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Cellular senescence has been identified as a pathological mechanism linked to tau and amyloid beta (Aβ) accumulation in mouse models of Alzheimer's disease (AD). Clearance of senescent cells using the senolytic compounds dasatinib (D) and quercetin (Q) reduced neuropathological burden and improved clinically relevant outcomes in the mice. Herein, we conducted a vanguard open-label clinical trial of senolytic therapy for AD with the primary aim of evaluating central nervous system (CNS) penetrance, as well as exploratory data collection relevant to safety, feasibility, and efficacy. Participants with early-stage symptomatic AD were enrolled in an open-label, 12-week pilot study of intermittent orally-delivered D+Q. CNS penetrance was assessed by evaluating drug levels in cerebrospinal fluid (CSF) using high performance liquid chromatography with tandem mass spectrometry. Safety was continuously monitored with adverse event reporting, vitals, and laboratory work. Cognition, neuroimaging, and plasma and CSF biomarkers were assessed at baseline and post-treatment. Five participants (mean age: 76±5 years; 40% female) completed the trial. The treatment increased D and Q levels in the blood of all participants ranging from 12.7 to 73.5 ng/ml for D and 3.29-26.30 ng/ml for Q. D levels were detected in the CSF of four participants ranging from 0.281 to 0.536 ng/ml (t(4)=3.123, p=0.035); Q was not detected. Treatment was well-tolerated with no early discontinuation and six mild to moderate adverse events occurring across the study. Cognitive and neuroimaging endpoints did not significantly differ from baseline to post-treatment. CNS levels of IL-6 and GFAP increased from baseline to post-treatment (t(4)=3.913, p=008 and t(4)=3.354, p=0.028, respectively) concomitant with decreased levels of several cytokines and chemokines associated with senescence, and a trend toward higher levels of Aβ42 (t(4)=-2.338, p=0.079). Collectively the data indicate the CNS penetrance of D and provide preliminary support for the safety, tolerability, and feasibility of the intervention and suggest that astrocytes and Aβ may be particularly responsive to the treatment. While early results are promising, fully powered, placebo-controlled studies are needed to evaluate the potential of AD modification with the novel approach of targeting cellular senescence.

Background Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer’s disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [18F]FPEB to investigate mGluR5 binding in early AD. Methods Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [18F]FPEB using a bolus-plus-constant-infusion method (Kbol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [18F]FPEB binding (BPND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects. Results Linear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BPND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BPND = 0.76 ± 0.41) compared to CN (BPND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BPND = 1.57 ± 0.25) compared to CN (BPND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function. Conclusions [18F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments.

Wernekinck commissure syndrome should be considered in the cases of acute bilateral ataxia.

In the last few years, an improved understanding of dementia biomarkers has significantly increased the diagnostic accuracy for dementias. The National Institutes of Health Biomarkers Definitions Working Group defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” In the field of dementia, a biomarker is a biological measure pointing to a specific dementing pathology. Dementia biomarkers may also serve as surrogates for disease progression and as endpoints in clinical trials. Dementia biomarkers are best characterized for Alzheimer's disease, which is the most common form of primary dementia. The current “biological” conception of Alzheimer's disease is based on consideration of three biomarkers: amyloid, tau, and “neurodegeneration.” The status of these biomarkers may be determined by cerebrospinal fluid clinical chemistry or imaging. Biomarkers for other primary dementias are less reliable and rely chiefly on structural and functional imaging. When appropriate, genetic testing may help with diagnostic certainty in hereditary forms of dementia.

Mild cognitive impairment (MCI) represents an intermediate stage between normal cognition and dementia. Individuals with MCI are at increased risk of conversion to dementia, and the rate of progression of MCI to dementia is dependent on age, gender, and education. MCI may be diagnosed using neuropsychological criteria using cut-offs representing decrements in cognition, or using criteria to assess for a decline in functional status. The ability to determine the status of dementia-related biomarkers has allowed for better staging and prognostication in different forms of MCI. MCI is now recognized as a significant target stage for future therapies. These future therapies aim to reduce the rate of conversion of individuals with MCI to dementia. In this article, we review different conceptions of MCI, the diagnosis and prognostication of MCI, and presently available management approaches for this condition.

Dementia is a state of cognitive dysfunction which leads to functional decline. It is a syndrome caused by several medical and neurological causes, but most cases of dementia are due to “primary dementias.” Primary dementias are neurological diseases whose manifestations are predominantly cognitive. Most primary dementias are caused by neurodegenerative proteinopathies where an accumulation of misfolded proteins leads to neuronal loss, neuroinflammation and glial reaction. Each proteinopathy is characterized by the type of protein implicated in its pathophysiology. Neurodegenerative dementias include the most prevalent cause of dementia—Alzheimer's disease—as well as Lewy body dementia, Parkinson's disease dementia, frontotemporal dementias, and prion diseases. Vascular dementia, especially small vessel disease, though not a neurodegenerative condition, is often grouped together with primary dementias. Each type of proteinopathy, characterized by the location and nature of misfolded protein accumulation, may correspond to a particular clinical phenotype. The correspondence between pathologies and clinical phenotypes is not exclusive, and there is a large degree of overlap. Although in the research setting the clinicopathological construct is on the wane, in the clinic it is the most practical way of approaching primary dementias. In this article, we introduce the clinicopathological construct, the understanding of which will form the basis of the other articles in this volume.

Treatment of dementias represents an important but relatively neglected part of neurological care of the elderly population. Individual therapeutic interventions may make only small changes to the quality of life of individuals afflicted with dementia, but when used in combination these interventions synergize and can make a significant difference. Additionally, given the societal scale of the problem of dementia care, the overall impact, in economic and sociological terms, of such therapies is of consequence. Presently there are no disease-modifying treatments for any of the neurodegenerative dementias. Instead, the clinician has several therapeutic tools to mitigate cognitive and behavioral consequences of dementias. There are also strategies to minimize harm to patients with dementia. In this article, we aim to review these tools and place them in the greater context of dementia care.

Henry VIII of England is one of the most controversial figures in European history. He was born on 28 June 1491 as the second son of Henry VII and Elizabeth of York and became the heir to the English throne after his elder brother died prematurely. A contradictory picture of Henry's character emerges from history: the young Henry was a vigorous, generous and intelligent king who saw early military and naval successes. In contrast, in his later years he became cruel, petty and tyrannical. His political paranoia and military misjudgements are in direct contrast to his earlier successes and promise. Several hypotheses have been put forward regarding his transformation from a renaissance king to a later medieval tyrant, including endocrinopathies, psychiatric illnesses and traumatic brain injury. In this paper we examine the historical evidence linking the change in Henry's personality and health problems to traumatic brain injury. To our knowledge this is the first systematic neurological study of traumatic brain injury in Henry VIII.

Introduction Just-in-time teaching is an educational strategy that involves tailoring in-session learning activities based on student performance in presession assessments. We implemented this strategy in a third-year neurology clerkship. Methods Linked to core neurology clerkship lectures, eight brief video-based lectures and knowledge assessments were developed. Students watched videos and completed multiple-choice questions, and results were provided to faculty, who were given the opportunity to adjust the in-person lecture accordingly. Feedback was obtained by surveys of students and faculty lecturers and from student focus groups and faculty. Student performance on the end-of-clerkship examination was analyzed. Results Between October 2016 and April 2017, 135 students participated in the curriculum, and 56 students (41.5%) responded to the surveys. Most students agreed or strongly agreed that the new curriculum enhanced their learning and promoted their sense of responsibility in learning the content. Faculty agreed that this pedagogy helped prepare students for class. Most students watched the entire video-based lecture, although there was a trend toward decreased audience retention with longer lectures. There were no significant changes in performance on the end-of-clerkship examination after implementation of just-in-time teaching. In focus groups, students emphasized the importance of tying just-in-time teaching activities to the lecture and providing video-based lectures well in advance of the lectures. Discussion Just-in-time teaching using video-based lectures is an acceptable and feasible method to augment learning during a neurology clinical clerkship. We believe this method could be used in other neurology clerkships with similar success.

Myocardial perfusion imaging has long been used off label by practitioners attending for children with cardiac aliments. To provide clinicians with evidence-based dosage recommendation, a phase I-II, open-label, nonrandomized, multicenter trial was therefore designed using (99m)Tc-sestamibi in pediatric subjects (registered under www.clinicaltrials.gov identifier no. NCT00162045).Safety and pharmacokinetic data were collected from 78 subjects using either a 1-d imaging protocol (3.7-7.4 MBq/kg, followed by 11.1 MBq/kg) or a 2-d protocol (7.4 MBq/kg for both rest and stress). Anterior and posterior planar images were collected at 15 min, 1.5 h, 4 h, and 8 h. Blood and urine samples were collected at predetermined times.Subjects included 39 children (mean age ± SD, 8.5 ± 2.04 y) and 39 adolescents (mean age ± SD, 13.6 ± 1.39 y). Mean estimated organ-absorbed doses to the upper large intestine, small intestine, gallbladder wall, and lower large intestines were 0.082, 0.043, 0.042, and 0.035 mSv/MBq, respectively. All patients tolerated the radiotracer without serious adverse effects. Significant differences were observed in the liver, upper large intestine contents, and small intestine contents between rest and stress imaging. The effective dose equivalent and effective dose averages were lower in adolescents than younger children (0.011 and 0.019 mSv/MBq, respectively; P0.0001). Percentage injected doses (%IDs) corrected for radioactive decay in all dosimetry-evaluable subjects at 15 min and 4 h were 1.9% and 1.2% in the myocardium. Similarly in the lungs, the %ID for all dosimetry-evaluable subjects was 4.9% at 15 min after injection. At rest, the %ID in the liver decreased from a maximum of about 26% at 15 min to less than 9% at 90 min. With stress, values decreased from 15% to 7%, respectively.The estimates of radiation dosimetry, pharmacokinetic parameters, and safety profile in this study population are similar to published studies based on body-mass extrapolations from studies in adults. As such, applying current (99m)Tc-sestamibi dosing regimens for 1- and 2-d protocols based on those extrapolations will result in the expected radiation dose in children and adolescents.

Cognitive decline is an all-too frequent downstream consequence of stroke. Dementia associated with vascular disease has variable presentations and limited treatment options. Identifying these patients early, however, may enable the patient and family to adapt and develop techniques to work around the deficits. Here, we highlight the variable presentations of dementia associated with vascular disease, proper evaluation methods, and treatment options.

Oral Squamous Cell Carcinoma (OSCC) remains a public health scourge. Radiotherapy (RT) is a major treatment modality and has been implicated in possible formation of Second Primary Tumours (SPT). In a single centre retrospective study of 370 patients with OSCCs (1967-2004) associations between RT, diagnosis of SPTs, median SPT diagnostic time lag, Disease Free Survival (DFS) and overall survival (OS) were analysed. Sixty-eight (18.4%) patients developed metachronous SPTs. Two hundred and twenty patients (59.3%) underwent some form of RT whilst 151 (40.7%) patients were not exposed to RT. No significant increased incidence of SPTs was demonstrated in the RT group. No significant difference in SPT diagnostic time lag was noted amongst the groups. This study suggests that RT is neither a risk for SPT induction nor increases the relative diagnostic time delay of upper aero-digestive tract SPTs.

Objectives: Second primary tumors (SPTs) have been implicated in poor overall survival (OS) of head and neck squamous cell carcinomas (HNSCCs). Confusion remains regarding their actual incidence and prognostic impact. This study assessed the incidence of SPTs; the SPT diagnostic time lag; the impact on OS; and the mean annual risk. Methods: Nine hundred eighty seven consecutive patients treated for primary larynx SCC (1967-2004) were analyzed in this study. 96.3% and 91.4% of patients reached a minimum follow-up period of 3 and 5 years. Results: Two hundred eight (21.1%) patients were diagnosed with SPTs. One hundred forty three (14.5%) patients developed upper aerodigestive tract (UAD)-SPTs, 83 (8.4%) were HNSCCs, 56 (5.7%) were lung, and 4 (0.41%) were esophageal-SPTs. Survival analysis demonstrated clear superior OS rates for the UAD-SPT (P

Background: Field cancerization is a feature of head and neck squamous cell carcinoma. No biological marker in the index tumour has been correlated to the development of second primary tumours (SPT). Cyclin A1 is a cell cycle regulator and a downstream target of p53. This study assessed predictive correlation of cyclin A1 and mut-p53 with clinicopathological parameters and occurrence of (SPT) 7in the head and neck. Methods: Using immunohistochemistry 106 patients treated for primary laryngeal squamous cell carcinoma were investigated for expression of cyclin A1 and mut-p53. Results: Expression of cyclin A1 and mut-p53 were noted in 83 of 106 (78.3%) and 25 of 106 (23.6%) patients. There was a weak but significant correlation between mut-p53 and cyclin A1 (r = 0.301, P = 0.002) expression. During the follow-up period (median 41.0 months (range 1-205 months)), 21 of 106 (19.8%) patients developed an SPT. There was no statistically significant correlation between the markers investigated and disease recurrence, SPT diagnosis or clinicopathological parameters. Conclusion: Second primary tumours are an intriguing problem in treatment of HNSCC and a predictive marker identifying those greatest at risk would be a leap forward.

A 55-year-old woman sought assistance for intractable pruritus of 6-year duration, affecting the right side of the forehead. She had surgery on the right frontal area for treatment of a frontal sinus condition, a few years earlier. The itch failed to respond to a variety of medical interventions, including oral antipruritic agents and local injections of anesthetic. Administration of botulinum toxin A (Allergan Inc, Irvine, CA) into the pruritic area resulted in a significant relief of pruritus in this patient.

• We present a 39 year old woman with hereditary spastic paraparesis and cognitive impairment.

The organisation and cytoarchitecture of the serotonergic neurons in a diprotodont marsupial were examined by using serial sections of the brainstem processed for serotonin immunohistochemistry and routine histology. The topographic distribution of serotonergic neurons in the brainstem of the adult wallaby (Macropus eugenii) was similar to that of eutherian mammals. Serotonergic neurons were divided into rostral and caudal groups, separated by an oblique boundary through the pontomedullary junction. Approximately 52% of the serotonergic neurons in the wallaby brainstem were located in the rostral midline nuclei (caudal linear nucleus, dorsal, median, and pontine raphe nuclei and the interpeduncular nucleus), whereas 21% were found in the caudal midline region (nuclei raphe magnus, obscurus, and pallidus). The remaining serotonergic neurons (27%) were located in more lateral regions such as the pedunculopontine tegmental nuclei, the supralemniscal nuclei (B9 group), and the ventrolateral medulla. The largest serotonergic group, the dorsal raphe, contained one-third of the brainstem serotonergic neurons and showed five subdivisions, similar to that described in other species. In contrast, the median raphe did not show clear subdivisions. The internal complexity of the raphe nuclei and the degree of lateralisation of serotonergic neurons suggest that the wallaby serotonergic system is similar in organisation to that described for the cat and rabbit. This study supports the suggestion that the serotonergic system is evolutionally well conserved and provides baseline data for a quantitative study of serotonergic innervation of the developing cortex in the wallaby. J. Comp. Neurol. 411:535–549, 1999. © 1999 Wiley-Liss, Inc.

Intracranial hypotension (IH) has been a known entity in neurocritical care since 1938. Even though many cases are spontaneous, the incidence of intracranial hypotension in the neurocritical care setting is increasing by virtue of the increased number of neurosurgical interventions. Whether spontaneous or secondary in etiology, diagnosis of IH usually requires the presence of orthostatic symptoms, including headaches and nausea with low opening CSF pressure. However, typical clinical features in the appropriate clinical context and imaging, even with normal CSF pressure, can indicate IH. In the neurocritical care setting, challenges for accurate semiology include altered sensorium and reduced levels of responsiveness for which many etiologies may exist, including metabolic dysfunction, traumatic brain injury, IH, or nonconvulsive status epilepticus (NCSE). The authors describe 3 patients whose clinical picture and electroencephalography (EEG) findings initially suggested NCSE but who did not respond to treatment with antiepileptic drugs alone. Neuroimaging suggested IH, and subsequent treatment of IH successfully improved the patient's clinical status. To the authors' knowledge this paper is the first in the literature that reports a correlation of IH with electrographic findings similar to NCSE as cause and effect. The authors' hypothesis is that thalamocortical dysfunction causes EEG findings that appear to be similar to those in NCSE but that these conditions do not coexist. The EEG activity is not epileptogenic, and IH results in blocking network pathways producing thalamocortical dysfunction. The authors discuss the hypothesis and pathophysiology of these epileptiform changes in relation to IH.

Neuromuscular diseases are conditions of the motor unit affecting the nervous system, inclusively between the anterior horn cells and the muscle. The occurrence of some of these conditions can lead to admission to the intensive care unit (ICU): weakness can impair breathing and disrupt airway protection. Many neuromuscular diseases are also associated with autonomic instability. Furthermore, critically ill patients may develop neuromuscular involvement as a consequence of long ICU stays. In this chapter, we describe a general approach to the problems of the neuromuscular disease in the neurological ICU.

Posterior reversible encephalopathy syndrome (PRES) can present with focal neurologic deficits, mimicking a stroke and can often represent a diagnostic challenge when presenting atypically. A high degree of suspicion is required in the clinical setting in order to yield the diagnosis. Cerebral CT perfusion (CTP) is utilized in many institutions as the first line in acute stroke imaging. CTP has proved to be a very sensitive measure of cerebral blood flow dynamics, most commonly employed to delineate the infarcted tissue from penumbra (at-risk tissue) in ischemic strokes. But abnormal CTP is also seen in stroke mimics such as seizures, hypoglycemia, tumors, migraines and PRES. In this article we describe a case of PRES in an elderly bone marrow transplant recipient who presented with focal neurological deficits concerning for a cerebrovascular accident. CTP played a pivotal role in the diagnosis and initiation of appropriate management. We also briefly discuss the pathophysiology of PRES.

Objective: Second primary tumours (SPT) have been implicated in the dismal overall survival (OS) of head and neck Squamous cell carcinomas (HNSCC). The incidence of SPT, the SPT diagnostic time-lag and the impact on OS were assessed. Subjects and methods: 363 consecutive patients treated for primary Oral SCCs (1967-2004) were analyzed retrospectively in this study. 95.1% and 90.5% of patients reached a minimum follow-up period of 3 and 5 years respectively. Results: Of 363 patients; 68 (18.7%) were diagnosed with metachronous SPT, 49 (13.5%) developed upper aerodigestive tract (UAD)-SPT, 28 (7.7%) were diagnosed with HNSCC-SPT, and 21 (5.8%) developed lung or esophageal carcinoma. Patients with subsequent HNSCC-SPT had a better median survival during follow-up than those not diagnosed with SPTs (p=0.0018). The rate of mortality in these patients showed a substantial increase compared to patients with no subsequent SPT Diagnosis after 144 months. After 200 months the survival experience was no better than those without SPT. Conclusion: These results suggest a better OS for patients afflicted with HNSCC-SPT. This also reflects that at least some of the noted improved OS of HNSCC-SPT patients is due to temporally cumulated risk associated with developing SPT.

Objective. To investigate the efficacy and tolerability of Botulinum toxin A (BoNT-A) in allodynia of patients with complex regional pain syndrome. Design. A total of 14 patients were studied. Eight patients were participants of a randomized, prospective, double-blind, placebo-controlled protocol. Six patients were studied prospectively in an open-label protocol. Patients were rated at baseline and at 3 weeks and 2 months after BoNT-A administration. Ratings included brief pain inventory, McGill pain questionnaire, clinical pain impact questionnaire, quantitative skin sensory test, sleep satisfaction scale, and patient global satisfaction scale. BoNT-A was injected intradermally and subcutaneously, five units/site into the allodynic area (total dose 40–200 units). Results. None of the patients with allodynia showed a significant response after treatment. The treatment was painful and poorly tolerated. Conclusion. Intrademal and subcutaneous administration of BoNT-A into the allodynic skin of the patients with complex regional pain syndrome (CRPS) failed to improve pain and was poorly tolerated.

Second primary tumors (SPTs) have been implicated in poor overall survival (OS) of head and neck squamous cell carcinomas (HNSCCs). Confusion remains regarding their actual incidence and prognostic impact. This study assessed the incidence of SPTs; the SPT diagnostic time lag; the impact on OS; and the mean annual risk.Nine hundred eighty seven consecutive patients treated for primary larynx SCC (1967-2004) were analyzed in this study. 96.3% and 91.4% of patients reached a minimum follow-up period of 3 and 5 years.Two hundred eight (21.1%) patients were diagnosed with SPTs. One hundred forty three (14.5%) patients developed upper aero-digestive tract (UAD)-SPTs, 83 (8.4%) were HNSCCs, 56 (5.7%) were lung, and 4 (0.41%) were esophageal-SPTs. Survival analysis demonstrated clear superior OS rates for the UAD-SPT (P0.008) and HNSCC-SPT (P0.001) groups. A comparison of survival of subgroups showed lung/esophagus to have a poorer survival when compared to all other subgroups. OS after diagnosis of an SPT was poorer when compared with no-SPT group (P0.001). The mean annual risk of developing UAD-SPTs was 2.4%.These results suggest that HNSCC-SPT should not be viewed as an adverse prognostic factor. Reclassifications of UAD-SPTs into HNSCC-SPT and non-HNSCC-SPT better reflects their clinical behavior and prognosis.

Background. Field cancerization is a feature of HNSCCs. No biological marker in the index tumor has correlated with second primary tumor (SPTs) development. Changes in MDM-2 and epidermal growth factor receptor (EGFR) expression are known to be early neoplastic changes in HNSCC. EGFR expression is correlated with clinical outcomes. This study has assessed the predictive correlation of MDM-2 and EGFR protein expression with clinicopathological parameters and occurrence of SPTs in HNSCC. Methods. Using immunohistochemistry, 106 patients who were treated for primary laryngeal squamous cell carcinoma were investigated for expression of MDM-2 and EGFR. Results. Positive expression of MDM-2 and EGFR was found in 51 of 106 (48.1%) and 82 of 106 (77.4%) cases, respectively. EGFR expression was found to correlate with diagnosis of new primary tumors (P = 0.003), disease-free survival (P = 0.008), as well as overall survival (P = 0.003). MDM-2 expression correlated with nodal relapse (P = 0.03). Conclusions. SPTs relate to poor prognosis in HNSCC, indicating that closer clinical surveillance of this patient group would be beneficial. Examination of the expression of EGFR by the primary tumor could have potential clinical benefits because this study suggests that it may become a vital biomarker for patients who are most at risk of developing SPTs.

Aims: Larynx cancer is the most common form of head and neck squamous cell carcinoma (HNSCC). Radiotherapy is a major treatment modality and is implicated in the possible formation of second primary tumours (SPT). The aims of this retrospective study were to establish the incidence of SPTs and their correlation with previous radiotherapy and to establish overall survival and the SPT diagnostic time lag from the index tumour according to subtype as well as radiotherapy status. Materials and methods: In a retrospective study of 987 patients with larynx SCCs (1967-2004) associations between radiotherapy, diagnosis of SPTs, median SPT diagnostic time lag, disease-free survival and overall survival were analysed. Results: In total, 184 (18.6%) patients developed metachronous SPTs with an overall survival of 93.0 (standard error 6.8 months). One hundred and seventy (92.4%) underwent radiotherapy, whereas 14 (7.6%) patients were not exposed to radiotherapy. No significant increased incidence of SPT was shown in the radiotherapy group. A statistically non-significant increase in SPT diagnostic time lag trend was noted for both HNSCC SPTs (radiotherapy vs non-radiotherapy; 76.0 [standard error 6.7] vs 50.0 [standard error 23.0]) and lung SPTs (45.0 [standard error 12.1] vs 24.0 [standard error 4.9]) months. Conclusion: This study suggests that radiotherapy is not a risk for SPT induction; it may, however, neutralise a proportion of cancerised fields in the lung and head and neck areas without any significant benefit on overall survival.

Three patients with Sjogren's syndrome are presented in whom frequent tonic/dystonic spasms of the limbs developed during the course of the illness. These patients' clinical findings suggested spinal cord involvement, a localization that was confirmed by magnetic resonance imaging in two patients. In one patient the painful movements responded to treatment with phenytoin and in one other to baclofen. Sjogren's syndrome should be considered in the differential diagnosis of conditions that produce tonic/dystonic limb spasms.

Objective: To ascertain the relationship between depression score and visual analogue mood scale, quality of life and motor severity in Parkinson9s disease. Background Depression is the most common non-motor manifestation of Parkinson disease (PD), affecting up to 40 to 50 % of PD patients, far in excess of its prevalence of 6.7% in the general American population. Design/Methods: All patients seen at the University of Florida Movement Disorders Center, with a confirmed PD diagnosis and a recorded Beck Depression Inventory (BDI) on their first visit were included in this study. Using a cutoff of 14, we determined the prevalence of depressive symptoms in our whole population, in men versus women and in drug naive versus those treated with levodopa. Results: The depressed cohort had a mean BDI score of 19.41 whereas the mean for the non-depressed was 7.06. The HY with the last two having negative coefficients. The best predictor, not surprisingly was the SadTscore. Overall there is not a strong correlation between VAMS and BDI. Conclusions: There is a correlation between the severity of motor symptoms and the presence of depression pointing to the possibility of both organic and reactive components in PD depression. There was only poor correlation between the VAMS score and BDI, but the quality of life PDQ-39 paralleled the BDI score raising questions whether this is cause or effect. Disclosure: Dr. Salardini has nothing to disclose. Dr. Rodriguez has received personal compensation for activities with Allergan, Merz Pharmaceuticals, Lundbeck and Teva Pharmaceuticals as a consultant. Dr. Malaty has received research support from The National Parkinson Foundation. Dr. Okun has received personal compensation for activities with National Parkinson Foundation, Ask the Expert, and Neuropace Devices. Dr. Okun has received research support from the Michael J. Fox Foundation, the National Parkinson Foundation, the Parkinson Alliance and the National Institutes of Health. Dr. Fernandez has received personal compensation for activities with USF CME, Cleveland Clinic CME, Medical Communications Media, Health Professions Conferencing, Ipsen, Merz Pharmaceuticals, and US World Meds Dr. Fernandez has received personal compensation in an editorial capacity for the Movement Disorders Society Website. Dr. Fernandez has received royalty payments from Demos Publishing, Manson Publishing, and Springer Publishing. Dr. Fernandez has received research support from Abbott, Acadia, Biotie Therapeutics, EMD-Serono, Huntington Study Group, Ipsen, Merz Pharmaceuticals, Michael J. Fox Foundation, Movement Disorders Society, National Parkinson Foundation, NIH/NINDS, Novartis, Parkinson Study Group, Teva, but has no owner interest in any pharmaceutical company.

Objectives: Second Primary Tumours (SPTs) have been implicated in poor Overall Survival (OS) of Head and Neck Squamous Cell Carcinomas (HNSCCs). The incidence of SPTs; the SPT diagnostic time lag; the impact on OS; and the mean annual risk was assessed. Methods: 987 consecutive patients treated for primary larynx SCC (1967–2004) were analysed in this study. 96.3% and 91.4% of patients reached a minimum follow up period of 3 and 5 years. Results: 208 (21.1%) patients were diagnosed with SPTs. 143 (14.5%) patients developed upper aero-digestive tract UAD-SPTs, 83 (8.4%) were HNSCCs, 56 (5.7%) were lung, and 4 (0.41%) were oesophageal SPTs. Survival analysis demonstrated unexpected but clear superior OS rates for the UAD-SPT (p < 0.008) and HNSCC-SPTs (p < 0.001). Patients with synchronous SPTs had a poorer overall survival (p < 0.001). The mean annual risk of developing UAD-SPTs was 2.4%. Conclusion: These results suggest that HNSCC-SPT should not be viewed as an adverse prognostic factor. Reclassifications of UAD-SPTs into HNSCC-SPT and non HNSCC-SPT better reflects their clinical behaviour and prognosis.