Rob L. M. Strijers

Sleep loss affects vigilance: effects of chronic insomnia and sleep therapy

Although complaints of impaired daytime functioning are essential to the diagnosis of primary insomnia, objective evidence for cognitive dysfunction has been hard to establish. A prerequisite for understanding the neurocognitive consequences of primary insomnia is to establish task paradigms that robustly differentiate insomniacs from well‐sleeping subjects. We hypothesized that the decline in performance that typically occurs with an increasing cognitive demand would provide a more sensitive measure than performance on a single task version. The hypothesis was tested, first, by assessing the performance on two vigilance tasks with different cognitive demands in 25 elderly patients with primary insomnia and 13 healthy well‐sleeping age‐matched subjects. Secondly, we investigated the performance response to sleep therapy using a waiting‐list controlled design. Sleep therapy consisted of a multi‐component intervention including sleep restriction, cognitive behavioral therapy, bright‐light therapy, structured physical activity and body temperature manipulations. The results show that insomniacs differed markedly from controls in their reaction times across tasks with different cognitive demands: patients responded faster on the ‘simple’ vigilance task, yet slower on the ‘complex’ vigilance task. Sleep therapy effectively restored normal performance: patients became significantly slower on the ‘simple’ task and faster on the ‘complex’ task, returning to the performance levels of control subjects. These findings indicate that the performance decline associated with increasing cognitive demands is possibly the first sensitive and robust measure of the neurocognitive sequelae of insomnia. We suggest that future studies on cognition in primary insomnia should apply a design that varies task demands.

The diagnostic value of electroencephalography in mild senile Alzheimer's disease

OBJECTIVE We investigated the diagnostic value of the visually assessed electroencephalogram (EEG) in patients with mild Alzheimers disease (AD), using the grand total of EEG (GTE) score. METHODS Forty-nine non-demented control subjects with and without minimal cognitive impairment from the general population and 86 probable AD patients (NINCDS-ADRDA criteria), consecutively referred to a memory clinic, participated in this study. RESULTS Frequency of rhythmic background activity (P<0.05), diffuse slow activity (P<0.001), and reactivity of the rhythmic background activity (P<0.001) were statistically significant related to the diagnosis control subject or AD patient, using logistic regression analysis with adjustment for age and sex. When these subscores were used to confirm the diagnosis of AD, thus at high specificity of 89.1% (GTE cut-off point of 3), the sensitivity was 44.6% and positive predictive value was 88.1%. Incremental ruling-in and ruling-out curves showed a maximum diagnostic gain of 38% for a positive test result at a prior probability ranging from 30 to 40%. At high pretest probability levels of 80-90%, the diagnostic gain for a positive test result was low, varying from 7 to 14%. CONCLUSION In conclusion, the visually assessed EEG may give a clinically meaningful contribution to the diagnostic evaluation of AD when there is diagnostic doubt.

Fatigue, sleep disturbances and circadian rhythm in multiple sclerosis

The aim of this study was to investigate whether fatigue and sleep disturbances in multiple sclerosis (MS) patients might be due to disrupted circadian sleep wake regulation. Actigraphy and a multiple sleep latency test (MSLT) were performed in 16 MS patients with both prominent sleep complaints and fatigue. Actigraphy scores did not differ from control values, whereas sleep onset latency values were altered in subgroups of MS patients. No evidence was found for a generalized circadian disturbance in MS patients.

Seizure detection in the neonatal EEG with synchronization likelihood.

OBJECTIVE To investigate whether epileptic seizure activity can be distinguished from non-epileptic background activity in the neonatal electroenceplalogram (EEG), using synchronization likelihood as a measure of synchronization between EEG channels. METHODS Forty-two 21s EEG epochs and two complete EEGs from 21 different neonatal patients in a 12-channel bipolar recording were studied (AD-conversion 16bit; sample frequency 200Hz; filter setting 0.5-30Hz). For EEG of each patient, we selected one epoch with epileptic discharges and one without. Synchronization was calculated in all epochs. In two complete EEGs, synchronization was calculated and correlated with a visual scoring of the EEG. RESULTS Synchronization likelihood was higher in all the epochs with epileptic seizures as compared to the epochs without epileptic activity (P<0.01). When synchronization likelihood exceeded 0.11, the sensitivity for the presence of epileptic activity was 0.85 (95% confidence limits [CL(95)]=0.69-1) and the specificity was 0.75 (CL(95)=0.56-0.94).Analysis of EEG score and synchronization likelihood of two complete EEGs revealed a high correlation between the occurrence of epileptic seizures and elevated synchronization likelihood (Spearman r=0.707, P<0.001). CONCLUSIONS The results of this study demonstrate that synchronization likelihood is a potential tool in the automatic monitoring of high-risk infants for epileptic activity on neonatal wards.

The caudate: a key node in the neuronal network imbalance of insomnia?

Although insomnia is common and disabling, its neural correlates remain enigmatic. Stoffers et al. use structural and functional MRI to demonstrate that hyperarousal, its clearest characteristic, involves reduced recruitment and connectivity of the left caudate that may predispose to insomnia and perpetuate it.

Is Disturbed Intracortical Excitability a Stable Trait of Chronic Insomnia? A Study Using Transcranial Magnetic Stimulation Before and After Multimodal Sleep Therapy

BACKGROUND Chronic insomnia is a poorly understood disorder. Risk factors for developing chronic insomnia are largely unknown, yet disturbances in brain indexes of arousal seem to accompany the disorder. We here investigate whether insomnia patients and control participants differ with respect to brain responses to direct stimulation, i.e., cortical excitability. Transcranial magnetic stimulation (TMS) offers a method to directly investigate the excitability level of the human cerebral cortex in psychiatric and neurological disease. METHODS We investigated cortical excitability in 16 insomnia patients and 14 carefully matched control participants using absolute and relative amplitudes of motor evoked potentials in response to single- and paired-pulse stimulation using TMS. RESULTS Nonmedicated insomnia patients showed, first, an exaggerated absolute response to both suprathreshold single- and paired-pulse stimulation compared with control participants and second, a reduced relative response to paired-pulse stimulation at long interpulse intervals (i.e., a reduced intracortical facilitation). The abnormal excitability persisted despite sleep therapy that effectively improved sleep quality as well as behavioral and neuroimaging indexes of brain function. CONCLUSIONS The results suggest that a subtly disturbed intracortical excitability characterizes patients with chronic insomnia: a relatively reduced intracortical facilitation in the context of a globally increased absolute excitability. The findings do not resemble TMS findings after sleep deprivation or in sleep apnea and thus seem specific to insomnia. They may offer diagnostic value and implications for assessment of risk to develop this common and disabling disorder.

Investigation of resting-state EEG functional connectivity in frontotemporal lobar degeneration

OBJECTIVE To investigate the presence of EEG abnormalities in frontotemporal lobar degeneration (FTLD) in comparison with Alzheimers disease (AD) and non-demented individuals with subjective memory complaints (SMC), using an elaborated visual EEG rating scale; furthermore, to investigate whether assessment of resting-state functional connectivity of the EEG is superior to visual evaluation in distinguishing between FTLD, AD and non-demented controls. METHODS EEGs of 15 patients with FTLD, 20 with AD and 23 individuals with SMC were visually compared using the Grand Total EEG (GTE) score. The synchronization likelihood (SL) as a measure of functional connectivity between different EEG channels was calculated for the 0.5-4Hz, 4-8Hz, 8-10Hz, 10-13Hz, 13-30Hz and 30-45Hz frequency bands. Patients had mild to moderate dementia. RESULTS In AD, as expected, the GTE revealed significant differences from FTLD and SMC, indicating more EEG slowing and loss of reactivity. Patients with FTLD, however, could not be discriminated from individuals with SMC by the GTE score. Analysis of resting-state functional connectivity showed decreased SL in AD compared to both FTLD and SMC in the lower and higher alpha frequency band and decreased SL in AD compared to SMC in the beta frequency band, whereas no differences between FTLD and AD or SMC were found. CONCLUSIONS In patients with mild to moderate FTLD both the visually rated EEG and EEG measures of resting-state functional connectivity are normal. SIGNIFICANCE Although widespread neuronal degeneration takes place in frontotemporal lobar degeneration, this is not reflected in the EEG during the mild to moderate stages of the disease. An abnormal EEG in a mildly demented subject favours a diagnosis of AD.

Short- and long-term effects of selective dorsal rhizotomy on gross motor function in ambulatory children with spastic diplegia

OBJECT The primary aim of this prospective cohort study was to evaluate the short-term (1 year) and long-term (mean 6 years) effects of selective dorsal rhizotomy (SDR) on gross motor function and spasticity in ambulatory children with spastic diplegia. Secondary aims were to investigate side effects, additional treatment during follow-up (botulinum toxin type A injections or orthopedic surgery), and parental satisfaction. METHODS Thirty-three children who had undergone SDR at a mean age of 6 years and 7 months (± 2 years) were included. There were 7 children at Gross Motor Function Classification System (GMFCS) Level I, 7 at Level II, and 19 at Level III. Gross motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66). Spasticity was measured according to a modified Tardieu scale. Side effects, additional treatment, and parental satisfaction were recorded using a parental questionnaire and medical records. RESULTS At 1-year follow-up, mean GMFM-66 scores improved significantly by 4.3 ± 4.1 points. Children at GMFCS Levels I and II showed significantly more improvement (7.2 points) on the GMFM-66 compared with children at GMFCS Level III (2.9 points). On long-term follow-up (mean 6 years ± 22 months), mean GMFM-66 scores improved significantly by 6.5 ± 5.9 points, without a difference between children at GMFCS Levels I and II and Level III. No relapse of spasticity was noted. Ten children (30%) needed orthopedic surgery and 13 children (39%) received botulinum toxin type A treatment after SDR. Twenty (91%) of the 22 parents who answered the questionnaire at long-term follow-up believed that their childs functioning had improved after SDR. CONCLUSIONS Selective dorsal rhizotomy resulted in short- and long-term improvements in gross motor function, without relapse of spasticity. However, the majority of the children still needed additional surgery or botulinum toxin A treatment.

Diagnosing Alzheimer's Disease in Community-Dwelling Elderly: A Comparison of EEG and MRI

In a study on the course of cognitive impairment in people over 65 years of age, 58 randomly selected community dwelling elderly underwent EEG and MRI studies. The EEG was visually and quantitatively (qEEG) assessed. Nine out of 58 subjects appeared to have Alzheimer dementia (AD) according to CAMDEX criteria. In this group medial temporal lobe atrophy on MRI, as an objective criterium for AD, showed a total accuracy of 72%, visually assessed EEG 81% and qEEG 81-84%. There was an incomplete overlap in subjects regarding MRI and EEG abnormalities, implying that both methods may be complementary.

Long-term effect of selective dorsal rhizotomy on gross motor function in ambulant children with spastic bilateral cerebral palsy, compared with reference centiles

The aim of this study was to evaluate the long‐term effect of selective dorsal rhizotomy (SDR) on the gross motor function of ambulant children with spastic bilateral cerebral palsy (CP), compared with reference centiles.