Endocrine system involvement in patients with RASopathies: A case series.

Background and Objectives: Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies. Study Design: 72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in PTPN11 and NF1, N=3) and an age- and sex-matched healthy controls were included in the study. Endocrine system involvement was investigated by assessing the thyroid function, pubertal development, auxological parameters, adrenal function and bone metabolism. Results: Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups. Conclusions: The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.

Risk of autoimmune diseases in patients with RASopathies: systematic study of humoral and cellular immunity.

BACKGROUND: Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies. STUDY DESIGN: A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at "Scuola Medica Salernitana", Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels, CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls. RESULTS: Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%), low CD8 T cells in 13/35 patients (37.14%). Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0.00685; p 0.000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease. CONCLUSIONS: Patients affected by RASopathies are at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommended in patients with RASopathy.

Anorectal malformations (ARM): quality of life assessed in the functional, urologic and neurologic short and long term follow-up.

UNLABELLED: Imperforate anus represents a wide spectrum of anorectal malformations associated with urologic, neurologic and orthopedic malformations. The outcome from the various corrective measures has improved due to new surgical techniques as well as to a better understanding of the pathology. Other factors which influence the overall outcome include the degree of patient acceptance, family support as well as the ability of the health care structure to support the patient's needs on a clinical, functional and psychologic level. AIM OF THE STUDY: Assess (with the new techniques available) the quality of life in the adult patient with ARM and compare it to that experienced by a younger patient; also we wish to determine the correlation between the observed abnormalities with the functional, neurologic and urologic outcome. MATERIALS & METHODS: Sixty-six patients were subjected to PSARP (36 M; 30 F). Six presented with cloaca and 60 with ARM (23 high and 37 low). All patients underwent the same workup to include L/S MRI diagnostics, evaluation for incontinence (urinary and bowel), a urology screening, and if required, a subsequent urodynamic study with rehabilitation and/or bowel management. All answered questionnaires (AIMAR: Italian parent's association of ARM) in order to assess their satisfaction with the current health condition, with the information received and with the treatment and follow-up sessions. The patients were classified into one of two groups. Group A, totaled 33 patients (4 cloacae) with an age range between 2 and 12 years who were operated after 1995. The second, group B, was made up of 33 patients who had been surgically treated before 1995 (age range 15-41 years), had followed the study protocol and had also a neuropsychiatry consult. RESULTS: Overall fecal continence was 69% and of this number 37% were clean without constipation. Twe2nty-one patients (32%) suffered from some form of constipation. Constipation was the most common functional disorder observed in patients who have undergone PSARP. The highest incidence of constipation was found in the ARM (low type), a favorable prognostic group with 43% constipation. Patient with "high" defects and a cloaca had a lower incidence of constipation (18%). Of the 59 patients evaluated, 85% were urinary continent and 15% were incontinent. All of the incontinent patients were in the unfavorable prognostic group of malformations. Urodynamic studies showed 7 neurogenic bladders (NB) and 2 patients with a neurovescical dysfunction (NVD). Of the 50 "dry" patients. 20 had voiding disturbances due to a voiding dysfunction, in the absence of neurologic abnormalities, and presented occasional daytime or nighttime wetting. There was no correlation between the level of the anatomic defect and the urodynamic patterns in the group. Abnormal MRI findings were observed in thirty out of fifty-two patients evaluated. The MRI findings were classified as follows. Severe abnormalities: 7 patients (13%) presented with a combination of skeletal (sacral/lumbar) and spinal cord anomalies. Only spinal cord abnormalities: 12 patients (21%). Only skeletal abnormalities: 11 (19%) patients. Patients were divided into high, low and cloacal malformations. A high degree of statistical correlation was noted between the patients belonging to the cloacae and high defect groups and the abnormal MRI findings. No significant correlation was found between the low defect group and dysrafism, abnormal MRI results and the severity of the malformation. The incidence of Tethered Cord (TC) in our limited number of patients was limited in our study (9% in the high and 7% in the low defect group) when compared to the current literature. Furthermore there was no statistically conclusive evidence that TC by itself affects the urinary or fecal control in our patients. Our recommendation is nevertheless to obtain an MRI study in all patients with ARM. CONCLUSION: All patients 17 and older reported a "good quality of life". Four are married, two with children. Aclose working relationship with the medical personnel is not only necessary but is also well received by the family particularly when younger patients are involved. The adult patient easily adapts even when information is initially scarce. He quickly reaches autonomy with personalized solutions but prefers a longer follow-up time during which, specialized medical facilities will play an important role in the treatment of ARM. Our findings illustrate the importance of both global disease-specific functioning and perceived psychosocial competencies for enhancing the QL of these patients.

Intracranial dislocation of the mandibular condyle: report of two cases and review of the literature.

Fractures of the mandibular condylar process are common and account for up to 40% of all mandibular fractures. Penetration of the condylar head into the middle cranial fossa is, however, rare. We have found reports of only 43 cases since 1834. The diagnosis of intracranial condylar dislocation is difficult, there are usually no particular symptoms or neurological signs. As a result, detailed radiological studies are necessary. In the absence of clear radiographic images of the condylar structures, computed tomography (CT) is essential to locate the fragments and to investigate and monitor intracranial lesions. This paper describes the diagnostic and surgical procedures used in two cases of condylar dislocation and discusses them with reference to previous cases. The use of a titanium screw, which was positioned intracranially in the first case, has not, to our knowledge, been described previously.

Brain density changes during renal replacement in critically ill patients with acute renal failure. Continuous hemofiltration versus intermittent hemodialysis.

Computerized tomography (CT) studies of the brain were made on 12 patients with acute renal failure from different origin. Patients were treated for two subsequent days in random sequence with intermittent hemodialysis (HD) (one 4-h session and Kt/V > or = 1) and continuous veno-venous hemofiltration (CVVH) (one 24-h session and Kt/V > or = 1). CT scans were done before and after the HD and CVVH session in each patient. In baseline conditions, the only macroscopic morphological alteration was a slight brain edema in some patients. Significant changes in the density of white and gray matter were observed after the HD session in all patients (gray matter from 52.3 +/- 5.2 to 38.9 +/- 5.3 and white matter from 36.7 +/- 3.5 to 24.8 +/- 3.2 Hounsfield units, average delta -26.7%). No changes were observed after CVVH. We conclude that intermittent HD involves a remarkable degree of "unphysiology", leading to increased water content in the brain after each session. In acute patients this may lead to a post-dialytic brain edematogenic state. The physiological stability provided by continuous therapies such as CVVH avoids this unwanted effect, and suggests that continuous renal replacement therapies should be a first choice in these patients.

Spontaneous healing of cerebral aneurysm at the beginning of left posterior inferior cerebellar artery (PICA). Case report.

We present the clinical and neuroradiological features of a ruptured aneurysm at the beginning of the left PICA suffering from subarachnoid hemorrhage (SAH). The young patient refused surgery, endovascular treatment and also follow-up. After 4 and 5 years she repeated the left vertebral angiography that showed a spontaneous thrombosis of the aneurysm. After 8 years MR angiogram images confirmed the total obliteration of the aneurysm.

Haemangioma of the zygoma: case report.

Haemangioma of bone in the zygoma is extremely rare. We report two cases presenting with swelling of the zygomatic region. The literature is reviewed and CT, angiographic and MRI findings are discussed.

Frontoethmoidal meningoencephalocele. A one-stage correction, reconstruction, and plating by means of the micro system.

This case report on one stage surgical treatment of meningoencephalocele offers the opportunity for a revision of the most recent trends expressed by other authors on this topic. Surgical technique involved a system of rigid fixations by means of microplates which, according to our experience in other cases, is particularly advisable in pediatric age. We find that the simultaneous utilization of calvarial bone grafts facilitates a better reconstruction of the cranial base, and also offers greater stability in results.

Radiotherapeutic treatment for breast cancer choroidal metastases.

A series of 14 eyes (11 patients) with choroidal metastases from breast cancer were reported. The lesions were classified into three grades according to the severity and extent of involvement. Eleven eyes (9 patients) were treated by radiotherapy with two opposed lateral fields using a 4 MeV linear accelerator. The contralateral eye received a prophylactic irradiation. An average dose of 42 Gy was delivered (range, 30-50). Results of radiotherapy were the following: 5 CR and 2 PR in grade II (9 eyes) and 2 PR in grade III (2 eyes). We conclude that radiotherapy is useful to control choroidal metastases of breast cancer. No contralateral metachronous involvement was found. Quality of life of responders showed a marked improvement. Radiation-induced injury was not seen.

Tangier disease: central nervous system impairment in a case of syringomyelia-like syndrome.

A neuroradiological investigation of the central nervous system (CNS) in a case of Tangier disease presenting as a syringomyelia-like syndrome is reported. No syringomyelinic cavities were found. However, MRI showed cervical spinal cord atrophy and scattered foci of greater density with T2 weighted images in the white matter of the frontal, parietal and occipital lobes. Cerebral and cervical spinal cord involvement in the course of Tangier disease is now shown for the first time. The authors postulate that the MRI detected alterations are related to the underlying illness.

[Nephroblastoma with prevalent rhabdomyosarcomatous component. Description of a case with early cerebral metastasis]. / Nefroblastoma a prevalente componente rabdomiosarcomatosa. Descrizione di un caso con metastasi cerebrale precoce.

The malignant rhabdoid tumor of the kidney determines clinical and prognostic evaluations due to the poor therapeutic answer and to the uncertain prognosis. The Authors describe a case of nephroblastoma with anaplasia of the blastemal elements associated to rhabdomyosarcoma areas.

Computed tomography of epidural fibrosis after discectomy: a comparison between symptomatic and asymptomatic patients.

The evaluation of patients with symptoms recurrent after disc surgery is a difficult diagnostic problem. The most common causes are recurrent herniation and postoperative scarring; routine x-ray and myelographic differentiation between herniation and scarring is difficult or impossible. High resolution computed tomography (CT) has shown some results in the evaluation of postoperative patients, but the role of epidural fibrosis in failed back surgery syndrome (FBSS) is not clear. Some knowledge of the "normal" CT physiological healing and scarring after disc surgery is necessary. We scanned 20 asymptomatic operated patients and 20 patients with recurrent sciatic nerve pain after disc surgery who did not have bony stenosis, recurrent disc herniation, or other causes of FBSS. Our observations showed no important differences in the fibrosis demonstrated by CT between symptomatic and asymptomatic patients. The degree and type of fibrosis are not related to recurrent symptoms.

Recovery from herpes simplex encephalitis: selective impairment of specific semantic categories with neuroradiological correlation.

The clinical, neuropsychological and neuroradiological features of two patients affected by herpes simplex virus type 1 (HSV-1) encephalitis are described. An experimental study for the assessment of naming, recognition and description displayed in one patient a persistent significant impairment in naming living things. The other patient showed a failing "semantic memory" for the same categories, although a significant impairment emerged only for plants. In both patients, the late neuroradiological sequelae were localised mainly in the inferior and middle gyri of the left temporal lobe and in the left-side insula. In one patient, the right-side insula was also involved. The selective cerebral damage induced by HSV-1 is stressed and a correlation between the neuroradiological and neuropsychological findings is attempted. The stereotyped anatomical and neuropsychological changes lead to the belief that the virus may recognise, within the limbic system, particular cellular "strains" on the basis of their molecular specificity.

Radiosurgery using a 4MV linear accelerator. Technique and radiobiologic implications.

In the authors' technique, the stereotactically localized target is fixed to the isocenter of a 4 MV linear accelerator. The irradiation is carried out along 9-17 non-coplanar arcs distributed on a 160 degrees cylindrical sector. High doses (10-50 Gy) are delivered in one or two sessions. From 1982, 65 patients have been treated (shortest follow-up 6 months). The dose was chosen according to the pathology and to the volume of the lesion. Good clinical results have been obtained in low-grade gliomas, acoustic neuromas, arteriovenous malformations, and other selected types of intracranial lesions. Therapeutic effects in terms of clinical condition and size of the lesions have been plotted in relation to time elapsed and dose employed.

[A combined method of sialography and CT scan of the parotid gland]. / Metodica combinata scialografia+TC per la parotide.

Computed tomography (CT) of parotid gland was performed on 40 patients, immediately following sialography. The results of the combined CT-sialography were compared with those of sialography alone and are presented here. We have come to the conclusion that the main indication for this method, in the study of the parotid gland, is the mass-pathology, particularly situated in deep-lobe and in the pharyngo-maxillary space.

Studies on brain density in hemodialysis and peritoneal dialysis.

30 patients on hemodialysis or peritoneal dialysis have been investigated by computerized tomographic (CT) scan. To evaluate possible cerebral alterations induced by dialysis, CT examinations were carried out before, immediately after and 6 h after the end of dialysis with an Evaluskop, which provides an objective precise evaluation of even slight variations in brain density. No morphological variations were noted after dialysis, while the brain density fell significantly during and after the treatment. A decrease in density was not observed in normal subjects or in patients on continuous peritoneal dialysis. The changes in the densitometric values of brain tissue suggest that there is a postdialysis gain in cerebral water linked to the intermittent treatment. CT may represent a simple reliable method for studying uremic encephalopathy and investigating the pathogenesis of the dialysis disequilibrium syndrome.

Changes of cerebral density in dialyzed patients.

CT studies were made on 38 patients receiving different dialytic treatment, 10 patients with chronic renal failure not yet dialyzed, and 15 healthy subjects. No morphological modifications were observed. On the contrary, significant changes of density were demonstrated after a dialysis session in the population treated intermittently. In these patients the density values were similar to those registered in the controls 1-6 h after a dialysis session. End stage renal failure and CAPD patients always had normal density values. Therefore cerebral density changes are caused only by the intermittent dialytic treatment.