Simplifying the diagnosis of optic tract lesions.

Optic tract lesions (OTL) are often difficult to diagnose. We suggest an algorithm to simplify the often-challenging diagnosis of OTL. Clinical and imaging data were retrospectively collected from the electronic files of 6 patients diagnosed with OTL at a tertiary medical center in 2016-2020. The series included 4 children and 2 adults with an OTL caused by a glioma (n = 5) or motor vehicle accident (n = 1). Magnetic resonance imaging (MRI) revealed a suprasellar glioma involving the chiasm and tract alone (n = 1) and the ipsilateral optic nerve (n = 2) and only optic tract (3). Perimetry showed incongruent homonymous hemianopia in 3 patients. In two patients, perimetry could only be performed in one eye, and demonstrated hemianopia. In one patient perimetry was unreliable. Fundus examination revealed bow-tie atrophy in all patients. On optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (RNFL) horizontal thinning was observed in the contralateral eye (n = 6). By presenting the information in a predefined order-visual field damage, OCT RNFL thickness, and MRI-the diagnosis could be easily reached even in children, and when other structures like the chiasm were involved. Fundus photographs easily detect bow tie atrophy in children. Systematic presentation of the data in a predefined order can ease the diagnostic process of OTLs.

Are Hounsfield Unit Measurements of Bony Absorption Changes in Cholesteatoma Helpful?

Abstract Introduction High-resolution computed tomography (HRCT) scans of the temporal bone are used to assess the bony erosion of the middle-ear structures whenever cholesteatoma is suspected. Objective To study the differences in HRCT Hounsfield unit (HU) index measurements of middle-ear bony structures between an ears with and without cholesteatoma. Methods A retrospective study of 59 patients who underwent surgery due to unilateral cholesteatoma. The HRCT HU index of the scutum, of three middle-ear ossicles, of the lateral semicircular canal (LSCC), and of the fallopian canal was measured in both ears. A comparison was made between the cholesteatoma and the non-cholesteatomatous ear (control). All measurements were conducted by an otolaryngologist. To assess the interobserver bias, 10% of the samples were randomly and independently assessed by another otolaryngologist and a neuroradiologist who were blinded. Results The average HU index was lower in the ear with cholesteatoma when compared with the non-cholesteatomatous ear. While the differences were statistically significant regarding the measurements of the scutum (516.02 ± 311.693 versus 855.64 ± 389.999; p = 0.001), the malleus (1049.44 ± 481.765 versus 1413.47 ± 313.376; p = 0.01), and the incus (498.03 ± 264.184 versus 714.25 ± 405.631; p = 0.001), the differences in the measurements of the LSCC (1042.34 ± 301.066 versus 1154.53 ± 359.609; p = 0.69) and of the fallopian canal (467.19 ± 221.556 versus 543.51 ± 263.573; p = 0.108) were not significantly different between both groups. The stapes was immeasurable in both groups due to its small size. Conclusion Hounsfield unit index measurements are a useful tool that may aid in the diagnosis of early-stage cholesteatoma.

Are Hounsfield Unit Measurements of Bony Absorption Changes in Cholesteatoma Helpful?

Introduction High-resolution computed tomography (HRCT) scans of the temporal bone are used to assess the bony erosion of the middle-ear structures whenever cholesteatoma is suspected. Objective To study the differences in HRCT Hounsfield unit (HU) index measurements of middle-ear bony structures between an ears with and without cholesteatoma. Methods A retrospective study of 59 patients who underwent surgery due to unilateral cholesteatoma. The HRCT HU index of the scutum, of three middle-ear ossicles, of the lateral semicircular canal (LSCC), and of the fallopian canal was measured in both ears. A comparison was made between the cholesteatoma and the non-cholesteatomatous ear (control). All measurements were conducted by an otolaryngologist. To assess the interobserver bias, 10% of the samples were randomly and independently assessed by another otolaryngologist and a neuroradiologist who were blinded. Results The average HU index was lower in the ear with cholesteatoma when compared with the non-cholesteatomatous ear. While the differences were statistically significant regarding the measurements of the scutum (516.02 ± 311.693 versus 855.64 ± 389.999; p = 0.001), the malleus (1049.44 ± 481.765 versus 1413.47 ± 313.376; p = 0.01), and the incus (498.03 ± 264.184 versus 714.25 ± 405.631; p = 0.001), the differences in the measurements of the LSCC (1042.34 ± 301.066 versus 1154.53 ± 359.609; p = 0.69) and of the fallopian canal (467.19 ± 221.556 versus 543.51 ± 263.573; p = 0.108) were not significantly different between both groups. The stapes was immeasurable in both groups due to its small size. Conclusion Hounsfield unit index measurements are a useful tool that may aid in the diagnosis of early-stage cholesteatoma.

[DIAGNOSIS AND TREATMENT OF A GIRL SUFFERING FROM DRUG RESISTANT EPILEPSY WITH AN INNOVATIVE MINIMALLY INVASIVE APPROACH].

INTRODUCTION: About one percent (over 81,000 patients) of the Israeli population suffer from epilepsy. The main treatment for this condition is medication, but about a third of the patients suffer from drug-resistant epilepsy (DRE). Each year about 5,000 new patients are diagnosed with epilepsy, of whom 3,000 are children. For these patients, an evaluation in designated centers is required in order to diagnose possible foci and propose neurosurgical treatment alternatives. BACKGROUND: A model for diagnosis and treatment of the epileptic network in a minimally invasive approach is presented through the description of a case study. Phase I: includes diagnosis of the semiology, neuropsychological assessment, video EEG recording and performing a PET-MRI-FMRI-EEG synchronized examination. Phase II: involves stereo-electroencephalography (SEEG) minimally invasive diagnosis to target the epileptic area and accurately map adjacent functional areas and assessment of cortical redundancy. Phase III: includes radiofrequency ablation of the foci without any further surgery. This procedure is performed under clinical monitoring (the patient is awake during treatment) and continuous EEG monitoring. CONCLUSIONS: This case study demonstrates the multi-dimensional model performed by a multidisciplinary team, combining innovative technologies. This model is essential for the precision of the diagnosis and treatment methods of focal epilepsy and allows preservation of function based, among other factors, on the identification of cortical redundancy. DISCUSSION: The preoperative assessment identified focal epilepsy adjacent to the motor area dominating the right hand. A combined PET-FMRI-MRI-EEG examination enabled detecting redundancy of motor functions beyond the epileptic focus. Based on this information, a targeted implantation of depth electrodes (SEEG) was performed, the epileptic foci were identified and targeted ablations were performed during clinical monitoring and continuous EEG. This resulted in the cessation of seizures in parallel with the disappearance of the pathological signal in the EEG, all while preserving the patient's hand function.

Dual BRAF/MEK blockade restores CNS responses in BRAF-mutant Erdheim-Chester disease patients following BRAF inhibitor monotherapy.

BACKGROUND: Erdheim-Chester disease (ECD), a rare inflammatory myeloid neoplasm, is known to be fundamentally reliant on the constitutive activation of the MAPK signaling pathway in the majority of patients. Consequently, inhibition of the V600E-mutant BRAF kinase has proven to be a safe and efficacious long-term therapeutic strategy for BRAF-mutant ECD patients. Nevertheless, in a subset of patients with CNS disease, the efficacy of long-term treatment may diminish, facilitating suboptimal responses or disease progression. METHODS: We retrospectively describe 3 BRAF-mutant ECD patients whose treatment with Vemurafenib was upgraded to Vemurafenib/Cobimetinib due to either disease progression, insufficient response, or unacceptable toxicity. CNS response to therapy was evaluated using magnetic resonance imaging (MRI) and extra-cranial disease was monitored using 18F-fludeoxyglucose positron emission tomography/computed tomography (PET/CT). RESULTS: Three patients with a mean age of 52.6 years were treated with Vemurafenib for a mean duration of 26.6 months (range: 6-52). Monotherapies were upgraded to Vemurafenib/Cobimetinib dual therapy. The combination therapy was administered for a mean duration of 21 months (range: 19-23). All patients exhibited clinical and neurological improvement. Regression of lesions on MRI was noted in 2 patients. Both patients characterized by a PET-avid disease responded to the biological treatment regimen with complete metabolic remissions. CONCLUSION: Dual inhibition of BRAF and downstream MEK may be a safe and effective therapeutic strategy for BRAF-mutant ECD patients for whom BRAF inhibitor therapy proved insufficient and as such appropriate for the long-term management of CNS disease in ECD.

Proptosis due to intraorbital space-occupying lesions in children.

PURPOSE: To report the 10-year experience of two tertiary medical centers with children presenting with proptosis due to an intraorbital space-occupying lesion. METHODS: Patients were identified by file review. Data were collected on demographics, findings on ophthalmologic and imaging evaluations, etiology, treatment, and outcome. RESULTS: Nineteen children (7 male) were included. Eleven patients had optic nerve glioma, including 9 with substantially decreased visual acuity. Treatment consisted of chemotherapy alone or with radiation, resection or anti-VEGF agents, MEK inhibitor, or observation only (n = 1). Visual and cosmetic outcomes were poor in all cases. Outcome for arteriovenous malformations was good following corticosteroid treatment (n = 1), but catheterization led to persistent proptosis and fluctuating visual acuity (n = 1). Compound capillary hemangioma (n = 1) was treated with laser and systemic beta blockers with satisfactory results. Rhabdomyosarcoma had a good prognosis in one patient treated with resection and radiation but was fatal in another even after chemotherapy. Juvenile xanthogranuloma, frontal bone osteoma, and localized hypertrophic neuropathy of the supraorbital nerve (n = 1 each) were treated by resection with good visual and cosmetic outcomes. CONCLUSIONS: Proptosis accompanied by visual loss is an uncommon presentation in children and suggests an orbital tumor. We found that visual outcome was better when the nerve was not involved by tumor. Optic nerve glioma was the most common cause and failed to respond to various treatments. Catheterization for arteriovenous malformation did not prevent proptosis, and final visual acuity fluctuated. Surgery for rhabdomyosarcoma and xanthogranuloma led to remission with preservation of vision in 2 of 3 cases.

Likelihood of Diagnosing Neuroblastoma in Isolated Horner Syndrome.

BACKGROUND: The need for an extensive evaluation for neuroblastoma in children with Horner syndrome is controversial. METHODS: A retrospective study design was used. The cohort included 47 children with anisocoria who were diagnosed with Horner syndrome and 135 children with neuroblastoma evaluated at a pediatric medical center between 2007 and 2015. To detect neuroblastoma, patients with Horner syndrome underwent brain and cervical MRI, abdominal ultrasound, and/or measurement of urinary vanillylmandelic acid (VMA). The neuroblastoma group was evaluated for signs/symptoms of Horner syndrome at the time of diagnosis. RESULTS: Seven patients with Horner syndrome were lost to follow-up, and the findings of the remaining 40 were categorized according to the age of the patient. Horner syndrome most frequently was idiopathic (58%), and in only 1 patient did the discovery of neuroblastoma precede the appearance of Horner syndrome. In the 21 patients aged 1-18 years, Horner syndrome was acquired in 15 patients and congenital in 6. The most common etiology was trauma (62%). Imaging was performed in 14 patients and VMA testing in 13. Neuroblastoma was diagnosed in 5 patients; in none was it related to Horner syndrome. In the 135 patients with neuroblastoma, most of the tumors were diagnosed at Stage 4 (60%) or Stage 3 (30%) with 53% originating in the abdomen. In one patient (0.74%) with signs/symptoms of Horner syndrome at diagnosis of neuroblastoma, the tumor had been identified prenatally and the diagnosis confirmed by imaging postnatally. CONCLUSIONS: The absence of occult neuroblastoma in children with Horner syndrome and of signs/symptoms of Horner syndrome in the children diagnosed with neuroblastoma suggests that Horner syndrome might not be as frequent a cause of neuroblastoma as previously thought. We recommend that full investigation for neuroblastoma be reserved for suspicious cases associated with additional systemic signs or symptoms.

Use of Optical Coherence Tomography to Detect Retinal Nerve Fiber Loss in Children With Optic Pathway Glioma.

Optic pathway glioma (OPG) presents in childhood and can cause significant morbidity and visual loss. Magnetic resonance imaging (MRI) is the current imaging modality of choice for evaluation of OPG progression, but it is a relatively limited resource often requiring sedation in the pediatric age group. Additionally, OPG progression on MRI does not always correlate with clinical progression. As a result, several other modalities for evaluating OPG are being investigated, including optical coherence tomography (OCT), a readily available imaging technique in ophthalmic practice. The purpose of the present study was to examine the association between retinal nerve fiber layer (RNFL) thickness measured using OCT and optic nerve function in children with OPG with and without neurofibromatosis-1 (NF-1). A retrospective chart review was conducted to identify children diagnosed with OPG from 2001 to 2015 at a tertiary pediatric medical center. The correlation between OCT measurements and clinical visual parameters was statistically analyzed. Included were 23 children with imaging-confirmed OPG and spectral domain OCT: 10 with NF-1 (mean age at diagnosis 5.8 years) and 13 without (mean age at diagnosis 5.9 years). The glioma involved the chiasma-hypothalamus in 19 patients, optic nerve in 11, and optic tract in 7; more than one anatomic site was affected in 15. Symptoms were reported in 2 patients with NF-1 and most patients without NF-1. Visual field defects included monocular, bitemporal, nasal, and homonymous hemianopia. Initial mean RNFL was 85.4 µm in the NF-1 group and 65 µm in the non-NF-1 group. Visual acuity deteriorated in 1/10 patients and 5/13 patients, respectively. Repeated OCT showed continued RNFL thinning in 3 patients (5 eyes) in the NF-1 group and in 8 patients (11 eyes) in the non-NF-1 group, often associated with a decrease in optic nerve function. In conclusion, visual function in children with OPG is correlated with repeated OCT measurements and weakly with neuroimaging. Children without NF-1 are usually symptomatic and have a worse clinical outcome. These findings may have important implications when considering initiating, continuing or stopping chemotherapy for OPG. The application of OCT in the assessment of OPG and the correlation of the findings to clinical progression can have a significant impact on OPG patient management.

Correlation between preoperative predictions and surgical findings in the parotid surgery for tumors.

BACKGROUND: To compare preoperative CT/MRI based predictions with real surgical findings for deep lobe parotid gland surgery. METHODS: The study analyzed 122 parotidectomies (2004-2014) for benign tumor removal. The facial nerve, the Utrecht line, the Conn's arc, and the retromandibular vein were used as landmarks for CT/MRI presurgical evaluation of patients. We assessed 106 CT images and 86 MRI images. The study compared preoperative evaluation of tumor location with its actual location that was revealed during the operation and assessed the importance of the landmarks. RESULTS: In general, the agreement between preoperative CT prediction and actual location of the parotid tumors was achieved in 88.7 % (n = 94/106) when facial nerve line was used as a landmark. However, out of 14 tumors in the deep lobe only 5 were located correctly (35.7 %). Of the other existing CT landmarks, none showed more precision over others. The agreement between MRI based prediction and surgical results on actual location of the tumor was achieved in 94.2 %. Out of 12 MRI-investigated tumors in the deep lobe nine were located correctly that gives 75 % agreement with surgical results. CONCLUSION: Our data suggests that no existing CT landmark can be accepted as completely reliable in cases when selective deep lobe parotidectomy is planned. If tumor location is suspected in the deep lobe of the gland, MRI imaging is necessary to confirm the diagnosis. An operating surgeon should be prepared that in some cases the true location of the tumor would be revealed only during surgery.

4D MRI for the Localization of Parathyroid Adenoma: A Novel Method in Evolution.

The sestamibi scan (MIBI) and ultrasound (US) are used for preoperative localization of parathyroid adenoma (PTA), with sensitivity as high as 90%. We developed 4-dimensional magnetic resonance imaging (4D MRI) as a novel tool for identifying PTAs. Eleven patients with PTA were enrolled. 4D MRI from the mandible to the aortic arch was used. Optimization of the timing of image acquisition was obtained by changing dynamic and static sequences. PTAs were identified in all except 1 patient. In 9 patients, there was a complete match between the 4D MRI and the US and MIBI, as well as with the operative finding. In 1 patient, the adenoma was correctly localized by 4D MRI, in contrast to the US and MIBI scan. The sensitivity of the 4D MRI was 90% and after optimization, 100%. Specificity was 100%. We concluded that 4D MRI is a reliable technique for identification of PTAs, although more studies are needed.

Difficulty in Distinguishing Posterior Reversible Encephalopathy Syndrome, Hypoxic-Ischemic Insult, and Acute Toxic Leukoencephalopathy in Children.

AIM: This study aims to describe our experience of unique pediatric neurological cases and associated difficulty in differentiating posterior reversible encephalopathy syndrome (PRES) from hypoxic-ischemic insult (HII), and acute toxic leukoencephalopathy (ATL). METHODS: The study included three children with a clinical picture suggestive of PRES, HII, and ATL of different etiologies who were diagnosed and treated at a tertiary pediatric medical center in 2011 to 2014. RESULTS: All patients presented with blindness following seizures with asphyxia/aspiration in a syndromatic child, too-rapid lipid infusion in a child with acute lymphoblastic leukemia, and repeated vomiting in a child with cerebral palsy, hydrocephalus, and malfunction of ventriculoperitoneal shunt. All patients had cortical blindness and high-signal foci in the cortical and subcortical regions on magnetic resonance imaging. All children improved. CONCLUSIONS: Familiarity with the clinical and radiological characteristics of neurological conditions leading to reversible cortical blindness is essential for diagnosis and management. Distinguishing PRES from HII and ATL can be challenging. Our cases most likely combined these etiologies, with the first patient diagnosed with PRES with HII, the second with PRES with ATL, and the third with focal HII. Given the diversity of the findings and the unclear prognostic significance, studies of the pathophysiology of PRES are warranted.

Acquired nystagmus as the initial presenting sign of chiasmal glioma in young children.

BACKGROUND/PURPOSE: The aim of the study was to investigate the incidence of nystagmus at diagnosis in children with optic pathway glioma involving the chiasm and hypothalamus. METHODS: Twenty-two patients with a measurable optic pathway/hypothalamic glioma (without neurofibromatosis-1) were followed in our center from 2001 to 2013. The medical files were retrospectively reviewed for demographic and clinical findings, and the imaging scans, for tumor characteristics. RESULTS: There were 9 boys and 13 girls of mean age 3.5 ± 4.4 years at diagnosis; 15 were aged <2 years. Tumor size ranged from 10 × 6 mm to 62 × 29 mm. Mean duration of follow-up was 8.3 ± 5.4 years. Nystagmus was detected at diagnosis in 10 children (45%), all <2 years old (66.6% of the younger group); no child older than 2 years presented with nystagmus. Nystagmus, once present, did not resolve and continued throughout follow-up. There were no cases of new onset of nystagmus during follow-up in the children in whom it was not detected at diagnosis. Treatment consisted of partial resection/biopsy with/without shunting (n = 13) and chemotherapy (n = 19) with (n = 2) or without adjuvant radiation. Of the 22 children, 6 had a radiographic response to treatment, 8 remained stable, and 8 (all of whom received chemotherapy) showed disease progression despite treatment. CONCLUSION: In conclusion, monocular nystagmus is a more common presenting sign of optic pathway/hypothalamic glioma in children <2 years old than previously estimated. Although subtle, nystagmus has a very narrow differential diagnosis, and its presence should raise suspicions of a chiasmal tumor with prompt referral for imaging. The visual prognosis is moderate to poor.