Increased EEG power and slowed dominant frequency in patients with neurogenic pain

To study the mechanisms of chronic neurogenic pain, we compared the power spectra of the resting EEG of patients (n = 15, 38-75 years, median 64 years, 6 women) and healthy controls (n = 15, 41-71 years, median 60 years, 8 women). On an average, the patient group exhibited higher spectral power over the frequency range of 2-25 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 7-9 Hz band in all electrodes. Frontal electrodes contributed most to this difference in the 13-15 Hz band. Bicoherence analysis suggests an enhanced coupling between theta (4-9 Hz) and beta (12-25 Hz) frequencies in patients. The subgroup of six patients free from centrally acting medication showed higher spectral power in the 2-18 Hz frequency range. On an individual basis, the combination of peak height and peak frequency discriminated between patient and control groups: discriminant analysis classified 87% of all subjects correctly. After a therapeutic lesion in the thalamus (central lateral thalamotomy, CLT) we carried out follow-up for a subgroup of seven patients. Median pain relief was 70 and 95% after 3 and 12 months, respectively. The average EEG power of all seven patients gradually decreased in the theta band and approached normal values only after 12 months. The excess theta EEG power in patients and its decrease after thalamic surgery suggests that both EEG and neurogenic pain are determined by tightly coupled thalamocortical loops. The small therapeutic CLT lesion is thought to initiate a progressive normalization in the affected thalamocortical system, which is reflected in both decrease of EEG power and pain relie

Transient cerebral ischemia activates processing of xbp1 messenger RNA indicative of endoplasmic reticulum stress

© 2003 The International Society for Cerebral Blood Flow and Metabolis

Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?

Ubiquitylated protein aggregates are characteristic features of neurodegenerative disorders that are also found in acute pathological states of the brain such as stroke. Many of the proteins connected to neurodegenerative diseases play a role in the ubiquitin-proteasomal pathway. Mutation of one of these proteins, the E3 ubiquitin ligase parkin, is the cause of autosomal recessive juvenile Parkinson's disease. Here we show that transient focal cerebral ischemia of 1-h duration induces marked depletion of parkin protein levels, to 60%, 36%, 33%, and 25% of controls after 1, 3, 6, and 24 h of reperfusion, but that ischemia does not cause lower protein levels of E2 ubiquitin-conjugating enzymes Ubc6, Ubc7, or Ubc9. After 3 h of reperfusion, when parkin protein levels were already reduced to <40% of control, ATP levels were almost completely recovered from ischemia and we did not observe DNA fragmentation, suggesting that parkin depletion preceded development of neuronal cell death. Up-regulation of the expression of parkin has been shown to protect cells from injury induced by endoplasmic reticulum (ER) dysfunction, and this form of cellular stress is also triggered by transient cerebral ischemia. However, in contrast to observations in neuroblastoma cells, we saw no up-regulation of parkin expression in primary neuronal cell cultures after induction of ER dysfunction. Our data thus suggest that ischemia-induced depletion of parkin protein may contribute to the pathological process resulting in cell injury by increasing the sensitivity of neurons to ER dysfunction and the aggregation of ubiquitylated proteins during the reperfusion period

Effects of Cerebellothalamic Tractotomy on Cognitive and Emotional Functioning in Essential Tremor: A Preliminary Study in 5 Essential Tremor Patients.

BACKGROUND: Subthalamic stereotactic interventions have recently caught renewed interest as a treatment for essential tremor (ET). However, it is not clear whether these interventions are associated with neurocognitive, mood or personality changes. OBJECTIVE: To investigate neurocognition, neuropsychiatric functions and personality variables in patients with ET and to explore the neurocognitive and neuropsychiatric effects of cerebellothalamic tractotomy (CTT), a form of subthalamotomy. METHODS: In our study, we investigated cognitive functions, frontal functions, mood and personality variables in 5 patients with intractable ET. Patients were tested before and 3 months after surgery using neuropsychological tests, clinical scales for depression, anxiety, anger regulation and a personality test. RESULTS: Before surgery, ET patients showed normal neurocognitive function, a slightly elevated frontal lobe score in the dimensions mental control and memory, without being indicative of a frontal lesion, and no elevated depression or anxiety scores compared to norm values. After surgery, there was no change in neurocognitive function and no increase in depression or anxiety scores. CONCLUSION: In this exploratory study on 5 ET patients, CTT was not associated with alterations of mood or neurocognitive functions

Cognitive functioning, emotional processing, mood, and personality variables before and after stereotactic surgery: a study of 8 cases with chronic neuropathic pain

BACKGROUND: Stereotactic central lateral thalamotomy (CLT) has been applied as a treatment for chronic intractable neuropathic pain. However, it is not clear whether this intervention influences the emotional and cognitive impairments observed in patients who have chronic neuropathic pain. OBJECTIVE: To investigate neuropsychological functions and emotional processing in patients with chronic neuropathic pain compared with healthy volunteers and to explore the neuropsychiatric effect of the CLT. METHODS: We investigated pain ratings, cognitive functions, emotional processes, and personality variables before and after surgery in 8 patients with intractable neuropathic pain. Patients were tested before and 3 months after CLT by the use of neuropsychological tests; clinical scales for depression, anxiety, anhedonia, and anger regulation; a personality test; and 2 experimental tasks testing the theory of mind as well as the ability to recognize facial emotional expressions. Nine age- and sex-matched control subjects were tested once using the same procedure. RESULTS: The comparison of the patient group before surgery with the control group evidenced significant differences on the cognitive assessments, the depression and anxiety scores, as well as on the somatic complaint subscale of the personality test. Three months after CLT, patients experienced a significant improvement in their depression scores. There were no additional postsurgical cognitive impairments. CONCLUSION: For our patients with chronic neuropathic pain, CLT provided pain relief and reduction of their depression scores without causing postsurgical cognitive impairments

Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

BackgroundNatalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce.ObjectiveTo evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ.MethodsWe retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation.Results195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p=0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p=0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p=0.004). The odds ratio for disability progression after 12months was 4.84 (95% CI 1.74-13.47, p=0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time).ConclusionOur findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ