The effects of surface electrical stimulation plus voice therapy in Parkinson's disease.

OBJECTIVE: This study aimed to assess the effects of surface electrical stimulation plus voice therapy on voice in dysphonic patients with idiopathic Parkinson's disease. METHOD: Patients were assigned to 3 treatment groups (n = 28 per group) and received daily treatment for 3 weeks on 5 days a week. All three groups received voice therapy (usual care). In addition, two groups received surface electrical stimulation, either motor-level or sensory-level stimulation. A standardised measurement protocol to evaluate therapeutic effects included the Voice Handicap Index and videolaryngostroboscopy. RESULTS: Voice Handicap Index and videolaryngostroboscopic assessment showed statistically significant differences between baseline and post-treatment across all groups, without any post-treatment differences between the three groups. CONCLUSION: Intensive voice therapy (usual care) improved idiopathic Parkinson's disease patients' self-assessment of voice impairment and the videolaryngostroboscopic outcome score. However, surface electrical stimulation used as an add-on to usual care did not improve idiopathic Parkinson's disease patients' self-assessment of voice impairment or the videolaryngostroboscopic outcome scores any further.

Swallowing Assessment in Parkinson's Disease: Patient and Investigator Reported Outcome Measures are not Aligned.

This study determines the relationship between patient and investigator reported outcome measures (PROMs versus IROMs) on oropharyngeal dysphagia (OD) in Parkinson's disease (PD). The PROMs used are the MD Anderson Dysphagia Inventory (MDADI) and the Dysphagia Severity Scale (DSS). The IROMs used are fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy of swallowing (VFS). Ninety dysphagic PD patients were included. Multilayer perceptron (MLP) neural network analysis was used to investigate the relationship between PROMs and IROMs on OD in PD. MLP neural network analysis showed a moderate agreement between PROMs and IROMs, with an area under the curve between 0.6 and 0.7. Two-step cluster analysis revealed several clusters of patients with similar scores on FEES and/or VFS variables, but with significant different scores on MDADI and DSS variables. This study highlights that there are PD patients with similar FEES and/or VFS findings that cannot be lumped together under the same pathophysiological umbrella due to their differences in PROMs. Since the exact origin of these differences is not fully understood, it seems appropriate for the time being to take into account the different dimensions of OD during the swallowing assessment so that they can be included in a patient-tailored treatment plan.

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts.

Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts.

[Delayed diagnosis of Huntington's disease in a psychiatric setting]. / Vertraagde diagnose van de ziekte van Huntington in een psychiatrische setting.

Huntington's disease (hd) is characterised by a triad of neuropsychiatric symptoms, motor disturbances and cognitive decline. If initial symptoms are of neuropsychiatric nature they maybe misinterpreted, which can lead to delayed diagnosis. Three examples of delayed hd diagnosis in a psychiatric setting are discussed.

Feasibility of electronic nose technology for discriminating between head and neck, bladder, and colon carcinomas.

Electronic nose (e-nose) technology has the potential to detect cancer at an early stage and can differentiate between cancer origins. Our objective was to compare patients who had head and neck squamous cell carcinoma (HNSCC) with patients who had colon or bladder cancer to determine the distinctive diagnostic characteristics of the e-nose. Feasibility study An e-nose device was used to collect samples of exhaled breath from patients who had HNSCC and those who had bladder or colon cancer, after which the samples were analyzed and compared. One hundred patients with HNSCC, 40 patients with bladder cancer, and 28 patients with colon cancer exhaled through an e-nose for 5 min. An artificial neural network was used for the analysis, and double cross-validation to validate the model. In differentiating HNSCC from colon cancer, a diagnostic accuracy of 81 % was found. When comparing HNSCC with bladder cancer, the diagnostic accuracy was 84 %. A diagnostic accuracy of 84 % was found between bladder cancer and colon cancer. The e-nose technique using double cross-validation is able to discriminate between HNSCC and colon cancer and between HNSCC and bladder cancer. Furthermore, the e-nose technique can distinguish colon cancer from bladder cancer.

Methadone is superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer.

BACKGROUND: Cancer pain is still inadequately treated in up to 60% of cancer patients. Based on the additional effect on the N-Methyl-d-Aspartate receptor, we expected that methadone (Met) could provide better pain relief than fentanyl (Fen) in cancer pain with a neuropathic pain component. METHODS: A randomised controlled trial was performed with 52 strong opioids naive patients with head-and-neck cancer with substantial pain (pain Numerical Rating Scale [NRS] > 4) and a neuropathic pain component (Douleur Neuropathique [DN4] > 4). Twenty-six patients were treated with Met and 26 with Fen. Patients were evaluated at 1, 3 and 5 weeks. The primary outcomes were reduction in average pain, clinical success (defined as 50% average pain decrease) and reduction in pain interference. Secondary outcomes were global perceived effect (GPE) and side-effects. FINDINGS: Reduction in NRS was higher with the use of Met at 1, 3 and 5 weeks (pain change 2.9, 3.1 and 3.1) compared to Fen (1.4, 1.7 and 2.0). This difference was significant at 1 (p = 0.011) and at 3 weeks (p = 0.03). Clinical success (>50% improvement) was higher with Met at 1 week (15% versus 50%, p = 0.012). The change in pain interference, the GPE and side-effect profile were not significantly different between the groups. INTERPRETATION: This is the first study to compare the effects of Met to Fen in cancer patients with a neuropathic pain component. Based on the results of this study, Met should be considered in the treatment of oncological pain with a neuropathic component.

Blood-brain barrier disruption during spontaneous canine visceral leishmaniasis.

Visceral leishmaniasis is a complex disease caused by Leishmania infantum, and in dogs, besides the classical symptoms, there are descriptions of inflammatory alterations in the brain. Brain inflammation is a strictly controlled process, and as the brain counts on the efficiency of the blood-brain barrier (BBB), we aimed to assess BBB integrity in dogs with spontaneous visceral leishmaniasis. Therefore, we evaluated markers in the cerebrospinal fluid (CSF) and in brain tissue related to BBB disruption and brain inflammation. Elevated albumin quota revealed BBB breakdown, corroborated by increased concentrations of anti-Leishmania antibodies in the CSF. In the brain, albumin and IgG staining formed halos around blood vessels, a classical indicator of BBB leakage. Soluble IgG was also detected in the choroid plexus and ependyma, and in these structures, IgG stained random resident cells. IgG(+) cells and Fcγ-RI(+) cells were identified in the choroid plexus, ependyma and perivascular in the brain parenchyma. The data support the occurrence of BBB disruption in dogs with spontaneous visceral leishmaniasis, and IgG as a key molecule that is capable of initiating and/or maintaining the inflammatory stimuli in the nervous milieu and the CSF as an important disseminator of inflammatory stimuli within the CNS.

Different prognostic models for different patient populations: validation of a new prognostic model for patients with oropharyngeal cancer in Western Europe.

OBJECTIVE: The presence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) is a major determinant in prognostic risk modelling. Recently, a prognostic model was proposed in which HPV status, comorbidity and nodal stage were the most important prognostic factors to determine high-, intermediate- and low-risk survival groups. Here, we report on the validation of this model using an independent single-institutional cohort. METHODS: A total number of 235 patients curatively treated for OPSCC in the period 2000-2011 at the MUMC (Maastricht University Medical Center, The Netherlands) were included. The presence of an oncogenic HPV infection was determined by p16 immunostaining, followed by a high-risk HPV DNA PCR on the p16-positive cases. The model variables included were HPV status, comorbidity and nodal stage. As a measure of model performance, the Harrell's Concordance index (Harrell's C-index) was used. RESULTS: The 5-year overall survival (OS) estimates were 84.6%, 54.5% and 28.7% in the low-, intermediate- and high-risk group, respectively. The difference between the survival curves was highly significant (P<0.001). The Harrell's C-index was 0.69 (95% confidence interval (CI): 0.63-0.75). CONCLUSION: In this study a previously developed prognostic risk model was validated. This model will help to personalise treatment in OPSCC patients. This model is publicly available at www.predictcancer.org.

[Subcutaneous nodules of the head and neck heralding giant cell arteritis]. / Nodules sous-cutanés cervico-céphaliques précédant l'apparition d'une artérite à cellules géantes.

BACKGROUND: Giant cell arteritis is the most common form of systemic vasculitis affecting individuals aged over 50 years. While its clinical manifestations are numerous, cutaneous involvement is uncommon and rarely constitutes the initial sign. We discuss a case of atypical skin involvement as the initial symptom of giant cell arteritis. OBSERVATION: An 86-year-old woman presented purplish and painful subcutaneous nodules on the scalp and neck. Biological explorations showed systemic inflammation. The skin biopsy was evocative of polyarteritis nodosa. The nodules spontaneously disappeared completely, and asthenia and bitemporal headache gradually appeared. In view of the persistent inflammatory syndrome, a diagnosis of giant cell arteritis was proposed and was later confirmed by the temporal artery biopsy sample, with its typical histological appearance. Systemic corticosteroids resulted in complete regression of symptoms within a few days. DISCUSSION: To our knowledge, inflammatory cervical subcutaneous nodules have never been described in giant cell arteritis. The case we report herein thus raises the issue of differential diagnosis between various forms of vasculitis. While classification of the latter continues to progress thanks to improvements in physiopathological knowledge, the distinction between vasculitis of the large and small vessels remains tenuous on occasion. We discuss the differential diagnoses. CONCLUSION: The dermatological presentation of giant cell arteritis in the present case suggests the existence of a continuum between small-, medium- and large-vessel vasculitis.

Allergic rhinitis is a risk factor for traffic safety.

BACKGROUND: Allergic rhinitis (AR) affects up to 30% of the adult population and symptomatic patients continue to engage in daily life activities, including car driving. Previous studies have shown that AR can impair cognitive functions, especially during longer-lasting tasks. Other reports suggest negative effects on psychomotor functions such as driving, but no clear evidence has been presented yet. OBJECTIVES: Primary objective was to determine the effect of AR per se on actual driving performance and compare it with the effects of treated AR. METHODS: Nineteen patients with documented AR history underwent a unique and validated 1-h on-the-road driving test outside the pollen season. In a 4-leg repeated measures design, patients underwent a nasal provocation test with either pollen or inactive control prior to the driving test. In the three conditions with pollen provocation, patients were pretreated with either cetirizine 10 mg, fluticasone furoate 27.5 µg, or placebo to alleviate the provoked AR symptoms. RESULTS: The driving performance of patients when symptomatic and not treated was significantly impaired compared to the placebo condition. When engaging in a secondary memory task during driving, their performance deteriorated further. The magnitude of impairment was relevant and comparable to that seen at a blood alcohol level of 0.05%, the legal limit in many countries. Treatment of AR symptoms partially counteracted the effect of AR on driving. CONCLUSIONS: Untreated AR can impair driving ability and put patients at risk. Drug therapy reduces this impairment, and AR patients should therefore be advised to always treat their condition.

Treatment effects for dysphagia in Parkinson's disease: a systematic review.

BACKGROUND: Dysphagia remains a common problem in Parkinson's disease (PD). Previous systematic reviews on therapy effects for oropharyngeal dysphagia in PD have shown a lack of evidence. In the past 5 years several placebo or sham-controlled trials with varying results have been published. OBJECTIVE: The aim of this systematic literature review is to summarize and qualitatively analyze the published studies on this matter. METHOD(S): Studies published up to December 2013 were found via a systematic comprehensive electronic database search using PubMed, Embase, and The Cochrane Library. Two reviewers independently assessed the studies using strict inclusion criteria. RESULT(S): Twelve studies were included and qualitatively analyzed using critical appraisal items. The review includes rehabilitative (exercises, electrical stimulation, bolus modification etc.) and pharmacologic treatment. Some well-designed controlled trials were included. However, none of the included studies fulfilled all criteria for external and internal validity. A meta-analysis was not carried out as most of the studies were not of sufficient quality to warrant doing so. CONCLUSION: Expiratory Muscle Strength Training (EMST) and Video-Assisted Swallowing Therapy (VAST) may be effective dysphagia treatments solely or in addition to dopaminergic therapy for PD. However, these preliminary results warrant further investigation concerning their clinical applicability, and further research should be based on randomized sham-controlled trials to determine the effectiveness and long-term effects of different therapies for dysphagia in PD.

[Embrace, a model for integrated elderly care]. / SamenOud, een model voor geïntegreerde ouderenzorg: studieprotocol van een gerandomiseerde studie naar de effectiviteit betreffende patiëntuitkomsten, kwaliteit van zorg, zorggebruik en kosten.

UNLABELLED: Ongoing growth in health care expenditures and changing patterns in the demand for health care challenge societies worldwide. The Chronic Care Model (CCM), combined with classification for care needs based on Kaiser Permanente (KP) Triangle, may offer a suitable framework for change. The aim of the present study is to investigate the effectiveness of Embrace, a population-based model for integrated elderly care, regarding patient outcomes, service use, costs, and quality of care. METHODS: The CCM and the KP Triangle were translated to the Dutch setting and adapted to the full elderly population living in the community. A randomized controlled trial with balanced allocation was designed to test the effectiveness of Embrace. Eligible elderly persons are 75 years and older and enrolled with one of the participating general practitioner practices. Based on scores on the INTERMED-Elderly Self-Assessment and Groningen Frailty Indicator, participants will be stratified into one of three strata: (A) robust; (B) frail; and (C) complex care needs. Next, participants will be randomized per stratum to Embrace or care as usual. Embrace encompasses an Elderly Care Team per general practitioner practice, an Electronic Elderly Record System, decision support instruments, and a self-management support and prevention program - combined with care and support intensity levels increasing from stratum A to stratum C. Primary outcome variables are patient outcomes, service use, costs, and quality of care. Data will be collected at baseline, twelve months after starting date, and during the intervention period. DISCUSSION: This study could provide evidence for the effectiveness of Embrace.

Chromosome instability predicts the progression of premalignant oral lesions.

OBJECTIVES: One of the main problems in reducing the incidence of oral squamous cell carcinoma (OSCC) is the inability to appropriately deal with leukoplakia. Accurately identifying lesions which will progress to malignancy is currently not possible. The present study aims to establish the value of chromosome instability (CI) detection by DNA image cytometry and FISH analysis for prognosis and monitoring of oral leukoplakia. MATERIALS AND METHODS: For this purpose, we included from our archives 102 oral leukoplakia cases, which had been diagnosed between 1991 and 2008. Patient follow-up data were collected and the histopathological diagnosis was revised. CI assessment was carried out on paraffin-embedded tissue sections using both DNA image cytometry (ICM) and dual target FISH for chromosomes 1 and 7. RESULTS: 16 of 102 Patients developed carcinoma in situ or OSCC. Both detection methods were found to yield prognostic information independent of the histopathological diagnosis. CI was a strong individual marker of progression, with hazard ratios (HRs) of 7.2 and 6.8 for ICM and FISH respectively. Moreover, this approach seems suitable for monitoring lesions over time (especially ICM). Combining histopathology and CI enables subdivision of patients into three risk groups, with different probabilities of malignant progression. CONCLUSION: CI detection seems a reliable method for risk assessment of oral premalignancies and its application may contribute to a better risk-counselling and appropriate treatment regimen or watchfull-waiting approach of patients.

Definitive radiation therapy for treatment of laryngeal carcinoma: impact of local relapse on outcome and implications for treatment strategies.

PURPOSE: The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures. METHODS AND MATERIALS: In all, 435 patients with laryngeal carcinoma (cT1-cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival. RESULTS: Median follow-up was 38 months (range 1-144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10%, cT2 18%, cT3 23%, and cT4 36% (p<0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76%). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68% for cT1, cT2, cT3, and cT4 tumors (p<0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26% (p<0.001), respectively. Overall survival at 5 years was 68% for patients without local relapse and 50% for patients experiencing local failure (p<0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3-4 tumors, only tumor volume remained statistically significant (HR 1.017, p=0.001) for local relapse-free survival. CONCLUSION: Local control rates for cT1-2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3-4 tumors treated with RT alone, initial local control rates are moderate, and in 60% of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy or radiochemotherapy.

Dating carbonaceous matter in archean cherts by electron paramagnetic resonance.

Ancient geological materials are likely to be contaminated through geological times. Thus, establishing the syngeneity of the organic matter embedded in a mineral matrix is a crucial step in the study of very ancient rocks. This is particularly the case for Archean siliceous sedimentary rocks (cherts), which record the earliest traces of life. We used electron paramagnetic resonance (EPR) for assessing the syngeneity of organic matter in cherts that have a metamorphic grade no higher than greenschist. A correlation between the age of Precambrian samples and the shape of their EPR signal was established and statistically tested. As thermal treatments impact organic matter maturity, the effect of temperature on this syngeneity proxy was studied; cyanobacteria were submitted to cumulative short thermal treatment at high temperatures followed by an analysis of their EPR parameters. The resulting carbonaceous matter showed an evolution similar to that of a thermally treated young chert. Furthermore, the possible effect of metamorphism, which is a longer thermal event at lower temperatures, was ruled out for cherts older than 2 Gyr, based on the study of Silurian cherts of the same age and same precursors but various metamorphic grades. We determined that even the most metamorphosed sample did not exhibit the lineshape of an Archean sample. In the hope of detecting organic contamination in Archean cherts, a "contamination-like" mixture was prepared and studied by EPR. It resulted that the lineshape analysis alone does not allow contamination detection and that it must be performed along with cumulative thermal treatments. Such treatments were applied to three Archean chert samples, making dating of their carbonaceous matter possible. We concluded that EPR is a powerful tool to study primitive organic matter and could be used in further exobiology studies on low-metamorphic grade samples (from Mars for example).

Late Devonian marine anoxia challenged by benthic cyanobacterial mats.

Mass occurrence of benthic cyanobacterial mats in a sequence of Late Devonian black shales and bituminous limestones of the Holy Cross Mts. (central Poland), enclosing the famous Kellwasser and Hangenberg extinction horizons, is reported. The microbiota forming the mats is compared with some modern benthic chroococcalean cyanobacteria. Similarly to their extant counterparts, the Devonian cyanobacteria must had been phototrophic and oxygenic aerobes which could, however, tolerate slightly sulfidic conditions characterizing the near-bottom waters of the Late Devonian epicontinental sea. The cyanobacterial mats successfully colonized the oxygen-deficient and H(2)S-enriched seabed otherwise unfavorable for most other benthic biota. The redox state of this sluggish Late Devonian sea, ascribed previously mostly to anoxic or euxinic conditions, is reassessed as probably pulsating between anoxic, dysoxic, and weakly oxic conditions. The redox state was dependent on the rate of oxygen production by the cyanobacterial mats, the intensity of H(2)S emissions from the decaying mat biomass, and the rate of planktonic production.

Autosomal recessive cerebellar ataxias: the current state of affairs.

Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, and the genetic heterogeneity often complicate the clinical management of such patients. Despite the steady increase in newly discovered ARCA genes, many patients with a putative ARCA cannot be genotyped yet, proving that more genes must be involved. This review presents an updated overview of the various ARCAs. The clinical and genetic characteristics of those forms with a known molecular genetic defect are discussed, along with the emerging insights in the underlying pathophysiological mechanisms.

3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy.

OBJECTIVE: 3-Methylglutaconic aciduria type I is a rare inborn error of leucine catabolism. It is thought to present in childhood with nonspecific symptoms; it was even speculated to be a nondisease. The natural course of disease is unknown. METHODS: This is a study on 10 patients with 3-methylglutaconic aciduria type I. We present the clinical, neuroradiologic, biochemical, and genetic details on 2 new adult-onset patients and follow-up data on 2 patients from the literature. RESULTS: Two unrelated patients with the characteristic biochemical findings of 3- methylglutaconic aciduria type I presented in adulthood with progressive ataxia. One patient additionally had optic atrophy, the other spasticity and dementia. Three novel mutations were found in conserved regions of the AUH gene. In both patients, MRI revealed extensive white matter disease. Follow-up MRI in a 10-year-old boy, who presented earlier with isolated febrile seizures, showed mild abnormalities in deep white matter. CONCLUSION: We define 3-methylglutaconic aciduria type I as an inborn error of metabolism with slowly progressive leukoencephalopathy clinically presenting in adulthood. In contrast to the nonspecific findings in pediatric cases, the clinical and neuroradiologic pattern in adult patients is highly characteristic. White matter abnormalities may already develop in the first decades of life. The variable features found in affected children may be coincidental. Long-term follow-up in children is essential to learn more about the natural course of this presumably slowly progressive disease. Dietary treatment with leucine restriction may be considered.