Antiepileptics in brain metastases: safety, efficacy and impact on life expectancy.

The aim of the study was to evaluate efficacy, safety and impact on life expectancy of levetiracetam (LEV), oxcarbazepine (OXC) and topiramate (TPM) monotherapy in patients with seizures related to brain metastases. We conducted a prospective observational study on 70 patients with brain metastases. Thirteen patients were excluded because they were in prophylactic therapy with antiepileptics, nine patients did not return to our Center. A total of 48 patients with epilepsy related to brain metastases were enrolled. Patients were treated with LEV, OXC and TPM in monotherapy and followed until their death. Eighteen patients dropped out. Therefore, we followed 30 patients. Mean duration of follow-up was 6.1 months. Upon visiting the patients prior to their death (i.e. last visit preceding the death of the patients), we observed a significant reduction (P < 0.001) in the mean monthly seizure frequency; with 19 patients (63.3%) obtaining complete seizure control in the whole population. A significant improvement of seizure frequency was also observed considering each antiepileptic treatment group separately. Median survival time was similar among the three groups of patients and was similar to Class I of prognostic factors of Radiation Therapy Oncology Group. Logistic regression showed that systemic treatments did not influence the antiepileptics' efficacy on seizure control (P = 0.614). In conclusion, regarding the use of newer antiepileptics in patients with seizures related to brain metastases, our data indicate that LEV, OXC and TPM significantly reduce seizure frequency (independently of systemic treatment), produce few side effects and appear not to affect life expectancy.

Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report.

BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). AIM OF THE STUDY: To evaluate efficacy and tolerability of ZNS as add-on in BTRE. METHODS: We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. RESULTS: Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. CONCLUSIONS: Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds.

Supportive therapy in neuro-oncology.

Patients with cerebral neoplasms often report pain or other kinds of symptoms which, even though not directly connected to the disease itself, can cause complications in the approach to therapy and worsen the quality of life of the patients. The therapies aimed at controlling these kinds of disturbances are referred to as supportive therapies as they do not cure the underlying disease. However, these therapies should not be underestimated, because, by controlling these disturbances, they are able not only to greatly improve the quality of life of the neuro-oncologic patients but also increase their survival. Based on this hypothesis, we will discuss and examine the drugs more frequently used for supportive therapy in neuro-oncologic patients. We assert, in fact, that the desire to offer neuro-oncologic patients better assistance guarantees not only adequate specialized input from the health operators involved, concerning the quality of life and the uniqueness of the 'person-patient', but also the ability to be able to listen to the patients, understand their choices and allow them to express their priorities.

Cerebellar atrophy and monoclonal gammopathy of undetermined significance: a possible correlation?

Central Nervous System involvement in Monoclonal gammopathies of undetermined significance has seldomly been reported and in all the cases a demyelinating disease was found. We report the case of a young man who had been suffering for five years of progressive cerebellar syndrome. MRI showed marked cerebellar vermis atrophy. An IgG lambda monoclonal gammopathy was revealed in the serum. Cerebrospinal fluid examination showed oligoclonal bands and elevated Link-Index. Serologic research for HBV, HCV, HIV, Lues, Rubella, Measles was negative, as also genetic analysis for SCA1, SCA2, SCA3, SCA7 and Friederich's ataxia. Nerve conduction studies were normal. Plasmatic vit.E was low, but treatment with high doses of tocopherol was ineffective. i.v. immunoglobulins and steroids obtained only transient clinical benefits. In conclusion, we hypothesize a pathogenetic role of the IgG in this cerebellar atrophy.

CCNU chemotherapy in adult patients with tumors of the basal ganglia and brain stem.

The present investigation evaluates those few patients of our series with basal ganglia and brain-stem tumor who refused either surgical decompression and biopsy or radiation therapy. Four patients were suffering from tumors of the basal ganglia and three from brain-stem tumors; all the tumors were diagnosed by classical neuroradiological investigations and computerized tomography. The patients were given CCNU by mouth, 13 mg/sq m every 6 weeks. No toxicity was recorded. Mean survival was 19 weeks for patients with basal ganglia tumors and 48 weeks for those with brain-stem tumors. All patients were evaluated with respect to the quality of survival. Results were compared with those obtained in a control group of patients who received methylprednisolone therapy only.

The pronator teres syndrome. Clinical and electrophysiological features in six surgically verified cases.

Six surgically verified cases of pronator teres syndrome are reported. The anatomy of the median nerve at the upper third of the forearm, the relationships between the nerve and the pronator teres muscle and the serial innervation of the muscles of the forearm supplied by the n. medians are described. Clinical and electrophysiological features are reported in detail and their contribution in diagnosing the lesion is discussed.

Entrapment neuropathy of the dorsal cutaneous nerve of the hand.

One case of entrapment neuropathy of the dorsal cutaneous nerve of the hand is presented. The anatomy of the region suggests the nerve may be entrapped when it crosses the ulna behind the tendon of flexor carpi ulnaris. The electrophysiological findings and the good results following a local treatment with steroids are reported.

Pseudoclaudication in lumbar disc protrusions. Contribution in understanding the etio-pathogenetic factors of the syndrome and surgical results in eight cases.

Eight cases of pseudoclaudication in patients with herniated lumbar discs are reported. Clinical features and variations in clinical patterns are briefly described. The hypotheses concerning the mechanisms causing pseudoclaudication, formulated by some authors, are discussed. It is suggested that this particular syndrome might be related to an arrangement of the spinal circulation with one lumbar or sacral accessory artery playing an important role in supplying the lower portion of the spinal cord.

Compression of the palmar cutaneous nerve by ganglions of the wrist.

Two cases of compression of the palmar cutaneous nerve by ganglion of the wrist are presented. The anatomy of the region, compression factors, mechanism and clinical features are discussed. Timely surgical removal of compression is recommended.

The effect of brain radiotherapy on the P3 component of ERP's.

Nine patients with lung cancer without brain metastasis were studied pre and post brain prophylactic radiotherapy (30 Gy) to verify the effect of radiation on the cognitive processes. The P3 component of event-related potentials was used in this study. The latencies pre and post-radiation were compared and a significant delay (p less than 0.01) was detected in patients after treatment. These results suggest that brain radiotherapy may produce a cognitive impairment, as reported by many Authors.

Early somatosensory evoked potentials in supratentorial brain tumors.

Early somatosensory evoked potentials were recorded in 33 patients with supratentorial brain tumors (9 benign tumors, 17 glioblastomas and 7 metastases). All the cases were studied with CT scan and all but 2 were surgically explored and histologically classified. Evoked potentials were statistically analyzed regarding the nature and site of the tumors. The temporal malignant tumors showed the most significant alterations in latencies, particularly for waves P25, N34 and P44.

Remarks concerning 102 watersoluble contrast ventriculographies.

The Authors report their experience in using water-soluble contrast medium in ventriculographies having carried out 102 ventriculographies partly with Dimer X and partly with "Uromiro 300". Their conclusions are practically similar to those already reported by the many Authors who have written on this subject: 1) facility of examination particularly in urgent cases; 2) excellent neuroradiological definition of the cases; 3) possibility of obtaining a selective ventriculography; 4) indication especially in space-occupying lesions of the posterior cranial contrast medium; 6) possibility of reducing complication rate by carefully carrying out the examination and by avoiding the use of excessive quantities of contrast. In particular the Authors describe some useful methods for obtaining better technical results from the examination and reducing the complication rate.

Lonidamine in the combined treatment of malignant gliomas. A randomized study.

Lonidamine (LND) is a drug that interferes with energy metabolism of cancer cells, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK). In such way LND could impair energy-requiring processes, as recovery from potentially lethal damage, induced by radiation treatment and by some cytotoxic drugs. A randomized study started in November 1983, to evaluate the efficacy of LND in association with radiotherapy as first line treatment in malignant gliomas, after surgical procedure. LND was also used in association with Lomustine (CCNU) at the moment of documented clinical and neuroradiological recurrence. At the present time 60 patients entered the study, and 47 are evaluable. Present preliminary results are not statistically significant, however indicate that LND tends to prolong the median survival time and the rate of one year survivors.

A pilot study on the relation between cisplatin neuropathy and vitamin E.

Peripheral sensory neuropathy is the main non-hematological side-effect related to cisplatin chemotherapy. The strong similarity between clinical and neuropathological aspects in peripheral neuropathy induced by cisplatin and neurologic syndromes due to vitamin E deficiency, prompted us to investigate the relationship between cisplatin neuropathy and plasmatic level of vitamin E (alpha-tocopherol). We measured vitamin E in the plasma of 5 patients (Group 1) which developed severe neurotoxicity after cisplatin treatment and in another group of 5 patients (Group 2) we analyzed the plasmatic level of vitamin E before and after 2 or 4 cycles of cisplatin treatment. The results showed that the patients of group 1 presented low plasmatic levels of vitamin E and that the patients of group 2 presented significantly lower levels of vitamin E after 2 or 4 cycles of cisplatin than before treatment. Our preliminary data suggest that an inadequate amount of the antioxidant vitamin E due to cisplatin treatment could be responsible of the peripheral nerve damage induced by free-radicals. Given the lack of toxicity of vitamin E, we need to systematically assess the possible neuroprotective role of vitamin E supplementation in patients treated with cisplatin chemotherapy.

Demyelinating disease in monoclonal gammopathy of undetermined significance.

We describe herein the case of a 57 year old man who, over the last five years, has presented ataxic and spastic gait on the right side, a reduction in fine motor movement of the fingers mainly on the right side, superficial right side brachiocrural hypoesthesia and a marked dysarthria associated with internuclear ophthalmoplegia. The neurological picture, after an initial progressive worsening which lasted some months, remained relatively stable over the years. Repeated magnetic resonance imaging (MRI) of the brain and spinal cord documented the presence of demyelinating plaques spread in the white matter of the periventricular region and the semioval centres, and a right side paramedian plaque at the C4-C5 level, none of which were in the active phase. Oligoclonal bands were revealed in the cerebrospinal fluid (CSF). Monoclonal IgM/lambda gammopathy with anti-myelin and anti-nucleo reactivity, found with serum immunofixation, were confirmed several times in successive annual controls, not associated to myeloproliferative pathology. The lack of progression in the clinical picture would seem to contradict the diagnosis of late Multiple Sclerosis. The presence of antibody activity against the myelin might support the hypothesis of a pathogenetic role of the immunoglobulins at the onset of the demyelinating disease in this patient. However, in the end, there is the possibility of casual association with a poorly functioning immune system connected to age.

Epilepsy and gliomas: incidence and treatment in 119 patients.

One hundred and nineteen consecutive patients affected by supratentorial gliomas were studied in order to determine the incidence of seizure at diagnosis, the occurrence of subsequent seizures and the efficacy of anticonvulsant treatment. The overall incidence of seizures as presentation symptom was 52% (62 patients). Preoperative seizures were present in 83% of patients affected by low-grade astrocytoma, in 46% of patients affected by anaplastic astrocytoma and in 36% of patients affected by glioblastoma. Postoperative epilepsy refractory to anticonvulsant treatment significantly related to low-grade histology and presence of preoperative seizures occurred in 48% of patients. Adverse effects associated with anticonvulsants were observed in 33.8% of patients treated with phenobarbital, 14.3% in the group treated with carbamazepine and 12% of patients treated with vigabatrin. We conclude that anticonvulsant treatment in patients affected by gliomas is often ineffective and prophylactic treatment should be discontinued after 6 months in patients preoperative seizures free. In patients with high risk of seizures antiepileptic drugs with good efficacy and lower incidence of adverse effects than phenobarbital are indicated.

Entrapment neuropathies of the median nerve at and above the elbow.

Three surgically verified cases of median nerve entrapment at and above the elbow are reported: one involved a compression of the nerve beneath the Struthers ligament in absence of supracondylar bony spur, and two concerned a compression beneath the lacertus fibrosus bicipitis (aponeurosis musculi bicipitalis brachii). Of the two latter cases, the first entrapment was caused by a hematome and the second the nerve was found to be entrapped between the lactertus and an underlying hypertrophic brachial muscle. The compression mechanisms and clinical and electromyographic findings are presented.