Rem sleep brady-arrhythmias: an indication to pacemaker implantation?

OBJECTIVES: Important adjustments in the autonomic nervous system occur during sleep. Bradycardia, due to increased vagal tone, and hypotension, caused by reduction of sympathetic activity, may occur during non rapid eye movement (REM) sleep (NREM). Increased sympathetic activity, causing increased heart rate, is conversely a feature of phasic REM sleep. During REM sleep, sinus arrests and atrioventricular (AV) blocks unrelated to apnea or hypopnea have been described. These arrhythmias are very rare and only a few cases have been reported in the literature. PATIENTS/METHODS: Following an ECG performed for other reasons, two patients with no history of sleep complaints nor symptoms of heart failure or heart attack were referred to our center for nocturnal brady-arrhythmias. RESULTS: 24h ECG Holter recorded several episodes of brady-arrhythmia with sinus arrest in the first patients and brady-arrhythmias with complete AV block in the second patient. In both patients, episodes of brady-arrhythmia were prevalent in the second part of the night. Nocturnal polysomnography (PSG) demonstrated that episodes occurred only during REM sleep, particularly during phasic events. Treatment with pacemaker was considered only for the patient with complete AV blocks. CONCLUSIONS: These types of brady-arrhythmias are usually detected accidentally due to their lack of symptoms. It has been suggested that in some patients they may lead to sudden unexpected death. Thus, the identification of predisposing factors is mandatory in order to prevent potentially dangerous arrhythmic events.

Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: a population-based study.

OBJECTIVE: The occurrence of dementia among the elderly has been associated with several, often not modifiable, risk factors. Recent epidemiological studies focused their interest on a possible association between cognitive decline and sleep, a potentially modifiable risk factor. Due to controversial results and limitations of the previous studies, we decided to reexamine the relationship between disturbed sleep and cognitive impairment in the elderly. METHODS: Seven hundred fifty subjects aged 65years or older were recruited. The Mini-Mental State Examination (MMSE) and the Global Deterioration Scale (GDS) scores were used to evaluate the severity of cognitive decline. Diagnosis of dementia was made by means of the DSM-IV criteria. The older adults were interviewed in order to assess the presence of several sleep complaints (insomnia, snoring and/or witnessed sleep apneas, restlessness and/or leg jerks, sleepwalking and nightmares). Excessive daytime sleepiness was evaluated by means of a validated questionnaire. The principal caregiver of each older adult took part in the interview, providing the information if the subject was unable to answer because of mental impairment. RESULTS: Eighty-six individuals were diagnosed as demented; a large part of them (47.8%), in particular, were recognized as being affected by Alzheimer's disease. The prevalence of each sleep complaint in the older adults was as follows: insomnia 84.7%, snoring and/or witnessed sleep apneas 26.2%, restlessness and/or jerks in the legs 25.7%, sleepwalking 0.5%, nightmares 6.4% and daytime somnolence 30.6%. Among sleep disturbances, excessive daytime sleepiness was independently associated with the presence of dementia in the elderly. In addition, the frequency of excessive daytime sleepiness increased progressively across the different categories of cognitive decline, as measured by means of MMSE and GDS scores. CONCLUSIONS: Insomnia, the most common sleep complaint in our sample, was not associated with the presence of cognitive decline. As opposed to insomnia, excessive daytime sleepiness was significantly related to dementia. Further studies are needed in order to investigate the direction of this association and to evaluate the possible role of daytime somnolence as an early marker of neurodegenerative disease, particularly Alzheimer's disease, in some older adults.

Drugs with anticholinergic properties as a risk factor for psychosis in patients affected by Alzheimer's disease.

Emerging evidence suggests that psychosis in persons with Alzheimer's disease (AD) may be linked to the cholinergic deficit associated with the disease. This study sought to evaluate whether anticholinergic (ACH) drugs could be a risk factor for psychosis onset. A total of 230 patients affected with probable AD were recruited. Data on behavioral and psychological symptoms were collected using the Neuropsychiatric Inventory, and diagnosis of psychosis was performed. Patients were divided into those who used ACH drugs and those who used non-ACH drugs. Those using ACH drugs (18.3%) were more likely to have psychosis than those using non-ACH drugs (odds ratio (OR)=2.52; 95% confidence interval (CI), 1.27-5.00); this association remained significant even after adjusting for potential confounding variables (OR=2.13; 95% CI, 1.03-4.43). Our data suggest that patients with AD are frequently treated with ACH drugs and that ACH drug intake should be regarded as a potential risk factor for psychosis.

Spreading of autoimmunity from central to peripheral myelin: two cases of clinical association between multiple sclerosis and chronic inflammatory demyelinating polyneuropathy.

Demyelinating inflammatory diseases of central and peripheral myelin share similar aetiopathogenesis but rarely occur simultaneously in the same individual. Here we report two clinical cases of temporal association between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Our finding supports the hypothesis that clinically manifested central and peripheral demyelinating diseases could result from a common pathogenic event characterised by T-cell autoimmunity spreading from central to peripheral myelin.

Changes in hemodynamics during isoflurane and propofol anesthesia: a comparison study.

OBJECTIVES: Volatile anesthetics are thought to impair cerebral autoregulation more than i.v. anesthetics. However, few comparative studies have been carried out in humans. The aim of our study was to evaluate the differences in cerebral hemodynamic changes after introduction of isoflurane (a volatile anesthetic) and propofol (an i.v. anesthetic). METHODS: Eighteen consecutive patients submitted to laparoscopic cholecystectomy were selected. After the induction, anesthesia was maintained by isoflurane (one minimum alveolar anesthetic concentration) during the first part of the surgical operation, and then by propofol (5 mg/kg/hour i.v.). Ventilation was adjusted to maintain a constant end-tidal CO(2). Middle artery flow velocity was assessed by means of transcranial Doppler ultrasonography. Arterial blood pressure, heart rate (HR), capnometry, pulse oxymetry, inspired fraction of O(2), and body temperature, were monitored. RESULTS: Cerebral artery velocity, HR, and mean arterial pressure all significantly increased from baseline after the introduction of isoflurane (p<0.05); the HR and mean arterial blood pressure showed no significant difference between the isoflurane and propofol phases. Isoflurane anesthesia induced a significant increase in cerebral blood velocity. Propofol introduction led to a significant decrease in cerebral artery velocity (p<0.05). CONCLUSIONS: Propofol but not isoflurane decreased cerebral blood velocity thus restoring cerebral autoregulation and the coupling between cerebral blood flow and cerebral metabolism.

Hemifacial spasm due to a tentorial paramedian meningioma: a case report.

Hemifacial spasm (HFS) is a movement disorder characterised by involuntary paroxysmal facial movements that usually involve the orbicularis oculi and then spread to the other facial muscles. A microvascular compression and demyelination of the seventh nerve at its exit from the brain stem is considered to be the main aetiology of HFS. In addition to rare idiopathic (cryptogenetic) cases, others causes of HFS exist: tumours or vascular malformations have been described, of both the ipsilateral and contralateral cerebellopontine angle (CPA). However, space-occupying lesions in locations other than CPA are usually not thought to be responsible for HFS. Here we describe the case of a 45-year-old woman suffering from HFS, who dramatically improved after surgical removal of a tentorial paramedian meningioma.

p27/kip1 expression in oligodendrogliomas and its possible prognostic role.

p27/kip1 regulates the G1-S transition of the cell cycle by inhibiting cyclinD-CDK4, cyclinE-CDK2 and cyclinA-CDK2 complexes. Regulation of p27 levels occurs mainly post-translationally by ubiquitin-mediated proteasomal proteolysis. Although genetic changes of p27/kip1 are extremely rare, in many human carcinomas p27 levels are reduced, correlate with histological malignancy, and are associated with poor prognosis. In astrocytic gliomas, p27 decreases with anaplasia and is almost absent in glioblastomas. p27/kip1 was immunohistochemically studied in 37 oligodendrogliomas, categorized according to WHO classification. In this series, the immunohistochemical reaction for p27 was confined to nuclei. p27 score showed a tendency to decrease with malignancy. When the p27 score was considered as high versus low expression (cut-off of p27 labeling index, LI, at 25%), it represented an independent prognostic factor in univariate (P = 0.02) and in multivariate analysis (P = 0.04). The risk ratio suggested that the p27 low expression group had a threefold increased possibility to show a reduced survival. Moreover, p27 levels did not correlate with MIB-1 LI, suggesting that p27 is not merely associated with the control of proliferation.

Proteasome-dependent degradation of p27/kip1 in gliomas.

p27/kip1 regulates the G1-S transition of the cell cycle by inhibiting cyclin D-CDK4, cyclin E-CDK2, and cyclin A-CDK2. Modulation of p27 cellular abundance occurs mainly at post-translational level by the ubiquitin-proteasome proteolysis. Although rearrangements and mutations of p27/kip1 are extremely rare events, p27 levels are reduced and associated with a poor prognosis in many human carcinomas. In astrocytic tumors, p27 decreases with advancing anaplasia and is almost absent in glioblastomas. To verify whether the degradation of p27 protein was responsible for its reduced levels in malignant gliomas, p27 degradation activity was tested in 22 tissue extracts that represented high, low, and absent p27 protein levels. p27 protein expression was detected by immunohistochemistry and immunoblot analysis and comparable results between the 2 methods were obtained. Low or undetectable p27 degradation activity was found in samples that displayed high levels of p27, i.e. all 4 normal brain biopsies, and 4 out of 6 grade II astrocytomas. Enhanced degradation activity resulted in malignant gliomas with low or absent p27 protein levels. The proteasome inhibitor LLnL abolished p27 degradation, demonstrating that it occurs in a proteasome-dependent manner. These data suggest that proteasome degradation of p27 may be instrumental in the deregulation of the cell cycle and to the malignant transformation of gliomas.

Cell-cycle inhibitor p27/Kip-1 expression in non-astrocytic and non-oligodendrocytic human nervous system tumors.

p27/kip-1 is a 'universal inhibitor' which inhibits cyclin complexes with cyclin-dependent kinases (CDKs), preventing cell cycle from the G1-S progression. It is expressed in normal oligodendrocytes and in differentiated glial tumors, decreasing with anaplasia and malignancy. In non-astrocytic and non-oligodendrocytic tumors of the nervous system, such as meningiomas, schwannomas, medulloblastomas, neuroblastomas and malignant lymphomas, p27/kip-1 is inconstantly and sometimes poorly expressed. This can be due to the lacking of p27 expression in the normal counterpart of tumor cells. In some tumors, p27/kip-1 expression can be attributed to a differentiation process, as in the pale islands of desmoplastic medulloblastoma and in neuroblastomas. A correlation of p27/kip-1 expression with histology was not found, with the exception of apoptosis in medulloblastomas. p27/kip-1 is in feed-back with cyclins and CDKs for the control of cell proliferation and its expression may occur where requested by the interplay with cyclins and other inhibitors.