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Michael L. J. Apuzzo, Martin H. Weiss, Viesturs Petersons, R. Baldwin Small, Theodore Kurze, and James S. Heiden

✓ This study was designed to define the effect of positive end expiratory pressure (PEEP) ventilation on intracranial pressure (ICP). In 25 patients with severe head trauma with and without associated pulmonary injury the following parameters were simultaneously monitored under mechanical ventilation with and without PEEP: ICP, arterial blood pressure, central venous pressure, arterial blood gases, and cardiac rate. In addition, the volume-pressure response (VPR) was evaluated in each patient to assess cerebral elastance. The results indicate a significant increase in ICP with the application of PEEP only in the 12 patients who manifested increased cerebral elastance by VPR. Half of this latter group manifested impairment of cerebral perfusion pressure to levels less than 60 mm Hg. Return to baseline ICP levels was observed with termination of PEEP. No significantly consistent changes in other parameters were noted.

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Steven M. Grunberg, Anna Marie Daniels, Helmut Muensch, John R. Daniels, Leslie Bernstein, Virginia Kortes, and Martin H. Weiss

✓ Several investigators have detected progesterone receptors in a high percentage of meningioma specimens and have noted progesterone receptors to be more common than estrogen receptors in these specimens. However, a functional significance of such hormone receptor positivity in control of meningioma growth has not been described. This paper describes a paired test of the estrogen and progesterone receptor assay as the biochemical assay and of the human tumor stem-cell clonogenic assay (HTSCCA) as the functional assay in 17 meningioma specimens. Only one (6%) of the 17 specimens was estrogen receptor-positive, while 11 (69%) of 16 specimens were progesterone receptor-positive. The HTSCCA revealed that only two (15%) of 13 specimens were sensitive to estradiol while five (31%) of 16 specimens were sensitive to progesterone. Comparison of progesterone results for the 15 specimens on which both hormone receptor assay and HTSCCA were performed revealed correlation in a majority of cases; four specimens were positive for both assays and five specimens were negative for both assays. No specimen that was negative for progesterone receptors was sensitive to progesterone by HTSCCA. These results suggest that the hormone receptor and sensitivity pattern of meningiomas may differ from that of breast cancer, and that progesterone addition or ablation may be a reasonable therapeutic approach for meningiomas.

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Acute fractures of the odontoid process

An analysis of 45 cases

Michael L. J. Apuzzo, James S. Heiden, Martin H. Weiss, Truman T. Ackerson, J. Paul Harvey, and Theodore Kurze

✓ Between 1969 and 1974, 45 cases of acute odontoid fracture were diagnosed and treated at this institution. The group consisted of 35 men and 10 women; 24 were between 19 and 40 years of age, and 21 were over 40 years old. Detectable myelopathy was appreciated in eight cases (18%). Diagnosis was established within 72 hours of the traumatic event. Initial evaluation disclosed displacement of the fracture in 17 cases (38%). Following reduction, the initial treatment was posterior fusion in three cases, and external immobilization in 42 cases. Excluding two deaths within the first week of treatment, 40 cases were available for follow-up analysis. Bone union failed to occur following periods of immobilization ranging from 4 to 6 months in 13 cases (33%). Fibrous union with no evidence of instability was apparent in two cases. Nonunion in displaced fractures was seen in 60%, with a rate of 88% in those displaced more than 4 mm. The rate of nonunion in undisplaced fractures was 16%. The rates of incidence of displacement (53% vs 26%) and nonunion (78% vs 33%) in those displaced were higher in individuals over 40 years of age than in those under 40 years. The incidence of nonunion in individuals aged under 40 with nondisplaced fractures was 12%; it was 25% for individuals over 40 years old. A total of 13 patients underwent posterior fusion. All eventually manifested stability at the C1–2 level. However, 69% failed to show bone union at the fracture site in a 6- to 18-month follow-up period.

This review indicates that in consideration of the fracture, external immobilization is the initial treatment of choice in all nondisplaced fractures. Displaced fractures occurring in patients over 40 years old, and those displaced more than 4 mm are candidates for internal stabilization and fusion as a primary mode of treatment.

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Mamoru Kittaka, Steven L. Giannotta, Vladimir Zelman, Jorge D. Correale, Christopher M. DeGiorgio, Martin H. Weiss, and Berislav V. Zlokovic

✓ reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca++ channel (VSCC) antagonist, exerts neuroprotective effects when administered 10 minutes following an ischemic insult, and if it does, whether this is due to its vasodilatory action and effect on cerebral blood flow (CBF) or to direct blockade of Ca++ entry into ischemic brain cells. An increase in the intracellular calcium, [Ca++]i, plays a major role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, inconsistent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats 10 minutes after the onset of ischemia, and 8, 16, and 24 hours after occlusion. Cortical CBF was determined by laser-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific marker for the incidence of neuronal injury, was measured in plasma. The CBF and other physiological parameters were not affected by nicardipine during occlusion or reperfusion. However, nicardipine treatment significantly improved motor neurological outcome by 29%, and the infarction and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 27%, 37%, and 52%, respectively. Nicardipine also reduced the neuron-specific enolase plasma levels by 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respectively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous effects that do not depend on CBF.

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Michelle Lin, Michelle A. Wedemeyer, Daniel Bradley, Daniel A. Donoho, Vance L. Fredrickson, Martin H. Weiss, John D. Carmichael, and Gabriel Zada

OBJECTIVE

Rathke’s cleft cysts (RCCs) are benign epithelial lesions of the sellar region typically treated via a transsphenoidal approach with cyst fenestration and drainage. At present, there is limited evidence to guide patient selection for operative treatment. Furthermore, there is minimal literature describing factors contributing to cyst recurrence.

METHODS

The authors conducted a retrospective analysis of 109 consecutive cases of pathology-confirmed RCCs treated via a transsphenoidal approach at a single center from 1995 to 2016. The majority of cases (86.2%) involved cyst fenestration, drainage, and partial wall resection. Long-term outcomes were analyzed.

RESULTS

A total of 109 surgeries in 100 patients were included, with a mean follow-up duration of 67 months (range 3–220 months). The mean patient age was 44.6 years (range 12–82 years), and 73% were women. The mean maximal cyst diameter was 14.7 mm. Eighty-eight cases (80.7%) were primary operations, and 21 (19.3%) were reoperations. Intraoperative CSF leak repair was performed in 53% of cases and was more common in reoperation cases (71% vs 48%, p < 0.001). There were no new neurological deficits or perioperative deaths. Two patients (1.8%) developed postoperative CSF leaks. Transient diabetes insipidus (DI) developed in 24 cases (22%) and permanent DI developed in 6 (5.5%). Seven cases (6.4%) developed delayed postoperative hyponatremia. Of the 66 patients with preoperative headache, 27 (44.3%) of 61 reported postoperative improvement and 31 (50.8%) reported no change. Of 31 patients with preoperative vision loss, 13 (48.1%) reported subjective improvement and 12 (44.4%) reported unchanged vision. Initial postoperative MRI showed a residual cyst in 25% of cases and no evidence of RCC in 75% of cases. Imaging revealed evidence of RCC recurrence or progression in 29 cases (26.6%), with an average latency of 28.8 months. Of these, only 10 (9.2% of the total 109 cases) were symptomatic and underwent reoperation.

CONCLUSIONS

Transsphenoidal fenestration and drainage of RCCs is a safe and effective intervention for symptomatic lesions, with many patients experiencing improvement of headaches and vision. RCCs show an appreciable (although usually asymptomatic) recurrence rate, thereby mandating serial follow-up. Despite this, full RCC excision is typically not recommended due to risk of hypopituitarism, DI, and CSF leaks.

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Charles B. Stillerman, Thomas C. Chen, William T. Couldwell, Wei Zhang, and Martin H. Weiss

Object. The authors aimed to develop management strategies for the treatment of herniated thoracic discs and to define indications for selection of surgical approaches. Symptomatic thoracic discs requiring surgery are rare. Between 1971 and 1995, 71 patients with 82 herniated thoracic discs were surgically treated by the authors. The treated group included 34 men and 37 women whose ages ranged from 19 to 75 years, with a mean age of 48 years. The most common sites of disc herniation requiring surgery were from T-8 to T-11. Evidence of antecedent trauma was present in 37% of the patients. Preoperative symptoms included pain (localized, axial, or radicular) in 54 (76%) of the 71 patients, evidence of myelopathy, that is, motor impairment in 43 (61%), hyperreflexia and spasticity in 41 (58%), sensory impairment in 43 (61%), and bladder dysfunction in 17 (24%).

Methods. Radiological diagnosis for the patients in this series was accomplished by means of myelography, computerized tomography myelography, or magnetic resonance imaging. Classification of the disc location into two groups reveals that 94% were centrolateral and 6% were lateral. Evidence of calcification was present in 65% of patients, and in 7% intradural extension was noted at surgery. Ten patients (14%) were found to have multiple herniations. Four surgical approaches were used for the removal of these 82 disc herniations: transthoracic in 49 (60%), transfacet pedicle-sparing in 23 (28%), lateral extracavitary in eight (10%), and transpedicular in two (2%). Postoperative evaluation revealed improvement or resolution of pain in 47 (87%) of 54, hyperreflexia and spasticity in 39 (95%) of 41, sensory changes in 36 (84%) of 43, bowel/bladder dysfunction in 13 (76%) of 17, and motor impairment in 25 (58%) of 43. Complications occurred in a total of 12 (14.6%) of 82 discs treated surgically. Major complications were seen in three patients and included perioperative death from cardiopulmonary compromise, instability requiring further surgery, and an increase in the severity of a preoperative paraparesis.

Conclusions. Review of this series, with the attendant complications, together with evaluation of several contemporary thoracic disc series, has facilitated the authors' decision-making process when considering the comprehensive management of these patients, including the selection of a surgical approach.

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Michael L. J. Apuzzo, William R. Dobkin, Chi-Shing Zee, James C. Chan, Steven L. Giannotta, and Martin H. Weiss

✓ Infestations of the human brain with the larval stage of Taenia solium, once an infrequent diagnosis in the United States, is now a more frequently encountered clinical entity especially in population centers with high immigrant flux. During a recent 5-year period 45 cases of intraventricular cysticercosis have been evaluated and treated. Modes of involvement included isolated cyst formation, ependymitis, or combinations of both. Evidence of associated parenchymatous involvement was present in 20% of cases. Sites of infestation included the lateral ventricle (five cases), third ventricle (12 cases), Sylvian aqueduct (four cases), and fourth ventricle (24 cases). Mean post-therapy follow-up periods for this series exceed 36 months. This experience indicates that direct excision is the treatment of choice for ventricular cystic lesions, but that management, operative planning, and expectations should be influenced by considerations of: 1) the potential for acute clinical deterioration (38%); 2) the potential for cyst migration; 3) attendant ependymitis, defined by computerized tomography or verified at surgery; 4) the potential for increase in cyst volume with local mass effect; 5) selection and institution of corridors of surgical access that establish alternative routes of cerebrospinal fluid flow; and 6) the possibility of cyst excision by a stereotaxic endoscopic procedure.

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H. Bruce Hamilton, David R. Hinton, Ronald E. Law, Rayudu Gopalakrishna, Yu Zhuang Su, Zhen-Hai Chen, Martin H. Weiss, and William T. Couldwell

✓ Protein kinase C (PKC) is an enzyme involved in the regulation of cellular growth, proliferation, and differentiation in a number of tissues including the anterior pituitary, in which it is also believed to play a role in hormone secretion. Protein kinase C activity and expression have been found to be greater in adenomatous pituitary cells than in normal human and rat pituitary cells and higher in invasive pituitary tumor cells than in noninvasive ones. Inhibition of PKC activity has been shown in a variety of tumor cells to inhibit growth in a dose-related fashion. The purpose of the current study was to determine whether hypericin, a potent inhibitor of PKC activity that may be administered clinically, alters the growth and proliferation in established pituitary adenoma lines and to determine if inhibition of PKC activity induces apoptosis, as reported in some other tumor cell types. Two established pituitary adenoma cell lines, AtT-20 and GH4C1, were treated with hypericin in tissue culture for defined periods following passage. Inhibition of growth was found to be dose dependent in all three cell lines in low micromolar concentrations of hypericin, as determined by viable cell counts, methylthiotetrazole assay, and [3H]thymidine uptake studies. Concentrations of hypericin as low as 100 nM also induced apoptosis in these established lines, whereas treatment of normal human fibroblasts with a concentration of 10 µM failed to induce apoptosis. The potential use of hypericin in the therapy of pituitary adenomas warrants additional in vitro investigations with the aim of later moving toward therapeutic trials in selected patients in whom surgical or medical therapy has failed.