Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review.

Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated.

Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients.

BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. METHODS: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. CONCLUSION: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Time course of frontal somatosensory evoked potentials. Relation to L-dopa plasma levels and motor performance in PD.

OBJECTIVE: To verify whether the change in L-dopa plasma levels after a single dose of carbidopa/L-dopa 50/200 (controlled-release) transiently modifies frontal components of somatosensory evoked potentials (SEPs) in patients with PD in parallel with improvement of motor performance. BACKGROUND: Apomorphine, a potent dopamine-agonist drug, transiently increases frontal SEP components, which may be depressed in PD; however, relationships between clinical status, frontal SEPs, and therapy are still unclear. METHODS: Nineteen PD patients (mean age 65.9 years, range 52 to 77, responders to L-dopa therapy, were studied in the same day at times T0 (baseline predose level), T1 (presumed L-dopa peak time), and T2 (end of dose-induced motor response). The following were monitored: L-dopa plasma concentration, tapping test, reaction times, peak latency (with central conduction times), and amplitude of cervical, subcortical, as well as cortical parietal and frontal SEP components elicited by median nerve stimulation of the more clinically affected arm. RESULTS: The average amplitude of frontal components of PD patients was significantly reduced at T0 with respect to control subjects. A significant and transient amplitude increase of frontal SEPs was found at T1, in parallel with the L-dopa peak concentration and improvement in motor performance (tapping and reaction times), without significant changes in amplitude of parietal SEP waves. No latency shifts were observed in brain and spinal waves. CONCLUSIONS: L-Dopa may influence the responsiveness of the parkinsonian brain as assessed by frontal somatosensory evoked potentials. The time course of these modifications coincides with that of the clinical response in the motor performance.

Polysomnographic characterization of pergolide-induced sleep attacks in idiopathic PD.

Both dopamine agonists and levodopa may induce episodes termed "sleep attacks" in patients with PD. These episodes are well detailed behaviorally, but little is known about their neurophysiologic characterization. The authors performed a 24-hour polysomnography (PSG) in a PD patient taking pergolide in combination with levodopa, in which four of these diurnal sleep episodes occurred. PSG findings were followed up after pergolide withdrawal. Sleep episodes shared with narcolepsy both behavioral and EEG findings. However, pergolide partly restored a more physiologic sleep architecture, which was disrupted during therapy with levodopa alone.

Italian multicenter study of reversible cerebral ischemic attacks. Part 5. Risk factors and cerebral atherosclerosis.

As part of a prospective study, the influence of several premorbid and environmental factors on the presence, extent and severity of cerebral vessel atherosclerosis was studied in 462 patients with clinical diagnosis of RIA who underwent cerebral angiography. The extent and severity of atherosclerosis of the cerebral vessels was quantified using extracranial and intracranial cerebrovascular scores (ECS, ICS) based on the number and severity of the lesions in 11 extracranial and 21 intracranial arterial segments. Results of univariate and multivariate analyses indicate that the presence of atherosclerotic changes of cerebral vessels, as shown by angiography, was strongly related with age in both sexes. The lesions were more frequent in males, in particular under age 55. Elevated cholesterol was associated with a higher incidence of atherosclerotic lesions. Smoking was associated with a higher incidence of extracranial lesions. Age, smoking and history of hypertension were the best predictors of the extent and severity of cerebral vessel atherosclerosis.

Diagnostic specificity of sensory and motor nerve conduction variables in early detection of carpal tunnel syndrome.

In the carpal tunnel syndrome (CTS) sensory nerve conduction is more sensitive than motor conduction. However, 8%-25% of the sensory distal latencies in symptomatic hands may still be normal. A systematic study was made of the median, ulnar and radial orthodromic nerve conduction velocities (SNCV) stimulating each of the fingers separately. Four SNCVs from the median nerve, two SNCVs from the ulnar nerve and one from the radial nerve were obtained, and the ratio of the median to radial SNCV and the ratios of the median and ulnar SNCVs were estimated. The significance of these parameters in the diagnosis of the CTS was studied, and a rapid technique for the screening of nerve entrapment in the initial stages of the disease is proposed. Three hundred and seventy-five symptomatic hands were examined. Seventy-five hands showed normal distal latency, in which cases, however, the SNCV of the ring finger was always outside the normal range, while the SNCVs of the thumb, index and middle fingers were abnormal in 64%, 80% and 92% of cases respectively. The amplitudes of the sensory responses were the least sensitive of the parameters studied. Our results suggest that a study of the median nerve digital branch to the ring finger may be of value in providing an easily performed and rapid technique for screening an early median nerve entrapment at the wrist.

Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal electrophysiological study.

OBJECTIVE: To evaluate the effects of mechanical compression of the brain-stem in patients with vertebrobasilar dolichoectasia (VBD). METHODS: In the framework of a prospective, observational study that collected clinical and laboratory data in patients with VBD, we studied 20 patients with compression of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral lesions other than small lacunae in the white matter of the cerebral hemispheres were excluded from the study. Patients underwent vestibular and auditory function testing, including brain-stem auditory evoked potentials (BAEPs), blink reflex (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs). RESULTS: Almost all of the patients complained of auditory or vestibular symptoms and none had symptoms or signs of impairment of long tracts or the facial and trigeminal nerves. The most consistent findings were BR abnormalities with prolongation of ipsilateral R1 latency in cases of compression of the pons (10/16) and prolongation of the R2 and R2c latencies with compression of the medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was found in 13 out of 25 instances of compression, and this was more frequent with compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered, and only in cases with compression of the pons. CONCLUSIONS: Neurovascular compression of the brain-stem, even with severe distortion, is seldom associated with overt clinical signs, whereas subclinical dysfunctions are relatively frequent. The central pathways of the BR and the corticospinal pathways are more susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP data provide a functional evaluation of the brain-stem and some cranial nerves, which is lacking in imaging studies. Functional investigations may be useful in the long-term management of these patients, since VBD may be progressive and surgical correction may be required at some stage.

Multifocal neural conduction impairment in forestry workers exposed and not exposed to vibration.

OBJECTIVE: The aim of the study was to assess peripheral neural involvement induced by exposure to hand-arm vibration. METHODS: Twenty lumberjacks, working regularly with chain-saws and exposed to hand-arm vibration (group E) and 20 forestry workers performing heavy manual work and not exposed to vibration (group NE) were matched with a control group of 20 healthy non-manual workers (group C). The subjects of groups E and NE, all symptomatic, and of group C underwent extensive bilateral neurophysiological examination consisting of: sensory conduction (velocity and amplitude) of radial, median and ulnar nerves in digit-wrist segments; sensory conduction (velocity) of median nerve in wrist-elbow segment; mixed conduction (velocity and amplitude) of median and ulnar nerves in palm-wrist segments; motor conduction velocity, including distal motor latencies, and amplitude of median (elbow-wrist) and ulnar (elbow-wrist and across the elbow) nerves. RESULTS: Electrophysiological abnormalities were found in 85% of group E's limbs, versus 62.5% of group NE's limbs. The most frequent pathological pattern in group E was a 'multifocal' impairment (multiple sites of several nerve segments), with a prevalent involvement of sensory rather than motor fibres in the hand, seldom extending to the forearm. Multivariate analysis showed that the neurographic parameters which better characterized workers exposed to hand-arm vibration had a pattern different from that usually found in idiopathic carpal tunnel syndrome (CTS). CONCLUSION: These results suggest that vibration-induced neural involvement can be considered neither pure digital neuropathy, nor definite CTS, as previously described.

Somatosensory processing during movement observation in humans.

OBJECTIVES: A neural system matching action observation and execution seems to operate in the human brain, but its possible role in processing sensory inputs reaching the cortex during movement observation is unknown. METHODS: We investigated somatosensory evoked potentials (SEPs), somatosensory evoked fields (SEFs) and the temporal spectral evolution of the brain rhythms (approximately 10 and approximately 20 Hz) following electrical stimulation of the right median nerve in 15 healthy subjects, during the following randomly intermingled conditions: a pure cognitive/attentive task (mental calculation); the observation of a motoric act (repetitive grasping) with low cognitive content ('Obs-grasp'); and the observation of a complex motoric act (finger movement sequence), that the subject had to recognize later on, therefore reflecting an adjunctive cognitive task ('Obs-seq'). These conditions were compared with an absence of tasks ('Relax') and actual motor performance. RESULTS: The post-stimulus rebound of the approximately 20 Hz beta magnetoencephalographic rhythm was reduced during movement observation, in spite of little changes in the approximately 10 Hz rhythm. Novel findings were: selective amplitude increase of the pre-central N(30) SEP component during both 'Obs-grasp' and 'Obs-seq', as opposed to the 'gating effect' (i.e. amplitude decrease of the N(30)) occurring during movement execution. The strength increase of the 30 ms SEF cortical source significantly correlated with the decrease of the approximately 20 Hz post-stimulus rebound, suggesting a similar pre-central origin. CONCLUSIONS: Changes took place regardless of either the complexity or the cognitive content of the observed movement, being related exclusively with the motoric content of the action. It is hypothesized that the frontal 'mirror neurons' system, known to directly facilitate motor output during observation of actions, may also modulate those somatosensory inputs which are directed to pre-central areas. These changes are evident even in the very first phases (i.e. few tens of milliseconds) of the sensory processing.

Depression of cerebral glucose utilization during animal hypnosis in the rabbit.

The rates of local cerebral glucose utilization have been measured in normal conscious and hypnotized rabbits by the [14C]deoxyglucose method. In control rabbits the rates vary widely throughout the brain, with the values in gray matter broadly distributed around an average which is about 3 times greater than that of white matter. The higher values area in structures of auditory system (superior olive, inferior colliculus, auditory cortex). Animal hypnosis reduces the rates of glucose utilization in all structures of the rabbit brain, particularly in the caudate nucleus, putamen and sensory and motor cortices.

Regional cerebral blood flow changes following chronic administration of antidepressant drugs.

1. Twenty-six patients with major unipolar depression were rated clinically and regional cerebral blood flow (rCBF) determined prior to and after six months of treatment with 75-100 mg/day amitriptyline (n. 16) or 200 mg/day amineptine (n. 10). 2. rCBF was measured in 16 regions over each hemisphere by the Xenon 133 inhalation method and was computed as the initial slope index (ISI). The severity of depression was quantified by the Hamilton rating scale for depression. 3. Baseline rCBF values of depressed patients tended to be lower than those of normal subjects. Significant reductions were observed for all probes exploring the frontal region of the left hemisphere and for some probes exploring the frontal region of the right hemisphere. Chronic treatment with amitriptyline induced a significant increase in rCBF in the left frontal region. Similar results were obtained after treatment with amineptine. 4. Besides confirming frontal lobe dysfunction in depressed patients which is reversed by treatment with classic tricyclic antidepressants, the present results show that this dysfunction may also be reversed by treatment with dopaminergic drugs.

Provocative tests in different stages of carpal tunnel syndrome.

The frequency of positive results of four conventional provocative tests (Phalen sign, Tinel sign, wrist extension and pressure provocation test) was evaluated in 179 patients with clinical and electrophysiological findings consistent with idiopathic carpal tunnel syndrome (CTS), 147 control subjects and 39 patients with polyneuropathy. The diagnostic accuracy was evaluated for each test alone and in combination and the sensitivity correlated with the clinical and electrophysiological severity of CTS. For comparison of the CTS group with the control group, none of the tests reached sufficient diagnostic accuracy. The same was found for comparison of the CTS group with the polyneuropathy group, the Tinel sign being the least accurate. The combination of signs was not found to be more useful than single signs. The sensitivity of all signs was much less in severe clinical stages of CTS, especially for tests that increase the intra-carpal canal pressure. Traditional provocative tests, such as those tested here, have limited or no value for distinguishing patients with and without CTS, one reason being that their sensitivity depends largely on the clinical and electrophysiological severity of CTS. This correlation may also explain the contradictory results in the literature.

Bilateral vestibular loss in vertebrobasilar dolichoectasia.

Bilateral vestibular loss (BVL) is a relatively uncommon syndrome that may produce problems of balance; unsteady gait, especially in the dark; and visual disorders and/or oscillopsia associated with walking and head movements. Sometimes patients with BVL remain asymptomatic. Ototoxic drugs are the most frequently identified cause of BVL, but there are many other possible causes. The aetiology remains unknown in a large percentage of patients. In some, vascular aetiology may be suspected. Here we report 4 cases of vertebrobasilar dolichoectasia (VBD) and symptomatic BVL. In 3 subjects, hearing was preserved, but in the 4th, there was retrolabyrinthine hearing loss. In our opinion, VBD may be the cause of BVL associated or not associated with hearing loss, the reason being that since the anterior vestibular artery is small and has no anastomoses, the horizontal semicircular canal is selectively susceptible to ischemia.

Effect of pentoxifylline on cerebral blood flow in patients with chronic cerebrovascular disease.

The effect of pentoxifylline on cerebral blood flow (CBF) was studied with the intravenous 133Xe clearance technique in eleven patients with chronic cerebrovascular disease. Pentoxifylline was administered orally at a dose of 1200 mg/day over a period of 30 days (eight patients) or by intravenous infusion of 100 ml saline containing 400 mg of the drug in 1 hour (three patients). CBF was measured before and after pharmacological treatment. CBF was found to be significantly increased by both acute and chronic administration of pentoxifylline.

An electromyographic evaluation of motor complications in thoracic herpes zoster.

Motor complications in thoracic herpes zoster were evaluated in 52 patients by electromyographic examination of the paraspinal muscles. At the initial EMG examination, abnormal findings were observed in 18 patients (35%). In 8 patients the myomers involved coincided in location with affected dermatomes, while in 10 patients, in addition to the involvement of myomers corresponding to affected dermatomes, there also appeared an involvement of one or more contiguous myomers not corresponding to affected dermatomes. Our study demonstrated that motor involvement in thoracic HZ is much more common than previously suggested and its incidence (35%) appears to be greater than that reported in both cervical and lumbosacral HZ.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.