Discordance Between Perceptions and Experience of Lumbar Puncture: A Prospective Study.

Background and Objectives: Novel diagnostic techniques and neurologic biomarkers have greatly expanded clinical indications for CSF studies. CSF is most commonly obtained via lumbar puncture (LP). Although it is generally believed that LPs are well tolerated, there is a lack of supportive data for this claim, and patients anticipate LP to be painful. The objective of this study was to prospectively investigate discordance between patient perception and tolerability of LP. Methods: Adult patients were surveyed before and after LP regarding their perceptions and experience of LP. Physician perceptions were gathered through a web-based survey. Relative risk and Spearman correlation were used to assess the relationship between responses. Paired binomial and paired ordinal responses were compared by McNemar and paired Wilcoxon rank-sum tests. Results: A total of 178 patients completed the surveys. About half of the patients (58%) reported anxiety pre-LP, at median 3.0 of 10. Physicians overpredicted patients' pre-LP anxiety (median score 5.0, p < 0.001). Experienced pain was significantly less than predicted pain (median scores 0 and 3.0, respectively, p < 0.001). Patients who predicted pain were more likely to report pain from LP (relative risk [RR] 1.3). Predicting pain was also correlated with anxiety before LP (p < 0.001). Discussion: LP was generally well tolerated. The majority of patients experienced minimal pain. Anticipation of pain was correlated with both feeling anxious and experiencing pain. The results of this study can be used to reassure patients and providers that LP is indeed not as painful as imagined, which may both reduce pre-LP anxiety and improve LP tolerability.

Challenging Cases in Neuroimmunology.

Neuroimmunology is rapidly evolving field extending from well-known, but incompletely understood conditions like multiple sclerosis, to novel antibody-mediated disorders, of which dozens have been described in the past 10 years. The ongoing expansion in knowledge needed to effectively diagnose and treat these patients presents myriad challenges for clinicians. Here, we discuss six informative cases from our institution. By highlighting these challenging cases, we hope to instill fundamental points on the nuances of diagnosis and management for conditions including tumefactive multiple sclerosis, antibody-mediated encephalitis, antiphospholipid antibody syndrome, neuromyelitis optica, and myelin oligodendrocyte glycoprotein IgG-associated disease.

Efficient Online Object Tracking Scheme for Challenging Scenarios.

Visual object tracking (VOT) is a vital part of various domains of computer vision applications such as surveillance, unmanned aerial vehicles (UAV), and medical diagnostics. In recent years, substantial improvement has been made to solve various challenges of VOT techniques such as change of scale, occlusions, motion blur, and illumination variations. This paper proposes a tracking algorithm in a spatiotemporal context (STC) framework. To overcome the limitations of STC based on scale variation, a max-pooling-based scale scheme is incorporated by maximizing over posterior probability. To avert target model from drift, an efficient mechanism is proposed for occlusion handling. Occlusion is detected from average peak to correlation energy (APCE)-based mechanism of response map between consecutive frames. On successful occlusion detection, a fractional-gain Kalman filter is incorporated for handling the occlusion. An additional extension to the model includes APCE criteria to adapt the target model in motion blur and other factors. Extensive evaluation indicates that the proposed algorithm achieves significant results against various tracking methods.

Radial Undersampling-Based Interpolation Scheme for Multislice CSMRI Reconstruction Techniques.

Magnetic Resonance Imaging (MRI) is an important yet slow medical imaging modality. Compressed sensing (CS) theory has enabled to accelerate the MRI acquisition process using some nonlinear reconstruction techniques from even 10% of the Nyquist samples. In recent years, interpolated compressed sensing (iCS) has further reduced the scan time, as compared to CS, by exploiting the strong interslice correlation of multislice MRI. In this paper, an improved efficient interpolated compressed sensing (EiCS) technique is proposed using radial undersampling schemes. The proposed efficient interpolation technique uses three consecutive slices to estimate the missing samples of the central target slice from its two neighboring slices. Seven different evaluation metrics are used to analyze the performance of the proposed technique such as structural similarity index measurement (SSIM), feature similarity index measurement (FSIM), mean square error (MSE), peak signal to noise ratio (PSNR), correlation (CORR), sharpness index (SI), and perceptual image quality evaluator (PIQE) and compared with the latest interpolation techniques. The simulation results show that the proposed EiCS technique has improved image quality and performance using both golden angle and uniform angle radial sampling patterns, with an even lower sampling ratio and maximum information content and using a more practical sampling scheme.

Spatio-Temporal Context, Correlation Filter and Measurement Estimation Collaboration Based Visual Object Tracking.

Despite eminent progress in recent years, various challenges associated with object tracking algorithms such as scale variations, partial or full occlusions, background clutters, illumination variations are still required to be resolved with improved estimation for real-time applications. This paper proposes a robust and fast algorithm for object tracking based on spatio-temporal context (STC). A pyramid representation-based scale correlation filter is incorporated to overcome the STC's inability on the rapid change of scale of target. It learns appearance induced by variations in the target scale sampled at a different set of scales. During occlusion, most correlation filter trackers start drifting due to the wrong update of samples. To prevent the target model from drift, an occlusion detection and handling mechanism are incorporated. Occlusion is detected from the peak correlation score of the response map. It continuously predicts target location during occlusion and passes it to the STC tracking model. After the successful detection of occlusion, an extended Kalman filter is used for occlusion handling. This decreases the chance of tracking failure as the Kalman filter continuously updates itself and the tracking model. Further improvement to the model is provided by fusion with average peak to correlation energy (APCE) criteria, which automatically update the target model to deal with environmental changes. Extensive calculations on the benchmark datasets indicate the efficacy of the proposed tracking method with state of the art in terms of performance analysis.

Medical Student Usage of the American College of Radiology Appropriateness Criteria.

RATIONALE AND OBJECTIVES: Educating medical students on appropriate imaging utilization has been increasingly recognized as important for patient care. The American College of Radiology Appropriateness Criteria (ACR-AC) is designed to support evidence-based imaging examination selection. We sought to assess whether medical students order imaging studies independently, what resources they use for guidance, and whether they use the ACR-AC in clinical practice. A secondary aim was to determine whether increasing familiarity with the ACR-AC could impact student usage. MATERIALS AND METHODS: We surveyed third year medical students at a single institution on their imaging practices, familiarity with the ACR-AC, and preferences among available resources to guide proper examination selection. The survey was performed in person before a lecture. We also designed a brief intervention to improve familiarity with the ACR-AC and then reassessed students to determine any effect on utilization. RESULTS: The response rate for the initial survey was 103 of 109 (94%) and the response rate for the second survey was 99 of 109 (91%).Our initial survey found students initiated imaging orders independently (74 of 100, 74.8%) and consulted resources to assist in examination selection (50 of 74, 67.6%). Students expressed a preference for non-ACR-AC resources, notably Up to Date via its online mobile application.Few students (8 of 71, 11.3%) were familiar with the ACR-AC. After an intervention to increase familiarity with the ACR-AC, student awareness of the ACR-AC increased to 61 of 74 (82.4%). However, usage among those familiar with the resource remained low, 13 of 61(21.3%) versus 3 of 8 (37.5%). CONCLUSIONS: Use of the ACR-AC was low among third year medical students. After increasing students' familiarity with the ACR-AC, their usage in a clinical setting did not increase. The largest barrier to use may be the lack of a quick, easy to use online mobile application-based interface.

Verbal creativity in semantic variant primary progressive aphasia.

Emergence of visual and musical creativity in the setting of neurologic disease has been reported in patients with semantic variant primary progressive aphasia (svPPA), also called semantic dementia (SD). It is hypothesized that loss of left anterior frontotemporal function facilitates activity of the right posterior hemispheric structures, leading to de novo creativity observed in visual artistic representation. We describe creativity in the verbal domain, for the first time, in three patients with svPPA. Clinical presentations are carefully described in three svPPA patients exhibiting verbal creativity, including neuropsychology, neurologic exam, and structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) was performed to quantify brain atrophy patterns in these patients against age-matched healthy controls. All three patients displayed new-onset creative writing behavior and produced extensive original work during the course of disease. Patient A developed interest in wordplay and generated a large volume of poetry. Patient B became fascinated with rhyming and punning. Patient C wrote and published a lifestyle guidebook. An overlap of their structural MR scans showed uniform sparing in the lateral portions of the language-dominant temporal lobe (superior and middle gyri) and atrophy in the medial temporal cortex (amygdala, limbic cortex). New-onset creativity in svPPA may represent a paradoxical functional facilitation. A similar drive for production is found in visually artistic and verbally creative patients. Mirroring the imaging findings in visually artistic patients, verbal preoccupation and creativity may be associated with medial atrophy in the language-dominant temporal lobe, but sparing of lateral dominant temporal and non-dominant posterior cortices.

Satiety-related hormonal dysregulation in behavioral variant frontotemporal dementia.

OBJECTIVE: To investigate whether patients with behavioral variant frontotemporal dementia (bvFTD) have dysregulation in satiety-related hormonal signaling using a laboratory-based case-control study. METHODS: Fifty-four participants (19 patients with bvFTD, 17 patients with Alzheimer disease dementia, and 18 healthy normal controls [NCs]) were recruited from a tertiary-care dementia clinic. During a standardized breakfast, blood was drawn before, during, and after the breakfast protocol to quantify levels of peripheral satiety-related hormones (ghrelin, cortisol, insulin, leptin, and peptide YY) and glucose. To further explore the role of patients' feeding abnormalities on hormone levels, patients were classified into overeating and nonovereating subgroups based on feeding behavior during separate laboratory-based standardized lunch feeding sessions. RESULTS: Irrespective of their feeding behavior in the laboratory, patients with bvFTD, but not patients with Alzheimer disease dementia, have significantly lower levels of ghrelin and cortisol and higher levels of insulin compared with NCs. Furthermore, while laboratory feeding behavior did not predict alterations in levels of ghrelin, cortisol, and insulin, only patients with bvFTD who significantly overate in the laboratory demonstrated significantly higher levels of leptin compared with NCs, suggesting that leptin may be sensitive to particularly severe feeding abnormalities in bvFTD. CONCLUSIONS: Despite a tendency to overeat, patients with bvFTD have a hormonal profile that should decrease food intake. Aberrant hormone levels may represent a compensatory response to the behavioral or neuroanatomical abnormalities of bvFTD.

TDP-43 frontotemporal lobar degeneration and autoimmune disease.

BACKGROUND: The aetiology and pathogenesis of non-genetic forms of frontotemporal dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis remains elusive. Given the association between systemic inflammation and other neurodegenerative processes, links between autoimmunity and FTD need to be explored. OBJECTIVE: To describe the prevalence of systemic autoimmune disease in semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in progranulin (PGRN) mutation carriers compared with neurologically healthy normal controls (NC) and Alzheimer's disease (AD) as dementia controls. DESIGN: Case control. SETTING: Academic medical centres. PARTICIPANTS: 129 svPPA, 39 PGRN, 186 NC and 158 AD patients underwent chart review for autoimmune conditions. A large subset of svPPA, PGRN and NC cohorts underwent serum analysis for tumour necrosis factor α (TNF-α) levels. OUTCOME MEASURES: χ(2) Comparison of autoimmune prevalence and follow-up logistic regression. RESULTS: There was a significantly increased risk of autoimmune disorders clustered around inflammatory arthritides, cutaneous disorders and gastrointestinal conditions in the svPPA and PGRN cohorts. Elevated TNF-α levels were observed in svPPA and PGRN compared with NC. CONCLUSIONS: svPPA and PGRN are associated with increased prevalence of specific and related autoimmune diseases compared with NC and AD. These findings suggest a unique pattern of systemic inflammation in svPPA and PGRN and open new research avenues for understanding and treating disorders associated with underlying transactive response DNA-binding protein 43 aggregation.

Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features.

OBJECTIVE: To describe the phenotype of patients with C9FTD/ALS (C9ORF72) hexanucleotide repeat expansion. METHODS: A total of 648 patients with frontotemporal dementia (FTD)-related clinical diagnoses and Alzheimer disease (AD) dementia were tested for C9ORF72 expansion and 31 carried expanded repeats (C9+). Clinical and neuroimaging data were compared between C9+ (15 behavioral variant FTD [bvFTD], 11 FTD-motor neuron disease [MND], 5 amyotrophic lateral sclerosis [ALS]) and sporadic noncarriers (48 bvFTD, 19 FTD-MND, 6 ALS). RESULTS: All C9+ patients displayed clinical syndromes of bvFTD, ALS, or FTD-MND. At first evaluation, C9+ bvFTD patients had more delusions and greater impairment of working memory, but milder eating dysregulation compared to bvFTD noncarriers. C9+FTD-MND patients had a trend for longer survival and had an earlier age at onset than FTD-MND noncarriers. Voxel-based morphometry demonstrated more thalamic atrophy in FTD and FTD-MND carriers than in noncarriers. CONCLUSIONS: Patients with the C9ORF72 hexanucleotide repeat expansion develop bvFTD, ALS, or FTD-MND with similar clinical and imaging features to sporadic cases. Other FTD spectrum diagnoses and AD dementia appear rare or absent among C9+ individuals. Longer survival in C9+ FTD-MND suggests slower disease progression and thalamic atrophy represents a novel and unexpected feature.

Atypical, slowly progressive behavioural variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion.

BACKGROUND: Some patients meeting behavioural variant frontotemporal dementia (bvFTD) diagnostic criteria progress slowly and plateau at mild symptom severity. Such patients have mild neuropsychological and functional impairments, lack characteristic bvFTD brain atrophy and have thus been referred to as bvFTD 'phenocopies' or slowly progressive (bvFTD-SP). The few patients with bvFTD-SP that have been studied at autopsy have demonstrated no evidence of FTD pathology, suggesting that bvFTD-SP is neuropathologically distinct from other forms of FTD. Here, two patients with bvFTD-SP with chromosome 9 open reading frame 72 (C9ORF72) hexanucleotide expansions are described. METHODS: 384 patients with an FTD clinical spectrum and Alzheimer's disease diagnoses were screened for C9ORF72 expansion. Two bvFTD-SP mutation carriers were identified. Neuropsychological and functional data, as well as brain atrophy patterns, assessed using voxel based morphometry (VBM), were compared with 44 patients with sporadic bvFTD and 85 healthy controls. RESULTS: Both patients were aged 48 years at baseline and met possible bvFTD criteria. In the first patient, VBM revealed thalamic and posterior insula atrophy. Over 7 years, his neuropsychological performance and brain atrophy remained stable. In the second patient, VBM revealed cortical atrophy with subtle frontal and insular volume loss. Over 2 years, her neuropsychological and functional scores as well as brain atrophy remained stable. CONCLUSIONS: C9ORF72 mutations can present with a bvFTD-SP phenotype. Some bvFTD-SP patients may have neurodegenerative pathology, and C9ORF72 mutations should be considered in patients with bvFTD-SP and a family history of dementia or motor neuron disease.

The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease.

OBJECTIVE: To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease. METHOD: Systematic, retrospective, blinded chart review was performed of 252 patients with a neurodegenerative disease diagnosis seen in our specialty clinic between 1999 and 2008. Neurodegenerative disease diagnoses included behavioral-variant frontotemporal dementia (n = 69), semantic dementia (n = 41), and progressive nonfluent aphasia (n = 17) (all meeting Neary research criteria); Alzheimer's disease (n = 65) (National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association research criteria); corticobasal degeneration (n = 25) (Boxer research criteria); progressive supranuclear palsy (n = 15) (Litvan research criteria); and amyotrophic lateral sclerosis (n = 20) (El Escorial research criteria). Reviewers remained blinded to each patient's final neurodegenerative disease diagnosis while reviewing charts. Extensive caregiver interviews were conducted to ensure accurate and reliable diagnostic histories. For each patient, we recorded history of psychiatric diagnosis, family psychiatric and neurologic history, age at symptom onset, and demographic information. RESULTS: A total of 28.2% of patients with a neurodegenerative disease received a prior psychiatric diagnosis. Depression was the most common psychiatric diagnosis in all groups. Behavioral-variant frontotemporal dementia patients received a prior psychiatric diagnosis significantly more often (50.7%; P < .001) than patients with Alzheimer's disease (23.1%), semantic dementia (24.4%), or progressive nonfluent aphasia (11.8%) and were more likely to receive diagnoses of bipolar disorder or schizophrenia than were patients with other neurodegenerative diseases (P < .001). Younger age (P < .001), higher education (P < .05), and a family history of psychiatric illness (P < .05) increased the rate of prior psychiatric diagnosis in patients with behavioral-variant frontotemporal dementia. Cognitive, behavioral, and emotional characteristics did not distinguish patients who did or did not receive a prior psychiatric diagnosis. CONCLUSIONS: Neurodegenerative disease is often misclassified as psychiatric disease, with behavioral-variant frontotemporal dementia patients at highest risk. While this study cannot rule out the possibility that psychiatric disease is an independent risk factor for neurodegenerative disease, when patients with neurodegenerative disease are initially classified with psychiatric disease, the patient may receive delayed, inappropriate treatment and be subject to increased distress. Physicians should consider referring mid- to late-life patients with new-onset neuropsychiatric symptoms for neurodegenerative disease evaluation.