Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome: Treatment approach depends on disease course.

INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory central nervous system (CNS) disorder, chiefly involving the brainstem, especially the pons. The diagnosis is challenging, requires careful exclusion of alternative diagnoses and a targeted therapeutic approach. CLIPPERS is known to respond well to corticosteroids, but the treatment needs to be long-term and can cause significant side-effects. Moreover, subsequent corticosteroid withdrawal often leads to a relapse. It has been suggested that anti-CD20 molecules could benefit several antibody-mediated CNS inflammatory diseases, including CLIPPERS. CASE REPORT: This paper describes two cases of CLIPPERS. The first demonstrates the benefit of early introduction of corticosteroids with side effects in cases of long-term use. The second demonstrates the efficacy of ocrelizumab (anti-CD20 molecule) in a severe course of CLIPPERS. CONCLUSION: These two cases bring attention to this rare, often misdiagnosed but treatable disease.

Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study.

BACKGROUND: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke. PATIENTS AND METHODS: We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). RESULTS: Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001). CONCLUSION: This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy.

Risk factors for depression and anxiety in painful and painless diabetic polyneuropathy: A multicentre observational cross-sectional study.

BACKGROUND: Despite the high prevalence of depression and anxiety in chronic pain conditions, current knowledge concerning emotional distress among painful diabetic polyneuropathy (pDSPN) and other diabetes mellitus (DM) sufferers is limited. METHODS: This observational multicentre cohort study employed the Hospital Anxiety and Depression Scale, the Beck Depression Inventory II and the State-Trait Anxiety Inventory to assess symptoms of depression and anxiety in several groups with diabetes, as well as in a control group. The study cohort included 347 pDSPN patients aged 63.4 years (median), 55.9% males; 311 pain-free diabetic polyneuropathy (nDSPN) patients aged 63.7 years, 57.9% males; 50 diabetes mellitus (DM) patients without polyneuropathy aged 61.5 years, 44.0% males; and 71 healthy controls (HC) aged 63.0 years, 42.3% males. The roles played in emotional distress were explored in terms of the biological, the clinical (diabetes-, neuropathy- and pain-related), the socio-economic and the cognitive factors (catastrophizing). RESULTS: The study disclosed a significantly higher prevalence of the symptoms of depression and anxiety not only in pDSPN (46.7% and 60.7%, respectively), but also in patients with nDSPN (24.4% and 44.4%) and DM without polyneuropathy (22.0% and 30.0%) compared with HCs (7.0% and 14.1%, p < 0.001). Multiple regression analysis demonstrated the severity of pain and neuropathy, catastrophic thinking, type 2 DM, lower age and female sex as independent contributors to depression and anxiety. CONCLUSIONS: In addition to the severity of neuropathic pain and its cognitive processing, the severity of diabetic polyneuropathy and demographic factors are key independent contributors to emotional distress in diabetic individuals. SIGNIFICANCE: In large cohorts of well-defined painless and painful diabetic polyneuropathy patients and diabetic subjects without polyneuropathy, we found a high prevalence of the symptoms of depression and anxiety, mainly in painful individuals. We have confirmed neuropathic pain, its severity and cognitive processing (pain catastrophizing) as dominant risk factors for depression and anxiety. Furthermore, some demographic factors (lower age, female sex), type 2 diabetes mellitus and severity of diabetic polyneuropathy were newly identified as important contributors to emotional distress independent of pain.

A 10-yr follow-up study for the detection of peripheral neuropathy in young patients with type 1 diabetes.

OBJECTIVE: The main objective of this work was to follow-up the development of diabetic neuropathy (DN) and its severity in patients with type 1 diabetes over 10 yr. Our intention was also to observe risk factor changes and verify which of them influence the development of neuropathy. The other objective was longitudinal study of electrophysiological parameters, focusing on the early diagnosis of DN. METHODS: The prospective study comprised of 62 young patients with type 1 diabetes mellitus (DM) aged 13.9 ± 5.89 yr, with diabetes duration of 5.56 ± 5.11 yr, treated with an intensified insulin regimen. All patients underwent a detailed clinical neurological examination, nerve conduction study (NCS) and biothesiometry three times (baseline, after 5 yr, after 10 yr). RESULTS: During the follow-up there was an increase in DN prevalence from 24.2% to 62.9% (p < 0.001). The proportion of patients with subclinical neuropathy increased from 17.7% to 46.8% (p < 0.001) and patients with clinical neuropathy from 6.5% to 16.1% (p < 0.001). The main contribution factors for rapid growth of the DN prevalence were poor glycaemic control, diabetes duration and patient's age. Regarding the conduction parameters, the most significant changes were observed in sural nerve SNAP amplitude (-5.2 m/s, p < 0.001) and sural nerve conduction velocity (-8.2 uV, p < 0.001). In contrast, the least significant changes were in peroneal nerve CMAP amplitude (-0.65 mV, p = 0.008). CONCLUSIONS: The results of the study demonstrated a progressive increase in the DN prevalence over time, in particular its subclinical stages. The long-term poor glycaemic control was a determining factor in the rapid DN development. The sensory conduction parameters deteriorated faster than the motor parameters. The present study is one of few of those in type 1 DM, which in relation to risk factors assess not only the presence of neuropathy, but also its severity. The results support the necessity of a regular diagnostic search for DN in diabetic children.