Polygenic risk score analysis of pathologically confirmed Alzheimer disease

Previous estimates of the utility of polygenic risk score analysis for the prediction of Alzheimer disease have given area under the curve (AUC) estimates of <80%. However, these have been based on the genetic analysis of clinical case–control series. Here, we apply the same analytic approaches to a pathological case–control series and show a predictive AUC of 84%. We suggest that this analysis has clinical utility and that there is limited room for further improvement using genetic data. Ann Neurol 2017;82:311–314.     

Naturally acquired West Nile virus encephalomyelitis in transplant recipients: clinical, laboratory, diagnostic, and neuropathological features

BACKGROUND: In the 2003 West Nile virus (WNV) epidemic, Colorado reported more WNV cases than any other state, including an unprecedented number in organ transplant recipients. METHODS: Physicians caring for transplant recipients hospitalized with naturally acquired WNV encephalitis provided data to characterize the clinical symptoms, results of diagnostic studies, and outcomes. RESULTS: Eleven transplant recipients were identified (4 kidney, 2 stem cell, 2 liver, 1 lung, and 2 kidney/pancreas). Seven were directly admitted to 1 of the 2 hospitals in the study, and 4 were referred to 1 of these centers from regional hospitals. All but 1 patient had a prodrome typical of WNV encephalitis in nonimmunosuppressed patients. Ten patients developed meningoencephalitis, which in 3 cases was associated with acute flaccid paralysis. One patient developed acute flaccid paralysis without encephalitis. Six patients had significant movement disorders including tremor, myoclonus, or parkinsonism. All patients had cerebrospinal fluid pleocytosis and WNV-specific IgM in the cerebrospinal fluid and/or serum. Cerebrospinal fluid cytologic studies (n = 5) showed atypical lymphocytes, some resembling plasma cells; however, flow cytometry (n = 3) showed that cells were almost exclusively of T-cell (not B-cell or plasma cell) lineage. Magnetic resonance images of the brain were abnormal in 7 of 8 tested patients, and electroencephalograms were abnormal in 7 of 7, with 2 showing periodic lateralized epileptiform discharges. Nine of 11 patients survived infection, but 3 had significant residual deficits. One patient died 17 days after admission, and autopsy findings revealed severe panencephalitic changes with multifocal areas of necrosis in the cerebral deep gray nuclei, brainstem, and spinal cord as well as diffuse macrophage influx in the periventricular white matter. A second patient died of complications of WNV encephalitis 6 months after hospital admission. CONCLUSIONS: Naturally acquired WNV encephalitis in transplant recipients shows diagnostic, clinical, and laboratory features similar to those reported in nonimmunocompromised individuals, but neuroimaging, electroencephalography, and autopsy results verify that these patients develop neurological damage at the severe end of the spectrum.     

Effect of the p38 kinase inhibitor, SB 203580, on allergic airway inflammation in the rat

Tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have been implicated in the pathogenesis of asthma. The p38 kinase inhibitor, SB 203580 inhibits TNF-alpha and IL-1beta production in vitro and in vivo. In this study the effect of SB 203580 on allergen-induced airway TNF-alpha production and inflammatory cell recruitment was investigated in sensitized Brown Norway rats. The allergen-induced increase in bronchoalveolar lavage (BAL) TNF-alpha was inhibited by SB 203580 at every dose tested (10 - 100 mg kg(-1), p.o.). In contrast, neither ovalbumin-induced eosinophilia or neutrophilia were inhibited by SB 203580 (10 - 100 mg kg(-1), p.o.). In conclusion, SB 203580 inhibits BAL TNF-alpha production by 95% without inhibiting either antigen-induced airway eosinophilia or neutrophilia. This data suggests that either the residual TNF-alpha is sufficient to drive allergen-induced inflammatory cell recruitment into the lung or that TNF-alpha is not involved in allergen-induced inflammatory cell recruitment.     

The diagnosis of a pleural lipoma by CT and fine-needle biopsy to avoid thoracotomy

We report a patient with a rare benign pleural lipoma diagnosed using computed tomography and fine-needle biopsy, thus avoiding unnecessary exploratory surgery.     

What's in Your Mouth? The CT Appearance of Comestible Intraoral Foreign Bodies

BACKGROUND AND PURPOSE: Comestible or chewable intraoral foreign bodies (IOFB), such as candies, gum, and chewing tobacco, are seen incidentally on many CT scans of the head and neck. If these foreign bodies are misinterpreted as pathology, patients may be subjected to unnecessary distress or unneeded radiation from additional imaging. The purpose of this study was to characterize the CT appearance of comestible IOFBs and to find characteristics that distinguish them from true pathology.MATERIALS AND METHODS: With institutional review board approval, 30 patients who were already scheduled to undergo CT examinations of the head and neck were enrolled in this study. Nine typical IOFBs with different physical characteristics were selected for inclusion. Each patient placed 1 IOFB in his or her mouth before the initiation of the routine clinical scan. The resulting scans were evaluated by 2 head and neck radiologists. In vivo and ex vivo attenuation measurements were obtained for each IOFB.RESULTS: The attenuation of comestible IOFBs ranged from 184 to 475 Hounsfield units. Large, hard IOFBs were most easily distinguished from mucosal lesions, but might be mistaken for odontogenic or bone tumors. Small, hard IOFBs could be mistaken for calculi, tooth fragments, or enhancing vessels. Soft IOFBs generally had more confusing configurations and more heterogeneous densities and, thus, might be mistaken for enhancing mucosal lesions. Foci of gas were often identified within chewable IOFBs, mimicking an abscess. Because all of the IOFBs had higher densities than soft tissue, they could all be mistaken for calcified, enhancing, or bony lesions.CONCLUSION: Radiologists frequently encounter IOFBs on CT examinations of the head and neck. Familiarity with the expected appearance of these incidental pseudolesions is important to prevent misdiagnosis as a true pathologic process.

The presence of an intraoral foreign body (IOFB) on a CT examination of the head and neck may result in a surprisingly difficult diagnostic challenge. When patients undergo imaging that includes the oral cavity, they are routinely asked to remove foreign bodies such as dentures, chewing gum, and chewing tobacco. Occasionally, patients do not comply with this request, and the unexpected IOFB can masquerade as true pathology of the oral cavity. Such a misdiagnosis can result in additional scans with unnecessary irradiation, distraction from more relevant pathology, and unnecessary patient distress.Previous studies on the radiographic appearance of comestible foreign bodies have focused on the abdomen, including reports of soft candies mimicking abdominal calcifications,¹ and on the high attenuation of ingested chewing gum in the abdominal cavity.² Studies regarding foreign bodies in the orbit tend to focus on the appearance of wood, metal, glass, or other penetrating objects.^3-5 Previous literature on IOFBs has been restricted to metallic piercings, chronically retained food, or surgical material.^6,7 There is currently no literature on the CT appearance of comestible IOFBs. The purpose of this study was to characterize the CT appearance of comestible IOFBs and to find characteristics that distinguish them from true pathology.     

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids following influenza vaccination

Inflammatory processes within the central nervous system are challenging for the clinician, radiologist, and pathologist alike. They often can mimic other more well-known and defined disease processes. We present the case of a patient with a newly described inflammatory process that primarily involves the pons and adjacent structures, which is called chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). An 80-year-old man presented with numbness of his right hand that ultimately progressed to involve both lower extremities and face and was associated with mild dysarthria and ataxia. He had received the influenza vaccination 2?weeks prior. The biopsy revealed primarily reactive T-cell lymphocytic infiltrates with macrophages and gliosis. Treatment required long-term immunosuppressive therapy. CLIPPERS is a recently described central nervous system inflammatory condition that should be considered in the differential diagnosis when a prominent lymphocytic inflammatory infiltrate is encountered in brainstem, spinal cord, midbrain, or cerebellar biopsies.     

Superior semicircular canal dehiscence: oblique reformatted CT images for diagnosis

PURPOSE: To retrospectively determine, by using thin-section multi-detector row computed tomography (CT), whether additional reformations in the planes of Stenver and P?schl change the diagnostic interpretation for superior semicircular canal dehiscence (SSCD) when compared with the diagnostic interpretation of standard coronal reformations for SSCD. MATERIALS AND METHODS: Institutional review board approval was obtained, patient anonymity was maintained, and the study was HIPAA compliant. Twenty-seven patients (17 men, 10 women; average age, 45 years; range, 19-72 years) suspected of having SSCD who underwent temporal bone multi-detector row CT were retrospectively identified from electronic medical records. An additional 27 control subjects (nine men, 18 women; average age, 50 years; range, 18-87 years), who underwent temporal bone multi-detector row CT for other reasons, were retrospectively selected from the same period. Two neuroradiologists with certificates of added qualification, one with 5 years and one with 9 years of experience interpreting temporal bone CT images, independently reviewed the 108 temporal bones twice. One review was restricted to transverse images and coronal reformations. The other review used transverse images, coronal reformations, and oblique reformations in the planes of Stenver and P?schl. The observers were blinded to clinical history, and the two reviews took place 3 months apart to avoid recall bias. The primary outcome measure was the intraobserver discordance rate between the two reviews. kappa Statistics were used to evaluate both intraobserver and interobserver variability. Results: Observer 1 diagnosed SSCD in 25 of 108 (23%) temporal bones and had no discordances between the two reviews. Observer 2 diagnosed SSCD in 21 of 108 (19%) temporal bones and had one intraobserver discordance. After a post hoc consensus review of this one discordance, the radiologic diagnosis remained equivocal. The discordance involved the right temporal bone of a patient suspected of having SSCD in the left temporal bone, so no clinical follow-up was available. CONCLUSION: Coronal reformations from multi-detector row CT of the temporal bone are sufficient for the evaluation of SSCD. Additional reformations in the planes of Stenver and P?schl do not change the radiologic diagnosis and may be reserved for equivocal or confusing cases.