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Transient Delayed Hyponatremia after Transsphenoidal Surgery: Attempting to Enlighten the Epidemiology and Management of a Still-Obscure Complication
No full textAlthough the occurrence of transient delayed hyponatremia after transsphenoidal surgery is well known, the need for more and better knowledge of this phenomenon remains. The vast majority of patients have asymptomatic hyponatremia, which explains the great disparities reported in the prevalence of the disorder, from 2% to 35% on the basis of different inclusion criteria.1-12 The more the patients perform daily venous samples for serum sodium assay during the postoperative period, the more frequent the occurrence of asymptomatic hyponatremia becomes, because a large number of cases will be discovered.4,11
It is well known that delayed hyponatremia after transsphenoidal surgery, defined as a serum sodium level of less than 135 mmol/L on or after postoperative day 3, usually occurs around postoperative day 7 (between 3 and 11 days after surgery) as an isolated entity or, much more rarely, as an interphase in the triphasic postoperative diabetes insipidus. As a result, hyponatremia often occurs when the patient already has been discharged, making the postoperative care troublesome. Furthermore, in the case of readmission because of delayed hyponatremia after transsphenoidal surgery, the cost of overall care of this patient population increases relevantly.
For a long time after Cusick et al.1 reported the inappropriate secretion of antidiuretic hormone (SIADH) as the possible cause of delayed symptomatic hyponatremia after transsphenoidal surgery in 1984, the debate regarding the pathophysiology of the disorder had a checkered history. Given the whole body of evidence collected during the last 3 decades, the syndrome of SIADH would seem the more plausible cause of hyponatremia in this setting1-12; however, some studies in which the authors suggest cerebral salt wasting syndrome (CSWS) as another possible cause have also been published.13,14 The most likely explanation for these puzzling findings is the difficulty from the patient bedside in evaluating the extracellular volume status, which highlights the real difference between these 2 conditions. On the other hand, when faced with a hyponatremic patient, the physician has to bear in mind that the clinical evaluation of the extracellular volume status is mandatory for a correct diagnosis and an effective treatment. Both SIADH and CSWS share similar laboratory tests (plasma osmolality, urinary osmolality, and urinary sodium concentrations) but differ in the extracellular volume status, which is expanded in the former (despite the patient is clinically euvolemic) and depleted in the latter.
Some retrospective studies have identified factors associated with increased risk for delayed hyponatremia after transsphenoidal surgery, including sex (female), tumor size, hypopituitarism, transient diabetes insipidus, and Cushing disease.5,6,8,10,13,15,16 Concerns have been raised, however, about the real impact of these findings, and no consensus exists. The group of patients affected with Cushing disease, for example, could represent a distinct cohort, in which the postoperative hyponatremia may have a different pathophysiology, namely the secondary adrenal insufficiency occurring after remission of Cushing disease. Keeping in mind, however, the relevant role of delayed hyponatremia in the postoperative management and the additional cost of this complication, there is no doubt that the identification of predictive factors may be relevant to identify patient subpopulations at greater risk and keep them under a strict surveillance after discharge.
In January 2016, Bohl et al.17 identified delayed symptomatic hyponatremia as the primary cause of unplanned readmission after transsphenoidal surgery for pituitary tumors. In their retrospective cohort of 303 patients, 27 (8.9%) were readmitted within 30 days. Of these, 15 (55.6%) had delayed hyponatremia. As a result, of all the patients discharged after pituitary surgery, 5% (15/303) were readmitted because of symptomatic hyponatremia. Other less-frequent causes of unplanned readmission were diabetes insipidus (4 cases), secondary adrenal insufficiency (2 cases), cerebrospinal fluid leak, epistaxis, cardiac arrhythmia, pneumonia, urinary tract infection, and hypoglycemia (1 case each). Another recent retrospective cohort of 466 consecutive patients who underwent endoscopic transsphenidal surgery showed a slightly greater readmission rate for epistaxis than hyponatremia (2.1% and 1.5%, respectively).18
Some years ago, we evaluated retrospectively the prevalence, risk factors, course, and management of symptomatic delayed postoperative hyponatremia in our cohort of 1098 consecutive patients who underwent pituitary surgery by endoscopic endonasal approach from 1998 to 2010, and the results of the study were presented in 2011 at the Italian Society of Endocrinology's 35th Meeting in Pescara, Italy. Ninety-five patients were excluded on the basis of the following exclusion criteria: postoperative triphasic diabetes insipidus, diuretic treatment, drug-induced SIADH, and scant laboratory data. Therefore, a total of 1003 patients (median age, 50 years, range, 3–89 years; 52% females; 87% pituitary adenomas; 5% craniopharyngiomas; 5% Rathke cleft cysts; 2% metastases; 1% meningiomas) were eligible for the study. Forty-one patients (4%) developed symptomatic delayed hyponatremia, which occurred after discharge in all patients but 3. Nadir of medians of serum sodium (124 mmol/L) occurred on postoperative day 8. Both the clinical assessment of extracellular volume status and laboratory tests were consistent with the diagnosis of hypotonic hyponatremia due to SIADH in all cases (no case of CSWS was recorded in our cohort). Age, tumor size, and tumor type (including corticotroph cell adenoma associated with Cushing disease) did not correlate with the development of symptomatic hyponatremia. Interestingly, female patients were more likely to develop symptomatic hyponatremia than males (female to male ratio: 3.1; P < 0.05). Fluid intake restriction was successfully used in 16 patients (39.1%); the remaining 25 (60.9.%) were treated with 3% NaCl hypertonic saline infusion (0.5–2 mL/kg/hour). No case of osmotic demyelination syndromes occurred. The recommended limits of correction in serum sodium concentration in the first 24 hours were 6–8 mmol/L. The apparently high percentage of patients treated with hypertonic saline was attributable to the inclusion criteria. Indeed, we evaluated only patients with symptomatic hyponatremia who were readmitted after transsphenoidal surgery. We continue to be successful in using the same protocol for the management of transient delayed hyponatremia after transsphenoidal surgery. As a matter of fact, the choice of treating patients with severe symptoms of hyponatremia (vomiting, abnormal somnolence, cardiorespiratory distress) with 3% NaCl hypertonic saline independently by the biochemical degree of hyponatremia is now accepted widely and the recommended limits of correction of serum sodium as well.19
To date, the systematic review recently published in WORLD NEUROSURGERY by Cote et al.20 represents a more accurate and updated review of the literature on the delayed hyponatremia after transsphenoidal surgery. The authors have chosen 10 studies for a total of 2947 patients. Despite some limitations of the studies, mainly from the heterogeneity of the including criteria, which makes the pool analysis not so meaningful as expected, the authors have found a number of predictive factors for developing delayed postoperative hyponatremia: young age, female sex, greater tumor size, greater rate of decline of serum sodium, and Cushing disease. Again, the heterogeneity of the inclusion criteria remains the main concern regarding the possibility of considering their findings to be conclusive. However, the systematic review of Cote et al. represents a key step toward improving the postoperative management of postoperative hyponatremia in patients undergoing transsphenoidal surgery. Furthermore, the authors encourage the research in this field, with the aim to recognize the causes and the mechanisms of this fascinating electrolyte disorder.
One way to do so is to design a large prospective cohort study that allows investigators to avoid confounding factors, such as uncertainties in the postoperative management of patients with Cushing disease, lack of assessment of extracellular volume status, and scant laboratory data (urinary osmolality and urinary sodium, for example, are mandatory for a correct diagnosis of hyponatremia, but these data sometimes have not been recorded in previous studies), in order to ascertain the epidemiology, the proper management, and the causes of this still-obscure and challenging postoperative complication
Cesare Cavina (1888-1935): a father of transsphenoidal surgery
No full textAmong the fathers of transsphenoidal surgery, a relevant role should be reserved for Cesare Cavina (1888â1935). He had the merit to develop and popularize in Italy this approach for pituitary tumors, performing 47 transsphenoidal hypophysectomies out of his personal series of 66 patients between 1927 and 1935. He contributed to this surgery by introducing radiological control of the surgical trajectory to reduce the risk of complications and increase the safety of this approach. We think that both his short lifespan (he died when he was 47Â years old) and the language of his papers (Italian and not English) are two important factors that have contributed to forgetting his role in the history of transsphenoidal surgery. We think that Prof. Cesare Cavina is definitively one of the fathers of transsphenoidal surgery and that it is important to preserve his memory
Endoscopic endonasal odontoidectomy: Clinical series
No full textSTUDY DESIGN.: This study evaluates a series of consecutive endoscopic endonasal odontoidectomies performed since 2008 in our center. OBJECTIVE.: The aim of the study was to analyze the outcome and the surgical technique to enlighten advantages and limitations of this procedure. SUMMARY OF BACKGROUND DATA.: Odontoidectomy represents the treatment of choice in selected cases of basilar invagination. Transoral-transpharyngeal odontoidectomy is the "gold standard" and more experienced technique. Recently, the endoscopic endonasal approach has been proposed as an alternative route. METHODS.: All patients underwent a pre- and postoperative evaluation of neurological status using physical neurological examination, assessment of American Spinal Injury Association impairment scale score, and neurophysiological investigations. Pre- and postoperative neuroradiological examinations consisted of magnetic resonance imaging, computed tomography, and radiography in flexion and extension. Surgical complications, time of orotracheal extubation and of resumption of oral feeding after surgery were considered, basing on medical records. RESULTS.: The series is composed of 5 cases. All cases presented a progressive tetraparesis despite a posterior occipitocervical arthrodesis. Two patients presented with irreducible atlantoaxial subluxation in Down syndrome, whereas the others presented with an atlanto-occipital malformation with platybasia and basilar invagination. No complications were observed. In all except one case, orotracheal intubation was removed immediately at the end of surgery. Oral feeding was resumed 1 day after surgery in all but one case that initially required an orogastric tube. At follow-up (mean: 34.2 mo; range: 3-57 mo), neurological symptoms have been shown to improve in 2 cases and stabilization, arresting the neurological worsening, in 3 cases. CONCLUSION.: Endoscopic endonasal odontoidectomy resulted in a safe, effective, and well-tolerated procedure. From our experience, we conclude that the different approaches for odontoidectomy should be considered to be complementary rather than alternative: the endonasal endoscopic can be advantageous in selected cases presenting some anatomical conditions related (micrognathia and macroglossia) to the oral cavity and to high position of the odontoid.Level of Evidence: 4 © 2014 Lippincott Williams & Wilkins
The Endoscopic Endonasal Management of Anterior Skull Base Meningiomas
No full textIntroduction The endoscopic endonasal approach (EEA) might seem an "unnatural" route for intradural lesions such as meningiomas. The aim of this study is to critically revise our management of anterior skull base meningiomas to consider, in what cases it may be advantageous. Material and Methods Each consecutive case of anterior skull base meningioma operated on through an EEA or combined endoscopic-transcranial approach at our institution, between 2003 and 2017, have been included. Tumors were classified on the basis of their location and intra or extracranial extension. Follow-up consisted of an MRI (magnetic resonance imaging) and a clinical examination 3 months after the surgery and then repeated annually. Results Fifty-seven patients were included. The most common location was the tuberculum sellae (62%), followed by olfactory groove (14%), planum sphenoidale (12%), and frontal sinus (12%). Among these, 65% were intracranial, 7% were extracranial, and 28% both intra and extracranial. Radical removal was achieved in 44 cases (77%). Complications consisted in 10 CSF (cerebrospinal fluid) leaks (17.6%), 1 overpacking (1.7%), and 1 asymptomatic brain ischemia (1.7%). Visual acuity and campimetric deficits improved respectively in 67 and 76% of patients. Recurrence rate was of 14%. Conclusions EEA presents many advantages in selected cases of anterior skull base meningioma. However, it is hampered by the relevant risk of CSF leak. We consider that it could be advantageous for planum/tuberculum sellae tumors. Conversely, for olfactory groove or frontal sinus meningiomas, it can be indicated for tumors with extracranial extension, while its role is still debatable for purely intracranial forms as considering our surgical results, it could be advantageous for midline planum/tuberculum sellae tumors. Conversely, it can be of first choice for olfactory groove or frontal sinus meningiomas with extracranial extension, while its role for purely intracranial forms is still debatable
Endoscopic endonasal surgery: New perspectives in recurrent and residual pituitary adenomas
No full textThe study by Alahmadi et al. discusses the suitability of the endoscopic endonasal approach in recurrent or residual tumors and compares the endoscopic approach with the previous microscopic approach, suggesting that inadequate exposure is a cause of incomplete tumor removal. With regard to the first point, the conclusions of Alahmadi et al., supported by their experience, are noteworthy; endoscopic endonasal surgery is safe and effective, and the low complication rate encourages its use in reinterventions. Reinterventions using the microscopic transseptal approach may be difficult right from the beginning of the procedure. The scarring process may make the septal route extremely difficult, leading to a chain of errors that, in association with the anatomic distortion, may favor disorientation. Conversely, the endoscopic technique is an endonasal procedure and is not affected by septal problems resulting from previous surgery. Furthermore, the learning curve of endoscopic surgeons depends on the knowledge of the anatomy of the region. Anatomic knowledge, associated with the panoramic view of the endoscope, which allows the exposure of many anatomic landmarks, is of paramount importance in avoiding errors of orientation. These are the main reasons why the endoscopic technique is more suitable for reinterventions.
Instruments, such as a navigation system can help in anatomic orientation. However, in our opinion, to be used safely, it should not serve as a substitute for anatomic knowledge, but as a confirmation of previous anatomic recognition.
The second point, the comparison of the endoscopic with the microscopic approach, is more open to criticism. We agree with the remark that limited exposure, sphenoidal and/or sellar, is a factor favoring the incomplete removal of primary adenomas. However, this defect is not exclusive to the microscopic approach. A comparison between the endoscopic and the microscopic technique based on cases with incomplete tumor resection is misleading. In agreement with Alahmadi et al., these microscopic cases are not to be considered representative of the microscopic approach in general. In addition to the debatable comparison, the fact remains that inadequate exposure, sphenoidal and/or sellar, is an error regardless of the technique. Concerning the results of the study it is surprising that, even when correct exposure was obtained in residual tumors, gross total removal was obtained in only 41% of the cases, whereas in recurrent tumors, the percentage of removal was 70%. Therefore, it appears that surgical management of an adenoma with aggressive behavior inducing a true recurrence may be more satisfactory than the surgical management of a tumor remnant, independent of its biology. This discrepancy may be partially explained by assuming that the residual tumors were mainly located in the cavernous sinus and keeping in mind that Alahmadi et al. refrained from surgery in the cavernous sinus. Nevertheless, if surgery was carried out, it means that components within the cavernous sinus were symptomatic and/or were growing, even if radiosurgical treatment was carried out. If and when this occurs, the chance to resect the tumor is less than 50%. Therefore, every effort should be made to prevent this severe condition. We are against not operating in the cavernous sinus in the case of pituitary adenomas. We believe that radiosurgery is a useful procedure. However, we believe that it should follow resection of the tumor but not be used as a substitute for this procedure.
The abstention, which we criticize, is the consequence of disillusionment after the morbidity observed 30 years ago when craniotomic cavernous sinus surgery was in vogue. Since that time, great improvement in knowledge, technique, and instrumentation has occurred. We have learned that, in selected patients, cavernous sinus surgery is safe and effective (1). Selection criteria depend on the nature of the tumor and its location with respect to the dural plane. Adenomas are the prototype of tumors amenable to surgery because they do not infiltrate vessels and/or nerves, and because they are generally soft and removable by simple suction.
Furthermore, when a parasellar tumor is extradural, it can be resected using an extradural approach, such as the endoscopic extended transsphenoidal approach, which is a minimally invasive approach.
Returning to the excellent study of Alahmadi et al., some operative suggestions are useful to improve the surgical management of residual and recurrent pituitary adenomas. Furthermore, it points out the poorer surgical outcome of remnants with respect to recurrences, particularly if located in the cavernous sinus. This suggestion may contribute to changing the prevailing attitude toward surgery in the cavernous sinus; lack of intervention is not justifiable owing to the current innovations in this type of surgery, especially after the advent of extended endoscopic endonasal surgery
Myasthenia gravis imitating pituitary apoplexy in macroprolactinoma
No full textMyasthenia gravis (MG) is an autoimmune disease affecting neuromuscular transmission that manifests with muscle weakness and typically involves the eye muscles, often producing diplopia and ptosis. Recent studies suggest that hyperprolactinaemia may have a role in the development of MG, although its association with prolactinoma is extremely rare. We report the unusual case of a 71-year-old male affected with macroprolactinoma, who presented at our Center 2 weeks after starting cabergoline treatment because of acute onset of headache, diplopia, and ptosis. On admission, he presented with drowsiness, dropped head, swallowing impairment and bilateral ptosis, which rapidly worsened. Based on clinical manifestation and history, emergency surgery was performed on suspicion of pituitary apoplexy (PA), the typical complication occurring in patients with macroadenomas who present these symptoms. No pituitary haemorrhage was found. The symptoms initially resolved after surgery, but soon returned and worsened day by day, especially in the evening, despite the increase of cortisone replacement doses. MG was thus suspected and confirmed by the detection of antibodies to the acetylcholine receptor. Pyridostigmine was started with prompt improvement of neurological symptoms. In conclusion, although very rare, MG should be considered in the differential diagnosis of patients with macroprolactinomas and suggestive neurological symptoms in order to provide early and appropriate treatment. The role of hyperprolactinaemia in MG onset and evolution is also discussed
Cavernous sinus apoplexy presenting isolated sixth cranial nerve palsy: Case report
No full textThe clinical and radiological findings of a patient affected by apoplexy of an adenoma located within cavernous sinus and presenting isolated Cranial Nerve (CN) VI palsy are reported. The differential diagnosis with other pathologies is debated, and pathogenesis of isolated abducens nerve palsy is investigated. The pertinent literature of this uncommon case of apoplexy is reviewed. A 59-year-old female presented sudden appearance of CN VI palsy associated to violent headache. Endocrinological assessment did not show pituitary insufficiency; MRI depicted an adenoma located within the left CS. She underwent an endoscopic endonasal procedure with extensive opening of the cavernous sinus, occupied by an ischemic adenoma. Afterward, neurological symptoms promptly resolved and the patient was discharged after 5 days. At 3 months follow-up MRI radical tumor removal was assessed, and the patient resulted neurologically intact. The review of the pertinent literature shows that apoplexy of pituitary tumor exclusively located within the Cavernous Sinus is a very uncommon event. The distinctive clinical presentation is represented by the sudden abducens nerve palsy and the absence of pituitary insufficiency and it could be explained by the vulnerability of the nerve along its course within the cavernous sinus, and by the sparing of the sellar content by the adenoma. © 2011 Springer Science+Business Media, LLC
Endoscopic and Microscopic Transsphenoidal Surgery of Craniopharyngiomas: A Systematic Review of Surgical Outcomes Over Two Decades
No full textObjective Few studies have compared transsphenoidal endoscopic (TE) and transsphenoidal microscopic (TM) techniques for the treatment of craniopharyngiomas. Design We performed a systematic review of published series. The results were stratified in two time periods from 1995 to 2016. Results A total of 48 articles and 1,186 patients met the inclusion criteria. Overall, 60% of endoscopic cases were supradiaphragmatic, and 76% of microsurgical cases were infradiaphragmatic. Mean tumor size was 3 cm and 2.4 cm in the TE and TM series, respectively ( p = 0.008). Total resection rate was similar (66%) between TE and TM. Considering the surgical outcome for different tumor locations, total resection rate was slightly higher in the TE for supradiaphragmatic lesions (59% versus 42.5%; p = 0.26). Recurrence rate was higher in the endoscopic series (21.7% versus 12%). Mortality and the overall complication rates were similar ( p = 0.84). However, hydrocephalus (7.6%) and cognitive dysfunction (15.8%) were more common in TE, and meningitis (6%) and endocrinologic complications were more common in the TM series. In the past 6 years, the rate of cerebrospinal fluid leak in TE was significantly lower (13%) and was comparable between TE and TM. Conclusion Both techniques appear comparable for infradiaphragmatic lesions; however, TE seems to yield better results for supradiaphragmatic tumors. In conclusion, more complex lesions with difficult locations can be effectively treated with endoscopic surgery
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