Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.

The subthalamic nucleus (STN) has a key role in the pathophysiology of Parkinson's disease and is the primary target for high-frequency deep brain stimulation (DBS). The STN rest electrical activity in Parkinson's disease, however, is still unclear. Here we tested the hypothesis that pharmacological modulation of STN activity has rhythm-specific effects in the classical range of EEG frequencies, below 50 Hz. We recorded local field potentials (LFPs) through electrodes implanted in the STN of patients with Parkinson's disease (20 nuclei from 13 patients). After overnight withdrawal of antiparkinsonian therapy, LFPs were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine. In the off-state, STN LFPs showed clearly defined peaks of oscillatory activity below 50 Hz: at low frequencies (2-7 Hz), in the alpha (7-13 Hz), low-beta (13-20 Hz), and high-beta range (20-30 Hz). In the on-state after levodopa and apomorphine administration, low-beta activity significantly decreased and low-frequency activity increased. In contrast, orphenadrine increased beta activity. Power changes elicited by levodopa and apomorphine at low frequencies and in the beta range were not correlated, whereas changes in the alpha band, which were globally not significant, correlated with the beta rhythm (namely, low beta: 13-20 Hz). In conclusion, in the human STN, there are at least two rhythms below 50 Hz that are separately modulated by antiparkinsonian medication: one at low frequencies and one in the beta range. Multiple rhythms are consistent with the hypothesis of multiple oscillating systems, each possibly correlating with specific aspects of human STN function and dysfunction.

Visualisation of the subthalamic nucleus: a multiple sequential image fusion (MuSIF) technique for direct stereotaxic localisation and postoperative control.

A novel multiple, sequential image fusion (MuSIF) procedure merging stereotaxic CT with frameless magnetic resonance imaging (MRI) is used since June 2000 to visualise and directly localise the subthalamic nucleus (STN) on T2 images. In 13 consecutive Parkinson's cases, intraoperative recording and stimulation verified bilateral electrode implantation guided by fused T2 images. In 85% of sides, final implantation opted for visualised target track. Implanted electrode position on postoperative T2 images matched planned target. Clinical follow-up reproduces literature's best results. This MuSIF technique, effective for direct STN targeting, has practical advantages: MRI can be performed regardless of surgery time; regular MR scanning to correct real image distortion is unneeded; and the need for multiple localising tracks is reduced by enabling us to account for each patient's STN anatomy.

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2.

Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. This study demonstrates that a fragment derived from the autocatalytic digestion of matrix metalloproteinase (MMP)-2, called PEX, acts simultaneously as an inhibitor of glioma angiogenesis, cell proliferation, and migration. PEX is detected in the cultured medium of various human glioma, endothelial, breast, and prostate carcinoma cell lines. PEX is purified from the medium of glioma cell lines by chromatography, where PEX is constitutively expressed as a free and a TIMP-2-bound form. In human glioma tissue, PEX expression correlates with histological subtype and grade and with alpha v beta 3 integrin expression to which it is bound. Systemic administration of PEX to s.c. and intracranial human glioma xenografts results in a 99% suppression of tumor growth with no signs of toxicity. Thus, PEX is a very promising candidate for the treatment of human malignant gliomas.

Giant temporo-occipital sinus pericranii. A case report.

A rare case of a giant, temporo-occipital sinus pericranii is presented. A 38-year-old male presented with minor symptoms of headache and heaviness over an enlarging temporo-occipital bone defect. Within the defect a soft, compressible, mass lesion was observed, which varied in size with changes in intracranial pressure. Radiological imaging demonstrated bone erosion around a fluid filled mass, which on angiography communicated via a series of channels with the transverse sinus. A diagnosis of sinus pericranii was made. Due to the risk of future complication the patient elected to undergo surgery, which successfully resected the mass and obliterated the venous communications with the diploic veins and transverse sinus. The classification, aetiology, differential diagnosis, radiological characteristics and management options relating to sinus pericranii are discussed.

Isolated cervical juvenile xanthogranuloma in childhood.

STUDY DESIGN: This is a report of an exceptional case of isolated cervical juvenile xanthogranuloma in a child. OBJECTIVES: This case report draws attention to the fact that isolated xanthogranuloma of the central nervous system should be considered among possible diagnosis of subdural extramedullary spinal masses in children and young adults. SUMMARY AND BACKGROUND DATA: Isolated juvenile xanthogranuloma of the central nervous system is extremely rare. When located in the spinal canal it behaves like any extramedullary mass-occupying lesion. MRI depicts the tumor's association with adjacent structures. In cases in which a subtotal surgical removal was possible, radiotherapy has been indicated. METHODS: A three-year-old girl presented severe pain in the right shoulder and spastic tetraparesis. The MRI showed an intradural extramedullary mass homogeneously enhancing after DTPA-gadolinium infusion. Complete surgical removal of the tumor was performed through open-door laminoplasty. RESULTS: The child was pain free immediately after the surgical removal of the tumor. A gradual complete recovery of the neurologic deficits followed. Open-door laminoplasty provided sufficient operative space, and it minimized the impact on the growing spinal column. CONCLUSIONS: Isolated juvenile xanthogranuloma does not show any predilections of localization inside the central nervous system. Both intracranial and spinal juvenile xanthogranulomas appear isointense in MRI and enhance homogeneously with gadolinium. Whenever possible, total surgical removal alone seems to be curative. Otherwise, a subtotal removal of the tumor might be followed by radiotherapy. Immunohistochemical tests ensure the diagnosis.

Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation.

OBJECTIVES: To assess the incidence of shoulder-hand syndrome (SHS) in neurosurgical patients (head injuries, intracranial ruptured aneurysms and intracranial meningiomas), treated with barbiturates. SHS is a chronic condition characterized by intense tenderness and functional impairment affecting one hand, the shoulder or both. Barbiturates have been identified as cause of SHS, although there is controversial evidence on the incidence of this disorder in patients started on long-term Phenobarbital (PB) therapy. METHODS: One hundred and twenty-six neurosurgical patients, treated with barbiturates, and a control group of 108 patients, treated with carbamazepine or phenytoin, were enrolled. Both groups were followed up for at least 24 to 36 months. RESULTS: Thirty-five PB-treated patients (27.6%) experienced SHS. In these patients SHS developed during the first 7 months of therapy and regressed after PB discontinuation or, in 2 cases, after dosage reduction. None of the patients in the control group developed SHS. CONCLUSIONS: The occurrence of SHS in the study group was much more common than that reported previously. This higher incidence should depend upon the coexistence of separate risk factors such as age over 50 years, surgery and intracranial pathology. Early diagnosis and rapid withdrawl of treatment are important for symptomatic relief and full functional recovery.

Alpha(v)beta3 and alpha(v)beta5 integrin expression in meningiomas.

OBJECTIVE: Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two alpha(v) integrins, i.e., alpha(v)beta3 and alpha(v)beta5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas. METHODS: Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of alpha(v)beta3 and alpha(v)beta5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the alpha(v)beta3 ligand vitronectin. RESULTS: Alpha(v)beta3 and alpha(v)beta5 integrins were expressed by neoplastic vasculature and cells. Alpha(v)beta3 and alpha(v)beta5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. Alpha(v)beta3 was more strongly expressed than alpha(v)beta5 in two cases of histologically benign meningiomas with aggressive clinical behavior. Alpha(v)beta3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas. CONCLUSION: Our data demonstrate the expression of alpha(v)beta3 and alpha(v)beta5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly alpha(v)beta3, in meningioma angiogenesis.

Combined treatment of fourth ventricle ependymomas: report of 26 cases.

BACKGROUND: This study investigated the relevance of prognostic factors and the impact of histological features in posterior fossa ependymoma. METHODS: The charts of 26 patients (aged 1-59 years, mean 20.6 years; 11 adults) with posterior fossa ependymoma operated on between January 1983 and December 1994 were reviewed and patients followed up (mean: 93 months). RESULTS: Gross total resection was performed in 18 patients (69%), subtotal in seven patients (27%), biopsy in one patient (4%). One patient (3.8%) developed respiratory complications and died. All patients underwent posterior fossa radiotherapy (5000 cGy) after surgery. Four children first received chemotherapy and then radiotherapy only when at least 3 years old. Eleven patients (42%) received radiotherapy and subsequently chemotherapy. The 5-year survival rate was 90% for adults and 40% for children (

Mortality and morbidity in patients operated on for ruptured intracranial aneurysms.

It is generally agreed, mortality and morbidity rates, in patients operated on for ruptured intracranial aneurysm, strictly depend upon the state at admission. Nevertheless, a precise definition of surgical mortality is still not available. Even the term morbidity still remains rather controversial for the lack of accurate evaluation scales. The wide range of parameters, affecting the composition of sample and outcome of patients, such as age, blood at CT scan and atherosclerosis at angiography, makes harder a correct statistical analysis of mortality and morbidity. Moreover, the gap between bleeding and admission, the management and choice of treatment, the selection of unicentric or multicentric studies, the level of the hospital introduce even more striking bias errors. Recent papers reported concrete improvements obtained by means of both aggressive therapeutical behaviour and adequate intensive care management. Among factors, producing improvement of the overall outcome, have to be also reported the encouraging preliminary results supplied by the interventional neuroradiological techniques. However, the overall mortality rate of SAH remains high. Thus, a coded scheme for detection and prevention of risk factors significatively associated to mortality and outcome can be only worked out by employing an appropriate therapeutical behaviour and an adequate intensive care management. Furthermore, employment of feasible evaluation scales will be essential to point out the most accurate procedure for management and treatment of patients with intracranial ruptured aneurysm. We think CESE, developed by one of the authors, to be considered as an adequate method for the assessment of results at follow-up.

Long-term results of treatment for craniopharyngioma in children.

Results of the treatment of 27 children with craniopharyngioma are reported. A subfrontal pterional approach was used in 55.6% of cases, a transsphenoidal and a transcallosal or transcortical approach in 25.9% and 18.5% of cases, respectively. Radical removal was the goal of surgery and was achieved in 70.8% of cases treated as primary surgery. The operative mortality was 3.7% and was due to hypothalamic failure. Most (81.4%) patients were followed up, for a mean of 7 years. Patients were evaluated according to a functional evaluation scale and outcome categories proposed by us. The scale takes account of tumor (recurrences and their eventual evolution); visual functions; endocrine functions (mainly hypothalamic), attainment of endocrine balance and drug regimen; headache; and psychosocial function. Recurrences were observed in 17.6% of patients treated with radical surgery and in 42.8% of those treated with limited surgery plus radiotherapy. A progressive amelioration of visual, endocrine and neuropsychosocial functions from the intervention to follow-up was observed in the majority of patients. Complete tumor excision was associated in 85% of cases with a low score on the functional scale, reflecting a high functional performance. Adequate substitution therapy maintained endocrine balance in 81% of patients. Since the intervention a progressive decrease in the number and dosages of medications has been observed. The majority of patients were again able to lead a normal social life. Small stature, obesity, headache, and emotional and sexual disturbances were frequent cause of long-term disability even despite adequate drug regimens. The functional evaluation scale we propose is a simple and effective tool that can be easily used during routine evaluation of patients with craniopharyngioma.

Cavernous hemangioma of the cavernous sinus. Complete disappearance of the neoplasma after subtotal excision and radiation therapy. Case report.

A case of a 46-year-old woman with a left cavernous sinus hemangioma is reported. The onset of symptoms consisted in left orbital pain and ocular diseases. The suspected diagnosis were among Tolosa-Hunt syndrome and, after neuroimaging researches, cavernous sinus meningioma, trigeminal neurinoma, craniopharyngioma and adenoma with extrasellar extension. The lesion was partially removed with additional neurological deficit of the left 3rd cranial nerve. The patient underwent 7 months later focal radiation therapy of 45 Gray and a 19 months follow-up showed the complete disappearance of the mass and partial recovery of the 3rd cranial nerve function.

Early postoperative seizures and endovenous phenytoin. Preliminary clinical data.

Early seizures represent a major complication in the post operative course of patients operated on for supratentorial tumors or AVMs. The real effectiveness of the AEDs prophylaxis to reduce the occurrence of post operative seizures is controversial. We proposed a prophylactic treatment with endovenous PHT consisting of two infusions of PHT (mean dosage of 18 mg/kg; mean time of 1 hr) perioperatively and during the first postoperative day. The interruption of the previous oral anticonvulsant treatment is not required. The endovenous route should permit a rapid reach of the therapeutical range. Sixty-six patients were treated. Fifty-one patients received two infusions and 15 patients only one infusion. The serum concentration of PHT performed at 24 hrs of operation was in most of patients (more than 80%) in the lower part of the therapeutical range while at 24 hrs of the second infusion was in the higher part or over the range. The overall prevalence of seizures was 10.6%. In the first group the incidence was 7.8%, in the second one was 20%. All the seizures appeared within 48 hrs of the operation. All the patients in the first group had single seizures, 2 patients of the second one experienced two seizures. No status epilepticus was observed. Alteration of consciousness and mild hypotension were the most common side effects. They never required major measurements and were mild, transient and completely reversible. We are starting with a randomized study based on a larger sample of patients which will allow a more reliable statistical analysis.

Postoperative pain in neurosurgery: a pilot study in brain surgery.

The incidence, magnitude, and duration of acute pain experienced by neurosurgical patients after various brain operations are not precisely known, because of a lack of well-designed clinical and epidemiological studies. We assessed these important pain variables in 37 consecutive patients who underwent various brain neurosurgical procedures. Postoperative pain was more common than generally assumed (60%). In two-thirds of the patients with postoperative pain, the intensity was moderate to severe. Pain most frequently occurred within the first 48 hours after surgery, but a significant number of patients endured pain for longer periods. Pain was predominantly superficial (86%), suggesting somatic rather than visceral origin and possibly involving pericranial muscles and soft tissues. Subtemporal and suboccipital surgical routes yielded the highest incidence of postoperative pain. Age and sex were significantly associated with the onset of pain, with female and younger patients reporting higher percentages of postoperative pain. Psychological Minnesota Multiphasic Personality Inventory profiles of patients with and without pain significantly differed on the Hypochondriasis scale, with patients without pain scoring unexpectedly higher than patients with pain. It is possible that hypochondriasis serves as a defense mechanism against pain, at least in some patients. Results of this pilot study indicate that postoperative pain after brain surgery is an important, although neglected, clinical problem, that deserves greater attention by surgical teams, to provide better and more appropriate treatment.

Cavernous haemangioma of the pineal region.

Cavernous haemangiomas rarely occur in the pineal region, only eight histologically verified cases have been reported to date. Clinically and radiographically, they are often confused with other tumours of the pineal region, particularly germ cell tumours. When radiotherapy is performed without the benefit of biopsy, cavernous haemangiomas as well as other radioresistant neoplasms may be unnecessarily treated. We report two surgically treated cases of cavernous haemangioma of the pineal region, and comment upon one treated by shunt placement alone. Two cases were associated with an adjacent venous malformation. In all instances, magnetic resonance imaging (MRI) permitted a correct pre-operative diagnosis. We conclude that surgical exploration and total resection is the treatment of choice when the diagnosis of cavernous haemangioma is suspected on the basis of neuro-imaging. A conservative attitude is justifiable in the case of elderly patients with a higher surgical risk.

Human neuronal cells in culture: from concepts to basic methodology.

The paper reviews some conceptual and methodological aspects of the tissue culture models which, during the past three decades, demonstrated a remarkable mimicry of many important structures and functions of the mammalian Central Nervous System (CNS) and related peripheral sensory and motor elements. Emphasis is placed on an original human neuronal tissue culture model obtained from selective CNS areas. The different cell types were identified and the neurotrophic interactions preliminary characterized. Neuropathological findings suggest hypothesis that can be fully tested using in vitro human models of affected cerebral specific areas.

Cavernous angiomas of the central nervous system.

The histopathological, epidemiological, clinical and neuroradiological findings of the cavernous angiomas of the central nervous system have been reviewed, based on an analysis of the literature. C.A. was considered a very rare lesion in the pre-CT era (5% of the vascular malformations). In the past mainly the cavernous angiomas operated on were responsible for a hemorrhagic syndrome or a space-occupying lesion syndrome and less frequently did they present with seizures. Since the introduction of the CT and moreover of MRI the reported cases of cavernous angiomas in the C.N.S. have increased considerably (25.1% of the vascular malformations). Familial cases, multiple localizations, association with tumors and other vascular malformations and extracerebral dural localizations have been documented. Angiographic examination can be negative, but in some cases a capillary blush in the late venous phase has been demonstrated. CT scan and MRI are the best procedures for the diagnosis of cavernous angiomas. MRI is able to demonstrate small and no recent traces of bleeding, but CT is more sensitive in distinguishing calcifications. Surgical results depending on the site of the angioma have been reported. Radical removal and good recovery have been documented in supratentorial cases, while partial removal and poor results have been reported in deeply sited cases (including spinal cord).

Clinicoradiological and therapeutic considerations in severe diffuse traumatic brain injury in children.

Forty-one children with severe head injuries and diffuse brain lesions were selected from a consecutive series of 62 children in traumatic coma (21 focal mass lesions) and studied. According to the CT pattern, two main types of intracranial lesions were considered: diffuse axonal injury (DAI) and diffuse brain swelling (DBS). High mortality, due to secondary increases of intracranial pressure (ICP), correlated well with the patterns of severe DBS, absence of perimesencephalic cisterns, and obliteration of the ventricles. However, children with normal CTs, and/or obvious shearing injuries indicative of DAI, had favorable outcomes; there was no mortality if increased ICP was not present. We conclude that although there does not seem to be any routine indications for ICP monitoring in children with pure DAI, early ICP monitoring and aggressive management of increasing ICP should be considered in comatose children with DBS, especially when associated with subarachnoid hemorrhage and respiratory or circulatory failure.

Treatment of non-neoplastic stenosis of the aqueduct of Sylvius with extrathecal CSF shunts.

A series of 185 patients operated on with extrathecal shunts for non-neoplastic aqueductal stenosis has been reviewed. The longterm results of 84 of them, followed-up for 2 to 20 years after primary surgery, are illustrated and critically analyzed. This study indicates that a normal mental development or normalization of mental and neurological conditions can be expected in a high percentage of patients after the CSF diversional procedure which nonetheless is still associated with a high percentage of even serious complications.