Treatment of neurocysticercosis: current status and future research needs.

Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies.

Sero-prevalence of Taenia solium cysticercosis and Taenia solium taeniasis in California, USA.

OBJECTIVES: Taenia solium Cysticercosis is a leading cause of epilepsy and neurological disability in the developing world. It is caused by ingestion of the eggs of the tapeworm, T. solium Taeniasis. The prevalence of either T. solium Cysticercosis or T. solium Taeniasis in the United States in populations at risk is poorly understood. The primary objectives of this study are to perform the first study of the sero-prevalence of T. solium Cysticercosis and T. solium Taeniasis in an at-risk community in the USA, specifically rural Southern California; identify T. solium Taeniasis positive individuals, and treat positive individuals for the tapeworm T. solium Taeniasis. METHODS: Community based sero-prevalence study of antibodies to T. solium Cysticercosis and T. solium Taeniasis in 449 subjects living in a federally funded, predominantly Hispanic residential community; and in two migrant farm worker camps in rural Ventura County, California, USA. For this study, fingerstick blood samples were obtained. Serum immunoblots for both T. solium Cysticercosis and T. solium Taeniasis were performed. RESULTS: The sero-prevalence of T. solium Cysticercosis was 1.8% and the sero-prevalence of T. solium Taeniasis by serum immunoblot was 1.1%. Taenia solium Cysticercosis and T. solium Taeniasis antibodies were not detected in children. The sero-prevalence of T. solium Taeniasis was highest in the migrant farm worker community. Handwashing frequency was correlated with T. solium Taeniasis sero-positivity. CONCLUSION: The sero-prevalence of T. solium Cysticercosis and T. solium Taeniasis in this population, as detected by serum immunoblot, approximates the prevalence in some endemic areas of Latin America. Importantly, most patients likely had prior exposure, not active infection. This study establishes for the first time, the relative sero-prevalence of T. solium Cysticercosis and T. solium Taeniasis in at-risk populations in the United States.

Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging.

OBJECTIVE: To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS: We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS: The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS: VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen.

The present clinical trial was undertaken to assess the clinical safety and possible efficacy of administering tamoxifen to patients with recurrent malignant glial tumors at dosages calculated to achieve levels sufficient to inhibit protein kinase C within the tumor cells. Chronic p.o. tamoxifen was administered in very high dosages to 32 patients (20 males and 12 females; age range, 26-75 years; mean, 49 years) with histologically verified malignant glioma [anaplastic astrocytoma (12 patients) or glioblastoma multiforme (20 patients)] who had demonstrated clinical and radiographical progression or recurrence following external beam radiation therapy (and additional chemotherapy in 11; immunotherapy in 2). The dosage of tamoxifen administered was 200 mg/day to males and 160 mg/day to females given in a twice daily schedule. Clinical and radiographical (defined as a greater than 50% decrease in volume of the enhancing lesion volume on magnetic resonance imaging and a decrease in metabolic activity on serial positron emission tomographic scans) response was noted in 8 patients (25%; 4/12 with anaplastic astrocytoma and 4/20 glioblastoma multiforme), with an additional 6 patients (19%) exhibiting stabilization of disease with minimal side effects. Median survival from the time of diagnosis for the entire cohort was 24 months (104 weeks), for the anaplastic astrocytoma group 42.5 months (185 weeks), and for the glioblastoma group 17.4 months (75.5 weeks). From the initiation of tamoxifen, median survival for the entire cohort was 10.1 months (44 weeks), for the anaplastic astrocytoma group 16 months (69 weeks), and for the glioblastoma group 7.2 months (31 weeks). The mean length of follow-up of all patients after initiating tamoxifen was 16 months (69 weeks), while the mean length of follow-up of alive patients is 22.6 months (98 weeks) (range up to 51 months). These data suggest that a subgroup of patients with malignant gliomas respond or stabilize with chronic high-dose tamoxifen therapy. This therapy may represent an alternative or adjuvant to existing chemotherapies for these tumors; further clinical trials are warranted.

Limited efficacy of experimental anti-epileptic drugs in refractory temporal lobe epilepsy: implications for patient management and study recruitment.

Patients with refractory temporal lobe epilepsy (TLE) are commonly recruited for investigational anti-epileptic drug (XAED) studies. However, the long-term outcome of TLE after exposure to XAEDs is poorly documented. In this pilot study, we report the USC Epilepsy Center's experience of 19 patients with TLE enrolled in three XAED trials. The data reinforce that TLE is a drug-resistant epilepsy, and referral of good surgical candidates for surgery rather than XAED trials is more likely to result in remission.

Ventroposterior medial pallidotomy in patients with advanced Parkinson's disease.

In a preliminary study, the effects of ventroposterior medial pallidotomy were evaluated in five patients with advanced Parkinson's disease in whom medical therapy had failed. The mean age was 67.0 +/- 5.6 years, and the mean Hoehn and Yahr stage when "off" was 3.9 +/- 1.3. Three patients received unilateral pallidotomies; two of these received another pallidotomy after 8 weeks. Two other patients received staged bilateral pallidotomies. No significant differences in overall function could be seen before and after the first surgical procedure. All three patients with peak-dose dyskinesias or dystonia had marked contralateral reduction in these symptoms. Ventroposterior medial pallidotomy can ameliorate peak-dose dyskinesias in patients with advanced Parkinson's disease. Overall function improvement is not remarkable.

CSF neuron-specific enolase after methohexital activation during electrocorticography.

We report changes in CSF and serum neuron-specific enolase (NSE) before and after methohexital infusion during electrocorticography in three patients undergoing epilepsy surgery. NSE is a critical enzyme for energy metabolism that accounts for 1.5% of all soluble brain protein and is an accepted marker of neuronal injury. CSF NSE rose three- to fourfold from baseline within 60 minutes after methohexital activation. Serum NSE was unchanged. This report supports evidence that CSF NSE rises acutely after induction of epileptiform activity and suggests that CSF NSE is a marker of seizure activity.

Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen.

Previous work has demonstrated the importance of the Protein Kinase C (PKC) signal transduction system in regulating the growth rate of malignant gliomas in vitro. Tamoxifen inhibits PKC in a minority of malignant gliomas within the micromolar concentration range in vitro, a property distinct from its estrogen receptor blockade effect. Tamoxifen was administered orally in very high dosages to 11 patients (9 males:2 females, age range 26-73, mean 45 years) with malignant gliomas (anaplastic astrocytoma or glioblastoma multiforme) who had failed treatment with external beam radiation therapy (and additional chemotherapy in 2). The dosage administered was estimated to be that necessary to achieve tissue concentrations within the low micromolar range, shown necessary to inhibit PKC in these tumors in vitro, and is approximately 5 times that used for standard antiestrogen therapy. Tumor reduction on radiographic images (MRI and PET [18FdG uptake]) with clinical improvement occurred in 3 patients; halting of tumor progression clinically and radiographically occurred in an additional patient. Of the remaining seven patients, three patients had marked and rapid progression of their disease despite treatment (dead after 3, 4, and 6 months respectively). Complications of treatment included a deep venous thrombosis requiring anticoagulation in one patient, nausea in one patient, and "hot-flashes" in a third patient. Tumor biopsy and measurement of tamoxifen and its active metabolite within the tumor of one patient (non-responder) showed levels within the middle of the in vitro therapeutic range. Follow-up of alive patients ranges from 4-18 months (mean 10 months). These encouraging preliminary results in a minority of these patients suggests some potential for this type of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Compulsive polydipsia following meningioma resection: an epileptic phenomenon? Case report.

The authors report the case of an individual who developed compulsive polydipsia following resection of a left sphenoidal ridge meningioma. The episodic, stereotyped nature of his symptoms, response to treatment, and electroencephalographic and magnetic resonance imaging findings are all highly consistent with temporal lobe-onset epilepsy. The pathophysiology of this underrecognized phenomenon is discussed.

Unruptured intracranial aneurysms: seizures and antiepileptic drug treatment following surgery.

Twenty-one patients operated on for unruptured intracranial aneurysms were studied retrospectively in order to identify the incidence of postoperative seizures, factors predictive of seizures, and the response to discontinuation of antiepileptic drugs. The overall risk of postoperative seizures in initially seizure-free patients was 15.7%. Although seizures were not uncommon, antiepileptic drugs were successfully tapered in most of the patients before 12 months.