Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme.

BACKGROUND: To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation. METHODS: A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months. RESULTS: Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status. CONCLUSIONS: Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.

[Torticollis and seizures due to neuroborreliosis in a child]. / Een kind met torticollis en insulten bij neuroborreliose.

BACKGROUND: In children, neuroborreliosis often manifests itself as cranial neuritis (particularly facial palsy) or aseptic meningitis. Presentation with torticollis and simple partial seizures resulting from diffuse leptomeningeal inflammation is rare. CASE DESCRIPTION: A seven-year-old boy who had developed torticollis and partial seizures, lost weight and was complaining of tiredness was seen by a paediatric neurologist. A brain and spinal cord MRI showed diffuse leptomeningeal enhancement, in combination with a hyperintense cervical cord lesion. Laboratory testing of serum and cerebrospinal fluid confirmed the diagnosis of neuroborreliosis. The boy was treated with intravenous ceftriaxone for 30 days and made a full recovery. CONCLUSION: As illustrated by this case neuroborreliosis can manifest itself atypically with torticollis, seizures and diffuse leptomeningeal enhancement due to inflammation. If there is leptomeningeal enhancement on MRI then neuroborreliosis should be included in the differential diagnosis. In childhood neuroborreliosis can be successfully treated and the prognosis is good.

[Reversible thrombocytopenia and polyneuropathy: the pleiotropic aspects of hypothyroidism]. / Reversibele trombocytopenie en polyneuropathie: de pleiotrope aspecten van hypothyreoïdie.

Although the relationship between hyperthyroidism and thrombocytopenia is well documented, the relationship between hypothyroidism and thrombocytopenia is less well known. We describe a 69-year-old man with severe hypothyroidism, mild thrombocytopenia and sensorimotor axonal polyneuropathy. After thyroid hormone replacement therapy, he became euthyroid and his platelet count normalized over a period of three months. The thrombocytopenia may have been due to an immunomodulatory effect of thyroid-stimulating hormone (TSH). His neurological complaints disappeared and even though electromyography still showed signs of axonal polyneuropathy, nerve conduction velocities normalized and he had signs of re-innervation. Our case clearly demonstrates that hypothyroidism is a heterogeneous disease. As symptoms may be reversible with thyroid hormone replacement therapy, it should not be overlooked.

Efficacy of anti-epileptic drugs in patients with gliomas and seizures.

Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000-2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.6% had a low-grade glioma, 53.6% a high-grade glioma, and 22.8% belonged to a mixed group existing of ependymoma, meningioma, and brain metastasis. Epilepsy as the presenting sign was more frequent in low-grade vs. high-grade gliomas (69.7 vs. 52%, P = 0.087), and a total of 75.8% of patients developed seizures with low-grade and of 80.0% with high-grade gliomas. Of all 99 patients with seizures, 80.1% received valproic acid (VPA) as first choice, and either levetiracetam (LEV), carbamazepine (CBZ) or lamotrigine (LMT) as the most frequent next choice. Patients treated with a combination of VPA and LEV showed the highest percentage of responders (81.5%), with a decline in seizure frequency of more than two categories in 55.6% and seizure freedom in 59%. No correlation was found between the use of VPA and survival. A combination of VPA and LEV seems effective, if seizure control cannot be achieved by VPA alone. This indicates that adding levetiracetam may be preferable over sequential trials of AED monotherapy in treatment-resistant seizures in patients with brain tumors.

Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management.

Epilepsy is common in patients with brain tumours and can substantially affect daily life, even if the tumour is under control. Several factors affect the mechanism of seizures in brain tumours, including tumour type, tumour location, and peritumoral and genetic changes. Prophylactic use of antiepileptic drugs is not recommended, and potential interactions between antiepileptic and chemotherapeutic agents persuades against the use of enzyme-inducing antiepileptic drugs. Multidrug-resistance proteins prevent the access of antiepileptic drugs into brain parenchyma, which partly explains why seizures are frequently refractory to treatment. Lamotrigine, valproic acid, and topiramate are first-line treatments of choice; if insufficient, add-on treatment with levetiracetam or gabapentin can be recommended. On the basis of clinical studies, we prefer to start treatment with valproic acid, adding levetiracetam if necessary. Risks of cognitive side-effects with antiepileptic drugs can add to previous damage by surgery or radiotherapy, and therefore appropriate choice and dose of antiepileptic drug is crucial.

Optimizing therapy of seizures in patients with brain tumors.

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with structural brain lesions, and a role for multidrug-resistance proteins has been suggested. The medical treatment of epilepsy in brain tumor patients has mainly been studied retrospectively, and the optimal management of seizures with antiepileptic drugs (AEDs) is unclear. Enzyme-inducing anticonvulsants are generally not recommended because they can lead to insufficient serum levels of concomitantly administered chemotherapeutic drugs. Although valproic acid is an enzyme inhibitor and may therefore lead to toxic levels of simultaneously administered chemotherapeutic agents, this does not appear to be a major problem in patients with brain tumors. Preliminary observations of add-on treatment with the AEDs levetiracetam or gabapentin suggest that these non-enzyme-inducing AEDs can be useful for control of seizures in patients with brain tumors. Conversely, prophylactic use of AEDs in brain tumor patients is generally not recommended.

Supratentorial arterial ischemic stroke following cerebellar tumor resection in two children.

We describe two children who developed ischemic strokes in the territory of the middle cerebral artery, one 7 days and one 11 days after resection of a cerebellar tumor. In the first child, another infarction occurred in the territory of the contralateral middle cerebral artery 5 days after the first stroke. No specific cause or underlying risk factor other than the surgical procedure was found. The subacute clinical course at stroke onset resembled that of the 'posterior fossa syndrome', suggesting a common underlying mechanism.

Optimal seizure management in brain tumor patients.

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with a structural brain lesion, and a role for multidrug resistance proteins has been suggested. Until now, the medical treatment of epilepsy in brain tumor patients has only been studied retrospectively. Therefore, the optimal seizure management by antiepileptic drugs (AEDs) in this patient category is essentially unsure. Choices depend on the outcome of retrospective studies, a few nonrandomized series, extrapolation from other studies in symptomatic epilepsy, and anticipated interactions, most notably between AEDs and anticancer agents. The newly developed AEDs levetiracetam and gabapentin are recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents. The use of prophylactic AEDs in brain tumor patients is disputable and generally not advised.