Delivery systems for the treatment of proliferative vitreoretinopathy: materials, devices and colloidal carriers.

Proliferative vitreoretinopathy (PVR), the most serious complication causing retinal detachment surgery to fail, is one of the leading causes of vision-loss in developed countries. The pharmaceutical treatment of this disease, located in the posterior segment of the eye, is problematic because it is difficult to achieve effective drug levels in the vitreous and the retina through conventional forms of administration (topical or systemic). Intravitreal injections can deliver drugs to the retina without the side-effects associated with systemic administration. However, because PVR is a long-term complication and the half-life of most drugs in the vitreous cavity is short, repeated injections are needed but this can cause complications. Recent advances in ocular drug delivery methods and the development of novel bioactive compounds could lead to new ways for the treatment of PVR. This review will summarize recent literature concerning intraocular drug delivery of biopharmaceutical agents for the treatment and prevention of PVR.

Neurophysiologic assessment of trigeminal function after surgery for trigeminal neuralgia.

To assess the function of the three trigeminal divisions, we studied corneal reflex, early and late blink reflexes, early and late masseter silent periods, and jaw jerk in normal subjects and in 35 patients submitted to surgery for trigeminal neuralgia. The corneal reflex was most sensitive to thermocoagulation and the jaw jerk to microcompression; the other reflexes showed an intermediate behavior, depending on afferent fiber size. Trigeminal function was less impaired after microcompression and recovered earlier than after thermocoagulation.

Synthetic neoglycolipids for biological applications: correlation between their structures and their interactions with membrane proteins.

Synthetic glycolipids are of interest for their biological applications requiring interactions with membrane proteins. Depending on their structures, new series of glycolipids have applications in extraction of membrane proteins or medical applications as mimics of natural ligands of proteins.

Treatment of trigeminal neuralgia by thermocoagulation, glycerolization, and percutaneous compression of the gasserian ganglion and/or retrogasserian rootlets: long-term results and therapeutic protocol.

From 1976 to 1986, 681 patients with drug-refractory trigeminal neuralgia (TN)--typical in 641, symptomatic of multiple sclerosis in 23 and of tumor in 10, atypical in 5, and postherpetic in 2--were treated with various percutaneous procedures. Controlled differential thermocoagulation of the gasserian ganglion and/or retrogasserian rootlets was performed in 533 patients; glycerolization of the trigeminal cistern in 32; and compression of the gasserian ganglion by balloon catheter in 159. Results and complications of each procedure are assessed at a mean follow-up of 6.5 years for thermocoagulation, 5 years for glycerolization, and 3.5 years for compression. The following therapeutic protocol is proposed: 1) in TN patients at first operation: a) gasserian compression (or glycerolization, if experience warrants it) is indicated in all cases of typical TN, unless the 3rd division alone is affected; b) in the latter case and in symptomatic TN, we suggest thermocoagulation; 2) in recurrences: a) after glycerolization or gasserian compression, gasserian compression (or glycerolization) is indicated; b) after thermocoagulation or open surgery, thermocoagulation is suggested.

Intracranial arteriovenous malformations. Conservative and surgical treatment.

The authors present a consecutive series of 145 patients admitted to the Institute of Neurosurgery of Rome University with an intracranial arteriovenous malformation (AVM). Of these, 95 received surgical care, and 50 were treated conservatively. Total removal of the AVM was performed in all but three of the patients treated surgically, and all underwent postoperative angiography. The postoperative mortality was 6.3%. A long-term follow-up study showed a mortality rate of 20% in the group of patients receiving conservative treatment, while no recurrence of bleeding was observed in the surgical group. The choice of treatment of these malformations is still an open question. The authors' contribution to the discussion is based on the late results of both surgical and conservative treatment.

Posterior partial rootlet section in the treatment of spasticity.

Twenty-six patients were operated on using a techinal modification of Förster's method of treating spasticity, which consists of a partial section of the roolets constituting the posterior roots. Many patients had mild cerebral spastic quadriplegia or spastic diplegia: several of them were nearly independent when standing or walking, and two of them completely independent. The spastic disorders that were not made worse by voluntary movements were reduced or abolished in all but one patient, in whom rootlet section was insufficient. The spastic disorders that were made worse by voluntary movements were only partially reduced; after operation they were scarcely evident or absent in a static position, but evident during voluntary movements. No improvement was observed in one patient who suffered from spastic disorders that were evident only during voluntary movements, or in one patient suffering from dystonia. The procedure caused no sensory disorders. The operation was especially useful in patients who were acquiring or had already acquired independence when standing or walking.

Cystic pilocytic astrocytomas of the cerebral hemispheres. Surgical experience with 51 cases and long-term results.

This study concerns 51 cases of cystic pilocytic astrocytoma of the cerebral hemispheres. At operation these tumors closely resembled cerebellar astrocytomas, presenting as a big cyst contiguous with the lateral ventricle and containing a small mural nodule. The nodule was in a deep location in 26 cases, and always showed marked contrast enhancement on computerized tomography scans. The most frequent presenting symptom was epilepsy (68%), and the most common sign was papilledema (85%). The major goal of surgery was extirpation of the nodule. The follow-up period of the 34 cases available for long-term review ranged from 6 to 31 years (mean 17 years). Of these, 28 patients (82%) had a good outcome; four (12%) had a fair result, and two (6%) had a poor response. An analysis of these results shows that total extirpation of the mural tumor was associated with the best outcome, whether or not the cyst wall was completely removed. Radiation therapy was irrelevant to the prognosis for these patients. On the other hand, partial excision of the nodule, correlated with the deep location of the tumor, was the cause of the two poor results in this series and resulted in multiple operations for recurrences in two other patients. Nevertheless, two of these patients are still alive and well many years after incomplete surgical treatment. On the basis of this study, the importance of recognizing the occurrence of this "benign" tumor of the cerebral hemispheres is stressed, and the hypothesis of a common origin from subependymal glia of all pilocytic astrocytomas is supported.

Neurosurgical use of human dura mater sterilized by gamma rays and stored in alcohol: long-term results.

Surgical experience with grafts of human dura mater sterilized by gamma rays and preserved in alcohol is reported in 804 cases. The method of graft preparation is a simple, cheap, and practical technique for making available a plentiful quantity of large and small pieces of dura to use for plastic reconstruction in everyday neurosurgical practice. Annual inspection for sterility and immunogenicity over an 18-year period indicates that this system of preservation is valid for an unlimited period of time.

Tentorial meningiomas: surgical experience with 61 cases and long-term results.

The authors report their experience and long-term results in the surgical treatment of 61 tentorial meningiomas. These cases were operated on between 1951 and 1985 and represented 4.8% of all intracranial meningiomas operated on in that period. The mean duration of clinical history was 29 months, except for cases of meningioma of the posteromedial border, for which it was 5 years. Plain x-ray films and cerebral angiograms were obtained in all cases. Computerized tomography, performed in the last 20 cases (32.7%), supplied much better lesion topography and early diagnosis. The tumor site was posterolateral in 26 cases (42.6%), anterolateral in 14 (22.9%), posteromedial in eight (13.1%), at the free border in seven (11.4%), and in the tentorium itself in six (9.8%). Lateral and medial tumors with solely or mainly supratentorial development were approached from above. The approach from below was reserved for meningiomas with subtentorial involvement only. In meningiomas with both supra- and subtentorial growth, a supratentorial bone flap was combined with a suboccipital craniectomy using a retromastoid incision. The mortality rate was 9.8%. Of the remaining 42 patients, who were followed for at least 5 years, long-term results were good in 26 cases (61.9%), fair in 11 (26.2%), and poor in five (11.9%). Postoperative complications arose in 34% of the patients, but cleared in 27%.

Epidermoid and dermoid cysts. Clinical evaluation and late surgical results.

The authors report on the clinical data, operating technique, postoperative complications, and late results in a series of 31 epidermoid and 21 dermoid cysts of the central nervous system.

Management of carotid-ophthalmic aneurysms.

The authors present 26 cases of carotid-ophthalmic aneurysms that were surgically treated. Contrary to the opinion that these aneurysms, which often are of giant size, must be treated conservatively or by common carotid ligation, the authors favor radical surgery, believing that carotid ligation does not provide assurance against the risk of rebleeding, and frequently is associated with failure to restore useful vision. Often these aneurysms have a neck more suitable for ligation than shown by angiography, since a giant aneurysm may overlap the carotid artery in the angiogram. Preoperative criteria and some details of radical treatment are discussed.

Long-term results of the surgical treatment of 129 intramedullary spinal gliomas.

The authors report the late results of surgical treatment of 129 intramedullary gliomas (48 ependymomas, 53 astrocytomas, 13 spongioblastomas, five glioblastomas, one oligodendroglioma, and nine others), with follow-up periods ranging from 1 to 27 years. The value of surgical treatment is considered in relation to postoperative results.

Craniovertebral junction malformations. Clinicoradiological findings, long-term results, and surgical indications in 63 cases.

The fate of a series of 63 patients operated on between 1953 and 1979 was studied retrospectively to assess the efficacy of neurosurgical treatment in relieving symptoms associated with craniovertebral junction (CVJ) malformations. Fifty-eight patients underwent posterior cervicomedullary decompression, and the other five underwent transoral clivus-atlanto-odontoidectomy. Long-term results with the posterior approach showed that 50% of the patients benefited from surgery, 25% remained unchanged, and 25% continued to deteriorate or died. Patients with dorsal nervous tissue and/or meningeal anomalies, such as Arnold-Chiari malformation, hydrosyringomyelia, dural fibrous ring, or obstruction of the cisterna magna, did better than patients with ventral cervicomedullary indentation caused by a clivus-atlanto-odontoid bone complex. Anterior decompression is preferable to a posterior approach only if the CVJ malformation involves a ventral deformity in the absence of dorsal compression by soft tissue.

Lymphocytic infiltrates in primary glioblastomas and recidivous gliomas. Incidence, fate, and relevance to prognosis in 228 operated cases.

The correlation existing in several human malignancies between lymphocytic infiltration and prolonged survival prompted this study. Two hundred selected patients who were operated on for glioblastoma were reviewed to investigate the incidence of the lymphocytic infiltration in the histological slides and its possible relevance to a better clinical course. The group that exhibited a definite lymphocytic infiltration (Group A, 11.5%) had a significantly longer preoperative history and postoperative survival (p less than 0.01) than the other two groups that presented slight or no infiltration (Group B, 23%, and Group C, 65%, respectively). In addition, biopsies of 28 recidivous gliomas were reviewed to study the fate of this lymphocytic infiltration in relation to time and therapy, such as irradiation and steroids which are known to depress the immune response. The authors found that severe lymphocytic infiltration is a rare immunobiological reaction which significantly improves the prognosis of a malignant brain tumor and seems not to be influenced by time, local x-ray therapy, or steroids.

Multiple intracranial meningiomas.

The authors report 14 cases of multiple intracranial meningiomas representing 1.1% of all meningiomas operated on at their hospital in the past 35 years. Differentiation of multiple meningiomas, especially from meningiomatosis, must be strict. Since the introduction of computerized tomography scanning, the frequency of these cases has risen from 0.58% to 4.5% in the authors' meningioma series. Despite the multiplicity of sites, multiple meningiomas do not differ in prognosis from benign solitary meningiomas.

The management of arteriovenous malformations of the corpus callosum.

A series of 15 arteriovenous malformations (AVMs) of the corpus callosum--9% of 170 intracranial AVMs admitted to the School of Medicine of the University of Rome during a 30-yr period--was studied. In all cases the lesion concerned mainly the corpus callosum, although in some it also involved the surrounding structures, such as septum pellucidum, tela choroidea, and the mesial hemisphere. These malformations are divided into three groups, namely, those involving mainly the genu, the truncus, or the splenium of the corpus callosum. The last predominated in the present series. Each type has a peculiar angiographic appearance. In general these lesions are fed by branches from the anterior cerebral and/or posterior cerebral arteries, although in some cases minor contributions from the middle cerebral artery may also be present. Vascularization is often bilateral. Venous drainage occurs through the inferior and/or superior sagittal sinuses and/or the Galen system. As to clinical presentation, Subarachnoid Hemorrhage (SAH) is the usual presenting symptom and tends to recur frequently. Neurological localizing symptoms are infrequent, as are seizures; psychological symptoms are an exception. Of the 4 cases managed conservatively, only one had no further episodes of bleeding and remained free of complaints. On the other hand, surgical results of the 11 operated patients were satisfactory, in the sense that no mortality and low morbidity were recorded. Accordingly, surgical treatment of AVMs of the corpus callosum is recommended as a rule.

Patient characteristics and pre-operative therapeutic modalities.

The International Cooperative Study on the Timing of Aneurysm Surgery included 68 participating centers from 16 different countries. Eight Italian neurosurgical units participated in the Study: Bellaria Hospital, Bologna; Neurological Institute of Milan, Milan; University Hospital, Brescia; University of Milan, Milan; University of Padova, Padova; University of Rome, Rome; Civil Hospital, Verona; and Civil Hospital, Vicenza. The overall case contribution from the Italian centers was 485 cases, 14.1% of the total study population. As compared to the other centers included in the Study, the Italian centers exhibited a higher percentage of patients with impaired consciousness; a later interval of planned surgery from SAH; frequent use of preoperative lumbar drainage, as well as antihypertensives, anticonvulsants, antifibrinolytics, steroids, diuretics and LMW dextran; and less frequent use of sedatives and narcotics. The individual Italian centers differed significantly in regard to patient characteristics and preoperative therapeutic modalities. There was a relatively high number of stuporous or comatose patients admitted to Centers 1, 7 and 8, very few admitted to Centers 5 and 6, and none admitted to Center 2. The different distribution of key prognostic factors prevents a direct comparison of the overall management results of the centers. A stratification of the patients according to a risk scale and/or a prognostic model is required for comparison of the management results.

Surgical findings and postoperative therapeutic modalities.

The 8 Italian centers participating in the International Cooperative Study on Timing of Aneurysm Surgery operated upon 68% of their patients eligible for the study. This low operative rate is mainly explained by the prevailing use of a delayed surgical policy. Only 28% of cases were operated on within 3 days of hemorrhage. Although early surgery was applied in more than 50% of patients from Centers 2, 6 and 7, most other centers operated on approximately 10% of patients within this time interval. Italian centers exhibited a wide variation in planned and actual surgery interval, with only 48% of their patients eventually operated on at the planned time. Differences from planned and actual timing of surgery were less consistent in the units performing early surgery. Preoperative conditions were different between the individual centers. The percent of patients alert at the time of surgery varied from approximately 50% in Centers 3 and 7 to 90% in Center 5. Centers 2 and 6 never operated on comatose patients and rarely stuporous patients. During surgery, induced hypotension was used in 67% of Italian patients. The brain was tight at exposure in 42% of patients from Italian centers; the difference from the other study centers was very significant (p = 0.0009). Consequently major brain resection was more frequently performed in Italy than in the other centers. Brain conditions depended mainly upon timing of surgery and preoperative grade (except for comatose patients) and varied accordingly between the individual centers. Temporary arterial occlusion was rarely used in Italian centers. Intraoperative bleeding from the aneurysm was slightly more frequent than in the other centers. The overall incidence of intraoperative complications was unremarkable. There were significant differences between the Italian and the other centers regarding the use of postoperative routines and medications. In Italian centers ventricular CSF drainage, shunt insertion, ICP monitoring, sedatives and analgesics were less frequently used; lumbar CSF drainage, anticonvulsants, steroids, and diuretics were applied more frequently. In the individual centers the major differences were in the use of antihypertensives, vasopressor agents, diuretics, hypervolemia, and low-molecular weight dextran.

Results of treatment.

Overall results of management in patients admitted to the 8 Italian centers participating in the International Cooperative Study on Timing of Aneurysm Surgery were rather unsatisfactory, with good recovery in only 42% of patients, and death in 45% of patients. As compared to the other centers included in the Study, Italian centers exhibited a significantly lower recovery rate and a significantly higher mortality rate. There were significant differences also between the individual Italian centers; independently of admission neurological status and timing of surgery, the outcome was better in centers 2 and 6 (a mortality rate under 20%) and worse in centers 1 and 8 (a mortality rate around 60%). Using prognostic factor models, higher than expected mortality rates were observed in 4 centers, and lower than expected good recovery rates in 3 centers. In Italian centers vasospasm accounted for the highest morbidity and mortality rate; the difference in mortality rate from vasospasm between Italian and other centers was very significant. Other important causes of death and disability were constituted by direct effect of the initial bleed and by recurrent hemorrhage. Patients operated on in Italian centers exhibited a good recovery in 57% of cases; the mortality was 27%. Differences from the other centers were less marked than for the overall management results. Mortality rates from vasospasm and from surgical complications were significantly higher in Italian than in the other study centers. Between the individual Italian centers, vasospasm accounted for the highest mortality rate in centers 7 and 8 (17% and 28% respectively). Postoperative pneumonia was significantly more frequent in Italian than in the other centers. In regard to timing of surgery, the differences in results between Italian and other centers were less marked when surgery was performed after 10 days from hemorrhage. In Italian centers as a whole, a delayed operation was linked with a better outcome than an early or subacute operation. The lowest recovery rate was observed in drowsy patients operated on between 4 and 10 days from the hemorrhage. Focal ischemic deficits and pneumonia were prevalent after an operation within 3 days of hemorrhage, while postoperative brain swelling was most frequent in patients operated on between 4 and 10 days from hemorrhage. The differences in results between Italian and other centers and among the individual Italian centers are widely discussed; possible explanations include inadequate modalities of treatment (especially inadequate management of vasospasm) and structural deficiencies of intensive care management in seriously ill patients.

Benign extramedullary tumors of the foramen magnum.

This paper analyzes the clinical, diagnostic and surgical data of 18 benign extramedullary tumors at the foramen magnum extending into the posterior fossa and the spinal canal. These cases represent 30% of 60 foramen magnum tumors operated on between 1952 and 1978, among 4187 brain tumors and 587 tumors of the spinal cord. Foramen magnum meningiomas constitute 11 of this series (1.2% of 873 meningiomas, 113 of which were spinal). The considerable difficulty in early diagnosis is emphasized. However, in the present series, myelography showed positive findings in all cases, and angiography in most of them. CT scan, performed in one case, demonstrated the lesion. Surgical mortality was 11% (two deaths). On both patients who died after the operation, multiple surgical procedures had been performed because of erroneous diagnoses made in another unit. At the time of operation neurological symptoms were very advanced, and large tumors were located anteriorly. The review of the remaining patients showed a regression of preoperative symptoms with good to excellent results in all. No recurrences were recorded.