A useful maneuver to simplify sellar floor repair following endoscopic transnasal pituitary surgery.

The watertight closure of the skull base after endonasal surgery is and has always been critical in cranial base surgery. Nowadays, endoscopic transsphenoidal surgery is the standard of treatment for most of the sellar tumors. Reconstruction of the sella is not always deemed necessary, and generally it is reserved for patients with macroadenomas or with intraoperative evidence of cerebrospinal fluid leak. We herein report our experience with a simple maneuver that, in our opinion, simplifies sellar floor reconstruction.

Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study.

OBJECTIVE: Acromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality. DESIGN AND METHODS: The mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis. RESULTS: Twenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43-1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (P=0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06-28.77, P=0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56-309.04, P=0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease. CONCLUSIONS: Therapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients.

The contribution of Carlo Giacomini (1840-1898): the limbus Giacomini and beyond.

Carlo Giacomini (1840-1898) was a prominent Italian anatomist, neuroscientist, and professor at the University of Turin. Early in his career, he conducted clinical investigations with the physiologist Angelo Mosso (1846-1910) that culminated in the first recording of brain pulsations in a human subject. Anatomic features named after him include the limbus Giacomini, Giacomini vertebrae, and the vein of Giacomini. Pushing anatomy research to reconsider anthropological studies of the late 19th century, Giacomini strongly refuted the theory connecting criminality to atavistic morphological characteristics. A tireless scientist, he was the first to describe the os odontoideum in 1886 and to suggest that the presence of an incompetent odontoid process may alter the motion of craniovertebral junction, anticipating the concept of spinal instability. In this essay, we highlight the life and scientific contributions of Carlo Giacomini, with emphasis on his contributions to neuroscience.

Usefulness of salivary cortisol in the diagnosis of hypercortisolism: comparison with serum and urinary cortisol.

OBJECTIVE: Several tests have been proposed to diagnose patients with Cushing's syndrome (CS). The aims of the study were: i) to evaluate the performance of salivary cortisol (SC) in hypercortisolism and ii) to compare SC with serum cortisol (SeC) and urinary cortisol. DESIGN AND PATIENTS: This was a diagnostic study. Twenty-seven patients with untreated Cushing's disease (CD untr), 21 women consuming oral contraceptive pill (OCP), 18 pregnant women, and 89 healthy subjects (controls) were enrolled. METHODS: SC and SeC at baseline and after the low-dose dexamethasone suppression test (LDDST) and urinary free cortisol (UFC) were measured. RESULTS: Midnight SC had a sensitivity of 100% in the CD untr group and a specificity of 97.7% in the controls. Specificity remained high (95.2%) in women taking OCP, while in pregnant women, it decreased to 83.3%. SC after the LDDST showed a sensitivity of 96.3% in the CD untr group; specificity was 97.7% in the controls and 90.5% in OCP women. Midnight SeC had a sensitivity of 100% in the CD untr group. SeC after the LDDST had a sensitivity of 100% in the CD untr group while specificity was 97.7% in the controls and 61.9% in women taking OCP. For UFC, sensitivity was 92.6% in the CD untr group while specificity was 97.7% in the controls and 100% in the OCP group. CONCLUSIONS: SC is a reliable parameter for the diagnosis of severe hypercortisolism, with high sensitivity and specificity. In women during pregnancy or taking OCP, the measurement of SC, identifying the free fraction, could be helpful to exclude CS.

A functioning FSH-secreting pituitary macroadenoma causing an ovarian hyperstimulation syndrome with multiple cysts resected and relapsed after leuprolide in a reproductive-aged woman.

Bioactive gonadotropin-secreting pituitary adenomas are very rare in fertile women and can cause an ovarian hyperstimulation syndrome (OHSS). A 31-year-old woman with oligo-amenorrhea, severe ovarian cystic swelling and high serum estradiol was submitted to the resection of ovarian cysts and then treated with long-acting leuprolide 11.25 mg. Two months later, the ovarian multicystic hyperplasia relapsed, thus a pituitary MRI was performed and a pituitary macroadenoma was detected. In January 2010, she was referred to our Endocrinology Department where her hormonal evaluation showed high serum estradiol, FSH, α-subunit and inhibin with low LH. In April 2010, she underwent a trans-sphenoidal pituitary adenomectomy, which rapidly regularized the hormonal profile, the ovary and pituitary morphology and the menses. The case presented confirms that gonadotrophinomas occurring in reproductive-aged women frequently produce symptoms of ovarian hyperstimulation and proves that the use of GnRH analogs is not indicated in this condition.

Impact of different cut-off limits of peak GH after GHRH-arginine stimulatory test, single IGF1 measurement, or their combination in identifying adult patients with GH deficiency.

OBJECTIVE: To evaluate the impact of different peak GH cut-off limits after GHRH-Arg test, IGF1 measurement, or their combination in identifying patients with GH deficit (GHD). DESIGN AND PATIENTS: Totally, 894 normal subjects (used for determining IGF1 normative limits) and 302 patients with suspected GHD were included. Different peak GH cut-off limits (used by European (depending on body mass index (BMI)) or North American (4.1 µg/l) Endocrine Societies, by HypoCCs (2.5 µg/l), or with 95% specificity (based on BMI), Method 1, 2, 3, or 4 respectively) and IGF1 were considered. METHODS: Peak GH after GHRH-Arg and IGF1. RESULTS: Different peak GH cut-off limits recognized different proportions of GHD (range, 24.8-62.9%). Methods 1 and 2 with high sensitivity recognized a higher proportion (95.5 and 92.5% respectively) of GHD among patients with three (T) pituitary hormone deficits (HD), whereas Method 4 (with high specificity) identified 96.7% normal subjects among those without pituitary HD; on the contrary, Method 4 identified only 75% GHD among patients with THD, whereas Method 1 recognized a high proportion (40%) of GHD among subjects without HD. Of the total patients, 82% with THD and 84.5% without HD were recognized as GHD or normal respectively by IGF1. Among the remaining patients with THD and normal IGF1, 75% was recognized as GHD by Method 1; among patients without HD and abnormal IGF1, 87.5% was identified as normal by Method 4. Overall, combination of IGF1 and Method 1 or Method 4 identified 95.5% GHD among patients with THD and 98.1% normal subjects among those without HD. CONCLUSIONS: Single peak GH cut-offs have limits to sharply differentiate GHD from normal subjects; IGF1 may be used for selecting patients to be submitted to the GHRH-Arg test; the peak GH cut-off limits to be used for identifying healthy or diseased patients depend mainly on the clinical context.

Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing's syndrome: results from a prospective study before and after surgery.

OBJECTIVES: To evaluate whether patients with Cushing's syndrome (CS) had i) changes in coagulative and fibrinolytic parameters associated with CS activity and ii) higher prevalence of venous thromboembolic events (VTE). DESIGN: Prospective study conducted on patients with CS evaluated at diagnosis and 12 months after surgery. PATIENTS AND METHODS: Forty patients with active CS (36 with Cushing's disease (CD) and 4 with an adrenal adenoma) were evaluated. Forty normal subjects and 70 patients with non-ACTH-secreting pituitary adenomas served as controls. All patients and controls underwent an assessment of coagulation and fibrinolysis indexes before and after surgery. RESULTS: CS patients at baseline had a hypercoagulative phenotype when compared with normal subjects (activated partial thromboplastin time (aPTT), fibrinogen, D-Dimer, von Willebrand factor (VWF), plasminogen activator inhibitor 1 (PAI-1 or SERPINE1), antithrombin III (ATIII or SERPINC1), P<0.0001, α(2) antiplasmin, P=0.0004, thrombin-antithrombin complex (TAT), P=0.01, factor IX (F9), P=0.03). Patients with still active disease after surgery had higher coagulative parameters than those in remission (VWF (P<0.0001), PAI-1 (P=0.004), TAT (P=0.0001), ATIII (P=0.0002) and α(2) antiplasmin (or SERPINF2; P=0.006)), whereas aPTT levels (P=0.007) were significantly reduced. VTE occurred in three patients with CD (7.5%): one had a pulmonary embolism and two patients had a deep venous thrombosis; no patients submitted to transsphenoidal surgery for non-Cushing's pituitary adenoma had VTE (P=0.04). CONCLUSIONS: Patients with CS have a procoagulative phenotype due to cortisol-associated changes in haemostatic and fibrinolytic markers, leading to increased incidence of VTE. Thromboprophylaxis seems to be appropriated in patients with active disease, particularly in the postoperative period.

Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma.

CONTEXT: Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown. OBJECTIVE: The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome. DESIGN: This was a prevalence case-control study. PATIENTS AND SETTING: Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center. INTERVENTION: Pit Abs were measured using immunofluorescence in all cases and controls (n = 714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n = 72). MAIN OUTCOME MEASURE: Clinical response of pituitary adenoma after surgery was evaluated. RESULTS: Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than normal pituitary (P = 0.01) and lower than in autoimmune hypophysitis (P < 0.0001). No correlation between Pit Abs and TILs was found (P = 0.78). A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P = 0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma. CONCLUSIONS: TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.

Progressive hemispheric shrinking in hemimegalencephaly: a possible role for seizure-related neuronal loss.

Hemimegalencephaly (HME) is a developmental brain lesion consisting of a unilateral enlarged, dysplastic, and often highly epileptogenic cerebral hemisphere. Most patients exhibit early onset intractable seizures, status epilepticus, hemiplegia, hemianopsia, and developmental delay. Major surgical procedures are advocated for limiting the devastating consequences of epilepsy. We studied a female with HME, early onset intractable seizures and recurrent status epilepticus, in whom progressive hemiatrophy of the enlarged hemisphere and normal growth of the contralateral hemisphere, exceeding the size of the dysplastic hemisphere, was demonstrated by magnetic resonance imaging. Histopathology, following functional hemispherectomy at the age of 7 years, demonstrated severe neuronal loss with an elevated number of cells exhibiting the morphological and biochemical features of apoptosis. Eighteen months after surgery the patient was seizure-free (Engel class I) and exhibited improved motor and language skills, alertness and social behaviour. We hypothesize that nearly continuous seizure activity might sustain seizure-induced brain injury in the dysplastic hemisphere but causal heterogeneity and associated anatomical factors may influence differently the individual predisposition to atrophic changes.

Tumors in the temporal horn of the lateral ventricle as a cause of epilepsy.

Three neoplastic lesions located in the temporal horn of the lateral ventricle were diagnosed after the onset of seizures. Neither hydrocephalus nor temporal horn entrapment were present. The complete surgical removal of the tumor resulted in the disappearance of the epileptic episodes in 2 cases; the third patient refused surgery, and his lesion appears unmodified after a 3-year follow-up. Histological examination led to a diagnosis of choroid plexus papilloma in 1 case and of neurocytoma in the other; in the third case, the nonextracted lesion was presumed to be a partially calcified choroid plexus papilloma. The mechanism underlying the seizures in the 2 operated children is speculated to be a compression exerted upon the mesial temporal structures that form the medial wall of the temporal horn of the lateral ventricles; this compressive activity was resolved by removal of the tumor, and the epileptic episodes consequently disappeared in the 2 operated children; seizures were controlled by drugs in the third child.

Primary intra-diploic meningioma in a child.

BACKGROUND: Primary intra-diploic meningiomas are uncommon in childhood and, at the clinical onset, may be confused with other and more frequent bone tumours because they lack specific clinical and radiological characteristics. Surgery is indicated not only to remove the lesion but also to obtain an accurate histological diagnosis. CASE REPORT: We report the case of a young girl who presented with a recently developed subcutaneous hard mass in the left pterional region. Neuroradiological investigations revealed an intra-osseous lytic mass with a sclerotic reaction. Diagnosis was possible only after the total removal of the tumour and its histological examination.

Intramedullary capillary hemangioma associated with hydrocephalus in an infant.

This 3-month-old child presented with an enlarging head circumference arising from communicating hydrocephalus with large subarachnoid spaces in the posterior fossa. Neuroimaging performed to clarify the origin and pathogenesis of the hydrocephalus revealed a vascular lesion within the dorsal spinal cord. Insertion of a cerebrospinal fluid shunt and total removal of the spinal tumor were performed successfully. Histological examination of the medullar lesion demonstrated a capillary hemangioma. Proposed mechanisms for increased intracranial pressure and spinal cord lesions are presented. A spinal hemangioma in this age range associated with hydrocephalus has not been reported previously, but spinal lesions must be considered in the presence of hydrocephalus with no clear origin.

Benefícios da hemisferectomia em pacientes com hemimegalencefalia / Hemispherectomy of hemimegalencephaly

A hemisferectomia é realizada em muitos casos de hemimegalencefalia para controlar a epilepsia refratária ao tratamento medicamentoso. No entanto, apesar de haver concordância sobre a efetividade desse procedimento para controle das crises, a escolha da técnica cirúrgica utilizada ainda é motivo de debate. Relatamos os casos de três crianças com hemimegalencefalia submetidas à hemisferectomia para tratamento de suas crises refratárias: uma foi submetida à hemisferectomia anatômica e as outras duas, à hemisferectomia funcional. Os resultados confirmam a efetividade da hemisferectomia para o controle das crises epilépticas nesses casos.

Bilateral thalamic tumors in children.

INTRODUCTION: The actual incidence of thalamic tumors is not known, but the frequency of the bilateral tumoral involvement of both thalami is even less defined. CASE REPORT: In the present paper we report 4 new pediatric cases of primary bilateral thalamic tumors (PBTTs) observed in the Pediatric Neurosurgery Section at the Catholic University Medical School, Rome. Neuroimaging studies could not detect the presence of abnormal neoplastic tissue at the level of the midline basal subependymal region of the third ventricle, in the midbrain, and in the pineal gland in any of these 4 patients, thus apparently excluding the diffusion of a firstly unilateral thalamic tumor to the contralateral thalamus. In all of the patients, the lesions appeared as large symmetrical masses on both sides of the third ventricle, a feature that seems to further exclude the contralateral growth of a previously unilateral tumor. PBTTs appear to remain confined to the thalamic nuclei for a long time, and, unlike the unilateral form, the border between gray and white matter may not be violated for a relatively long time. Unlike in adults, PBTTs do not present with dementia in children. Signs and symptoms of increased intracranial pressure (3 cases) and movement disorders (tremor, 2 cases) were the presenting clinical manifestations in our 4 patients. CONCLUSIONS: The diffuse and bilateral involvement of both thalami makes surgical therapy barely feasible, even at the present time. Today, the main role of surgery is still to obtain a histological diagnosis. Generally, PBTTs are low-grade astrocytomas (grade II in the WHO classification), but limited anaplastic areas may be found in some patients, so that grade III and IV astrocytomas may be expected in a significant proportion of cases.