Consultation Requests and Satisfaction with a Telehealth Network for Epilepsy: Longitudinal Analysis of the Epilepsy Network Hessen Evaluation.

Background: Telemedicine improves access to specialized medical expertise, as required for paroxysmal disorders. The Epilepsy Network Hessen Evaluation (ENHE) is a pilot cross-sectoral teleconsultation network connecting primary neurologists and pediatricians with epilepsy centers in Hessen, a federal German state. Methods: We prospectively and longitudinally evaluated telehealthcare in the ENHE. Participating physicians rated each consultation for satisfaction and impact on further management. The survey was administered at each consultation and 3 months later. Results: We analyzed 129 consultations involving 114 adult and pediatric patients. Their mean age was 34 years (standard deviation: 26, range: 0.1-91 years), 48% were female, and 34% were children and adolescents. The most common consultation requests were co-evaluation of an electroencephalogram (electroencephalogram [EEG]; 76%) and therapeutic (33%) and differential diagnosis (24%) concerns. Physicians transmitted one paraclinical examination on average (range: 1-4), predominantly EEG (85%), followed by magnetic resonance imaging (17%) and written records (9%). Response rates were 72% for the initial and 67% for the follow-up survey. Across respondents, 99% (n = 92) were satisfied with the ENHE. Overall, 80% of the consultations contributed to the diagnosis, and 90% were considered helpful for treatment, influencing it in 71% of cases. Seizure frequency had decreased more often (96%) than increased (4%) at 3 months. The initial diagnosis was confirmed in 78% of patients. Discussion: In this pilot teleconsultation network for paroxysmal disorders, diagnostic and therapeutic advice was perceived as helpful. Clinical outcomes were largely positive, suggesting tele-epileptology is viable for paroxysmal (seizure) disorders.

Why Do Our Cancer Patients Sleep So Badly? Sleep Disorders in Cancer Patients: A Frequent Symptom with Multiple Causes.

INTRODUCTION: On the one hand, sleep disorders in cancer patients are reported in 30-50% of cancer patients. On the other hand, specific causes for these sleep disorders are little known. This study was done to evaluate factors which may affect sleep of cancer patients. To our knowledge, this is the first study which includes return to work as one factor of sleep disturbance. METHODS: 107 patients with various types of cancer treated in 2 hospitals were interviewed with a battery of questionnaires after having given informed consent. The questionnaires intended to detect abnormalities of sleep and related pain, breathing disorders, restless legs syndrome, depression, rumination, medication, and psychosocial distress. The study was approved by the ethics committee of the University of Marburg. RESULTS: The analysis of the 6 sleep-related questionnaires indicated a sleep disorder of any kind in 68% of all patients. Insomnia symptoms were present in 48 patients (44.9%). Pain, depression, anxiety, and worries about the workplace were significantly related to sleep disorders. CONCLUSION: Sleep disorders are common in cancer patients. The causes are manifold and should be considered by caregivers during diagnosis, therapy, and aftercare of cancer patients. Tumour patients should actively be asked about sleep disorders. If these are present, they should be addressed, and as they have a large impact on quality of life, treatment options should be offered in cooperation with sleep specialists.

Predictors of New Cerebral Microbleeds in Patients with Antiplatelet Drug Therapy.

BACKGROUND: Cerebral microbleeds (CMB) are associated with an increased risk for ischemic and especially hemorrhagic stroke. The aim of the present study is to identify patients at high risk for the development of new CMB after initiation of an antiplatelet drug therapy. METHODS: Patients received magnetic resonance imaging (MRI) within 1 week after initiation of an antiplatelet drug treatment due to a first ischemic stroke (n = 58) and after a follow-up period of 6 months (n = 40). We documented the presence and the number of CMB at baseline and follow-up and analyzed the influence of possible risk factors including vascular risk factors, stroke etiology, and number of CMB at baseline using stepwise logistic regression and Spearman's correlation coefficient. We compared progression rates of CMB in relation to each risk factor using the Mann-Whitney U-test. RESULTS: The logistic regression model could correctly predict the presence of CMB in 70.7% of patients at baseline and 80% at follow-up. The model correctly identified 85% of patients with new CMB. We observed progression of CMB in 40% of the patients. The overall progression rate was .8 CMB per patient. The progression rate was significantly influenced by age more than 70 years and atherothrombotic stroke. The number of new CMB correlated significantly with the number of CMB at baseline. CONCLUSIONS: We found several predictors of CMB after initiation of antiplatelet drug therapy. The results help to identify patients who need closer monitoring and thorough control of risk factors in order to lower the risk of new CMB and associated complications.

Pain in Parkinson's Disease: Current Concepts and a New Diagnostic Algorithm.

BACKGROUND: Pain is a significant burden for patients with Parkinson's disease (PD) with a high impact on quality of life. The present article aims at summarizing epidemiological, pathophysiological, clinical, and neurophysiological data regarding pain in PD. METHODS: In this domain, a procedure of systematic assessment is still lacking for the syndromic diagnosis and should take into account pain characteristics, effects of dopaminergic treatment, motor fluctuations, and non-PD-associated pain. FINDINGS: We propose an original questionnaire addressing an algorithm suitable for daily clinical practice. The questionnaire is based on a three-step approach addressing first the relationship between pain and PD (including temporal relationship with the course of the disease, association with motor fluctuations, and impact of antiparkinsonian treatment), before classifying pain into one of three main syndromes (i.e., musculoskeletal pain, psychomotor restlessness pain, and neuropathic pain). CONCLUSIONS: The proposed questionnaire allows the characteristics of each pain type to be determined according to its relationship with the disease and its treatment. The validation of the clinical use of this questionnaire will be the goal of a forthcoming work.

Diffusion tensor imaging in episodic cluster headache.

BACKGROUND: Cluster headache (CH) is a rare headache disorder with severe unilateral headache bouts and autonomic symptoms. The pathophysiology of CH is not completely understood. Using a voxel-based morphometric paradigm or functional imaging, a key role of the hypothalamus and the pain matrix could be demonstrated during CH episodes. However, there are no diffusion tensor imaging (DTI) data investigating the white matter microstructure of the brain in patients with CH. Therefore, we used DTI to delineate microstructural changes in patients with CH in a headache-free state. METHODS: Seven male patients with episodic CH and 7 healthy subjects were included and examined with a routine 1.5 T magnetic resonance imaging scanner. Whole-head DTI scans measuring fractional anisotropy were analyzed without a priori hypotheses using track-based spatial statistics. RESULTS: We found significant microstructural brain tissue changes bilaterally in the white matter of the brainstem, the frontal lobe, the temporal lobe, the occipital lobe, the internal capsule, and on the right side of thalamus and cerebellum. There were further lesions in the basal frontal lobe that were part of the olfactory system. Alterations of fractional anisotropy in the brainstem might indicate changes of the medial lemniscus and central sympathetic pathways. CONCLUSIONS: Patients with episodic CH have microstructural brain changes in regions that belong to the pain matrix. Furthermore, we were able to detect structural changes suggesting an involvement of the olfactory system as well as lesions in the brainstem indicating an involvement of trigeminal and sympathetic systems.

The effects of oral contraceptives on detection and pain thresholds as well as headache intensity during menstrual cycle in migraine.

BACKGROUND: Clinically, oral contraceptives (OC) can influence pain in both migraine headache and temporomandibular pain disorders. Estrogen as an ingredient of OC might be a responsible factor for these observations. We conducted the present study to test whether OC are able to alter the severity of headache attacks as well as the detection or pain thresholds over the course of the menstrual cycle in patients with migraine. METHODS: Thirteen healthy and regularly menstruating women and 26 migraineurs (13 using OC and 13 not using OC) were studied on the days 1, 4, 14, and 22 of their menstrual cycle. In all participants, saliva was collected first for determination of estrogen on each study day. Then, detection thresholds (warmth, cold, electrical current) and pain thresholds (cold, heat, pressure, electrical current) were assessed. Migraineurs were asked for headache attacks occurring in a period of 24 hours before testing and to estimate pain intensity on a verbal rating scale. RESULTS: On day 4 of the menstrual cycle, migraineurs using OC suffered significantly more from severe migraine attacks than migraineurs not taking OC. With respect to detection and pain thresholds, no effects of OC could be observed as concerning the differences between migraineurs with or without OC medication. On day 22, the severity of migraine headache was significantly related with the pain thresholds for pressure and electrical current, suggesting paradoxically more severe headache attacks in patients presenting with higher pain thresholds. Healthy volunteers disclosed higher salivary estrogen levels than migraineurs and migraineurs not using OC higher concentrations than migraineurs using OC throughout the menstrual cycle. CONCLUSIONS: In this study, the use of OC intensified migraine (however only at the end of menstruation) however had no influence on detection and pain thresholds in migraineurs. Possible reasons for this dissociation will be discussed.

Effects of paired-pulse transcranial magnetic stimulation of the motor cortex on perception of experimentally induced pain.

OBJECTIVE: We investigated the influence of paired-pulse transcranial magnetic stimulation (ppTMS) of the motor cortex (M1) on perception of noxious electrical stimuli. The nociceptive flexion reflex response was assessed to determine spinal effects. METHODS: In the first experiment, the effect of ppTMS of M1 on perception of noxious stimulation of the sural nerve was assessed by varying the stimulus onset asynchronies (SOAs) and the order of the stimulations (-400, -75, -25, 25, 125, 400 ms and control ppTMS, negative sign: ppTMS precedes the noxious stimulation). Effects of a preceding ppTMS on the RII and the RIII response of the nociceptive flexion reflex were investigated for SOAs of -400 and -75 ms. The effects of ppTMS of M1 and of the occipital cortex (Oz) on noxious stimulation of the radial nerve were investigated in a second experiment. Visual analogue scales were used to assess pain intensity and unpleasantness. RESULTS: The results revealed increased pain unpleasantness scores for SOAs of -75, -25, 25, and 400 ms and decreased pain intensity scores for a SOA of -400 ms, when the sural nerve and M1 were stimulated. An increase of the area of the RII response was found for a SOA of -75 ms. For stimulation of the radial nerve, ppTMS of Oz but not of M1 increased the perceived pain at a SOA of 25 ms. DISCUSSION: The facilitatory component of ppTMS led to increased pain perception when applied during the cortical process of Adelta fiber-mediated input, whereas the subsequent inhibitory component may lead to the opposite effect on the subsequent noxious stimulation.

Serum concentrations of s100b and NSE in migraine.

BACKGROUND: The protein s100b indicates astrocytal damage as well as dysfunction of the blood-brain barrier (BBB), and neuron-specific enolase (NSE) is regarded as a marker for neuronal cell loss. Recently, s100b was shown to be a potentially useful marker for migraine in children. In this study, we investigated the levels of s100b and NSE in adult migraineurs during and after migraine attacks in order to gain some more insight into migraine pathophysiology. METHODS: Serum levels of s100b and NSE were measured in 21 migraineurs and compared with 21 healthy subjects matched by sex and age. In migraineurs, blood samples were taken during a migraine attack and following a pain-free period of 2-4 days. RESULTS: During migraine attacks elevated s100b levels could be observed. Maximal concentrations were detected in the pain-free period after 2-4 days. Regarding NSE, serum levels were decreased slightly during and after migraine bouts. CONCLUSIONS: Our data suggest a prolonged disruption of BBB during and after migraine attacks. Other possible explanations concerning the detected serum levels of s100b and NSE will be discussed; however, neuronal cell death can be ruled out by the decreased serum concentrations of NSE. With regard to the results of the present study, further research is necessary to evaluate the role of s100b and NSE in migraine.

Effects of oxidative challenge and calcium on ATP-levels in neuronal cells.

BACKGROUND: Neurocellular overload with hydrogen peroxide (H2O2) induces oxidative stress and may initiate a cascade of intracellular toxic events leading to energy failure, increased lipid peroxidation and subsequently cell death. Studies suggest that hippocampal neurons may be more vulnerable to oxidative stress than cortical cells pointing to a differential vulnerability of neuronal cells. Since disturbed ATP- and calcium (Ca2+)-metabolism may be involved in this process, we here evaluated the effects of H2O2-induced oxidative stress and the involvement of Ca2+-regulation on neuronal energy metabolism. METHODS: Using primary cortical and hippocampal neurons as well as immortalized hippocampal HT22 cells, we determined ATP-levels and accompanying cell death after oxidative challenge with H2O2. Additionally, the combined effects of H2O2 and alterations in Ca2+-concentrations were pharmacologically characterized in more detail. RESULTS: H2O2-incubation decreased ATP-levels in a dose- and time-dependent manner in all neuronal cell systems tested. Such effects were most pronounced in primary hippocampal neurons. In cortical cells, increased ATP-levels were notable under low H2O2-concentrations. A dose-dependent decrease in ATP-concentrations was observed after treatment with Ca2+, which was further enhanced by additional H2O2-challenge. CONCLUSIONS: Our data underline that both, H2O2- and Ca2+-treatment, are able to disturb intracellular energy metabolism. Out of the different systems studied, the ATP-decrease is most pronounced in hippocampal primary neurons, suggesting that this mechanism contributes to the selective neuronal vulnerability to oxidative stress in these neurons.

2-OH-estradiol, an endogenous hormone with neuroprotective functions.

We compared the neuroprotective effects of the catecholestrogen 2-hydroxy-estradiol (2-OH-E(2)) to the actions of 17-beta-estradiol (E(2)), since catecholestrogens have been clinically implicated in the pathophysiology of major depression and other psychiatric diseases. Using the hippocampal HT22 cell line as a well-established in vitro model system, we here show that the extent of the neuroprotective effects of 2-OH-E(2) was significantly increased compared to the physiological estrogen E(2) at equimolar concentrations after a toxic challenge with hydrogen peroxide. Statistically significant effects of neuroprotection as measured by survival of HT22 cells were detectable at concentrations of 1 and 10 microM of 2-OH-E(2) or E(2). Studies on the time-dependence of the evoked reactions showed that a pre-incubation and a post-incubation up to 30 min with a dose of 10 microM of 2-OH-E(2) resulted in a significant decrease in cell death after incubation with hydrogen peroxide if compared to E(2). Further characterization of the effects in rat brain homogenates with an assay for the induction of cellular lipid peroxidation (LPO) revealed, that 2-OH-E(2) was more effective in the reduction of LPO than E(2) in equimolar concentrations. This indicates a pharmacologically relevant effect of this hormone metabolite and a mechanism of action, which does not involve the classical estrogen receptor. In conclusion, the catecholestrogen 2-OH-E(2) induces increased neuroprotective actions in comparison to the major physiological estrogen E(2), suggesting a clinically relevant physiological function of catecholestrogens during health and disease.

Myoclonic encephalopathy caused by chronic bismuth abuse.

Bismuth (Bi) is used for the treatment of different gastrointestinal symptoms and disorders such as gastric ulcers. In Germany, Bi medication is available without prescription as over-the-counter-medication even though it can cause severe myoclonic encephalopathy if ingested chronically in high doses. We report a 49 year-old woman with chronic gastric ulcers and 5 years of Bi abuse who developed the typical clinical course of Bi encephalopathy. She presented with progressive dementia, dysarthria and myoclonic jerks one week after increasing the Bi dosage. The EEG showed generalized spike-wave complexes suggesting that the myoclonus was epileptic in nature. Bi intake was stopped and valproate was given, which decreased the frequency of the myoclonic jerks. Administration of the metal chelator D,L-2,3-dimercaptopropane- 1-sulfonic acid (DMPS) led to increased urine excretion of Bi, but was accompanied by a clinical deterioration which resulted in it being discontinued. The subsequent clinical recovery of the patient was documented over 40 days by EEG, video and neuropsychological testing. A time lag of two weeks was observed between falling plasma levels and clinical improvement. In conclusion, Bi-induced encephalopathy is a differential diagnosis for myoclonic encephalopathies. Treatment with metal chelators may aggravate the encephalopathy. The over-the-counter availability of medications containing Bi should be questioned. (Published with video sequence.)