu indicated that the female surgeons, acknowledged "Tabibe", had been allowed to practice alone in Anatolia. Tabibes are illustrated in the miniatures practicing on the management of dead foetus with foetal hydrocephalus and macrocephalus which were the first clues by means of Turkish women in Neurosurgery.

First illustrations of female "Neurosurgeons" in the fifteenth century by Serefeddin Sabuncuoglu

Los hombres han dominado la medicina durante muchos siglos. Las mujeres no aparecen en la historia de la medicina hasta el final del siglo XVIII, aunque siempre han estado en la medicina como curanderas. Vale la pena mencionar que las primeras ilustraciones que indican la presencia de mujeres en la cirugía se encontraron en un libro escrito en turco por Serefedd in Sabuncuoglu en el siglo XV, mientras Europa todavía despertaba de la oscuridad y el Oriente Medio está bajo la influencia de las estrictas reglas de la cultura Arábiga e Islámica. Serefeddin Sabuncuoglu (1385-1470) fue el autor del primer texto quirúrgico ilustrado Cerrahiyyetu'l-Haniyye (Cirugía Imperial) en Literatura Turca. Las miniaturas dibujadas por Sereffeddin Sabuncuoglu indicaban que las mujeres cirujanos, conocidas como "Tabibe", estaban autorizadas para practicar sólo en Anatolia. Se ilustra, en miniaturas, cómo las Tabibes actuaban en el tratamiento de fetos muertos con hidrocefalia y macrocefalia que fueron, por supuesto, los primeros datos de mujeres turcas en la Neurocirugía

Males have dominated medicine for many centuries.Females could not appear in the medical history equallytill the end of the 18th century; although they always have been in medicine as healers. It is worth mentioning that first illustrations indicating female surgeons were found in the book written in Turkish by Serefedd in Sabuncuoglu in the 15th century; while Europe was newly waking up from its dark ages and Middle East was under the influence of strict rules of Arabic and Islamic culture. Serefeddin Sabuncuoglu (1385-1470)was the author of the first illustrated surgical textbook Cerrahiyyetu'l-Haniyye (Imperial surgery) in Turkish Literature. Inside miniatures drawn by Serefeddin Sabuncuoglu indicated that the female surgeons, acknowledged "Tabibe", had been allowed to practice alone in Anatolia. Tabibes are illustrated in the miniatures practicing on the management of dead foetus with foetal hydrocephalus and macrocephalus which were the first clues by means of Turkish women in Neurosurgery