Ultra-High-Field Targeted Imaging of Focal Cortical Dysplasia: The Intracortical Black Line Sign in Type IIb.

BACKGROUND AND PURPOSE: Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. MATERIALS AND METHODS: Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. RESULTS: We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). CONCLUSIONS: The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.

Semiautomated Evaluation of the Primary Motor Cortex in Patients with Amyotrophic Lateral Sclerosis at 3T.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis is a neurodegenerative disease involving the upper and lower motor neurons. In amyotrophic lateral sclerosis, pathologic changes in the primary motor cortex include Betz cell depletion and the presence of reactive iron-loaded microglia, detectable on 7T MR images as atrophy and T2*-hypointensity. Our purposes were the following: 1) to investigate the signal hypointensity-to-thickness ratio of the primary motor cortex as a radiologic marker of upper motor neuron involvement in amyotrophic lateral sclerosis with a semiautomated method at 3T, 2) to compare 3T and 7T results, and 3) to evaluate whether semiautomated measurement outperforms visual image assessment. MATERIALS AND METHODS: We investigated 27 patients and 13 healthy subjects at 3T, and 19 patients and 18 healthy subjects at 7T, performing a high-resolution 3D multiecho T2*-weighted sequence targeting the primary motor cortex. The signal hypointensity-to-thickness ratio of the primary motor cortex was calculated with a semiautomated method depicting signal intensity profiles of the cortex. Images were also visually classified as "pathologic" or "nonpathologic" based on the primary motor cortex signal intensity and thickness. RESULTS: The signal hypointensity-to-thickness ratio of the primary motor cortex was greater in patients than in controls (P < .001), and it correlated with upper motor neuron impairment in patients (ρ = 0.57, P < .001). The diagnostic accuracy of the signal hypointensity-to-thickness ratio was high at 3T (area under the curve = 0.89) and even higher at 7T (area under the curve = 0.94). The sensitivity of the semiautomated method (0.81) outperformed the sensitivity of the visual assessment (0.56-0.63) at 3T. CONCLUSIONS: The signal hypointensity-to-thickness ratio of the primary motor cortex calculated with a semiautomated method is suggested as a radiologic marker of upper motor neuron burden in patients with amyotrophic lateral sclerosis. This semiautomated method may be useful for improving the subjective radiologic evaluation of upper motor neuron pathology in patients suspected of having amyotrophic lateral sclerosis.

Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1) in patients with upper motor neuron (UMN) impairment is pronouncedly hypointense in Magnetic Resonance (MR) T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution. MR raw data were used for Quantitative Susceptibility Mapping (QSM). Measures of magnetic susceptibility correlated with the expected concentration of non-heme iron in different regions of the cerebral cortex in healthy subjects. In ALS patients, significant increases in magnetic susceptibility co-localized with the T2* hypointensity observed in the middle and deep layers of M1. The magnetic susceptibility, hence iron concentration, of the deep cortical layers of patients' M1 subregions corresponding to Penfield's areas of the hand and foot in both hemispheres significantly correlated with the clinical scores of UMN impairment of the corresponding limbs. QSM therefore reflects the presence of iron deposits related to neuroinflammatory reaction and cortical microgliosis, and might prove useful in estimating M1 iron concentration, as a possible radiological sign of severe UMN burden in ALS patients.

Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis.

Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. MATERIALS AND METHODS: Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. RESULTS: Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). CONCLUSIONS: The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis.

Ultra-high-field MR imaging in polymicrogyria and epilepsy.

BACKGROUND AND PURPOSE: Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential of 7T imaging in characterizing polymicrogyria to determine whether additional features could be identified. MATERIALS AND METHODS: Ten adult patients with polymicrogyria previously diagnosed by using 3T MR imaging underwent additional imaging at 7T. We assessed polymicrogyria according to topographic pattern, extent, symmetry, and morphology. Additional imaging sequences at 7T included 3D T2* susceptibility-weighted angiography and 2D tissue border enhancement FSE inversion recovery. Minimum intensity projections were used to assess the potential of the susceptibility-weighted angiography sequence for depiction of cerebral veins. RESULTS: At 7T, we observed perisylvian polymicrogyria that was bilateral in 6 patients, unilateral in 3, and diffuse in 1. Four of the 6 bilateral abnormalities had been considered unilateral at 3T. While 3T imaging revealed 2 morphologic categories (coarse, delicate), 7T susceptibility-weighted angiography images disclosed a uniform ribbonlike pattern. Susceptibility-weighted angiography revealed numerous dilated superficial veins in all polymicrogyric areas. Tissue border enhancement imaging depicted a hypointense line corresponding to the gray-white interface, providing a high definition of the borders and, thereby, improving detection of the polymicrogyric cortex. CONCLUSIONS: 7T imaging reveals more anatomic details of polymicrogyria compared with 3T conventional sequences, with potential implications for diagnosis, genetic studies, and surgical treatment of associated epilepsy. Abnormalities of cortical veins may suggest a role for vascular dysgenesis in pathogenesis.

Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

BACKGROUND AND PURPOSE: Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. MATERIALS AND METHODS: Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. RESULTS: Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. CONCLUSIONS: Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study.

Short-term side-effects of brain MR examination at 7 T: a single-centre experience.

OBJECTIVE: To study patient tolerability of brain imaging that employs an ultrahigh field (7 T) MR system METHODS: We examined 180 subjects that underwent brain MR examination at 7 T. A tolerability test consisting of two parts (during patient table motion and during the examination) was administered to all subjects in order to monitor their discomfort. The scores range from 0 to 5 for the first part, and from 0 to 10 for the second part, the total score of each subject therefore ranging from 0 (no side effects reported) to 15 (lowest tolerability) RESULTS: A total of 51% of subjects reported at least one side effect but all were mild in intensity and did not require examination interruption. No serious adverse event was reported. The total score (mean ± standard deviation) was 1.1 ± 1.5 out of 15 (mean score 0.4 ± 0.7 out of 5 during patient table motion and 0.7 ± 1.1 out of 10 during MR). Patient discomfort was not related to gender or health status, but it was reduced with time after system installation with increasing operator experience in performing UHF MR examinations. CONCLUSIONS: Ultrahigh field MRI is well tolerated without excessive discomfort to subjects. KEY POINTS: • 7-T MRI is well tolerated with low incidence of side effects • The subjects' discomfort during 7-T MRI is reduced as the operators' experience increases • 7-T MRI is practicable in healthy subjects and patients with neurodegenerative diseases.

Language organisation in left perinatal stroke.

Right-hemispheric organisation of language has been observed following early left-sided brain lesions. The role of the site of damage is still controversial, as other aspects influence the pattern of speech organisation including timing of the lesion and the presence of epilepsy. We studied a group of 10 term-born children homogeneous for timing/type of lesion and clinical picture. All subjects had left perinatal arterial stroke, right hemiplegia, normal cognitive functions and no or easily controlled epileptic seizures. In half the patients, the lesion clearly involved Broca's area, in the other half it was remote from it. Language lateralization was explored by an fMRI covert rhyme generation task. Eight of 10 subjects showed a right lateralisation of language, including all five patients with a damaged left Broca and 3/5 of those without it. Group analysis in patients with right hemispheric organisation showed brain activations homotopic to those found in the left hemisphere of a matched control group. Our findings confirm that, at the end of gestation, the human brain exhibits extraordinary (re-)organisational capabilities. Language organisation in the right hemisphere is favoured by the presence of destructive lesions of the left Broca's area at birth, and occurs in brain regions homotopic to those usually involved in language processing.

Acquired focal brain lesions in childhood: effects on development and reorganization of language.

In the present paper, we address brain-behaviour relationships in children with acquired aphasia, by reviewing some recent studies on the effects of focal brain lesions on language development. Timing of the lesion, in terms of its occurrence, before or after the onset of speech and language acquisition, may be a major factor determining language outcome. However, it is still unclear which are the effects of aphasia occurring between 2 and 5 years of age, a time window which is crucial for acquiring and automatizing the basic rules of native language. A comprehensive review of the literature on acquired childhood aphasia precedes the description of long-term follow-up (20 years) of two identical twins, one of whom became aphasic at 3 years and 4 months after infarction of the left sylvian artery. Psycholinguistic analysis and fMRI data show a slow and incomplete recovery from non-fluent aphasia associated to an intra-hemispheric organization of language. These data, which support the potential but also the limits of neural plasticity during language development, are discussed in the light of the literature on the time-course and neural bases of acquired childhood aphasia.

Brain representation of phonological processing in Italian: individual variability and behavioural correlates.

Neuroimaging literature on phonological processing during reading lacks of studies taking into account orthographic differences across languages and behavioural variability across subjects. The present study aimed at investigating brain representation of phonological processing in reading Italian, a language with regular orthography, with particular regard to inter-individual variability and brain-behavioural correlates. Ten Italian adults performed a rhyme generation and a rhyme judgment task during fMRI acquisition and were tested with behavioural measures of phonological processing. Results for both tasks showed activations of the left Inferior Frontal Gyrus and Dorsolateral Prefrontal Cortex, likely underlying output sublexical strategies, for all or most of the subjects, while a minority of subjects activated the Superior Temporal Sulcus and the Temporo-Parietal-Occipital Junction. These results suggest that phonological processing of written Italian is based on the prevalent use of frontal structures. However, it is of interest that the activation of the Superior Temporal Sulcus, involved in phonological input, was associated to better behavioural performances in tasks of phonological processing. Our findings may contribute to understand neural correlates of phonological processing of languages with regular orthography.

[Video-assisted treatment for biliary atresia]. / Trattamento videoassistito dell'atresia delle vie biliari.

BACKGROUND: The surgical treatment of biliary atresia is still a great challenge for pediatric surgeons. Kasai's operation usually needs a wide, painful, muscle-cutting laparotomies that quite often are followed by pain and peritoneal adhesion. These possible complications may disturb the post-operative course and humper liver transplantation. Advancements in minimally invasive surgery have allowed even the most complex procedures to be approached using these techniques. METHODS: The authors present a case of successful Roux-en-Y laparoscopic portoenterostomy for the treatment of biliary atresia. We report a case of a 3-month-old patient with biliary atresia who weighted Kg 5,300 at the operation. The patient was placed in supine position. The procedure was performed with 4 trocars of 3 mm and 1 of 10 mm. The umbilical site was used for extracorporeal Roux-en-Y enteroenterostomy. CO2 was insufflated at a pressure of 8 mmHg and a flow of 0.5 L/min. A drain was placed through the lower trocar site with the tip near the anastomosis. RESULTS: The procedure was free of neither intraoperative nor post-operative complications. Feeding by nasogastric tube was started after 2 days. Total oral feeding was possible after 8 days. CONCLUSION: Laparoscopic approach to perform Kasai's operation is technically feasible and thanks to a magnified vision, it allows to abtain a good visualization of the portal structures with an adequate retraction of the liver. This procedure can avoid or decrease the post-operative complications such as pain, breathing difficulty, adhesions and resulting in very small scars. Anyway laparoscopic Kasaiportoenterostomy should be done by a surgeon with a good experience in laparoscopic hand-suturing and neonatal experience and with the support of an experienced in neonatal and infantile videosurgery anaesthesiologist.

[Laparoscopic surgery in Hirschsprung's disease]. / Trattamento laparoscopico nel megacolon agangliare.

The laparoscopic treatment of benign conditions of the colon represents only one of the numerous application fields of the modern laparoscopic techniques in pediatric surgery. Until the half of the 1990's, the surgical treatment of choice for Hirschsprung's disease has been the procedure ideated by Soave in the early 1960's. Nowadays, the optimal treatment in the classic forms of aganglionic megacolon consists in performing, in neonatal age or in the first months of life, a transanal extramucous pull-through. This approach can be integrated by a laparoscopic step. From September 2000, at the Department of Pediatric Surgery, Bologna University, we have operated 21 cases of congenital aganglionic megacolon with this technique.

Reorganisation of the somatosensory system after early brain damage.

OBJECTIVE: To examine the reorganisation of the somatosensory system after early brain lesions. METHODS: We studied 12 young patients with congenital hemiplegia. Causative lesions were brain malformations, periventricular injuries and cortico-subcortical lesions. We explored the somatosensory system using evoked potentials, fMRI during sensory stimulation and clinical assessment of sensory function. To correlate sensory and motor function, we also performed transcranial magnetic stimulation, fMRI of hand movement and assessment of motor function by means of Melbourne test. RESULTS: Eleven patients showed a perilesional reorganisation of primary somatosensory function, as expressed by short latency potentials following stimulation of the paretic hand; in a remaining patient, delayed latency responses (N27.1) were only elicited over the ipsilateral undamaged hemisphere. Five of the eleven patients with perilesional somatosensory representation of the affected hand showed contralesional shifting of motor function, thus exhibiting sensory-motor dissociation. Significant correlation was found between sensory deficit and fMRI activation during sensory stimulation. CONCLUSIONS: In subjects with early brain lesions, somato-sensory function is generally reorganised within the affected hemisphere. A contralesional shifting is uncommon and poorly efficient in function restoration. SIGNIFICANCE: This study confirms and further explores the difference in reorganisation capabilities of the motor and sensory system following early brain injury of different etiologies and timing.

[Thoracoscopic treatment of oesophageal atresia]. / Correzione toracoscopica dell'atresia esofagea.

BACKGROUND: Advancements in minimally invasive surgery in newborns have allowed even the most complex neonatal procedures to be approached using these techniques. Other authors have demonstrated its efficacy in the treatment of the esophageal atresia with distal fistula. METHODS: We report our experience based on the thoracoscopic repair of esophageal atresia with distal fistula in two newborns. Birth weights were 2.800 g and 2.300 g respectively. The patients were intubated endotracheally and placed in a left prone position. Four trocars were inserted: the first one of 5 mm was positioned in the fifth intercostal space for the camera, the other two of 3 mm were positioned in the fourth intercostal space on the anterior and posterior axillary line respectively for the operative instruments. The last trocar of 3 mm was inserted in the third intercostal space on the anterior axillary line for the lung retractor. CO2 was insufflated at a pressure of 8 mm Hg and a flow of 0.5 L/min. The fistula was first isolated then ligated and cut with scissors. The proximal esophagus was opened and an anastomosis was made over a 6F or 8F nasogastric tube with interrupted 4-0 Vicryl sutures. A tube chest was placed through the lower trocar site with the tip near the anastomosis. RESULTS: These two procedures were free of neither intraoperative nor post-operative complications. Feeding by nasogastric tube was started after a mean of 4 days. Barium swallow made on day 7 demonstrated no leakage and no stenosis of the anastomosis. Total oral feeding was possible after 8 days. Mean hospitalization was 14 days. CONCLUSION: This initial report shows, as demonstrated by the experience since 1999 by other authors, that the thoracoscopic esophageal repair in the newborns is technically feasible and, thanks to a magnified vision, it allows to abtain a good isolation of the esophagus and of the tracheo-esophageal fistula respecting the anatomical structures. Moreover the advantages are in terms of exposure and esophageal length, avoiding the significant short and long-term morbidity associated with thoracotomy.

Sensory-motor cortex activity modulation by hypnotic susceptibility and hypnosis during finger movement.

The aim of the experiment was to study whether the activity of the primary sensory-motor (S1/M1), supplementary motor (SMA) and pre-motor (PMA) areas during fingers movement is modulated by hypnotic susceptibility and hypnosis. Cortical activity was studied through functional Magnetic Resonance Imaging (fMRI) during a finger-to-thumb opposition task in awake (Highs) and hypnotized highly susceptible (H-Highs) as well as in awake non susceptible subjects (Lows). Results did not show any significant difference in sensory-motor areas activation between Highs and Lows (trait effect) and between Highs and H-Highs (state effect). The activation in 3 subjects among Highs and only 1 among Lows (out of 5) of the caudal S1, receiving the most part of the cutaneous input, appears noteworthy and prompts further investigation on possible hypnotizability-related differences in sensory-motor integration.

Laparoscopic antireflux surgery in neurologically impaired children.

From May 1996 to April 2002, 48 laparoscopic fundoplications were performed after failure of medical treatment in 47 neurologically impaired infants and children affected by gastroesophageal reflux. Indications for surgery included vomiting, recurrent upper airway infections, failure of medical therapy, feeding difficulties with failure to gain weight, and instrumental (barium swallow and pHmetry) diagnosis of gastroesophageal reflux. A standard approach was adopted, with minimal access modifications according to the patients' characteristics. In two patients, laparoscopic surgery had to be converted to open surgery because of severe kyphoscoliosis and accidental left emidiaphragm perforation. In another patient undergoing a laparoscopic Nissen fundoplication, a re-do laparoscopic operation was performed. Postoperative analgesia was administered during the first 12 h, and fluid intake and feeding were begun on days 1 and 2, respectively. All patients clinically improved except two; a paraesophageal hernia developed in one, and a stenosis developed in the other. We strongly believe that laparoscopic fundoplication can be successfully adopted in neurologically impaired children as well as in pediatric patients as a whole, with the same advantages and far fewer drawbacks than are expected in adults.

[Mammography and prevention of breast carcinoma. Epidemiological considerations concerning female population of a Rome district]. / Mammografia e prevenzione del carcinoma della mammella. Considerazioni epidemiologiche sulla popolazione femminile di un quartiere di Roma.

At the present time breast cancer represents the primary reason of death caused by cancer amongst the female population of the western countries. Since the actuation of primary prevention programmes results impossible, the aim that must be considered primary is to attain a diagnosis of such tumour as precociously as possible. This research proposes to value the inclination of the female population of a District in Rome, of different classes of age, to have a mammography test in a state of spontaneous screening, in view of a next institution of a structured program of secondary prevention in the area of reference. The results have been examined with relation to the age limits considered as optimum for a correct application of this diagnostic methodology, in line with technical and epidemiological considerations.

[Parametric methods applied to the standardization of gestational reference intervals for blood renin activity, aldosterone and cortisol using the transversal and longitudinal approach]. / Metodi parametrici applicati alla standardizzazione degli intervalli di normalità gestazionale di attività reninica, aldosterone e cortisolo plasmatici mediante approccio trasversale e longitudinale.

This investigation is devoted to define monthly-qualified gestational reference intervals for plasma renin, aldosterone and cortisol as derived by transverse or longitudinal approaches. Reference intervals refer to 95% confidence interval, 90% tolerance interval, the 95% predictive interval, in addition to the mean plus or minus the standard error and standard deviation. By applying both methodological approaches it has been found that plasma renin and aldosterone exhibit a progressive gestational increase. By contrast, cortisol shows an initial increase and thereafter stays on the same values. Statistical analysis revealed the transversally--and longitudinally--derived reference intervals to be not statistically different. Because of such a similarity, laboratory medicine can interchangeably use both kinds of reference intervals for estimating the normality of plasma renin, aldosterone and cortisol values in a single case of pregnancy. This interchangeability of values leads to simplify the methodology for measuring plasma renin and aldosterone in pregnancy since it is not necessary to standardize the gestational nomograms for renin-sodium and/or aldosterone-sodium relationship. This is a real way to reduce the costs and to optimize the compliance in the monitoring of pregnancy.