Sleep spindles and K-complex activities are decreased in spinocerebellar ataxia type 2: relationship to memory and motor performances.

BACKGROUND: Sleep spindles and K-complexes are electroencephalographic hallmarks of non-rapid eye movement (non-REM) sleep that provide valuable information into brain functioning, plasticity and sleep functions in normal and pathological conditions. However, they have not been systematically investigated in spinocerebellar ataxias (SCA). To close this gap, the current study was carried out to quantify sleep spindles and K-complexes in SCA2 and to assess their relationship with clinical and molecular measures, as well as with memory and attention/executive functioning. METHODS: In this study, 20 SCA2 patients, 20 preclinical carriers and 20 healthy controls underwent whole-night polysomnographic (PSG) recordings as well as sleep interviews, ataxia scoring and neuropsychological assessments. Sleep spindles and K-complexes were automatically detected during non-REM sleep stage 2 (N2). Their densities were evaluated as events/minute. RESULTS: Compared to controls, sleep spindle density was significantly reduced in SCA2 patients and preclinical subjects. By contrast, K-complex density was specifically and significantly decreased only in SCA2 patients. Reduced spindle activity correlated with measures of verbal memory, whereas reduced K-complex activity correlated with age, ataxia severity and N3 sleep percentage in SCA2 patients. CONCLUSIONS: Findings document an impairment of N2 sleep microstructure in SCA2 already in prodromal stages, suggesting an early involvement of thalamo-cortical and/or cortical circuits underlying the generation of sleep spindles and K-complexes. Thus, sleep spindle density may serve as useful biomarker for deficits of neural plasticity mechanisms underlying verbal memory alterations in patients. It may also serve as promising outcome measure in further therapeutical trials targeting memory decline in SCA2. With regard to K-complexes, they have potential usefulness as marker of sleep protection.

Decrease of respiratory events in patients with obstructive sleep apnea-hypopnea syndrome using a mandibular advancement device assessed with split night polysomnography.

INTRODUCTION: Mandibular advancement device (MAD) may represent a feasible choice in the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS), in well selected patients. OBJECTIVE: The aim of this study is to assess the efficacy of MAD in patients with OSAHS, using split night polysomnography (SNP). METHOD: We performed an auto controlled clinical trial to assess the efficacy of MAD in 30 patients with snoring and OSAHS. Clinical evaluation was made every 2 weeks to adjust treatment and observe changes in clinical symptoms. Three-months after placement of the MAD, a SNP was performed, using the MAD in the second half of the night, in order to compare the respiratory results. RESULTS: SNP show significant changes with use of MAD (p<0.05) such as: Decrease in Snore index (from 159.95 to 32.46/h) and in Apnea-hypopnea index (AHI, from 22.45 to 4.63/h), increase in oxygen saturation (SaO2, from 89.98% to 91.39%) and somnolence improvement, using the Epworth Sleepiness Scale (from 14.4 to 4.6 points). CONCLUSION: Our data supports that the use of MAD is an alternative in the management of OSAHS, in well selected patients, used in a multidisciplinary fashion, and evaluated using a SNP.

Recessive spinocerebellar ataxia with paroxysmal cough attacks: a report of five cases.

Hereditary ataxias are a heterogeneous group of neurological diseases characterized by progressive cerebellar syndrome and numerous other features, which result in great diversity of ataxia subtypes. Despite the characterization of a number of both autosomal dominant and autosomal recessive ataxias, it is thought that a large group of these conditions remains to be identified. In this study, we report the characterization of five patients (three Mexicans and two Italians) who exhibit a peculiar form of recessive ataxia associated with coughing. The main clinical and neurophysiological features of these patients include cerebellar ataxia, paroxysmal cough, restless legs syndrome (RLS), choreic movements, atrophy of distal muscles, and oculomotor disorders. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy, while video polysomnography (VPSG) studies showed a severe pattern of breathing-related sleep disorder, including sleep apnea, snoring, and significant oxygen saturation in the absence of risk factors. All patients share clinical features in the peripheral nervous system, including reduction of amplitude and prolonged latency of sensory potentials in median and sural nerves. Altogether, clinical criteria as well as molecular genetic testing that was negative for different autosomal dominant and autosomal recessive ataxias suggest the presence of a new form of recessive ataxia. This ataxia, in which cerebellar signs are preceded by paroxysmal cough, affects not only the cerebellum and its fiber connections, but also the sensory peripheral nervous system and extracerebellar central pathways.

Sleep apnea in patients with acromegaly. Frequency, characterization and positive pressure titration.

OBJECTIVES: to describe the frequency of sleep apnea in patients with acromegaly;to identify the proportion of candidates for treatment with positive airway pressure;to report our experience with the positive pressure titration process in acromegaly patients. METHODS: A cross-sectional study that included the acromegaly cohort at the Centro Medico Nacional "20 de Noviembre" in Mexico City (n=44). A standard polysomnography (PSG) was carried out for each patient. A second PSG was done for purposes of CPAP titration. RESULTS: A total of 35 patients were studied (80% of the cohort, 20 [57%] women). Polysomnography results showed that 34 subjects (97%, 95%CI 91-100%) had apnea hypopnea indexes (AHI) ≥ 5. No patient had central apnea. We identified 19 subjects with AHI ≥5 and Epworth ≥10, for a frequency of obstructive sleep apnea syndrome of 54% (95%CI 36-71%). A total of 31 patients (88%; 95%CI 77-99%) were deemed to be candidates for positive pressure treatment, but only 8 of them accepted CPAP. They required pressures that ranged from 10 to 18 cmH(2)O. CONCLUSIONS: Our results confirm a high prevalence of sleep apnea in patients with acromegaly, and provide evidence that the majority of those patients are candidates for treatment with positive pressure. Contrary to what has been reported, we identified no patients with central apnea.

Lisuride reduces involuntary periodic leg movements in spinocerebellar ataxia type 2 patients.

Periodic leg movements (PLMs) are a common sleep disorder in spinocerebellar ataxia type 2 (SCA2) being associated to higher disease severity and altered sleep patterns. To assess the efficacy and safety of lisuride for the treatment of PLMs in SCA2 patients, an open-label clinical trial was conducted in 12 SCA2 patients suffering from PLMs associated to other subjective sleep complaints. All subjects received 0.1 mg of oral lisuride daily for 4 weeks. Primary outcome measure was the change of PLMs index. Changes in the subjective sleep quality, other polysomnographical sleep parameters, Scale for the Assessment and Rating of Ataxia score, and saccadic velocity were assessed as secondary outcome parameters. Safety assessments included hemoglobin, hematocrit, cholesterol, creatinine, and TGP. A significant decrease in both the PLMs index and R stage latency were observed during the treatment, associated to subjective improvement of frequent awakenings, early insomnia, restless leg syndrome, and nocturnal limb paresthesias in most cases. Ataxia score and saccadic pathology were unchanged. No significantly adverse events were observed. Our study suggests the efficacy of dopamine agonist therapy in the treatment of PLMs in SCA2, improving various subjective sleep complaints. These findings serve to promote the adequate management of sleep-related disorders in SCA2, which could improve the life quality of the patients.

Sleep disorders in spinocerebellar ataxia type 2 patients.

BACKGROUND: Sleep disturbances are common features in spinocerebellar ataxias (SCAs). Nevertheless, sleep data on SCA2 come from scarce studies including few patients, limiting the evaluation of the prevalence and determinants of sleep disorders. OBJECTIVE: To assess the frequency and possible determinants of sleep disorders in the large and homogeneous SCA2 Cuban population. METHODS: Thirty-two SCA2 patients and their age- and sex-matched controls were studied by video-polysomnography and sleep interviews. RESULTS: The most striking video-polysomnography features were rapid eye movement (REM) sleep pathology and periodic leg movements (PLMs). REM sleep abnormalities included a consistent reduction of the REM sleep percentage and REM density as well as an increase in REM sleep without atonia (RWA). REM sleep and REM density decreases were closely related to the increase in ataxia scores, whereas the RWA percentage was influenced by the cytosine-adenine-guanine (CAG) repeats. PLMs were observed in 37.5% of cases. The PLM index showed a significant association with the ataxia score and disease duration but not with CAG repeats. CONCLUSIONS: REM sleep pathology and PLMs are closely related to SCA2 severity, suggesting their usefulness as disease progression markers. The RWA percentage is influenced by the CAG repeats and might thus be a sensitive parameter for reflecting polyglutamine toxicity. Finally, as PLMs are sensible to drug treatment, they represents a new therapeutic target for the symptomatic treatment of SCA2.

Sleep disorders in spinocerebellar ataxia type 2 patients

Background: Sleep disturbances are common features in spinocerebellar ataxias (SCAs). Nevertheless, sleep data on SCA2 come from scarce studies including few patients, limiting the evaluation of the prevalence and determinants of sleep disorders. Objective: To assess the frequency and possible determinants of sleep disorders in the large and homogeneous SCA2 Cuban population. Methods: Thirty-two SCA2 patients and their age- and sex-matched controls were studied by video-polysomnography and sleep interviews. Results: The most striking video-polysomnography features were rapid eye movement (REM) sleep pathology and periodic leg movements (PLMs). REM sleep abnormalities included a consistent reduction of the REM sleep percentage and REM density as well as an increase in REM sleep without atonia (RWA). REM sleep and REM density decreases were closely related to the increase in ataxia scores, whereas the RWA percentage was influenced by the cytosine-adenine-guanine (CAG) repeats. PLMs were observed in 37.5% of cases. The PLM index showed a significant association with the ataxia score and disease duration but not with CAG repeats. Conclusions: REM sleep pathology and PLMs are closely related to SCA2 severity, suggesting their usefulness as disease progression markers. The RWA percentage is influenced by the CAG repeats and might thus be a sensitive parameter for reflecting polyglutamine toxicity. Finally, as PLMs are sensible to drug treatment, they represents a new therapeutic target for the symptomatic treatment of SCA2(AU)

Low delta sleep predicted a good clinical response to olanzapine administration in schizophrenic patients.

INTRODUCTION: Schizophrenic patients show sleep abnormalities, consisting mainly of decreased delta sleep time, short rapid eye movement (REM) sleep latency, and a reduction in sleep continuity variables. Olanzapine is a novel antipsychotic drug with an atypical profile. The goals of the present study were to determine if pre-treatment sleep variables and the initial response to olanzapine administration on the sleep variables can predict the clinical improvement after eight weeks of treatment. MATERIAL AND METHODS: Twenty-one schizophrenic (DSM-IV) patients were studied. They were clinically evaluated using the positive and negative syndrome scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Sleep recordings were as follows: one acclimatization nigh, one night of baseline recordings, and two nights in which the patients receives olanzapine 10 mg, one hour before bedtime. For sleep-comparison purposes, a group of normal volunteers were also studied with acclimatization and baseline nights. After the sleep recordings ended patients continued with the administration of 10 mg/d of olanzapine, that was titrated as needed up to 20 mg/d or down to 5 mg/d. Evaluations were conducted weekly. RESULTS: Awakening and sleep latency variables were significantly higher in schizophrenic patients compared to normal volunteers. Delta sleep was lower in patients than in normal subjects, with no detectable values in some of the schizophrenics. There was not correlation at baseline, between psychopathological scores and delta sleep or other sleep variables. The acute administration of olanzapine 10 mg produced an improvement in continuity sleep variables as well as increase in deltas sleep percentage. Having less than 10% of delta sleep at baseline predicted a good clinical outcome. Eleven of 18 patients showed good clinical improvement after eight weeks of treatment with olanzapine, those were the subjects that had an augmentation of delta sleep above 10% with the first two doses of olanzapine, with minimal side effects. CONCLUSIONS: To have low delta sleep at baseline and the effect of the augmentation of this variable in schizophrenic patients seems to predict a good response to olanzapine. Olanzapine was therapeutically useful, well-tolerated medication, with a favorable safety profile.

Efectos de la manipulación del sueño sobre los niveles plasmáticos de inmunoglobulinas, albúmina y cortisol en sujetos voluntarios sanos / Sleep manipulation effects on plasmatic levels of inmunoglobulins albumin and cortisol in voluntary health subjects

Se estudió el efecto que dos formas de manipulación del sueño tiene sobre las inmunoglobulinas, la albúmina y el cortisol plasmáticos. Los 24 voluntarios sanos estudiados se asignaron al azar, a 3 grupos: en el primero se les privó totalmente de sueño (PST) durante 40 hr, y se recolectaron muestras plasmáticas antes de la manipulación experimental (BSL), durante la privación (TRANS) y en el seguimiento (POST). las muestras se tomaron a las 06:00 hr. A un segundo grupo de voluntarios se le privó del sueño de movimientos oculares rápidos (PSMOR-2); y al tercer grupo de sujetos se le privó de SMOR durante 6 noches (PSMOR-6). A estos dos grupos se les tomó sangre (en la situación basal y en la última nohe de manipulación del sueño), a las 06:00 hrs. En los resultados se obsevó que el grupo de PTS mostraba una disminución de los niveles de IgG en las condiciones TRANS y POST, sin cambios en el resto de las inmunoglobulinas o la albúmina, mientras que el cortisol se elevó en forma significativa en la situación TRANS. En el grupo PSMOR-2, únicamente se encontró una elevación de cortisol plasmático y, finalmente, en el grupo PSMOR-6 se detectó una elevación de la IgM

Características polisomnográficas de enfermos narcolépticos comparadas con las de otro tipo de hipersomnia / Polysomnographic characteristics of narcoleptic patients compared with another hipersomnia type

Se estudiaron 6 pacientes narcolépticos, los cuales fueron comparados con 4 pacientes con hipersomnia idiopática y 2 pacientes con hipersomnia debido al síndrome de sueños en fase retrasada. Todos los pacientes completaron cuatro pruebas de latencias múltiples al sueño (PLMS) a las 10:00,12:00, 14:00 y 16:00 hrs; y dos noches de registro polisomnográfico (noches de habituación y basal). Ambos grupos de pacientes, los narcolépricos y los hipersomnes no narcolépticos, mostraron una latencia al sueño menor de 10 minutos, por lo menos en dos ocasiones. Pero solamente los narcoléoticos tuvieron al menos dos ingresos a sueño en fase de SMOR en las siestas. En las noches de registro basal, los narcolépticos mostraron un mayor número de despertares, y un aumento en el tiempo de despertarses después del inicio del sueño. Los pacientes narcolépticos tuvieron más alteraciones en el SMOR, tales como inicio del sueño en fase de SMOR y fragmentación del SMOR, en comparación con los pacientes hipersomnes no narcolépticos. Estos datos sugieren que la narcolepsia no es únicamente un trastorno por alteración del SMOR, ya que estos pacientes presenta una incapacidad para permanecer en un estado neural específico, en comparación con los sujetos normales y aun con pacientes con otras formas de trastornos por somnolencia excesiva diurna