Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain.

OBJECTIVES: To determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity. METHODS: This prospective multicentre study included outpatients with RA scheduled for escalation of anti-inflammatory treatment due to active disease and severe pain (Disease Activity Score 28 (DAS28)>3.2 and Visual Analogue Scale (VAS)>50). At week 24, patients were stratified into reference group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score<50), non-responders (DAS28 improvement≤1.2 and DAS28>3.2, regardless of VAS pain score) and persisting pain group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score≥50). The former two subgroups ended the study at week 24. The latter continued until week 48. Demographic data, DAS28-C reactive protein, VAS for pain, painDETECT Questionnaire (PD-Q) to identify neuropathic pain (NeP) and the Pain Catastrophising Scale were assessed and tested for relation to persisting pain. RESULTS: Of 567 patients, 337 (59.4%) were classified as reference group, 102 (18.0%) as non-responders and 128 (22.6%) as patients with persisting pain. 21 (8.8%) responders, 28 (35.0%) non-responders and 27 (26.5%) persisting pain patients tested positive for NeP at week 24. Pain catastrophising (p=0.002) and number of tender joints (p=0.004) were positively associated with persisting pain at week 24. Baseline PD-Q was not related to subsequent persisting pain. CONCLUSIONS: Persisting and non-nociceptive pain occur frequently in RA. Besides the potential involvement of NeP, pain catastrophising and a higher number of tender joints coincide with persisting pain.

[The EAN-NeuPSIG guideline on the diagnosis of neuropathic pain-a summary]. / Die EAN-NeuPSIG-Leitlinie zur Diagnostik bei neuropathischen Schmerzen ­ eine Kurzfassung.

In this joint guideline of the scientific societies and working groups mentioned in the title, evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain were developed. The systematic literature search and meta-analysis yielded the following results: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I­DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, while S­LANSS (self-administered LANSS) and PainDETECT received weak recommendations for their use in the diagnostic workup of patients with possible neuropathic pain. There was a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials. The role of confocal corneal microscopy is still unclear. Functional imaging and peripheral nerve blocks are helpful in elucidating the pathophysiology, but current literature does not support their use in diagnosing neuropathic pain. In selected cases, genetic testing in specialized centers may be considered.

Neuropathic Pain: Mechanism-Based Therapeutics.

Neuropathic pain (NeP) can result from sources as varied as nerve compression, channelopathies, autoimmune disease, and incision. By identifying the neurobiological changes that underlie the pain state, it will be clinically possible to exploit mechanism-based therapeutics for maximum analgesic effect as diagnostic accuracy is optimized. Obtaining sufficient knowledge regarding the neuroadaptive alterations that occur in a particular NeP state will result in improved patient analgesia and a mechanism-based, as opposed to a disease-based, therapeutic approach to facilitate target identification. This will rely on comprehensive disease pathology insight; our knowledge is vastly improving due to continued forward and back translational preclinical and clinical research efforts. Here we discuss the clinical aspects of neuropathy and currently used drugs whose mechanisms of action are outlined alongside their clinical use. Finally, we consider sensory phenotypes, patient clusters, and predicting the efficacy of an analgesic for neuropathy.

Beyond biopsychosocial: The keystone mechanism theory of pain.

Pain is a deeply personal experience, with interindividual differences in its chronification and treatment presenting a formidable healthcare challenge. The biopsychosocial model (BPSm) has been hugely influential within nascent attempts at precision pain medicine, steering the field away from a reductionist biomechanical viewpoint and emphasising complex interactions of biological, psychological, and social factors which shape the individuality of pain. However, despite offering a strong theoretical foundation and holistic perspective, we contend that the BPSm remains limited in its capacity to deliver truly mechanistically informed treatment of pain. We therefore propose the keystone model of pain which offers a pragmatic balance between the dimensionality expansive BPSm and overly reductive approaches, providing both theoretical and practical advantages for the transition from treating populations to individual people.

Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

Sensory Profiles in Patients with Low Back Pain with and Without Radiculopathy.

OBJECTIVE: During routine clinical evaluation, it can be challenging to differentiate between lumbar radiculopathy (RAD) and lower back pain with non-radicular somatic referred pain (SRP) or even axial non-radiating low back pain (LBP). The aim of this study was to characterize patients with RAD, axial LBP (aLBP), and SRP on the basis of somatosensory profiles. METHODS: Patients with LBP (n = 54) were assessed with quantitative sensory testing in the area of LBP and, in cases of RAD, additionally in the area of projecting pain. Questionnaires (PainDETECT®, EuroQol-5D, Medical Outcomes Study Sleep Scale, Hannover Functional Ability Questionnaire for Back Pain, Roland Morris Disability Questionnaire, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale) were answered by all patients. RESULTS: Patients with RAD (n = 12) had higher pain intensity scores (numeric rating scale: 5.7 ± 1.5 vs 4.1 ± 2.2; P < 0.05) and higher PainDETECT scores (14.6 ± 6.13 vs 9.7 ± 6.2; P < 0.05) than did patients with aLBP and SRP (n = 42). Patients with RAD had a more pronounced loss of small-fiber function, increased mechanical hyperalgesia, and a trend toward increased sensitivity to thermal pain in the area of LBP compared with patients with aLBP and SRP. Within patients with RAD, sensory profiles of the area of projecting pain and the area of LBP did not differ. Pressure pain hyperalgesia (measured by pressure pain threshold) and loss of mechanical detection (measured by mechanical detection threshold) in combination with the PainDETECT items numbness and prickling reached the best predictive value in detecting a radiculopathy. CONCLUSIONS: Patients with RAD demonstrated more somatosensory abnormalities than did patients with aLBP and SRP, including increased mechanical hyperalgesia and a loss of mechanical detection. The combination of pressure pain threshold, mechanical detection threshold, numbness, and prickling in the area of LBP can be a time-efficient tool to identify patients with RAD.

Precision Medicine in Neuropathic Pain.

Neuropathic pain is a common chronic pain condition that is caused by a lesion or disease of the somatosensory nervous system. The multitude of sensory negative and positive sensations and associated comorbidities have a major impact on quality of life of affected patients. Current treatment options often only lead to a partial pain relief or are even completely ineffective. In addition, many clinical trials for the development of new drugs have not met the primary endpoint. Therefore, there is still an unmet clinical need in neuropathic pain syndromes. One reason for this therapeutic dilemma could be the heterogeneity of neuropathic pain with a variety of pathophysiological pain mechanisms that are expressed differently in each patient regardless of the underlying disease etiology. Reclassification of neuropathic pain syndromes therefore focuses on the underlying mechanisms of pain development rather than the disease etiology. A priori stratification of patients based on these individual mechanisms could allow the identification of potential treatment responders and thus realize the concept of a mechanism-based treatment. As no biomarkers for pain mechanisms have been discovered yet, one has to rely on surrogate markers that are thought to be closely related to these mechanisms. In this chapter, we present promising predictive biomarkers, focusing in particular on sensory symptoms and signs assessed by patient-reported outcome measures and sensory testing, and discuss how these tools might be used in clinical trials in the future.

Turning When Using Smartphone in Persons With and Those Without Neurologic Conditions: Observational Study.

BACKGROUND: Turning during walking is a relevant and common everyday movement and it depends on a correct top-down intersegmental coordination. This could be reduced in several conditions (en bloc turning), and an altered turning kinematics has been linked to increased risk of falls. Smartphone use has been associated with poorer balance and gait; however, its effect on turning-while-walking has not been investigated yet. This study explores turning intersegmental coordination during smartphone use in different age groups and neurologic conditions. OBJECTIVE: This study aims to evaluate the effect of smartphone use on turning behavior in healthy individuals of different ages and those with various neurological diseases. METHODS: Younger (aged 18-60 years) and older (aged >60 years) healthy individuals and those with Parkinson disease, multiple sclerosis, subacute stroke (<4 weeks), or lower-back pain performed turning-while-walking alone (single task [ST]) and while performing 2 different cognitive tasks of increasing complexity (dual task [DT]). The mobility task consisted of walking up and down a 5-m walkway at self-selected speed, thus including 180° turns. Cognitive tasks consisted of a simple reaction time test (simple DT [SDT]) and a numerical Stroop test (complex DT [CDT]). General (turn duration and the number of steps while turning), segmental (peak angular velocity), and intersegmental turning parameters (intersegmental turning onset latency and maximum intersegmental angle) were extracted for head, sternum, and pelvis using a motion capture system and a turning detection algorithm. RESULTS: In total, 121 participants were enrolled. All participants, irrespective of age and neurologic disease, showed a reduced intersegmental turning onset latency and a reduced maximum intersegmental angle of both pelvis and sternum relative to head, thus indicating an en bloc turning behavior when using a smartphone. With regard to change from the ST to turning when using a smartphone, participants with Parkinson disease reduced their peak angular velocity the most, which was significantly different from lower-back pain relative to the head (P<.01). Participants with stroke showed en bloc turning already without smartphone use. CONCLUSIONS: Smartphone use during turning-while-walking may lead to en bloc turning and thus increase fall risk across age and neurologic disease groups. This behavior is probably particularly dangerous for those groups with the most pronounced changes in turning parameters during smartphone use and the highest fall risk, such as individuals with Parkinson disease. Moreover, the experimental paradigm presented here might be useful in differentiating individuals with lower-back pain without and those with early or prodromal Parkinson disease. In individuals with subacute stroke, en bloc turning could represent a compensative strategy to overcome the newly occurring mobility deficit. Considering the ubiquitous smartphone use in daily life, this study should stimulate future studies in the area of fall risk and neurological and orthopedic diseases. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022998; https://drks.de/search/en/trial/DRKS00022998.

The solitary nucleus connectivity to key autonomic regions in humans.

The nucleus tractus solitarius (NTS) is a key brainstem structure relaying interoceptive peripheral information to the interrelated brain centres for eliciting rapid autonomic responses and for shaping longer-term neuroendocrine and motor patterns. Structural and functional NTS' connectivity has been extensively investigated in laboratory animals. But there is limited information about NTS' connectome in humans. Using MRI, we examined diffusion and resting state data from 20 healthy participants in the Human Connectome Project. The regions within the brainstem (n = 8), subcortical (n = 6), cerebellar (n = 2) and cortical (n = 5) parts of the brain were selected via a systematic review of the literature and their white matter NTS connections were evaluated via probabilistic tractography along with functional and directional (i.e. Granger causality) analyses. The underlying study confirms previous results from animal models and provides novel aspects on NTS integration in humans. Two key findings can be summarized: (1) the NTS predominantly processes afferent input and (2) a lateralization towards a predominantly left-sided NTS processing. Our results lay the foundations for future investigations into the NTS' tripartite role composed of interoreceptors' input integration, the resultant neurochemical outflow and cognitive/affective processing. The implications of these data add to the understanding of NTS' role in specific aspects of autonomic functions.

Chemotherapy-induced peripheral neuropathy (CIPN): current therapies and topical treatment option with high-concentration capsaicin.

Cancer diagnosis and treatment are drastic events for patients and their families. Besides psychological aspects of the disease, patients are often affected by severe side effects related to the cancer itself or as a result of therapeutic interventions. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of oral or intravenous chemotherapy. The disorder may require dose reduction of chemotherapy and is accompanied by multiple symptoms with long-term functional impairment affecting quality of life (QoL), e.g., sensory and functional deteriorations as well as severe pain. Although CIPN may reverse or improve after termination of the causative chemotherapy, approximately 30-40% of patients are faced with chronicity of the symptoms. Due to the advantages in cancer diagnosis and treatments, survival rates of cancer patients rise and CIPN may occur even more frequently in the future. In this review, we summarize current recommendations of leading national and international societies regarding prevention and treatment options in CIPN. A special focus will be placed on current evidence for topical treatment of CIPN with high-dose capsaicin. Finally, an algorithm for CIPN treatment in clinical practice is provided, including both pharmacologic and non-pharmacologic modalities based on the clinical presentation.

Persistent Spinal Pain Syndrome: A Proposal for Failed Back Surgery Syndrome and ICD-11.

OBJECTIVE: For many medical professionals dealing with patients with persistent pain following spine surgery, the term Failed back surgery syndrome (FBSS) as a diagnostic label is inadequate, misleading, and potentially troublesome. It misrepresents causation. Alternative terms have been suggested, but none has replaced FBSS. The International Association for the Study of Pain (IASP) published a revised classification of chronic pain, as part of the new International Classification of Diseases (ICD-11), which has been accepted by the World Health Organization (WHO). This includes the term Chronic pain after spinal surgery (CPSS), which is suggested as a replacement for FBSS. METHODS: This article provides arguments and rationale for a replacement definition. In order to propose a broadly applicable yet more precise and clinically informative term, an international group of experts was established. RESULTS: 14 candidate replacement terms were considered and ranked. The application of agreed criteria reduced this to a shortlist of four. A preferred option-Persistent spinal pain syndrome-was selected by a structured workshop and Delphi process. We provide rationale for using Persistent spinal pain syndrome and a schema for its incorporation into ICD-11. We propose the adoption of this term would strengthen the new ICD-11 classification. CONCLUSIONS: This project is important to those in the fields of pain management, spine surgery, and neuromodulation, as well as patients labeled with FBSS. Through a shift in perspective, it could facilitate the application of the new ICD-11 classification and allow clearer discussion among medical professionals, industry, funding organizations, academia, and the legal profession.

Proposed Mobility Assessments with Simultaneous Full-Body Inertial Measurement Units and Optical Motion Capture in Healthy Adults and Neurological Patients for Future Validation Studies: Study Protocol.

Healthy adults and neurological patients show unique mobility patterns over the course of their lifespan and disease. Quantifying these mobility patterns could support diagnosing, tracking disease progression and measuring response to treatment. This quantification can be done with wearable technology, such as inertial measurement units (IMUs). Before IMUs can be used to quantify mobility, algorithms need to be developed and validated with age and disease-specific datasets. This study proposes a protocol for a dataset that can be used to develop and validate IMU-based mobility algorithms for healthy adults (18-60 years), healthy older adults (>60 years), and patients with Parkinson's disease, multiple sclerosis, a symptomatic stroke and chronic low back pain. All participants will be measured simultaneously with IMUs and a 3D optical motion capture system while performing standardized mobility tasks and non-standardized activities of daily living. Specific clinical scales and questionnaires will be collected. This study aims at building the largest dataset for the development and validation of IMU-based mobility algorithms for healthy adults and neurological patients. It is anticipated to provide this dataset for further research use and collaboration, with the ultimate goal to bring IMU-based mobility algorithms as quickly as possible into clinical trials and clinical routine.

Oral or Topical Pain Therapy-How Would Patients Decide? A Discrete Choice Experiment in Patients with Peripheral Neuropathic Pain.

To ensure an adequate pain therapy with high patient adherence, it is necessary to know and consider patient preferences. A discrete choice experiment was used to obtain patients' preferences regarding treatment with systemic or topical pain medication. Patients with peripheral neuropathic pain (pNP) were recruited in two pain-focused practices in Germany. To identify relevant attributes of topical or systemic pain medication, a literature review and face-to-face interviews with experts for pain treatment were conducted. The attributes used in the choice scenarios were noticeable onset of effect, time spent in medical office, risk of systemic and local side effects, and impairment of daily life with regard to sleep quality and sexuality. The model was estimated with a mixed multinomial logit regression model. The study included 153 participants suffering from moderate to severe pNP. Most important attributes from patient's perspective was noticeable onset of effect (odds ratio 2.141 [95% confidence interval 1.837 to 2.494]), followed by risk of systemic side effects (2.038 [1.731 to 2.400]) and risk of sexual dysfunction (1.839 [1.580 to 2.140]), while risk of local side effects regarding skin ranked fourth (1.612 [1.321 to 1.966]). The impairment of sleep quality was also significant but less important (1.556 [1.346 to 1.798]). Local side effects were more likely to be accepted than systemic side effects. The risk of sexual dysfunction as a side effect of treatment is very important for patients, although it has received little attention in the literature.

The cornucopia of central disinhibition pain - An evaluation of past and novel concepts.

Central disinhibition (CD), as applied to pain, decreases thresholds of endogenous systems. This provokes onset of spontaneous or evoked pain in an individual beyond the ability of the nervous system to inhibit pain resulting from a disease or tissue damage. The original CD concept as proposed by Craig entails a shift from the lateral pain pathway (i.e. discriminative pain processing) towards the medial pain pathway (i.e. emotional pain processing), within an otherwise neurophysiological intact environment. In this review, the original CD concept as proposed by Craig is extended by the primary "nociceptive pathway damage - CD" concept and the secondary "central pathway set point - CD". Thereby, the original concept may be transferred into anatomical and psychological non-functional conditions. We provide examples for either primary or secondary CD concepts within different clinical etiologies as well as present surrogate models, which directly mimic the underlying pathophysiology (A-fiber block) or modulate the CD pathway excitability (thermal grill). The thermal grill has especially shown promising advancements, which may be useful to examine CD pathway activation in the future. Therefore, within this topical review, a systematic review on the thermal grill illusion is intended to stimulate future research. Finally, the authors review different mechanism-based treatment approaches to combat CD pain.

Do doctors treat themselves differently than their patients? Study on the self-treatment of migraine among German neurologists and pain specialists.

AIM: To investigate whether the self-treatment of migraine among neurologists and pain specialists corresponds to national medical guidelines and treatment of patients. METHODS: An email cross-sectional survey was sent to members of the German Society for Neurology, German Pain Society and German Migraine and Headache Society containing questions on demographics, professional experience and specialization and - in case participants suffered from migraine - questions about their migraine and its treatment. RESULTS: 175/418 (41.9%) participants suffered from migraine (m: 29.3%; f: 55.2%, 45.9 ± 10.7 years). For acute migraine attacks, 96.6 % of them use a first-line treatment according to the medical guidelines. Seventeen (9.7%) are currently taking a migraine prophylaxis, 52.9% of these use a recommended first-line prophylaxis. In all, 21.7% are not taking a prophylactic treatment despite an indication (based on number of monthly migraine days) for it, due to fear of side-effects, low intensity of migraine attacks and a sufficient effect of acute medication. This group of participants was younger, less experienced and specialized and was mainly employed (vs. self-employed) compared to those taking a prophylaxis. A total of 96.6% reported treating their patients in line with current guidelines; 14.3% would treat themselves differently when they were their own patients. CONCLUSION: The self-treatment of acute migraine attacks for the most part complies with the guidelines but, regarding the indication for a prophylaxis, a more divergent treatment approach was observed among younger, less experienced physicians. For the majority of physicians there is no difference between self-treatment and treatment of migraine patients.

Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment - the ComOn-study.

BACKGROUND: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). METHODS: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. DISCUSSION: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.

[Syncopes]. / Synkopen.

Syncopes are defined as sudden and short unconsciousness with loss of muscular tonus which are reversible without further intervention. Differentiation from other short-lasting changes of consciousness as in seizures, blood flow abnormalities of brainstem, metabolic disorders, intoxication or traumatic loss of consciousness is important for further diagnostic and adequate treatment.

Neurogeriatrics-a vision for improved care and research for geriatric patients with predominating neurological disabilities.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson's disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.

The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts.

BACKGROUND: Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.

Up-date on Clinical Management of Postherpetic Neuralgia and Mechanism-Based Treatment: New Options in Therapy.

Patients with postherpetic neuralgia may experience various sensory signs and symptoms of pain. Despite this, the recommendations for medicinal treatment do not differ accordingly. In order to find the appropriate treatment options for postherpetic neuralgia, several attempts have been made in the past. The crucial obstacle to these attempts was insufficient or no subgrouping of patients according to their sensory phenotype, mostly resulting in an unsatisfactory treatment response. Recently, a new concept of retrospective stratification according to the patients' sensory phenotype has been made in a large cohort of pain patients. This new stratification tool allows a predictive validity for treatment response in subgroups of patients and might be of potential value in determining the optimal treatment in postherpetic neuralgia patients.