Epilepsy determinants

Mr. Parks, age 32 years, has recently received a diagnosis of epilepsy. He has been taking the anticonvulsant carbamazepine, but his seizures are not yet under control. Mr. Parks asks you how long it will take to cure his epilepsy. Determine how you would respond to Mr. Parks. 

Browne Szabo GK, Leppik IE, Josephs E, Paz J, Baltes E, Jensen CM. Absence of pharmacokinetic drug interaction of levetiraeetam with phenytoin in patients with epilepsy determined by new technique. J Clin Pharmacol (2000) 40, 590-5. 

The disruption of C1C-2 in mice leads to male infertility, blindness, and leukodystrophy, and was attributed to defective extracellular ion homeostasis in narrow clefts. C1C-2 yields currents that slowly activate upon hyperpolarization. It is also activated by cell swelling and by extracellular acidification. Structural determinants that are essential for these types of activation were identified by mutagenesis. There is a report that C1C-2 might be mutated in human epilepsy, but this has not been confirmed in fiuther studies. 

Epilepsy may be defined as a permanent, recurrent seizure disorder. Examples of the known causes of epilepsy include brain injury at birth, head injuries, and inborn errors of metabolism, hi some patients, the cause of epilepsy is never determined. 

Classification of epilepsies and epilepsy syndromes is helpful in determining appropriate pharmacotherapy. This classification scheme is based on the type of seizures a patient has and an attempt to identify the etiology of the epilepsy or epilepsy syndrome. 

Once it is concluded that the patient has seizures, the type of seizure and epilepsy syndrome, if any, must be determined. Proper identification and classification of the seizure type is most helpful in selecting appropriate pharmacotherapy. Without an accurate classification of the seizure type, it is possible to select a medication that is ineffective or even harmful to the patient. 

Additionally, the risk of a subsequent seizure must be determined. If there is an underlying treatable cause, such as hyponatremia or a CNS infection, the risks of another seizure and the development of epilepsy are very small. In these cases, the only pharmacotherapy that is necessary is to correct the underlying problem and possibly short-term use of an AED. Risk factors for repeated seizures in patients without an underlying disorder include ... 

Many forms of epilepsy have genetic determinants 635... 

There are numerous metabolic diseases, infantile and other tetanies, steatorrhea, osteomalacia, arthritis of old age, epilepsy, etc., in which calcium either is or may be implicated. Each of these diseases needs to be studied against a background of wide variability in calcium needs, probably genetically determined, and involving "normal" individuals as well as those having overt disease. 

Kulak JM, Nguyen TA, Olivera BM, McIntosh JM (1997) Alpha-conotoxin Mil blocks nicotine-stimulated dopamine release in rat striatal synaptosomes. J Neurosci 17 5263-5270 Kuryatov A, Gerzanich V, Nelson M, Olale F, Lindstrom J (1997) Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca + permeabihty, conductance, and gating of human a4 32 nicotinic acetylcholine receptors, J Neurosci 17 9035-9047 Kuryatov A, Olale FA, Choi C, Lindstrom J (2000) Acetylchohne receptor extracellular domain determines sensitivity to nicotine-induced inactivation, Eur J Pharmacol 393 11-21 Langley JN (1880) On the antagonism of poisons. J Physiol 3 11-21... 

Regular monitoring of blood phenytoin levels provides a valuable contribution to the management of patients with epilepsy. The value of determining the blood level of other anticonvulsant drugs is unconfirmed. At present such work should be undertaken only as prospective research procedures combining clinical and biochemical methods of assessment and patient-management. 

M15. Meinardi, H., Workshop on the determination of anti-epileptic drugs in body fluids I. Eur. Symp. Epilepsy, 6th, London, 1972. 

Rubidium metal and its salts bave very few commercial apphcations. They are used in research involving magnetohydrodynamics and thermoionic experiments. Rubidium is used in pbotocells. The metal also is a getter of oxygen in vacuum tubes. The beta-emitter rubidium -87 is used to determine age of some rocks and minerals. Radioisotopes of rubidium have been used as radioactive tracers to trace the flow of blood in the body. The iodide salt treats goiters. Rubidium salts are in pharmaceuticals as soporifics, sedatives, and for treating epilepsy. 

Lapierre YD, Browne M, Horn E, et al Treatment of major affective disorder with fluvoxamine. J Clin Psychiatry 48 65-68, 1987 Lapierre YD, Ravindran AV, Bakish D Dysthymia and serotonin. Int Clin Psychopharmacol 8 (suppl 2) 87-90, 1993 Lapin 1, Oxenkrug G Intensification of the central serotonergic process as a possible determinant of thymoleptic effect. Lancet 1 132-136, 1969 Larkin JG, McKee PJ, Blacklaw J, et al Nimodipine in refractory epilepsy a placebo-controlled, add-on study. Epilepsy Res 9 71-77, 1991 Larsson LI, Rehfeld JF Localization and molecular heterogeneity of cholecystokinin in the central and peripheral nervous system. Brain Res 165 201-218, 1979 Laruelle M, Abi-Dargham A, Casanova M, et al Selective abnormality of prefrontal serotonergic receptors in schizophrenia a post mortem study. Arch Gen Psychiatry 50 810-818, 1993... 

Cost-effectiveness is an economic evaluation in which both the costs and the consequences of treatments are examined. The denominator of the cost-effectiveness ratio can be an intermediate outcome, such as a delay in the progression of a disease, or a final outcome, such as life-years saved. Once the outcome is measured, the costs associated with attaining this outcome form the numerator of the ratio. For example, suppose our interest is determining the relative value of drug therapy for epilepsy versus epilepsy... 

Several types of drugs are currently available, and certain compounds work best in specific types of epilepsy. Consequently, the type of epilepsy must be determined by observing the patient and using diagnostic tests such as electroencephalography (EEG).21 The classification system most commonly used in characterizing epilepsy is discussed here. 

Nervous system The existence of neurologic disorders (for example, epilepsy, myasthenia gravis) influences the selection of an anesthetic. So, too, would a patient history suggestive of a genetically-determined sensitivity to halogenated hydrocarbon-induced malignant hyperthermia (see p. 113). 

Q4 An electroencephalogram (EEG) is a recording of electrical activity arising from the cortical surface of the brain. It is recorded from scalp electrodes on 16 channels simultaneously. The technique is non-invasive and is not painful. The main uses of electroencephalography are to investigate sleep and its disorders and to diagnose epilepsy. The wave/spike patterns produced can be analysed to reveal alterations in or to localize areas of the specific electrical activity associated with seizures. The EEG can also be used medico-legally to determine whether a person is actually brain dead . 

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