Christiane Hansen

Clinical evaluation criteria for the assessment of impaired pain sensitivity by thulium-laser evoked potentials

OBJECTIVES Cortical potentials evoked by carbon dioxide laser pulses have been applied in clinical practice to study nociceptive pathways for several years. In this study, we evaluate the properties of an infrared laser (thulium-YAG) with a penetration depth in the skin that matches the intracutaneous depth of nociceptors. METHODS Temperature measurements and modelling showed that the thulium laser generates painful intracutaneous temperatures with less surface heating than the carbon dioxide laser and with no side effects (up to 600 mJ pulse energy). To develop clinical evaluation criteria, laser-evoked potentials (LEPs) were recorded from 3 midline positions (Fz, Cz, Pz) versus linked earlobes in 23 healthy subjects. Within a session, two skin areas were studied twice in a balanced sequence using randomized interstimulus intervals and two intensities in randomized order. RESULTS After hand and foot stimulation with 540 mJ pulses, all subjects showed reproducible biphasic vertex potential, consisting of a negativity (hand: 210 ms, foot: 250 ms) and a positivity (hand: 330 ms, foot: 380 ms). Mean habituation of the vertex potential amplitude across runs was 25% (hand) or 16% (foot); due to the balanced sequence it did not affect the other comparisons. Following foot stimulation, peak latencies were significantly longer (by 40-50 ms) and amplitudes were significantly smaller than following hand stimulation (22.5+/-6.7 vs. 30.3+/-10.9 microV, mean+/-SD). Using 2. 5 standard deviations from the mean as a cut-off, absolute normative values were determined for peak latencies and amplitudes. In addition, relative normative values were determined for paired comparisons (hand-hand, foot-foot, hand-foot). CONCLUSIONS The thulium-YAG laser is a useful tool for assessment of impaired pain sensitivity. Representative case reports illustrate that unlike for early SEP components, the most frequent LEP abnormalities were amplitude differences.

Laser-evoked potentials after painful hand and foot stimulation in humans: evidence for generation of the middle-latency component in the secondary somatosensory cortex

The vertex potential (N2, P2) of the laser-evoked potential (LEP) is preceded by a small negativity (N1). The role of the secondary somatosensory cortex (SII) in generation of the N1 is established for the upper but not for the lower limb. We therefore investigated the N1 after painful radiant heat stimulation of hand and foot dorsum in 22 subjects. LEPs were recorded from the scalp with midline and temporal electrodes. After hand stimulation N1 was maximal in the contralateral temporal lead (mean peak latency 156 +/- 23 ms). After foot stimulation N1 was maximal in the same lead (200 +/- 22 ms). In the ipsilateral temporal lead, N1 appeared significantly smaller and later. N2 and P2 were maximal in midline electrodes for both stimulus sites. The latency shift between hand and foot stimulation was identical for all three components. These results suggest a contribution of temporo-parietal cortex (e.g. SII) to the N1 generation for stimulation of upper and lower limb.

Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis

OBJECTIVE Somatosensory evoked potentials (SEPs) play a less important role in the diagnosis of multiple sclerosis (MS) than visually evoked potentials. Since standard SEPs only reflect the dorsal column function, we now investigated spinothalamic tract function in patients with MS using laser-evoked potentials (LEPs). METHODS LEPs to thulium laser stimuli (3ms, 540 mJ, 5mm diameter) were recorded from 3 midline positions (Fz, Cz, Pz) in 20 patients with MS, and 6 patients with possible but unconfirmed MS. Peak latencies and peak-to-peak amplitude of the vertex potential negativity (N2) and positivity (P2) were evaluated and compared with normative values from 22 healthy control subjects. Median and tibial nerve SEPs were recorded with standard methods. Depending on the results of sensory testing, two skin areas (both hands, both feet, or one hand and foot of the same body side) were assessed in each patient. RESULTS In group comparisons, LEPs in patients with MS were significantly delayed and reduced in amplitude compared with healthy subjects (P<0.001) or patients with suspected but unconfirmed MS (P<0.05). In intraindividual comparisons within the patients with MS, LEP amplitude was significantly lower (P<0.01) and latencies were significantly longer (N2: P<0.01; P2: P<0.05) for a clinically hypoalgesic skin area than an unaffected control area. On a single case basis, LEPs were abnormal in 12 (60%) and SEPs in 8 (40%) of the patients with MS; combined analysis of LEPs and SEPs raised sensitivity to 75% (15 patients). LEPs were also abnormal for 7 skin areas with clinically normal nociception and thermal sensitivity, indicating subclinical lesions. Standard SEPs detected subclinical lesions in 5 areas with normal tactile sensitivity. CONCLUSIONS In patients with multiple sclerosis, spinothalamic tract function and LEPs were impaired more often than dorsal column function and SEPs. LEPs also detected subclinical lesions. Combined assessment of LEPs and SEPs can help to document dissemination of demyelinating CNS lesions and thus contribute to the diagnosis of multiple sclerosis.

Plasma glycosaminoglycans in endocrine ophthalmopathy

With evidence on the important role of glycosaminoglycans (GAG) in the pathogenesis of endocrine ophthalmopathy (EO) having accumulated, the present study focused on the biochemical assessment of plasma GAG content in 37 EO patients as compared to 20 controls. Glycosaminoglycans were isolated from plasma samples by protein elimination, dialysis, and precipitation with ethanol and cetylpyridinium chloride. Patients (9.71, 5.09, 15.09 mg/100 ml; median, 25th, 75th percentile) exhibited significantly (p=0.0021) higher plasma GAG levels than controls (4.6, 3.38, 6.8 mg/100 ml). Plasma GAG content was unrelated to age, sex, or antithyroid treatment. However, an even higher level of significance (p=0.0001) was reached when discriminating between untreated patients with EO of recent onset (14.16,10.35,15.51 mg/100 ml) and controls. By contrast, steroid therapy of EO led to values (3.82, 1.85, 6.52 mg/100 ml) indistinguishable from those of the controls. Further statistical analysis of the results, based on a specificity of 95% for the control group, revealed a sensitivity of 91 % for patients with untreated EO of recent onset, and a specificity of 100% for patients receiving steroid therapy. In comparison, plasma GAG content was determined in 8 untreated and in 6 treated EO patients by a second method already published. All untreated patients exhibited high GAG levels (median 2.23 mg/100 ml) whereas in treated EO patients normal plasma GAG values (0.17–0.34 mg/100 ml) were found. Follow-up determination of plasma GAG content in 7 patients undergoing steroid treatment unveiled a marked decrease of initially elevated values. These findings correlated well with clinical improvement of thyroid eye disease. Further studies involving a larger collective will permit a clinical evaluation of this parameter in the management of EO.

Abolished laser-evoked potentials and normal blink reflex in midlateral medullary infarction

Abstract We investigated two patients presenting with the rare finding of almost isolated hemianalgesia with a sensory level on the contralateral side sparing the face. Clinical findings, electrophysiological studies (absent laser-evoked pain-related somatosensory potentials, normal electrically evoked somatosensory potentials, magnetically evoked potentials, and blink reflexes), and magnetic resonance imaging showed the ventrolateral medullar tegmentum containing the spinothalamic tract to be affected by lacunar infarction. The blink reflex R2 component was unimpaired in both patients.

Bioäquivalenz eines Kombinationspräparates aus Levothyroxin und Jodid im Vergleich zum Monopräparat Levothyroxin

BACKGROUND Iodine deficiency is the main cause of endemic goitre. Iodine supplementation and decrease of pituitary TSH are the therapeutical aims. In this study, bioavailability of levothyroxine combined with iodide and the same dose of levothyroxine alone were compared. PATIENTS AND METHODS Fourty-eight subjects aged 18 to 40 years were randomly assigned for 6 days either 150 micrograms levothyroxine and 150 micrograms iodide (group A, n = 25) or 150 micrograms levothyroxine (group B, n = 23). Baseline TSH and thyroid hormones were measured 2 days before starting therapy as well as daily till day 6. TRH-test (delta TSH) and thyroid sonography were performed at day -2 and 6. RESULTS During therapy baseline TSH decreased markedly from 1.26 to 0.35 mU/ml (median) in group A and from 1.37 to 0.39 to 0.39 mU/ml in group B (both p < 0.001), as well as delta TSH (A from 5.66 to 2.61 mU/ml; B from 6.3 to 2.95 mU/ml; p < 0.001). Difference of delta TSH (day -2 versus day 6) was negatively correlated to body surface (r = -0.307; p < 0.05). TT4 levels increased in both groups (A from 7.1 to 9.1 microU/dl; B from 7.2 to 9.4 microU/dl; p < 0.005). No significant differences were noted between both groups for thyroid-related parameters. In both groups, confidence intervals for baseline TSH and TT4 were in the expected range. CONCLUSION In this study, similar bioavailability and bioequivalence for levothyroxine and the combination of levothyroxine with iodide were demonstrated.Zusammenfassung□ FragestellungDer alimentäre Jodmangel ist eine, der Hauptursachen der endemischen Struma. Bei der Strumatherapie sollten der intrathyreoidale Jodgehalt erhöht und das TSH gesenkt werden und so ein Rückgang der Schilddrüsengröße erreicht werden. Ziel dieser Studie war es, die Bioverfügbarkeit eines Kombinationspräparates aus Levothyroxin und Jodid mit der eines Monopräparates derselben Levothyroxindosierung zu vergleichen.□ Patienten und MethodenInsgesamt 48 männliche Probanden zwischen 18 und 40 Jahren (Altersmedian 25 Jahre) erhielten nach Randomisierung über sechs Tage entweder 150 μg Levothyroxin und 150 μg Jodid (Gruppe A, 25 Personen) oder 150 μg Levothyroxin (Gruppe B, 23 Personen). Zwei Tage vor Beginn der Medikation (Tag-2) wurden das basale und stimulierte TSH, die Schilddrüsenhormone Gesamttrijodthyronin (TT3) und -thyroxin (TT4) sowie das Schilddrüsenvolumen sonographisch bestimmt. Zusätzlich wurden an jedem der Einnahmetage das basale TSH, TT3 und TT4 gemessen. Zudem wurden unerwünschte Wirkungen erfaßt.□ ErgebnisseZu Beginn der Medikation befanden sich alle Parameter im Normbereich. Im Vergleich zu den Ausgangswerten nahm das basale TSH in Gruppe A im Median von 1,26 auf 0,35 mU/ml und in Gruppe B von 1,37 auf 0,39 mU/ml deutlich ab (p<0,001), ebenso das ΔTSH im TRH-Test (Gruppe A von 5,66 auf 2,61 mU/ml; Gruppe B von 6,3 auf 2,95 mU/ml; p<0,001). Die Differenz des ΔTSH vom Tag-2 und vom Tag 6 korrelierte negativ mit der Körperoberfläche der Probanden (r=−0,307; p<0,05). Die TT4-Spiegel stiegen in beiden Gruppen gleichermaßen an (Gruppe A von 7,1 auf 9,1 μU/dl; Gruppe B von 7,2 auf 9,4 μU/dl; p<0,005). Das Schilddrüsenvolumen reduzierte sich tendenziell in beiden Gruppen. Unterschiede zwischen den beiden Behandlungsgruppen A und B ergaben sich nicht. Die Konfidenzintervalle der beiden Gruppen für das basale TSH und das TT4 unterschieden sich nicht wesentlich.□ SchlußfolgerungBeide Therapeutika zeigten aufgrund der gleichen Verläufe der Parameter und der formalen Konfidenzintervallberechnung die gleiche Bioverfügbarkeit. Die Ergebnisse bestätigten die Bioäquivalenz zwischen dem Levothyroxinmonopräparat und dem Kombinationspräparat gleicher Levothyroxindosierung und Jodid, so daß ein Medikamentenwechsel bei gleichbleibender Levothyroxindosis komplikationslos sein dürfte.Abstract□ BackgroundIodine deficiency is the main cause of endemic goitre. Iodine supplemention and decrease of pituitary TSH are the therapeutical aims. In this study, bioavailability of levothyroxine combined with iodide and the same dose of levothyroxine alone were compared.□ Patients and MethodsFourty-eight subjects aged 18 to 40 years were randomly assigned for 6 days either 150 μg levothyroxine and 150 μg iodide (group A, n=25) or 150 μg levothyroxine (group B, n=23). Baseline TSH and thyroid hormones were measured 2 days before starting therapy as well as daily till day 6. TRH-test (ΔTSH) and thyroid sonography were performed at day-2 and 6.□ ResultsDuring therapy baseline TSH decreased markedly from 1.26 to 0.35 mU/ml (median) in group A and from 1.37 to 0.39 mU/ml in group B (both p<0.001), as well as ΔTSH (A from 5.66 to 2.61 mU/ml; B from 6.3 to 2.95 mU/ml; p<0.001). Difference of ΔTSH (day-2 versus day 6) was negatively correlated to body surface (r=−0.307; p<0.05). TT4 levels increased in both groups (A from 7.1 to 9.1 μU/dl; B from 7.2 to 9.4 μU/dl; p<0.005). No significant differences were noted between both groups for thyroid-related parameters. In both groups, confidence intervals for baseline TSH and TT4 were in the expected range.□ ConclusionIn this study, similar bioavailability and bioequivalence for levothyroxine and the combination of levothyroxine with iodide were demonstrated.