Objective and subjective sleep measures are associated with HbA1c and insulin sensitivity in the general population: Findings from the ORISCAV-LUX-2 study.

AIM: To analyze the association of objective and subjective sleep measures with HbA1c and insulin sensitivity in the general population. METHODS: Using a cross-sectional design, data from 1028 participants in the ORISCAV-LUX-2 study from the general population in Luxembourg were analyzed. Objective sleep measures were assessed using accelerometers whereas subjective measures were assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Sleep measures were defined as predictors, while HbA1c and quantitative insulin sensitivity check index (QUICKI) scores were considered outcomes. Linear and spline regression models were fitted by progressively adjusting for demographic and lifestyle variables in the total sample population as well as by stratified analyses using gender, obesity status, depressive symptoms and diabetes status. RESULTS: In fully adjusted models, total and deep sleep durations were associated with lower HbA1c (mmol/mol) levels, whereas sleep coefficients of variation (%) and poor sleep efficiency, as measured by PSQI scores (units), were associated with higher HbA1c levels. In stratified models, such associations were observed mainly in men, and in subjects who had depressive symptoms, were overweight and no diabetes. In addition, total sleep, deep sleep, coefficients of variation and poor sleep efficiency as measured by PSQI revealed non-linear associations. Similarly, greater insulin sensitivity was associated with longer total sleep time and with PSQI-6 (use of sleep medication). CONCLUSION: Associations were more frequently observed between sleep characteristics and glycaemic control with the use of objective sleep measures. Also, such associations varied within subgroups of the population. Our results highlight the relevance of measuring sleep patterns as key factors in the prevention of diabetes.

Fibroblast mitochondria in idiopathic Parkinson's disease display morphological changes and enhanced resistance to depolarization.

Mitochondrial dysfunction is a hallmark in idiopathic Parkinson's disease (IPD). Here, we established screenable phenotypes of mitochondrial morphology and function in primary fibroblasts derived from patients with IPD. Upper arm punch skin biopsy was performed in 41 patients with mid-stage IPD and 21 age-matched healthy controls. At the single-cell level, the basal mitochondrial membrane potential (Ψm) was higher in patients with IPD than in controls. Similarly, under carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) stress, the remaining Ψm was increased in patients with IPD. Analysis of mitochondrial morphometric parameters revealed significantly decreased mitochondrial connectivity in patients with IPD, with 9 of 14 morphometric mitochondrial parameters differing from those in controls. Significant morphometric mitochondrial changes included the node degree, mean volume, skeleton size, perimeter, form factor, node count, erosion body count, endpoints, and mitochondria count (all P-values < 0.05). These functional data reveal that resistance to depolarization was increased by treatment with the protonophore FCCP in patients with IPD, whereas morphometric data revealed decreased mitochondrial connectivity and increased mitochondrial fragmentation.

Enteric neurons from Parkinson's disease patients display ex vivo aberrations in mitochondrial structure.

Based on autopsy material mitochondrial dysfunction has been proposed being part of the pathophysiological cascade of Parkinson's disease (PD). However, in living patients, evidence for such dysfunction is scarce. As the disease presumably starts at the enteric level, we studied ganglionic and mitochondrial morphometrics of enteric neurons. We compared 65 ganglia from 11 PD patients without intestinal symptoms and 41 ganglia from 4 age-matched control subjects. We found that colon ganglia from PD patients had smaller volume, contained significantly more mitochondria per ganglion volume, and displayed a higher total mitochondrial mass relative to controls. This suggests involvement of mitochondrial dysfunction in PD at the enteric level. Moreover, in PD patients the mean mitochondrial volume declined in parallel with motor performance. Ganglionic shrinking was evident in the right but not in the left colon. In contrast, mitochondrial changes prevailed in the left colon suggesting that a compensatory increase in mitochondrial mass might counterbalance mitochondrial dysfunction in the left colon but not in the right colon. Reduction in ganglia volume and combined mitochondrial morphometrics had both predictive power to discriminate between PD patients and control subjects, suggesting that both parameters could be used for early discrimination between PD patients and healthy individuals.

[Akinetic mutism due to fulminant multilocular cerebral venous thrombosis, including the vein of Galen]. / Akinetischer Mutismus bei fulminanter multilokulärer Sinus- und Venenthrombose einschließlich der Vena Galeni.

Cerebral venous thrombosis may present with multifaceted symptoms and therefore be difficult to diagnose. Only few evidence-based data exist with respect to therapy and prognosis, especially concerning the deep cerebral venous system. A thrombosis of the vein of Galen is deemed to have a poorer prognosis. Our case report describes the local combined neuro-interventional therapy as an individual attempt to cure a patient with a fulminant disease course.

[Pathogenesis of narcolepsy: from HLA association to hypocretin deficiency]. / Zur Pathogenese der Narkolepsie: Vom HLA-Typus als Risikoprofil zum Hypocretinmangel als Ursache.

Narcolepsy is a rare and chronic sleep disorder, characterised by excessive daytime sleepiness. Frequently associated signs are cataplexy, sleep paralysis and hypnagogic or hypnopompic hallucinations. Advances in understanding the pathogenesis of the disease have essentially been elucidated during the last fifteen years. The most significant finding has been the discovery of hypocretin-1 and -2 in 1998. Hypocretin-containing cells have widespread projections throughout the entire CNS and play a crucial role in the regulation of the sleep-wake cycle. They also contribute to olefaction and to the regulation of food intake. Animal models and human studies concordantly show that the disturbed hypocretin system is the probable cause of narcolepsy. However, it remains unclear why there is neuronal death of hypocretin-producing cells in the lateral hypothalamus. As the HLA-allele DQB1*0602 is associated with narcolepsy and hypocretin deficiency, an autoimmune reaction against hypocretin-producing neurons has been vigorously discussed. Newly discovered gene polymorphisms as well as previously unknown pathogenetic mechanisms, linking the sleep-wake cycle with the immune system, may also contribute to the pathogenetic cascade. Worthy of mention in this context is, e.g., the "insulin-like growth factor"-binding protein 3 (IGFBP3), whose overexpression causes a down-regulation of the hypocretin production. Substitution of the deficient neuropeptides by hypocretin agonists may become the causal treatment strategy of the future, if an adequate administration route can be found. Presently, animal trials, including genetic therapy, cell transplantations or the administration of hypocretin receptor agonists, are underway.

Vitamin B1 in the treatment of Wernicke's encephalopathy due to hyperemesis after gastroplasty.

Wernicke's encephalopathy (WE) is a severe brain disorder, first described in 1881, and is caused by a nutritional deficiency of thiamine (vitamin B1) found mostly in patients suffering from chronic alcoholism. In addition, WE can also complicate bariatric surgery if adequate vitamin supplementation is not insured. Without immediate treatment, the prognosis is poor and the mortality rate is high. Most patients present with atypical neurological symptoms, which hampers rapid diagnosis. We present a 40-year-old woman who underwent gastroplasty combined with gastric banding for severe obesity. She experienced repetitive vomiting and her diet was without vitamin supplementation. After three months she developed convergent strabismus, apathy and urinary incontinence, which was diagnosed as WE and treated as such. Six months later her recovery was incomplete, still showing gait difficulties and nystagmus. We aim to show that adequate vitamin supplementation in patients undergoing gastroplasty is necessary, especially considering the risk of permanent neurological deficits.

Early decompressive hemicraniectomy in fulminant herpes simplex encephalitis.

Herpes encephalitis can be a life-threatening condition, despite early instauration of acyclovir treatment. In particular patients may succumb to rapidly progressive cerebral oedema. We report a 66-year patient with a Glasgow Coma Score (GCS) of 6 and incipient uncus herniation of the right temporal lobe on the third day. Decompressive hemicraniectomy was immediately performed. The long-term outcome was satisfactory with unassisted gait and a Barthel Index score of 70 after 9 months.

Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo.

OBJECTIVE: Although Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) show a wide clinical and neuropathologic overlap, they are differentiated according to the order and latency of cognitive and motor symptom appearance. Whether both are distinct disease entities is an ongoing controversy. Therefore, we directly compared patients with DLB and PDD with multitracer PET. METHODS: PET with (18)fluorodopa (FDOPA), N-(11)C-methyl-4-piperidyl acetate (MP4A), and (18)fluorodeoxyglucose (FDG) was performed in 8 patients with PDD, 6 patients with DLB, and 9 patients with PD without dementia vs age-matched controls. Data were analyzed with voxel-based statistical parametric mapping and region of interest-based statistics. RESULTS: We found a reduced FDOPA uptake in the striatum and in limbic and associative prefrontal areas in all patient groups. Patients with PDD and patients with DLB showed a severe MP4A and FDG binding reduction in the neocortex with increasing signal diminution from frontal to occipital regions. Significant differences between PDD and DLB were not found in any of the radioligands used. Patients with PD without dementia had a mild cholinergic deficit and no FDG reductions vs controls. CONCLUSIONS: Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain.

Slow wave sleep and dopaminergic treatment in Parkinson's disease: a polysomnographic study.

BACKGROUND: In Parkinson's disease (PD), there is entanglement of disease-inherent and treatment-induced sleep abnormalities. So far, there has been no study specifically investigating the influence of diurnal dopaminergic medication (DM) on nocturnal slow wave sleep (SWS). METHODS: Polysomnographic analysis in 62 PD patients. RESULTS: PD patients had a sleep efficiency of 70 +/- 17% and an SWS amount of 16 +/- 11%. Linear regression analysis showed no significant correlation between the amounts of SWS and DM. However, patients with a medium DM dosage (300-600 mg of levodopa equivalents) preserved a SWS percentage >25% (p = 0.035, chi(2) test) more frequently than patients with higher or smaller DM. The DM dosage had no effect on other main sleep parameters. Psychotropic comedication had no effect on SWS percentage. In contrast, SWS amount was inversely correlated with both disease duration and age. It was independent of rapid eye movement sleep amount. The natural female bonus effect on SWS amount was absent in women with PD. CONCLUSION: Diurnal dopaminergic treatment has no major impact on SWS in PD, which, however, decreases with disease duration. Disease-dependent, but treatment-independent decrease in SWS suggests primary degeneration of sleep-regulating systems in PD.

Early decompressive hemicraniectomy in fulminant herpes simplex encephalitis.

Herpes encephalitis can be a life-threatening condition, despite early instauration of acyclovir treatment. In particular patients may succumb to rapidly progressive cerebral oedema. We report a 66-year patient with a Glasgow Coma Score (GCS) of 6 and incipient uncus herniation of the right temporal lobe on the third day. Decompressive hemicraniectomy was immediately performed. The long-term outcome was satisfactory with unassisted gait and a Barthel Index score of 70 after 9 months.

Ventral intermediate thalamic stimulation in complex tremor syndromes.

BACKGROUND/AIMS: We report on deep brain stimulation (DBS) in the ventral intermediate part of the thalamus in 4 patients with complex tremor syndromes, 2 classified as Holmes tremor (HT) and 2 as thalamic tremor (TT). RESULTS: Three out of 4 patients showed intraoperative improvement and underwent DBS implantation. One patient with TT without intraoperative improvement was not provided with an implant. A sustained beneficial effect was present after a follow-up ranging from 20 months to 7 years, although there was partial persistence of the intentional tremor and of proximal myoclonic-dystonic movements. The mean global clinical impression score was 2. In 1 HT patient the benefit persisted after battery failure. CONCLUSION: The study confirms that ventral intermediate thalamic DBS can provide long-term efficacy for HT and TT. While the patients experienced considerable and lasting functional improvement, the effect was incomplete and not all elements of their complex movement disorders were equally suppressed.

Creutzfeldt-Jakob disease with slow progression. A mimickry of progressive supranuclear palsy.

Sporadic Creutzfeldt-Jakob disease (sCJD) does not always present with typical clinical signs, such as myoclonus in association with periodic sharp-wave complexes. We present a 67-year old female patient with initial falls and vertical gaze palsy, suggesting the diagnosis of Progressive Supranuclear Palsy (PSP). EEG and MRI were not contributory. Typical clinical and paraclinical CJD signs were only seen after 17 months. The diagnosis was confirmed by autopsy. - CJD can be a neurodegenerative chameleon. The present case adds to the scare literature of slowly evolving CJD mimicking Parkinsonism related to tauopathies.

[The neurology of REM sleep. A synoptic tour de force]. / Zur Neurologie des Traumschlafs. Versuch einer Synopsis.

REM or dreaming sleep is one of three states of consciousness. It is characterized by rapid eye movements, muscle atonia, desynchronized EEG, and autonomic dysregulation. A dysfunction of one of these four cardinal traits explains the primary disorders of REM sleep, including REM sleep behavior disorder and narcolepsy. Although seen in other stages, sleep apnea syndrome, coronary syndromes, and stroke are strongly triggered by the autonomic dysregulation of REM sleep. REM sleep has an antiepileptic effect, which has not yet been used in clinical practice. It favors procedural memory, but not declarative memory. While present neurophysiologic theories, backed up by new neuroimaging techniques, preferentially explore the genesis of REM sleep, psychodynamic theories have searched for its raison d'être by focusing on mentally stabilizing or purifying effects of dreaming. The exploding interest in dreaming sleep, images, and imaging may also yield a harvest for clinical medicine, and further perplexing findings, such as RBD as harbinger of parkinsonism should be expected.

Cervical artery dissection: An atypical presentation with Ehlers-Danlos-like collagen pathology?

The authors took skin biopsies of the macroscopically normal skin of seven consecutive patients with spontaneous cervical artery dissection (SCAD). Histologically, alterations of the collagen and elastic fiber networks were found in six patients. In five, the histologic, immunohistochemical, and ultrastructural changes were similar to those usually found in Ehlers-Danlos syndrome (EDS). This suggests that SCAD is frequently associated with the dermal alterations seen in EDS.

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

[Visual hallucinations in Parkinson and Charles Bonnet Syndrome patients. A phenomenological and pathogenetic comparison]. / Die optischen Halluzinationen des Parkinson-Patienten und das Charles Bonnet-Syndrom. Eine phänomenologische und pathogenetische Gegenüberstellung.

UNLABELLED: Visual hallucinations (VH) are seen in about a third of all patients with Parkinson's disease (PD) and are usually considered to be an early marker or clinical component of a dopaminergic psychosis. Their peculiar phenomenology has not yet been studied in a systematic manner. METHODS: A semi-structured interview was performed twice in 62 PD patients. Different motoric and cognitive disease scales were used. The patients were not demented or depressed and had no other psychotic features other than hallucinations. Their visions was at least 0.6. RESULTS: 22 patients (36%) reported complex visual hallucinations or illusions in both interviews. These patients were not different from the non-hallucinating patients in terms of age, duration and stage of the disease, dosage and type of medication and frequency of cataracts. VH were diurnal in 41% of the patients, nocturnal in 18% of the patients and mixed in 41 patients. They were seen at least once weekly in 67% and they lasted always less than an hour. VH most frequently involved adults, children and pets. They were often mobile and had normal size and physiognomy. Notable emotional reactions were only reported by 18% of the patients. DISCUSSION: The phenomenology of VH in PD differs from VH in exogenous or endogenous psychoses, but is similar to the Charles Bonnet-syndrome (CBS), appearing in elderly patients with different visual deficits. As PD patients suffer regularly from visual deficits of contrast and color perception, a similar pathogenesis to CBS can be hypothesized, with these "minor" and benign VH being due to "release phenomena" in relation to partial visual deprivation. The lack of multimodality hallucinations and of secondary paranoia as well as the clear sensorium are helpful features in distinguishing them from toxic psychosis.

Decreased color discrimination and contrast sensitivity in Parkinson's disease.

Patients with Parkinson's disease (PD) often complain of blurred vision or even of distinctive visual disturbances like hallucinations and illusions. Recent studies have emphasized the potential influence of primary visual deficits of color and contrast discrimination. To study primary visual function, we studied color discrimination (CD) and contrast sensitivity (CS) during 'on' medication in PD patients and compared them to non-PD subjects. Twenty one PD patients were compared to 30 age-matched controls using CD tested by the D-15 Lanthony test (D15) and the Farnsworth-Munsell 100 Hue test (FM) and CS tested by the Pelli-Robson (PL) and the Vis-Tech tables (VT). We excluded subjects with a visual acuity

Visual hallucinations induced by deep brain stimulation in Parkinson's disease.

We report a patient with idiopathic Parkinson's disease who underwent bilateral deep brain stimulation (DBS) of the nucleus subthalamicus (STN) and developed visual hallucinations (VH) while taking no medications only when the DBS was turned on. The hallucinations resolved when the stimulator was turned off. The phenomenology and the prompt response to clozapine suggest that DBS-induced VH mimic pharmacologically-induced VH.