Karina Reynolds MD FRCS MRCOG
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A mechanism similar to that in pattern-sensitive epilepsy, in which generalized activity is activated by the occipital cortical stimuli, may operate in some cases of primary reading epilepsy in which bilateral myoclonic attacks or bilaterally synchronous epileptiform activity is triggered. Primary reading epilepsy generally responds well to valproate, and benzodiazepines or lamotrigine are expected to be useful as well, but patients often decline treatment especially if they have only jaw jerks. Language-Induced Epilepsy Geschwind and Sherwin (128) described a patient whose seizures were induced by three components of language: speaking, reading, and writing. In some patients, isolated components of language were the only effective seizure triggers. Writing (132,133), typing (134), listening to spoken language (135), and singing or recitation (136) have been reported as isolated triggers. Writing or speaking may activate patients with reading epilepsy (131,137), and exceptionally, reading epilepsy occurred in a patient who was also activated by card games (125). We consider activation by drawing (138) to be part of seizures induced by thinking, and other patients believed to have language-induced epilepsy may have thinking-induced seizures. This heterogeneity suggests that the definition of a language-induced epilepsy is not clear-cut. Cases may form part of relatively more stereotyped syndromes of reading epilepsy, whose definition should be broadened. The association of reflex language-induced epilepsy and idiopathic generalized epilepsy was explored Chapter 24: Epilepsy with Reflex Seizures 311 by Valenti et al. Musicogenic Epilepsy the rare musicogenic epilepsy consists of seizures provoked by hearing music. The music that triggers seizures is often remarkably specific in any one patient and no consistent epileptogenic features of musical sound can be identified. Some attacks can be provoked by music and by nonmusical sounds such as ringing or whirring noises. In some patients, an effective musical stimulus often induces emotional and autonomic manifestations before the clinical seizure begins.
The majority of children who experience a first unprovoked seizure will have few or no recurrences. Treatment has been shown in several studies combining both children and adults to reduce the risk of seizure recurrence; however, there is a relative paucity of data from studies involving only children after a first seizure. This publication recommends an approach to the standard and optimal management of infants with seizures. When possible, recommendations are evidence-based; however, when no evidence was available, recommendations are based on expert opinion and standard practice. However, in the acute treatment of febrile seizures, it is important to treat seizures lasting 10 minutes or longer. In an otherwise healthy infant, a policy of "wait and see" is reasonable after the first afebrile seizure. It is intended for internal use only and should be disseminated only to authorized recipients. The contents of the therapeutic class overviews on this website ("Content") are for informational purposes only. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always seek the advice of a physician or other qualified health provider with any questions regarding a medical condition. Clinicians should refer to the full prescribing information and published resources when making medical decisions. Recommendations include the following: Phenobarbital should be used as the first-line agent for treatment of neonatal seizures and should be made readily available in all settings. In neonates who continue to have seizures despite administering the maximum tolerated dose of phenobarbital, either a benzodiazepine, phenytoin, or lidocaine may be used as the second-line agent for control of seizures (use of phenytoin or lidocaine requires cardiac monitoring). Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society (Harden et al 2009A).
Neonatal seizures carry a risk for increased mortality, probably from the underlying brain disease rather than from the seizures themselves (57). In the neonatal period, subtle, frequently refractory seizures may occur, as well as tonic, focal clonic, myoclonic seizures and multifocal clonic jerks. Not all paroxysmal events are seizures; however, some are brainstem release phenomena. Because the initial insult usually occurs in utero, ventilation, cerebral perfusion, and adequate glucose levels must be maintained as preventive measures. Porphyria the disorders of heme biosynthesis are classified into two groups: erythropoietic and hepatic. Seizures and other neurologic manifestations occur only in the hepatic group, which comprises acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria (48). Seizures affect approximately 15% of patients, usually during an acute attack (49) often precipitated by an iatrogenically introduced offending agent. The generalized (occasionally focal) seizures may begin up to 28 days after exposure to the agent. Arguments for aggressive therapy have been based on the realization that seizures may compromise ventilation and increase systemic blood pressure and cerebral perfusion, leading to hemorrhagic infarction, intraventricular hemorrhage, or both (58,59). Seizures may also result in cellular starvation through exhaustion of cerebral glucose and high-energy phosphate compounds. Adult Anoxia and Hypoxia In adults, anoxic or posthypoxic seizures are residuals of cardiac arrest, respiratory failure, anesthetic misadventure, carbon monoxide poisoning, or near-drowning. Precipitating cardiac sources typically are related to embolic stroke, 13% of which involve seizures (60) or hypoperfusion or hyperperfusion of the cerebral cortex (2). In patients with respiratory disorder, acute hypercapnia may lower seizure threshold, whereas chronic stable hypoxia and hypercapnia rarely cause seizures. Subacute bacterial endocarditis can lead to septic emboli and intracranial mycotic aneurysms, which can produce seizures either from focal ischemia or from rupture and subarachnoid hemorrhage. Seizures may involve only minimal facial or axial movement (62), although nonconvulsive status epilepticus typically signifies a poor prognosis (63,64). Myoclonic status epilepticus or generalized myoclonic seizures that occur repetitively for 30 minutes are usually refractory to medical treatment (65). Concern has been raised that myoclonic status epilepticus may produce progressive neurologic injury in comatose patients resuscitated from cardiac arrest (65).
The percentage of children with rolandic sharp waves who develop clinically apparent seizures is unclear. Rolandic spikes have also been reported in children with brain tumors, cortical dysplasia, Fragile X syndrome, and Rett syndrome. Neurocognitive deficits appear to correlate with the amount and location of interictal spike discharge. Those with bilateral discharge scored the lowest overall; those with only right-sided discharge performed best. However, those with left centrotemporal discharge demonstrated bihemispheric representation of language, raising the possibility that focal epileptic activity may alter cerebral mechanisms that underlie cognitive functioning. Weglage studied 40 righthanded children with rolandic spikes (20 with and 20 without seizures) (88). Neuropsychological deficits were not related to presence or absence of seizures, seizure frequency, lateraliza- tion of the rolandic focus, or time since diagnosis, but higher spike frequency correlated with greater deficits. In a study of academic performance in 20 children with rolandic epilepsy, Piccinelli found greater cognitive difficulties in those with seizure onset before age 8 years and those with greater activation of epileptiform discharge during sleep (89). Prospective studies (80,90,91) have shown that, like the seizures and epileptiform discharges, the cognitive difficulties also appear to resolve with time. Because they appear to correlate with the amount and side of interictal spike discharge, these discharges may cause "transient cognitive impairment. The latter finding may indicate maturational delay with defective myelination, but the hippocampal changes were unexplained. A no-medication strategy is reasonable for the majority of children who have infrequent, nocturnal, partial seizures. If recurrent generalized or diurnal seizures occur, or if the seizures are sufficiently disturbing to the child or the family, treatment is generally started. However, treatment does not necessarily relieve parental anxiety or monitoring (96).
The overall dropout rate caused by adverse effects in clinical trials was 12% (33). As expected with most drugs, this rate is higher in community practice-21% in one open-label series (57). Interactions with renally excreted drugs such as levetiracetam, gabapentin, pregabalin, and vigabatrin have not been reported and would not be expected. Doses in the clinical trials were limited to 3600 mg/day for adults and 45 mg/kg/day for children, with most research patients achieving these targets without dose-limiting toxicities. Detailed review of the first 31 cases according to International Agranulocytosis and Aplastic Anemia Study criteria revealed that 23 (74%) met criteria for a diagnosis of aplastic anemia (60). Based on a 1997 estimate of 110,000 patients exposed, the authors of this review suggested a most probable incidence of 127 per million (1/8000 cases), compared with a population rate of 2 per million per year (60). Patients developing aplastic anemia were more likely to have histories of blood dyscrasias, especially cytopenia, autoimmune disorders, and rashes or significant toxicities with previous drugs (62). Caucasian women were the demographic group most likely to develop aplastic anemia (62). Children may be safer; only one child, a postpubescent 14-year-old reported in 2007, has been affected (61). Both felbamate and its initial metabolite, 2-phenyl-1,3-propanediol monocarbamate, cause apoptosis of bone marrow progenitor cells in vitro (67). A Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society has formulated practice guidelines for use in specific patient populations (68) (Table 62. All patients or their caretakers must be able to report side effects reliably, comply with blood testing, and understand the potential risks and benefits. Of these, eight cases could have been caused by other factors-five associated with status epilepticus and one case each of hepatitis A, acetaminophen poisoning, and severe hypotension. Using population exposure estimates (62), this implies a risk of about 1 per 10,000 patient exposures. Maintenance Dosage the target adult dose is 3600 mg/day; the target pediatric dose is 45 mg/kg/day. Lower doses may be effective, and some patients have tolerated doses as high as 7200 mg (adults) or 100 mg/kg/day (children) (69). Higher relative doses may be necessary for younger children in whom clearance is increased (38).
Olchi (Sour Cherry). Topamax.
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In addition to retail prescription drug sales to consumers, drugs may also be administered by providers such as hospitals and physicians. According to estimates by the Office of the Assistant Secretary for Planning and Evaluation, retail and provider-administered drugs combined represented about 17 percent of personal health care expenditures in 2015. See, Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation, Observations on Trends in Prescription Drug Spending (March 8, 2016). Drugs are a global industry that encompasses a variety of companies, including large multinational pharmaceutical corporations that traditionally focus on developing chemical and biologic drugs; makers of generic versions of such drugs; and small, research-oriented biotechnology companies. For the purposes of this review, we refer to pharmaceutical and biotechnology companies collectively as drug companies, unless otherwise noted. Further, some drug companies have undergone mergers and acquisitions, leading to concerns about reduced competition and higher drug prices. Economists have expressed apprehension that reduced competition may also decrease the amount of industry research and development (R&D) invested into new drugs, which could result in fewer drug choices for consumers and fewer treatment options for providers. Amid these questions, you asked us to provide an overview of the drug industry and the potential effects of consolidation on drug prices and new drug development. In addition, for all objectives, we interviewed industry experts, including representatives from industry groups, advocacy organization, economists, and federal agencies. For all of the data analyzed, we took steps to assure their reliability, including interviewing knowledgeable officials, conducting data checks, and comparing to published information when available. After taking these steps, we determined that the data were sufficiently reliable for the purposes of our reporting objectives. Appendix I provides additional details on our scope and methodology, including 6 Specifically, we analyzed claims for the orphan drug credit, research credit, and deductions for qualified research expenses by pharmaceutical companies, all industries, and certain additional industries. We conducted this performance audit from April 2016 to November 2017 in accordance with generally accepted government auditing standards. Those standards require that we plan and perform the audit to obtain sufficient, appropriate evidence to provide a reasonable basis for our findings and conclusions based on our audit objectives. We believe that the evidence obtained provides a reasonable basis for our findings based on our audit objectives. Background the drug industry encompasses a variety of companies involved in the research, development, distribution, and payment for chemically synthesized and biologic drugs. For the purpose of our review, the drug industry includes pharmaceutical companies that traditionally concentrate on developing or manufacturing drugs derived from chemicals and biotechnology companies that develop or manufacture biologics-more complex drugs derived from living cells.
The pharmacokinetics is linear and time invariant, with low individual variability (11). The effects of the agent are increased in the elderly (primarily due to impaired renal clearance) and in patients with renal impairment (11,12). Thus, dosage should be reduced in patients with impaired renal function and supplemental doses should be given after hemodialysis (11). Minimal plasma protein binding makes interactions due to competition for protein-binding sites unlikely (13). The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. Responder rates (50% or more reduction in seizure frequency compared with baseline) of 37. A significant reduction in weekly seizure frequency compared with that of the baseline period was observed during the first 2 weeks of the titration period, indicating that the agent has a rapid clinical effect at an initial dose (19,41). Open-label community trials confirmed the results noted in the pivotal trials, with efficacy achieved in patients at a dose of only 500 mg b. The half-life in children is 4 to 8 hours, compared with approximately 7 hours in adults. Elderly In older adults, total body clearance decreased by 38%, and the half-life was 2. Seizure frequency in these children was evaluated and compared with a 4-week baseline seizure frequency, using a 6-week titration to a target dose of 40 mg/kg/day. Twelve children (52%) responded (50% seizure reduction), with two patients remaining seizure-free during the entire study period (32).
Ketogenic diet: stringent, high fat, low carbohydrate diet that can control seizures in some children. Less stringent similar diets can be used at times, a modified Atkins diet or low glycemic index diet Lafora disease: a rare form of myoclonic epilepsy leading to progressive disability, dementia and a shortened lifespan. Landau-Kleffner syndrome: a rare, childhood condition producing seizures and progressive loss of the ability to speak. Lennox-Gastaut syndrome: debilitating epileptic syndrome in children characterized by myoclonic, absence and tonic-clonic seizures. Lobe: any rounded, projecting part of the anatomy; the brain has four lobes: frontal, parietal, temporal and occipital. Lobectomy: surgical removal of all or part of the lobe of the brain bearing abnormal seizure-causing tissue (see also: surgery for epilepsy). March: progression of muscular convulsions from one muscle or muscle group to another. Multifocal epilepsy: epilepsy in which the seizures come from a number of locations in the brain. Myoclonic seizures: a type of generalized seizure causing massive, rapid clonic spasms of muscle(s). Neurocystircercosis: a parasitic brain infection from eating bad pork; a common cause of seizures in some U. Neurologist: a specialist in the diagnosis and treatment of nervous system diseases and disorders such as epilepsy. Neurons (or nerve cells): the cells that form the brain and send and receive messages to and from the rest of the body. Nocturnal seizures: seizures that occur routinely in the evening hours and, especially, during sleep. Nonepileptic seizures: seizures with a psychological cause or which are due to a sudden drop in blood pressure, low blood sugar or other temporary condition. Partial seizure: main classification of seizure involving only one part of the brain, categorized as either simple partial or complex partial in the older classification of seizures (see also: focal seizure). Perinatal: the fetal development period from the 28th week of gestation to seven days after delivery.
Orknarok, 60 years: Consciousness is maintained and additional symptoms reflect the area of the brain that is affected. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function. Importance and management the clinical study suggests that peppermint oil may modestly increase the bioavailability of felodipine, which might therefore increase the incidence of adverse effects such as headache, lightheadedness and flushing. Many specific aspects of cognitive behavioral therapy address anxiety; they all help the child interrupt and change the negative thoughts that sometimes pile on when things are not going well.
Umbrak, 44 years: The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Urine toxicology screens in drivers suspected of driving while impaired from drugs. Epilepsy: chronic neurological disorder characterized by recurrent seizures, estimated to affect 2. High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy.
Tempeck, 61 years: To some extent, the differential diagnosis can be pared down by calling to mind a discrete list of diseases for each of the different epilepsy syndromes (see Table 32. Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays. Green tea (Camellia sinensis) extract does not alter cytochrome p450 3A4 or 2D6 activity in healthy volunteers. The hypothesis that this question is based on is that multifocal epilepsy is the observed phenotype of a primary seizure focus driving a complex epileptic network.
Kamak, 50 years: However, the increases seen in ambulatory blood pressure after 7 days of regular consumption of green or black tea were small and not different to that of caffeine. For information on the pharmacokinetics of individual flavonoids found in elder, see under flavonoids, page 186. Depending on the demographic region, the street purity of heroin can range from 11-72% (average U. Experimental evidence In a study of the interactions of various genotypes of hops, mice were given paracetamol 80 mg/kg after they had received four intraperitoneal doses of a 0.
Lester, 45 years: In one meta-analysis of 5 randomised studies of the effect of tea consumption for at least 7 days (median 4 weeks) on blood pressure, tea consumption was associated with no 384 Tea inflammation: a double-blind placebo controlled trial. In an otherwise healthy infant, a policy of "wait and see" is reasonable after the first afebrile seizure. Biotin is a water-soluble vitamin that is an indispensable coenzyme for four important carboxylases. Nevertheless, bear in mind that high doses of isoflavones might modestly increase theophylline levels and that this could be clinically important in patients with theophylline levels already at the higher end of the therapeutic range.
References
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