A single institution series of cavernomas of the brainstem.

We retrospectively analyzed a series of patients with brainstem cavernomas of the medulla, pons, or midbrain to attempt to define the natural history, indications for surgery, and outcome after surgical resection. Between 1993 and 2008, 52 patients with cavernomas of the brainstem presented to our institute and were managed either surgically or conservatively. Twenty-three patients underwent surgical excision using standard skull base approaches. Outcomes were correlated to the number of preoperative hemorrhages, location of the cavernoma, timing of surgery in relation to the hemorrhage and the preoperative neurological status. Nine patients improved after surgery, 12 deteriorated and two died. In the conservatively managed group, 15 patients had a good outcome, 11 deteriorated and one died. Multiple hemorrhages, poor preoperative neurological status and surgery during the acute phase were predictive of the surgical outcome. Excision of brainstem cavernomas should be considered in patients with symptomatic hemorrhages whose lesions approach the pial surface. Patients with minimal stable neurologic deficits without recurrent bleeds should be managed conservatively.

Bilateral thalamic lesions.

OBJECTIVE: Bilateral thalamic lesions are rare and relatively obscure neoplasms. We present our experience with nine cases of bilateral thalamic lesions and attempt to analyse them in the background of available literature. MATERIALS AND METHODS: Retrospective analyses of the case records of 9 cases of bilateral thalamic lesions treated in our department since January 2002, which have a minimum of 1 year follow-up. RESULTS: The study group included four males and five females with a mean age of 14.6 years (5 years to 29 years). Seven of these patients had radiological evidence of bilateral thalamic lesions at presentation and 2 patients had involvement of the opposite thalamus at a later stage of the disease. All patients except one presented with raised intracranial pressure symptoms. Focal motor deficits (4/9), behavioral and memory disturbances (3/9) were the other major presenting symptoms. Biopsy confirmation was possible in six patients and histopathology was suggestive of low grade fibrillary astrocytoma in all six patients. Seven patients required CSF diversion procedure for associated hydrocephalus. Eight of our nine patients underwent radiotherapy. On last follow-up, 3 patients were clinically stable with images suggestive of arrested disease, four patients had evidence of progressive disease both clinically and radiologically and there were two recorded cases of mortality. CONCLUSION: Primary bilateral thalamic lesions have characteristic neuroradiological properties and are distinct from unilateral thalamic tumours with bilateral progression. Almost all of these lesions on histology prove to be gliomas but decompressive surgery is seldom feasible. Surgical intervention is limited to biopsy and CSF diversion for hydrocephalus. Bilateral thalamic lesions remain unresponsive to adjuvant therapy and generally carry a poor prognosis.

Non-surgical management of cystic prolactinomas.

Cystic prolactinomas are considered not amenable to dopamine agonist therapy. We present the results of dopamine agonist therapy in six patients with cystic prolactinomas. The inclusion criteria of patients were: (i) cystic macroadenomas with the cyst occupying more than 50% of the tumour volume; (ii) a serum prolactin value more than 150 ng/mL. All patients were males with a mean age of 35 years. The clinical presentations were erectile dysfunction in 66.6%, visual deficits in 50% and headache in 50% of patients. All patients were treated with bromocriptine only except one who was treated with both bromocriptine and cabergoline. The mean duration of follow up was 57.1 months. At the final follow-up 50% of patients had hormonal cure, 50% had radiological cure and 50% had reduction in the size of the tumour. Hence, it is appropriate to consider dopamine agonist therapy in patients with cystic prolactinomas before considering surgery.

Intracranial intradural aneurysmal bone cyst: a unique case.

Aneurysmal bone cyst (ABC) of the skull is exceedingly rare. We report a unique case of an intradural ABC without bone involvement presenting with raised intracranial pressure. The patient was a 14-year-old boy who presented with headache, vomiting and right focal seizure. Imaging showed a large multicystic left frontal lesion without any evidence of bone involvement. The lesion adherent to an intact sphenoid wing dura was completely excised. The histopathology report was consistent with an ABC. This case represents the first report of an ABC without involvement of the skull bones or any evidence of dural erosion. The possible mechanism of origin at this unusual location is hypothesized.

Childhood and adolescent meningiomas: a report of 38 cases and review of literature.

BACKGROUND: The aim is to study the clinical, radiological and pathological features of childhood and adolescent meningiomas and analyse outcome prognosticators. METHOD: A retrospective analysis of the case records of patients less than 20 years of age operated for a meningioma in our institute since 1982 was performed. The variables analysed included age, sex, presentation, associated neurofibromatosis (NF), imaging characteristics, extent of resection and histopathology. RESULTS: The study group included 20 males and 18 females with a mean age of 15.53 years. Eleven children (28.9%) had evidence of NF of whom three had NF2 with bilateral vestibular schwannomas. The common presenting symptoms were seizures (76.3%), raised intracranial tension (71%), and focal neurological deficits (39.4%). The location of the operated tumours were as follows: ten skull base (24.4%), ten falx/parasagittal (24.4%), eight spinal (19.5%), five convexity (12.2%), three posterior fossa (7.3%), three intraventricular (7.3%) and two optic nerve sheath (4.9%). Two children (4.9%) had cystic meningiomas. Grade I excision was achieved only in twenty tumours (48.8%). On histopathology, thirty (73.2%) were grade I, nine (21.9%) were grade II and two (4.9%) were grade III meningiomas. Seven tumours recurred of which six were located at the skull base. During the mean follow up period of 4.74 years, the majority, 32 (84.2%) had a good outcome and five (13.2%) had a poor outcome. One child (2.6%) expired due to post-operative sepsis. CONCLUSION: Childhood meningiomas are uncommon but not rare lesions with a marginal male predominance. Absence of large series with long follow up precludes any definite conclusions on the clinical course and outcome. Uniform observations made in different series including ours, include a higher incidence of the skull base location and tumours with atypical histopathology. Favourable prognostic factors include younger age (< than 10 years), superficial location, total excision and absence of neurofibromatosis. Location and extent of excision appear to be more important than histopathology grade in predicting outcome.

Pre-coronal, paramedian minicraniotomy: a minimal access approach for microsurgical, transcallosal, transforaminal removal of colloid cysts of the third ventricle.

OBJECTIVE: Microsurgical excision of colloid cysts of the third ventricle is accomplished along the transcallosal or the transfrontal routes. In the transcallosal approach, venous tributaries of the superior sagittal sinus can often act as an impediment to entry into the interhemispheric fissure for accessing the corpus callosum. We propose a paramedian minicraniotomy anterior to the coronal suture for removing colloid cysts via the transcallosal approach as veins are relatively rare in this area. METHODS: A triangular minicraniotomy was designed with each side measuring 3 cm based on the midline in the pre-coronal area of the frontal bone on the right side. Nineteen cases of symptomatic colloid cysts of the third ventricle whose diagnoses were proven by CT and/or MRI were subjected to microsurgery in the period from June 2004 to May 2007. Following the minicraniotomy the cysts were removed utilizing the transcallosal transforaminal route. RESULTS: Venous tributaries crossing the interhemispheric fissure were seen in 2 patients and these could be avoided to access the corpus callosum. Complete excision could be achieved in all cases. All patients had a good outcome although one patient had transient left lower limb weakness. The mean operating time was 163 minutes, while the mean duration of stay in the intensive care unit and hospitalization were 1.35 days and 3.73 days, respectively. CONCLUSION: The pre-coronal, paramedian minicraniotomy is safe and effective for the total excision of colloid cysts of the third ventricle. As a minimal access approach, it needs only a short duration of postoperative hospitalized care.

Dissecting intracranial aneurysms presenting as subarachnoid haemorrhage: report of two cases and review of literature.

Subarachnoid haemorrhage due to intracranial non-traumatic dissecting aneurysms is rare. Most of the published reports refer to dissecting aneurysms in the vertebrobasilar territory. Anterior circulation dissecting aneurysms are rare and their pathogenesis, clinical features, angiographic findings and management are a matter of debate. Management of patients with intracranial arterial dissection is unclear. Unlike the well-established proximal occlusion and trapping approaches to vertebral artery dissections, choices of interventions for anterior circulation and basilar dissecting aneurysms are limited, and most reports have been limited to wrapping techniques for arterial wall reinforcement. The role of anticoagulation therapy in the presence of subarachnoid haemorrhage is also a matter of debate. As no clear-cut guidelines are available, treatment should be tailored to the individual patient. We describe two cases of intracranial dissecting aneurysms, which presented as subarachnoid haemorrhage (SAH) and discuss the management issues.

Malignant astrocytoma following radiotherapy for craniopharyngioma.

Radiation induced gliomas are uncommon. Occurrence of glioma following radiotherapy for craniopharyngiomas is extremely uncommon and only eight case reports have been so far published. We present our experience with one similar case of temporal gliomas occurring twelve years following radiotherapy for a sub totally excised craniopharyngioma. Although the exact mechanism of gliomas formation is unclear, their occurrence following conventional radiotherapy is a distinct possibility and signifies a poor prognosis.

Telovelar approach: technical issues for large fourth ventricle tumors.

OBJECTS: Fourth ventricle is conventionally accessed via resection of the part of the vermis for total excision of the tumors at the expense of significant morbidity. Numerous avenues have been identified to minimize the morbidity; some of which include transforaminal, subtonsillar, telovelar approaches, etc. These approaches are devised on the basis that accurate dissection along the natural avascular planes will avoid injury to the important structures in this area minimizing morbidity. We attempt to emphasize the technique of telovelar approach and the problems encountered while employing this technique for excision of large fourth ventricle tumors. MATERIALS AND METHODS: Fifteen patients with fourth ventricle tumors were operated during January to September 2005 at Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. Fourteen of these cases were medulloblastomas, and one was ependymoma. All the patients were operated in prone oblique position via telovelar approach. CONCLUSION: Clear understanding of the normal anatomy will help in meticulous dissection and will result in reduced morbidity. Significant incidence of postoperative ataxia and mutism is seen with this approach in large tumors, and this can be avoided by staged dissection of the uvulotonsillar cleft.

Composition and larvicidal activity of leaves and stem essential oils of Chloroxylon swietenia DC against Aedes aegypti and Anopheles stephensi.

The laboratory bioassay of the essential oil and the isolated compounds from Chloroxylon swietenia against Aedes aegypti and Anopheles stephensi was carried out to evaluate the larvicidal activity. LC50 value estimated for A. aegypti and An. stephensi were 16.5 and 14.9 microg/ml and 20.2 and 19 microg/ml for leaf and stem oils, respectively. The three sesquiterpenes pregeijerene, geijerene and germacrene D were isolated and their Larvicidal activity was evaluated. Pregeijerene and geijerene were observed for the first time in the volatile constituents of C. swietenia, however, leaves contained higher amount of geijerene compared to stems.

Ascorbyl palmitate vesicles (Aspasomes): formation, characterization and applications.

Vesicles with biological activity or with a targeting function in addition to carrier properties will have an added advantage. Vesicles prepared with amphiphiles having antioxidant property may have potential applications towards disorders implicated with reactive oxygen species. Ascorbyl palmitate (ASP) was explored as bilayer vesicle forming material. It formed vesicles (Aspasomes) in combination with cholesterol and a negatively charged lipid (dicetyl phosphate). Aspasomes were prepared by film hydration method followed by sonication in which aqueous azidothymidine (AZT) solution was encapsulated in aqueous regions of bilayer. Aspasomes were obtained with all compositions containing 18-72 mol% cholesterol. Differential scanning calorimetric data of aspasome dispersion and anhydrous mixtures of ascorbyl palmitate, cholesterol and dicetyl phosphate confirm the formation of bilayered vesicles with ascorbyl palmitate. Cholesterol content in aspasome did not exhibit any relation with vesicle size, zeta potential or percent entrapment. A substantial change in release rate of azidothymidine from aspasome was noticed on varying the proportion of cholesterol. Release rate and cholesterol content in Aspasomes did not exhibit any relation. A preparation with 45 mol% of cholesterol showed maximum retardation in release rate, than other compositions. The change in capture volume with time (latency) was studied for 8 h and with such a short duration study it was difficult to predict long term stability of these vesicles. But release experiments do indicate stability up to 18 h. Percent reducing activity of aspasome was estimated by measuring the absorbance of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) at 517 nm after addition of test antioxidant samples. These studies revealed that the antioxidant potency of ascorbyl moiety is retained even after converting ascorbyl palmitate into vesicles (Aspasomes). The antioxidant potency of Aspasomes was assessed by measuring the protection offered by this preparation against quinolinic acid induced lipoperoxidation of whole human blood in vitro, where in the lipoperoxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) levels. Aspasome rendered much better antioxidant activity than ascorbic acid. Transdermal permeation of aspasomal AZT, ASP-AZT aqueous dispersion and AZT-solution across excised rat skin was investigated in vitro using Franz diffusion cell. Permeation of aspasomal AZT was much higher than the other two preparations. However, ASP-AZT aqueous dispersion has also enhanced permeation of AZT significantly over the AZT-solution, indicating skin permeation enhancing property of ascorbyl palmitate.

Chordoid meningioma: a report of two cases.

Chordoid meningioma is an uncommon histopathological variant of meningioma. We report 2 cases of chordoid meningioma occurring in adult patients.

1-O-Alkylglycerol vesicles (Algosomes): their formation and characterization.

1-O-alkylglycerols (ALKG) have exhibited several biological activities and a prominent effect on blood-brain barrier permeability. They have markedly improved brain uptake of cancerostatic agents. Since ALKG are amphiphilic, we explored their tendency to assemble into bilayer vesicles, which can be applied as carriers for drugs. Vesicles (Algosomes) were formed by film hydration method using ALKG (tetra-, penta-, hexa-, hepta-, octa- or nona-decylglycerols) in combination with cholesterol (CHOL) and dicetyl phosphate (DCP) (1-O-alkylglycerol:CHOL:DCP in 45:45:10 molar ratio). On microscopic examination, the algosomes were found to be conspicuously spherical and the dispersion was a mixture of multi-lamellar and small-unilamellar vesicles. Phase transition temperatures of 1-O-hexadecylglycerol (HXDG) and CHOL mixtures were tested by differential scanning calorimetry (DSC). The changes in phase transition temperatures indicate the vesicle forming tendency of ALKG in presence of CHOL. Alkyl chain length dependent variations in vesicle size, zeta-potential (ZP) and capture volume (CV) could not be observed. Vesicles of 1-O-tetradecylglycerol (TTDG) showed improvement in CV with increase in CHOL content from 15 to 55 mol%. However the vesicle size decreased. On challenging algosomes with hypertonic salt solution [potassium iodide (KI) in water], vesicle size decreased and thus algosomes were found to be osmotically sensitive. Algosome dispersions on addition of higher concentrations of KI (40-100 mM) brought about increases in vesicle size and at concentrations 60 mM and above showed aggregation. All vesicular dispersions were stable for only a few days.

Water soluble fractions of rose-scented geranium (Pelargonium species) essential oil.

The essential oil of rose-scented geranium (Pelargonium species, family: Geraniaceae) obtained through steam or water plus steam distillation of shoot biomass is extensively used in the fragrance industry and in aromatherapy. During distillation, a part of the essential oil becomes dissolved in the distillation water (hydrosol) and is lost as this hydrosol is discarded. In this investigation, hydrosol was shaken for 30 min with hexane (10:1 proportion) and the hexane was distilled to yield 'secondary' or 'recovered' essential oil. The chemical composition of secondary oil was compared with that of 'primary' oil (obtained directly by distilling shoot biomass of the crop). Primary oil accounted for 93.0% and secondary oil 7.0% of the total oil yield (100.2 ml from 100 kg green shoot biomass). Fifty-two compounds making up 95.0-98.5% of the primary and the secondary oils were characterized through gas chromatography (GC) and gas chromatography-mass spectroscopy (GC--MS). Primary oil was richer in hydrocarbons (8.5-9.4%), citronellyl formate (6.2-7.5%), geranyl formate (4.1-4.7%), citronellyl propionate (1.0-1.2%), alpha-selinene (1.8-2.2%), citronellyl butyrate (1.4-1.7%), 10-epi-gamma-eudesmol (4.9-5.5%) and geranyl tiglate (1.8-2.1%). Recovered oil was richer in organoleptically important oxygenated compounds (88.9-93.9%), commercial rhodinol fraction (74.3-81.2%), sabinene (0.4-6.2%), cis-linool oxide (furanoid) (0.7-1.2%), linalool (14.7-19.6%), alpha-terpineol (3.3-4.8%) and geraniol (21.3-38.4%). Blending of recovered oil with primary oil is recommended to enhance the olfactory value of the primary oil of rose-scented geranium. Distillation water stripped of essential oil through hexane extraction can be recycled for distilling the next batch of rose-scented geranium.

Extreme lateral approach to ventral and ventrolaterally situated lesions of the lower brainstem and upper cervical cord.

Lesions situated ventrally and ventrolaterally to the lower brainstem and upper cervical spinal cord test the skills of neurosurgeons. We present our experience with eight such patients who underwent the extreme lateral craniocervical approach. The pathologies encountered include three distal vertebral aneurysms, one prepontine epidermoid, one anterior foramen magnum meningioma, and three high cervical dumbbell neurofibromas. All lesions were treated effectively. Postoperatively, the patients improved significantly. Complications included transient lower cranial nerve paresis in three patients, meningitis in one patient, and a pseudomeningocele in two patients. All complications improved with therapy. We conclude that the extreme lateral approach offers excellent visualization and access with minimal neural retraction for treating these difficult lesions.

Pharmacokinetics of zidovudine following intravenous bolus administration of a novel niosome preparation devoid of cholesterol.

A novel niosome preparation composed of nonionic surfactants, polyglyceryl-3-diisostearate and polysorbate-80, bilayers stabilized by myristyl alcohol instead of cholesterol was developed. Polyglyceryl-3-diisostearate, myristyl alcohol and polysorbate-80 were in 1:2:1 molar ratio in which 85% zidovudine (3'-azido-3'-deoxythymidine, azidothymidine, AZT, CAS 30516-87-1) was found to be encapsulated in aqueous core. Pharmacokinetic and tissue distribution studies were conducted on this niosome preparation using rabbits and albino rats, respectively, as animal models. AZT levels in rabbit serum were higher following application of niosomal AZT than with AZT solution. Such levels were maintained for prolonged time. T1/2 increased, clearance became slow and as a result AUC and AUMC increased and consequently MRT increased following niosomal AZT treatment. Tissue distribution studies on albino rats also confirmed higher concentration and slower decline of serum levels of AZT due to niosomal AZT. In addition niosomal AZT escaped uptake by reticuloendothelial tissues (liver, spleen, and kidney). Invitro release of AZT from niosomes was slow, about 20% releasing in 18 h. The prolonged AZT levels in rabbit serum following the treatment with niosomal AZT appear to be due to the combined effect of slow invivo release and avoidance of extravascular distribution. Though this preparation seems to maintain AZT levels in serum for a prolonged time, its therapeutic efficacy cannot be claimed as the present method estimates total AZT in the preparation and not free AZT. Further no specific experiments were conducted to substantiate its therapeutic effect.

Vertebral artery aneurysms.

Vertebral artery (VA) aneurysms are rare. We present our experience with three cases of VA aneurysms. Two aneurysms were located close to the origin of basilar artery while the third patient had a giant posterior inferior cerebellar artery aneurysm. These aneurysms were operated by the far lateral inferior suboccipital approach with good results.

Lack of pharmacokinetic interaction between sumatriptan and naproxen.

Sumatriptan is a 5HT1D agonist used in the treatment of migraine. Nonsteroidal anti-inflammatory drugs, beta-blockers, and calcium channel-blocking antagonists are used in the prophylaxis of migraine. Hence, there is a need to investigate the interaction of these prophylactic drugs with sumatriptan. The interaction of sumatriptan with propranolol, flunarizine, pizotifen, and butorphanol were reported earlier. Naproxen is shown to be effective in prophylactic treatment of migraine. In this study, the authors have investigated the circadian rhythm effect of naproxen on the pharmacokinetics of sumatriptan at 1000 and 2200 hours. Twelve healthy volunteers were treated with 100 mg sumatriptan succinate either alone or along with 500 mg naproxen orally at either 1000 or 2200 hours in a randomized Latin square design with a washout period of 10 days. Serum samples were collected at predetermined time intervals and analyzed for unchanged sumatriptan by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by using model-independent methods. Naproxen had no statistically significant (p > 0.05) effect on any pharmacokinetic parameters of sumatriptan both at 1000 and 2200 hours treatment. The results of this study suggest that no alteration in the sumatriptan dosage will be necessary for migraine patients taking naproxen prophylactic therapy.

Biliary lipid peroxidation products in gallbladder cancer: increased peroxidation or biliary stasis?

Gallbladder cancer is a common malignancy among women in India. The aetiology of gallbladder carcinoma is still obscure and although numerous factors have been implicated, none has stood the test of time. This study was carried out to evaluate the role of lipid peroxidation product 4-hydroxynonenal (HNE) in gallbladder carcinogenesis. High-performance liquid chromatography (HPLC) analysis was carried out in 30 bile samples obtained during laparotomy from patients with gallbladder cancer (n = 10), cholelithiasis (n = 10) and age- and sex-matched controls (n = 10). A significantly high concentration of HNE and lower concentration of biliary pH and electrolyte was observed in patients with carcinoma of the gallbladder compared with controls and patients with cholelithiasis. A significant correlation was also observed between biliary Na+ and K+ (r = 0.72), biliary Ca2+ and Na+ (r = 0.69) among controls. However, there was no correlation between HNE, electrolytes and pH among cancer patients. An increased concentration of biliary HNE and decreased concentration of electrolytes suggest biliary stasis rather then increased peroxidation in cancer patients.