'Wind-up' in Parkinson's disease: A functional magnetic resonance imaging study.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder mainly marked by selective degeneration of dopaminergic neurons that leads to disabling motor and cognitive impairment. This condition is less widely appreciated as a disease associated with a substantial variety of pain syndromes, although the prevalence of pain is relatively high. Repeated painful stimulation of peripheral nerves can cause pain 'wind-up' if the frequency of the stimulation is adequate and specifically stimulates the afferent C-fibres. We presumed that in case of PD, pain or pain severeness might be frequently caused by the aggravation of the 'wind-up' phenomenon due to any central or peripheral lesions or functional alterations. METHODS: To test for this hypothesis, we compared three groups (patients with left- and right-dominant PD and control subjects) using functional magnetic resonance imaging and thermally induced pain. RESULTS: Patient showed higher average 'wind-up' scores, compared to the healthy subjects, with lower values on the more affected sides compared to the less affected ones. In group level comparisons, patients had higher activation during 'wind-up' compared to control subjects in two main areas; these were the posterior division of cingulate gyrus and the precuneus cortex. In case of patients, further analyses showed that applied heat pain on the less affected side elicited higher activation in the supramarginal and postcentral gyri. CONCLUSIONS: These differences may arise from the deficiency in the efferent information, as well as the alterations in the central processing. It is highly likely that both processes contribute to this phenomenon simultaneously.

Cortical involvement during myotonia in myotonic dystrophy: an fMRI study.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is a common adulthood muscular dystrophy, characterized by muscle wasting, myotonia, and multisystemic manifestations. The phenomenon of involuntary muscle contraction during myotonia offers a unique possibility of investigating brain motor functions. This study explores cortical involvement during grip myotonia in DM1. MATERIALS AND METHODS: Sixteen DM1 patients were enrolled in the study. Eight patients had apparent grip myotonia, while eight patients did not (control subjects). All patients underwent functional MRI grip task examination twice: prior a warm-up procedure (myotonia was elicited in patients with apparent grip myotonia) and after a warm-up procedure (myotonia was attenuated in patients with apparent grip myotonia). No myotonia was elicited during either examination in patients without apparent grip myotonia. Cerebral blood oxygen level-dependent (BOLD) signals were compared both between groups with and without apparent myotonia, and between pre- and post-warm-up sessions. RESULTS: Significantly higher BOLD signal was found during myotonia phase in patients with apparent grip myotonia compared to corresponding non-myotonia phase of patients without apparent grip myotonia in the supplementary motor area and in the dorsal anterior cingulate cortex. Significant differences in BOLD signal levels of very similar pattern were detected between prewarm-up session myotonia phase and post-warm-up session myotonia absent phase in the group of patients with apparent grip myotonia. CONCLUSION: We showed that myotonia is related to cortical function in high-order motor control areas. This cortical involvement is most likely to represent action of inhibitory circuits intending motor termination.

The rubber hand illusion increases heat pain threshold.

BACKGROUND: Accumulating evidence shows that manipulations of cortical body representation, for example, by simply viewing one's own body, can relieve pain in healthy subjects. Despite the widespread use of the rubber hand illusion (RHI) as an effective experimental tool for the manipulation of bodily awareness, previous studies examining the analgesic effect of the RHI have produced conflicting results. METHOD: We used noxious heat stimuli to induce finger pain in 29 healthy subjects, and we recorded the participants' pain thresholds and subjective pain ratings during the RHI and during the control conditions. Two control conditions were included in our experiment - a standard one with reduced illusion strength (asynchronous stroking control) and an additional one in which the participants viewed their own hand. RESULTS: Raw data showed that both the RHI and the vision of the own hand resulted in slightly higher pain thresholds than the asynchronous stroking control (illusion: 47.79 °C; own-hand: 47.99 °C; asynchronous: 47.52 °C). After logarithmic transformation to achieve normality, paired t-tests revealed that both increases in pain threshold were significant (illusion/asynchronous: p = 0.036; own-hand/asynchronous: p = 0.007). In contrast, there was no significant difference in pain threshold between the illusion and the own-hand conditions (p = 0.656). Pain rating scores were not log-normal, and Wilcoxon singed-rank tests found no significant differences in pain ratings between the study conditions. CONCLUSION: The RHI increases heat pain threshold and the analgesic effect of the RHI is comparable with that of seeing one's own hand. The latter finding may have clinical implications.

Irony comprehension and context processing in schizophrenia during remission--a functional MRI study.

Schizophrenic patients have Theory of Mind (ToM) deficits even during remission, but it is yet unknown whether this could be influenced. We examined the neural correlates of irony understanding in schizophrenic patients, as an indicator of ToM capacity, and evaluated how linguistic help inserted into the context phase could affect irony comprehension. Schizophrenic patients in remission and healthy controls were subjected to event-related functional MRI scanning while performing irony, 'irony with linguistic help', and control tasks. Patients understood irony significantly worse than healthy controls. The patients showed stronger brain activity in the parietal and frontal areas in the early phase of irony task, however the healthy controls exhibited higher activation in frontal, temporal and parietal regions in the latter phase of the irony task. Interestingly the linguistic help not only improved the patients' ToM performance, but it also evoked similar activation pattern to healthy controls.

Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease.

INTRODUCTION: Among the non-motor features of Parkinson's disease (PD), cognitive impairment is one of the most troublesome problems. Highly sensitive and specific screening instruments for detecting dementia in PD (PDD) are required in the clinical practice. METHODS: In our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke's Cognitive Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating Scale, MDRS) in 73 Parkinson's disease patients without depression. By receiver operating characteristic curve analysis, these screening instruments were tested against the recently established clinical diagnostic criteria of PDD. RESULTS: Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%, specificity = 78.1%). For FAB the most optimal cut-off value was 12 points (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries, MDRS had the best clinicometric profile for detecting PDD. CONCLUSION: Although the types of applied screening instruments might differ from movement disorder clinic to clinic within a country, determination of the most specific and sensitive test for the given population remains to be an important task. Our results demonstrated that the specificity and sensitivity of MDRS was better than those of ACE, FAB and MMSE in Hungary. However, further studies with larger sample size and more uniform criteria for participation are required to determine the most suitable screening instrument for cognitive impairment.

Lateralisation of non-metric rhythm.

There are contradictory results on lateralisation and localisation of rhythm processing. Our aim was to test whether there is a hemispheric dissociation of metric and non-metric rhythm processing. We created a non-metric rhythm stimulus without a sense of metre and we measured brain activities during passive rhythm perception. A total of 11 healthy, right-handed, native female Hungarian speakers aged 21.3 ± 1.1 were investigated by functional magnetic resonance imaging (fMRI) using a 3T MR scanner. The experimental acoustic stimulus consisted of comprehensive sentences transformed to Morse code, which represent a non-metric rhythm with irregular perceptual accent structure. Activations were found in the right hemisphere, in the posterior parts of the right-sided superior and middle temporal gyri and temporal pole as well as in the orbital part of the right inferior frontal gyrus. Additional activation appeared in the left-sided superior temporal region. Our study suggests that non-metric rhythm with irregular perceptual accents structure is confined to the right hemisphere. Furthermore, a right-lateralised fronto-temporal network extracts the continuously altering temporal structure of the non-metric rhythm.

Quantitative proton MRI and MRS of the rat brain with a 3T clinical MR scanner.

OBJECTIVE: To demonstrate the capability of a clinical 3T human scanner in performing quantitative MR experiments in the rat brain. MATERIAL AND METHODS: In vivo, measurements on eight Wistar rats were performed. Longitudinal relaxation time (T1) and transverse relaxation time (T2) measurements were set up at a spatial resolution of 0.3×0.3×1mm(3). Diffusion-weighted imaging was also applied and the evaluation included both mono- and biexponential approaches (b-value up to 6000s/mm(2)). Besides quantitative imaging, the rat brain was also scanned at a microscopic resolution of 130×130×130µm(3). Quantitative proton spectroscopy was also carried out on the rat brain with water as internal reference. RESULTS: T1 and T2 for the rat brain cortex were 1272±85ms and 75±2ms, respectively. Diffusion-weighted imaging yielded accurate diffusion coefficient measurements at both low and high b-value ranges. The concentrations of MR visible metabolites were determined for the major resonances (i.e., N-acetyl-aspartate, choline and creatine) with acceptable accuracy. CONCLUSION: The results suggest that quantitative imaging and spectroscopy can be carried out on small animals on high-field clinical scanners.

Periictal heart rate variability analysis suggests long-term postictal autonomic disturbance in epilepsy.

BACKGROUND: One of the possible pathomechanisms of sudden death in epilepsy (SUDEP) is a postictal dysregulation of autonomic nervous system. We performed a heart rate variability (HRV) analysis of the periictal state to analyze whether a cardiac autonomic disturbance exists after an epileptic seizure. METHODS: We included 31 periictal video-EEG-ECG recordings of 31 patients with epilepsy who had consecutively undergone pre-surgical evaluation. Nine generalized tonic-clonic (GTCS), 15 complex partial, and seven simple motor seizures were included. HRV was evaluated by analyzing 5-min-long ECG epochs, sampling from baseline, direct preictal, early-postictal (<15 min after the seizure), and late-postictal (5-6 h after the seizure) periods. RESULTS: The heart rate was elevated immediately after the seizures, but 5-6 h postictally returned to the baseline level. Time-domain components of HRV decreased after the seizure and this decrease lasted for 5-6 h. Low-frequency power decreased in the early-postictal phase and high-frequency power of HRV dropped in the late-postictal phase. GTCS had an impact on short-term but not on long-term postictal HRV decrease. CONCLUSIONS: We found decreased HRV immediately after the seizures, which lasted at least 5-6 h postictally, indicating a long-term postictal disturbance of the autonomous nervous system. GTCS were accompanied by a more decreased HRV than other seizures. Our results may have relevance in explaining pathomechanism of SUDEP.

Peri-ictal vegetative symptoms in temporal lobe epilepsy.

We investigated peri-ictal vegetative symptoms (PIVS) in 141 patients with adult temporal lobe epilepsy (TLE) and assessed frequency, gender effect, and lateralizing value of peri-ictal autonomic signs. We recorded abdominal auras in 62%, goosebumps in 3%, hypersalivation in 12%, spitting in 1%, cold shivering in 3%, urinary urge in 3%, water drinking in 7%, postictal nose wiping (PNW) in 44%, and postictal coughing in 16%. At least one vegetative sign appeared in 86% of the patients. The presence of PIVS did not have a significant lateralizing value. PNW occurred in 52% of women and in 33% of men, whereas any PIVS was present in 93% of women and 77% of men. In summary, contradictory to previous studies, the presence of PIVS has no lateralizing value, which may be linked to a low frequency of occurrence of PIVS. PIVS, especially PNW, occurred more frequently in women, supporting the gender differences in epilepsy.

Presurgical seizure frequency and tumoral etiology predict the outcome after extratemporal epilepsy surgery.

OBJECTIVE: To examine the predictive value of demographic data for the seizure outcome after extratemporal epilepsy surgery. METHODS: Eightyone patients who underwent resective extratemporal epilepsy surgery were retrospectively studied concerning (a) age at surgery, (b) onset of epilepsy, (c) duration of epilepsy, (d) number of seizures at the time of presurgical evaluation, (d) number of presurgically tested antiepileptic substances and (f) number of seizure types. The data were correlated to the postoperative seizure outcome after two years. RESULTS: 33 patients (40.7%) were seizure free two years after surgery. Univariate and multivariate analysis revealed that both tumor etiology and low presurgical seizure frequency were independently associated with seizure freedom after epilepsy surgery. The recurrence rate in patients with one or more seizures per day was more than two-fold if compared with patients with fewer seizures. The remaining demographic factors did not show a significant association with seizure outcome in our 81 patients. CONCLUSIONS: Fewer than daily seizures prior to surgery and a tumoral etiology independently increase the likelihood of remaining seizure free two years after extratemporal epilepsy surgery.

Patients' ability to react before complex partial seizures.

OBJECTIVE: The purpose of the study described here was to investigate the pathophysiology of patients' ability to react during the conscious (aura) phase of complex partial seizures (CPS) originating from the temporal lobe. METHODS: We reviewed video recordings of CPS experienced by 130 adult patients who had undergone epilepsy surgery for intractable medial temporal lobe epilepsy. All patients were instructed to push the alarm button when they felt an aura. We defined the preictal reactivity as the ability to push the alarm button before the complex partial (unconscious) phase of seizures. RESULTS: Seventy-seven patients (59%) pushed the alarm button before seizures. Patients with preictal reactivity were significantly younger, more often had lateralized EEG seizure patterns, and had a better postoperative outcome. Patients who did not push the alarm button had secondarily generalized seizures more often. CONCLUSIONS: Ability to react before CPS is associated with a circumscribed region involved at seizure onset and spread, and with a seizure-free postoperative outcome.

Unilateral hand automatisms in temporal lobe epilepsy.

OBJECTIVES: To analyse the lateralising value of unilateral manual automatism (UMA), its relation to contralateral dystonia and the hand by which the UMA was performed. METHODS: In this retrospective study, we reviewed video recordings of 141 patients (mean age 34.1+/-10) who had consecutively undergone presurgical evaluations with ictal video-EEG recordings and high-resolution MRI, had had epilepsy surgery due to intractable medial temporal lobe epilepsy with complex partial seizures due to unilateral medial temporal lobe lesions. The video recordings were prospectively reviewed by one of the authors blinded to patient's clinical data except the diagnosis of medial temporal lobe epilepsy. Altogether 310 archived seizures were analysed. RESULTS: Hand automatisms occurred in 86.5% of patients. UMA occurred in 53% of patients. If UMA was accompanied by contralateral hand dystonia, it had a high lateralising value to the ipsilateral epileptic focus (EF), it was ipsilateral in 85% of patients. Conversely, if UMA occurred without contralateral dystonia, it had only a limited lateralising value because it was ipsilateral to the EF in only 63% of patients. However, we found that left-sided UMA without dystonia had a high lateralising value to the left hemisphere (ipsilateral to the EF in 82%), while right-sided UMA without dystonia has practically no lateralising value. CONCLUSIONS: UMA with contralateral dystonia has a high lateralising value to the ipsilateral hemisphere. Left-sided UMA without contralateral dystonia has a lateralising value to the left hemisphere. Right-sided UMA without contralateral dystonia has no lateralising value.

Lateralizing value of postictal automatisms in temporal lobe epilepsy.

PURPOSE: To describe clinical characteristics and lateralizing value of postictal automatisms in patients with temporal lobe epilepsy (TLE). METHODS: One hundred and ninety-three videotaped seizures of 55 consecutive patients with refractory TLE and postoperatively seizure-free outcome were analyzed. Ictal as well as postictal (manual, oral and speech) automatisms were monitored. RESULTS: Thirty-four (62%) of the 55 patients showed PA at least once during their seizures. Postictal automatism was observed in 70 (36%) attacks as manual (21%), oral (13%) or speech (9%) automatisms. Fifteen seizures contained a combination of two different postictal automatisms. The presence of postictal oral automatisms did not lateralize the seizure onset zone (p=0.834). Speech automatisms (repetitive verbal behavior) occurred more frequently after left-sided seizures (p=0.002). Postictal unilateral manual automatism showed no lateralizing value occurring by the ipsilateral hand in 10 and the contralateral upper limb in 6 seizures (p=0.454). CONCLUSION: : Postictal automatism is a relatively frequent phenomenon in TLE. Postictal speech automatism lateralizes the seizure onset zone to the left hemisphere. Our observation can help the presurgical evaluation of TLE because verbal perseveration frequently occurs spontaneously, even in seizures without appropriate postictal language testing.

Electrode manipulation automatism during temporal lobe seizures.

OBJECTIVE: To describe clinical characteristics and lateralizing value of peri-ictal electrode manipulation automatism (EMA) in patients with temporal lobe epilepsy (TLE) and compare our data with ictal manual automatisms described in the literature. METHODS: Two-hundred and five videotaped seizures of 55 consecutive patients with refractory TLE and postoperatively seizure-free outcome were analyzed and EMA (tugging, scratching or adjusting the electrodes and cables) were monitored. RESULTS: Twenty-eight (51%) patients showed EMA during 47 (23%) seizures. Ictal start was noted in 22 seizures and in 19/22 cases EMA finished before the end of seizure. Ictal EMAs were always associated with automotor seizure components. During 25 seizures, exclusively postictal EMAs were observed. Electrode manipulation was presented during 24/112 left-sided and 23/93 right-sided seizures (p = 0.742). Peri-ictal EMA was unilateral (completed by one hand) in 24/47 seizures (10 ictal, 14 postictal); it was done by the hand ipsilateral to the seizure onset zone in 17/24 and by contralateral hand in 7/24 cases (p = 0.064). We observed concomitant contralateral dystonic posturing during 3/10 seizures with unilateral ictal EMA. Unilateral hand automatism, temporally independent from the EMA appeared in 30 (64%) of the 47 seizures. CONCLUSION: Peri-ictal EMA is a frequent phenomenon but shows no lateralizing value in TLE. The mechanism of EMA is in many ways dissimilar from that of earlier described manual automatisms.

Laughter and the mesial and lateral premotor cortex.

We report the induction of laughter and smiling by cortical electrical stimulation of the frontal lobe of two patients: an 18-month-old boy with a left frontal cortical lesion extending to the vertex and the central gyrus, and a 35-year-old woman with a lesion in the right supplementary sensorimotor area (SSMA). The subjects underwent presurgical epilepsy evaluation with subdural grid electrodes to determine surgical candidacy. Stimulation of the prefrontal area reproducibly induced laughter. The adult patient reported absence of emotional content. Slowing of speech occurred under stimulation of electrodes in the upper and posterior vicinity. In this patient laughter was elicited in the anterior part of the SSMA. In the child, this response was induced by stimulation of the lateral prefrontal cortex near the midline. We conclude that the anterior portion of the SSMA/lateral premotor cortex is involved in generating the motor pattern of laughter.

Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course.

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.

Vagus nerve stimulation: predictors of seizure freedom.

OBJECTIVES: To identify predictive factors for the seizure-free outcome of vagus nerve stimulation (VNS). METHODS: All 47 patients who had undergone VNS implantation at one centre and had at least one year of follow up were studied. They underwent complete presurgical evaluation including detailed clinical history, magnetic resonance imaging, and long term video-EEG with ictal and interictal recordings. After implantation, adjustment of stimulation parameters and concomitant antiepileptic drugs were at the discretion of the treating physician. RESULTS: Mean (SD) age of the patients was 22.7 (11.6) years (range 7 to 53). Six patients (13%) became seizure-free after the VNS implantation. Only two variables showed a significant association with the seizure-free outcome: absence of bilateral interictal epileptiform discharges (IED) and presence of malformation of cortical development (MCD). Epilepsy duration showed a non-significant trend towards a negative association with outcome. By logistic regression analysis, only absence of bilateral IED correlated independently with successful VNS treatment (p<0.01, odds ratio = 29.2 (95% confidence interval, 2.4 to 353)). Bilateral IED (independent or bilateral synchronous) was found in one of six seizure-free patients and in 33 of 41 non-seizure-free patients. When bilateral IED were absent, the sensitivity for seizure-free outcome was 0.83 (0.44 to 0.97), and the specificity was 0.80 (0.66 to 0.90). CONCLUSIONS: Bilateral IED was independently associated with the outcome of VNS. These results are preliminary because they were based on a small patient population. They may facilitate prospective VNS studies enrolling larger numbers of patients to confirm the results.

Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome.

Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the type of epilepsy most frequently operated on. The predictors for long-term seizure freedom after surgery of TLE-HS are unknown. In this study, we aimed to identify prognostic factors which predict the outcome 6 months and 2, 3 and 5 years after epilepsy surgery of TLE-HS. Our working hypothesis was that the prognostic value of potential predictors depended on the post-operative time interval for which the assessment was made. We included 171 patients (100 females and 71 males, aged 16-59 years) who had undergone presurgical evaluation, including video-EEG, who had had MRI-defined HS, and who had undergone temporal lobectomy. We found that secondarily generalized seizures (SGTCS) and ictal dystonia were associated with a worse 2-year outcome. Both these variables together with older age and longer epilepsy duration were also related to a worse 3-year outcome. Ictal limb dystonia, older age and longer epilepsy duration were associated with long-term surgical failure evaluated 5 years post-operatively. In order to determine the independent predictors of outcomes, we calculated multivariate analyses. The presence of SGTCS and ictal dystonia independently predicted the 2-year outcome. Longer epilepsy duration and ictal dystonia predicted the 3-year outcome. Longer epilepsy duration (P = 0.003) predicted a poor 5-year outcome. Conclusively, predictors for the long-term surgical results of TLE with HS are different from those variables that predict the short-term outcome. Epilepsy duration is the most important predictor for long-term surgical outcome. Our results strongly suggest that surgery for TLE-HS should be performed as early as possible.