Alpha-methyl acetyl-coA racemase deficiency. Magnetic resonance imaging findings of three patients with encephalopathy, epilepsy, and stroke-like episodes.

Alpha-methyl acyl-CoA racemase deficiency (AMACRD) is a rare peroxisomal disorder that results in the accumulation of pristanic acid and 16 cases have been reported in the literature. Here, we present three additional patients, two confirmed by genomic study and one suspected. Three siblings who were born to healthy unrelated parents developed recurrent episodes of encephalopathy, seizures, and behavioral disturbances. In all 3, brain MRI showed lesions in the thalami, cerebral peduncles, and mesencephalic tegmentum, as well as brain volume loss. In addition, one patient had a chronic hemispheric infarct and an acute contralateral infarct, and another had a subacute infarct involving multiple vascular territories without abnormalities on MR angiography.

Association between peripheral blood cytopenia and cancer mortality: A race-specific risk factor for cancer death.

BACKGROUND: Cytopenia is associated with cancer through mechanisms including clonal hematopoiesis and chronic inflammation. Cytopenia is more prevalent in Black people but its relationship with racial disparities in cancer mortality is unknown. METHODS: Cytopenia was defined in 19,028 Black and White participants recruited between 2003 and 2007 for the REasons for Geographic and Racial Differences in Stroke cohort, based on age-, sex-, and race-adjusted ranges for blood counts. Cancer death was ascertained from Social Security Death and National Death Indexes. Multivariable Cox models estimated the risk of cancer mortality associated with cytopenia, adjusting for demographics (model1), anemia and cancer risk factors (model2), and socioeconomics (model3). Racial differences in the cytopenia-cancer death association were tested by cross-product interaction terms. RESULTS: Cytopenia was identified in 383 (2%) participants, 250 (65%) White, and 113 (35%) Black people. With median follow-up 11.3 years, 1,224 (6.4%) cancer deaths occurred. Cytopenia was associated with increased risk of cancer mortality in model1 (HR = 1.57, 95%CI 1.15-2.24), model2 (HR = 1.67, 95%CI 1.22-2.30), and model3 (HR = 1.59, 95%CI 1.17-2.17). Participants with cytopenia had twofold increased cumulative incidence of cancer death (13% vs. 6.5%, p < 0.01). Race by cytopenia interaction terms showed higher HR for cancer death in Black compared to White participants: 2.01 versus 1.41 (pinteraction  = 0.016, model1), 2.12 versus 1.45 (pinteraction  = 0.009, model2), and 1.82 versus 1.44 (pinteraction  = 0.04, model3). CONCLUSION: In this large, observational biracial prospective study, cytopenia was a risk factor for cancer death, with stronger association in Black than White people. Though race impacted the association of cytopenia with cancer mortality, cytopenia was not a mediator of the racial disparity in cancer mortality.

Unrelated Allogeneic Stem Cell Transplant in Relapsed/Refractory AML: Widening the Yellow Brick Road.

A sizable proportion of patients with acute myeloid leukemia (AML) fail to achieve remission. Hematopoietic stem cell transplantation (HSCT) is the only intervention with potential of long-term survival. A recent Acute Leukemia Working Party (ALWP)/European Society for Blood and Marrow Transplantation (EBMT) analysis reports substantial posttransplant survival gains for patients with active disease who received transplants. Decreased relapse was the largest contributor to survival, a cause for optimism in this challenging population. See related article by Nagler et al., p. 4258.

Ruxolitinib in CMML: A Case Study of Innovative Trial Design in a Rare Cancer.

Alternative statistical designs cannot fully mitigate the limitations of traditional clinical trials in rare cancers. Creative study designs that integrate early clinical data and correlative outcomes from concomitant translational and laboratory models to evaluate the efficacy of druggable targets can potentially expedite access to novel therapies for these patients.See related article by Hunter et al., p. 6095.

Response of Leptomeningeal Metastases in EGFR-Mutated Non-Small-Cell Lung Cancer to Afatinib in the Absence of Radiotherapy.

Palliative radiotherapy is currently the medical standard of care for non-small-cell lung cancer (NSCLC) patients with symptomatic CNS and leptomeningeal disease. We report the case of a 62-year-old male patient with EGFR mutation (del19+) NSLC with symptomatic lymph node, bone, CNS, and leptomeningeal metastases. Taking into account on one hand the response to tyrosine kinase inhibitors (TKIs) and on the other hand the short- to medium-term side effects of radiotherapy and the lack of timely availability in our healthcare system, the patient was treated with afatinib (40 mg daily) and exhibited a rapid response with improvement of neurological symptoms. The patient presented partial response of extracranial, CNS, and leptomeningeal lesions at 3, 6, and 12 months of treatment, currently completing 16 months of progression-free survival despite presenting mild dermatological and gastrointestinal toxicities. Afatinib is an effective and safe option in patients with NSLC EGFR mutation del19+ with CNS and leptomeningeal compromise avoiding or delaying radiotherapy and its side effects, especially in countries where there is a lack of access to this kind of therapy.

ß-Tubulinopathy caused by a mutation of the TUBB2B gene: magnetic resonance imaging findings of the brain.

Patients with mutations in tubulin-related genes usually present with brain malformations, intellectual disability, epilepsy, microcephaly and ocular abnormalities. In these patients the diagnosis can be suggested by neuroimaging findings. We report a 5-year-old patient with characteristic magnetic resonance imaging findings including malformation of cortical development, fused basal ganglia, large head of the caudate nuclei, absent anterior limbs of the internal capsules, corpus callosum dysgenesis and dysplastic cerebellar vermis. Sequencing of the TUBB2B gene confirmed a heterozygous mutation: c. 260C>A (p. Pro87Gln).

Chronic Hematic Cyst of the Right Maxillary Sinus and Orbit Presenting as Proptosis.

A 28-year-old man presented to the emergency room complaining of right proptosis. He also manifested eye pain and facial fullness and redness in this side. Seven years ago, he had right hemifacial gunshot trauma treated with surgical reconstruction. The CT scan showed expansion of the right maxillary sinus due to a hypodense nonenhancing lesion extending to the nasal cavity, masticatory space, and extraconal space of the orbit. MRI was performed showing high signal intensity of the lesion on T2-weighted images indicating a cystic nature. T1-weighted images also demonstrated high signal intensity of the lesion suggesting hemorrhage. At endoscopic maxillary antrostomy, the diagnosis of a chronic hematic cyst was confirmed. Chronic hematic cysts of the orbit should be included in the differential diagnosis of proptosis, especially if there is clinical history of past trauma. Due to the fact that physical examination is nonspecific, radiologic evaluation is useful to confirm the diagnosis and for presurgical planning.

Impressive and durable response to nivolumab in a patient with metastatic type 2 papillary renal cell carcinoma: On-label but without evidence.

Nivolumab is a treatment option for patients with metastatic renal cell carcinoma (RCC) previously treated with targeted antiangiogenic therapy. Papillary renal cell carcinoma (PRCC) comprises 10-15% of RCC cases but non-clear cell subtypes were excluded from the immunotherapy trials. We report the case of a woman with recurrent metastatic PRCC who had an impressive therapeutic response to nivolumab with no significant adverse events. She had previously been treated with sunitinib and pazopanib with no response. She showed a remarkable clinical improvement after only the first 2 immunotherapy cycles and subsequent radiographic studies demonstrated a marked decrease in tumor burden. At present, she continues to show a durable benefit after 8 months of treatment. Her tumor had <1% positivity for PD-L1 staining and a low tumor mutational burden with no actionable mutations on genomic sequencing. Considering its high genetic variation, checkpoint blockade immunotherapies (CBIs) are attractive treatment options in PRCC. This is the third case that reports objective responses of nivolumab in PRCC. We believe our patient's experience supports the inclusion of non-clear cell RCC on clinical trials using CBIs. PD-L1 status and TMB may not serve as predictive biomarkers for response.

Fetal Magnetic Resonance Imaging Findings in Prenatal Zika Virus Infection.

Brain lesions and malformations have been described on ultrasonography of prenatal Zika infection; however, there are scarce reports about fetal magnetic resonance (MR) findings. We report 3 cases of fetuses with confirmed intrauterine Zika virus infection evaluated by ultrasound and fetal MR. Various morphometric measurements were assessed and brain maturation was calculated with the fetal total maturation score. Fetuses with prenatal Zika virus infection showed retardation in brain maturation indexes evaluated by fetal MR. Brain calcifications were demonstrated by neurosonography in all cases, while fetal MR characterized the specific type of cortical development malformation.

Contrast-enhanced T2-FLAIR MR imaging in patients with uveitis.

To report MRI findings which reflect a pathological inflammatory condition of the uveal tract. This study includes single-center retrospective case series of five patients with clinical diagnosis of uveitis. There were 1 male (20 %) and 4 female patients (80 %). The average age was 29.6 years (range 25-38 years). Patients and 50 age-range-matched control subjects were scanned using a 1.5 T scanner. Ten additional control subjects scanned at 3 T were evaluated to have reference images at that high field. All patients (n = 5, 100 %) presented uveal tract enhancement on post-contrast T2-FLAIR fat-suppressed images and only 2 (40 %) had enhancement on T1-weighted images. The enhancement was anterior in 2 (40 %), pan-uveal in 2 (40 %), and posterior in 1 patient (20 %). Two patients (40 %) had unilateral increased vitreous signal on T2-FLAIR. One patient (20 %) had bilateral retrobulbar fat enhancement in both post-contrast T2-FLAIR and T1-weighted images. Post-contrast T2-FLAIR images can reveal abnormal enhancement of the uveal tract and retrobulbar fat as well as increased vitreous signal in patients with uveitis. In our small series, the sensitivity of post-contrast T2-FLAIR was higher than the conventional post-contrast T1-weighted images. Nonetheless, when bilateral uveal tract enhancement is present, there should be discretion before calling uveitis because the finding has been reported in different eye conditions as well as in a small percentage of healthy subjects at 1.5 T. In addition, it should be noted that post-contrast T2-FLAIR enhancement of the uveal tract is a normal finding at 3 T imaging.

Síndrome de vasoconstricción cerebral reversible: Presentación como hemorragia subaracnoidea de la convexidad / Reversible Cerebral Vasoconstriction: Subarachnoid Convexity Hemorrhage

Objetivo: El propósito de este estudio es describir las características clínicas, epidemiológicas e imaginológicas de 5 pacientes con diagnóstico de síndrome de vasoconstricción reversible. Métodos: Se hizo una evaluación retrospectiva de las historias clínicas de cinco pacientes con clínica e imágenes compatibles con síndrome de vasoconstricción cerebral reversible en un hospital de alta complejidad de la ciudad de Medellín. Resultados: Los cinco casos correspondían a mujeres con una edad promedio de 50 años. En un caso se identificó como posible agente causal el consumo de bebidas energizantes con alto contenido de taurina. Todos los pacientes se presentaron con hemorragia subaracnoidea en la convexidad y evolucionaron de forma favorable. Conclusión: El síndrome de vasoconstricción cerebral reversible debe ser uno de los diagnósticos diferenciales etiológicos de hemorragia subaracnoidea de la convexidad; se presenta predominantemente en mujeres entre la cuarta y sexta década de la vida y usualmente tiene un curso benigno.

Objective: The purpose of this study is to describe the clinical, epidemiological and imaging characteristics of 5 patients with a diagnosis of reversible vasoconstriction syndrome. Methods: A retrospective evaluation of the clinical records of 5 patients with clinical and imaging diagnosis of reversible cerebral vasoconstriction syndrome was carried out in a high complexity hospital in the city of Medellín. Results: The five cases were women with an average age of 50 years. In one case, the consumption of energy drinks with a high taurine content was identified as a possible causative agent. All cases presented with brain convexity subarachnoid haemorrhage. The clinical outcome was favorable. Conclusion: The reversible cerebral vasoconstriction syndrome should be included in the differential diagnosis of convexity subarachnoid haemorrhage. It occurs predominantly in women between the fourth and sixth decade of life and usually has a benign course.

Characteristic brain MRI findings in ataxia-neuropathy spectrum related to POLG mutation.

Patients with mutations in the polymerase gamma gene (POLG) may present with progressive ataxia and in such situations neuroimaging findings may suggest the diagnosis. Herein we report a patient with a POLG gene W748S homozygous mutation and characteristic lesions in the thalamus, cerebellum and inferior olivary nucleus seen on magnetic resonance imaging.

Intracranial Aneurysms in Children: The Role of Stenting and Flow-Diversion.

OBJECTIVE: To report a single-center experience in the endovascular management of cerebral aneurysms in children with stenting and flow-diversion techniques. METHODS: During a 7-year period, 5 male patients with six intracranial aneurysms (IA) were treated by endovascular therapy with stenting or flow-diversion. The average age was 11 years (range 6-18 years). RESULTS: The etiology of the aneurysms was vasculopathic in 3 cases (50%), traumatic in 2 patients (33.3%), and idiopathic in 1 case (16.7%). Two-thirds of the aneurysms were giant in size. The aneurysms were most frequently located in the anterior circulation (66.7%). Fifty percent of the aneurysms were treated with stenting and coiling, and 50% were treated with flow-diversion stents alone. After treatment, occlusion was graded as: partial in five aneurysms (88.3%) and complete in 1 case (16.7%). Most cases (83.3%) had a good outcome after the procedure. During follow-up, most aneurysms had progressive occlusion (80%), while the rest were unchanged (20%). Most stents and flow-diverter devices remained patent (80%). However, one Pipeline flow-diverter device in the Anterior cerebral artery (ACA) A2 segment had an asymptomatic occlusion. CONCLUSIONS: In this series, device-assisted endovascular techniques were a relatively safe and effective method of treatment of pediatric aneurysms. However, continued follow-up is required after treatment, because there are unsolved issues regarding the durability of flow-diverters and stents.

Myelomatous Pleural Effusion Presenting with Extreme Hyperferritinemia and Severe Inflammatory Response.

Myelomatous involvement of pleural effusions developing in patients with multiple myeloma is extremely rare and only a few cases have been reported so far. It is thought to represent an aggressive clinical progression of disease and is usually associated with severe complications, poor prognosis and high mortality. Ferritin is a marker of inflammatory pathways that plays a significant role in plasma cell malignancies and has been studied as a prognostic factor for multiple myeloma. In severe inflammatory states such as septic shock or hemophagocytic lymphohistiocytosis, extreme levels of ferritin are thought to precipitate a cytokine storm associated with poor clinical outcomes. We present a case of myelomatous pleural effusion associated with extreme levels of ferritin and explore the possibility of a connection between this rare entity and other severe inflammatory states, which could account for its ominous outcomes and poor prognosis.

Congenital and Acquired Conditions of the Mesial Temporal Lobe: A Pictorial Essay.

PURPOSE: Our goal is to pictorially review a wide spectrum of congenital and acquired conditions affecting the medial aspect of the temporal lobe. CONCLUSION: After completing this article, the reader will have knowledge of the imaging appearance of diverse developmental, malformative, and acquired lesions of the mesial temporal lobe, which will be useful when evaluating pathology in this location.

Deformidad de Madelung, a propósito de una serie de casos / Déformation de Madelung, à propos d'une série / Madelung's deformity, apropos of a case series

Introducción: la deformidad de Madelung es consecuencia de una alteración de crecimiento de la fisis distal del radio. Puede ocasionar dolor y pérdida de la función. Objetivos: revisar el estado actual de la enfermedad y conocer los resultados de una serie de pacientes, que han recibido tratamiento quirúrgico. Métodos: se trata de una serie de casos de pacientes (12 pacientes) recopilados entre los años 2005-2012, que fueron tratados en la consulta de cirugía de mano (entre 2005 y 2012). Los procedimientos quirúrgicos usados fueron osteotomía de radio con placa o con tutor, osteotomía de cúbito (de acortamiento y corrección angular) y resección distal del cúbito (Darrach). Se estudiaron variables de movilidad, radiología y satisfacción de la cirugía. Se analizaron los datos radiológicos de inclinación cubital y de inclinación del semilunar, además, de un análisis cualitativo de la corrección del cúbito. Resultados: en los 8 pacientes operados (11 muñecas: 9 corrección de la angulación del radio mediante osteotomías, y 2 con tutor), los resultados estéticos fueron buenos. En cuanto a la función, todos los parámetros de movilidad mejoraron. En las 7 muñecas en las que se realizó Darrach, mejoró el aspecto dorsal de la muñeca. Luego de poco tiempo no se observó traslación cubital del carpo. El aspecto radiológico mejoró notablemente: la inclinación cubital del radio cambió de 37º prequirúrgico a 28º posquirúrgico, y el ángulo de fosa del semilunar de 55º a 36º, respectivamente. Conclusiones: lo reducido de la serie y el poco tiempo de seguimiento constituye una limitación de este estudio, aunque se muestra que con la combinación oportuna de algunas técnicas de cirugía, se pueden lograr mejorías estéticas y funcionales en la deformidad de Madelung(AU)

Introduction: Madelung deformity is due to a growth disturbance of distal radius physis. It can cause pain and loss of function. Objectives: to review the current status of this disease and the results of a series of patients who received surgical treatment. Methods: this is a case series of patients (12 patients) collected from 2005 to 2012, which were treated in hand surgery consultation. Radio osteotomy plate or guardian ulna osteotomy (shortening and angular correction) and distal resection of the ulna (Darrach) were the surgical procedures used. Mobility variables, radiology, and surgery satisfaction were studied. Ulnar inclination and the lunate tilt radiological data were analyzed; also a qualitative analysis of the correction of the ulna was conducted. Results: in the 8 patients operated (11 wrists: 9 angle correction by osteotomy of the radius, and 2 with tutor), the aesthetic results were good. In terms of function, all mobility parameters improved. In the 7 cases of wrist where Darrach was performed, the dorsal aspect of the wrist improved. After a short time, no ulnar translation of the carpus was observed. The radiographic appearance markedly improved: the ulnar inclination changed from preoperative 37º to postoperative 28º and the lunate fossa angle changed from 55° to 36°, respectively. Conclusions: the smallness of the series and the short follow-up time is a limitation of this study, although it is shown that with the right combination of some surgical techniques aesthetic and functional improvements in Madelung deformity can be achieved(AU)

Introduction: la déformation de Madelung est due à une altération de la croissance distale du radius. Elle peut provoquer une douleur et une perte de la fonction. Objectifs: le but de cette étude est de réviser l'état actuel de la maladie et de connaître les résultats d'une série de patients ayant subi un traitement chirurgical. Méthodes: il s'agit d'une série de 12 patients traités entre 2005 et 2012 au Service de chirurgie de main. Les gestes chirurgicaux utilisés ont compris l'ostéotomie du radius par plaque ou par tuteur, l'ostéotomie de cubitus (raccourcissement et correction angulaire), et la résection distale du cubitus (Darrach). Des variables de mobilité, de radiologie et de satisfaction de la chirurgie ont été examinées. Les données radiologiques de la pente du cubitus et de la pente du semi-lunaire, ainsi qu'une analyse qualitative de la correction du cubitus, ont été évaluées. Résultats: on a réussi des résultats esthétiques très bons chez les 8 patients opérés (11 poignets: 9 corrections de l'angulation du radius par ostéotomie, et 2 corrections par tuteur. Tous les paramètres de mobilité par rapport au plan fonctionnel sont améliorés. L'image dorsale des 7 poignets opérés par la technique de Darrach est améliorée. Puis à près, la translation cubitale du carpe a disparu. L'image radiologique est remarquablement améliorée ; il y a eu un changement pré- et postopératoire de la pente cubitale du radius respectivement de 37° à 28°, et de l'angle de la fossette du semi-lunaire respectivement de 55° à 36°. Conclusions: quoique la faiblesse du nombre de la série et du temps du suivi ait limité cette étude, on a démontré que la combinaison de quelques techniques chirurgicales peut aboutir à l'amélioration esthétique et fonctionnelle de la déformation de Madelung(AU)

Radiographic follow-up of 84 operatively treated scapula neck and body fractures.

BACKGROUND: Certain scapula fractures may warrant surgical management to restore shoulder anatomy and promote optimal function. The purpose of this study is to determine the early radiographic follow-up of open reduction internal fixation (ORIF) for displaced, scapular fractures involving the glenoid neck and body. METHODS: Eighty-four patients with a scapula body or neck fracture (with or without articular involvement) underwent ORIF between 2002 and 2010 at a single level I trauma centre. This study represents a retrospective review of data prospectively collected into a dedicated scapula fracture database. All patients met at least one of the following operative criteria: ≥20 mm medial/lateral (M/L) displacement (lateral border offset), ≥45° of angular deformity on a scapular-Y X-ray, the combination of angulation ≥30° plus M/L displacement ≥15 mm, double disruptions of the superior shoulder suspensory complex both displaced ≥10 mm, glenopolar angle (GPA) ≤22° and open fractures. Eighty-eight percent (74/84) had sufficient follow-up defined as at least 6 months. Measured outcomes included rates of scapula union and malunion, as well as surgical complications and re-operations. RESULTS: All fractures were caused by high-energy trauma with 24 (29%) resulting from motor-vehicle collisions. Associated injuries occurred in 94% of patients, most commonly involving the chest (70%) and ipsilateral shoulder girdle (43%). Forty-eight patients had M/L displacement as an operative indication with a mean displacement of 25.7 mm (range=20-40). Thirty-eight (45%) had ≥2 operative indications. A single surgeon performed ORIF in all patients using a posterior approach. Five patients also required an anterior (deltopectoral) approach. The fixation strategy included lateral and vertebral border stabilisation with dynamic compression and reconstruction plates, respectively. Union was achieved in all cases. There were three cases of malunion based on a GPA difference >10° from the uninjured shoulder. Re-operations included removal of hardware (seven patients) and manipulation under anaesthesia (three patients). There were no infections or wound dehiscence. CONCLUSIONS: ORIF for displaced scapula fractures is a relatively safe and effective procedure for restoration of anatomy and promotion of union. LEVEL OF EVIDENCE: Therapeutic study, level IV.

[Clinical application of diffusion tensor imaging and tractography in a child with holoprosencephaly]. / Aplicación clínica de las imágenes de resonancia magnética potenciadas en difusión y tractografía en un niño con holoprosencefalia.

Diffusion tensor imaging and fiber tracking can be methods used for the study of congenital brain malformations associated to white matter bundle abnormalities.Their use is illustrated in a child with semilobar holoprosencephaly in whom diffusion tensor imaging and tractography showed diencephalic ventral induction failure and abnormal white matter fascicles in brain and brainstem.