[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.

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.

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.

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.

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.

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.

Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson's disease.

OBJECTIVE: To determine the occurrence of REM sleep behavior disorder (RBD) and sleep-related injury (SRI) in an outpatient PD practice. BACKGROUND: RBD is a frequent cause of SRI in older individuals. Although RBD is seen in PD, the association of SRI and RBD in PD has not been previously assessed. DESIGN/METHODS: Consecutive patients with PD and their caregivers were interviewed using a structured questionnaire assessing the presence of RBD and SRI. Patients fulfilling the International Classification of Sleep Disorders (ICSD) criteria for RBD were compared with non-RBD patients. In a separate analysis, patients with a prior SRI were compared to those without. RESULTS: Of the 61 patient/caregiver pairs, 15% (7 men and 2 women) met the clinical criteria for RBD. There were more episodes of SRI in the RBD group, with 33% causing injury to themselves or to their caregivers compared with 6% of the non-RBD group (chi(2) = 13, p = 0.005). In the second analysis, 15% (all men) patient/caregiver pairs reported SRI. Of these, 66% of the patients had behaviors resembling those seen in RBD, and 33% had recalled dream content. There is a significant association between SRI and RBD for dream-enacting sleep behaviors (Fisher's exact test, p = 0.0001). CONCLUSION: PD patients with SRI frequently have behavioral features of RBD. If RBD underlies most SRI, treatment with appropriate pharmacologic agents, such as clonazepam, may prevent future occurrences of SRI.

Blinded evaluation confirms long-term asymmetric effect of unilateral thalamotomy or subthalamotomy on tremor in Parkinson's disease.

In the past, stereotactic surgery was a regular treatment for prominent unilateral tremor in Parkinson's disease (PD), but follow-up studies were usually short-term and always unblinded. We examined 17 PD patients in long-term follow-up (mean, 10.9 years after surgery) and used videotapes and the Unified Parkinson's Disease Rating Scale to blindly compare tremor ipsilateral and contralateral to the side of surgery. Since the patients were specifically selected for stereotactic surgery because of asymmetric tremor, and the surgical side chosen was contralateral to the predominant tremor, a sign of long-term efficacy would be current postoperative reversal of tremor side predominance. Upper extremity tremor was significantly better contralateral to the surgery compared with the ipsilateral side. We conclude that stereotactic surgery improved the absolute magnitude of tremor or ameliorated its rate of progression. Since asymmetric bradykinesia and dyskinesia were not a prerequisite for the choice of surgical side, we cannot make any conclusion about long-term impact of surgery on these features.

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.

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.

Poor visual discrimination and visual hallucinations in Parkinson's disease.

This study examined the relationship between deficits in color and contrast discrimination and visual hallucinations (VH) in patients with Parkinson's disease (PD) and normal visual acuity. Thirty-five nondemented and nonpsychotic PD patients with normal visual acuity and without major ophthalmologic disease were interviewed twice and divided into two groups: hallucinators (n = 14) and non-hallucinating controls (n = 21). The groups were compared for color vision (assessed by Lanthony D-15 [LD] and Farnsworth-Munsell 100 hue [FM] tests), and for contrast sensitivity (tested by Vis tech tables [VT] and monocular and binocular Pelli-Robson test [PR]). There was no difference in age, duration or stage of PD, or dosage or duration of levodopa therapy between the two groups. Parkinson's disease patients showed impairment on all visual tests, with the hallucinators performing worse than the controls on all tests. This difference was significant for the LD (p < 0.007), the VT at 1.5 and 3 cycles per degree (p < 0.037 and 0.043, respectively) and the monocular PR tests (p < 0.049). The results led the authors to conclude that in patients with normal visual acuity, those with VH show added visual deficits of color and contrast discrimination. These ophthalmopathies may therefore be facilitating factors for visual hallucinations in PD and justify more focused research on the pathophysiology of visual hallucinations in Parkinson's disease.

Dopaminergic agonists in the treatment of Parkinson's disease.

Dopaminergic agonists are drugs that directly stimulate the dopamine receptors of the striatum and have proved useful in treating Parkinson's disease. In the United States, they are primarily used in conjunction with levodopa. Most have long half-lives and have been particularly useful in controlling and attempting to prevent motor fluctuations.

Drug-induced movement disorders.

Drug-induced movement disorders are often unrecognized, especially when not due to dopamine receptor blockers. This review discusses acute, subacute, and chronic syndromes. Pathophysiology relates almost always to dopaminergic transmission. Patient-dependent vulnerability and drug-dependent sensitivity are contributing factors. Young patients are more prone to acute reactions, and tardive or chronic conditions are more frequent in the elderly. Subclinical Parkinsonism can be unmasked by medication exposure. Treatment of tardive dyskinesia remains a challenging task for the clinician, but novel antipsychotics and dopamine depleting agents can be beneficial.

[Brain involvement in acquired immunodeficiency syndrome (AIDS): computed tomography (CT) and magnetic resonance tomography (MR)]. / Zerebrale Beteiligung bei erworbenem Immunmangelsyndrom (AIDS). Computertomographie (CT) und Kernspintomographie (MR).

Involvement of the central nervous system in acquired immune deficiency syndrome (AIDS) is usually due to opportunistic infections; these frequently offer a difficult differential diagnostic problem. Imaging methods play an important part in the elucidation of symptoms. CT and MR findings were analysed in 13 patients with AIDS and neurological symptoms. Some infections of the central nervous system (encephalitis of unknown aetiology, cytomegalic encephalitis, meningitis) may show cerebral atrophy or even no morphological changes. Toxoplasmosis and PML are the most common opportunistic infections typical changes on CT and MR may lead to diagnosis. MR offers advantages compared with CT in its higher sensitivity for the demonstration even of small lesions.