Cortico-juxtacortical involvement increases risk of epileptic seizures in multiple sclerosis.

OBJECTIVES: Previous studies have reported an increased risk for epileptic seizures in multiple sclerosis (MS) patients. However, data on the pathogenesis of seizures remain inconclusive. The aim of our study is to evaluate prevalence, clinical and paraclinical features of epileptic attacks in our MS cohort and to search MS-specific risk factors for epileptic seizures. MATERIALS AND METHODS: In this cohort of 428 MS patients, 13 patients were identified with epileptic seizures occurring at any point during the course of MS including at MS onset. As a control group, we selected 26 MS patients without seizures and matched for gender, age and date of MS onset. We compared demographic features and clinic-radiological findings between the both groups. RESULTS: Thirteen patients (3%) were identified as having epileptic attacks. Ten patients (77%) experienced focal seizures, half of whom had confirmed secondary generalization. We did not find an association between seizures and disease course. Most patients had a single or few (2-5) seizures. MS patients with seizures had a significantly higher number of cortical and juxtacortical lesions on T2-weighted/fluid attenuation inversion recovery magnetic resonance imaging than control group [OR = 2.6 CI95% (1.0-6.5); P = 0.047]. CONCLUSIONS: Our findings support a credible role of cortical and juxtacortical involvement in the development of epileptic seizures in MS.

[Sleep-related movement and behavioural disorders in adults]. / Trastornos del movimiento y de la conducta durante el sueño en el adulto.

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions.

TITLE: Trastornos del movimiento y de la conducta durante el sueño en el adulto.Los trastornos del movimiento y de la conducta durante el sueño pueden tener un impacto en la calidad del sueño del paciente y dar lugar a síntomas diurnos. En estos grupos de enfermedades se incluyen entidades como el síndrome de piernas inquietas, los movimientos periódicos de las piernas y las parasomnias del sueño de movimientos oculares rápidos (REM) y no REM. El conocimiento de sus características clínicas y nociones sobre su manejo es de gran importancia para el neurólogo y especialista en sueño por su frecuencia e impacto en la calidad del sujeto. Con frecuencia, estos pacientes son referidos a dichos especialistas, y es relevante conocer que ciertos trastornos del sueño pueden asociarse a otras enfermedades neurológicas.

[An epidemiological, clinical and developmental study of 37 patients with early-onset benign occipital epilepsy of childhood]. / Estudio epidemiológico, clínico y evolutivo de 37 pacientes con epilepsia occipital benigna infantil de comienzo precoz.

AIM: To analyse the epidemiological, clinical and developmental characteristics of early-onset benign occipital epilepsy of childhood in order to facilitate its diagnostic suspicion in daily clinical practice. PATIENTS AND METHODS: The medical records of 37 patients with early-onset benign occipital epilepsy of childhood were reviewed in order to collect epidemiological and clinical features, results of complementary examinations and developmental data. The diagnostic criteria applied were those of the ILAE (International League Against Epilepsy). RESULTS: The mean age at diagnosis was 5.4 years. In all, 64.9% were diagnosed at a pre-school age, with a greater prevalence of females (67.6%). The mean number of seizures per patient was 3.3 and they were mainly characterised by impaired consciousness (90.3%), vomiting (70.1%), eye deviation and/or headaches (30.6%), and generalised (32.8%) or partial (11.2%) motor crises. Seizures occurred during sleep in 67.2% of cases. In 28 cases (75.7%) occipital paroxysms were observed that coexisted with generalised and/or multifocal paroxysms. Of all recurrences, 71.3% occurred during the first 6 months, and from 2 years onwards 82.9% of the patients had no seizures; no developmental differences were found between treated and non-treated patients. One patient with an atypical development was recorded. CONCLUSIONS: Early-onset benign occipital epilepsy of childhood is relatively frequent at the paediatric age, especially in the pre-school years. Although its semiological sequence is quite characteristic, the fact that it lacks clinical and neurological specificity makes diagnostic suspicion more difficult. Its prognosis is especially favourable; however, since their progress may develop in an atypical manner, a rigorous developmental control of these patients would be of the highest priority.

[A comparative study of three systems for quantifying the spike and wave index in patients with continuous spikes and waves during slow sleep]. / Estudio comparativo entre tres sistemas de cuantificacion del indice de punta-onda en pacientes con punta-onda continua del sueño lento.

INTRODUCTION: Continuous spikes and waves during slow sleep (CSWS) is an epileptic encephalopathy of childhood with a pattern of epileptiform discharges during sleep, which, if prolonged over time, produce severe neuropsychological impairment. Quantification of the paroxysms by means of a spike and wave index (SWI) > 85% establishes a presumptive diagnosis and allows early therapy to be started to prevent such impairment. AIMS: To compare the results of the classic method for calculating the SWI against two proposals that optimise the relation between the analysis time employed and the diagnostic sensitivity. PATIENTS AND METHODS: The nocturnal electroencephalographic registers of 17 patients with CSWS were studied. Two observers calculated the SWI with the classic method, as well as with two other methods, M2 and M3, first in the active phase and then in the remission phase. The time required by each method, the individual SWI values and the agreement between methods and observers were compared. RESULTS: With M3 two of the patients failed to reach the cut-off point of SWI > 85%. Agreement in the active phase of CSWS after M2 and M3 was 0.762 and 0.704, respectively, while in the remission phase it was 0.951 and 0.830. Inter-observer agreement exceeded 0.905 in all cases. CONCLUSIONS: The two abbreviated methods can be used in both the active and the remission phases, with a substantial reduction in the analysis time that is needed. Our results support the current tendency to consider SWI > 60% as suggestive of CSWS. Method M2 yields results that are closer to those of the classic method than those of M3.

TITLE: Estudio comparativo entre tres sistemas de cuantificacion del indice de punta-onda en pacientes con punta-onda continua del sueño lento.Introduccion. La punta-onda continua del sueño lento (POCS) es una encefalopatia epileptiforme infantil con un patron de descargas epileptiformes durante el sueño que, prolongadas en el tiempo, producen un grave deterioro neuropsicologico. La cuantificacion de los paroxismos mediante el indice de punta-onda (SWI) > 85% establece un diagnostico de sospecha y permite iniciar una terapia precoz que puede evitar dicho deterioro. Objetivos. Comparar los resultados del metodo clasico de calculo del SWI con dos propuestas que optimicen la relacion entre el tiempo de analisis empleado y la sensibilidad diagnostica. Pacientes y metodos. Se estudiaron los registros electroencefalograficos nocturnos de 17 pacientes con POCS. Dos observadores calcularon el SWI con el metodo clasico, asi como con otros dos metodos, M2 y M3, primero en la fase activa y posteriormente en la fase de remision de la POCS. Se comparo el tiempo consumido por cada metodo, los valores individuales de SWI y la concordancia entre metodos y observadores. Resultados. Con el M3 dos pacientes no alcanzaron el corte del SWI > 85%. La concordancia en la fase activa de la POCS tras el M2 y el M3 fue de 0,762 y 0,704, respectivamente, mientras que en la fase de remision fue de 0,951 y 0,830. La concordancia entre observadores supero el 0,905 en todos los casos. Conclusiones. Los dos metodos abreviados se pueden utilizar tanto en la fase activa de la POCS como en la fase de remision, con una sustancial reduccion del tiempo de analisis empleado. Nuestros resultados apoyan la tendencia actual de considerar el SWI > 60% como sugestivo de POCS. El metodo M2 arroja resultados mas cercanos a los del metodo clasico que los de M3.

Gamma band activity in an auditory oddball paradigm studied with the wavelet transform.

OBJECTIVES: To examine the characteristics of evoked and induced gamma band oscillatory responses occurring during P300 development in an auditory oddball paradigm. METHODS: A time-frequency analysis method was applied to an auditory oddball paradigm in 7 healthy subjects. This method combines a multiresolution wavelet algorithm for signal extraction and the Gabor transform to represent the temporal evolution of the selected frequency components. Phase-locked or evoked activity and also non-phase-locked activity were computed for both standard and target stimuli. RESULTS: The gamma band frequency components differed between target and non-target stimuli processing. The study showed an early and mainly phase-locked oscillatory response appearing around 26--28 ms after both standard and target stimuli onset. This response showed a spectral peak around 44 Hz for both stimuli. A late oscillatory activity peaking at 37 Hz with a latency around 360 ms was observed appearing only for target stimuli. The latency of this late oscillatory activity had a high correlation (P=0.002) to the latency of the P300 wave. CONCLUSIONS: EEG signal analysis with wavelet transform allows the identification of an early oscillatory cortical response in the gamma frequency range, as well as a late P300-related response.

Gamma band responses to target and non-target auditory stimuli in humans.

We studied the EEG oscillatory changes in the gamma band during auditory oddball paradigms in two different conditions (counting targets and reading). A time-frequency analysis was performed for standard and target stimuli. The study revealed an early (26-59 ms) phase-locked oscillation. Around 200 ms, a non-phase locked response was found for standard and target stimuli in temporal posterior electrodes. At about 360 ms, a phase-locked oscillation was observed only after target stimuli in the "counting targets" condition. During the "reading" task this late activity was not found, and energy increases were lower than during "counting" task. The early oscillation may be related to the sensory processing of the stimuli. The response around 200 ms may be involved in auditory mismatch and/or memory retrieval, and late activity is probably a P300-related response. Attention enhances all these activities.

Beta electroencephalograph changes during passive movements: sensory afferences contribute to beta event-related desynchronization in humans.

Non-phase-locked beta oscillatory changes during passive movements were studied in six healthy volunteers, and compared with those observed in a similar group during ballistic movements. Passive movements consisted of brisk wrist extensions done with the help of a pulley system. Changes in the beta band were determined by means of wavelet and Gabor transforms, and compared statistically with a pre-movement period. In this paradigm, a marked beta energy loss (event-related desynchronization, ERD) was present after the beginning of the movement, followed by a beta energy increase (event-related synchronization, ERS). The ERD/ERS was similar to that observed during ballistic movements, but without pre-movement components. Although both changes were maximal in the contralateral central electrode, the beta ERD showed a more bilateral topography. These findings suggest that afferent proprioceptive inputs may play a role in the final part of the beta ERD observed during voluntary movements.

Brainstem auditory evoked potentials (BAEPs) in the cynomolgus macaque monkey. Equivalence with human BAEPs and proposal of a new nomenclature.

Several groups have studied brainstem auditory evoked potentials (BAEPs) in non-human primates. However, the nomenclature of the waves elicited and their correspondence with human waves I-V differ among authors. BAEPs were recorded from six anaesthetised young cynomolgus macaques (Macaca fascicularis), using different sound stimuli parameters. A constant pattern of four main waveforms was present in all the animals with stimulus intensities over 60 dB SPL, although up to four smaller waveforms were observed in some of the individuals. Latency values increased with decreasing stimulus intensities and with increasing repetition rates. These results were similar to the BAEPs observed in other species of macaques. Although an approximate equivalence between human and monkey BAEPs is possible, some discrepancies suggest that there may be generators which contribute to different waves in both species. This is the reason for our proposal of a new nomenclature for BAEP waveforms in monkeys, following a descriptive order with Arabic numerals preceded by the letter M.

Development of myasthenia gravis after interferon alpha therapy.

Interferon (IFN) alpha is now used in the treatment of some malignant diseases and chronic viral hepatitis. There have been several reports of development of autoantibodies and autoimmune diseases or the deterioration of preexisting disorders in patients under treatment. We enclose a case of myasthenia gravis (MG) which developed after six weeks of treatment as fluctuating bilateral ptosis, intermittent diplopia, and mild weakness of limb and neck muscles. A test dose of edrophonium chloride was administered, resulting in improved muscle strength. Elevated anti acetylcholine receptor (AChR) antibody titer was found. Single fiber electromyography showed an increased jitter from extensor digitorum communis, frequently accompanied by transmission blocking. Repetitive electric 3 Hz stimulation of the abductor pollicis brevis muscle, revealed an abnormal decrement of 28% in compound motor action potential. Myasthenia gravis was diagnosed and the patient was given pyridostigmine, immunoglobulines and prednisone with benefit. Six months latter he developed an acute myasthenic crisis with severe respiratory failure and high anti AChR antibody titer. IFN-alpha can induce MG or simply manifests a preexisting subclinical disease, but otherwise its therapeutic efficacy in MG has been shown in experimental and clinical studies. Autoimmune mechanisms, as the release of different cytokines as IFN, by immunocompetent cells, may be involved in the pathogenesis of both MG and chronic active hepatitis. Autoantibody production against postsynaptic membrane structures by IFN-alpha could be the underlying pathophysiology.

[The characteristics of evoked potentials due to omission of stimuli in a sequence of rhythmic auditory tones]. / Características de los potenciales evocados por la omisión de estímulos en una secuencia de tonos auditivos rítmicos.

INTRODUCTION: The detection of absence of a stimulus from a sequence of rhythmic stimuli generates potentials which may express different cognitive processes from the P300 wave. PATIENTS AND METHODS: In nine healthy subjects we studied the differences between the P300 wave obtained by the 'odd ball' paradigm and the potentials evoked by random omission of an auditory tone in a rhythmic sequence of tones of 1,000 Hz. Stimulation was biaural at a frequency of 0.7 Hz and a proportion of stimuli were frequent/infrequent or omitted 3/1. The subjects indicated appearance of an infrequent stimulus or its omission by moving a finger. The potentials were registered on all the points of the international system 10-20. RESULTS: All the subjects evoked potentials P300 and P3o with a range of maximum latencies between 212 and 424 ms, without any differences between the two conditions being observed. The amplitude of P3o was significantly less than that of the P300 for all the electrodes. The topographical distribution of both waves, although predominantly in the midline, was more posterior in the case of P3o with lateralization to the left parietal region. CONCLUSION: The potentials omitted show some differences from the P300 wave and this may be derived from the process of estimation and production of a time interval, which is essential in detecting omission of a stimulus, and is useful in the study of time perception and the generation of internal rhythms.

[Neuromuscular disorders in critically ill patients]. / Alteraciones neuromusculares del paciente crítico.

INTRODUCTION AND OBJECTIVE: Critically ill patients admitted to the Intensive Care Unit (ICU) often develop neuromuscular disorders. The objective of this study was to diagnose these and determine the causes. MATERIAL AND METHODS: We present a series of 13 critically ill patients who developed weakness or paresia, reduced or absent ROT and normal brain stem reflexes, in whom ENG and EMG studies were done in EESS and II which were considered together with data from general laboratory analysis, radiological and microbiological examinations, medication given and posterior clinical course of the patient. Muscle biopsy was not done in any patient. RESULTS: All the patients were intubated, with signs of sepsis, multiple-organ failure and malnutrition. All had received cortico-steroids and amino-glucosides and 8/13 neuromuscular blockers. Neurophysiological study showed that in all cases there was axon type neuropathy, mainly motor and in the lower limbs. Fifty four percent of the patients died. The neuropathy improved in the others. CONCLUSIONS: Critically ill patients often have axon type neuropathy. In our series, the causes of this were sepsis and multiple organ failure. It is important that this pathology be ruled out in the critically ill patient whom it is difficult to disintubate and/or has generalized muscle weakness.

[Multiple sclerosis and epileptic seizures]. / Esclerosis múltiple y crisis epilépticas.

INTRODUCTION: Although epileptic seizures are uncommon in multiple sclerosis they are more prevalent than in the general population, which supports an aetiological relationship. Similarly in a considerable proportion of patients with multiple sclerosis and epileptic seizures, alterations in magnetic resonance and electroencephalogram studies which could be correlated with the clinical features of epilepsy were observed. Nevertheless, it is difficult to establish definite clinical characteristics in these patients since the underlying pathogenic mechanisms are poorly understood and there is great variability with regard to the type of seizure, point at which this occurs during the course of the disease, degree of recurrence and other aspects. CLINICAL CASE: We report the clinical, electroencephalographical and neuroimaging findings of seven patients with multiple sclerosis who had epileptic seizures and those in whom there was no evidence of other potentially epileptogenic pathology. In two patients the epileptic seizures formed part of the first episode of their illness. One patient presented more than one type of epileptic seizure. These seizures were generalized in two cases, partial sensory and/or motor with secondary generalization in three, simple partial motor in one and partial complex in two. The epileptic seizures coincided with other clinical features of episodes in three cases and the electroencephalogram showed anomalies in five cases. CONCLUSIONS: The findings observed were of a wide variety, as was found in other reported series. We point out certain correlations between the clinical data, magnetic resonance and electroencephalogram which may help to orientate the management of these patients.

[Andermann syndrome: presentation of a case]. / Síndrome de Andermann. Presentación de un caso.

INTRODUCTION: Peripheral neuropathy with agenesis of the corpus callosum (or Andermann's syndrome) is a hereditary autosomal recessive disorder rarely found outside certain regions of Quebec Province (Canada). It is associated with mental retardation and various dysmorphic changes. Deterioration is usually progressive with loss of motor skills, development of scoliosis during adolescence, tendency to behaviour disorders and death during the third decade (approximately). CLINICAL CASE: We present a 13 year old girl diagnosed as having the spastic tetraparesic type of PCI, who was sent to us so that we could reconsider the diagnosis in view of the atypical course of the illness. The patient had an unusual phenotype with dysmorphic changes (mainly facial), axial hypotonia with flexion-retraction of the hands, generalized arreflexia, neurogenic bladder, skin changes with ulcers on the legs and mental retardation. Neurophysiological studies showed a predominantly motor polyneuropathy. There were signs of axonal neuropathy on both sural nerve and skeletal muscle biopsies. The clinical features, phenotype, microcephaly with agenesis of the corpus callosum and a posterior fossa cyst, associated with spinal atrophy indicated the diagnosis of Andermann's syndrome. CONCLUSIONS: This case is of interest in view of the exceptional rarity of Andermann's syndrome in our population.

[Familial benign partial epilepsy of early infancy]. / Epilepsia parcial benigna familiar de la infancia temprana.

INTRODUCTION AND CLINICAL CASES: We present two patients who at the ages of 5 and 17 months respectively presented with convulsive crises with motor signs, of partial onset and secondary generalization, which eventually became normal. Both patients had a family history of first degree relatives with similar illnesses and are at present-five years later-well and with normal development, school achievement and neurological examination findings. The clinical characteristics, normal biochemical and neuroimaging investigations and EEG characteristics suggest the diagnosis of benign partial epilepsy of early infancy. This syndrome is characterized by its appearance during the first year of life, having no known etiological factors, with partial crises occurring several times a day and with a course leading to remission. Its frequency may be greater than is thought. There is a pattern of dominant autosomal inheritance, with a gene recently found on chromosome 19. CONCLUSION: We consider that this syndrome should be included in the International Classification of Epilepsy and Epileptic Syndromes as benign familial idiopathic partial epilepsy.

[Clinical and neuropathological study of two brothers with Cockayne syndrome]. / Estudio clínico y neuropatológico en dos hermanos con síndrome de Cockayne.

INTRODUCTION: Cockayne syndrome (CS) is a rare autosomal recessive disease which is characterized by physical and mental retardation, progressive neurological disfunction, photosensitivity and other cutaneous features. Usually they present ophthalmologic abnormalities as well as other heterogenous clinical, radiological and pathologic features as leucodistrophy and calcifications in central nervous system and segmental demyelination in peripheral nervous system. CLINICAL CASES: Two brothers, sons of healthy unrelated parents, are presented. The first patient was referred at 8 months of age because of psychomotor retardation and the second one at 5 months old because of a cataract. At the age of 2 years both presented a complex clinical picture with photosensitivity, growth and mental retardation, peripheral neuropathy, neurosensorial deafness, and cerebral atrophy and calcifications in neuroimaging diagnosis tests. In the following years the older brother presented signs of renal failure, cataracts and retinopathy, and died at 9 years old because of a respiratory infection. The neuropathologic study showed a discrete neuronal loss and diffuse demyelination with calcium deposits in cerebral white matter and basal ganglia. Today the second patient is 8 years old and shows a clinical course similar to that of his brother. CONCLUSIONS: Clinical, radiologic and pathologic features in our patients support the diagnosis of CS type II.

[Tolerance to interferon beta-1b amongst patients with remittent recurrent multiple sclerosis after more than one year of treatment]. / Tolerancia al interferón beta-1b en pacientes con esclerosis múltiple remitente recurrente después de más de un año de tratamiento.

INTRODUCTION: Interferon beta-1b modifies the natural history of the remittent recurrent forms of multiple sclerosis. An analysis was made of its efficiency, tolerance and adverse effects on patients with over one year of treatment. MATERIAL AND METHODS: 16 patients were studied (10 women, 6 men) with ages between 19 and 51 years, incapacity scale (EDSS) 2.61 +/- 1.07 and an annual rate of outbreaks before treatment of 1.65 +/- 0.25, who received 4 MUI/48 h/s.c. of interferon beta-1b x 15 days, afterwards continuing with 8 MUI/48 h/s.c. Corticoids were associated in four cases. Biochemical controls and mass neurological evaluations were carried out as well as a watch being kept for clinical and analytical secondary effects. RESULTS: The annual rate for outbreaks was 0.68 +/- 0.29. Amongst the most frequent adverse effects the pseudoflu syndrome was notable (87%), with an average duration of 10.46 +/- 1.4 weeks, well tolerated with paracetamol. The local reactions (87%) were light and not related to the zone of injection. The patients experienced a sensation of fatigue following the injection in 50% of the cases, although in only one case did this reach a moderate intensity. Analytical alterations were found to be 43.7%, always within the margins of grade 1 of the clinical toxicity scale. With one patient developed an acute depressive syndrome, during which treatment was interrupted, later restarted at half the maintenance dosage. CONCLUSIONS: In our series, just as in other studies, pseudoflu syndrome and local reactions were the most frequent secondary effects. Both complications are light, of brief duration and well tolerated by the patients.

Benchmark quantum Monte Carlo calculations of the ground-state kinetic, interaction and total energy of the three-dimensional electron gas.

We report variational and diffusion quantum Monte Carlo ground-state energies of the three-dimensional electron gas using a model periodic Coulomb interaction and backflow corrections for N = 54, 102, 178, and 226 electrons. We remove finite-size effects by extrapolation and we find lower energies than previously reported. Using the Hellman-Feynman operator sampling method introduced in Gaudoin and Pitarke (2007 Phys. Rev. Lett. 99 126406), we compute accurately, within the fixed-node approximation, the separate kinetic and interaction contributions to the total ground-state energy. The difference between the interaction energies obtained from the original Slater-determinant nodes and the backflow-displaced nodes is found to be considerably larger than the difference between the corresponding kinetic energies.

[Bilateral facial palsy due to Epstein-Barr virus Infection]. / Parálisis facial bilateral secundaria a infección por virus de Epstein-Barr.

Two young patients with bilateral facial palsy are described. They initially presented unilateral facial palsy, followed by contralateral facial nerve involvement a few days later, together with clinical and serologic evidence of acute Epstein-Barr virus infection. The outcome was favourable in one patient but severe sequels persisted in the second. These two cases show that this infrequent complication of Epstein-Barr virus infection may not always have a good outcome. The pathogenic mechanism of bilateral facial palsy is discussed.

Application of a novel automatic duration method measurement based on the wavelet transform on pathological motor unit action potentials.

OBJECTIVE: To evaluate a recently published automatic duration method based on the wavelet transform applied on normal and pathological motor unit action potentials (MUAPs). METHODS: We analyzed 313 EMG recordings from normal and pathological muscles during slight contractions. After the extraction procedure, 339 potentials were accepted for analysis: 68 from normal muscles, 124 from myopathic muscles, 20 from chronic neurogenic muscles, 83 from subacute neurogenic muscles and also 44 fibrillation potentials, as an example of very low duration muscular potentials. A "gold standard" of the duration positions (GSP) was obtained for each MUAP from the manual measurements of two senior electromyographists. The results of the novel method were compared to five well-known conventional automatic methods (CAMs). To compare the six methods, the differences between the automatic marker positions and the GSP for the start and end markers were calculated. Then, for the different groups of normal and pathological MUAPs, we applied: a one-factor ANOVA to compare their relative mean differences, the estimated mean square error (EMSE) and a Chi-square test about the rate of automatic marker placements with differences to the GSP greater than 5 ms, taken as gross errors. RESULTS: The mean and the standard deviation of the differences, the EMSE and the gross errors for the novel method were smaller than those observed with the CAMs in the five different MUAP groups and significantly different in most of the cases. CONCLUSIONS: The novel automatic duration method is more accurate than other available algorithms in normal and pathological MUAPs. SIGNIFICANCE: Accurate MUAP duration automatic measurement is an important issue in daily clinical practice.