Neurological comorbidity and epilepsy: implications for treatment

Epilepsy is a chronic condition that may be associated with several other diseases. In these cases, we should consider the following points: (1) antiepileptic drug (AED) treatment may positively or negatively affect comorbid disease, (2) drugs used for treatment of co‐morbid disease may influence seizure threshold, (3) AED toxicity can be affected by a comorbid condition and (4) co‐administration of AEDs with drugs used for treatment of comorbid conditions can be associated with clinically relevant drug–drug interactions. In this article, we discuss problems that are usually encountered when an appropriate AED treatment has to be selected in newly diagnosed epileptic patients who also have (an)other neurological disease(s). Comorbidity of epilepsy with cerebrovascular diseases, dementias, mental retardation, attention deficit and hyperactivity disorder, brain tumours, infections of the CNS, migraine, sleep disturbances (obstructive sleep apnoea syndrome), substance abuse and multiple sclerosis is discussed.

[1]  F. Patti,et al.  Epilepsy and Multiple Sclerosis in Sicily: A Population‐based Study , 2003, Epilepsia.

[2]  Jennie Z. Ma,et al.  Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. , 2004, Archives of general psychiatry.

[3]  J. Pellock,et al.  Treatment of epilepsy in the multiply handicapped. , 2000, Mental retardation and developmental disabilities research reviews.

[4]  B. Malow,et al.  Obstructive sleep apnea is associated with seizure occurrence in older adults with epilepsy , 2007, Neurology.

[5]  Thomas R Kosten,et al.  Novel Approaches to the Treatment of Cocaine Addiction , 2005, CNS drugs.

[6]  S. Sisodiya,et al.  Drug resistance in epilepsy: human epilepsy. , 2002, Novartis Foundation symposium.

[7]  M. A. Mansoor,et al.  Antiepileptic drugs as independent predictors of plasma total homocysteine levels , 2001, Epilepsy Research.

[8]  Z. Ikezawa,et al.  The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations , 2007, The British journal of dermatology.

[9]  C. Vecht,et al.  Interactions between antiepileptic and chemotherapeutic drugs , 2003, The Lancet Neurology.

[10]  Jaroslaw Harezlak,et al.  ADHD and epilepsy in childhood. , 2003, Developmental medicine and child neurology.

[11]  J. Szaflarski,et al.  Incidence of seizures in the acute phase of stroke: A population‐based study , 2008, Epilepsia.

[12]  S. Rosemberg,et al.  Optimizing therapy of seizures in patients with HIV and cysticercosis , 2006, Neurology.

[13]  G. Holmes,et al.  Gabapentin in the treatment of refractory partial epilepsy in children with intellectual disability. , 1998, Journal of intellectual disability research : JIDR.

[14]  M. Tohyama,et al.  Association of human herpesvirus 6 reactivation with the flaring and severity of drug‐induced hypersensitivity syndrome , 2007, The British journal of dermatology.

[15]  M. D. Cano,et al.  [Serum lipids. lipoproteins, and apolipoproteins in adult epileptics treated with carbamazepine, valproic acid, or phenytoin]. , 1998, Revista de neurologia.

[16]  Tracy Glauser,et al.  ILAE Treatment Guidelines: Evidence‐based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes , 2006, Epilepsia.

[17]  V. Bonavita,et al.  Migraine and epilepsy: clinical and pathophysiological relations , 2007, Neurological Sciences.

[18]  M. Sillanpää,et al.  Concurrent Illnesses in Adults with Childhood‐Onset Epilepsy: A Population‐Based 35‐Year Follow‐Up Study , 1996, Epilepsia.

[19]  B. Ehrenberg,et al.  Migraine‐related seizures in adults with epilepsy, with EEG correlation , 1993, Neurology.

[20]  T. Lackner.  Interaction of Dexamethasone with Phenytoin , 1991, Pharmacotherapy.

[21]  C. Marosi,et al.  P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy , 2005, Journal of Neuro-Oncology.

[22]  B. Johnson.  Recent Advances in the Development of Treatments for Alcohol and Cocaine Dependence , 2005, CNS drugs.

[23]  Azeem Majeed,et al.  The Epidemiology of the Comorbidity of Epilepsy in the General Population , 2004, Epilepsia.

[24]  P. Hantson,et al.  How epileptogenic are the recent antibiotics? , 1999, Acta clinica Belgica.

[25]  H. Schultz,et al.  Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy. , 1999, Acta oncologica.

[26]  P. Tariot,et al.  Valproate therapy for agitation in dementia: open-label extension of a double-blind trial. , 2003, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[27]  Josemir W Sander,et al.  Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[28]  M. Maschio,et al.  Levetiracetam therapy in patients with brain tumour and epilepsy , 2006, Journal of Neuro-Oncology.

[29]  G. Zaccara,et al.  Central nervous system adverse effects of new antiepileptic drugs A meta-analysis of placebo-controlled studies , 2008, Seizure.

[30]  V. Myllylä,et al.  Serum lipid levels during carbamazepine medication. A prospective study. , 1993, Archives of neurology.

[31]  M. Mula,et al.  Optimizing therapy of seizures in adult patients with psychiatric comorbidity , 2006, Neurology.

[32]  C. Johannessen Landmark,et al.  Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. , 2008, CNS drugs.

[33]  R. Borgatti,et al.  Relationship Between Migraine and Epilepsy in Pediatric Age , 2006, Headache.

[34]  P. Tariot,et al.  Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. , 1998, The American journal of psychiatry.

[35]  A. Torres,et al.  Attention-deficit/hyperactivity disorder in pediatric patients with epilepsy: Review of pharmacological treatment , 2008, Epilepsy & Behavior.

[36]  J. Brust.  Seizures and substance abuse , 2006, Neurology.

[37]  H. Mrabet,et al.  Epidemiological and medical aspects of epilepsy in the elderly. , 2007, La Tunisie medicale.

[38]  E. Kossoff,et al.  Migraine and epilepsy. , 2010, Seminars in pediatric neurology.

[39]  C. Sawka,et al.  Add-on Gabapentin for Refractory Seizures in Patients With Brain Tumours , 1996, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[40]  W. Hauser,et al.  Seizures and myoclonus in patients with Alzheimer's disease , 1986, Neurology.

[41]  Michael C. Smith.  Optimizing therapy of seizures in children and adolescents with developmental disabilities , 2006, Neurology.

[42]  A. Rowan.  Management of Seizures in the Elderly , 2000, Pharmacotherapy.

[43]  A. Bava,et al.  Gabapentin for the Treatment of Behavioural Alterations in Dementia , 2003, Drugs & aging.

[44]  E. Gaily,et al.  Oxcarbazepine in the treatment of epilepsy in children and adolescents with intellectual disability. , 1998, Journal of intellectual disability research : JIDR.

[45]  L. Recht,et al.  Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors , 2000, Neurology.

[46]  G. Zaccara,et al.  Adverse motor effects induced by antiepileptic drugs. , 2004, Epileptic disorders : international epilepsy journal with videotape.

[47]  The Lancet Neurology.  Epilepsy and HIV—a dangerous combination , 2007, The Lancet Neurology.

[48]  G. Zaccara,et al.  Comparison of the efficacy and tolerability of new antiepileptic drugs: what can we learn from long‐term studies? , 2006, Acta neurologica Scandinavica.

[49]  P. Ryvlin,et al.  Optimizing therapy of seizures in patients with renal or hepatic dysfunction , 2006, Neurology.

[50]  H. Diener,et al.  European Stroke Initiative Recommendations for Stroke Management – Update 2003 , 2003, Cerebrovascular Diseases.

[51]  M. Castro‐Gago,et al.  Effects of long‐term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy , 1995, Neurology.

[52]  M. Maschio,et al.  Outcome and tolerability of topiramate in brain tumor associated epilepsy , 2007, Journal of Neuro-Oncology.

[53]  P. Calabresi,et al.  Levetiracetam monotherapy in Alzheimer patients with late‐onset seizures: a prospective observational study , 2007, European journal of neurology.

[54]  P. Calabresi,et al.  Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms. , 2007, Trends in pharmacological sciences.

[55]  M. Kerr,et al.  A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy , 2001, Seizure.

[56]  I. Tuxhorn,et al.  Levetiracetam in children with refractory epilepsy: A multicenter open label study in Germany , 2005, Seizure.

[57]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[58]  Samuel Wiebe,et al.  Somatic Comorbidity of Epilepsy in the General Population in Canada , 2005, Epilepsia.

[59]  I. Leppik,et al.  Hyponatremia from oxcarbazepine and carbamazepine , 2005, Neurology.

[60]  R. Schuurman,et al.  Carbamazepine–Indinavir Interaction Causes Antiretroviral Therapy Failure , 2000, The Annals of pharmacotherapy.

[61]  P. Höllinger,et al.  Epilepsy and Obstructive Sleep Apnea , 2006, European Neurology.

[62]  M. Druet‐Cabanac,et al.  Epidemiology and aetiology of epilepsy in sub-Saharan Africa , 2005, The Lancet Neurology.

[63]  M. Arvio,et al.  Topiramate in long-term treatment of epilepsy in the intellectually disabled. , 2005, Journal of intellectual disability research : JIDR.

[64]  G. Zaccara,et al.  Influence of Single and Repeated Doses of Oxcarbazepine on the Pharmacokinetic Profile of Felodipine , 1993, Therapeutic drug monitoring.

[65]  M. Brodie,et al.  A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: Impact on seizures, severity, and quality of life , 2005, Epilepsy & Behavior.

[66]  J M Zabramski,et al.  Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. , 1999, Stroke.

[67]  J. De Keyser,et al.  Seizures in multiple sclerosis , 2008, Epilepsia.

[68]  D. Wingerchuk,et al.  Current Evidence and Therapeutic Strategies for Multiple Sclerosis , 2008, Seminars in neurology.

[69]  M. Boaz,et al.  Monotherapy of Lamotrigine Versus Carbamazepine in Patients With Poststroke Seizure , 2007, Clinical neuropharmacology.

[70]  D. Back,et al.  Protease Inhibitors in Patients with HIV Disease , 1997, Clinical pharmacokinetics.

[71]  M. Weller,et al.  Pharmacotherapy of Epileptic Seizures in Glioma Patients: Who, When, Why and How Long? , 2005, Oncology Research and Treatment.

[72]  M. Topbaş,et al.  Effect of Antiepileptic Drugs on Plasma Lipids, Lipoprotein (a), and Liver Enzymes , 2006, Journal of child neurology.

[73]  L. Boothby,et al.  Clinical assessment and treatment of ADHD in children , 2007, International journal of clinical practice.

[74]  C. Vecht,et al.  Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management , 2007, The Lancet Neurology.

[75]  P. Kwan,et al.  Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment? , 2001, Epilepsia.

[76]  N. Stone.  Secondary causes of hyperlipidemia. , 1994, The Medical clinics of North America.

[77]  Josemir W Sander,et al.  Epilepsy and comorbidity: infections and antimicrobials usage in relation to epilepsy management , 2003, Acta neurologica Scandinavica. Supplementum.

[78]  J. Hildebrand.  Management of epileptic seizures , 2004, Current opinion in oncology.

[79]  R. Levy,et al.  Risk and predictability of drug interactions in the elderly. , 2007, International review of neurobiology.

[80]  F. Romanelli,et al.  The Use of Valproic Acid in HIV-Positive Patients , 1999, The Annals of pharmacotherapy.

[81]  W. Hauser,et al.  Risk of Epilepsy in Patients with Multiple Sclerosis: A Population‐Based Study in Iceland , 1999, Epilepsia.

[82]  A. Aldenkamp,et al.  Optimizing therapy of seizures in children and adolescents with ADHD , 2006, Neurology.

[83]  W. Hauser,et al.  Incidence of Epilepsy and Unprovoked Seizures in Rochester, Minnesota: 1935–1984 , 1993, Epilepsia.

[84]  C. Vecht,et al.  Optimizing therapy of seizures in patients with brain tumors , 2006, Neurology.

[85]  H. Hunter.  The treatment of epilepsy. , 1948 .

[86]  P. Ryvlin,et al.  Optimizing therapy of seizures in stroke patients , 2006, Neurology.

[87]  A R Feinstein,et al.  THE PRE-THERAPEUTIC CLASSIFICATION OF CO-MORBIDITY IN CHRONIC DISEASE. , 1970, Journal of chronic diseases.

[88]  S. Benbadis,et al.  CPAP: a treatment for epilepsy? , 2007, Neurology.

[89]  B. Steinhoff.  Optimizing therapy of seizures in patients with endocrine disorders , 2006, Neurology.

[90]  G. Zaccara,et al.  Idiosyncratic Adverse Reactions to Antiepileptic Drugs , 2007, Epilepsia.

[91]  K. Iinuma,et al.  Long-term effects of zonisamide in the treatment of epilepsy in children with intellectual disability. , 1998, Journal of intellectual disability research : JIDR.

[92]  T. George,et al.  Tiagabine increases cocaine-free urines in cocaine-dependent methadone-treated patients: results of a randomized pilot study. , 2003, Addiction.

[93]  L. Volicer,et al.  Effect of seizures on progression of dementia of the Alzheimer type. , 1995, Dementia.

[94]  E. Perucca,et al.  Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs , 2003, The Lancet Neurology.

[95]  Olafur Kjartansson,et al.  Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study , 2005, The Lancet Neurology.

[96]  C. J. Landmark,et al.  Antiepileptic Drugs in Non-Epilepsy Disorders , 2012 .

[97]  O. Devinsky,et al.  Psychotropic Effects of Antiepileptic Drugs , 2005, Epilepsy currents.

[98]  M. Harrison,et al.  Phenytoin and dyskinesias: A report of two cases and review of the literature , 1993, Movement disorders : official journal of the Movement Disorder Society.

[99]  A. Hammer,et al.  Adjunctive Lamotrigine for Refractory Epilepsy in Adolescents with Mental Retardation , 2006, Journal of child neurology.

[100]  于红,et al.  European Stroke Initiative Recommendations for Stroke Management-Update 2003 , 2004 .

[101]  D. Pearl,et al.  Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients , 2006, Journal of Neuro-Oncology.

[102]  L. Gjerstad,et al.  Poststroke Epilepsy: Occurrence and Predictors—A Long‐term Prospective Controlled Study (Akershus Stroke Study) , 2005, Epilepsia.

[103]  B. Johnson.  Topiramate-induced neuromodulation of cortico-mesolimbic dopamine function: a new vista for the treatment of comorbid alcohol and nicotine dependence? , 2004, Addictive behaviors.

[104]  M. Tohyama,et al.  Reactivation of human herpesvirus (HHV) family members other than HHV‐6 in drug‐induced hypersensitivity syndrome , 2006, The British journal of dermatology.

[105]  P. Groenewegen,et al.  Comorbidity was associated with neurologic and psychiatric diseases: a general practice-based controlled study. , 2006, Journal of clinical epidemiology.

[106]  E. Beghi,et al.  Epileptogenic drugs: a systematic review , 2006, Expert review of neurotherapeutics.

[107]  D. West,et al.  Increased Risk of Erythema Multiforme Major with Combination Anticonvulsant and Radiation Therapies , 1999, Pharmacotherapy.

[108]  R. Michelucci.  Optimizing therapy of seizures in neurosurgery , 2006, Neurology.

[109]  C. V. van Donselaar,et al.  Levetiracetam: preliminary experience in patients with primary brain tumours , 2003, Seizure.

[110]  E. Perucca.  British Journal of Clinical Pharmacology Clinically Relevant Drug Interactions with Antiepileptic Drugs , 2022 .

[111]  J. Breustedt,et al.  Effects of Taurine and Glycine on Epileptiform Activity Induced by Removal of Mg2+ in Combined Rat Entorhinal Cortex–Hippocampal Slices , 2003, Epilepsia.

[112]  C. Molina,et al.  Gabapentin in late-onset poststroke seizures , 2002, Neurology.

[113]  M. Gilbert,et al.  Antiepileptic drugs for preventing seizures in people with brain tumors. , 2008, The Cochrane database of systematic reviews.

[114]  R. Maciunas,et al.  The course of seizure disorders in patients with malignant gliomas. , 1995, Archives of neurology.

[115]  M. Mendez,et al.  Seizures in Elderly Patients with Dementia , 2003, Drugs & aging.

[116]  J. French,et al.  Meta-Analysis and Indirect Comparisons of Levetiracetam With Other Second-Generation Antiepileptic Drugs in Partial Epilepsy , 2005, Clinical neuropharmacology.