Unfavorable Clinical Evolution Research Articles

Clinical Outcome of CF Patients with CF Related Diabetes: Do We Need to Change Our Policy?

Background: Many studies have shown that CFRD has a negative impact on CF prognosis. Current guidelines advise to screen for CFRD with an OGTT yearly from the age of 10 - 12. In our center we do not routinely screen for CFRD because the OGTT is cumbersome and not an ideal screening test. We therefore want to exclude unfavourable clinical evolution due to late diagnosis. Methods: 23 CF patients with diagnosis of CFRD < 18 years old were matched to a control patient. Clinical evolution (BMI, lung function, and chronic infection treatment burden) was analyzed starting 2 years before until 2 years after diagnosis of CFRD. Results: In the 2 years before diagnosis of CFRD, BMI and LF were similar for both groups while need for IV AB treatment was higher in the CFRD group. In the 2 years following diagnosis and treatment, LF decline was worse in the CFRD despite more IV AB treatments. BMI was still comparable. We conclude that clinical status was comparable between cases and controls in the 2 years preceding the diagnosis of CFRD. However, the need for IV antibiotic treatment seems to precede the faster lung function decline after CFRD diagnosis.

TIMP-2 gene methylation in cervical precursor and invasive lesions

ObjectiveTo analyze the presence of HPV-DNA and TIMP-2 gene methylation in cervical precursor and invasive lesions, as well as to study the associations among the latter, the presence of HPV-DNA, and the clinical evolution of such lesions. MethodsCross-sectional study that includes 49 biopsy or brush smear samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal cervices were analyzed. ResultsTIMP-2 gene methylation was detected in 86.8% (33/38) of the samples from the group with lesions and 50% (4/8) of the normal samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was more frequent in the methylated samples (50%), and the group with methylation had a higher risk of unfavorable evolution than the group without methylation; however, such observations were not statistically significant (p=0.19). ConclusionTIMP-2 gene methylation and the presence of HPV-DNA were characteristic of the group with cervical lesions. Methylation was not associated with the presence of HPV-DNA or an unfavorable clinical evolution.

The impact of the staphylococcus aureus infection on the evolution of children with cystic fibrosis from a regional centre in north-eastern Romania

Introduction. Chronic bacterial infections and – often – acute infectious exacerbations are characteristic to the lung disease of the cystic fibrosis (CF). The objective of this study was to identify children with CF and Staphylococcus aureus infection and quantify the impact of this infection on their clinical status. Material and methods. A prospective study was carried out during 3 years on a batch of 37 children with CF registered in the records of the Regional Monitoring Centre of the 3rd Clinic of Pediatrics of Iasi, Romania. In these patients, we searched for the presence of S. aureus, the prevalence of methicillin-resistant S. aureus (MRSA) strains, the impact of the chronic infection with MRSA on the lung function concomitant with the presence of severity elements in CF. Results. 22 of the 37 patients with CF had positive culture for S. Aureus; at 9 of them was isolated MRSA and 5 had chronic infection. The MRSA positive group of patients presented significantly lower values of the FEV1, a more poor nutritional status, severe bronchiectasis, a larger number of pulmonary exacerbations and implicitly hospitalizations, pancreatic insufficiency in most cases and a higher degree of association with the F508del genotype. Conclusions. S. aureus remains an important pathogen in CF. Due to its high pathogeny, S. aureus and especially the MRSA strains can contribute to an unfavourable clinical evolution.

La sciatique discale : histoire naturelle et traitement

Sciatica is a frequent spinal condition with a clinical course worse than previously described and for which many gray areas persist. This radiculopathy is due to a combination of a herniated disc near the nerve root and the development of a local inflammation, for which we do not know the exact pathophysiology. Treatment is generally non surgical, however, due to the paucity of randomized trials, no universal recommendations are available. Several minimally invasive techniques have been developed but none has proven its efficacy. In case of unfavorable clinical evolution, surgery is superior to conservative treatment over several months but this difference decreases over time. Thus, shared decision-making process is recommended in order to choose the optimal treatment for each patient.

Chronic venous insufficiency in patients with absence of the inferior vena cava

Up until now, knowledge of absence of the inferior vena cava (AIVC) is limited to case reports and small case series, usually reported shortly after diagnosis. To characterize long-term evolution of outcomes of patients with AIVC, weperformed a survey of current practice in Belgium, TheNetherlands, and Luxembourg (Benelux). Vascular surgeons and phlebologists in the Benelux area were asked to complete a questionnaire on medical history and treatment of each patient in follow-up at their practice with a diagnosis of AIVC. The Benelux survey yielded 35 patients with AIVC, with a follow-up ranging from 0 to 28 years. Their median age was 40 years (range, 14-65 years), and 26 (74%) were male. Diagnosis of AIVC was made in 26 patients at the time of presentation with deep vein thrombosis (DVT). DVT was bilateral in 15 patients and involved one or both iliac veins in 21 (81% of all AIVC patients with acute DVT). Computed tomography scanning was used to detect AIVC in 29 patients. Thrombophilia was present in 16 (46%). The CEAP C classification was C4-6 in 17 right legs (49%) and 15left legs (43%). Unilateral or bilateral ulceration had occurred in 11 patients in the past, and three had active ulceration. Long-term conservative treatment consisted of oral anticoagulant treatment in 28 patients and compression stockings in27. The results of this survey on AIVC illustrate the unfavorable long-term clinical evolution of these patients. They frequently present with advanced stages of chronic venous insufficiency at a relatively young age, with the development of unilateral or bilateral extensive DVT and subsequent moderate to severe post-thrombotic syndrome.

Guillain-Barré Syndrome after H1N1 Shot in Pregnancy: Maternal and Fetal Care in the Third Trimester—Case Report

Guillain-Barré syndrome is a rare neurological disease of progressive installation, usually following a previous acute infectious state, has a rare incidence, especially in pregnancy, and can induce major complications and high mortality risk. Its occurrence, after immunization to influenza during the last trimester pregnancy, has not been reported before. We presented a case of a 36-year-old pregnant woman that was immunized to H1N1 in the last trimester; 10 days later she developed shoulder and lumbar spine's pain, limbs weakness and facial paralysis with unfavorable clinical evolution and was submitted to intensive therapy care. We described clinical and obstetrical approach, pointing out peculiarities involved in this pathology in pregnancy.

Soluble Angiogenic Factors in Patients With Acute Pancreatitis

Angiogenic factors are involved in the physiopathology of several inflammatory diseases and they probably play a role in the pathogenesis of acute pancreatitis (AP). To investigate if angiogenic factors are elevated in patients with AP, their relationship with severity and clinical evolution of AP, and their use as prognosis markers of AP. A case (25)-control (30) study was carried out. Patients with AP were classified according to severity (using Ranson and Glasgow scores) and according to their clinical evolution (taking into account the development of complications during hospital stay). Platelet-derived growth factor (PDGFBB), angiopoietin-1, angiopoietin-2 (Ang-2), angiopoietin tyrosine-kinase receptor, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), VEGF tyrosine-kinase receptor 1, and VEGF tyrosine-kinase receptor 2 were determined at 12 hours and then at 5 days after hospitalization. PDGFBB, Ang-2, angiopoietin tyrosine-kinase receptor, and HGF were significantly higher in cases (P<0.001), and in patients with unfavorable clinical evolution (P<0.001). PDGFBB and HGF were significantly higher in patients with severe AP (P<0.05). To predict unfavorable clinical evolution, PDGFBB, Ang-2, and HGF showed an area under receiver operating characteristic curve of 0.97. PDGFBB and HGF are related to severity of AP. These factors along with Ang-2 are related to clinical evolution and are useful in predicting the development of several complications during hospital stay. Therefore, these angiogenic factors could be useful as prognosis markers of AP.

Dipyridamole and Low Doses of Heparin as a New Successful Physiopathologic and Therapeutic Approach in 2 Cases of Disseminated Intravascular Coagulation

OPERATIVE: We report 2 cases of disseminated intravascular coagulation (DIC) successfully treated with the combination of the platelet adhesiveness blocker dipyridamole and low doses of intravenous heparin. The first patient was a 17-year-old boy with septic arthritis; the second patient was a 12-year-old boy with a liver abscess. Both had hemocultures positive for Staphylococcus aureus. The diagnosis of DIC was defined by clinical signs of septicemia with fever, tachypnea, peripheral vasoconstriction, and low platelet counts (67,000/mm3 and 47,000/mm3, respectively). The second patient also presented with acute ischemia of the fingers and toes. General care was provided in the intensive care unit, and high doses of antibiotics were provided continuously (metronidazole and oxacillin or ceftriaxone). A 5% glucose solution containing dipyridamole (Persantine; Istituto De Angeli/Boheringer Ingelheim, Reggello, Italy) was administered by continuous intravenous infusion (20 mg/24 hours). In addition, regular heparin (Liquemin; Roche, Indianapolis, IN, USA) was administered at a dosage of 250 microg/kg per hour or 25 IU/kg per hour (6 mg/kg per 24 hours). These heparin doses are not able to promote complete blood anticoagulation. Treatment with heparin and dipyridamole was maintained for 10 days in the first patient and for 18 days in the second. By 48 hours after treatment with dipyridamole and low-dose heparin, both patients recovered and presented with a good clinical condition and increased numbers of circulating platelets. Both patients were discharged in a safe clinical condition in the second month after hospital admission. Successful clinical recovery of 2 young patients with DIC with an unfavorable clinical evolution and a prognosis for a lethal outcome was achieved with the combination of a continuous infusion of dipyridamole and low doses of heparin.

Cytomegalovirus infection in children undergoing hematopoietic stem cell transplantation in Chile

Cytomegalovirus (CMV) infection remains as an important cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Our aim was to assess the incidence, risk factors, and outcome related to CMV infection in children after HSCT in a developing country. From October 1, 1999, to December 31, 2005, we prospectively studied all patients admitted to the HSCT unit at Hospital Luis Calvo Mackenna in Santiago, Chile. Serologic studies before transplantation and weekly CMV infection surveillance (antigenemia or quantitative PCR) were routinely obtained. Patients with positive antigenemia or quantitative PCR received pre-emptive therapy with ganciclovir, and cases of unfavorable clinical evolution, persistent positive antigenemia, or quantitative PCR after 14 days of ganciclovir were treated with foscarnet. Ninety-seven patients received HSCT. Their median age was 8 years (range, 3 months to 24 years) and their overall survival was 67%. CMV reactivation was diagnosed in 26 patients. Of these, three developed CMV disease (two interstitial pneumonia, one hemorrhagic cystitis). One of the patients with pneumonia died. Risk factors identified were pre-transplant serologic status (positive recipient), acute and chronic graft versus host disease (GvHD), GvHD prophylaxis, and treatment with antithymocyte globulin. The rate and prognosis of CMV infection among children treated at our HSCT unit is similar to those reported from industrialized countries. These findings reflect adequate prevention and management of CMV infection within our program.

Effective application of Ligasure in laparoscopic splenectomy for splenic abscess in an old woman – case report

Materials and methods We present the case of an 84-year-old woman, affected by essential thrombocythemia, monoclonal gammopathy and senile dementia, who was admitted in our Hospital for abdominal pain and high white blood cells levels. An abdominal CT scan showed splenic infarctual abscess and a broad-spectrum antibiotic therapy was arranged. Because of the unfavourable clinical evolution, a laparoscopic splenectomy was indicated.

Efectividad de anticuerpos antitransglutaminasa IgA en la evaluación de la dieta sin gluten en pacientes celiacos. Evolución de la hipertransaminasemia y ferropenia

Objective To analyze the validity of antitransglutaminase antibodies (tTGA) as a serological marker of response to the gluten-free diet (GFD) in celiac patients and to determine the outcome of hypertransaminasemia (HT) and ferropenia found at the time of diagnosis. Material and methods We have retrospectively analyzed the data from 172 patients with celiac disease (CD) (141 children and 31 adults) following a GFD. We have collected clinical and diet information and also histological, biochemical and serological data. The tTGA was measured with a human recombinant antibody. Results After a median follow-up time of 1.5 years in GFD, 114 (81%) of the children had normal levels of tTGA, 17 (12%) showed values in the “grey zone” and only 10 (7%) had elevated levels of this marker. This contrasts with the figures found in adults, corresponding to 15 (48.3%), 11 (33.5%) and 5 (17.2%), respectively. In our series we have performed 27 intestinal biopsies during follow-up (26 children and 1 adult). The concordance rate between the results of this biopsy and the tTGA determination was high, with a Kappa Index=0.898. We have detected dietary transgressions in 7 patients (4 occasional and 3 frequently) and 6 of these 7 patients showed high levels of tTGA. The GFD was correctly followed by children according to the international recommendations, but only 40% of the adults followed the GFD adequately. In both populations we have found a significant decrease in HT and normalization of the ferropenia found at diagnosis ( P<0.001). Conclusions tTGA is a useful indirect marker for evaluation of GFD in a pediatric population, with a high concordance between serum levels of the marker and histological findings in the intestinal biopsy. However, tTGA cannot substitute biopsy in cases of diet transgressions or unfavourable clinical evolution. In our environment it is still essential to increase the awareness of the adult population regarding the importance of diet in CD and also of the serious complications associated with untreated disease.

Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer

Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.

Interferon (IFN)–γ, Tumor Necrosis Factor–α, Interleukin‐6, and IFN‐γ Receptor 1 Are the Major Immunological Determinants Associated with Post–Kala Azar Dermal Leishmaniasis

Semiquantitative reverse-transcription polymerase chain reaction was used to analyze intralesional cytokine gene expression in 28 patients with post-kala azar dermal leishmaniasis (PKDL) and 14 patients with kala azar (KA). The data revealed mixed T helper cell type 1 (Th1) and T helper cell type 2 (Th2) responses, as reflected by elevated expression of interferon (IFN)-gamma , tumor necrosis factor (TNF)-alpha , transforming growth factor (TGF)-beta , interleukin (IL)-10, IL-6, and IL-4 mRNA, with minimal expression of IFN-gamma receptor 1 (IFN-gamma R1) mRNA in PKDL lesions, compared with that in normal skin tissue. In comparison with those in KA lesions, mRNA levels for IFN-gamma , TNF-alpha , and IL-6 were found to be significantly elevated in PKDL lesions, implying that these cytokines play an important role in PKDL pathogenesis. In the presence of elevated levels of IFN-gamma and TNF-alpha , interference with type 1 effector activity in PKDL may be due to minimal expression of the IFN-gamma R1 gene or the simultaneous presence of elevated levels of IL-10, IL-6, and TGF-beta , which have counteracting effects. After treatment, the restoration of IFN-gamma R1 at both mRNA and protein levels, coupled with down-regulation of counteracting cytokines, may facilitate the action of signals associated with IFN-gamma , yielding parasite clearance. Therefore, unfavorable clinical evolution in PKDL may not be due to the absence of an intralesional Th1 response but rather may be due to the presence of counteracting cytokines along with the down-modulation of IFN-gamma R1.

Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with γc cytokines

AbstractThe unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4+ and CD8+ T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor. In peripheral blood or in lymph nodes and bone marrow, and, in comparison to healthy donors, patients' T cells showed a skewed differentiation toward Tnaive and Tcentral memory stages, with low expression of granzyme B and perforin. T-cell culture with autologous tumor in the presence of IL-2, IL-15, and autologous bone marrow–derived cells led to massive T-cell expansion and to differentiation of cytotoxic factor+ CD8+ T cells releasing IFN-γ and killing autologous B-cell tumor in an HLA-class I–restricted fashion. These results suggest impaired T-cell differentiation to effector stage in patients with B-cell NHL, but indicate that T-cell responsiveness to γc cytokines is retained, thus allowing to promote generation of antitumor T cells for immune intervention.

Pulmonary sarcoidosis

Sarcoidosis is a multisystemic disease of unknown aetiology characterized by the formation of immune granulomas in involved organs. It is a worldwide disease that mainly affects 25-40 years old people with a lifetime incidence rate of 0.85-2.4%. Multiple clinical phenotypes are observed according to presentation, involved organs, disease duration and severity. Sarcoidosis primarily affects the lungs and the lymphatic system. The prevailing pathogenic hypothesis is that various antigens could promote sarcoidosis in genetically susceptible hosts, both these factors modulating the incidence and the clinical phenotype of sarcoidosis. So far, environmental agents have been suspected, including possible mycobacteria and propionibacteria. Interferon-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and IL-18 play a critical role in driving the Th1 commitment in the course of granulomatous process. Evolution of sarcoidosis is often marked by spontaneous resolution within 12-36 months, but can be severe because of chronic cases with pulmonary fibrosis or involving other organs, including heart, central nervous system and eyes. Mortality, ranging between 0.5 and 5%, is most often related to pulmonary fibrosis. Corticosteroids can reverse the granulomatous process, but are only suspensive, and their long-term benefit remains under question. Corticosteroids are recommended when sarcoidosis shows unfavourable clinical tolerance and evolution. Alternative and corticosteroid-sparing therapies are of increased interest in difficult cases, while targeted new drugs such as anti-TNF-alpha are still under investigation.

Impaired intravascular triglyceride lipolysis constitutes a marker of clinical outcome in patients with stable angina undergoing secondary prevention treatment: A long-term follow-up study

ObjectivesWe sought to verify whether the intravascular metabolism of chylomicron-like emulsion may predict the clinical evolution of patients with coronary artery disease (CAD) undergoing secondary prevention therapy of CAD. BackgroundCase-control studies have suggested an association between impaired intravascular catabolism of triglyceride (TG)-rich lipoproteins and CAD. However, evidence is lacking with respect to the potential clinical relevance of this metabolic disorder in CAD patients. MethodsDuring a period of 4.5 ± 0.9 years, we followed up 63 stable CAD patients (mean age 60 ± 10 years) undergoing secondary prevention therapy (low-density lipoprotein cholesterol <100 mg/dl) in whom kinetic studies of the in vivo catabolism of chylomicron-like emulsions were performed. At enrollment into the study, fasting patients were injected intravenously with a chylomicron-like emulsion labeled with radioactive triglyceride (3H-TG) and cholesteryl esters (14C-CE) to evaluate the efficacy of intravascular TG lipolysis. ResultsAt baseline, CAD patients displayed a diminished fractional clearance rate (FCR) for 3H-TG (−26%; p = 0.027), for 14C-CE (−37%; p = 0.015), and for delipidation index (DI) (−26%; p = 0.02) as compared with 35 control subjects. During follow-up of secondary prevention therapy, 33% of CAD patients (n = 21) presented with clinically refractory angina and aggravated coronary angiographic severity. The FCR for 3H-TG (−44%; p = 0.005) and DI (−41%; p = 0.006) in those patients with refractory angina was significantly lower than that observed in those with stable evolution. Moreover, in a Cox multivariate regression analysis, the presence of a DI less than the median value was an independent predictor of an unfavorable clinical evolution (adjusted hazard ratio 3.32; 95% confidence interval 1.21 to 9.14; p = 0.020). ConclusionsThe current study establishes that delayed intravascular TG lipolysis is a strong and independent predictor of evolution to severe angina among patients undergoing secondary prevention therapy of CAD.

Concurrent infectious mononucleosis and measles: a potentially life-threatening association sharing underlying immunodeficiency

We report lethal interstitial pneumonia in an 18-year-old young man with measles infection following recent infectious mononucleosis. We speculate that the documented T cell immune impairment caused by the concurrent Epstein-Barr and measles viral infections (as expressed by a proportionately low CD4+ lymphocyte count) was responsible for the complicated clinical course and unfavorable outcome.

Objective biologic parameters and their clinical relevance in assessing salivary gland neoplasms.

This review summarizes research advances of cytometric, proliferation, cytogenetic, and molecular "objective" measurable parameters, as additional aids to prognostic information of salivary gland tumors provided by classical clinicopathologic indicators. Flow cytometric DNA ploidy and S-phase fraction seem to be of value as predictors of tumor behavior, aneuploidy, and high S-phase identifying an unfavorable clinical evolution of salivary gland neoplasms. Cell proliferation markers assessed by immunohistochemistry (e.g., PCNA, Ki-67) also appear to have predictive significance, but some conflicting results, in part related to technical procedures, limit their routine clinical application. Silver-stained methods (AgNORs) show a scarce value in estimating prognosis of salivary gland malignancies. p53 and c-erbB-2 as well as karyotyping, are of disputable benefit for clinical use, but the biologic information they provide give a better understanding on the molecular mechanisms involved in the development and progression of tumors. Further studies, with large databases, long follow-up information, uniformized histologic classification, and standardized methodologies, are needed to establish how these "objective" parameters would be of truly beneficial for the treatment of patients with salivary gland tumors.

Natural history of migraine in childhood.

Epidemiological studies have shown that 3-7% of the paediatric population suffer from migraine. Despite this high prevalence little has been published about the natural history of migraine or of its prognosis. The objectives of this study were: (i) to outline the natural history of migraine in childhood; and (ii) to identify early predictors of an unfavourable clinical evolution. A prospective, longitudinal, 10-year follow-up study was conducted of the clinical evolution of 181 paediatric patients with migraine. Data analysis was performed by statistical significance and logistic regression tests. In our study 24.3% of children with migraine had their onset before age 6 years and another 57% between 6 and 10 years of age. A positive family history of migraine was recorded in 77.5%. Eighty-eight percent of patients followed a favourable clinical course. The remaining 12% of patients had to be placed on prophylactic treatment owing to the increasing of their headache. Of all parameters investigated, the age of onset was the only statistically significant predictor of an unfavourable clinical evolution. We conclude: (i) most patients with migraine headache starting in childhood do not require prophylactic treatment; (ii) the earlier the disease begins the more likely is an unfavourable clinical course; (iii) genetic factors play an important role in the phenotypic expression of the disease; (iv) our study suggests the existence, at least, of two different populations among childhood migraine patients.

Magnetic resonance imaging cranial and cerebral dimensions: is there a relationship with Chiari I malformation? A preliminary report in children

The pathogenesis of idiopathic Chiari I malformation (CM I) remains poorly understood, although it is thought to be due to disproportion between hindbrain structures and the posterior fossa (PF) dimensions. This study was undertaken to determine whether CM I and its possible complications are associated with disproportion between cranial and cerebral dimensions. Surface of the vermis, PF and supratentorial (ST) area were measured on magnetic resonance imaging midsagittal sections and were correlated with age in 19 children with CM I and 43 controls. The ratio of the PF/ST area and of the vermis/PF area were also plotted against age in the two groups and against length of the tonsils herniation in the CM I malformation group. Only the vermis midsagittal area and the vermis/PF ratio were found to be significantly higher in CM I malformation subjects. There was no correlation between the length of tonsils herniation and the vermis/PF area or the PF/ST area ratio in this group. The most severe complications (large syrinx and hydrocephalus) were not associated with particular measurements or calculated ratios in the children with CM I malformation except for the relatively small PF area in a neonate. We conclude that factors responsible for the appearance of clinical signs remain largely unknown. In particular, cranial and brain measurements alone do not seem to predict complications or unfavourable clinical evolution.