Body Schema Self-Awareness and Related Dream Content Modifications in Amputees Due to Cancer.

PURPOSE: the evaluation of body image perception, pain coping strategies, and dream content, together with phantom limb and telescoping phenomena in patients with sarcoma who underwent surgery for limb amputation. MATERIAL AND METHODS: consecutive outpatients were evaluated at T0 (within 3 weeks after surgery) and T1 (4-6 months after surgery) as follows: demographic and clinical data collection; the Groningen Questionnaire Problems after Arm Amputation; the West Haven-Yale Multidimensional Pain Inventory; the Body Image Concern Inventory, a clinical trial to identify telescoping; and a weekly diary of dreams. Dream contents were coded according to the Hall and Van de Castle coding system. RESULTS: Twenty patients completed the study (15 males and 5 females, mean age: 53.9 ± 24.6, education: 7.8 ± 3.4). All subjects experienced phantom limb and 35% of them experienced telescoping soon after surgery, and 25% still after 4-6 months. Both at T0 and T1, that half of the subjects reported dreams about still having their missing limbs. At T1 the patients' perceptions of being able to deal with problems were lower, and pain and its interference in everyday life were higher yet associated with significant engagement in everyday activities and an overall good mood. The dream content analysis highlighted that males were less worried about health problems soon after amputation, and women showed more initial difficulties that seemed to be resolved after 4-6 months after surgery. CONCLUSIONS: The dream content analysis may improve clinicians' ability to support their patients during their therapeutic course.

Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep.

Environmental temperature can strongly affect sleep. The habitual sleep phase is usually located between evening decline and morning rise of the circadian rhythm of core body temperature (CBT). However, the thermophysiological mechanisms promoting or disturbing sleep are not yet fully understood. The purpose of this study was to examine the effects of a high heat capacity mattress (HHCM) on CBT, skin temperatures and sleep in comparison to a conventional low heat capacity mattress (LHCM). Based on the higher heat capacity of HHCM an increase in conductive body heat loss enhances the nocturnal decline in CBT can be expected. Based on previous findings this may then be accompanied by an increase in slow wave sleep (SWS). The mattresses were studied in a randomized single-blind crossover design in fifteen healthy young men (Age: 26.9±2.1yr, BMI: 22.2±0.4kg/m2) by overnight in laboratory standard video-polysomnography in a temperature stabilized setting. CBT, room temperature, and skin and mattress surface temperatures were continuously recorded in order to get information about inner and outer body heat flow. Additionally, subjective sleep quality was estimated by visual analogue scale. In comparison to LHCM sleep on HHCM exhibited a selective increase in SWS (16%, p<0.05), increased subjective sleep quality and sleep stability [reduced cyclic alternating pattern (CAP) rate; 5.3%, p<0.01]. Additionally, analyses of the sleep stages showed in the second part of the night a significant increase in SWS and a decrease in REMS. In addition, HHCM induced a greater reduction in CBT (maximally by -0.28°C), reduced the increase in proximal skin temperatures on the back (PROBA; maximally by -0.98°C), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 6.12°C). Thus, the CBT reduction can be explained by an increase in conductive heat loss to the mattress via proximal back skin regions. Regression analysis identified PROBA as the critical variable to predict inner conductive heat transfer from core to shell and SWS. In conclusion, the study expands the previous findings that a steeper nocturnal decline in CBT increases SWS and subjective sleep quality, whereas inner conductive heat transfer could be identified as the crucial thermophysiological variable, and not CBT.

Clinical and functional prediction of moderate to severe obstructive sleep apnoea.

INTRODUCTION: Upper airway inflammation and narrowing are characteristics of obstructive sleep apnoea (OSA). Inflammatory markers have been found to be increased in exhaled breath and induced sputum of patients with OSA. OBJECTIVES: The aim of this study was to investigate if the measurement of exhaled nitric oxide (F(ENO) ), as marker of airway inflammation, together with the forced mid-expiratory/mid-inspiratory airflow ratio (FEF(50) /FIF(50) ), as marker of upper airway narrowing, may help to predict OSA. METHODS: Two hundred one consecutive outpatients with suspected OSA were prospectively studied between January 2004 and December 2005. All patients underwent clinical examination, spirometry with measurement of FEF(50) /FIF(50) , maximum inspiratory pressure, arterial blood gas analysis, exhaled nitric oxide (F(ENO) ) and overnight polysomnography. Linear regression models were used to evaluate the effect of measured variables on the apnoea-hypopnoea index (AHI). Models were cross-validated by bootstrapping. RESULTS: Most of the patients were obese and had severe OSA. FEF(50) /FIF(50) , F(ENO) and an interaction term between smoking and F(ENO) contributed significantly to the predictive model for AHI, in addition to age, neck circumference, body mass index and carboxyhaemoglobin saturation. A nomogram to predict AHI was obtained, which converted the effect of each covariate in the model to a 0-100 scale. The nomogram showed a good predictive ability for AHI values between 25 and 64. CONCLUSIONS: The measurement of F(ENO) and of FEF(50) /FIF(50) improves the ability to predict OSA and may be used to identify patients who require a sleep study.

Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis.

BACKGROUND: Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides. OBJECTIVES: Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease. METHODS: Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis). RESULTS: In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing-remitting MS during relapses and in progressive MS patients, compared with relapsing-remitting MS patients during remissions and with non-inflammatory controls. CONCLUSIONS: PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.

Sexual behaviors during sleep associated with polysomnographically confirmed parasomnia overlap disorder.

Parasomnia overlap disorder (POD) refers to a sleep disorder characterized by the association of REM sleep behavior disorder (RBD) with NREM sleep parasomnia in the same patient. Sexual behaviors during sleep (SBS) can include most wakeful sexual activities and are classified in the ICSD-2 as a variant of confusional arousals and sleepwalking, both NREM parasomnias. A case of SBS associated with sleepwalking and possible RBD has been previously described, but it was not confirmed by polysomnography (PSG). We report two patients with SBS associated with POD documented by PSG. In one patient (60-year-old female) SBS was video-polysomnographically demonstrated: a few minute episode of masturbation occurring during slow-wave sleep (SWS) and preceded by hypersynchronous delta pattern. During the episode, the EEG pattern showed the persistence of delta rhythms with increasing alpha activity. When awoken by technicians, the patient was not aware of her sexual behavior and did not report any dream. The other patient, a 41-year-old male with a history of sleepwalking and RBD, was legally charged with repeatedly sexually fondling a young girl during the night. The POD was documented by PSG. The parasomnia defense, including sleepsex, was accepted by the Court and the patient was acquitted. This is an unprecedented report of SBS in patients with PSG-confirmed POD and of SBS documented during video-PSG.

Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: clinical and biological results from a prospective multicenter study.

Granulocyte colony-stimulating factor (G-CSF) induces a transient mobilization of hematopoietic progenitor cells from bone marrow to peripheral blood. Our aim was to evaluate safety of repeated courses of G-CSF in patients with amyotrophic lateral sclerosis (ALS), assessing disease progression and changes in chemokine and cytokine levels in serum and cerebrospinal fluid (CSF). Twenty-four ALS patients entered an open-label, multicenter trial in which four courses of G-CSF and mannitol were administered at 3-month intervals. Levels of G-CSF were increased after treatment in the serum and CSF. Few and transitory adverse events were observed. No significant reduction of the mean monthly decrease in ALSFRS-R score and forced vital capacity was observed. A significant reduction in CSF levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-17 (IL-17) was observed. G-CSF treatment was safe and feasible in a multicenter series of ALS patients. A decrease in the CSF levels of proinflammatory cytokines MCP-1 and IL-17 was found, indicating a G-CSF-induced central anti-inflammatory response.

Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.

OBJECTIVE: To perform an extensive screening for mutations of amyotrophic lateral sclerosis (ALS)-related genes in a consecutive cohort of Sardinian patients, a genetic isolate phylogenically distinct from other European populations. DESIGN: Population-based, prospective cohort study. PATIENTS: A total of 135 Sardinian patients with ALS and 156 healthy control subjects of Sardinian origin who were age- and sex-matched to patients. INTERVENTION: Patients underwent mutational analysis for SOD1, FUS, and TARDBP. RESULTS: Mutational screening of the entire cohort found that 39 patients (28.7%) carried the c.1144G>A (p.A382T) missense mutation of the TARDBP gene. Of these, 15 had familial ALS (belonging to 10 distinct pedigrees) and 24 had apparently sporadic ALS. None of the 156 age-, sex-, and ethnicity-matched controls carried the pathogenic variant. Genotype data obtained for 5 ALS cases carrying the p.A382T mutation found that they shared a 94-single-nucleotide polymorphism risk haplotype that spanned 663 Kb across the TARDBP locus on chromosome 1p36.22. Three patients with ALS who carry the p.A382T mutation developed extrapyramidal symptoms several years after their initial presentation with motor weakness. CONCLUSIONS: The TARDBP p.A382T missense mutation accounts for approximately one-third of all ALS cases in this island population. These patients share a large risk haplotype across the TARDBP locus, indicating that they have a common ancestor.

Amyotrophic lateral sclerosis-frontotemporal lobar dementia in 3 families with p.Ala382Thr TARDBP mutations.

BACKGROUND: TAR DNA-binding protein 43, encoded by the TARDBP gene, has been identified as the major pathological protein of frontotemporal lobar dementia (FTLD) with or without amyotrophic lateral sclerosis (ALS) and sporadic ALS. Subsequently, mutations in the TARDBP gene have been detected in 2% to 3% of patients with ALS (both familial and sporadic ALS). However, to our knowledge, there is only 1 description of 2 patients with FTLD and TARDBP gene mutations who later developed motor neuron disease. OBJECTIVE: To describe cognitive abnormalities in 3 Italian families with familial ALS and TARDBP gene mutations. DESIGN, SETTING, AND PARTICIPANTS: Genetic, neuropsychological, and neuroimaging analyses in 36 patients with familial non-superoxide dismutase 1 gene (SOD1) ALS and 280 healthy controls. Main Outcome Measure We identified 3 index cases of familial ALS carrying the p.Ala382Thr missense mutation of the TARDBP gene and with clinical, neuroimaging, and neuropsychological features of FTLD. RESULTS: The p.Ala382Thr missense mutation of the TARDBP gene was absent in the 280 controls. It was present in all affected members of the 3 families for whom DNA was available. All affected members of the 3 families developed FTLD after the onset of ALS, confirmed by neuropsychological testing and hypometabolism in frontal associative areas assessed with fludeoxyglucose F 18 positron emission tomography and computed tomography. CONCLUSIONS: Three apparently unrelated families with familial ALS carrying the p.Ala382Thr TARDBP missense mutation developed FTLD. In these families, FTLD cosegregates with ALS. Patients with ALS carrying TARDBP mutations may develop FTLD.

Neuropsychological and functional study in a case of partial cerebellar agenesis.

Cerebellar agenesis is a rare disorder. We present the neurological and neuropsychological features of a patient with partial cerebellar agenesis (TZ), together with SPECT perfusion and fMRI activation during a finger tapping task. TZ shows only mild cerebellar signs, while neuropsychological testing discloses severe deficits in many domains, in accordance with the theorized role of the cerebellum in cognition. FMRI and SPECT demonstrate an activation and a symmetrical perfusion of the cerebellar remnants, that can be related to the residual cerebellar motor function. The left frontal and parieto-temporal cortex hypoperfusion can explain the severe cognitive impairment and could be linked to the abnormal cerebellar development.

Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter.

Gray matter (GM) lesions are recognized as important components of the pathology of multiple sclerosis (MS), and involvement of the deep gray matter (DGM) is suggested by magnetic resonance imaging. The aims of this study were to determine the frequency and distribution of lesions and characterize the inflammatory and neurodegenerative changes in DGM of MS patients. Histochemistry, immunohistochemistry, and morphometry were performed on whole coronal sections of 14 MS and 12 control (6 normal, 6 from amyotrophic lateral sclerosis patients) brains. Demyelinating lesions were frequent in MS DGM; most often in the thalamus and caudate, but they were also seen in the putamen, pallidum, claustrum, amygdala, hypothalamus, and substantia nigra. Most DGM lesions involved both GM and white matter. Inflammation in active DGM lesions was similar to that in lesions only in white matter but was less intense, and there was a preponderance of activated microglia, scarce myelin-laden macrophages, and a lesser extent of axonal damage. Neuronal loss was observed both in DGM lesions and nondemyelinated DGM with neuron atrophy in nondemyelinated DGM. In conclusion, demyelination and neurodegenerative changes are common in MS DGM and may contribute to clinical impairment. Inflammation in DGM lesions is intermediate between the destructive inflammation of white matter lesions and the minimal inflammation of cortical lesions. We hypothesize that alterations of glutamate reuptake mechanisms may contribute to these differences.

ALS in Italian professional soccer players: the risk is still present and could be soccer-specific.

We previously found an increased risk for ALS in Italian professional soccer players actively engaged between 1970 and 2001 (n =7325). The present study extends previous work with a prospective follow-up of the original cohort to 2006 and investigates the risk of ALS in two other cohorts of professional athletes, basketball players (n =1973) and road cyclists (n =1701). Standardized morbidity ratios (SMRs) were calculated. Among soccer players three new cases of ALS were identified, reaching a total of eight ALS cases (mean age of onset, 41.6 years). The number of expected cases was 1.24, with an SMR of 6.45 (95% CI 2.78-12.70; p<0.00001). The risk of ALS was higher for careers lasting >5 years, for midfielders, and for players engaged after 1980. No basketball player and no cyclist developed ALS. This prospective extension of the Italian soccer players cohort survey confirms the highly significant risk of developing ALS, the young age of onset, the dose-effect risk and a predilection for midfielders. The absence of ALS cases in professional road cyclists and basketball players indicates that ALS is not related to physical activity per se.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

Anti-brain antibodies in adult patients with obsessive-compulsive disorder.

BACKGROUND: An autoimmune hypothesis has been suggested for a subtype of Obsessive-Compulsive Disorder (OCD) with childhood onset: obsessions, compulsions and/or tics would result from anti-streptococcal antibodies that cross-react with basal ganglia tissue based on molecular mimicry. Consistent with this hypothesis anti-brain antibodies were detected in sera of children with OCD and/or Tourette's syndrome. In the present study, we tested whether adults with OCD have anti-brain antibodies or other antibodies that serve as markers of autoimmunity. METHODS: Seventy-four DSM-IV OCD (YBOCS> or =16) subjects were recruited and compared to 44 controls with a current Major Depressive Episode for neurological symptoms, ALSO titres, anti-tissue and anti-thyroid antibodies. Anti-brain antibodies were tested by immunohistochemistry and Western blotting methods. RESULTS: The proportion of subjects with tic comorbidity or positive ASLO titre (>200 IU/ml) was significantly greater in OCD than in MDE patients (21.6 vs. 2.3% and 16.3 vs. 2.3%, respectively). No other differences in antibody parameters were found. 4/74 OCD patients (5.4%) and none of the controls resulted positive for anti-brain antibodies, with a band around 50-60 kDa at the Western blot analysis. LIMITATIONS: The methodology used to assess anti-brain antibodies. CONCLUSIONS: The majority of adult OCD patients do not seem to have autoimmunity disturbances as compared to a control group. However, a greater percentage of subjects with positive ASLO titres were found among OCD patients. For a small proportion of OCD patients, moreover, autoimmune reactions towards neuronal structures are present although further investigations are needed to demonstrate its etiopathogenetic relevance.

Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: a neuropathological study.

An immunological function has been proposed for the choroid plexus (CP). In multiple sclerosis (MS) brains, CPs show (immunohistochemistry to HLA-DR, CD3, CD20, CD68, VCAM-1, CD138) T lymphocytes in vessels and stroma, VCAM-1 expression on endothelia, intense HLA-DR immunostaining on cells in CP stroma, among CP epithelium and on epiplexus cells. CPs in control or amyotrophic lateral sclerosis brains do not show such inflammatory changes. Intense CP inflammation is observed in viral encephalitis. Changes in MS CPs suggest persisting immune activation, with intensity similar to acute encephalitis, even in MS phases in which neurodegeneration prevails. In MS, CPs could represent a site for lymphocyte entry in the CSF and for CSF antigens presentation.

Altered glutamate reuptake in relapsing-remitting and secondary progressive multiple sclerosis cortex: correlation with microglia infiltration, demyelination, and neuronal and synaptic damage.

Cortical involvement in multiple sclerosis (MS) is emerging as an important determinant of disease progression. The mechanisms responsible for MS cortical pathology are not fully characterized. The objective of this study was to assess the role of excitotoxicity in MS cortex, evaluating excitatory amino acid transporter (EAAT) expression and its relationship with demyelination, inflammation, gliosis, and neuronal and synaptic pathology. EAATs are essential in maintaining low extracellular glutamate concentrations and preventing excitotoxicity. Ten MS brains (3 relapsing-remitting MS cases and 7 secondary progressive MS cases) were evaluated by immunohistochemistry for myelin basic protein, CD68, HLA-DR, EAAT1, EAAT2, glial fibrillary acidic protein, phosphorylated c-Jun N-terminal kinase (pJNK), synaptophysin, and neurofilaments. Cortical lesions were frequently observed in MS brains in variable numbers and extensions. In cortical lesions, activated microglia infiltration correlated with focal loss of EAAT1, EAAT2, and synaptophysin immunostaining, and with neuronal immunostaining for pJNK, a protein involved in response to excitotoxic injury. No reduction of EAATs or synaptophysin immunostaining was observed in demyelinated cortex in the absence of activated microglia. Alterations of the mechanisms of glutamate reuptake are found in cortical MS lesions in the presence of activated microglia and are associated with signs of neuronal and synaptic damage suggestive of excitotoxicity. Excitotoxicity may be involved in the pathogenesis of demyelination and of neuronal and synaptic damage in MS cortex.

Diuretics in obstructive sleep apnea with diastolic heart failure.

BACKGROUND: Upper airway edema might contribute to pharyngeal collapsibility and account for the high prevalence of obstructive sleep apnea (OSA) in patients with heart disease. The aim of this study was to evaluate if intensive unloading with diuretics improves sleep-disordered breathing and increases pharyngeal caliber in patients with severe OSA and diastolic heart failure. METHODS: Fifteen patients with severe OSA, hypertension, and diastolic heart failure were hospitalized to receive IV furosemide, 20 mg, and spironolactone, 100 mg, bid for 3 days. Polysomnography was performed for assessment of apnea-hypopnea index (AHI), acoustic pharyngometry was performed for assessment of the oropharyngeal junction (OPJ) area, and forced midinspiratory flow (FIF(50)), forced midexpiratory flow (FEF(50))/FIF(50) percentage, and exhaled nitric oxide (FeNO) were measured before and after diuretic treatment. RESULTS: Diuretic treatment produced a significant decrease in body weight, BP, and AHI (from 74.89 +/- 6.95 to 57.17 +/- 5.40/h, p < 0.001), associated with an improvement in OPJ area (from 1.33 +/- 0.10 to 1.78 +/- 0.16 cm(2), p = 0.007), FIF(50) (from 3.16 +/- 0.4 to 3.94 +/- 0.4 L/s, p = 0.006), and FEF(50)/FIF(50) percentage (from 117.9 +/- 11.8 to 93.15 +/- 10.1%, p = 0.002). Weight loss was significantly related to the decrease of AHI (R = 0.602; p = 0.018), to the increase of FIF(50) (R = 0.68; p = 0.005), and to the decrease of FEF(50)/FIF(50) (R = 0.635; p = 0.011). CONCLUSIONS: These findings suggest that pharyngeal edema contributes to sleep-disordered breathing in obese patients with severe OSA, hypertension, and diastolic heart failure. Upper airway edema may contribute to the frequent occurrence of OSA in patients with heart disease.

Effects of levetiracetam on nocturnal sleep and daytime vigilance in healthy volunteers.

PURPOSE: Individuals with epilepsy commonly report daytime sleepiness, attributed to sleep disruption (frequent arousals, awakenings, and stage shifts) induced by ictal and interictal activity or antiepileptic drugs (AEDs) or both. To study the effect of levetiracetam (LEV) on sleep, at full doses but without the interference of epilepsy, we investigated the sleep architecture and daytime vigilance in healthy adults after 3 weeks of treatment. METHODS: The study was of a double-blind crossover design with random allocation of multiple doses of two different treatments (randomly first LEV

Tooth loss and obstructive sleep apnoea.

BACKGROUND: Complete tooth loss (edentulism) produces anatomical changes that may impair upper airway size and function. The aim of this study was to evaluate whether edentulism favours the occurrence of obstructive sleep apnoea (OSA). METHODS: Polysomnography was performed in 48 edentulous subjects on two consecutive nights, one slept with and the other without dentures. Upper airway size was assessed by cephalometry and by recording forced mid-inspiratory airflow rate (FIF50). Exhaled nitric oxide (eNO) and oral NO (oNO), were measured as markers of airway and oropharyngeal inflammation. RESULTS: The apnoea/hypopnoea index (AHI) without dentures was significantly higher than with dentures (17.4 +/- 3.6 versus 11.0 +/- 2.3. p = 0.002), and was inversely related to FIF50 (p = 0.017) and directly related to eNO (p = 0.042). Sleeping with dentures, 23 subjects (48%) had an AHI over 5, consistent with OSA, but sleeping without dentures the number of subjects with abnormal AHI rose to 34 (71%). At cephalometry, removing dentures produced a significant decrease in retropharyngeal space (from 1.522 +/- 0.33 cm to 1.27 +/- 0.42 cm, p = 0.006). Both morning eNO and oNO were higher after the night slept without dentures (eNO 46.1 +/- 8.2 ppb versus 33.7 +/- 6.3 ppb, p = 0.035, oNO 84.6 +/- 13.7 ppb versus 59.2 +/- 17.4 ppb, p = 0.001). CONCLUSION: These findings suggest that complete tooth loss favours upper airway obstruction during sleep. This untoward effect seems to be due to decrease in retropharyngeal space and is associated with increased oral and exhaled NO concentration.

Angiotensin-converting enzyme inhibitors and obstructive sleep apnea.

Angiotensin-converting enzyme (ACE) inhibitors may induce cough and rhinopharyngeal inflammation. Obstructive sleep apnea (OSA) is characterized by upper airway inflammation. We describe a patient who, during enalapril treatment, developed cough, upper airway symptoms, and diurnal sleepiness, with an increased number of obstructive apnea-hypopnea episodes (apnea-hypopnea index [AHI], 25) during sleep. Her symptoms and AHI improved 1 month after enalapril was discontinued and diuretic therapy (hydrochlorothiazide-spironolactone) was initiated. Similar findings were observed in 4 other patients with OSA who had ACE inhibitor-induced cough. The mean +/- SD AHI was 33.8+/-21.0 during enalapril treatment and 20.0+/-17.0 after withdrawal of this drug (P = .04). Exhaled nitric oxide, a marker of airway inflammation, was increased during enalapril treatment (15.0 +/- 4.3 parts per billion) and decreased after discontinuation of this drug (9.0 +/- 2.6; P = .03). No significant difference in the AHI and exhaled nitric oxide was observed in 4 patients with OSA who did not experience cough, before or after withdrawal of ACE inhibitor treatment. These findings suggest that ACE inhibitor treatment may contribute to OSA by inducing upper airway inflammation.