Clinical Neuroscience

[The role of zonisamide in the management of pediatric partial epilepsy]

ROSDY Beáta, KOLLÁR Katalin, MÓSER Judit, MELLÁR Mónika

JULY 30, 2016

Clinical Neuroscience - 2016;69(07-08)


[In our review we discuss the group of approved antiepileptic drugs for children in Hungary. We cite the results of the review conducted by the International League Against Epilepsy on antiepileptic drug efficacy and effectiveness as initial monotherapy for newly diagnosed epileptic seizures and syndromes in pediatric age group. 25% of pediatric epilepsy is therapy resistant, so we further need new drugs, which must be investigated according to the rules of the European Medicine Agency. The ethical dilemmas of childhood drug studies lead to the situation that the new antiepileptic drugs, approved as monotherapy in adult epilepsies, are in the majority just in add-on regimen tested in pediatric patients. As clinicians we appreciate open label extension safety studies. An old-new antiepileptic drug in Europe is zonisamide. Though it was approved for first line monotherapy in pediatric and adult patients with partial and generalised epilepsy in 1989 in Japan, the European Medicine Agency licensed its use as adjunctive therapy in children aged 6 years or older with partial seizures (with or without secondary generalisation) just in 2013. The results of the openlabel extension study appeared in 2014. The mean dose received was 7.5 mg/kg/day. During the open label phase 11% of the patients achieved seizure freedom and it was maintained throughout the study. The drug was generally well tolerated. The most frequently reported treatment-related adverse events were decreased weight (6%), decreased appetite (4%), and headache (2%). No new or unexpected side effects emerged. In conclusion oral zonisamide as adjunctive therapy in pediatric patients aged 6-17 years with partial seizures demonstrated an acceptable safety and tolerability profile and efficacy over a period at least 1 year. So it is a good treatment option in this population.]



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Clinical Neuroscience

Association of anterior thoracic meningocele and azygos lobe of the lung

DENIZ Ersay Fatih, SENAYLI Atilla, BICAKCI Ünal

Here we report an anterior thoracic meningocele case. Twoyears- old female patient was presented with kyphosis. Azygos lobe of the lung was also demonstrated during radiological studies. Posterolateral thoracotomy incision and extralpeural approach was performed for excision of the anterior meningocele to untether the cord. Although both anomalies are related to faulty embryogenesis and it is well known that faulty embryogenesis may also reveal coexisting abnormalities, we could not speculate a common mechanism for anterior thoracic meningocele and azygos lobe of the lung association.

Clinical Neuroscience

[Meningioma and pregnancy]


[Meningiomas are one of the most frequent primary intracranial tumours, representing one-third of all intracranialneoplasms. The vast majority of meningiomas are histologically benign, but recurrence and progression is quite frequent. They occur usually between the 6th and 7th decade, the female/male ratio is 3:2. Although rare in pregnancy, when occurring, they can cause serious, life-threatening complications due to rapid growth and unfavourable localisation. There are two dominant hypothesis explaining rapid growth in pregnancy: the role of hormonal effects and hemodynamic changes. Several studies tested these theories but none provided unequivocal answer probably because the pathomechanism is complex and multifactorial. We provide an overview of the pathomechanism of meningiomas in pregnancy with emphasis on data obtained by advanced neuropathological, molecular biological, bioinformatic, imaging and epidemiological methods. A better understanding of the processes leading to meningioma development and growth in pregnancy will help us to design personalized therapy and reduce morbidity and mortality.]

Clinical Neuroscience

Syndrome of trephined-underestimated and poorly understood complication after decompressive craniectomy


Decompressive craniectomy (DC) is still a matter of debate, with a numerous complications as expansion of haemorrhagic contusions, external cerebral herniation, subdural hygromas, post-traumatic hydrocephalus (HC). The often overlooked “syndrome of the trephined” (ST) as a delayed complication of DC also known as sinking skin flap sy initially described in 1939.ST is characterised by the neurological changes associated with alteration of the pressure/volume relationship between intracranial pressure (ICP), volume of cerebrospinal fluid (CSF), blood, and brain tissue in patients with large bone defects. This review aims at elucidating the mechanisms responsible for the development of ST, and providing useful tips and red-flag signs for healthcare professionals involved with care of post DC patients. Symptoms identified on time could help to develop appropriate treatment strategies for this suddenly deteriorating, but possible reversible condition. Although the treatment strategy is straightforward, calling for a prompt cranioplasty, the correction of HC through CSF diversion devices might require a lengthy optimisation period. Continuous changes in the setting of the shunting systems or spinal tap might lead to dangerous swinging of the midline structures causing further neurological deterioration. Thus, finding the right balance in terms of clinical management often represents a significant challenge.

Clinical Neuroscience

[Angioneuritic edema in ischaemic stroke patients treated with rt-PA]


[Data of our 254 patients who were treated with rt-PA between 1st of Jan, 2011 and 31st of Dec, 2014 were processed. We focused on angioneurotic oedema as allergic complication of thrombolysis which caused life threatening respiratory obstruction in two cases. We describe these two patients’ history. Out of 254 patients six (2.3%) suffered angioneurotic edema caused respiratory obstruction in two (0.90%) cases. This occurrence is approximately 1.3-5.1% in literature. Five, out of six patients who suffered from angioneurotic oedema, had been treated with ACE inhibitors or ARB before. The role of ACE inhibitors is known in metabolism of bradykinin cascade. Plasmin which present during thrombolysis, precipitates biochemical mechanisms of this potential life threatening complication. Therefore rt-PA alone can be the cause of angioedema, but it can be more frequent together with ACE inhibitors therapy.]

Clinical Neuroscience

[Transthyretin familial amyloid polyneuropathy - three Hungarian cases with rare mutations (His88Arg and Phe33Leu)]

CSILLIK Anita, POZSONYI Zoltán, SOÓS Krisztina, BALOGH István, BODÓ Imre, ARÁNYI Zsuzsanna

[Introduction - Transthyretin familial amyloid polyneuropathy is a rare autosomal dominant progressive systemic disesase of adults caused by endoneural amyloid deposition due to point mutations of the transthyretin gene. It is the most severe form among hereditary polyneuropathies, being fatal within 10 years if left untreated. The disease is underdiagnosed, the late onset forms (above the age of 50) being probably more widespread than previously thought. Early diagnosis is essential as the early introduction of causal therapy (tafamidis) slows progression and prolongs survival. Patients - We report here three non-related Hungarian cases of transthyretin familial amyloid polyneuropathy with non- Val30Met mutations (His88Arg in two cases, Phe33Leu in one case). They were all characterized by late-onset, progressive, length-dependent, axonal, sensorimotor polyneuropathy and the simultaneous presentation of severe restrictive cardiomyopathy. In all three cases, clinical and electrophysiological signs of myopathy were also present, suggesting the involvement of skeletal muscles as well. In two cases, high resolution ultrasound of the peripheral nerves was also performed, which showed segmental structural alterations (change or loss of fascicular structure) and some increase of echogenicity of the interfascicular epineurium, without substantial enlargement of the nerves. Conclusion - In Hungary, mainly the rare, non-Val30Met mutation forms of transthyretin familial amyloid polyneuropathy are encountered, as in our cases. As opposed to the Val30Met forms, these mutations are characterized by late onset and simultaneous presentation of severe cardiomyopathy. Our report highlights the importance of considering transthyretin familial amyloid polyneuropathy in the differential diagnosis of late-onset, progressive, axonal polyneuropathies of unknown etiology, particularly if associated with cardiac disease.]

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Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]


[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]

Clinical Neuroscience

[The role of zonisamide in the treatment of women with epilepsy]


[The antiepileptic drugs can effect fertility, development of gynecological diseases and occurence of sexual problems. They can cause a number of “cosmetic” problem and also influence the selection of safe contraceptive method. Many antiepileptic drugs can cause congenital malformations or affect the new-born child’s psychomotor and cognitive development, therefore during pregnancy should be treated with extreme caution in women with epilepsy. Most types of epilepsies accompany the patient through their whole life. Women spend almost the third of their lives after menopause and - due to the formation of associated diseases as well - this period is also special. According to the 2013 recommendation of International League Epilepsy (ILAE), zonisamide is one of the first-line antiepileptic drugs in focal epilepsy. In my review I discuss women’s epilepsy in the viewpoint of the application of zonisamid. ]

Clinical Neuroscience

[Our clinical experience with zonisamide in resistant generalized epilepsy syndromes]

KELEMEN Anna, RÁSONYI György, NEUWIRTH Magdolna, BARCS Gábor, SZŰCS Anna, JAKUS Rita, FABÓ Dániel, JUHOS Vera, PÁLFY Beatrix, HALÁSZ Péter

[Purpose - Zonisamide is licensed in the European Union for adjunctive therapy for partial epilepsy, but its efficacy in generalized epilepsy was less explored. Methods - This prospective observational study included 47 patients (mean age 29 years, range 3-50) with different resistant generalized epilepsy syndromes: idiopathic generalized syndromes (IGE) 15 patients, (juvenile myoclonic epilepsy four, absence epilepsy four, myoclonic absence two, unclassified IGE five), progressive myoclonic epilepsy type 1 (PME1) four, severe myoclonic epilepsy of infancy (SMEI) three, borderline SMEI three, Lennox-Gastaut syndrome/secondary generalized epileptic encephalopties 23 patients. All patients were followed up for at least six months. The mean dose given was 367 mg/day (range 100-600 mg/day), the patients received at least one and no more than two concomitant AE. Response was defined as more than 50% seizure reduction or seizure freedom. Results - The best effect was achieved in PME one, all the patients were responders. Myoclonic seizures were reduced 80%, none of the patients had generalized tonic clonic (GTC) seizures. In two of the four patients all other antiepileptics were tapered of (including piracetam), so they were GTC seizure and almost myoclonia free on zonisamide only. Responder rates were in GEFS ± SME 62.5%, in resistant IGE 62.5%, and in epileptic encephalopathies 33.3% patients. Tolerance after initial efficacy developed in six patients. Adverse effects were mild: weight loss, somnolence and confusion were repeatedly reported. Three patients reported cognitive improvement. Conclusion - Clinical benefit of a broad spectrum antiepileptic zonisamide extends across seizure types, ages and epilepsy syndromes. The efficacy in PME proved to be excellent.]