Pallidal and thalamic deep brain stimulation in myoclonus‐dystonia

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus‐dystonia (MD). We investigated short‐ and long‐term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi‐ and VIM‐DBS in MD. Ten MD‐patients (nine ε‐sarcoglycan‐mutation‐positive) were evaluated pre‐ and post‐surgically following continuous bilateral GPi‐ and VIM‐DBS at four time points: presurgical, 6, 12, and as a last follow‐up at a mean of 62.3 months postsurgically, and in OFF‐, GPi‐, VIM‐, and GPi‐VIM‐DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL‐scores. MD‐symptoms significantly improved at 6 months post‐surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long‐term evaluation post‐surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long‐lasting stimulation‐related adverse events (AEs) were observed. Both GPi‐ and VIM‐DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation‐induced events of GPi‐DBS in comparison with VIM‐DBS, GPi‐DBS seems to be preferable. Combined GPi‐VIM‐DBS can be useful in cases of incapaciting myoclonus, refractory to GPi‐DBS alone. © 2010 Movement Disorder Society     

Neurosurgical treatment of tremor in mitochondrial encephalopathy

A 53‐year‐old woman underwent several ischemic stroke‐like episodes and later developed incomplete, bilateral ophthalmoplegia, left vision deterioration, and bilateral tremor. The clinical course, laboratory data, and muscle histology led to a diagnosis of mitochondrial encephalomyopathy. No other etiology could be identified in the background of her disabling bilateral postural–kinetic tremor. As this tremor did not respond to pharmacological therapy, left thalamotomy and subsequently right thalamic deep brain stimulator (DBS) implantation were performed, which resulted in an excellent clinical outcome. The Fahn–Tolosa–Marin Tremor Rating Scale improved from 110 to 11 points. This case suggests that the rare tremor caused by mitochondrial encephalopathy may be treated long‐term with either thalamotomy or thalamic DBS implantation. © 2006 Movement Disorder Society     

Psychogenic tremor: Long term prognosis in patients with electrophysiologically‐confirmed disease

We describe the presenting features and long‐term outcomes of patients with electrophysiologically‐confirmed psychogenic tremor. Clinical information for all patients with psychogenic tremor confirmed by our Movement Disorders Neurophysiology Laboratory (2003–2004) was reviewed. A follow‐up questionnaire was administered to all included patients in 2007. Psychogenic tremor was documented in 62 patients; 33 responded to the questionnaire (53%). Median onset‐age was 50 years (range, 15–71); 23 were female (70%). Clinical certainty of psychogenic etiology was: definite, 8 (24%); probable, 16 (49%), and possible, 9 (27%). Characteristic electrodiagnostic features of psychogenic tremor were documented in all. All but two patients were ultimately given a definite diagnosis of psychogenic tremor; recommended psychiatric consultation was only done by 12 (36%). Twenty‐one patients (64%) rated tremor disability as moderate or severe after a median follow‐up of 5.1 years (range, 3.3–19). Improvement occurred spontaneously in 5 (15%), and after a specific intervention in 4 (12%), whereas 3 (9%) had mild but unchanged symptoms. The mean duration of symptoms, prior to diagnosis with psychogenic tremor, was significantly shorter for patients with mild or no tremor at follow‐up (P = 0.037). Physiologically‐confirmed psychogenic tremor carries a poor prognosis, with unremitting or worse tremor persisting 3‐years after diagnosis in most. © 2008 Movement Disorder Society     

Long‐term deep brain stimulation for essential tremor: 12‐year clinicopathologic follow‐up

We describe the clinical course and postmortem pathological findings in a patient with essential tremor (ET) treated with deep brain stimulation (DBS) for 12 years. This 75 year old woman had a 13‐year history of progressive ET prior to implantation of bilateral quadripolar DBS electrodes in the region of her ventral intermediate thalamic nuclei in 1996, producing immediate relief of arm tremor. Histopathological examination of the brain, performed 12 years after the initial implantation, demonstrated electrode catheter tracts rimmed by 20‐25 micron fibrous sheaths, with multinucleated giant cells and reactive gliosis. Lymphocytic infiltration was seen by L26 immunoreactivity with CD3 (T cells) staining predominating over CD20 (B cells). Cerebellar axonal spheroids and Purkinje cell loss were found. The minimal foreign body reaction and gliosis around the electrodes 12 years after implantation supports the long‐term safety of DBS. The case represents the longest reported follow‐up with autopsy examination after DBS and confirmed histological changes associated with ET. © 2009 Movement Disorder Society     

Long‐term follow‐up of DYT1 dystonia patients treated by deep brain stimulation: An open‐label study

Long‐term efficacy of internal globus pallidus (GPi) deep‐brain stimulation (DBS) in DYT1 dystonia and disease progression under DBS was studied. Twenty‐six patients of this open‐label study were divided into two groups: (A) with single bilateral GPi lead, (B) with a second bilateral GPi lead implanted owning to subsequent worsening of symptomatology. Dystonia was assessed with the Burke Scale. Appearance of new symptoms and distribution according to body region were recorded. In the whole cohort, significant decreases in motor and disability subscores (P < 0.0001) were observed at 1 year and maintained up to 10 years. Group B showed worsening of the symptoms. At 1 year, there were no significant differences between Groups A (without subsequent worsening) and B; at 5 years, a significant difference was found for motor and disability scores. Within Group B, four patients exhibited additional improvement after the second DBS surgery. In the 26 patients, significant difference (P = 0.001) was found between the number of body regions affected by dystonia preoperatively and over the whole follow‐up. DBS efficacy in DYT1 dystonia can be maintained up to 10 years (two patients). New symptoms appear with long‐term follow‐up and may improve with additional leads in a subgroup of patients. © 2009 Movement Disorder Society     

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study

Background and purpose: Deep brain stimulation of the internal globus pallidus (GPi‐DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer‐blinded outcome assessment of long‐term GPi‐DBS, with 1‐year follow‐up. Methods: In this prospective, single‐centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi‐DBS for median (range) 30 (12–48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short‐Form Health Survey‐36 (SF‐36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow‐up. Results: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19–30) to 8 (4–23) (P = 0.028), thus a 70% (23–82) score reduction. In the open evaluation, median Severity score improvement at the last follow‐up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF‐36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. Conclusions: This single‐blinded study shows good long‐term efficacy of GPi‐DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.     

Thalamotomy versus thalamic stimulation for multiple sclerosis tremor.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.     

Long‐term outcomes of surgical therapies for Parkinson's disease

The surgical lesion of different brain structures has been used as a treatment for Parkinson's disease (PD) for several decades. More recently, the favored therapeutic approach has involved the administration of levodopa and the use of DBS. These two major therapeutic advances have greatly modified both the clinical condition of patients and the history of the disease. With the introduction of L ‐dopa in 1967, patients could regain mobility, because their akinesia, tremor, and rigidity were greatly improved, with consequent significant improvement in quality of life and increased life expectancy. However, after the so‐called “honeymoon” period in which the disease seemed to be controlled, motor fluctuations and L ‐dopa‐induced dyskinesias mitigated the initial enthusiasm. In the 1990s, unilateral pallidotomy and DBS of the globus palllidus internus and STN reduced these motor fluctuations and dyskinesias remarkably, thereby inaugurating a new era in the surgical treatment of PD. Short‐ and medium‐term follow‐up studies of patients who underwent surgery have documented sustained, significant motor benefits. However, given the progressive nature of PD and the purely symptomatic effects of pallidotomy and DBS, the long‐term clinical evolution of these surgical patients currently seems to be associated with a new PD phenotype, mainly characterized by axial motor problems and cognitive impairment. Here, we analyze the long‐term clinical outcomes of surgical PD patients with at least 5‐year follow‐up, focusing on the long‐term motor symptoms that were initially responsive to surgery. © 2012 Movement Disorder Society     

Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life

Objectives – To report long‐term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health‐related quality of life (HRQoL) in patients with essential tremor (ET). Materials and methods – Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview. Results – There was a decrease of DBS efficacy on tremor between 1 and 7 years post‐operatively. The marked improvement in ADL at 1 year was no longer sustained at long‐term, except for the ability to eat. Social life remained improved. Conclusion – Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co‐morbidities may impact on the well‐being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.     

Long‐term levetiracetam treatment in patients with epilepsy: 3‐year follow up

Kuba R, Novotná I, Brázdil M, Ko?varová J, Tyrlíková I, Mastík J, Rektor I. Long‐term levetiracetam treatment in patients with epilepsy: 3‐year follow up.
Acta Neurol Scand: 2010: 121: 83–88.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To assess the long‐term efficacy and tolerability of levetiracetam in routine clinical practice. Materials and methods – We retrospectively analysed 218 patients, mostly adults, presenting mostly with localisation‐related epilepsy, treated with levetiracetam as adjunctive therapy or monotherapy for up to 36 months. The primary points evaluated were: long‐term retention rate, reasons for discontinuing levetiracetam and the percentage of seizure‐free patients. Results – The retention rate at 6, 12, 24 and 36 months following the commencement of levetiracetam treatment was 91.7, 75.2, 60.1 and 53.7% respectively. Sixty‐seven (30.7%) patients discontinued levetiracetam treatment. During the clinical audit evaluation period, surgical resection or implantation of VNS was performed in 31 (14.3%) patients. In 53 of the 67 patients (79.1%), the treatment was discontinued due to lack of efficacy; in 14 patients (20.9%) treatment was discontinued due to adverse events. In total, 24 of 218 patients (11.0%) were seizure‐free for 36 months. Conclusions – Levetiracetam is an effective and well‐tolerated option for long‐term treatment of epilepsy in adults.     

Long‐Term Follow‐Up Study of Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Cervical Dystonia

Objectives. Medically refractory cervical dystonia has recently been treated using deep brain stimulation (DBS), targeting the subthalamic nucleus (STN). There has been limited literature regarding short‐term outcomes and no literature regarding long‐term outcomes for refractory cervical dystonia following DBS of the STN. Materials and Methods. Two patients with medically refractory cervical dystonia underwent STN DBS. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and immediately postoperatively as well as just prior to turning on the stimulators and subsequently at 24–48 hours, six months, one, two, and three years after stimulation. Microrecordings were used to identify the STN and substantia nigra reticulata (SNr). Results. Significant immediate and sustained long‐term improvements were seen in motor, disability, pain, and total TWSTRS scores. In one patient, only unilateral stimulation was required. The STN and SNr were easily identified as having activity similar to off‐state Parkinson's patients. Conclusions. DBS therapy for cervical dystonia utilizing the STN as the surgical target may be novel and may be an alternative target to the globus pallidus internus as supported by this first long‐term outcome report. Further studies need to be performed to confirm these conclusions.     

Surgical therapy for tremor in multiple sclerosis: an evaluation of outcome measures.

OBJECTIVE: To assess the reliability, validity, and sensitivity of outcome measures that might be used in a clinical trial of surgery for the treatment of severe tremor associated with MS (MS tremor). METHODS: Nine patients with MS tremor were evaluated before and 3 and 12 months after thalamic surgery (six thalamotomy, three deep brain stimulation). A clinical tremor rating scale (CTRS), a novel quantitative movement analysis technique (QMA), and a variety of measures of disability, neurologic impairment, and quality of life was utilized. RESULTS: Both the CTRS and QMA were reliable measures of tremor and both were sensitive to the improvement in tremor following surgery. However, QMA correlated with disability measures and corresponded better to patient and examiner assessment of surgical results. The disability scales used were insensitive to functional improvements that may follow surgery. The box and blocks test clearly separated three patients who had excellent results from three who had poor results. Baseline QMA values predicted improvement on the box and blocks test. CONCLUSIONS: 1) QMA is a reliable, objective and valid measure of MS tremor that could be used in a clinical trial. 2) The box and blocks test can detect the improvement in prehensile function that follows surgery, but standard disability scales are poorly responsive to this change. 3) Preoperative QMA values may predict which patients are most amenable to functional improvement after surgery.     

Deep brain stimulation and cognitive functions in Parkinson's disease: A three‐year controlled study

There is debate over the cognitive and behavioral effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD). To evaluate these effects, we performed a prospective, naturalistic controlled, 3‐year follow‐up study. A total of 65 PD patients were enrolled, of whom 32 underwent STN‐DBS (PD‐DBS) and 33, even though eligible for this treatment, declined surgery and chose other therapeutic procedures (PD‐control). Motor and neuropsychological functions were assessed in all the subjects at baseline (T0) and 36 months (T36). The PD‐DBS patients were also evaluated at 1, 6, 12, and 24 months after surgery (T1, T6, T12, and T24). At T1, compared with T0, the PD‐DBS patients recorded worse logical executive function task and verbal fluency (FAS) scores, whereas their performance of memory tasks remained stable. At T12, their cognitive profile had returned within the pre‐DBS range, thereafter remaining stable until T36. FAS scores at T36 were significantly worse in the PD‐DBS compared with the PD‐control patients. This is the first long‐term naturalistic controlled study of cognitive functions in PD patients submitted to STN‐DBS. Our results confirm previous reports of a worsening of verbal fluency after DBS, but show that STN‐DBS seems to be relatively safe from a cognitive standpoint, as the short‐term worsening of frontal‐executive functions was found to be transient. © 2009 Movement Disorder Society     

A Comparison of LEDD and Motor Scores Following STN‐DBS Treatment in Patient with Young Onset vs. Late Onset Parkinson's Disease

Introduction: We compared the role of subthalamic nucleus deep brain stimulation (STN‐DBS) in the management of medically refractory idiopathic Parkinson's disease in patients with relatively young onset (<40 years of age) Parkinson's disease (YOPD) and patients with relatively late onset Parkinson's disease (≥56 years of age, rLOPD). Methods: A total of 33 patients with YOPD (18 patients, median age 32.5 years, range, 20–40 years) and rLOPD (15 patients, median age 58.0 years, range, 56.0–67.0 years) underwent STN‐DBS between May 2000 and May 2008. We divided the patients into YOPD and rLOPD as the age of disease onset. The median follow‐up period was 43 months (range, 12–95 months). We assessed Hoehn and Yahr stages, activities of daily living, and Unified Parkinson's Disease Rating Scale (UPDRS) motor scales (III) for all patients preoperatively and at six months postoperatively. We measured levodopa equivalent doses (LEDD) and stimulation parameters preoperatively, six months postoperatively, and 12 months postoperatively. Results: There were no significant differences in UPDRS motor scales between two groups at preoperative and six‐month postoperative drug off/stim on, but UPDRS III was lower in rLOPD at six‐month postoperative drug on/stim on state. A significant difference was noted in the improvement of UPDRS III between two groups for preoperative drug off and drug on conditions, but no difference was seen between two groups in a comparison of drug off/stim on vs. drug on/stim on conditions. Stimulation parameters and postoperative LEDD were not different between the two groups. Preoperative dyskinesia was more common in YOPD patients and, psychotic problems were more common in rLOPD patients. Conclusions: Patients with YOPD and rLOPD exhibited comparable UPDRS motor scores and LEDD six months postoperatively. Levodopa could be prescribed at optimum doses following STN‐DBS in patients with YOPD as abnormal movements are better controlled following STN‐DBS implantation. Stimulation parameters were not different between the two groups. Our results suggest the age of onset does not influence response to STN‐DBS Parkinson's disease patients.     

Simultaneous Thalamic and Posterior Subthalamic Electrode Insertion With Single Deep Brain Stimulation Electrode for Essential Tremor

Objectives: The optimal target location of deep brain stimulation (DBS) is the subject of some controversy. We implanted electrodes that could stimulate both posterior subthalamic area (PSA) and ventralis intermedius nucleus of thalamus (Vim), and examined the benefits of bilateral DBS of Vim, PSA, and Vim + PSA in patients with essential tremor (ET). Materials and Methods: Electrodes were inserted into the Vim and PSA in ten hemispheres of five consecutive patients. All patients were assessed for action tremor, including postural and kinetic tremors, both preoperatively and at six months and one year postoperatively. Results: The preoperative mean postural tremor score was 1.9 (range 1.0–2.5) and kinetic tremor score was 2.6 (range 2.0–3.0). One year after surgery, these scores had decreased significantly to 0.1 (range 0.0–1.0) and 0.6 (range 0.0–1.5), respectively. The postural and kinetic tremor scores at six‐months and one‐year post‐surgery were similar for Vim, PSA, and Vim + PSA stimulation. Conclusions: We were able to identify the optimal electrode placement site for each patient based on his or her individualized response to the stimulation. Overall, there was no statistically significant difference among the DBS sites in terms of the benefits afforded by the stimulation. We propose that our technique may be a useful surgical method to treat ET.     

Long term safety and efficacy of unilateral deep brain stimulation of the thalamus for parkinsonian tremor

The objective was to investigate the long term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in Parkinson's disease. Twelve patients with Parkinson's disease underwent unilateral DBS of the thalamus for medication resistant tremor between 1994 and 1997. Patients were evaluated with the motor section of the unified Parkinson's disease rating scale (UPDRS) in the medication on state at baseline, 3 months, 12 months, and yearly thereafter.Three patients were lost to follow up. Nine patients had follow up evaluations greater than 24 months and were included in the analyses. The last postsurgical follow up occurred on average 40.0 (SD 17.2) months after surgery. Tremor scores were significantly improved with stimulation on at the long term follow up compared with baseline. There was no significant change in UPDRS motor scores at long term follow up compared with baseline. There was no significant change in any stimulus parameters from 3 months to the long term follow up. Two patients had asymptomatic intracerebral haemorrhages and one patient had a subcutaneous haematoma over the implantable pulse generator site. Stimulus related adverse reactions were mild and easily controlled with changes in stimulus parameters. Two patients had replacement of the implantable pulse generator due to normal battery depletion, one patient had lead repositioning due to migration, and one patient had the lead extension wire replaced due to erosion. In conclusion, unilateral DBS of the thalamus has long term efficacy for treatment of tremor due to Parkinson's disease.     

Long‐term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short‐term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long‐term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke–Fahn–Marsden Dystonia Rating Scale showed a mean improvement of 45% at short‐term follow‐up (4.4 ± 1.5 months; P < 0.001) and of 53% at long‐term follow‐up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long‐term follow‐up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years. © 2011 Movement Disorder Society     

Long‐term add‐on pregabalin treatment in patients with partial‐onset epilepsy: Pooled analysis of open‐label clinical trials

Purpose: To evaluate the safety, tolerability, and efficacy of long‐term pregabalin as add‐on therapy for patients with poorly controlled partial seizures. Methods: Analysis of data from six long‐term clinical trials involving 2,061 patients receiving open‐label pregabalin 75–600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. Results: Total pregabalin exposure was 3,877 person‐years. The mean duration of pregabalin treatment was 534 days (range 0.3–8 years) and 59% completed 1 year. One‐third of patients discontinued for lack of efficacy. The most common dose was ≥300 mg/day; over half took ≥450 mg/day. There was a mean reduction in the 28‐day seizure rate of 25–40%, and more than 40% of all patients had a ≥50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6‐month period continuously free of seizures. In the last year, 6% were seizure‐free for the entire year. Pregabalin was generally well‐tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short‐term placebo‐controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. Conclusions: Adjunctive pregabalin was effective, generally well tolerated, and safe in the long‐term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow‐up.     

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease

Constantinescu R, Holmberg B, Rosengren L, Corneliusson O, Johnels B, Zetterberg H. Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 206–210.
© 2010 John Wiley & Sons A/S. Objectives – Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non‐specific marker of neuronal damage, are normal in Parkinson’s disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF‐NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. Materials and methods – CSF‐NFL levels were measured consecutively in eight patients with PD before and after STN‐DBS treatment. Results – CSF‐NFL levels were normal prior to STN‐DBS and increased sharply during the first 2 weeks post‐operatively, but normalized after 12 months or more. Conclusion – The STN‐DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF‐NFL levels at 12 months post‐operatively and beyond suggest the absence of any long‐term neuronal damage caused by long‐term STN‐DBS stimulation.     

Specific T‐cell proliferation to myelin peptides in relapsing‐remitting multiple sclerosis

Background: The identification of major immunogenic peptides in multiple sclerosis (MS) is of great importance for the development of antigen‐specific therapies. Cellular reactivity against a selected mix of seven myelin peptides was evaluated in vitro. The evolution of this reactivity over time and its correlation with clinical variables was also analysed. Material and methods: Forty‐two patients with MS, 15 with other demyelinating diseases and 40 healthy donors (HD) were studied. Cell proliferation was measured by 3[H] thymidine incorporation into samples obtained at 0, 3, 6 and 12 months of MS patient follow‐up. Results: A positive reaction to the peptide mix was detected in 31 of the 42 patients (74%), 12 of the 40 HD (30%) and 6 of the 15 (40%) patients with other demyelinating diseases. Patients with positive proliferation had greater disability (EDSS score, 3 [1–5.5] vs. 1.0[1–2], P = 0.021), higher number of relapses (7 ± 4.1 vs. 3 ± 1.2, P < 0.001) and shorter time since the last relapse (9 ± 7.5 vs. 32 ± 12.3 months, P = 0.036). After 12 months of follow‐up, cell reactivity was maintained in 33 patients (78%). Conclusion: A high percentage of patients exhibit a significant and maintained reactivity to myelin peptides over time. Therefore, this mix may be useful as a source of antigen in the development of protocols aimed at inducing specific tolerance in MS.