Persistent lymph nodes after curative chemoradiotherapy for head and neck cancer: imaging predictors of response for decision-making.

PURPOSE: To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT). MATERIALS AND METHODS: Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed. RESULTS: The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004-0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11-17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2-42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79-8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004-1.13], p = 0.048). CONCLUSIONS: In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections.

Loss of smell in patients with traumatic brain injury is associated with neuropsychiatric behavioral alterations.

OBJECTIVE: We sought to identify and correlate the severity of traumatic brain injuries (TBIs) associated with olfactory dysfunction with cognitive and behavioral profiles. PARTICIPANTS AND SETTING: Patients with TBI undergoing treatment in a specialized neuro-rehabilitation hospital. DESIGN: Prospective study. MAIN MEASURES: Glasgow Coma Scale (GCS) at the time of injury and during posttraumatic amnesia. Motor functions were assessed with the Functional Instrument Measure and Disability Rating Scales. The Wechsler Adult Intelligence test was used for neuropsychologic assessment and the Neuropsychiatric Inventory was used to assess behavioral changes. The Barcelona Smell Test-24 was used to study subjective smell loss. RESULTS: A total of 111 patients with TBI were enrolled (33 females; mean age 32.86 years); 38.73% exhibited smell loss. Patients with no olfactory impairment (OI) had worse TBIs than those with OI (GCS scores 5.65 and 7.74, respectively); no significant differences in cognitive behaviors, such as attention memory, visuoperception, and visuoconstruction, were observed. However, patients with TBI and olfactory dysfunction showed statistically significant alterations in neuropsychiatric behavioral performances such as feeding when compared with patients with TBI without smell loss. CONCLUSION: Olfactory dysfunction in patients with a TBI correlates with altered neuropsychiatric behavioral performances such as feeding, sleeping, and motor behavior.

Long-term radiological findings after endonasal endoscopic approach to the skull base.

OBJECTIVE: To study the long-term radiological findings after endonasal endoscopic approach to the skull base. MATERIAL AND METHODS: Prospective study that included 55 patients who underwent advance endoscopic skull base surgery. All patients were evaluated with MRI before, 3 months and 12 months after surgery. We used the Lund-Mackay staging system for chronic rhinosinusitis to evaluate the paranasal cavities and the sinonasal scoring system to assess sinonasal symptoms. RESULTS: Seventeen patients (30.9%) underwent extended endonasal approach that required a nasoseptal flap (NSF) for reconstruction of skull base. At baseline the mean total Lund-Mackay score was 0.63 ± 1.2 (range 0-4), and at 3 and 12 months postoperatively the mean scores were 3.5 ± 3.8 (range 0-14) and 2.0 ± 2.5 (range 0-8) respectively. Patients who needed an NSF for reconstruction had a greater Lund-Mackay score (p<0.05). Moreover, NSF is correlated with sinonasal mucosal thickening and fluid retention at 3 months (r=0.45, p<0.01) and 12 months (r=0.4, p<0.01). Total 5-symptom score (T5SS) was similar between both groups at baseline. Patients with extended endoscopic approach reported more smell loss (40.1 ± 26.2; p<0.05) and posterior nasal discharge (49.3 ± 30.1; p<0.05) than TTEA patients (21.6 ± 30.9 and 22.5 ± 27.5 respectively). CONCLUSIONS: We observed that sinus opacity is still present after one year of advance endoscopic skull base surgery but symptoms seems to return to basal after 12 months of follow-up.

Increased signal intensity in FLAIR sequences in the resection cavity can predict progression and progression-free survival in gliomas.

OBJECTIVE: To determine if hyperintense fluid in the postsurgical cavity on follow-up fluid-attenuated inversion recovery (FLAIR) sequences can predict progression in gliomas. MATERIAL AND METHODS: Observational study of magnetic resonance imaging signal of fluid within the post-surgical cavity in patients with glioma (grade II-IV), with surgery and follow-up between 2007 and 2012. Qualitative comparison between the signal of fluid in the cavity and of the ventricular cerebrospinal fluid (CSF) was performed on FLAIR sequences. Fluid in the cavity was classified as isointense or hyperintense compared to CSF. Double-blind reading was performed. The signal intensity was correlated with tumour progression, assessed using Response Assessment in Neuro-Oncology criteria. RESULTS: A total of 107 patients were included, of whom 90 had high-grade gliomas. Inter-rater agreement was excellent, and intra-rater complete (k=0.94 and 1, p<.001). Hyperintense fluid in the resection cavity occurred more commonly (58.9% versus 29.4%, p=.025) and earlier (mean 4.5 versus 9.9 months, p<.001) in high-grade than in low-grade gliomas. Hyperintense fluid was associated with progression in high-grade gliomas, with a sensitivity of 65.7% (95%CI, 54.3-75.6%) and a specificity of 70.6% (95%CI, 46.6-87%), and in low-grade gliomas with a sensitivity of 50% (95%CI, 18.7-81.2%), and a specificity of 81.8% (95%CI, 51.1-96%). The positive predictive value of this sign was 90.6% (95%CI, 79.3-96.3%) for high-grade gliomas, and was higher for grade IV (93.2%, 95%CI, 87.3-99.1%) and lower for grade III (77.8%, 95%CI, 59.6-96%), and low-grade gliomas (60%, 95%CI, 22.9-88.4%). False-positives were identified in 7 patients, due to bleeding or infection. Hyperintense fluid in high-grade gliomas preceded progression in 22 patients (30.1%), with a mean of 4.1 months (SD 2.1, 95% CI, 3.2-5), and associated with poorer progression-free survival (mean 6.8 versus 11.7 months, p=.004). CONCLUSIONS: Hyperintense fluid in the resection cavity on follow-up FLAIR sequences occurs more frequently and earlier in high-grade gliomas, and is associated with poorer progression-free survival. Hyperintense fluid is associated with disease progression, and can predict the progression of resected gliomas. False-positives due to bleeding and infection can be observed, and are easily recognizable.

Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis.

OBJECTIVE: To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans-synaptic degeneration in multiple sclerosis (MS). METHODS: We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple linear regressions, and general linear models. RESULTS: VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (ß = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl aspartate in visual cortex (ß = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (ß = -2.551, 95% CI = -3.910 to -1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm(3) in visual cortex volume predicts a reduction of 0.6µm in RNFL thickness. This association was also observed after 1 year of follow-up. Patients with severe prior ON (adjusted difference = -3.01, 95% CI = -5.08 to -0.95) and mild prior ON (adjusted difference = -1.03, 95% CI = -3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON. INTERPRETATION: Our results suggest the presence of trans-synaptic degeneration as a contributor to chronic axon damage in MS.

The extended endoscopic endonasal transplanum transtuberculum approach to the anterior communicating artery complex: anatomic study.

BACKGROUND: When performing a transplanum transtuberculum approach, dealing with the anterior communicating artery (ACoA) complex is inevitable. The aim of this study is to provide quantitative anatomical information regarding the ACoA complex and its bony and neural relationships, when exposed through this approach. METHOD: The endoscopic endonasal transplanum transtuberculum approach was performed on ten human cadaver heads. In each specimen, radiological studies were performed. A three-dimensional model of the approach was reconstructed. Measured parameters were: exposure of the vessels; distance between the proximal anterior cerebral artery (A1) and the optic chiasm; dimension of the bone opening. The feasibility to perform clip placement was graded as "possible" or "not possible". RESULTS: Dimension of bone opening varied from 88 to 53 mm(2). The ACoA was exposed for 3 mm ± 2 mm, A1 for 17 mm ± 9 mm, the distal anterior cerebral artery (A2) for 12 mm ± 3 mm, the recurrent artery of Heubner (RAH) for 16 mm ± 4 mm. Clip placement was possible on the ACoA, A2, and distal segment of A1 in all cases, and on the proximal segment of A1 in one instance. The distance between A1 and the optic chiasm measured 9 mm ± 2 mm. CONCLUSIONS: The ACoA, A2, and the distal segment of A1 can be visualized and controlled through the transplanum transtuberculum approach. The relationship between A1, gyrus rectus, and optic chiasm is the main determinant for the exposure and control of the vessel. The olfactory nerve can represent a surgical landmark for the identification of the A1 origin. The whole course of the RAH can be visualized trough this approach.

Cognitive functions in multiple sclerosis: impact of gray matter integrity.

OBJECTIVES: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. METHODS: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. RESULTS: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36-51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. CONCLUSION: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.

Clinically reversible ustekinumab-induced encephalopathy: case report and review of the literature.

Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23 approved for the treatment of Crohn's disease, has shown to be an effective therapy with a favourable safety profile. Clinical trials and real-world studies have reported very few neurological adverse events, including posterior reversible encephalopathy syndrome, idiopathic intracranial hypertension and headache. We describe the case of a 48-year-old man with Crohn's disease who initiated treatment with ustekinumab on top of ongoing treatment with methotrexate 25 mg/week who presented with an acute-onset encephalopathy that rapidly evolved to severe tetraparesis and akinetic mutism, associated with extensive leukoencephalopathy and restricted diffusion on brain magnetic resonance imaging (MRI), 1 month after the second dose of ustekinumab. Comprehensive in-patient diagnostic testing ruled out vascular, demyelinating, metabolic, tumoral and infectious etiologies. Brain biopsy showed patchy infiltrates of foamy histiocytes with perivascular distribution, associated with edema, diffuse astrocytic gliosis and focal perivascular axonal destruction without demyelination, and ustekinumab-induced neurotoxicity was suspected. After drug discontinuation, the patient presented a complete clinical recovery despite the persistence of leukoencephalopathy. In conclusion, in an era in which biological therapies are continually evolving and expanding, knowledge about the potential neurotoxicity of these new therapies and their management becomes crucial. Although ustekinumab-induced encephalopathy is uncommon, the recognition of this potentially serious side effect is important because prompt withdrawal is associated with a favourable outcome. Whether methotrexate played an additional contributing role is currently unknown, but it is a factor that should be considered.

Salivary ATP13A2 is a potential marker of therapy-induced motor complications and is expressed by inclusions in submandibulary glands in Parkinson ´s disease.

Background: ATP13A2 holds promise as biomarker for Parkinsons disease (PD). No study has examined how salivary ATP13A2 is related to motor features in idiopathic PD. Methods: Salivary ATP13A2 concentration was evaluated with ELISA, and statistical correlations of ATP13A2 level with PD parameters were examined. The dose intensity of the dopaminergic medication regimen was expressed as levodopa equivalent daily dose (LEDD). ATP13A2 expression on histological sections of submandibular glands was evaluated using immunohistochemistry. Results: Salivary ATP13A2 was undetectable in many subjects (28 % of patients, 43.7 % of controls). However, all the patients with motor complications (n = 28) showed quantifiable levels of ATP13A2, that positively correlated with MDS-UPDRS (total, parts III and IV), and LEDD (p < 0.05). Dyskinetic patients showed the highest LEDD values (p < 0.05). The histological study revealed: a) ATP13A2 staining was very intense in duct cells and vascular endothelium, and b) two patterns of ATP13A2-positive deposits are observed: rounded inclusions of 10-20 µm in diameter located in the interlobular tissue of the patients, and amorphous aggregates inside duct lumen in controls and patients. Conclusions: The sensitivity of the ELISA assay was a major limitation for quantifying ATP13A2. However, salivary ATP13A2 was detected in all patients with motor complications, where a direct relationship among ATP13A2 concentration, levodopa equivalent daily dose, and MDS-UPDRS was found. Therefore, salivary ATP13A2 might be a reliable index of therapy-induced motor complications. ATP13A2 was expressed by rounded inclusions in the submandibulary gland of patients. This is the first description of ATP13A2-positive inclusions outside the nervous system.

Magnetic resonance imaging abnormalities as a marker of multiple system atrophy in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: Patients with isolated rapid eye movement (REM) sleep behavior disorder (IRBD) develop Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA). Magnetic resonance imaging (MRI) is abnormal in MSA showing abnormalities in the putamen, cerebellum, and brainstem. Our objective was to evaluate the usefulness of MRI to detect MRI abnormalities in IRBD and predict development of MSA and not PD and DLB. METHODS: In IRBD patients that eventually developed PD, DLB, and MSA, we looked for the specific structural MRI abnormalities described in manifest MSA (e.g. hot cross-bun sign, putaminal rim, and cerebellar atrophy). We compared the frequency of these MRI changes among groups of converters (PD, DLB, and MSA) and analyzed their ability to predict development of MSA. The clinical and radiological features of the IRBD patients that eventually converted to MSA are described in detail. RESULTS: A total of 61 IRBD patients who underwent MRI phenoconverted to PD (n = 30), DLB (n = 26), and MSA (n = 5) after a median follow-up of 2.4 years from neuroimaging. MRI changes typical of MSA were found in four of the five (80%) patients who converted to MSA and in three of the 56 (5.4%) patients who developed PD or DLB. MRI changes of MSA had sensitivity of 80.0%, specificity of 94.6%, positive likelihood ratio of 14.9 (95% CI 4.6-48.8), and negative likelihood ratio of 0.2 (95% CI 0.04-1.2) to predict MSA. CONCLUSIONS: In IRBD, conventional brain MRI is helpful to predict conversion to MSA. The specific MRI abnormalities of manifest MSA may be detected in its premotor stage.

Native α-Synuclein, 3-Nitrotyrosine Proteins, and Patterns of Nitro-α-Synuclein-Immunoreactive Inclusions in Saliva and Submandibulary Gland in Parkinson's Disease.

Background. Salivary α-synuclein (aSyn) and its nitrated form, or 3-nitrotyrosine-α-synuclein (3-NT-αSyn), hold promise as biomarkers for idiopathic Parkinson's disease (IPD). Nitrative stress that is characterized by an excess of 3-nitrotyrosine proteins (3-NT-proteins) has been proposed as a pathogenic mechanism in IPD. The objective is to study the pathological role of native αSyn, 3-NT-αSyn, and 3-NT-proteins in the saliva and submandibulary glands of patients with IPD. Methods. The salivary and serum αSyn and 3-NT-proteins concentration is evaluated with ELISA in patients and controls. Correlations of αSyn and 3-NT-proteins content with clinical features of the disease are examined. Immunohistochemical 3-NT-αSyn expression in submandibulary gland sections is analyzed. Results. (a) Salivary concentration and saliva/serum ratios of native αSyn and 3-NT-proteins are similar in patients and controls; (b) salivary αSyn and 3-NT-proteins do not correlate with any clinical feature; and (c) three patterns of 3-NT-αSyn-positive inclusions are observed on histological sections: rounded "Lewy-type" aggregates of 10-25 µm in diameter, coarse deposits with varied morphology, and spheroid inclusions or bodies of 3-5 µm in diameter. "Lewy-type" and coarse inclusions are observed in the interlobular connective tissue of the gland, and small-sized bodies are located within the cytoplasm of duct cells. "Lewy-type" inclusions are only observed in patients, and the remaining patterns of inclusions are observed in both the patients and controls. Conclusions. The patients' saliva presents a similar concentration of native αSyn and 3-nitrotyrosine-proteins than that of the controls, and no correlations with clinical features are found. These findings preclude the utility of native αSyn in the saliva as a biomarker, and they indicate the absence of nitrative stress in the saliva and serum of patients. As regards nitrated αSyn, "Lewy-type" inclusions expressing 3-NT-αSyn are observed in the patients, not the controls-a novel finding that suggests that a biopsy of the submandibulary gland, if proven safe, could be a useful technique for diagnosing IPD. Finally, to our knowledge, this is also the first description of 3-NT-αSyn-immunoreactive intracytoplasmic bodies in cells that are located outside the nervous system. These intracytoplasmic bodies are present in duct cells of submandibulary gland sections from all subjects regardless of their pathology, and they can represent an aging or involutional change. Further immunostaining studies with different antibodies and larger samples are needed to validate the data.

Long-Term Follow-Up of Single-Fiber Multiple Low-Intensity Energy Laser Ablation Technique of Benign Thyroid Nodules.

AIM: The short-term and long-term efficacy of different thermal percutaneous ablation techniques remains a topical issue. Our group implemented percutaneous laser ablation (LA), a moving-shot technique to increase efficiency and reduce costs and variability of LA by applying multiple lower-intensity energy illuminations (MLIEI) covering the nodular volume (V) through changes in position of a single laser fiber within the thyroid nodule. The aim of the present study was to evaluate the efficacy of the single-fiber LA-MLIEI during a 5-year follow-up and to identify possible predictors of the final outcome. METHODS: Prospective study: Thirty outpatients (23 women and seven men) with benign symptomatic thyroid nodules were assigned to single-fiber LA-MLIEI, between 2012 and 2015. A single LA session was performed under real-time ultrasound (US) guidance using a 1,064-nm continuous-wave laser at 3 W. A 400-µm optical fiber was inserted through a 21-gauge needle, and 3-10 illuminations were performed per nodule, administering between 400 and 850 J/illumination. The total administered energy was calculated on the initial V of the nodule and the estimated ablation area. US evaluation was performed after LA-MLIEI at 1 week and 1, 3, 6, and 12 months and after that annually up to 5 years. Clinical symptoms, laboratory thyroid function during follow-up, and acute and chronic complications of treatment were registered. RESULTS: On follow-up, 67% (n: 20) were responders to single-fiber LA-MLIEI, while 33% (n: 10) were non-responders. The responder group initiated V reduction (ΔV) at 1 month, with remission of symptoms, and presented a 50% ΔV at 3 months of treatment; the maximum response was achieved at 24 months and remained stable until the end of the study. The non-responder group presented a ΔV of less than 50% at 12 months; though a tendency to >50% ΔV was observed at 24-36 months, there was subsequent regrowth, and 40% of this group required surgery. ΔV was positively correlated with the total administered energy/V (J/V) and inversely with nodule V. No severe adverse effects were observed. Thyroid function remained normal in all patients. Remission of symptoms occurred rapidly after 1 month. CONCLUSIONS: LA with multiple fractional discharges employing a single fiber in a unique session is a safe and inexpensive technique that allows rapid reduction of thyroid nodules, with a stable response up to 5 years, similarly to what has been reported with the conventional LA. Total nodule volume appears as a predictive factor of the reduction.

Transoral laser microsurgery in locally advanced laryngeal cancer: Prognostic impact of anterior versus posterior compartments.

BACKGROUND: To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. METHODS: Two hundred and two consecutive pT3-T4a larynx carcinomas. Pre-epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease-specific survival (DSS), and laryngectomy-free survival (LFS) were evaluated. RESULTS: The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio [HR] = 0.289 [0.085-0.979]) and anterior (HR = 0.278 [0.128-0.605]) and posterior (HR = 0.269 [0.115-0.630]) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 [1.537-8.495]) and posterior (HR = 5.195 [2.167-12.455]) PGS involvement were independent factors of total laryngectomy. Five-year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5-year LFS. CONCLUSIONS: Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.

Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients.

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5-15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.

T2 hypointense rims and ring-enhancing lesions in MS.

BACKGROUND: Hypointense rims peripherally on T2-weighted MRI (rim lesions) have been associated with gadolinium ring-enhancing lesions in multiple sclerosis (MS) in pathological studies. However, little is known about their frequency, we analyzed clinical significance in a cohort of MS sufferers according to routine clinical practice. METHODS: We retrospectively reviewed all available MRI scans performed on our MS patients between 2000 and 2009. A total of 580 MRI scans from 257 patients were analyzed. The presence of rim lesions and ring enhancement was assessed and counted blind. Furthermore, the correlation between both patterns, and with clinical characteristics, was evaluated. RESULTS: Thirty-five rim lesions were identified and 9% (24/257) of the patients showed at least one of these lesions. Forty ring-enhancing lesions were counted and 12% (29/245) of the patients who had undergone gadolinium MRI presented at least one such lesion. Thirteen lesions co-localized both patterns (40% of the rim lesions and 33% of the ring-enhancing lesions). Rim lesions and ring-enhancing lesions were observed in patients with clinically isolated syndrome (7%, 7%), relapsing-remitting (11%, 15%) and secondary progressive (13%, 9%) but none with primary progressive MS. Presence of ring-enhancing lesions was significantly associated with a shorter time to reach EDSS (Expanded Disability Status Scale) 4.0 and 6.0 (hazard ratio 7.6, 95% confidence interval 2.3-24.6). CONCLUSIONS: Rim lesions and ring-enhancing lesions are present in close to 10% of patients with MS, and frequently both lesions appear independently one to the other. The association of ring enhancement with worst prognosis needs to be confirmed in prospective studies.

[Results of a functional magnetic resonance study of the primary auditory cortex (I): general characteristics and individual outcomes]. / Resultados en el estudio del córtex auditivo mediante resonancia magnética funcional (I): características generales y resultados individuales.

OBJECTIVE: To demonstrate and investigate the activation patterns of the primary auditory cortex (Heschl's gyrus) using functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: Pure tone stimuli at 750 Hz and 2000 Hz were delivered to the right and left ear of 32 normal-hearing volunteers (18-49 years old) in 20-second on-off cycles. The fMRI data were obtained using a 1.5 Tesla scanner and processed with SPM2. RESULTS: For both tone frequencies, bilateral hemispheric activation was identified in the transverse temporal gyrus (Heschl's gyrus) in 29 subjects (90.62 %) in response to pure tone stimuli with a probability level of p < 0.001. For monaural stimulation, bilateral hemispheric activation was observed with generally greater extent of activation in the Heschl's gyrus (HG) contralateral to the stimulated ear. CONCLUSIONS: These results demonstrate that fMRI is a useful imaging technique to investigate the auditory cortex. The contralateral auditory cortex is more responsive than the ipsilateral cortex to tones presented monaurally.

Olfactory Training Prevents Olfactory Dysfunction Induced by Bulbar Excitotoxic Lesions: Role of Neurogenesis and Dopaminergic Interneurons.

Glutamatergic excitotoxicity is involved in pathologies affecting the central nervous system, including traumatic brain injury (TBI) and neurodegenerative diseases, such as Parkinson's disease (PD), in which olfactory dysfunction is an early symptom. Interestingly, our group has recently shown that bilateral administration of the glutamate agonist, N-methyl-D-aspartate (NMDA) in the olfactory bulbs (OBs) induces an olfactory dysfunction 1 week after lesions. Although a wide range of treatments have been attempted, no standard therapy has been established to treat olfactory disorders. Increasing evidence suggests a beneficial effect of olfactory training (OT) in olfactory function. However, the mechanisms underlying OT effects remain unknown. We investigated the effects of OT on the olfactory dysfunction induced by excitotoxicity in bilateral OB NMDA-lesioned animals. We compared OT effects with the ones obtained with neuroprotective therapies (pramipexole and MK801). We studied the underlying mechanisms involved in OT effects investigating the changes in the subventricular zone (SVZ) neurogenesis and in the number of periglomerular dopaminergic interneurons. One week after lesion, NMDA decreased the number of correct trials in the olfactory discrimination tests in the non-trained group (p < 0.01). However, OT performed for 1 week after lesions prevented olfactory dysfunction (p < 0.01). Pramipexole did not prevent olfactory dysfunction, whereas MK801 treatment showed a partial recovery (p < 0.05). An increase in SVZ neurogenesis (p < 0.05) associated with an increase in OB dopaminergic interneurons (p < 0.05) was related to olfactory function prevention induced by OT. The present results suggest a role for dopaminergic OB interneurons underlying the beneficial effects of OT improving olfactory dysfunction in bilaterally OB NMDA-lesioned animals.

Factors of local recurrence and organ preservation with transoral laser microsurgery in laryngeal carcinomas; CHAID decision-tree analysis.

BACKGROUND: Indications of transoral laser microsurgery (TLM) are conditioned by the risk of local relapse. OBJECTIVE: To evaluate prognostic factors of local relapse and local control with TLM (LC-TLM). METHODS: Local relapse and LC-TLM were evaluated in 1119 patients. Logistic regression and CHAID decision tree analysis were performed. RESULTS: Local relapse correlated to previous radiotherapy failure (8.45, CI 95%: 2.64-27.03; P < .001), paraglottic involvement (2.42, CI: 1.41-4.15; P = .001), anterior commissure involvement (2.12, CI: 1.43-3.14; P < .001), grade of differentiation (1.74, CI: 1.18-2.57; P = .005), and alcohol consumption (1.4, CI: 0.99-1.98; P = .057). Local relapse tended to inversely correlate with experience (0.73, CI: 0.51-1.03; P = .078). The most important factors for local relapse were previous radiotherapy failure and anterior commissure involvement. LC-TLM inversely correlated with previous radiotherapy failure (0.09, CI: 0.03-0.28; P < .001), paraglottic involvement (0.25, CI: 0.14-0.43; P < .001), anterior commissure involvement (0.49, CI: 0.32-0.77; P = .007), margins (0.56, CI: 0.30-1.04; P = .068), and differentiation (0.68, CI: 0.44-1.05; P = .087). LC-TLM correlated with experience (1.71, CI: 1.13-2.55; P = .010). The most important factors for LC-TLM were previous radiotherapy failure and paraglottic involvement. CONCLUSION: Previous radiotherapy failure is the most important factor for local relapse and LC-TLM. In primary treatments, anterior commissure involvement and paraglottic involvement are the most important factors for local relapse and LC-TLM, respectively.

Assessing the long-term viability of facial fat grafts: an objective measure using computed tomography.

BACKGROUND: Autologous fat transplantation for soft tissue augmentation is a commonly used technique without a universally accepted approach. The literature includes a variety of reports describing varying degrees of success or failure. OBJECTIVE: To evaluate the behavior of facial fat grafts in humans with the use of an objective measuring tool. METHODS: A prospective randomized study, comparing patients pre- and postoperatively, was designed to evaluate the long-term viability of fat grafting. Participants were 18 men and 8 women between 34 and 59 years of age (mean, 45.07 yrs; standard deviation, 6.54 yrs). A total of 52 hemifaces in 26 patients diagnosed with HIV and demonstrating facial lipoatrophy were treated with fat transplantation using Coleman's technique. HIV-positive patients were chosen as study participants because their nearly total lack of subcutaneous fat diminishes the bias in the evaluation of fat volume. Fat graft viability was evaluated by measuring the volume of adipose tissue evolution via computed tomography scan before fat grafting, at the second month after fat grafting, and 1 year after fat grafting. Descriptive statistical analysis was performed. RESULTS: The mean volume on the right and left cheeks before fat grafting was 1.57 cc. The mean volume 2 months after the procedure was 2.93 cc with a statistically significant mean increase of 1.36 cc (P < .001) between baseline and the second month after the procedure. The mean volume after 12 months was 3.29 cc (P < .001), with a mean increase compared with the baseline of 1.72 cc, and of 0.36 cc between months 2 and 12. The statistically significant posttreatment improvement (P < .001) was maintained until month 12 of the follow-up period. CONCLUSIONS: Using objective measurement, this study demonstrates that with one fat grafting procedure a durable result can be achieved, persisting for a minimum of 12 months without any trend towards reabsorption.

Olfactory Training in Post-Traumatic Smell Impairment: Mild Improvement in Threshold Performances: Results from a Randomized Controlled Trial.

Traumatic Brain Injury (TBI) can be associated with partial or total smell loss. Recent studies have suggested that olfactory outcome can be positively modulated after olfactory training (OT). This study's aim was to investigate OT's potential role in smell recovery after TBI-induced olfactory loss. A prospective, randomized, and controlled study was developed. Patients with TBI-induced olfactory dysfunction (n = 42) were randomized into an experimental group with OT and a control group without (nOT). OT was performed twice daily with a six odor training set during 12 weeks. Olfactory loss was assessed using subjective olfactometry (Barcelona Smell Test [BAST] 24), a visual analogue scale (VAS), and n-butanol threshold (n-BTt) at baseline at 4, 12, and 24 weeks. Additionally, patients underwent MRI of the olfactory brain and olfactory bulbs (OB). Based on the MRI results, an overall score (0-16) was developed to associate the structural neurological damage with olfactory outcomes. The primary outcome was the change in olfactory measurements (VAS and BAST-24) between baseline and 12 weeks. The secondary outcome was the association of the MRI score with olfactory outcomes at baseline, and the impact on quality of life (QoL). After 12 weeks of training, OT patients showed a significant improvement in n-BTt (0.6 ± 1.7 OT vs. -0.6 ± 1.8 nOT, p < 0.05), but not in the smell VAS and BAST-24 scores. Olfactory outcomes (VAS, BAST-24, and n-BTt) were significantly associated with MRI structural findings (p < 0.001), but not with the OB volume or olfactory sulcus length. The present study suggests that 12 weeks of OT mildly improves the olfactory threshold in TBI, whereas the overall MRI score may be used as an imaging marker of olfactory dysfunction and disease severity in TBI patients.