Understanding spatial relationships in US: a computer-based training tool that utilizes inexpensive off-the-shelf game controllers.

The authors present a simulation-based ultrasonographic (US) training tool that can help improve the understanding of spatial relationships in US. Use of a game controller to simulate a US probe allows examination of different virtual three-dimensional (3D) objects. These 3D objects are either completely artificial simple geometric objects (eg, spheres, tubes, and ellipsoids, or more complex combinations thereof) or derived from photographed gross anatomic data (eg, the Visible Human dataset [U.S. National Library of Medicine]) or clinical computed tomographic (CT) data. The virtual US probe allows infinitely variable real-time positioning of a "slice" that is displayed as a two-dimensional (2D) cross-sectional image and as part of a 3D view. Combining the 2D and 3D views helps elucidate the spatial relationships between a 3D object and derived 2D images. This training tool provides reliable real-time interactivity and is widely available and easily affordable, since it utilizes standard personal computer technology and off-the-shelf gaming hardware. For instance, it can be used at home by medical students or residents as a complement to conventional US training. In the future, this system could be adapted to support training for US-guided needle biopsy, with use of a second game controller to control the biopsy needle. Furthermore, it could be used as a more general interactive visualization tool for the evaluation of clinical 3D CT and magnetic resonance imaging data, allowing efficient and intuitive real-time creation of oblique multiplanar reformatted images.

Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins.

We present four cases of fragile X premutation carriers with early neurological symptoms, including symptoms consistent with multiple sclerosis (MS) and fragile X-associated tremor/ataxia syndrome (FXTAS). Each patient had significant exposure to one or more environmental neurotoxicants that have documented neurotoxicity (i.e. hexachlorocyclopentadiene or C56, Agent Orange, and 2,4- or 2,6-toluene diisocyanate and dichlormate). We hypothesize that premutation carriers are a vulnerable group to neurotoxins because elevated mRNA in the premutation can lead to early cell death and brain disease, leading to neuropsychiatric and neurological symptoms consistent with FXTAS.

ACR Appropriateness Criteria on low back pain.

Acute low back pain with or without radiculopathy is one of the most common health problems in the United States, with high annual costs of evaluation and treatment, not including lost productivity. Multiple reports show that uncomplicated acute low back pain or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Guidelines for recognition of patients with more complicated status can be used to identify those who require further evaluation for suspicion of more serious problems and contribute to appropriate imaging utilization.

Clinical and neuropathologic findings in a woman with the FMR1 premutation and multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) and fragile X-associated tremor/ataxia syndrome (FXTAS) have overlapping clinical signs and symptoms. OBJECTIVES: To present a case with evidence of both MS and FXTAS and to discuss the relationship of both disorders. DESIGN: Case report. SETTING: Fragile X Research and Treatment Center at the University of California, Davis, Medical Center. Patient Woman with the FMR1 premutation who died of MS at the age of 52 years. MAIN OUTCOME MEASURES: Magnetic resonance imaging, physical examination, and neuropathologic examination results. RESULTS: Magnetic resonance imaging, physical examination, and autopsy neuropathologic examination revealed diagnostic features of MS and FXTAS. CONCLUSION: The molecular mechanism of RNA toxicity, including the elevation of alphaB-crystallin levels observed in FXTAS, may lead to enhanced predisposition to autoimmune diseases.

Computed tomography use in a tertiary care university hospital.

PURPOSE: Improvements in computed tomography (CT) technology, with shorter scan times and better image quality, have contributed to an increase in the use of CT in the United States in recent years. This increased use has implications for health policy and radiation risk assessment. The purpose of this study was to evaluate trends in CT use. METHODS: The CT performance records at a university-based, tertiary care, level 1 trauma center hospital were evaluated from 1998 to 2005. The hospital's decision support infrastructure was used to track overall patient visits and stays. From these data sets, the age and sex dependency of CT use rates were evaluated for outpatients, inpatients, and emergency department (ED) patients. RESULTS: Outpatient use rates averaged over the age groups of 21 to 30 years, 41 to 50 years, and 61 to 70 years were 20, 59, and 87 CT scans per 1,000 outpatient visits, respectively. Inpatient use rates for these same age groups were 88, 148, and 162 CT scans per 1,000 inpatient days, respectively. ED patient use rates for these same age groups were 705, 687, and 394 CT scans per 1,000 ED patient visits, respectively. Male patients outnumbered female patients for both ED and inpatient CT use from the early teens to the mid-40s age range. CONCLUSION: The overall CT use increased 27% and 48% from 2000 to 2004 for outpatient and inpatient visits, respectively. CT use in the hospital's high-volume ED increased 131% from 2000 to 2004, which may be partly attributable to the installation of 2 CT scanners near the ED.

Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome.

Peripheral neuropathy is common among patients with fragile X-associated tremor ataxia syndrome (FXTAS). Four patients with FXTAS are described with neuropathy as the presenting feature, two having received a prior diagnosis of Charcot-Marie-Tooth (CMT) disease. A fifth is described with neuropathy as the only clinical feature. A functional connection between FXTAS and neuropathy has been suggested by the presence of lamin A/C in the intranuclear, neuronal and astrocytic inclusions of FXTAS, since mutations in lamin A/C are known to give rise to an axonal form of CMT.

Fragile X-associated tremor/ataxia syndrome: clinical features, genetics, and testing guidelines.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55-200 repeats; premutation range) of a CGG trinucleotide in the fragile X mental retardation 1 (FMR1) gene, the same gene which causes fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made.

Cognitive, anxiety and mood disorders in the fragile X-associated tremor/ataxia syndrome.

OBJECTIVE: We evaluated patients with fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with a CGG repeat expansion in the premutation range in the fragile X mental retardation 1 (FMR1) gene. METHODS: Neurological, psychiatric and neuropsychological evaluations were performed on 15 male patients with FXTAS. RESULTS: Seven cases were diagnosed with dementia, and seven others were diagnosed with mood and/or anxiety disorders. Twelve subjects demonstrated deficits on neuropsychological testing. CONCLUSIONS: Physicians assessing dementia patients are urged to consider this newly described syndrome, especially in patients with dementia associated with a movement disorder and in those with a family history of mental retardation. If FXTAS is a possible diagnosis, physicians may carry out FMR1 DNA testing; patients who test positive on DNA testing should undergo magnetic resonance imaging, be referred to neurology and receive genetic counseling.

Cognitive impairment in a 65-year-old male with the fragile X-associated tremor-ataxia syndrome (FXTAS).

OBJECTIVE: This is the first case report of a comprehensive neuropsychologic examination of an older man with the fragile X-associated tremor-ataxia syndrome (FXTAS). BACKGROUND: FXTAS, a newly identified phenotype affecting older male carriers of the fragile X premutation allele, is a progressive disorder marked by gait ataxia, action tremor, peripheral neuropathy, executive cognitive deficits, generalized brain atrophy, and neuronal and astrocytic intranuclear inclusion bodies throughout the brain. The patient previously had undergone neurologic evaluation, molecular analysis, and magnetic resonance imaging. METHOD: The patient was administered a neuropsychologic examination, assessing motor and somatosensory functioning, visual and spatial functioning, speech and language, attention, executive abilities, learning and memory, and reasoning. RESULTS: The patient showed a pattern of cognitive impairment characterized by essentially normal speech and language, moderately impaired control of attention, and moderate to severe deficits in working memory, executive functioning, and both declarative and procedural learning. Visual and spatial abilities were relatively unimpaired, and verbal reasoning was only mildly deficient. CONCLUSIONS: The findings suggest that a cognitive disorder, with especially marked executive cognitive function and memory deficits, accompanies FXTAS. The findings in FXTAS are compared with those in several other neurodegenerative disorders.

Dementia with mood symptoms in a fragile X premutation carrier with the fragile X-associated tremor/ataxia syndrome: clinical intervention with donepezil and venlafaxine.

The authors present a case of a patient with dementia with mood symptoms and multiple neurological manifestations of fragile X-associated tremor/ataxia syndrome (FXTAS). Despite a gradually deteriorating neurological course, he was managed for 2 years with combination therapy of donepezil and venlafaxine, which resulted in improvement and relative stabilization of his psychiatric status. Psychiatrists are hereby alerted to the description of a novel dementia syndrome that may respond to pharmacological intervention commonly used for other dementias.

Paraneoplastic limbic encephalitis in a teenage girl with an immature ovarian teratoma.

Paraneoplastic limbic encephalitis (PLE) is an unusual disorder that is characterized by the association of clinical limbic system abnormalities with neoplasia, usually malignancy. It has rarely been reported in children and then manifests during the teenage years. Diagnosis is often delayed, especially when the tumor has not been recognized. In adults, the diagnosis can be revealed by the presence of antineuronal antibodies. We describe an unusual case of behavioral disturbance leading rapidly to coma in a 14-year-old girl with CSF pleocytosis who was found 10 weeks later to have an immature ovarian teratoma. Although her symptoms eventually improved slightly after tumor excision, she died while in rehabilitation. PLE is an important diagnosis to consider in the teenage girl with symptoms of a progressive limbic disorder and CSF pleocytosis, and whose brain MR imaging demonstrates no abnormality or mild T2-weighted temporal lobe signal abnormality. When this constellation of findings presents in a teenage girl, the possibility of an underlying ovarian teratoma should be considered.

Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population.

CONTEXT: Premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction. OBJECTIVE: To study the penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) among premutation carriers. DESIGN, SETTING, AND PARTICIPANTS: Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion. MAIN OUTCOME MEASURES: Penetrance of intention tremor and ataxia among adult carriers (aged > or =50 years) of premutation expansions of the FMR1 gene. RESULTS: Data from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and > or =80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P =.003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P<.05). Female carrier scores were also higher than those of female controls (P<.05) on 2 of the 3 neurological rating scales, but no participant was identified with probable or definite FXTAS. CONCLUSIONS: The study demonstrates that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing FXTAS. Since male premutation carriers are relatively common in the general population, older men with ataxia and intention tremor should be screened for the FMR1 mutation, especially if these signs are accompanied by parkinsonism, autonomic dysfunction, or cognitive decline, regardless of family history.

Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study.

PURPOSE: To determine the safety and efficacy of ferumoxtran 10-enhanced magnetic resonance (MR) imaging for diagnosis of metastases to lymph nodes and the clinical usefulness of ferumoxtran 10 in nodal staging. MATERIALS AND METHODS: One hundred fifty-two patients were injected with ferumoxtran 10. Readers independently evaluated precontrast MR images by using node size criteria and subjective assessment of other imaging features. Ferumoxtran 10-enhanced MR images were evaluated alone and paired with precontrast images for comparison. The diagnostic performances of precontrast MR size criteria and postcontrast MR imaging were evaluated with receiver operating characteristic (ROC) analysis. Lymph node signal intensity was correlated with histopathologic findings. MR imaging and histopathologic nodal stages were compared. RESULTS: Node-level sensitivity, specificity, and accuracy of precontrast MR imaging were 54%, 82%, and 68%, respectively, with node size criterion alone; 91%, 51%, and 71%, respectively, with subjective reader assessment; 85%, 85%, and 85%, respectively, with postcontrast MR imaging alone; and 83%, 77%, and 80%, respectively, with paired pre- and postcontrast MR imaging. Compared with size criteria, subjective reader assessment had higher sensitivity but substantially lower specificity. Areas under the ROC curve for pre- and postcontrast MR imaging were 0.76 and 0.83, respectively. Nonmetastatic nodes had significantly lower signal intensity than metastatic nodes on postcontrast T2-weighted MR images (P <.001). Postcontrast nodal staging was significantly more accurate than precontrast nodal staging (P <.01). Headache, back pain, vasodilatation, and urticaria each occurred in 6% of patients. CONCLUSION: Ferumoxtran 10-enhanced MR imaging was safe and effective and facilitated improved diagnostic performance. Use of iron oxide-enhanced MR imaging increased the positive predictive value by 20% and the accuracy by 14% compared with reader assessment. Differentiating patients with no nodal metastatic involvement was more reliable with ferumoxtran 10-enhanced MR imaging than with precontrast MR imaging.

Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates.

We present a series of 26 patients, all >50 years of age, who are carriers of the fragile X premutation and are affected by a multisystem, progressive neurological disorder. The two main clinical features of this new syndrome are cerebellar ataxia and/or intention tremor, which were chosen as clinical inclusion criteria for this series. Other documented symptoms were short-term memory loss, executive function deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower limb proximal muscle weakness, and autonomic dysfunction. Symmetrical regions of increased T2 signal intensity in the middle cerebellar peduncles and adjacent cerebellar white matter are thought to be highly sensitive for this neurologic condition, and their presence is the radiological inclusion criterion for this series. Molecular findings include elevated mRNA and low-normal or mildly decreased levels of fragile X mental retardation 1 protein. The clinical presentation of these patients, coupled with a specific lesion visible on magnetic resonance imaging and with neuropathological findings, affords a more complete delineation of this fragile X premutation-associated tremor/ataxia syndrome and distinguishes it from other movement disorders.

The fragile X premutation presenting as essential tremor.

CONTEXT: The fragile X premutation has recently been reported to be associated with a neurodegenerative syndrome, chiefly characterized by intention tremor, gait ataxia, and executive cognitive deficits in men older than 50 years. Essential tremor is a frequent cause of tremor in elderly patients and in some cases is associated with impaired tandem gait and cognitive deficits. OBJECTIVE: To describe 2 fragile X carriers whose clinical presentation mimicked essential tremor. DESIGN: The 2 patients described herein underwent neurologic examinations by experienced movement disorders neurologists, magnetic resonance imaging, and fragile X gene, messenger RNA, and protein analyses. One underwent detailed neuropsychological testing. SETTING: Patients were studied at 2 large university movement disorders clinics. PATIENTS: Both patients were white men older than 50 years who had been diagnosed as having essential tremor and then found to be fragile X carriers. RESULTS: Besides disabling intention tremor, the 2 patients had impaired tandem, generalized brain atrophy, and unusual bilateral T2 middle cerebellar hyperintensities on magnetic resonance imaging. The patient who underwent neuropsychological testing had frontal executive deficits. Both patients had elevated fragile X mental retardation gene 1 messenger RNA and reduced fragile X mental retardation 1 protein levels. CONCLUSION: The fragile X carrier state may underlie the clinical findings in some older men diagnosed as having essential tremor.

Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction.

BACKGROUND AND PURPOSE: Our purpose was to characterize the findings of MR imaging of the brain of adult male fragile X premutation carriers with a recently identified disorder characterized by ataxia, tremor, rigidity, and cognitive dysfunction. METHODS: MR imaging studies of the brain of 17 male patients were characterized for signal intensity and for size of ventricles, cerebral and cerebellar sulci, and brain stem. Comparison was made with age- and sex-matched control participants. Southern blot and/or polymerase chain reaction methods were used to analyze CGG trinucleotide repeats in the fragile X mental retardation 1 gene. RESULTS: Fifteen of 17 patients showed symmetrically decreased T1 and increased T2 signal intensity in cerebellar white matter lateral, superior, and inferior to the dentate nuclei. Fourteen of 17 had similar signal intensity alterations in the middle cerebellar peduncles. Cerebellar cortical atrophy was present in 16 of 17 and cerebral atrophy in 17 of 17. Evan's Index as a measure of ventricular size averaged 0.35 (range, 0.25-0.46), with that for age-matched control participants averaging 0.28 (range, 0.24-0.31) (P <.005). The mean third ventricle width was 11 mm (for control participants, 6 mm; P <.01). Corpus callosum was thinned in 14 of 16 participants. Middle cerebellar peduncles were atrophic when compared with those of control participants (P <.005). Pontine transverse dimension was 25 mm (for control participants, 31 mm; P <.005), and rostral-caudal length averaged 26 mm (for control participants, 29 mm; P <.005). CGG repeats clustered in the low to mid premutation range (86 +/- 10 CGG repeats) in the 17 patients. CONCLUSION: MR imaging findings in symptomatic male fragile X premutation carriers are characteristic of this disorder. Recognition of these alterations may support a specific diagnosis and may have implications for the potential occurrence of fragile X syndrome in the children of reproductive age female relatives.

CT findings in the infantile form of citrullinemia.

Citrullinemia is a rare autosomal recessive inborn error of the urea cycle due to a deficiency in argininosuccinic acid synthetase. We present two cases of the infantile form of citrullinemia in which CT revealed bilateral and symmetric corticosubcortical hypoattenuating areas, ulegyric changes, and atrophy in the frontal lobes, as well as atrophy in the gyrus cinguli, insulae, and temporal lobes.

Diffusion MRI: a new strategy for assessment of cancer therapeutic efficacy.

The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator or treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a nonvolumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.