[Show abstract][Hide abstract] ABSTRACT: Background/aims:
A substantial proportion of amyotrophic lateral sclerosis (ALS) patients develop cognitive impairments. Longitudinal investigations of cognition in ALS have shown mixed results. While some authors report that cognitive performance remains stable as the disease progresses, others have found evidence for deterioration in various domains. Our objective was to investigate cognitive performance in ALS longitudinally, using the example of executive functions.
93 ALS patients and 73 age-, sex- and education-matched healthy controls underwent up to four neuropsychological evaluations, separated by 3- to 6-month intervals. We examined whether performance declined longitudinally on seven tests assessing various sub-components of executive functioning. Furthermore, we assigned an executive-performance-based 'cognitive status' to each participant for every evaluation, examining whether cognitive deterioration (if present) was modulated by their baseline cognitive status and whether cognitive status changed over time.
Regardless of their cognitive status at baseline, ALS patients showed no significant decline in the sub-components of executive functioning.
Our findings imply that the executive deficits which develop in some ALS patients emerge before motor symptoms and remain stable after an initial decline. The discrepancy between this trajectory and the progressive decline in motor functions may result from a differential vulnerability of motor and non-motor prefrontal neurons to the pathomechanism of ALS.
Full-text · Article · Nov 2015 · Neurodegenerative Diseases
[Show abstract][Hide abstract] ABSTRACT: Main problem:
Spasticity is a common feature in patients with multiple sclerosis (MS). Although options have broadened over the last years, there are still patients with no response to common therapeutic agents. Intrathecal administered triamcinolone acetonide (TCA) has been tested for spasticity in patients with MS. However, the long run effects are not known so far. The aim of this study was to evaluate the effects of repeated cycles of intrathecal TCA instillations on clinical parameters.
A total of 54 patients with clinically definite MS and no response to commonly utilized antispastic drugs were enrolled. TCA was administered every 3 months for a period of 9 months. Clinical assessments including spasticity, disability (EDSS), mobility (walking distance, and timed 25-foot walk), bladder function, and quality of life were carried out prior to and at the end of each treatment cycle.
Repeated TCA treatment led to repeated effects on spasticity (P < 0.01). Bladder function improved in every 10th patient. Quality of life improved during each cycle but did not reach significance at the end of study (P = 0.09). However, long-lasting improvement on spasticity or EDSS was not shown at end of the study. Effects diminished over 3 months.
Repeated TCA instillations led to replicable effects on spasticity; subgroup analyses suggest that higher spasticity, more frequent treatments, and higher EDSS may lead to pronounced effects on spasticity and EDSS. Intrathecal TCA treatment was safe and no severe side effects occurred. We hypothesize a significant time dependence of re-administration of TCA and that an interval of 3 months between the treatments might be too long.
No preview · Article · Nov 2015 · CNS Neuroscience & Therapeutics
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:
Experience with therapeutic plasma exchange (TPE) for acute relapses in clinically isolated syndrome (CIS) or multiple sclerosis (MS) patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.
Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18-69 years).
Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS) scoring.
A clinical response to TPE was observed in 65 out of 90 patients (72.2%), with marked improvement in 18 (20.0%) and moderate improvement in 47 out of 90 patients (52.2%). The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001). Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001), no disease modifying drugs (p = 0.017), gadolinium-positive (Gd+) MRI lesions (p = 0.001) and EDSS ≤ 5.0 before TPE (p = 0.014). In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004).
Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.
[Show abstract][Hide abstract] ABSTRACT: Objective: It was planned to investigate whether certain electroencephalographic patterns obtained during the treatment of a status epilepticus (SE) were associated with a particular subtype of SE. Methods: In a retrospective databank analysis all treatment episodes of a SE between January 1st, 2000 and December 31st, 2009 in the department of Neurology at Rostock University were identified. The first EEG of each treatment episode, in which an EEG was recorded, was evaluated. Statistical analyses were performed in order to find out whether there is an association of a certain EEG pattern with a particular subtype of SE or whether some EEG patterns signify a worse outcome than others. Results: In 35 treatment episodes of an SE at least one EEG was obtained during the actual treatment. There was no association of a certain EEG pattern with a particular subtype of SE. Periodic epileptiform discharges were seen more often in non-limbic complex partial status epilepticus and cases of coma due to acute brain injury with epileptiform EEG changes than in non-convulsive status epilepticus (NCSE) in the postictal phase of tonic-clonic seizures. These results are at variance with the published literature, where the frequent occurrence of periodic epileptiform discharges in NCSE in the postictal phase of tonic-clonic seizures is reported. Background slowing with a frequency in the theta range or lower was associated with disability to perform the activities of daily life without any help. On discharge patients with periodic epileptic discharges were more disabled than those without this pattern. Conclusions: The concept of different subtypes of NCSE needs further evaluation especially with regard to its therapeutic relevance. In adults EEG patterns specific for a particular subtype of SE are rare.
No preview · Article · Aug 2015 · Klinische Neurophysiologie
[Show abstract][Hide abstract] ABSTRACT: Pronounced cognitive and behavioural impairments in amyotrophic lateral sclerosis (ALS) concern executive functions and executive behaviour. The valid measurement is challenging as motor disabilities may mask everyday functioning. The aim of this study was to determine a detailed characteristic pattern of executive impairment in ALS in order to effectively interpret their clinical impact. We investigated 98 ALS patients without or with frontotemporal dementia (FTD), and 70 healthy controls using a comprehensive neuropsychological test battery focusing on executive functions and executive behaviour. We analysed the impairment of executive functions and their clinical significance for patients' daily routines. Results demonstrated that around 70% of cognitively impaired ALS patients without FTD showed disturbances in executive functioning. Behavioural abnormalities primarily manifested in symptoms of apathy. Patients without FTD were most impaired in the executive domain regarding initiation and shifting; this contrasted their almost preserved processes relating to updating, inhibition, and complex problem solving. ALS-FTD patients showed deficits in all analysed processes. Our study suggests that executive dysfunctioning in cognitively impaired ALS patients without FTD does not preferentially affect the more complex regulatory processes. These findings indicate potential mechanisms for ALS patients to compensate for executive dysfunction in daily routine.
No preview · Article · May 2015 · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
[Show abstract][Hide abstract] ABSTRACT: The preliminary data presented here shall give an impression on how different criteria for the identification of an antiepileptic drug (AED) with a possible or certain treatment effect can have an influence on the results of retrospective case series. We present a data subset from a large retrospective study which, when completed, will cover all treatment episodes of status epilepticus (SE) at the neurological department of the Universitätsmedizin Rostock from January 2010 to June 2013. We compare and contrast the results of four different efficacy criteria for the effectiveness of phenytoin (PHT), valproate (VPA), levetiracetam (LEV), and lacosamide (LCM): criterion 1 = the last AED administered before SE termination; criterion 2 = the last drug introduced into the antiepileptic therapy within 72 h before SE termination and without changes in the comedication; criterion 3 = the last drug introduced into the antiepileptic therapy or increased in dose within 24 h before SE termination without changes in the comedication; and criterion 4 = the last drug introduced into the antiepileptic therapy within 72 h before SE termination, even allowing changes in the comedication. Thirty-seven treatment episodes in 32 patients (13 male and 19 female, mean age at first episode: 68 years, SD: 17) could be analyzed. In 31 episodes, at least one AED was given intravenously. Efficacy rates in the whole case series according to all four criteria were not significantly different between the four AEDs, but there was a considerable difference in the efficacy rates of each AED when evaluating them with the different efficacy criteria. Our data show that statistically significant results concerning the efficacy of different AEDs in different subtypes of SE may depend on the outcome criteria. Therefore, efficacy criteria for the effectiveness of AEDs in the treatment of SE should be standardized.
No preview · Article · May 2015 · Epilepsy & Behavior
[Show abstract][Hide abstract] ABSTRACT: Background:
IncobotulinumtoxinA (Xeomin(®)) is a purified botulinum neurotoxin type A formulation, free from complexing proteins, with proven efficacy and good tolerability for the treatment of neurological conditions such as blepharospasm, cervical dystonia (CD), and post-stroke spasticity of the upper limb. This article provides a comprehensive overview of incobotulinumtoxinA based on randomized controlled trials and prospective clinical studies.
IncobotulinumtoxinA provides clinical efficacy in treating blepharospasm, CD, and upper-limb post-stroke spasticity based on randomized, double-blind, placebo-controlled trials with open-label extension periods (total study duration up to 89 weeks). Adverse events were generally mild or moderate. The most frequent adverse events, probably related to the injections, included eyelid ptosis and dry eye in the treatment of blepharospasm, dysphagia, neck pain, and muscular weakness in patients with CD, and injection site pain and muscular weakness when used for treating spasticity. In blepharospasm and CD, incobotulinumtoxinA was investigated in clinical trials permitting flexible intertreatment intervals based on the individual patient's clinical need; the safety profile of intervals shorter than 12 weeks was comparable to intervals of 12 weeks and longer. There were no cases of newly formed neutralizing antibodies during the Phase III and IV incobotulinumtoxinA trials. Phase III head-to-head trials of incobotulinumtoxinA versus onabotulinumtoxinA for the treatment of blepharospasm and CD have demonstrated therapeutic equivalence of both formulations. Additional Phase III trials of incobotulinumtoxinA in conditions such as lower-limb spasticity, spasticity in children with cerebral palsy, and sialorrhea in various neurological disorders are ongoing.
IncobotulinumtoxinA is an effective, well-tolerated botulinum neurotoxin type A formulation. Data from randomized clinical trials and further observational studies are expected to help physicians to optimize treatment by tailoring the choice of formulation, dose, and treatment intervals to the patient's clinical needs.
Full-text · Article · Apr 2015 · Drug Design, Development and Therapy
[Show abstract][Hide abstract] ABSTRACT: The results of register studies suggest an association between Parkinson's disease (PD) and melanoma. We studied the frequency and profile of early markers of PD in patients with malignant melanoma.
100 participants were enrolled in a prospective observational study, of whom 65 had a history of high-risk cutaneous (n=53) or uveal (n=12) melanoma (31 women; age, 61.2±14.9 years) and another 35 served as control participants (19 women; 54.6±20.5 years). Participants underwent assessments of motor function (Unified PD Rating Scale; keyboard tapping test), olfactory function, colour vision, depressive symptoms, the Non-Motor Symptoms Questionnaire, and transcranial brain sonography. Raters were blinded to the diagnosis and clinical data of study participants.
Patients with melanoma showed increased frequency of substantia nigra hyperechogenicity and prodromal motor and non-motor features of PD, especially asymmetric motor slowing and apathy. Hyposmia and colour vision disturbance were, however, infrequent. Larger echogenicity of substantia nigra correlated with lower serum iron in patients with melanoma, similar to previously reported findings in PD, and independently from the earlier findings, with lighter skin pigmentation. Substantia nigra hyperechogenicity, combined with motor asymmetry or hyposmia, was present at baseline in all participants with mild or definite parkinsonism diagnosed after 1 year. Parkinsonism was specifically related to melanoma location at the sun-exposed skin of the head or neck.
History of melanoma was associated with increased prevalence of prodromal markers of PD. Their predictive value needs to be established in long-term investigations. The similarity of serum iron characteristics found in patients with melanoma and PD deserves further research.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
No preview · Article · Mar 2015 · Journal of neurology, neurosurgery, and psychiatry
[Show abstract][Hide abstract] ABSTRACT: A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients.
We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures.
Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts.
In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.
[Show abstract][Hide abstract] ABSTRACT: Glucocorticosteroids (GCS) are widely used for the treatment of neurological diseases, e.g. multiple sclerosis. High levels of GCS are toxic to the central nervous system and can produce adverse effects. The effect of methylprednisolone (MP) on mammalian neuronal networks was studied in vitro. We demonstrate a dose-dependent excitatory effect of MP on cultured neuronal networks, followed by a shut-down of electrical activity using the microelectrode array technique.
No preview · Article · Oct 2014 · Cellular and Molecular Neurobiology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Multiple sclerosis (MS) is an autoimmune disease affecting young people and is a major cause of disability. In the course of time, disability progresses and symptoms like spasticity may occur. Spasticity is a major cost factor in MS patients. Various agents are approved for the treatment of spasticity, but each of those agents may have several side effects. Intrathecally administered steroids (triamcinolone-acetonide (TCA)) may be efficient in treating spasticity in patients with lesions in the spinal cord and no response to first-line therapeutics. The aim of this study is to show effects of TCA treatment on clinical parameters in patients with MS.
This multicentre open label study included 54 patients with MS. The clinical outcome parameters were spasticity, disability, maximum walking distance, bladder function and quality of life. All patients received physiotherapy in addition to TCA treatment to obtain optimal effects on clinical parameters.
Spasticity, maximum walking distance as well as disability improved significantly (P ⩽ 0.001) during TCA applications. Bladder function improved in every seventh patient.
We observed the effects of intrathecally administered TCA on different clinical parameters including bladder function. TCA administration is a safe method to treat different symptoms in MS patients. Longitudinal trials with repeated TCA cycles are needed to show long-term effects. Besides TCA treatment, physiotherapy contributes to the improvement of clinical parameters.