Brain Dead and Pregnant.

The presence of pregnancy in a brain-dead woman is a rare circumstance. We present a case of a 31-year-old woman who was 22 weeks pregnant at the time of diagnosis of brain death after intracranial and subarachnoid hemorrhage. After a multidisciplinary approach, the decision was made to continue somatic support to maintain the pregnancy until optimal fetus viability. Cesarean section was performed after 11 weeks (33 weeks gestational age) of brain-death diagnosis with a successful delivery of a live infant. Management of brain-death complications during pregnancy is described.

Adeno-associated virus-mediated gene therapy in a patient with Canavan disease using dual routes of administration and immune modulation.

Gene replacement therapy is a rational therapeutic strategy and clinical intervention for neurodegenerative disorders like Canavan disease, a leukodystrophy caused by biallelic mutations in the aspartoacylase (ASPA) gene. We aimed to investigate whether simultaneous intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of rAAV9-CB6-ASPA provides a safe and effective therapeutic strategy in an open-label, individual-patient, expanded-access trial for Canavan disease. Immunomodulation was given prophylactically prior to adeno-associated virus (AAV) treatment to prevent an immune response to ASPA or the vector capsid. The patient served as his own control, and change from baseline was assessed by clinical pathology tests, vector genomes in the blood, antibodies against ASPA and AAV capsids, levels of cerebrospinal fluid (CSF) N-acetylaspartate (NAA), brain water content and morphology, clinical status, and motor function tests. Two years post treatment, the patient's white matter myelination had increased, motor function was improved, and he remained free of typical severe epilepsy. NAA level was reduced at 3 months and remained stable up to 4 years post treatment. Immunomodulation prior to AAV exposure enables repeat dosing and has prevented an anti-transgene immune response. Dual-route administration of gene therapy may improve treatment outcomes.

Pituitary Apoplexy (PA): Delayed Diagnosis of a Rare Clinical Syndrome in a Patient With a Known Pituitary Adenoma.

Pituitary apoplexy (PA) is a rare clinical syndrome in which the pituitary gland undergoes infarction or hemorrhage, predominantly in the setting of an underlying tumor. We report on apoplexy of an expanding pituitary macroadenoma that was compressing the optic chiasm in a patient with progressively worsening neurologic deficits. Due to the patient's rapidly declining clinical status and family's goals of care, no neurosurgical intervention took place, and the patient expired a few days following discharge to hospice. This case highlights the importance of early suspicion for apoplexy in a patient with a history of pituitary adenoma and signs of neurologic deficit.

Visualization of the perivenous glymphatic efflux in human brain after laser interstitial thermal therapy.

Recent studies have revealed that there is existence of a specific waste clearance pathway in the brain, coined the glymphatic system. This case report demonstrates supportive finding of drainage of Gadolinium and waste products released after Laser Interstitial Thermal Therapy via perivenous routes and a paradural lymphatic system. These findings provide further evidence of interstitial fluid drainage along the perivenous spaces in accordance with a glymphatic system theory.

Presumptive Diagnosis of Pallister-Hall Syndrome Using Magnetic Resonance Imaging.

Pallister-Hall syndrome (PHS) is an extremely rare genetic disorder for which the diagnosis is often overlooked. The objective of this case report is to highlight how clinical features used in conjunction with brain MRI findings can lead to an expeditious diagnosis without the need for invasive measures or genetic test results. We present the case of a three-day-old infant delivered at 34 and 4/7 weeks gestation who presented with mild respiratory distress and bilious emesis in the setting of an uncomplicated gestational course and vaginal delivery with no known teratogen exposure. A diagnosis of Pallister-Hall syndrome was made on the basis of physical exam findings, hormonal abnormalities and the identification of a hypothalamic hamartoma on brain MRI. The patient underwent multiple procedures for diagnosis and management of PHS complications, including a diverting jejunostomy for a long-segment Hirschsprung's and a laryngoscopy which identified a bifid epiglottis. The patient tolerated the interventions and did not have seizures on admission. The MRI brain detection of a hypothalamic hamartoma led to an earlier diagnosis of Pallister-Hall syndrome and thus further screening and identification of complications associated with this disorder were performed before genetic analyses or brain biopsies were obtained. Given the unique MRI features of hypothalamic hamartomas, brain MRI can be a useful tool for making an early PHS diagnosis when taken with clinical features concerning possible PHS.

Management of Cavernous Sinus Thrombosis Following Herpes Zoster Ophthalmicus.

Herpes zoster opthalmicus (HZO) is the reactivation of latent varicella zoster virus (VZV) within the ophthalmic branch of the trigeminal ganglion (V1). Common complications are postherpetic neuralgia and vasculopathy. Here, we report a rare case of a 47-year-old female presenting with HZO and aseptic cavernous sinus thrombosis (CST). Early screening for rare and deadly complications such as CST using CT cerebral venography (CTV) and magnetic resonance venography (MRV), as was done, is crucial to detection at earlier stages when intervention is most effective. Anticoagulation therapy was promptly started, and the patient's symptoms continued to improve during the hospital stay.

Pediatric craniosynostosis computed tomography: an institutional experience in reducing radiation dose while maintaining diagnostic image quality.

BACKGROUND: Children with craniosynostosis may undergo multiple computed tomography (CT) examinations for diagnosis and post-treatment follow-up, resulting in cumulative radiation exposure. OBJECTIVE: To reduce the risks associated with radiation exposure, we evaluated the compliance, radiation dose reduction and clinical image quality of a lower-dose CT protocol for pediatric craniosynostosis implemented at our institution. MATERIALS AND METHODS: The standard of care at our institution was modified to replace pediatric head CT protocols with a lower-dose CT protocol utilizing 100 kV, 5 mAs and iterative reconstruction. Study-ordered, protocol-utilized and radiation-dose indices were collected for studies performed with routine pediatric brain protocols (n=22) and with the lower-dose CT protocol (n=135). Two pediatric neuroradiologists evaluated image quality in a subset (n=50) of the lower-dose CT studies by scoring visualization of cranial structures, confidence of diagnosis and the need for more radiation dose. RESULTS: During the 30-month period, the lower-dose CT protocol had high compliance, with 2/137 studies performed with routine brain protocols. With the lower-dose CT protocol, volume CT dose index (CTDIvol) was 1.1 mGy for all patients (0-9 years old) and effective dose ranged from 0.06 to 0.22 mSv, comparable to a 4-view skull radiography examination. CTDIvol was reduced by 98% and effective dose was reduced up to 67-fold. Confidence in diagnosing craniosynostosis was high and more radiation dose was considered unnecessary in all studies (n=50) by both radiologists. CONCLUSION: Replacing the routine pediatric brain CT protocol with a lower-dose CT craniosynostosis protocol substantially reduced radiation exposure without compromising image quality or diagnostic confidence.

Cryptococcosis Presenting as Cerebrovascular Disease.

Infection plays a complex role in cerebrovascular disease and is believed to have both direct and indirect mechanisms on stroke pathogenesis. if not diagnosed and treated promptly, this may have devastating consequences. Management of infection-related strokes focuses on the treatment of the underlying infection with appropriate antimicrobial drugs and the prevention of medical complications. This can lead to devastating neurological deficits. We present two cases of cryptococcal meningoencephalitis that presented with an atypical cerebral infarction. A 55-year-old male with a history of unknown autoimmune disease presented with acute onset cognitive changes and no stroke-like symptoms. A 35-year-old male with no history of autoimmune disease or other existing immunodeficiency presented with breakthrough seizure a long with stroke-like symptoms. Both patients developed multiple cerebral infarcts in multiple vascular territories, with histologic and radiologic findings consistent with a central nervous system cryptococcosis. They were subsequently diagnosed with cryptococcal meningoencephalitis and started on the appropriate anti-fungal regimen with amphotericin B and flucytosine. Prior to discharge to an inpatient rehabilitation facility, both patients were notably improved and near their neurologic baseline. It is important to understand the pathogenesis of cryptococcal infection in the central nervous system because it produces a wide variety of clinico-radiographic features that can be overlooked. Clinicians should keep infection-mediated cerebral infarcts in mind, regardless of risk factors, in order to expedite antimicrobial therapy and minimize adverse events.

Moyamoya Disease in a Young Female With Neurofibromatosis Type 1.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the terminal portions of the internal carotid arteries (ICAs) and the development of a network of abnormal collateral vessels. This case depicts a 25-year-old African American female patient with neurofibromatosis type 1 (NF-1), whose initial hospital presentation occurred in a hypertensive emergency setting. Surveillance studies with magnetic resonance imaging (MRI) revealed multiple asymptomatic right cortical strokes. Genetic testing evidenced a novel, unique pathogenic variant on the NF-1 gene. The patient underwent combined bypass surgery first and then was placed on aspirin and a blood pressure control regimen. Our case illustrates the need for clinicians to include moyamoya disease in the list of differential diagnoses when encountering a young patient, without major risk factors, presenting with ischemic stroke. It should be considered even with no known history of previously diagnosed MMD or NF-1, as these pathologies may have yet to be evaluated in subclinical cases.

Gadolinium in tears: Evidence for an alternative cerebrospinal fluid absorption pathway in the setting of ischemia-induced blood brain barrier disruption.

Cerebral ischemia results in disruption of the blood-brain barrier (BBB) allowing leakage of gadolinium-based contrast media (GBCM) into cerebrospinal fluid (CSF) within the craniospinal and perineural subarachnoid spaces (SAS). This phenomenon is well visualized with fluid-attenuated inversion recovery MRI techniques and allows for visualization of CSF flow dynamics. We present a case of ischemia-induced BBB disruption resulting in accumulation of GBCM in the SAS and ocular chambers as well as within the precorneal tear film and nasolacrimal duct. We present imaging evidence for a hypothetical alternate CSF absorption pathway through the ocular structures in keeping with prior experimental evidence.

T2-blackout effect on DWI as a sign of early bone infarct and sequestration in a patient with sickle cell disease.

Differentiation of bone infarct from osteomyelitis is one of the most challenging issues in the evaluation of acute bone pain in sickle cell patients. The imaging modalities that are currently being used for assessment of bone marrow in this population have several limitations. We present a case of an 18-year-old male with a history of sickle cell disease, who was transferred to our emergency department with progressively severe headache and jaw pain for one-week. Initial evaluation was concerning for osteomyelitis and epidural abscess formation. Due to the lack of response to the current antibiotic treatment, he was transferred to our institution. On further review of the images, atypical DWI findings that were identified in the early phase of presentation helped to differentiate bone infarct from osteomyelitis. Radiologists should be aware of this phenomenon, as it can help in the differentiation between these two pathologies and can affect the patient's management overall.

Structural connectivity-based segmentation of the thalamus and prediction of tremor improvement following thalamic deep brain stimulation of the ventral intermediate nucleus.

OBJECTIVES: Traditional targeting methods for thalamic deep brain stimulation (DBS) performed to address tremor have predominantly relied on indirect atlas-based methods that focus on the ventral intermediate nucleus despite known variability in thalamic functional anatomy. Improvements in preoperative targeting may help maximize outcomes and reduce thalamic DBS-related complications. In this study, we evaluated the ability of thalamic parcellation with structural connectivity-based segmentation (SCBS) to predict tremor improvement following thalamic DBS. METHODS: In this retrospective analysis of 40 patients with essential tremor, hard segmentation of the thalamus was performed by using probabilistic tractography to assess structural connectivity to 7 cortical targets. The volume of tissue activated (VTA) was modeled in each patient on the basis of the DBS settings. The volume of overlap between the VTA and the 7 thalamic segments was determined and correlated with changes in preoperative and postoperative Fahn-Tolosa-Marin Tremor Rating Scale (TRS) scores by using multivariable linear regression models. RESULTS: A significant association was observed between greater VTA in the supplementary motor area (SMA) and premotor cortex (PMC) thalamic segment and greater improvement in TRS score when considering both the raw change (P = .001) and percentage change (P = .011). In contrast, no association was observed between change in TRS score and VTA in the primary motor cortex thalamic segment (P ≥ .19). CONCLUSIONS: Our data suggest that greater VTA in the thalamic SMA/PMC segment during thalamic DBS was associated with significant improvement in TRS score in patients with tremor. These findings support the potential role of thalamic SCBS as an independent predictor of tremor improvement in patients who receive thalamic DBS.

A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

PURPOSE: Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. METHODS: Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. RESULTS: The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. CONCLUSION: Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

Safety of Intradiaphragmatic Delivery of Adeno-Associated Virus-Mediated Alpha-Glucosidase (rAAV1-CMV-hGAA) Gene Therapy in Children Affected by Pompe Disease.

A first-in-human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory and neural dysfunction in early-onset Pompe disease was conducted. The primary objective of this study was to assess the safety of rAAV1-CMV-hGAA vector delivered to the diaphragm muscle of Pompe disease subjects with ventilatory insufficiency. Safety was assessed by measurement of change in serum chemistries and hematology, urinalysis, and immune response to GAA and AAV, as well as change in level of health. The data demonstrate that the AAV treatment was safe and there were no adverse events related to the study agent. Adverse events related to the study procedure were observed in subjects with lower baseline neuromuscular function. All adverse events were resolved before the end of the study, except for one severe adverse event determined not to be related to either the study agent or the study procedure. In addition, an anti-capsid and anti-transgene antibody response was observed in all subjects who received rAAV1-CMV-hGAA, except for subjects who received concomitant immunomodulation to manage reaction to enzyme replacement therapy, as per their standard of care. This observation is significant for future gene therapy studies and serves to establish a clinically relevant approach to blocking immune responses to both the AAV capsid protein and transgene product.

Incidence and clinical sequelae of portal and hepatic venous thrombosis following percutaneous cryoablation of liver tumors.

PURPOSE: To assess the incidence and sequelae of portal and hepatic venous thrombosis after percutaneous cryoablation of hepatic tumors. METHODS: From November 1998 through December 2010, 223 hepatic tumors were cryoablated during 170 ablation procedures in 135 patients. 24-h post-procedure MR images were reviewed retrospectively by two abdominal radiologists in consensus to identify tumor ablations that developed one or more new portal or hepatic venous thromboses in or outside the ablation zone. On follow-up MRI and CT examinations the outcomes of thromboses were classified as resolved, partially recanalized, persistent, or propagated. RESULTS: Venous thrombosis developed in association with 54 (24%) of 223 tumor ablations treated during 53 (31%) ablation procedures in 39 (28.8%) patients (15 women, 24 men; age range 40-82 years, mean 59 years). Of these 54 thromboses, 49 (91%) were located in portal vein branches, four (7%) in both portal and hepatic vein branches, and one (2%) in a hepatic vein branch. Thrombosed veins were outside but abutted the ablation zone in 36 (66.7%), and within it in 18 (33.3%). On follow-up imaging (n = 49), thrombi resolved in 29 (59%), partially recanalized in two (4%), persisted in 18 (37%) and propagated from sub-segmental or segmental branches to the left or right portal branches in five (10%). No thrombus propagated to the main portal vein or inferior vena cava. CONCLUSION: Portal and hepatic vein branch thromboses are common in small branches following percutaneous cryoablation of hepatic tumors and most resolve spontaneously without sequelae.

Contrast-enhanced CT and MR imaging of renal vessels.

In the evaluation of renal vessels, the accepted diagnostic gold standard digital subtraction angiography is now being challenged by state of the art CT and MR imaging. Currently in many centers, cross-sectional imaging modalities are being used as a first line diagnostic tool to evaluate arterial and venous system of the kidneys and conventional angiography has been reserved only for therapeutic intervention. CT and MR imaging display not only the lumen of the vessel as in conventional angiography, but also allow the visualization of the vessel wall, renal parenchyma, collecting system, and other adjacent soft tissue structures. Therefore, CT and MRI have each become a one-stop shop for a thorough evaluation of kidneys. In this pictorial essay, we reviewed normal anatomical variants and wide range of pathologies involving renal arteries and veins with illustrated contrast-enhanced CT and MR imaging samples.

Brief communication: pituitary volume and function in competing and retired male boxers.

BACKGROUND: Pituitary consequences of chronic head trauma in boxing have not been investigated in detail. OBJECTIVE: To investigate the pituitary function in retired or active amateur boxers. DESIGN: Cross-sectional, observational study. SETTING: Turkey. PARTICIPANTS: 61 actively competing (n = 44) or retired (n = 17) male boxers of the Turkish National Boxing Team. MEASUREMENTS: Body composition variables, pituitary volume (in 38 of 61 boxers), and pituitary function. RESULTS: 9 of 61 boxers (15%) had growth hormone (GH) deficiency and 5 of 61 boxers (8%) had adrenocorticotropic hormone deficiency. All boxers with GH deficiency except 1 were retired from boxing. Of 17 retired boxers, 8 (47%) had GH deficiency. Retired boxers with GH deficiency had significantly lower pituitary volume than retired boxers with normal GH. LIMITATION: Pituitary volume was measured in only 38 of 61 boxers, and the study had no comparison group. CONCLUSION: This study suggests that retired boxers have a high rate of pituitary dysfunction. Therefore, investigation of pituitary function in boxers, particularly retired ones, is recommended.