Quantity increase and functional affinity/avidity decrease of anti-FcεRI and anti-IgE autoantibodies in chronic spontaneous urticaria.

Summary: Background. Patients with autoimmune forms of chronic spontaneous urticaria (aiCSU) exhibit autoantibodies against the high-affinity IgE receptor (FcεRI) and IgE. As the presence of these autoantibodies does not correlate with disease activity, the functional affinity/avidity may be relevant in aiCSU. This exploratory study aimed to characterize the quantity and avidity of autoantibodies against IgE and FcεRI over 6 months. Methods. The serum of 49 patients with CSU and 30 healthy control subjects was obtained at baseline and 6 months. Serum was analyzed by ELISA, to determine the quantity and avidity of anti-IgE and anti-FcεRI autoantibodies, and by basophil activation test (CU-BAT). Results. An increase in the quantity of anti-FcεRI and anti-IgE antibodies and a simultaneous decrease in avidity was found in all patients with CSU after 6 months: median anti-IgE increased from 6.7 ng/mL (IQR 5.1-12.5) to 23.8 ng/mL (IQR 12.3-121.5), p less than 0.001, median anti-FcεRI from 52.4 ng/mL (IQR 26.3-111.4) to 129.5 ng/mL (IQR 73.7-253.7), p less than 0.001. Median anti-IgE avidity decreased from 75.8% (IQR 55.3-90.8) to 56.4% (IQR 30.6-76.2), p=0.019 and median anti-FcεRI avidity from 75.1% (IQR 49.8-90.0) to 52.2 (IQR 38.2-60.1), p less than 0.001. In contrast, the frequency of activated basophils did not change significantly over time. Surprisingly, autoantibody avidity did not correlate with basophil activation. Conclusions. Both the quantity and avidity of anti-FcεRI and anti-IgE antibodies change over time, demonstrating that the CU-BAT is more suitable to diagnose aiCSU. In addition, the avidity of anti-FcεRI and anti-IgE antibodies do not correlate with CU-BAT and disease activity, suggesting that further factors independent of anti-FcεRI and anti-IgE autoantibodies contribute to aiCSU.

Differential regulation of TRP channel gene and protein expression by intervertebral disc degeneration and back pain.

Intervertebral disc (IVD) degeneration and consequent low back pain (LBP) are common and costly pathological processes that require improved treatment strategies. Transient Receptor Potential (TRP) channels constitute a family of multimodal ion channels that have recently emerged as contributors to disc pathologies and were thus proposed as potential therapeutic targets, although limited data on their presence and function in the IVD exist. The purpose of this study was to determine the mRNA and protein expression of TRP channels in non-degenerated and degenerated human IVD tissue (with different pain intensity and chronicity) using gene array, conventional qPCR and immunohistochemistry. We could demonstrate that 26 out of 28 currently known TRP channels are expressed in the IVD on the mRNA level, thereby revealing novel therapeutic candidates from the TRPC, TRPM and TRPML subfamilies. TRPC6, TRPM2 and TRPML1 displayed enhanced gene and protein expression in degenerated IVDs as compared to non-degenerated IVDs. Additionally, the gene expression of TRPC6 and TRPML1 was influenced by the IVD degeneration grade. Pain intensity and/or chronicity influenced the gene and/or protein expression of TRPC6, TRPM2 and TRML1. Interestingly, decreased gene expression of TRPM2 was observed in patients treated with steroids. This study supports the importance of TRP channels in IVD homeostasis and pathology and their possible application as pharmacological targets for the treatment of IVD degeneration and LBP. However, the exact function and activation of the highlighted TRP channels will have to be determined in future studies.

Double-blind placebo-controlled trial of the effect of omalizumab on basophils in chronic urticaria patients.

BACKGROUND: Omalizumab has been shown to be effective in treating chronic spontaneous urticaria (CSU). The reduction in FcεRI receptor density on the surface of basophils and mast cells is thought to play a major role in its effectiveness. We conducted a double-blind, randomized, placebo-controlled trial to investigate the mode of action of omalizumab in patients with antihistamine-resistant CSU. METHODS: Thirty patients were randomized in a 2:1 ratio to receive either 300 mg omalizumab or placebo. Four monthly applications of omalizumab/placebo were followed up with a visit 2 months after the last injection. The primary endpoint was the FcεRI receptor density change on basophils. RESULTS: Omalizumab led to a significant reduction in FcεRI receptor density on basophils as soon as 1 week after the first injection: baseline omalizumab vs placebo group, 80.31 ± 47.18 × 10³ vs 78.29 ± 45.09 × 10³ receptors/basophil ± SD; 1 week, 72.89 ± 47.79 × 10³ vs 27.83 ± 20.87 × 10³, P = .001. This effect continued during the treatment phase and persisted for 2 months after the last injection: 93.81 ± 56.50 × 10³ vs 21.09 ± 15.23 × 10³, P = .002. Values for basophil "releasability" and the basophil activation test (CU-BAT) of patient serum using donor basophils were unchanged despite treatment: CU-BAT, CD63 10.75% (7.35) in the placebo group vs 8.35% (15.20) in the omalizumab group, P = .778. CONCLUSION: We demonstrated a rapid reduction of FcεRI receptor density on basophils following treatment with omalizumab. Because CU-BAT using well-characterized, omalizumab-naïve donor basophils did not change during the treatment phase, autoreactive serum factors seem to remain unaltered. This points towards a cellular effect of omalizumab on basophils. To predict the omalizumab response time and to monitor disease, FcεRI density and CU-BAT might be promising cellular-based assays.

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease.

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

Epigallocatechin 3-gallate suppresses interleukin-1ß-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats.

Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1ß, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB.

IL-33 is a mediator rather than a trigger of the acute allergic response in humans.

BACKGROUND: IL-33 enhances FcεRI-induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high IgE levels, IL-33 triggers degranulation and anaphylaxis of similar severity as specific allergen. Consistent with this view, sera of atopic patients contain elevated levels of IL-33 after anaphylaxis. In this study, we determined whether IL-33 is potentially anaphylactogenic in humans with high IgE levels by regulating exocytosis independent of FcεRI cross-linking. Furthermore, we investigated whether IL-33 is released upon allergen provocation in vivo. METHODS: In subjects with high serum IgE levels, we measured IL-33-induced histamine/LTC4 in vitro, CD63 translocation ex vivo, and responsiveness of mast cells in vivo by skin prick test (SPT). In asthma patients, release of IL-33 and its correlation with early (tryptase)- and late-phase markers (IL-13 levels, eosinophil numbers) of the allergic response were assessed in bronchoalveolar lavage fluids (BALFs) after allergen challenge. RESULTS: IL-33 itself does not trigger basophil degranulation in vitro and ex vivo, even in subjects with high serum IgE levels, and negative SPTs demonstrate that skin mast cells do not degranulate in response to IL-33. However, in response to allergen challenge, IL-33 is rapidly released into BALFs at levels that do not correlate with other immediate- and late-phase parameters. CONCLUSION: IL-33 is unlikely an independent trigger of anaphylaxis even in subjects with high IgE levels. However, the rapid release of IL-33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses.

[Significantly shorter anesthesia time for surgery of the lumbar spine : process analytical comparison of spinal anesthesia and intubation narcosis]. / Signifikant kürzere Anästhesiezeit bei lumbaler Wirbelsäulenchirurgie : Prozessanalytischer Vergleich von Spinalanästhesie und Intubationsnarkose.

INTRODUCTION: Most surgery of the lumbar spine is performed with the patient under general anesthesia (GA); however, qualitative benefits of spinal anesthesia (SA) have been reported. The goal of this study was to compare time efficiency between these two anesthesia methods in lumbar spine surgery. To test the hypothesis that the use of SA leads to significant time saving compared to GA for lumbar spine surgery, key points in the preoperative, intraoperative and postoperative anesthesiology care times were analyzed. The focus was on anesthesia time excluding surgery time. MATERIALS AND METHODS: Electronically based data of 473 anesthesia procedures (368 SA, 105 GA) for lumbar spine interventions performed in the prone position (i. e. decompression, discectomy and transpedicular instrumentation) were analyzed retrospectively. Patient population data including gender, age, American Society of Anesthesiologists (ASA) classification and body mass index (BMI) were analyzed. The focus was on the documented perioperative key time points which are defined as follows: (1) induction, (2) positioning (turning into prone position), (3) scrubbing and covering, (4) surgery time (knife to skin closure), (5) closing (end of surgery until leaving operating room) and (6) handing over to recovery. Differences in the amount of time for each perioperative period were calculated for SA and GA. RESULTS: In 7 out of the 368 SA patients SA failed and had to be converted to GA. There were no significant differences in BMI, ASA prevalence and gender between SA and GA patients but SA patients were significantly older (median 61.7 ± 15.4 years) than GA patients (median 56.1 ± 14.6 years). However, SA required significantly less time for induction (SA: 17.7 ± 7.0 min, GA: 21.6 ± 7.2 min), preoperative preparation (SA: 9.7 ± 3.6 min, GA: 13.3 ± 5.4 min) and closing period (SA: 4.9 ± 1.1 min, GA: 15.3 ± 5.7 min) compared to GA. Total anesthesia time with exclusion of the surgery time revealed a significant time reduction using SA of 19 min (95 % confidence interval: range 13.6-24.4 min, median in SA: 56.7 min, median in GA: 75.7 min, p < 0.0001). CONCLUSIONS: This study showed that in lumbar spine surgery 19 min of anesthesia time can be saved using SA compared to GA which could have an impact on economic aspects. Gender, BMI and ASA had no statistically detectable influence on the choice between the two anesthesia methods. The fact that time-intensive complex instrumentation is mainly performed in younger patients may explain why GA patients were younger than SA patients.

Radicular pain from lumbar canal stenosis in addition to pre-existing phantom limb pain.

Phantom limb (PL) is a term used to designate the sensation of the presence of an extremity following amputation, and it may be seen immediately after injury or years later in the part of the body that is deafferented or amputated. Phantom limb pain (PLP) is the term used to describe painful sensations referred to the absent limb. We present a case of a 71-year-old male with spinal claudication from discoligamentous lumbar canal stenosis L3-L4 and L4-L5 with L5 radicular pain in the left PL 13 years after the amputation. The patient had a disappearance of his radicular pain in the left PL following microsurgical lumbar decompression of L3-L4 and L4-L5. This is one of the rare cases reported in the literature in which a radicular pain in the PL disappeared following surgical decompression of the spinal canal.

Intravenous Immunoglobulin in Urticaria

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IgE to recombinant allergens Api m 1, Ves v 1, and Ves v 5 distinguish double sensitization from crossreaction in venom allergy.

BACKGROUND: Diagnostic tests in patients with Hymenoptera venom allergy are frequently positive to venoms of both honey bee and wasp (Vespula). Component-resolved analysis with recombinant species-specific major allergens (rSSMA) may help to distinguish true double sensitization from crossreactivity. METHODS: Included were 121 patients with systemic allergic reactions to Hymenoptera stings, 76 with double positivity of serum-specific IgE (sIgE) to both venoms, 45 with single positivity to bee or wasp venom, and 32 controls without history of systemic reactions to Hymenoptera stings and no sIgE to whole venoms. In venom-allergic patients and controls, sIgE to rSSMA Api m 1 of bee venom and to Ves v 1 and Ves v 5 of wasp venom were tested by ImmunoCAP. RESULTS: Only 47% of 76 patients with double positivity to whole venoms reacted also to rSSMA of both species. Specificity of sIgE to the 3 rSSMA was very high, with no sIgE to rSSMA of the other species in single-positive venom-allergic patients and only one control with low sIgE to Ves v 1. All wasp-allergic single-positive patients had sIgE to Ves v 5 and/or Ves v 1, and 78.3% of single-positive bee venom-allergic patients had sIgE to Api m 1. CONCLUSION: Specificity of sIgE to rSSMA of both species is excellent. Sensitivity of sIgE to rSSMA was optimal for wasp venom. Sensitivity of bee venom Api m 1 could be increased by adding rSSMA of other important bee venom allergens.

Etiology and pathogenesis of adverse drug reactions.

In clinical routine, adverse drug reactions (ADR) are common, and they should be included in the differential diagnosis in all patients undergoing drug treatment. Only part of those ADR are immune-mediated hypersensitivity reactions and thus true drug allergies. Far more common are non-immune-mediated ADR, e.g. due to the pharmacological properties of the drug or to the individual predisposition of the patient (enzymopathies, cytokine dysbalance, mast cell hyperreactivity). In true drug allergiesT cell- and immunoglobulin E (lgE)-mediated reactions dominate the clinical presentation. T cell-mediated ADR usually have a delayed appearance and include skin eruptions in most cases. Nevertheless, it should not be forgotten that they may involve systemic T cell activation and thus take a severe, sometimes lethal turn. Clinical danger signs are involvement of mucosal surfaces, blistering within the exanthematous skin areas and systemic symptoms, e.g. fever or malaise. Drug presentation via antigen-presenting cells to T cells can either involve the classical pathway of haptenization of endogenous proteins or be directly mediated via noncovalent binding to immune receptors (MHC molecules or T cell receptors), the so-called p-i concept. Flare-up reactions during the acute phase of T cell-mediated ADR should not be mistaken for true drug allergies, as they only occur in the setting of a highly activated T cell pool. IgE-mediated ADR are less frequent and involve mast cells and/or basophils as peripheral effector cells. Recent data suggest that certain patients with drug allergy have a preexistent sensitization although they have never been exposed to the culprit drug, probably due to cross-reactivity. Thus, allergic drug reactions on first encounter are possible. In general, the extent of cross-reactivity is higher in IgE-compared to T cell-mediated ADR. Based on a specific ethnic background and only for severe T cell-mediated ADR to certain drugs, a strong HLA association has been established recently.

Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug-specific T cells.

BACKGROUND: Up to 10% of patients with severe immune-mediated drug hypersensitivity reactions have tendencies to develop multiple drug hypersensitivities (MDH). The reason why certain individuals develop MDH and the underlying pathomechanism are unclear. We investigated different T cell subpopulations in MDH patients and compared them with patients allergic to a single drug and with healthy controls (HC). METHODS: We analyzed the in vitro reactivity of peripheral blood mononuclear cells from MDH patients (n=7), patients with hypersensitivity to a single drug (monoallergic, n=6), and healthy controls (HD) (n=6) to various drugs (mainly antibiotics and antiepileptics). By depleting and selectively re-adding CD4(+) CD25(bright) T cells (T regulatory cells, Treg), their effect on drug-specific T cell reactivity was analyzed. The phenotype of reacting T cells was determined ex vivo by staining for markers of activation (CD38) and cell exhaustion (PD-1). RESULTS: No functional deficiency of Treg cells was observed in all drug-allergic patients. Drug-reactive T cells from MDH patients were found in the CD4(+) CD25(dim) T cell fraction and showed enhanced CD38 and PD-1 expression, while those from monoallergic patients reside in the resting CD4(+) CD25(neg) T cell fraction. CONCLUSION: In patients with MDH, the drug-reactive T cells are contained in an in vivo pre-activated T cell fraction. Therefore, they may show a lower threshold for activation by drugs. The reason for this in vivo T cell pre-activation needs further investigations.

Continuous apple consumption induces oral tolerance in birch-pollen-associated apple allergy.

BACKGROUND: Patients with birch pollen allergy (major allergen: Bet v 1) have often an associated oral allergy syndrome (OAS) to apple, which contains the cross-reactive allergen Mal d 1. As successful birch pollen immunotherapy does not consistently improve apple related OAS symptoms, we evaluated whether regular apple consumption has an effect on OAS and immune parameters of Mal d 1 or Bet v 1 allergy. METHODS: A total of 40 patients with a clear history of birch pollen rhinoconjunctivitis and associated OAS to apple were included in an open, randomized, controlled clinical trial: 27 patients consumed daily defined amount of apple (1-128 g), doubling the amount every two to three weeks, while 13 patients remained untreated. Primary endpoint was the proportion of patients that achieved tolerance to at least 128 g of apple at the end of the study after 8 months. Exploratory endpoints were questionnaire about cross-reactive food and pollen allergy symptoms, conjunctival provocation test with birch pollen and Bet v 1, and in vitro tests (tIgE, sIgE, and IgG4 to Mal d 1 and Bet v 1; basophil activation test with both allergens). RESULTS: Seventeen of 27 patients in active group and none of 13 patients in control group (P = 0.0001) could tolerate a whole apple after the intervention. However, differences in endpoints reflecting systemic immune reactivity did not reach statistical significance. CONCLUSION: In patients with OAS to apple, tolerance can be safely induced with slowly, gradually increasing consumption of apple. However, the observation of a relapse after discounting of apple consumption and absence of immunologic changes suggest that induced tolerance is only transient.

An increase in serum tryptase even below 11.4 ng/mL may indicate a mast cell-mediated hypersensitivity reaction: a prospective study in Hymenoptera venom allergic patients.

BACKGROUND: During a systemic hypersensitivity reaction (SR), an increase in serum tryptase compared to the baseline value is an indicator of mast cell activation, most often due to an IgE-mediated mechanism. OBJECTIVE: To study the relevance of an increase in serum tryptase below the upper normal value of 11.4 ng/mL. METHODS: Serum tryptase levels were measured in 35 patients with Hymenoptera venom hypersensitivity before and during venom exposure. Of these, 20 developed SR to stings or following venom injections during immunotherapy (reactors), while 15 tolerated reexposure to stings or venom injections during immunotherapy without SR (non-reactors). Serum tryptase was estimated at 2, 5 and 24 h after exposure and was compared to a baseline value obtained before or at least 72 h after exposure. RESULTS: Considering circadian variation of serum tryptase, a relative increase to ≥135% of the baseline value (relative delta bound) was defined to indicate mast cell activation. Such an increase was observed in 17 of 20 reactors (85%), but none of 15 non-reactors. A serum tryptase of ≥11.4 ng/mL following venom exposure was observed in eight of the 20 reactors (40%) and 2 (13.3%) of the 15 non-reactors. Both these non-reactors also had an elevated baseline serum tryptase. CONCLUSIONS AND CLINICAL RELEVANCE: Serum tryptase values obtained during a suspected hypersensitivity reaction must always be compared to a baseline value. A relative tryptase increase to ≥135% of the baseline value during a suspected hypersensitivity reaction indicates mast cell activation even below 11.4 ng/mL.

Robust expression of CCR3 as a single basophil selection marker in flow cytometry.

BACKGROUND: Basophil activation tests (BAT) rely on different combinations of basophil selection and activation markers. Whereas activation markers, especially CD63, are widely validated, the most suitable and robust marker for basophil selection is still a matter of debate. AIMS: Comparison of cell surface expression of two commonly used basophil selection markers (IgE, CD123/HLA-DR) with CCR3 in an unselected group of atopic and nonatopic donors in resting and activated basophils. METHODS: EDTA blood of 94 healthy adults, about half of them atopic by history, was analyzed using two different staining strategies: anti-CD123-PE/anti-HLA-DR-PerCP/anti-lin1-FITC and anti-IgE-FITC/anti-CD3-PerCP/anti-CCR3-PE. Additionally 40 pollen-allergic patients were recruited for the assessment of CCR3 expression after basophil activation. RESULTS: In resting basophils, cell surface expression of the three basophil selection markers was most constant for CCR3. IgE gating strategy showed the highest variation and up to 80% of nonbasophils in the selected gate in certain donors. During basophil activation, a shift of the mean fluorescence intensity for CCR3 toward the lower third of the CCR3-positive population could be demonstrated, but neither were CCR3-positive cells significantly lost for further analysis nor was differentiation between CCR3-positive and CCR3-negative cell populations hampered by this shift. CONCLUSIONS: CCR3 is a stable and highly expressed basophil selection marker, independent of the atopic background or basophil activation state and allows an accurate identification of basophils without need of a second marker. The basophil markers CD123/HLA-DR and IgE showed significantly higher interindividual variability in cell surface expression and are therefore less suited as selection markers.

Unpredicted adverse reaction to omalizumab.

Despite promising reports of the use of omalizumab as add-on therapy in patients with systemic mastocytosis and recurrent anaphylaxis during specific venom immunotherapy (VIT), unpredicted adverse effects may lead to therapy failure. We present the case of a patient with systemic mastocytosis and Hymenoptera venom allergy who was administered omalizumab as add-on therapy to improve VIT tolerability after repeated severe adverse reactions despite H1/H2-antihistamine prophylaxis. We describe an unexpected discontinuation of omalizumab following successful initiation of VIT in a patient with systemic mastocytosis, with subsequent lack of tolerability of VIT. An interesting aspect of this case is the correlation of basophil activation test results with both clinical tolerability and VIT intolerance.

Lumbar spinal stenosis: assessment of cauda equina involvement by electrophysiological recordings.

UNLABELLED: The objective of this study was to investigate the relationship between electrophysiological recordings and clinical as well as radiological findings in patients suggestive to suffer from a lumbar spinal stenosis (LSS). We hypothesise that the electrophysiological recordings, especially SSEP, indicate a lumbar nerve involvement that is complementary to the neurological examination and can provide confirmatory information in less obvious clinical cases. In a prospective cohort study, 54 patients scheduled for surgery due to LSS were enrolled in an unmasked, uncontrolled trial. All patients were assessed by neurological examination, electrophysiological recordings, and magnetic resonance imaging (MRI) of the lumbar spine. The electrophysiological recordings focused on spinal lumbar nerve involvement. RESULTS: About 88% suffered from a multisegmental LSS and 91% of patients respectively complained of chronic lower back pain and/or leg pain for more than 3 months, combined with a restriction in walking distance. The neurological examination revealed only a few patients with sensory and/or motor deficits while 87% of patients showed pathological electrophysiological recordings (abnormal tibial SSEP in 78% of patients, abnormal H-reflex in 52% of patients). CONCLUSIONS: Whereas the clinical examination, even in severe LSS, showed no specific sensory-motor deficit, the electrophysiological recordings indicated that the majority of patients had a neurogenic disorder within the lumbar spine. By the pattern of bilateral pathological tibial SSEP and pathological reflexes associated with normal peripheral nerve conduction, LSS can be separated from a demyelinating polyneuropathy and mono-radiculopathy. The applied electrophysiological recordings, especially SSEP, can confirm a neurogenic claudication due to cauda equina involvement and help to differentiate neurogenic from vascular claudication or musculo-skeletal disorders of the lower limbs. Therefore, electro-physiological recordings provide additional information to the neurological examination when the clinical relevance of a radiologically-suspected LSS needs to be confirmed.