Biochemical predictors of outcome of pituitary surgery for Cushing's disease.

OBJECTIVE: Transsphenoidal surgery (TS) is the primary therapy for Cushing's disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS for CD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS. METHODS: We reviewed the long-term outcome in 79 patients with CD who underwent TS (median follow-up 84 months, range 6-197). Within 2 weeks after surgery, morning serum cortisol concentrations were obtained (n = 78) and corticotropin-releasing hormone (CRH) (n = 53) and metyrapone tests (n = 72) were performed. Three groups of outcome were identified: sustained remission, early failure (persistent CD), and late relapse. RESULTS: Immediate postoperative remission was achieved in 51 patients (65%), whereas 28 patients (35%) had persistent CD after TS. Ten patients developed recurrent CD after initial remission (20%). Morning cortisol: all relapses but one recorded serum cortisol >50 nmol/l. A cortisol threshold value of 200 nmol/l has a positive predictive value of 79% for immediate surgical failure (negative predictive failure [NPV] 97%). CRH test: CRH-stimulated peak cortisol > or =600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol >or =485 nmol/l. Metyrapone test: 11-deoxycortisol >or =345 nmol/l predicted an early failure in 86% of cases (NPV 94%). CONCLUSION: Predictive factors of surgical failure are morning cortisol >or =200 nmol/l, 11-deoxycortisol >or =345 nmol/l after metyrapone and CRH-stimulated cortisol >or =600 nmol/l. CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing.

Conquering the Rock-A Retrospective Single-Center Experience of the Transapical Petrosal Transtentorial (Kawase) Approach: Operative Technique and Impact on Cranial Nerve Function.

Since its description in 1985, the transapical petrosal transtentorial or Kawase approach has become a viable option of approaching lesions located in and around the apex of the petrous bone, Meckel's cave, and the anterolateral surface of the brain stem while preserving cranial nerve function. At the Brain Tumor Center, Erasmus MC, 25 patients were treated using the Kawase approach between 2004 and 2018 for various indications, including petroclival meningiomas, chondrosarcomas, pontine cavernomas, trigeminal schwannomas, and posterior circulation aneurysms. Hearing preservation was achieved in all patients; new abducens nerve and trochlear nerve palsies were present in three and six patients, respectively, of which a total of eight required ophthalmological correction. Seven patients experienced a cerebrospinal fluid fistula postoperatively, but this complication appeared self-limiting in all cases, with one patient experiencing secondary meningitis. After modifying our closure technique, the rate of fistulas dropped to zero. The observed direct postoperative mortality was 4% (one patient), although not related to the approach itself. In conclusion, the Kawase approach is a highly complex, but essential middle fossa approach, extremely robust, and able to serve a wide array of pathologies together with its extensions. It is very accurate for performing hearing preservation surgery, but not without caveats and inherent risk of complications.

Dutch Normal-Pressure Hydrocephalus Study: the role of cerebrovascular disease.

OBJECT: This study was conducted to determine the prevalence of cerebrovascular disease and its risk factors among patients with normal-pressure hydrocephalus (NPH) and to assess the influence of these factors on the outcome of shunt placement. METHODS: A cohort of 101 patients with NPH underwent shunt placement and was followed for 1 year. Gait disturbance and dementia were quantified using an NPH scale and handicap was determined using a modified Rankin scale (mRS). Primary outcome measures consisted of the differences between preoperative and last NPH scale and mRS scores. The presence of risk factors such as hypertension, diabetes mellitus, cardiac disease, peripheral vascular disease, male gender, and advancing age was recorded. Cerebrovascular disease was defined as a history of stroke or a computerized tomography (CT) scan revealing infarcts or moderate-to-severe white matter hypodense lesions. The prevalence of risk factors for cerebrovascular disease was higher in the 45 patients with cerebrovascular disease than the 56 without it. Risk factors did not influence outcome after shunt placement. Intent-to-treat analysis revealed that the mean improvement in the various scales was significantly less for patients with a history of stroke (14 patients), CT scans revealing infarctions (13), or white matter hypodense lesions (32 patients) than for those without cerebrovascular disease. The proportion of patients who responded to shunt placement was also significantly lower among patients with than those without cerebrovascular disease (p=0.02). CONCLUSIONS: The authors identified a subgroup of patients with NPH and cerebrovascular disease who showed disappointing results after shunt placement. Cerebrovascular disease was an important predictor of poor outcome.

Dutch normal-pressure hydrocephalus study: prediction of outcome after shunting by resistance to outflow of cerebrospinal fluid.

The authors examined whether measurement of resistance to outflow of cerebrospinal fluid (Rcsf) predicts outcome after shunting for patients with normal-pressure hydrocephalus (NPH). In four centers 101 patients (most of whom had idiopathic NPH) who fulfilled strict entry criteria underwent shunt placement irrespective of their level of Rcsf obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified by using an NPH scale and the patient's level of disability was assessed by using the modified Rankin scale (mRS). In addition the Modified Mini-Mental State Examination was performed. Patients were assessed prior to and 1, 3, 6, 9, and 12 months after surgery. Primary outcome measures were based on differences between the preoperative and last NPH scale scores and mRS grades. Improvement was defined as a change measuring at least 15% in the NPH scale score and at least one mRS grade. Intention-to-treat analysis of all patients at 1 year yielded improvement for 57% in NPH scale score and 59% in mRS grade. Efficacy analysis, excluding serious events and deaths that were unrelated to NPH, was performed for 95 patients. Improvement rose to 76% in NPH scale score and 69% in mRS grade. Six cut-off levels of Rcsf were related to improvement in NPH scale score using two-by-two tables. Positive predictive values were approximately 80% for an Rcsf of 10, 12, or 15 mm Hg/ml/minute, 92% for an Rcsf of 18 mm Hg/ml/minute, and 100% for an Rcsf of 24 mm Hg/ml/minute. Negative predictive values were low. More important was the highest likelihood ratio of 3.5 for an Rcsf of 18 mm Hg/ml/minute. Extensive comorbidity was a major prognostic factor. Measurement of Rcsf reliably predicts outcome if the limit for shunting is raised to 18 mm Hg/ml/minute. At lower Rcsf values the decision depends mainly on the extent to which clinical and computerized tomography findings are typical of NPH.

Analysis of hearing loss after shunt placement in patients with normal-pressure hydrocephalus.

OBJECT: Following shunt placement for treatment of normal-pressure hydrocephalus (NPH), several patients suffered hearing loss. The authors undertook a study to analyze this outcome. METHODS: Sixteen patients in whom NPH was diagnosed were treated by placement of a ventriculoperitoneal shunt. Their hearing was assessed pre- and postoperatively by using pure tone audiometry. Two thirds of the ears tested showed a postoperative hearing loss of more than 10 dB. Recovery of the hearing loss occurred 6 to 12 weeks after shunt placement in 75% of the ears examined. CONCLUSIONS: Although shunt insertion for treatment of NPH results in a decrease in hearing, most of the loss can be recovered.

Dutch Normal-Pressure Hydrocephalus Study: randomized comparison of low- and medium-pressure shunts.

OBJECT: The goal of this prospective study was to compare outcome after placement of a low- or medium-pressure shunt in patients with normal-pressure hydrocephalus (NPH). METHODS: Ninety-six patients with NPH were randomized to receive a low-pressure ventriculoperitoneal shunt (LPV; 40 +/- 10 mm H2O) or medium high-pressure ventriculoperitoneal shunt (MPV; 100 +/- 10 mm H2O). The patients' gait disturbance and dementia were quantified by applying an NPH scale, and their level of disability was evaluated by using the modified Rankin scale (mRS). Patients were examined prior to and 1, 3, 6, 9, and 12 months after surgery. Primary outcome measures were determined by differences between preoperative and last NPH scale scores and mRS grades. The LPV and MPV shunt groups were compared by calculating both the differences between mean improvements and the proportions of patients showing improvement. Intention-to-treat analysis of mRS grades yielded a mean improvement of 1.27 +/- 1.41 for patients with LPV shunts and 0.68 +/- 1.58 for patients with MPV shunts (p = 0.06). Improvement was found in 74% of patients with LPV shunts and in 53% of patients with MPV shunts (p = 0.06) and a marked-to-excellent improvement in 45% of patients with LPV shunts and 28% of patients with MPV shunts (p = 0.12). All outcome measures indicated trends in favor of the LPV shunt group, with only the dementia scale reaching significance. After exclusion of serious events and deaths unrelated to NPH, efficacy analysis showed the advantage of LPV shunts to be diminished. Reduction in ventricular size was also significantly greater for patients in the LPV shunt group (p = 0.009). Subdural effusions occurred in 71% of patients with an LPV shunt and in 34% with an MPV shunt; however, their influence on patient outcome was limited. CONCLUSIONS: Outcome was better for patients who had an LPV shunt than for those with an MPV shunt, although most differences were not statistically significant. The authors advise that patients with NPH be treated with an LPV shunt.

The Dutch normal-pressure hydrocephalus study. How to select patients for shunting? An analysis of four diagnostic criteria.

BACKGROUND: Comparison of the predictive value of four "diagnostic tests" for the outcome of shunting in patients with normal-pressure hydrocephalus (NPH). METHODS: Ninety-five NPH patients who received shunts were followed for 1 year. Gait disturbance and dementia were quantified by an NPH scale and handicap by a modified Rankin scale. Primary outcome measures were differences between the preoperative and last scores on both the NPH scale and the modified Rankin scale. Clinical and computed tomographic (CT) findings typical of NPH, absence of cerebrovascular disease, and a resistance to outflow of cerebrospinal fluid (CSF) >/= 18 mmHg/ml/minute were designated as a positive test outcome; clinical and CT findings compatible with NPH, presence of cerebrovascular disease, and an outflow resistance < 18 mmHg/ml/minute as a negative test outcome. RESULTS: For each of the four tests the percentage of patients classified as improved was significantly greater for those with positive than with negative test results. Measurement of CSF outflow resistance was the only significant prognostic factor for the improvement ratio in NPH scale and CT in the modified Rankin scale according to multivariate logistic regression analysis. The accurate predictive value of the combination of typical clinical and CT findings was 0.65, that of the positive test results of outflow resistance, clinical and CT findings was 0.74. CONCLUSION: The best strategy is to shunt NPH patients if their outflow resistance is >/= 18 mmHg/ml/minute or, when the outflow resistance is lower, if their clinical as well as their CT findings are typical of NPH.

Does CSF outflow resistance predict the response to shunting in patients with normal pressure hydrocephalus?

The value of the measurements of CSF outflow resistance (Rcsf) relative to predicting outcome after shunting was studied. In a group of 101 patients with mainly idiopathic normal pressure hydrocephalus (NPH) Rcsf was obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified using an NPH scale (NPHS) and disability by the Modified Rankin scale (MRS). Patients were assessed before and at 1, 3, 6, 9 and 12 months after surgery. Outcome measures were differences between the preoperative and last NPHS and MRS scores. Improvement was defined as a change of > or = 15% in NPHS and > or = 1 grade in MRS. Intention-to-treat analysis of all patients at one year yielded improvement of 57% in NPHS and 59% in MRS. Efficacy analysis, excluding comorbidity unrelated to NPH, revealed positive predictive values of around 80% at Rcsf < 18, and between 90% and 100% at Rcsf > or = 18 mm Hg/ml/min. For Rcsf > or = 18, the likelihood ratios were also higher. We conclude that the best predictor of the response to shunting is an Rcsf > or = 18 mm Hg/ml/min. Since two-thirds of the patients with Rcsf < 18 showed improvement as well, these patients should not be denied shunting.

[Acromegaly. Treatment of the causal factor and the oral sequelae]. / Acromegalie. Behandeling van de oorzaak en de orale gevolgen.

During the last few years, a 64-years-old man experienced a progressive enlargement of his hands, feet, and tongue and an alteration in the position of his frontal teeth. In a university medical clinic acromegaly was diagnosed, based on external features, serum tests, and an oral glucose tolerance test. A pituitary microadenoma was discovered. The most common oral features of acromegaly are a prognatic mandible, interdental spaces, macroglossy, and everted, swollen lips. In this article the primary treatment and the possible oral sequelae are described.

The prognostic value of clinical characteristics and parameters of cerebrospinal fluid hydrodynamics in shunting for idiopathic normal pressure hydrocephalus.

BACKGROUND: It is difficult to predict which patients with symptoms and radiological signs of normal pressure hydrocephalus (NPH) will benefit from a shunting procedure and which patients will not. Risk of this procedure is also higher in patients with NPH than in the overall population of hydrocephalic patients. The aim of this study is to investigate which clinical characteristics, CT parameters and parameters of cerebrospinal fluid dynamics could predict improvement after shunting. METHODS: Eighty-three consecutive patients with symptoms and radiological signs of NPH were included in a prospective study. Parameters of the cerebrospinal fluid dynamics were measured by calculation of computerised data obtained by a constant-flow lumbar infusion test. Sixty-six patients considered candidates for surgery were treated with a medium-pressure Spitz-Holter valve; in seventeen patients a shunting procedure was not considered indicated. Clinical and radiological follow-up was performed for at least one year postoperatively. FINDINGS: The odds ratio, the sensitivity and specificity as well as the positive and negative predictive value of individual and combinations of measured parameters did not show a statistically significant relation to clinical improvement after shunting. CONCLUSIONS: We conclude that neither individual parameters nor combinations of measured parameters show any statistically significant relation to clinical improvement following shunting procedures in patients suspected of NPH. We suggest restricting the term normal pressure hydrocephalus to cases that improve after shunting and using the term normal pressure hydrocephalus syndrome for patients suspected of NPH and for patients not improving after implantation of a proven well-functioning shunt.

Extraforaminal ligament attachments of human lumbar nerves.

STUDY DESIGN: An anatomic study of the extraforaminal attachments of the lumbar spinal nerves was performed using human lumbar spinal columns. OBJECTIVES: To identify and describe the existence of ligamentous structures at each lumbar level that attach lumbar spinal nerves to structures at the level of the extraforaminal region. SUMMARY OF BACKGROUND DATA: During the last 120 years, several mechanisms to protect the spinal nerve against traction have been described. All these structures involved are located in the spinal canal, proximal to the intervertebral foramen. METHODS: Five embalmed human lumbar spines (T12-S1) were used. Bilaterally, the extraforaminal region was dissected to describe and measure anatomic structures and their relationships. Histology was performed with staining on the sites of attachment and along the ligament. RESULTS: The levels T12-L2 show bilaterally 2 ligaments, a superior extraforaminal ligament and an inferior extraforaminal ligament. The superior extraforaminal ligament emerges from the joint capsule of the facet joints and inserts in both, the intervertebral disc and the ventral crista of the intervertebral foramen, passing the spinal nerve laterally. In one specimen on level L2-L3, the superior extraforaminal ligament is not attached to the spinal nerve. The inferior extraforaminal ligament emerges from the intervertebral disc, passing the nerve medially and attaching the spinal nerve. At the levels L2-L5, the inferior extraforaminal ligaments are only attached to the intervertebral disc, not to the joint capsule. Histologically, the ligaments consisted of mainly collagenous structures. CONCLUSION: Ligamentous connections exist between lumbar extraforaminal spinal nerves and nearby structures.

The first description of a device for repeated external ventricular drainage in the treatment of congenital hydrocephalus, invented in 1744 by Claude-Nicolas Le Cat.

An 18th century report of a device for repeated extracranial drainage of cerebrospinal fluid in the treatment of congenital hydrocephalus is reviewed. On 15th October 1744, the French surgeon Claude-Nicolas Le Cat (1700-1768) introduced a specially invented canula into the lateral ventricle of a newborn boy with hydrocephalus. The canula was used as a tap and was left in place for 5 days, until the death of the child. This procedure should be seen as the first documented description of a device for repeated ventricular taps in the treatment of hydrocephalus.

Hydrostatic and hydrodynamic considerations in shunted normal pressure hydrocephalus.

Symptoms of overdrainage, a frequent complication following shunting procedures especially in patients with normal-pressure hydrocephalus (NPH), are presumed to be caused by siphoning: gravity-enhanced flow of cerebro spinal fluid (CSF) through shunts in upright position. A critical reappraisal of siphoning and overdrainage (OD) is presented considering the occurrence of subdural hygromas (SDH) encountered in a group of patients shunted for NPH. The patients participated in the multicentre Dutch NPH study: 101 NPH patients were randomised for treatment with shunts with low or medium-high working pressure. Treatment with shunts with low working pressure resulted in an increased incidence of SDH (iSDH). Current physiological concepts of overdrainage are discussed and criticised. A new theory is presented on the basis of general physiological considerations. The theoretical model proposed yields a revised explanation for the origin of extremely low ventricular pressure in the upright position found with overdrainage. The efficacy of siphoning-preventing shunts and subtemporal decompression is explored in the light of the proposed theory.

Cerebral hemodynamics before and after shunting in normal pressure hydrocephalus.

OBJECTIVE: To study the relationship between cerebral hemodynamics and clinical performance in normal pressure hydrocephalus (NPH), before and after surgery. MATERIAL AND METHODS: Ten patients were studied prospectively before and 3 months after shunt surgery by means of transcranial Doppler (TCD). Clinical performance was scored by means of an NPH scale and the modified Rankin scale. RESULTS: Peak systolic and mean cerebral blood flow velocity (MCV) were lower and cerebrovascular CO2 reactivity was higher after shunt surgery. The three patients with clinical improvement had higher preoperative end diastolic cerebral blood flow velocity and MCV. All postoperative cerebral blood flow velocities were higher in patients with clinical improvement. CONCLUSION: Our data suggest that higher cerebral blood flow velocity before surgery in patients with NPH is related to clinical improvement after shunt surgery. Cerebral hemodynamic parameters may develop into predictors of successful shunt surgery in patients with normal pressure hydrocephalus.

Dutch normal pressure hydrocephalus study: baseline characteristics with emphasis on clinical findings.

We present the baseline characteristics of 101 patients with normal pressure hydrocephalus (NPH), entering a study that evaluates the diagnostic reliability of CSF outflow resistance. Patients were assessed by a gait scale consisting of 10 features of walking and the number of steps and seconds necessary for 10 m, a dementia scale comprising the 10 word test, trail making, digit span and finger tapping, the modified Mini Mental State Examination (3MSE) and the modified Rankin scale (MRS). Inclusion criteria were a gait and dementia scale ≥ 12 (range 2-40), a MRS ≥ 2 and a communicating hydrocephalus on CT. Gait disorder and dementia varied from mild to severe leading to MRS 2 in 17%, MRS 3 in 34%, MRS 4 in 21%, MRS 5 in 16% and MRS 6, including akinetic mutism, in 12%. Only one patient showed both normal tandem walking and turning. Small steps, reduced foot floor clearance and wide base were also frequently seen in the 67 patients walking independently; 34 needed assistance or could not walk at all. Applying the 3MSE, 64% were demented; the remaining 36% exhibited a milder cognitive deficit. The 10 word test and trail making decreased with increasing dementia. Digit span and finger tapping declined in the most demented patients. This group of elderly patients with NPH, mostly of the idiopathic type, proved to be vulnerable because of considerable disability and comorbidity.

Cerebrospinal fluid leakage during transsphenoidal surgery: postoperative external lumbar drainage reduces the risk for meningitis.

Postoperative meningitis is a well known complication of transsphenoidal surgery (TSS). The objective of this study was to evaluate whether postoperative external cerobrospinal fluid (CSF) drainage in case of intraoperative CSF-leakage, reduces the risk of postoperative meningitis. We retrospectively reviewed a series of 278 consecutive transsphenoidal operations. In all operations with intraoperative CSF leakage, an external lumbar drain (ELD) was inserted directly postoperatively, and removed after at least 5 days. The incidence of postoperative meningitis was compared with that in a previously studied series of 228 consecutive transsphenoidal operations, without insertion of an ELD in cases with intraoperative CSF leakage. In the present series, postoperative meningitis occurred in 2/278 (0.7%) operations, compared to 7/228 (3.1%) operations in the previous study period (P < 0.05). Intraoperative CSF leakage was noted in 70/278 (25.2%) operations. All these patients received an ELD immediately after surgery for at least 5 days. There were no reported complications of ELD insertion. In the present series, 1 of 70 (1.4%) patients with intraoperative CSF leakage developed meningitis, compared to 3 of 22 (13.6%) patients in the previous study (P < 0.05). The present report on 278 consecutive transsphenoidal operations shows that the routine insertion of an ELD in patients in whom intraoperative CSF leakage is observed significantly reduces the incidence of postoperative meningitis. Possibly, diversion of CSF prevents the formation of a CSF fistula and thereby the risk of infection. The role of prophylactic antibiotic treatment in patients with CSF rhinorrhea after TSS remains to be established.