Epileptic affections

Epileptic seizures affect 0.5% of the population, are more common in the young and, except for partial seizures, often decrease with age. Convulsions associated with metabolic disturbances are not considered to be epileptic. 

Use of diethylpropion for a period longer than 3 months is associated with an increased risk for development of pulmonary hypertension. When used as directed, reported common central nervous system adverse effects included overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, jitteriness, anxiety, nervousness, depression, drowsiness, malaise, mydriasis, and blurred vision. In addition, diethylpropion can decrease seizure threshold, subsequently increasing a patient s risk for an epileptic event. Other organ systems also can adversely be affected, resulting in tachycardia, elevated blood pressure, palpitations, dry mouth, abdominal discomfort, constipation,... 

The epilepsies constitute a common, serious neurological disorder in humans, affecting approximately 60 million people worldwide. Well in excess of 40 distinct epileptic syndromes have been identified to date. Current treatment is only symptomatic except in uncommon instances when surgical treatment is possible. While available antiseizure medications target ion channels such as the y-amino-butyric acid (GABA)a receptor and voltage activated sodium (Na+) channels, current research seeks to elucidate the cellular and molecular mechanisms by which a normal brain becomes epileptic. Hopefully, this research will lead to the identification of new targets for which small molecules can be identified and used for prevention or cure of epilepsy. 

Epilepsy is a chronic brain disease of diverse etiology it is characterized by recurrent paroxysmal episodes of uncontrolled excitation of brain neurons. Involving larger or smaller parts of the brain, the electrical discharge is evident in the electroencephalogram (EEG) as synchronized rhythmic activity and manifests itself in motor, sensory, psychic, and vegetative (visceral) phenomena Because both the affected brain region and the cause of abnormal excitability may differ, epileptic seizures can take many forms. Erom a pharmaco-therapeutic viewpoint, these may be classified as ... 

Epilepsy (or epilepsies, since markedly different clinical entities exist) is a common neurological abnormality affecting about 1% of the human population. Epilepsy is a chronic, usually life-long disorder characterized by recurrent seizures or convulsions and usually, episodes of unconsciousness and/or amnesia. Table 32.1 illustrates the major types of epileptic seizures. Patients often exhibit more than one type. In most instances, the cause of the seizure disorder is not known (idiopathic epilepsy), although trauma during birth is suspected of being one cause. 

Withdrawal of medication from an epileptic pregnant woman is not without its hazards, to the patient and possibly to the fetus. It is not clear whether maternal seizures can directly affect the fetus. If it is feasible, the physician should prescribe only one drug at the lowest effective dosage to minimize teratogenic risks. 

Maggi A, Enna SJ Regional alterations in rat brain neurotransmitter systems following chronic lithium treatment. J Neurochem 34 888-892, 1980 Maggi A, Perez J Minireview role of female gonadal hormones in the CNS clinical and experimental aspects, life Sci 37 893-906, 1985 Maitre L, Baltzer V, Mondadori C Psychopharmacological and behavioural effects of anti-epileptic drugs in animals, in Anticonvulsants in Affective Disorders. Edited by Emrich HM, Okuma T, Muller AA. Amsterdam, Excerpta Medica, 1984, pp 3-13... 

Marcotte D. Use of topiramate, a new anti-epileptic as a mood stabilizer. J Affect Disord 1998 50 245-251. 

PEM is one of the most frequent cancer-associated syndromes. This complex disorder usually affects several areas of the CNS. Cerebellar and brain stem disorders, as well as limbic encephalitis, are the most common clinical presentations of PEM [31, 32], Focal involvement of the sensorimotor cortex has been described in a few cases [33], and PEM may manifest as epileptic seizures or epilepsia partialis continua [33, 34], or as extrapyramidal symptoms [35], Two-thirds of the patients are affected in both the CNS and the peripheral nervous system. The predominant feature in more than half of these is SN [32, 36], hence the commonly used term is PEM/SN. Autonomic dysfunction is common in PEM/SN patients [36], often presenting as gastrointestinal dysmotility [37]. 

The genetic association of Kv7 channel mutations and neuronal hyper-excitability suggests that Kv7.x channels may also modulate the excitability of neurons involved in pain processing since many currently used anti-epileptic drugs which affect excitability are also used to treat pain. Kv7 channels are known to be expressed at multiple levels of pain pathways, including thalamic, spinal superficial dorsal horn and dorsal root ganglion neurons. Thus, small molecule openers of Kv7 channels may not only diminish the neuronal hyper-excitability associated with epilepsy, but may also be effective in treating pain conditions. 

Epilepsy affects 0.5% of the world s population and can have a multitude of underlying etiologies, including several mutations in CNS sodium channels. Sodium channel mutations linked to human epileptic syndromes typically shift activation to more hyperpolarized potentials, slow inactivation kinetics, accelerate recovery from inactivation, and/or increase the persistent current [48]. Seemingly paradoxically, some mutations appear to result in non-functional channels [48-50]. 

Digitalis purpurea (foxglove) (Scrophulariaceae) [digitalis] high dose yields cloudy yellow vision red-green perception changes (xanthopsia) - anti-epileptic use may have affected late yellow period of Vincent Van Gogh]... 

Moyamoya seems to be mainly confined to the Japanese and other Asians, and in most cases the cause is unknown (Bruno et al. 1988 Chiu et al. 1998). Some cases are familial (Kitahara et al. 1979) others appear to be caused by a generalized fibrous disorder of arteries (Aoyagi et al. 1996), and a few may result from a congenital hypoplastic anomaly affecting arteries at the base of the brain, or associated with Down s syndrome (Cramer et al. 1996). The syndrome may present in infancy with recurrent episodes of cerebral ischemia and infarction, mental retardation, headache, epileptic seizures and, occasionally, involuntary movements. In adults, subarachnoid or primary intracerebral hemorrhage are also common owing to rupture of collateral vessels. There have also been a few reports of associated intracranial aneurysms (Iwama et al. 1997) and also of cerebral arteriovenous malformations. 

A similar plant is water hemlock, which contains a different toxin, called cicutoxin. This is very potent and exposure to it is often fatal. One study of poisonings with this plant found that 30 per cent of victims died. It affects primarily the brain and the spinal cord, causing seizures and epileptic fits, possibly by overstimulating certain nerves (cholinergic pathways). 

These two molecules illustrate how subtle changes in molecular structure can affect action. Amobarbital requires 30 min to take effect and sedation lasts for 5-6 h, while pentobarbital takes effect in 15 min and sedation lasts only 2-3 h. Phenobarbital (R=ethyl, R =phenyl), on the other hand, requires over an hour to take effect, but sedation lasts for 6-10 h. When the alkyl chains are made much longer the sedative properties decrease and the substances become anticonvulsants, which are used to treat epileptic seizures. If the alkyl group is too long or is substituted at one of the two nitrogens, convulsants are produced. 

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