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Abstract: Nonconvulsive status epilepticus (NCSE) and epilepsia partialis continua (EPC) are common epileptic conditions for which straightforward recommendations based on controlled randomized trials for treatment in therapy refractory courses are lacking. In a large retrospective study on drug efficacy in status epilepticus (SE) we identified the patients treated in our department by searching for the term “status epilepticus” in the electronic archive of medical reports of our clinic. Here we present the subset of data concerning the patients treated with lacosamide (LCM). Ten episodes of SE in nine patients could be analyzed. To control for age dependency of results at discharge we calculated a Spearman correlation coefficient with age as independent variable and return to baseline Modified Rankin Score (mRS) at discharge=1, worsening of condition at discharge (i.e. new neurological deficit or worsening of mRS)=2 and death in hospital=3 as dependent variables. LCM was given in dosages of 50–100mg. It was not earlier administered than as fourth drug. Nevertheless it seemed to be effective for termination of status epilepticus in 20% of the episodes. But the outcome at discharge seemed considerably to depend on age of patients (r =0.94, explaining 89% of variance). [Copyright &y& Elsevier]

Abstract: This is a review on the use of injections of botulinum toxin for the treatment of focal dystonias. Disorders covered include cranial dystonia, cervical dystonia, spasmodic dysphonia, and focal hand dystonia. Considered are clinical aspects, alternative treatment strategies and principles of use of botulinum toxin injections. [Copyright &y& Elsevier]

Background Pallidal deep brain stimulation (DBS) is effective in alleviating motor symptoms of medication refractory cervical dystonia, but little is known about effects on cognitive functions. Methods As part of the first randomized, sham-controlled multicenter trial on DBS in medication-refractory primary cervical dystonia ( ClinicalTrials.gov , number NCT00148889 ), a subgroup of 13 patients aged 39 to 69 underwent prospective neuropsychological long-term follow-up assessments. Various cognitive domains (memory, executive functions, attention, visual perception, mental arithmetic and verbal intelligence) were examined before and after 12 months of continuous DBS. Results Only the number of produced words in a verbal fluency task which included alternating categories decreased after stimulation ( p = 0.020). All other cognitive domains remained unchanged. Conclusions These findings indicate that long-term pallidal DBS for the treatment of primary cervical dystonia seems to be safe regarding global cognitive functioning. [ABSTRACT FROM AUTHOR]

Abstract: Clinical, genetic, and pathological findings suggest a close relationship between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We studied the patterns of cortical atrophy across the spectrum between ALS and ALS-FTD. A surface-based morphometry analysis based on an age- and sex-matched sample of 81 ALS patients and 62 healthy control subjects (HC) was conducted. In addition, we used an age-matched subsample of 57 ALS patients and 31 HC to compare cortical thickness between 3 groups of neuropsychologically characterized ALS patients: (1) cognitively unimpaired; (2) cognitively impaired; and (3) ALS-FTD patients. Compared with HC, the entire sample of patients demonstrated cortical thinning in the bilateral precentral gyrus, right precuneus, and right frontal and temporal lobes. ALS-FTD patients showed cortical thinning in regions including the frontal and temporal gyri and the posterior cingulate cortex. Cognitively impaired ALS patients showed cortical thinning in regions largely overlapping with those found in ALS-FTD, but changes were less widespread. In conclusion, the cognitive status of ALS subjects is associated with different patterns of cortical atrophy. [Copyright &y& Elsevier]

Abstract: Central pathophysiological pathways of basal ganglia dysfunction imply a disturbed interaction of dopaminergic and cholinergic circuits. In Parkinson''s disease imbalanced cholinergic hyperactivity prevails in the striatum. As recently shown intrastiatal botulinum neurotoxin A (BoNT-A) improves motor function in hemiparkinsonian rats. Before going further steps in using intracerebral BoNT-injections as possible treatment we here explore whether pure BoNT-injections into normal rats’ striata affect their cognitive and emotional properties. Wistar rats were injected bilaterally with 1ng BoNT-A or vehicle (sham injection) into the striatum, whereas a naïve control group was left untreated. Locomotor activity, balance and coordination were assessed in open field and accelerod tests. Anxiety was evaluated in the open field and elevated plus maze. Spatial learning was assessed by radial and water maze tests. Intrastriatal BoNT-A, but also sham injections caused decreased motor activity and impaired balance and motor coordination of rats. Slight working memory deficits were observed in radial maze testing of both BoNT-A and sham injected animals arguing for a consequence of surgery rather than for a specific BoNT-A effect. In contrast, BoNT-A injected animals showed a reduced anxiety in open field and elevated plus maze compared to both sham-treated and naïve controls. As bilateral intrastriatal BoNT-A injections in normal rats do not cause cognitive impairments and reduce anxiety, and previous findings showed improvements of motor function in hemiparkinsonian rats following intrastriatal BoNT-A, it can be argued that intrastriatal BoNT-A could be a new therapeutic approach in Parkinson''s disease. [Copyright &y& Elsevier]

Abstract: In patients with deep brain stimulation (DBS), poor postoperative outcome or unexpected clinical change require brain imaging to check the lead location. Here, we studied safety, reliability and prognostic value of transcranial sonography (TCS) for DBS lead localization applying predefined TCS criteria. After measuring thermal effects of TCS and imaging artefact sizes of DBS lead using a skull phantom, we prospectively enrolled 34 patients with DBS of globus pallidus internus, ventro-intermediate thalamic or subthalamic nucleus. TCS had no influence on lead temperature, electrical parameters of DBS device or clinical state of patients. TCS measures of lead coordinates agreed with MRI measures in anterior-posterior and medial-lateral axis. Lead dislocation requiring reinsertion was reliably detected. Only patients with optimal lead position on TCS had favorable clinical 12-month outcome (>50% improvement), whereas unfavorable outcome (<25% improvement) was associated with suboptimal lead position. TCS may therefore become a first-choice modality to monitor lead location. [Copyright &y& Elsevier]

Abstract: In rat models of Parkinson’s disease, injections of 6-hydroxydopamine (6-OHDA) into different areas of the basal ganglia result in dopaminergic neurodegeneration in the substantia nigra. The extent and time course of the dopaminergic lesions varies between the models. While the effects on neurons have been extensively studied, little is known about the effects on astrocytes. We compared astrocytic activation (i.e. increase in number and staining intensity of glial fibrillary acidic protein immunoreactive cells) at the injection site and in downstream structures of the motor loop, i.e. the globus pallidus (GP) and the subthalamic nucleus (STN) following 6-OHDA lesion of the medial forebrain bundle (MFB) or the striatum. Lesions in both regions resulted in astrocytic activation at the lesion site, but their remote effects varied. MFB injections caused astrocytic activation in the ipsi- and contralateral striatum, whereas striatal injections resulted in astrocytic activation in the GP and STN. Since 6-OHDA injections into the MFB and the striatum result in complete and partial SNc lesions, respectively, we hypothesize that communication links exist between astrocytes, or between neurons and astrocytes, along neuronal pathways that transmit activating signals in response to neuronal damage—but only if the neuronal pathways are at least partially intact. [Copyright &y& Elsevier]

Background: Previous investigations using transcranial magnetic stimulation (TMS) have shown that neural inhibitory motor circuits are disturbed in ADHD children. We sought to investigate the influence of methylphenidate (MPH) on inhibitory and facilitatory motor circuits of ADHD children with TMS paired pulse protocols using surplus long interval inter-stimulus intervals (ISI) not investigated so far. Methods: Motorcortical modulation was tested with TMS paired pulse protocols employing ISI of 3, 13, 50, 100, 200, and 300 msec in 18 ADHD children before and on treatment with MPH. Clinical improvement by MPH was measured by the Conners score. Results: Analysis of variance (ANOVA) revealed a significant three-way interaction “Group × Amplitude × ISI,” p = .001. Subsequent two-factorial ANOVAs and t-tests showed group specific differences of motor evoked potential (MEP) amplitudes for inhibitory ISIs of 3 and 100 msec, and for facilitatory ISIs of 13 and 50 msec. Compared to controls, an adjustment of these parameters by MPH could be shown. On MPH, a significant bivariate correlation was found between the Conners score reduction and averaged MEP amplitude changes only for inhibitory ISIs (3 and 100 msec). Conclusions: In ADHD children, MPH modulates disturbed facilitatory and inhibitory motor circuits, which for the latter is associated with clinical improvement. [Copyright &y& Elsevier]

Abstract: Transcranial sonography (TCS) revealed reduced brainstem raphe (BR) echogenicity in major depressive disorder (MDD). Here, it was studied whether BR echogenicity discriminates MDD and adjustment disorder with depressed mood (ADDM), and whether BR echogenicity relates to depression severity or treatment responsivity. For this, 15 patients with single episodes of MDD (MDDs), 22 with recurrent MDD (MDDr), 15 with ADDM, and 50 healthy controls were investigated with TCS. Frequency of reduced BR echogenicity was similar in groups MDDs (53%), MDDr (50%) and ADDM (60%), but significantly lower in the controls (8%). Patients with reduced BR echogenicity had lower scores on the 21-item Hamilton Depression Rating Scale and the Motor Retardation Scale, compared with patients with normal BR echogenicity. BR echogenicity scores were significantly lower in SSRI responders to serotonin reuptake inhibitors (SRI) than in non-responders. Reduced BR echogenicity indicated SSRI responsivity with 70% sensitivity, 88% specificity and a positive predictive value of 88%. No impact of age, gender or antidepressant medication on BR echogenicity was found. These results indicate that reduced BR echogenicity is not related to diagnostic category of depressive state. Reduced BR echogenicity might reflect a pathology predisposing to a certain subtype of depression characterized by less psychomotor retardation and better responsivity to SRI. [Copyright &y& Elsevier]