Deep Brain Stimulation of Nucleus Basalis of Meynert improves learning in rat model of dementia.

Background: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been preliminarily investigated as a potential treatment for dementia. The degeneration of NBM cholinergic neurons is a pathological feature of many forms of dementia. Although stimulation of the NBM has been demonstrated to improve learning, the ideal parameters for NBM stimulation have not been elucidated. This study assesses the differential effects of varying stimulation patterns and duration on learning in a dementia rat model. Methods: 192-IgG-saporin (or vehicle) was injected into the NBM to produce dementia in rats. Next, all rats underwent unilateral implantation of a DBS electrode in the NBM. The experimental groups consisted of i-normal, ii-untreated demented, and iii-demented rats receiving NBM DBS. The stimulation paradigms included testing different modes (tonic and burst) and durations (1-hr, 5-hrs, and 24-hrs/day) over 10 daily sessions. Memory was assessed pre- and post-stimulation using two established learning paradigms: novel object recognition (NOR) and auditory operant chamber learning. Results: Both normal and stimulated rats demonstrated improved performance in NOR and auditory learning as compared to the unstimulated demented group. The burst stimulation groups performed better than the tonic stimulated group. Increasing the daily stimulation duration to 24-hr did not further improve cognitive performance in an auditory recognition task and degraded the results on a NOR task as compared with 5-hr. Conclusion: The present findings suggest that naturalistic NBM burst DBS may offer a potential effective therapy for treating dementia and suggests potential strategies for the reevaluation of current human NBM stimulation paradigms.

A rare encounter: Comprehensive case review of myxoid meningiomas with a representative case.

Meningiomas are the most diagnosed primary central nervous system tumor. Currently, 15 different subtypes of meningioma exist with various characteristics. One extremely rare subtype is myxoid meningioma, which is a World Health Organization grade 1 benign meningioma. These specific meningiomas have only been reported 12 times in the literature. In this representative case, we present a 46-year-old female patient with a left frontal myxoid meningioma, describe the findings on imaging, and provide the histopathological features that are needed for diagnosis. Furthermore, this report discusses the other existing myxoid meningioma case reports found throughout the literature.

Correlation Between Oligometastatic Tumor in Two Other Visceral Organs and Prognosis in Patients With Brain Metastases.

Background and Objective: A recent report indicated that metastases to other body organs commonly develop after stereotactic body radiation treatment for cure in patients with oligometastases (OGM) confined to one organ. This study was undertaken to determine if the presence of metastatic disease in two other visceral organs (TVO) in patients with conventionally treated brain metastases (BRM) was associated with poorer prognosis. Methods: This retrospective clinical investigation included 26 patients treated for palliation of OGM-BRM between May 1996 and February 2020. These individuals were classified according to the presence (13 patients) or absence (13 patients) of metastases in TVO. Results: With an overall mean follow-up of 16 months, 20 patients were deceased, and 6 patients were alive. The median survivals for the OGM-BRM-TVO and non-OGM-BRM-TVO subsets were 4 and 12 months, respectively; the corresponding crude survival rates at 12 months were 0% and 46% (p < 0.01). Subgroup analysis correlating prognosis to the number of BRM (single vs. multiple) and OGM-BRM categories (synchronous vs. metachronous) failed to reveal a survival advantage favoring a certain subgroup. Conclusion: Although the evidence is speculative, we believe that an aggressive disease condition is more likely present in patients with OGM-BRM-TVO. With the notion of an overall poor survival, we suggest a more tailored, less or nonharmful management approach (i.e., palliative therapy or hospice) for this particular patient cohort.

Deep Brain Stimulation Before Anterior Cervical Discectomy and Fusion for a Patient With Cervical Dystonia and Cervical Myelopathy: A Case Report.

Cervical dystonia with concurrent cervical myelopathy is a challenging pathology that requires thoughtful management. A 46-year-old female was referred to our center with this presentation. We elected to perform bilateral globus pallidus internus deep brain stimulation (DBS-GPi) prior to C5 to C7 anterior cervical discectomy and fusion (ACDF) to avoid the potential for dystonic movements to negatively impact cervical fusion. The patient was followed up at three months post C5 to C7 ACDF and nine months post DBS-GPi with complete control of tremor and no radiographic evidence of hardware loosening or malalignment. Though this strategy was successful in treating both our patient's cervical myelopathy and cervical dystonia, larger studies need to be conducted to optimize the treatment of patients presenting with these concurrent pathologies.

Healthy and pathological pallidal regulation of thalamic burst versus tonic mode firing: a computational simulation.

The mechanisms by which the basal ganglia influence the pallidal-receiving thalamus remain to be adequately defined. Our prior in vivo recordings in fully alert normal and dystonic rats revealed that normally fast tonic discharging entopeduncular [EP, rodent equivalent of the globus pallidus internus (GPi)] neurons are pathologically slow, highly irregular, and bursty under dystonic conditions. This, in turn, induces pallidal-receiving thalamic movement-related neurons to change from a healthy burst predominant to a pathological tonic-predominant resting firing mode. This study aims to understand the pallidal influence on thalamic firing modes using computational simulations. We inputted various combinations of healthy and pathological (dystonic) in vivo neuronal recordings to the Rubin and Terman's computational model of low threshold spiking pallidothalamic neurons. The input sets consist of representative tonic, burst, irregular tonic and irregular burst inputs collected from EP/GPi in our animal lab. Initial test combinations of EP/ GPi input to the model were identical to the neuronal population distributions observed in vivo. The thalamic neuron model outputted similar firing rate and mode as observed in corresponding in-vivo thalamus. Further influence of each individual patterns was also delineated. By simulating the firing properties of encountered neurons, the basal ganglia output is suggested to critically act as firing mode selector for thalamic motor relay neurons. By selecting and determining the timing and extent of opening of thalamic T-type calcium channels via GABAergic hyperpolarizing input, GPi neurons are in position to precisely orchestrate thalamocortical burst motor signaling.

PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury.

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of fission and fusion. Overall, these pathophysiological findings correlated with decreased protein arginine methyltransferase 7 (PRMT7) protein levels and activity post-rmTBI. Here, we increased PRMT7 levels in vivo to assess the role of the neurovasculature and mitochondria post-rmTBI. In vivo overexpression of PRMT7 using a neuronal specific AAV vector led to restoration of neurovascular coupling, prevented BBB leakage, and promoted mitochondrial respiration, altogether to suggest a protective and functional role of PRMT7 in rmTBI.

A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury.

Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation. Furthermore, microglia were assessed via enhanced iba1 protein levels and morphological changes using immunofluorescence. In addition, LC/MS analyses revealed excess glutamate production, as well as diffuse axonal injury via Bielschowsky's silver stain kit. Moreover, the heterogeneous nature of rmTBI has made it challenging to identify drug therapies that address rmTBI, therefore we sought to identify novel targets in the concurrent rmTBI pathology. The pathophysiological findings correlated with a time-dependent decrease in protein arginine methyltransferase 7 (PRMT7) protein expression and activity post-rmTBI along with dysregulation of PRMT upstream mediators s-adenosylmethionine and methionine adenosyltransferase 2 (MAT2) in vivo. In addition, inhibition of the upstream mediator MAT2A using the HT22 hippocampal neuronal cell line suggest a mechanistic role for PRMT7 via MAT2A in vitro. Collectively, we have identified PRMT7 as a novel target in rmTBI pathology in vivo and a mechanistic link between PRMT7 and upstream mediator MAT2A in vitro.

The Management of Recurrent Post-myelography Lumbar Pseudomeningocele With Epidural Blood Patch.

Pseudomeningoceles are a well-known potential postoperative complication of spinal and cranial surgeries that can occur after lumbar decompression and posterior fossa surgeries. They are often caused by incidental durotomies but may also occur as a result of dural puncture during diagnostic testing. This report describes a 59-year-old male that developed a recurrent pseudomeningocele after an L4 laminectomy for severe lumbar spinal stenosis that was ultimately treated with an epidural blood patch (EBP). His preoperative condition greatly improved, but he developed a pseudomeningocele that did not resolve after applying ice and light pressure. The patient subsequently underwent a wound exploration where no dural defect was identified. During this exploration, the dura was reinforced with dural onlays and sealant. Unfortunately, the patient developed another pseudomeningocele within a short interval. It was then suspected that the post-laminectomy site provided a space for the dural punctures from previous CT myelography to leak cerebrospinal fluid (CSF) into. The patient subsequently underwent ultrasound (US)-guided aspiration of the pseudomeningocele and EBP injections at the levels where his preoperative myelography was performed. The success of the EBP indicates that the previous CT myelography was the likely cause of the pseudomeningocele. Recurrent spinal pseudomeningoceles with no evidence of incidental durotomy may be caused by dural puncture from myelography. In such cases, EBP to the area that the previous myelography was performed can resolve the pseudomeningocele.

Health inequities and socioeconomic factors predicting the access to treatment for unruptured intracranial aneurysms in the USA in the last 20 years: interaction effect of race, gender, and insurance.

BACKGROUND: The literature suggests that minority racial and ethnic groups have lower treatment rates for unruptured intracranial aneurysms (UIA). It is uncertain how these disparities have changed over time. METHODS: A cross-sectional study using the National Inpatient Sample database covering 97% of the USA population was carried out. RESULTS: A total of 213 350 treated patients with UIA were included in the final analysis and compared with 173 375 treated patients with aneurysmal subarachnoid hemorrhage (aSAH) over the years 2000-2019. The mean (SD) age of the UIA and aSAH groups was 56.8 (12.6) years and 54.3 (14.1) years, respectively. In the UIA group, 60.7% were white patients, 10.2% were black patients, 8.6% were Hispanic, 2% were Asian or Pacific Islander, 0.5% were Native Americans, and 2.8% were others. The aSAH group comprised 48.5% white patients, 13.6% black patients, 11.2% Hispanics, 3.6% Asian or Pacific Islanders, 0.4% Native Americans, and 3.7% others. After adjusting for covariates, black patients (OR 0.637, 95% CI 0.625 to 0.648) and Hispanic patients (OR 0.654, 95% CI 0.641 to 0.667) had lower odds of treatment compared with white patients. Medicare patients had higher odds of treatment than private patients, while Medicaid and uninsured patients had lower odds. Interaction analysis showed that non-white/Hispanic patients with any insurance/no insurance had lower treatment odds than white patients. Multivariable regression analysis showed that the treatment odds of black patients has improved slightly over time, while the odds for Hispanic patients and other minorities have remained the same over time. CONCLUSION: This study from 2000 to 2019 shows that disparities in the treatment of UIA have persisted but have slightly improved over time for black patients while remaining constant for Hispanic patients and other minority groups.

Racial and socioeconomic disparities in the advanced treatment of medically intractable pediatric epilepsy.

OBJECTIVE: Racial and ethnic disparities in healthcare have gained significant importance since the Institute of Medicine published its report on disparities in healthcare. There is a lack of evidence on how race and ethnicity affect access to advanced treatment of pediatric medically intractable epilepsy. In this context, the authors analyzed the latest Kids' Inpatient Database (KID) for racial/ethnic disparities in access to surgical treatment of epilepsy. METHODS: The authors queried the KID for the years 2016 and 2019 for the diagnosis of medically intractable epilepsy. RESULTS: A total of 29,292 patients were included in the sample. Of these patients, 8.9% (n = 2610) underwent surgical treatment/invasive monitoring. The mean ages in the surgical treatment and nonsurgical treatment groups were 11.73 years (SD 5.75 years) and 9.5 years (SD 6.16 years), respectively. The most common insurance in the surgical group was private/commercial (55.9%) and Medicaid in the nonsurgical group (47.7%) (p < 0.001). White patients accounted for the most common population in both groups, followed by Hispanic patients. African American patients made up 7.9% in the surgical treatment group compared with 12.9% in the nonsurgical group. African American (41.1%) and Hispanic (29.9%) patients had higher rates of emergency department (ED) utilization compared with the White population (24.6%). After adjusting for all covariates, the odds of surgical treatment increased with increasing age (OR 1.06, 95% CI 1.053-1.067; p < 0.001). African American race (OR 0.513, 95% CI 0.443-0.605; p < 0.001), Hispanic ethnicity (OR 0.681, 95% CI 0.612-0.758; p < 0.001), and other races (OR 0.789, 95% CI 0.689-0.903; p = 0.006) had lower surgical treatment odds compared with the White population. Medicaid/Medicare was associated with lower surgical treatment odds than private/commercial insurance (OR 0.603, 0.554-0.657; p < 0.001). Interaction analysis revealed that African American (OR 0.708, 95% CI 0.569-0.880; p = 0.001) and Hispanic (OR 0.671, 95% CI 0.556-0.809; p < 0.001) populations with private insurance had lower surgical treatment odds than White populations with private insurance. Similarly, African American patients, Hispanic patients, and patients of other races with nonprivate insurance also had lower surgical treatment odds than their White counterparts after adjusting for all other covariates. CONCLUSIONS: Based on the KID, African American and Hispanic populations had lower surgical treatment rates than their White counterparts, with higher utilization of the ED for pediatric medically intractable epilepsy.

Meningioma with holo-sagittal sinus involvement treated successfully with intrinsic sinus surgery: illustrative case.

BACKGROUND: This report describes an unusual meningioma with a large left frontal component and extensive growth within the sagittal sinus and its successful treatment with a staged approach: left frontal craniotomy followed by a sagittal craniotomy and intrinsic removal of the tumor from the sagittal sinus. OBSERVATIONS: A previously healthy 27-year-old presented with 6 months of progressively worsening bilateral headaches, visual changes, and nausea. On examination she had a left cranial nerve VI palsy and severe papilledema. Magnetic resonance imaging revealed a 5.1 × 3.8 × 4.1 cm homogenously enhancing left superior frontal parafalcine extra-axial mass with surrounding vasogenic edema and growth through the sagittal sinus extending just short of the torcula. LESSONS: This case report describes a fast-growing meningioma with a unique pattern of spread, growing through the sagittal sinus as if it were a conduit and resulting in complete occlusion of flow in the sinus. An important recognition in this case was that a robust parasagittal venous plexus had developed on either side of the falx cerebri with drainage to the inferior sagittal sinus. This collateral drainage pattern allowed for an extradural opening of the sagittal sinus from front to back and intrinsic resection of the tumor from the sinus with preservation of the lateral walls of the sinus.

Attacked and Shaken by a Dog: A Cause of Traumatic Brain and Carotid Injury in an Infant.

BACKGROUND: Posttraumatic carotid artery dissection (PTCAD) is a common injury in motor vehicle accidents and other extension and rotation injuries, but rarely developed from being shaken vigorously. CASE DESCRIPTION: A 7-day-old infant presented to our facility after being attacked by a large dog. Initial examination revealed multiple puncture wounds and lacerations with visible dura. Head CT demonstrated subarachnoid, intraparenchymal, and epidural hemorrhages as well as left hemispheric loss of gray-white differentiation. Thus, the patient presented similarly to shaken baby syndrome (SBS). The patient was taken emergently to the operating room for hematoma evacuation and dural repair. Postoperatively, worsened left hemispheric ischemia was noted and an MRA demonstrated a Grade IV left ICA dissection. No intervention, including anticoagulation, was sought as the stroke was determined to be complete with irreversible damage. Hospital course was complicated by worsening exam, seizures, and a retinal hemorrhage. At 2 years follow-up, the patient still has notable delays but is progressing slowly through milestones. CONCLUSION: Large animal attacks are a rare cause of PTCAD but may be due to the mechanism of shaking during the attack. We propose either CTA or MRA be considered as part of the initial workup in cases where an infant is attacked by a dog or other large animals, preventing delay of treatment.

Neurologic Complications in Patients with Left Ventricular Assist Devices: Single Institution Retrospective Review.

BACKGROUND: Neurologic complications are common complications encountered by patients with left ventricular assist devices (LVADs). This single-center retrospective study aims to identify the incidence and risk factors of neurologic complications and interventions in patients supported with LVADs and define the associated anticoagulation management. METHODS: Between August 2009 and August 2017, 244 patients underwent LVAD implantation. Twenty-one patients were excluded for having neurologic complications before LVAD placement or for having previously undergone heart transplantation. RESULTS: Fifty-six patients (25%) suffered 61 complications, and 11 (19.6%) died as a result. Gender, type of LVAD, or chronic medical comorbidities evaluated did not contribute to a difference in complication rate; in contrast, length of LVAD implantation was directly related to risk of neurologic complication. Eleven patients (19.6%) underwent 13 surgical interventions including 5 mechanical thrombectomies. Anticoagulation was reversed in 16 patients and held without complication. Anticoagulation was not held for ischemic complications, and no clinically significant hemorrhagic transformation occurred. Intravenous tissue plasminogen activator was also successfully administered to 3 patients without complication. CONCLUSIONS: Neurologic complications were observed in 25% of patients supported with LVADs, of which 20% required neurosurgical intervention. Anticoagulation can be safely withheld in patients with hemorrhagic complications. Patients with ischemic complications can continue to be anticoagulated with no significant risk of hemorrhagic transformation. Length of LVAD implantation was directly related to the risk of neurologic complication. Finally, our study adds to existing literature that mechanical thrombectomy and even intravenous tissue plasminogen activator are options for LVAD patients with ischemic complications.

Gram-negative Cranial Bone Flap Infection Treated with Continuous Gentamicin Irrigation: A Case Report.

A 57-year-old male presented with severely altered mental status in the setting of diabetic ketoacidosis. Neuroimaging revealed two intracranial masses. Days following surgical resection of an olfactory groove meningioma, the patient developed Serratia marcescens bacteremia along with an enlarging epidural and subgaleal fluid collection. Subgaleal fluid aspiration was also positive. The patient later returned to the operating room for wound washout where purulent collections were discovered in the subgaleal, epidural, and left subdural spaces. The wound was evacuated and the bone flap was thoroughly cleansed with betadine and soaked in peroxide prior to replacement. Four drains were placed (two subgaleal and two epidural) with two serving as inlets and two as outlets. Continuous irrigation of the subgaleal and epidural spaces with gentamicin solution was performed for five days. The bone flap was successfully salvaged and the patient was discharged from inpatient rehab three weeks following washout.

A Comparative Study of Fiducial-Based and Fiducial-Less Registration Utilizing the O-Arm.

BACKGROUND: Frameless stereotactic surgery utilizing fiducial-based (FB) registration is an established tool in the armamentarium of deep brain stimulation (DBS) surgeons. Fiducial-less (FL) registration via intraoperative CT, such as the O-arm, has been routinely used in spine surgery, but its accuracy for DBS surgery has not been studied in a clinical setting. OBJECTIVE: We undertook a study to analyze the accuracy of the FL technique in DBS surgery and compare it to the FB method. METHODS: In this prospective cohort study, 97 patients underwent DBS surgery using the NexFrame and the O-arm registration stereotactic system. Patients underwent FB (n = 50) registration from 2015 to 2016 and FL (n = 47) O-arm registration from 2016 to 2017. RESULTS: The radial errors (RE) and vector/euclidean errors of FB and FL registration were not significantly different. There was no difference in additional passes between methods, but there was an increase in the number of RE ≥2.5 mm in the FL method. CONCLUSION: Although there was no statistically significant difference in RE or the need for additional passes, the increased number of errors ≥2.5 mm with the FL method (17 vs. 4% in FB) indicates the need for further study. We concluded that O-arm images of the implants should be utilized to assess and correct for this error.

Nucleus Basalis of Meynert Stimulation for Dementia: Theoretical and Technical Considerations.

Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) is currently being evaluated as a potential therapy to improve memory and overall cognitive function in dementia. Although, the animal literature has demonstrated robust improvement in cognitive functions, phase 1 trial results in humans have not been as clear-cut. We hypothesize that this may reflect differences in electrode location within the NBM, type and timing of stimulation, and the lack of a biomarker for determining the stimulation's effectiveness in real time. In this article, we propose a methodology to address these issues in an effort to effectively interface with this powerful cognitive nucleus for the treatment of dementia. Specifically, we propose the use of diffusion tensor imaging to identify the nucleus and its tracts, quantitative electroencephalography (QEEG) to identify the physiologic response to stimulation during programming, and investigation of stimulation parameters that incorporate the phase locking and cross frequency coupling of gamma and slower oscillations characteristic of the NBM's innate physiology. We propose that modulating the baseline gamma burst stimulation frequency, specifically with a slower rhythm such as theta or delta will pose more effective coupling between NBM and different cortical regions involved in many learning processes.

Traumatic lumbar spondylolisthesis resulting in complete thoracic spinal cord avulsion: an unusual presentation.

Traumatic spondylolisthesis is a known occurrence in trauma, but complete cord transection is relatively rare. Moreover, complete cord transection at a site distant from the traumatic spondylolisthesis without spondyloptosis is exceedingly rare. In this report, authors describe the first case of thoracic cord avulsion following a traumatic grade II lumbar spondylolisthesis. The unusual presentation of this case highlights the importance of further evaluating patients with neurological symptoms out of proportion with the injuries seen on initial imaging. Magnetic resonance imaging performed after initial imaging studies demonstrated T11 cord transection with the distal cord herniating into the lumbar paraspinal soft tissues, thus allowing for preoperative planning to prepare for a more significant intervention including complex dural repair and lumbar drain placement, in addition to instrumented fusion to stabilize the traumatic spondylolisthesis.

De Novo Spinal Dural Arteriovenous Fistula in a Patient with a Lipomyelomeningocele: Case Report.

BACKGROUND: Spinal dural arteriovenous fistula (AVF), the most common type of spinal vascular malformation, tends to manifest as progressive myelopathy over several years. Spinal dural AVFs are considered an acquired lesion and, in contrast to spinal arteriovenous malformations, are not often associated with other anomalies. The presence of a spinal dural AVF in the setting of a lipomyelomeningocele and tethered cord is extremely rare. Both lesions tend to cause similar symptoms, and patients with concomitant lesions generally require surgical intervention for both. CASE DESCRIPTION: A 57-year-old female with lifelong urinary incontinence and mild weakness in the left lower extremity presented with progressive worsening of left lower extremity weakness as well as worsening bowel and bladder incontinence. Magnetic resonance imaging (MRI) performed 4 years before our evaluation revealed a lipomyelomeningocele and a tethered cord; a new MRI demonstrated a new additional finding of flow voids suspicious of an underlying vascular malformation. Diagnostic angiography revealed a dural AVF fed by a left lateral sacral artery. Onyx embolization of the dural AVF was performed, and the patient improved steadily postoperatively without the need for surgically addressing the tethered cord. CONCLUSION: In this case report, we present evidence of de novo development of a spinal dural AVF associated with a lipomyelomeningocele. In addition, this is the second documented patient in the literature with a lipomyelomeningocele and concomitant dural AVF who did not undergo detethering of the cord as part of treatment.

An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation.

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.