Ana Isabel Penzlin

Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence

Several clinical studies have indicated that selective serotonin reuptake inhibitors (SSRIs) administered in patients after acute ischemic stroke can improve clinical recovery independently of depression. Due to small sample sizes and heterogeneous study designs interpretability was limited in these studies. The mechanisms of action whereby SSRI might improve recovery from acute ischemic stroke are not fully elucidated.

The Effects of Pretreatment versus De Novo Treatment with Selective Serotonin Reuptake Inhibitors on Short-term Outcome after Acute Ischemic Stroke

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) administered in patients following acute ischemic stroke have shown to improve clinical recovery independently of changes in depression. Animal studies have demonstrated that sustained SSRI treatment is superior to short-term SSRI in evoking neurogenesis but how this benefit translates into humans remains to be answered. We hypothesized that in acute ischemic stroke patients, SSRI treatment started before the event leads to improved short-term outcomes compared to de novo SSRI treatment poststroke. METHODS We performed an exploratory analysis in consecutive acute ischemic stroke patients and compared patients already receiving fluoxetine, citalopram, or escitalopram with those who started treatment de novo. RESULTS Of 2653 screened patients, 239 were included (age, 69 ± 14 years; 42% men, baseline median National Institutes of Health Stroke Scale score, 7 [IQR, 10]). Of these patients, 51 started treatment with SSRI before stroke and 188 were prescribed newly SSRIs during hospitalization. In the adjusted multivariate logistic regression models, SSRI pretreatment was associated with favorable functional outcome at discharge defined as a modified Rankin Scale score of 2 or less (odds ratio [OR], 4.00; 95% confidence interval [CI], 1.68-9.57; P < .005), improved early clinical recovery (OR, 2.35; 95% CI, 1.15-4.81; P = .02), and a trend toward prediction of superior motor recovery (OR, 1.82; 95% CI, .90-3.68; P < .01). CONCLUSIONS Our data suggest that SSRI pretreatment may improve clinical outcomes in the early stages of acute ischemic stroke supporting the hypothesis that prolonged SSRI treatment started prestroke is superior to poststroke SSRI.

Heart rate variability biofeedback in patients with alcohol dependence: a randomized controlled study

Background and objective In patients with alcohol dependence, ethyl-toxic damage of vasomotor and cardiac autonomic nerve fibers leads to autonomic imbalance with neurovascular and cardiac dysfunction, the latter resulting in reduced heart rate variability (HRV). Autonomic imbalance is linked to increased craving and cardiovascular mortality. In this study, we sought to assess the effects of HRV biofeedback training on HRV, vasomotor function, craving, and anxiety. Methods We conducted a randomized controlled study in 48 patients (14 females, ages 25–59 years) undergoing inpatient rehabilitation treatment. In the treatment group, patients (n=24) attended six sessions of HRV biofeedback over 2 weeks in addition to standard rehabilitative care, whereas, in the control group, subjects received standard care only. Psychometric testing for craving (Obsessive Compulsive Drinking Scale), anxiety (Symptom Checklist-90-Revised), HRV assessment using coefficient of variation of R-R intervals (CVNN) analysis, and vasomotor function assessment using laser Doppler flowmetry were performed at baseline, immediately after completion of treatment or control period, and 3 and 6 weeks afterward (follow-ups 1 and 2). Results Psychometric testing showed decreased craving in the biofeedback group immediately postintervention (OCDS scores: 8.6±7.9 post-biofeedback versus 13.7±11.0 baseline [mean ± standard deviation], P<0.05), whereas craving was unchanged at this time point in the control group. Anxiety was reduced at follow-ups 1 and 2 post-biofeedback, but was unchanged in the control group (P<0.05). Following biofeedback, CVNN tended to be increased (10.3%±2.8% post-biofeedback, 10.1%±3.5% follow-up 1, 10.1%±2.9% follow-up 2 versus 9.7%±3.6% baseline; P=not significant). There was no such trend in the control group. Vasomotor function assessed using the mean duration to 50% vasoconstriction of cutaneous vessels after deep inspiration was improved following biofeedback immediately postintervention and was unchanged in the control group (P<0.05). Conclusion Our data indicate that HRV biofeedback might be useful to decrease anxiety, increase HRV, and improve vasomotor function in patients with alcohol dependence when complementing standard rehabilitative inpatient care.

Randomized controlled trials – a matter of design

Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

Cutaneous Autonomic Pilomotor Testing to Unveil the Role of Neuropathy Progression in Early Parkinson’s Disease (CAPTURE PD): Protocol for a Multicenter Study

Background In Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function. Methods/design A prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation. Discussion We anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD. Clinical trail registration TRN NCT03043768.

Should Skin Biopsies Be Performed in Patients Suspected of Having Parkinson’s Disease?

In patients with Parkinsons disease (PD), the molecularly misfolded form of α-synuclein was recently identified in cutaneous autonomic nerve fibers which displayed increased accumulation even in early disease stages. However, the underlying mechanisms of synucleinopathic nerve damage and its implication for brain pathology in later life remain to be elucidated. To date, specific diagnostic tools to evaluate small fiber pathology and to discriminate neurodegenerative proteinopathies are rare. Recently, research has indicated that deposition of α-synuclein in cutaneous nerve fibers quantified via immunohistochemistry in superficial skin biopsies might be a valid marker of PD which could facilitate early diagnosis and monitoring of disease progression. However, lack of standardization of techniques to quantify neural α-synuclein deposition limits their utility in clinical practice. Additional challenges include the identification of potential distinct morphological patterns of intraneural α-synuclein deposition among synucleinopathies to facilitate diagnostic discrimination and determining the degree to which structural damage relates to dysfunction of nerve fibers targeted by α-synuclein. Answering these questions might improve our understanding of the pathophysiological role of small fiber neuropathy in Parkinsons disease, help identify new treatment targets, and facilitate assessment of response to neuroprotective treatment.

Subsequent Bilateral Hippocampal Diffusion Restriction and Atrophy in Repeated Status Epilepticus

ABSTRACT Background: Cortical lesions in status epilepticus have been reported but the underlying mechanisms are poorly elucidated. Case summary: We report on a female patient (75 years) with a history of alcohol abuse who presented with complex partial status epilepticus and lateralized epileptiform discharges in the left frontal and temporal regions in EEG. While cranial magnetic resonance imaging (MRI) showed left hippocampal T2-hyperintensity and diffusion restriction, cerebrospinal fluid was normal and revealed no limbic encephalitis-related antibodies. Following treatment with levitiracetam, seizures ceased and the patient was dismissed. Nine months later, she was readmitted with generalized status epilepticus. Cranial MRI now showed hippocampal diffusion restriction and T2 hyperintensity, but in the right hemisphere, as well as atrophy and partial gliotic transformation of the initially affected left hippocampus. Discussion: Although hippocampal damage due to antibody-negative limbic encephalitis cannot be ruled out, our observation of subsequent bilateral hippocampal diffusion restriction with gliotic transformation may demonstrate permanent seizure-induced structural brain damage and underlines the importance of further research to elucidate the effects of prolonged epileptic discharges on cerebral structural integrity.

Assessment of sudomotor function

PurposeTo review the currently available literature on clinical autonomic tests of sudomotor function.MethodsWe searched PubMED/MEDLINE for articles on technical principles and clinical applications of sudomotor tests with a focus on their drawbacks and perspectives in order to provide a narrative review.ResultsThe quantitative sudomotor axon reflex sweat test (QSART) is the most widely used test of sudomotor function. The technique captures pathology with low intra- and inter-subject variability but is limited by technical demands. The thermoregulatory sweat test comprises topographic sweat pattern analysis of the ventral skin surface and allows differentiating preganglionic from postganglionic sudomotor damage when combined with a small fiber test such as QSART. The sympathetic skin response also belongs to the more established techniques and is used in lie detection systems due to its high sensitivity for sudomotor responses to emotional stimuli. However, its clinical utility is limited by high variability of measurements, both within and between subjects. Newer and, therefore, less widely established techniques include silicone impressions, quantitative direct and indirect axon reflex testing, sensitive sweat test, and measurement of electrochemical skin conductance. The spoon test does not allow a quantitative assessment of the sweat response but can be used as bedside-screening tool of sudomotor dysfunction.ConclusionWhile new autonomic sudomotor function testings have been developed and studied over the past decades, the most were well-studied and established techniques QSART and TST remain the gold standard of sudomotor assessment. Combining these techniques allows for sophisticated analysis of neurally mediated sudomotor impairment. However, newer techniques display potential to complement gold standard techniques to further improve their precision and diagnostic value.

Patient mit Small-Fiber-Neuropathie — das können Sie tun

ZusammenfassungEine Schädigung der kleinkalibrigen peripheren unmyelinisierten C-Fasern und der gering myelinisierten A-delta-Fasern (Small Fibers), z. B. durch Diabetes mellitus oder Gifte bzw. Medikamente, kann zu ganz unterschiedlichen Symptomen führen. Neben schmerzhaften Parästhesien beeinträchtigen dyshidrotische, kardiovaskuläre, urogenitale oder gastrointestinale Beschwerden die Lebensqualität nachhaltig. Verschaffen Sie sich einen Überblick darüber, was Sie für betroffene Patienten tun können.