Paraneoplastic Morvan's syndrome following surgical treatment of recurrent thymoma: A case report.

Morvan's syndrome (MoS) is a rare, complex neurological disorder characterized by neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. The majority of MoS cases have a paraneoplastic aetiology, usually occurring prior to the diagnosis of the underlying tumour and showing improvement following its treatment. The present study reports the case of a 35-year-old Caucasian male patient who was diagnosed with stage IVA thymoma. Thymectomy, lung resection, diaphragmatic pleurectomy and pericardio-phrenectomy were performed 6 months after neoadjuvant chemotherapy. The pathological evaluation revealed a type B2-B3 thymoma with focal squamous differentiation. Two years later, the patient underwent new surgical treatment for a local recurrence of the same histological type, and 4 weeks later, the patient presented with complex neurological symptoms compatible with MoS, including neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. Electromyography was compatible with a diagnosis of neuromyotonia. Brain magnetic resonance imaging scan and tests for serum anti-acetylcholine receptor, anti-striated muscle antibodies and anti-30-kDa titin fragment antibodies were all negative, whereas tests for anti-voltage-gated potassium channel (VGKC)-complex antibodies (333.3 pmol/l), anti-leucine-rich glioma inactivated protein 1 and anti-contactin-associated protein-like 2 antibodies were positive. The patient underwent 3 cycles of intravenous administration of immunoglobulins (0.4 g/kg/day for 5 days every 4 weeks) with little clinical and electrophysiological improvement. We speculated that the late onset of the symptoms in the present patient may have been triggered by an increase in the serum level of anti-VGKC antibody, which was caused by the surgery performed for the treatment of recurrent thymoma. To the best of our knowledge, the present report is the first case of MoS associated with this histological type of thymoma uncommonly occurring upon surgical treatment of recurrent thymoma.

The importance of physician-patient relationship for improvement of adherence to long-term therapy: data of survey in a cohort of multiple sclerosis patients with mild and moderate disability.

Patient involvement in the improvement of health care is important for the best long-term treatment outcomes. Our objective is to assess patient satisfaction with offered care service and to identify parameters which influence the adherence to long-term therapy. A prospective single-center study based on the administration of a structured interview to multiple sclerosis (MS) patients attending our MS Centre with mild and moderate disabilities. The interview regarding clinical parameters, quality of life and satisfaction of care service was structured in three parts with multiple-choice answers to close- or open-ended questions. Patient satisfaction was evaluated by the concordance between the level of patient attention and judgment regarding the services offered. The impact of all variables on the adherence to therapy and on the perceived utility of treatment was evaluated. The concordance between patient attention and judgment on health care services resulted statistically significant for almost all parameters. The perceived utility of treatment was significantly correlated to patients feeling confident in the clinical staff, to their perception of being involved in therapeutic decision (p<0.05), and associated to therapy adherence (p=0.0001). In a multivariate model, the adherence to therapy resulted associated to possibility of choosing the physician (p=0.037) and inversely to therapy duration (p=0.001). Our conclusion reveals that, to improve the adherence to long-term therapy and the perceived utility of treatment, a particular attention should be devoted to physician-patient relationship.

Reversible erectile dysfunction in a patient with brain tumor-related epilepsy in therapy with zonisamide in add-on.

INTRODUCTION: Literature data do not report any cases of erectile dysfunction (ED) during treatment with new antiepileptic drugs in patients with brain tumors. AIM: Concerning zonisamide (ZNS) therapy, data on sexual dysfunction are not available either in patients with epilepsy or in patients with brain tumor-related epilepsy. METHODS: Our case study concerns one patient with partial epilepsy associated with oligoastrocytoma in whom reversible ED developed while taking ZNS. He came to our center already having undergone therapy with phenobarbital, oxcarbazepine, phenitoin, and clobazam. Due to the presence of psychomotor slowness and uncontrolled seizures, we substituted phenobarbital with ZNS 200 mg/day. Main Outcome Measures. The main outcome measures were seizure frequency and side effects. RESULTS: During ZNS therapy, we observed beneficial effects on seizure frequency with a notable reduction from 2-3 seizures per day to 2-3 per week. One month after starting therapy with ZNS, the patient complained about ED that disappeared when we suspended the drug. CONCLUSIONS: In the literature on patients with brain tumor-related epilepsy, sexuality is a subject that is often neglected by health-care providers who focus primarily on controlling systemic diseases and maintaining physical comfort. For this reason, the possible impact of antiepileptic therapies on sexuality should be taken into consideration.

Fatal herpetic encephalitis during brain radiotherapy in a cerebral metastasized breast cancer patient.

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality. The pathogenesis underlying the reactivation of latent herpes simplex virus (HSV) remains undefined. We present the case of a 55-year-old female who developed HSE type 1 during brain irradiation and antioedematous dexamethasone treatment for leptomeningeal metastasized breast tumor with epileptic seizures. During the radiotherapy (RT), after a total of 32 Gray administrated in 16 fractions, our patient developed cognitive impairment and partial epileptic status without fever. Two days later the patient's clinical conditions had deteriorated and high fever manifested. A diagnosis of HSE type 1 was made by a positive cerebrospinal fluid polymerase chain reaction. Antiviral therapy with high doses of acyclovir was practiced for four weeks but the comatose state persisted. The patient died 59 days after the last RT fraction. The temporal relationship of RT to the occurrence of HSE suggests that cranial irradiation may play a role in the reactivation of latent HSV. Although antiviral therapy resistance is infrequent in immunocompetent patients, it is one of the main problems in immunocompromized patients.

Bilateral whirlbone necrosis in a young multiple sclerosis patient.

A case of avascular necrosis of whirlbone in a young man affected by multiple sclerosis and treated with high doses of corticosteroids is described. The authors discuss the causes of this collateral effect underlining the risks of underevaluating the symptoms.

Sexual dysfunction following surgery for rectal cancer - a clinical and neurophysiological study.

BACKGROUND: Sexual dysfunction following surgery for rectal cancer may be frequent and often severe. The aim of the present study is to evaluate the occurrence of this complication from both a clinical point of view and by means of neurophysiological tests. METHODS: We studied a group of 57 patients submitted to rectal resection for adenocarcinoma. All the patients underwent neurological, psychological and the following neurophysiological tests: sacral reflex (SR), pudendal somatosensory evoked potentials (PEPs), motor evoked potential (MEPs) and sympathetic skin responses (SSRs). The results were compared with a control group of 67 rectal cancer patients studied before surgery. Only 10 of these patients could be studied both pre- and postoperatively. 10 patients submitted to high dose preoperative chemoradiation were studied to evaluate the effect of this treatment on sexual function. Statistical analysis was performed by means of the two-tailed Student's t test for paired observations and k concordance test. RESULTS: 59.6% of patients operated reported sexual dysfunction, while this symptom occurred in 16.4% in the control group. Moreover, a significantly higher rate of alterations of the neurophysiological tests and longer mean latencies of the SR, PEPs, MEPs and SSRs were observed in the patients who had undergone resection. In the 10 patients studied both pre and post-surgery impotence occurred in 6 of them and the mean latencies of SSRs were longer after operation. In the 10 patients studied pre and post chemoradiation impotence occurred in 1 patient only, showing the mild effect of these treatments on sexual function. CONCLUSION: Patients operated showed severe sexual dysfunctions. The neurophysiological test may be a useful tool to investigate this complication. The neurological damage could be monitored to decide the rehabilitation strategy.

The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine.

BACKGROUND: Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. METHODS: We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. RESULTS: Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. CONCLUSION: This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population.

Quality of life and seizure control in patients with brain tumor-related epilepsy treated with levetiracetam monotherapy: preliminary data of an open-label study.

The aim of this pilot study was to investigate the effects of levetiracetam monotherapy on seizure control, quality of life and neurocognitive performance in patients with brain tumor-related epilepsy. We present here preliminary data from 18 patients with follow-up of 6 months. We evaluated seizure frequency at baseline. We used administered Mini Mental State Examination (MMSE), Karnofsky Performance Status (KPS), Barthel index (BI), QOLIE 31P (V2), EORTC QLQ-C30 and Adverse Events Profile. After 6 months, 16 patients were seizure free (88.9%), 2 (11.1%) had reduction in seizure frequency >50%. Compared to baseline, we observed a worsening of performance (KPS p = 0.011; BI = 0.008) and global lower cognitive performance (MMSE p = 0.011); distress related to seizure frequency (p = 0.003) and medication effects (p = 0.046) were significantly lower. Levetiracetam caused mild and reversible side effects. These preliminary data on LEV monotherapy in patients with brain tumor-related epilepsy show that this antiepileptic drug is efficacious and well tolerated.

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation.

BACKGROUND: In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m(2) weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. METHODS: 40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m(2) to 100 mg/m(2). Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients. RESULTS: Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine. CONCLUSION: Low-dose fotemustine at 65-75 mg/m(2) (induction phase) followed by 75-85 mg/m(2) (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

End of life issues in brain tumor patients.

Despite aggressive antitumor treatment, the prognosis of brain tumor (BT) patients remains poor. In the last stage of disease, BT patients present severe symptoms due to the growing tumor or to treatment side-effects, which require adequate palliative management and supportive therapy. However, studies specifically addressing palliative care and end-of-life (EoL) issues in BT patients are lacking. This study explores symptoms experienced by BT patients in the last weeks of disease and EoL issues observed in a population of brain tumor patients followed at home until death by a neuro-oncological home care palliative unit set up in our Institution in 2000. From October 2000 to December 2005, 324 patients affected by brain tumor and discharged from our Institution were enrolled in a comprehensive program of neuro-oncological home care supported by the Regional Health System. Out of 324 patients enrolled in the home care program, 260 patients died of which 169 (65%) were assisted at home until the end of life and have been included in this study. Clinical symptoms, palliative treatments and EoL treatment decisions were collected from home clinical records. Among the 169 patients assisted at home until death, the most frequent symptoms observed in the last four weeks of life were: epilepsy 30%, headache 36%, drowsiness 85%, dysphagia 85%, death rattle 12%, agitation and delirium 15%. Palliative management of brain tumor patients requires a multidisciplinary approach performed by a well trained neuro-oncology team. Development of home care models of assistance may represent an alternative to in-hospital care for the management of patients dying of brain tumor and may improve the quality of end-of-life care.

Temozolomide treatment does not affect topiramate and oxcarbazepine plasma concentrations in chronically treated patients with brain tumor-related epilepsy.

OBJECTIVE: Medical management of brain tumor-related epilepsy is complicated by interactions between antiepileptic and chemotherapeutic drugs. We studied the effect of temozolomide therapy on the disposition of the new antiepileptic drugs topiramate (TPM) or oxcarbazepine (OXC). METHODS: Fifteen patients chronically treated with TPM or OXC in monotherapy starting a chemotherapeutic treatment with temozolomide were enrolled in the study, of which ten were available for the final analyses. Blood samples were collected before temozolomide treatment (T(0)), at its end (T(7)) and after further 1-3 weeks (T(14)-T(28)). For each patient, more than one treatment cycle was studied. Topiramate and OXC mono-10-hydroxy derivative (MHD) plasma concentrations were determined by hplc coupled with ion spray mass spectrometer (TPM) or ultraviolet (MHD) detection. RESULTS: Mean TPM concentrations were 5.4 +/- 2.4 microg/ml at T(0) vs. 5.5 +/- 2.4 microg/ml at T(7) (n = 14), and 5.4 +/- 2.4 microg/ml at T(0) vs. 5.6 +/- 2.8 microg/ml at T(14)-T(28) (n = 14). Mean MHD concentrations were 16.4 +/- 7.6 microg at T(0) vs. 18.5 +/- 9.0 microg/ml at T(7) (n = 5), and 16.8 +/- 7.0 microg/ml at T(0) vs. 18.0 +/- 8.7 microg/ml at T(14)-T(28) (n = 8) (all comparisons not statistically significant; Student's t-test for paired samples). CONCLUSION: Temozolomide treatment did not affect TPM plasma concentrations in chronically treated patients. Data for MHD in OXC-treated patients were similar, but, due to the small sample size, results should be interpreted cautiously.These findings confirm that TPM (and possibly OXC) are a reasonable choice of antiepileptic drug in patients with brain tumor-related epilepsy.

Peripheral neurotoxicity of weekly paclitaxel chemotherapy: a schedule or a dose issue?

PURPOSE: The rationale for intensification strategies is that more frequent exposure to chemotherapeutics could enhance antitumor activity. Several trials investigated weekly paclitaxel administration, but there are no clear data concerning peripheral neurotoxicity. The aim of this study was to assess the incidence of peripheral neurotoxicity in patients affected by advanced breast cancer treated with weekly paclitaxel. PATIENTS AND METHODS: Neurotoxicity was assessed with neurologic and neurophysiologic evaluation before treatment and after 12 weeks and 24 weeks. A total neurotoxicity score was assigned to each patient on the basis of neurophysiologic and neuropathic signs and symptom changes. Seventeen patients entered the study. RESULTS: After 12 weeks of treatment, 71% showed moderate clinical and/or neurophysiologic signs of neurotoxicity; after 24 weeks, the incidence of neurotoxicity increased to 96%. Sural amplitude at the 24-weeks examination significantly decreased from basal mean value (13.5 microv, standard deviation [SD] 6 microv vs. 7 microv, SD 5.9 microv, respectively; P = 0.01), whereas median sensory amplitude decreased after 24 weeks from 10.3 microv, SD 6.2 microv to 4.9 microv, SD 3.8 microv (P = 0.001). In a subset of 11 patients, we obtained a follow-up examination after 6 months from the end of treatment. In all patients, examined signs and symptoms of neurotoxicity improved with recovery of subjective neuropathic symptoms and neurophysiologic findings. CONCLUSION: Our results demonstrate, in a little population of patients evaluated with a comprehensive neurologic assessment, that weekly paclitaxel is related to a very high incidence of peripheral neurotoxicity. Follow-up data obtained in a subset of patients indicate that peripheral neurotoxicity is reversible.

Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up.

Oxaliplatin (L-OHP) has become a standard treatment for advanced colorectal cancer and a valid option for patients in the adjuvant setting. Compared with cisplatin, L-OHP has no renal toxicity, only mild hematological and gastrointestinal toxicity, while neurotoxicity is the limiting toxicity. This side effect has been described as a transient distal dysesthesia, enhanced by exposure to cold, and as a dose-related cumulative mild sensitive neuropathy. We studied two groups of patients (18 and 13) with advanced colorectal cancer, treated with median cumulative doses of L-OHP 862 mg/m2 and 1,033.5 mg/m2. All the patients had been evaluated previously, during treatment, after discontinuation and after a long follow-up of 5 years to verify the incidence and the characteristics of the neuropathy induced by this antineoplastic agent. The clinical and neurophysiological examinations showed an acute and transient neurotoxicity and a cumulative dose-related sensory neuropathy in nearly all the patients. The reversibility of these effects was studied. Five patients continue to manifest symptoms and signs of neurotoxicity after a long follow-up, indicating persistence of this peculiar type of neuropathy.

Issues related to the pharmacological management of patients with brain tumours and epilepsy.

The patient affected by epilepsy related to brain tumours presents certain features linked to the summation of his cancer-related problems and his epilepsy-related problems. Furthermore, epilepsy in brain tumour patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients due to the increased incidence of pharmacological interactions and adverse effects. Analysis of the data in the literature suggests that it is opportune, when planning antiepileptic therapy in these cases, to choose the new-generation drugs, as these show a lower incidence of pharmacological interactions with the therapies used in brain tumour patients (chemotherapies, radiotherapy and support therapies), have fewer adverse effects, and have less impact on neuropsychological functions, all factors that strongly influence the patient's quality of life. Of the new antiepileptic drugs, the following seem to be promising in the treatment of cancer-related epilepsy: oxcarbazepine, topiramate and levetiracetam (the latter as an add-on therapy). The pharmacokinetic features of these drugs, their effectiveness in controlling seizures, and the reduced incidence of adverse effects make them useful in this particular group of patients.

Levetiracetam therapy in patients with brain tumour and epilepsy.

Epilepsy is a common clinical problem in patients with brain tumours, strongly affecting patients' quality of life. Tumour-related seizures are often difficult to control, and the clinical picture is complicated by frequent interactions between antiepileptic drugs (AEDs) and antineoplastic agents. We studied the safety and efficacy of levetiracetam (LEV), a new AED with a different pharmacological profile from traditional anticonvulsants, in 19 patients (6 females; age range 28-70 years, mean 48 years) with supratentorial gliomas and epilepsy. Seizure types were simple partial in four patients, complex partial in 4, complex partial with secondary generalization in 7, and generalized tonic-clonic in 4. LEV was added to the existing AED treatment on account of persisting seizures, and titrated at dosages of 1,000-3,000 mg/day. Patients were seen at the Outpatient's Centre every 1-3 months, and followed-up for 7-50 months (mean 25 months, median 20 months). At the end of the observation period, nine patients were seizure free (seizure free period ranging from 7 to 33 months, mean 16, median 12) and five patients reported an improvement in seizure-frequency from daily to weekly (n=1) or from weekly to monthly (n=3). Seizure frequency was unmodified in four patients and increased (from monthly to weekly) in one. No LEV-related adverse effects were observed. LEV plasma concentrations monitored in 12 subjects ranged from 11.9 to 82.1 microg/ml. Our preliminary open data indicate that add-on treatment with LEV in patients with brain tumours is safe and appears to be effective in reducing seizure frequency. Controlled studies on larger populations are warranted to confirm these open observations.

Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy.

PURPOSE: The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy. METHODS: Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E. RESULTS: Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone. CONCLUSION: Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.