Tonic-clonic seizures,

Primidone [125-33-7] C22H24N2O2 (39) is an analogue of phenobarbital that is used for the treatment of generalized tonic-clonic seizures. It is metabolized in humans to phenobarbital (6) and phenylethyLmalondiamide [7206-76-0J, C22H24N2O2 (40) and these metaboUtes are probably responsible for its anticonvulsant actions. Primidone has many of the side effect HabiUties seen with phenobarbital. 

One of the oldest antiepileptic drugs, bromide, has been repotted to boost inhibition by an unknown mechanism. Bromide is still in use in certain cases of tonic-clonic seizures and in pediatric patients with recurrent febrile convulsions and others. The mechanism of action may include a potentiation of GABAergic synaptic transmission, although the precise target is not known. 

Generalized seizures include absence, myoclonic, and tonic-clonic. Manifestations of a generalized tonic-clonic seizure include alternate contraction (tonic phase) and relaxation (clonic phase) of muscles, a loss of consciousness, and abnormal behavior. Myoclonic seizures involve sudden, forceful contractions involving the musculature of the trunk, neck, and extremities. Absence seizures, previously referred to as petit mal seizures, are seizures characterized by a brief loss of consciousness during which physical activity ceases. The seizures typically last a few seconds, occur many times a day, and may go unnoticed by others. 

Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these dm have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic dm are not effective in controlling seizures. The oxazolidinediones may precipitate a tonic-clonic seizure... 

Similarly, convulsive seizures and a sustained epileptic state persisted after stomach contents were pumped and activated charcoal and anticonvulsive medication were administered in a 43-year-old man who ingested approximately 260 mg/kg endosulfan (Boereboom et al. 1998). At 4 days after exposure, the man was pronounced brain dead, and autopsy revealed cerebral hernia from massive cerebral edema. Eight additional accidental and/or intentional cases of acute poisoning with endosulfan resulting in adverse neurological effects have been reported in more recent studies, six by Blanco-Coronado et al. (1992), one by Lo et al. (1995), and one by Pradhan et al. (1997) two out of the eight resulted in death. Tonic-clonic convulsions were seen in the Blanco-Coronado et al. (1992) cases, whereas Lo et al. (1995) reported the development of muscle fasciculations and episodes of convulsions in their case. In the case reported by Pradhan et al. (1997), the patient had consumed about 75 mL of hquid endosulfan (35% w/v). In this case, in addition to tonic-clonic seizures and myoclonic jerks, the patient developed... 

It has become clear that drugs which are effective in protecting mice against PTZ are effective in absence seizures while those able to control the tonic response to maximal electroshock are effective in tonic-clonic seizure. Some drugs are effective in only one test and clinical condition whilst a few are active in both (Table 16.1). Experimental focal seizures are indicative of partial seizures. 

Phenobarbitone may be as effective as phenytoin and carbamazepine in partial and generalised tonic-clonic seizures but its other central effects such as sedation, depression, listlessness and cognitive impairment mar its usefulness. 

Clonazepam, a typical 1 4 benzodiazepine, is effective in absence seizures, myoclonic jerks and tonic-clonic seizures and given intravenously it attenuates status epilepticus. It is less sedative than phenobarbitone but tolerance develops and its withdrawal, as... 

Myoclonic Single and very brief jerks of all major muscle groups. Patients with these may not lose consciousness, due to the seizure lasting less than 3 to 4 seconds. Patients may describe these seizures as shoulder shrugs or spinal chills. Myoclonic seizures may cluster and build into a generalized tonic-clonic seizure. 

Juvenile absence epilepsy with generalized tonic-clonic seizure on awakening... 

Juvenile myoclonic epilepsy (JME) A primary generalized epilepsy syndrome that usually starts in the early to middle teenage years and has a strong familial component. Patients have myoclonic jerks and tonic-clonic seizures and may also have absence seizures. 

AG, a 20-year-old male college student, is seen by his physician 4 days after an apparent seizure during finals week. According to his roommate, he suddenly fell to the floor and had a generalized tonic-clonic seizure. This seizure lasted for 1 to 2 minutes. The patient was incontinent for urine during the seizure. He was sleepy and confused when the paramedics arrived 1 0 minutes later. Due to final examinations he reports being sleep-deprived. His physical exam is completely normal and no focal neurologic deficits were observed. 

BC, a 22-year-old woman, was diagnosed 2 years ago with juvenile myoclonic epilepsy. She has been treated with valproate 1500 mg/day. Since starting valproate she has gained 45 pounds (20.5 kg), continues to have occasional myoclonic jerks, had a generalized tonic-clonic seizure 3 months ago, and is sexually active. Additionally, she complains of easily falling asleep during the day. Due to adverse effects, poor seizure control, and the risk of birth defects with valproate, the decision is made to switch to a different antiepileptic drug. 

Patients with SE usually present with generalized, convulsive tonic-clonic seizure activity that is unresponsive to initial AED treatment. They may also be hypertensive, tachycardic, febrile, and diaphoretic however, these symptoms will resolve soon after the seizure is terminated. A loss of bowel or bladder function, respiratory compromise, and nystagmus may also... 

A 38 year-old male with a 15-year history of grand mal seizures is brought to the ED with generalized tonic-clonic seizures that are unremittent... 

Phenotype determined by cortical region activated (e.g. if motor cortex representing left thumb is activated, then left thumb jerking results). Consciousness is preserved Impaired consciousness lasting seconds to minutes, often associated with automatisms such as lip smacking Simple or partial complex seizure evolves into a tonic-clonic seizure with loss of consciousness. There are sustained muscular contractions (tonic) followed by periods of relaxation (clonic) lasting 1-2 min... 

A serum prolactin level obtained within 10 to 20 minutes of a tonic-clonic seizure can help differentiate seizure activity from pseudoseizure activity,... 

C. Secondarily generalized (partial onset evolving to generalized tonic-clonic seizures)... 

GTC seizures may be preceded by premonitory symptoms (i.e., an aura). A tonic-clonic seizure that is preceded by an aura is likely a partial seizure that is secondarily generalized. Tonic-clonic seizures begin with a short tonic contraction of muscles followed by a period of rigidity. The patient may lose sphincter control, bite the tongue, or become cyanotic. The episode may be followed by unconsciousness, and frequently the patient goes into a deep sleep. 

The traditional treatment of tonic-clonic seizures is phenytoin or phe-nobarbital, but the use of carbamazepine and valproic acid is increasing, as efficacy is equal and side effects are more favorable. 

Carbamazepine and valproic acid had equal retention rates for tonic-clonic seizures, but carbamazepine was superior for partial seizures, and valproic acid caused more adverse effects. 

It is a first-line AED for patients with partial seizures. It is also approved for tonic-clonic seizures in primary generalized epilepsy. 

Further work on ADH may identify the molecular mechanisms underlying the brain calcification and tonic-clonic seizures associated with the CASR-activating mutations. This information may refine therapy for ADH patients as well as hypoparathyroidism patients who harbor CASR mutations. Further details about ADH can be found in the CASR locus-specific database at http //www.casrdb. mcgill.ca/f4/). 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

The brief duration of a single epileptic fit makes acute drug treatment unfeasible. Instead, antiepileptics are used to prevent seizures and therefore need to be given chronically. Only in the case of status epilepticus (a succession of several tonic-clonic seizures) is acute anticonvulsant therapy indicated — usually with benzodiazepines given i.v. or, if needed, rectally. 

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