Alane B. Costanzo, MD
Pregabalin dosages: 150 mg, 75 mg
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A review of drowning deaths found that 40% of seizure-related drownings occurred during recreational activities (42). A study by Gotze found no increase in seizure occurrence during strenuous swimming (43). The available data on such seizures are limited, suggesting that sports participation does not provoke seizure recurrence (44), and in some cases may even reduce seizure occurrence (43). Recent opinion has encouraged sports participation for the person with epilepsy despite the potential risks (45,46). The decision regarding person with epilepsy participation in sporting activities must be made on an individual basis. For example, zonisamide reduces sweating in children and could potentially lead to heat-related injury in hot climates. Tremor associated with the use of valproic acid could be dangerous when shooting target pistols. Phenytoin-induced ataxia could potentially be deadly while riding a motorbike (47). Individualizing the specific drug side-effect profile, patient characteristics, and particular recreational activity generally should all be considered when advising the person with epilepsy about participation in recreational and sporting activities. In addition to the usual concerns persons with epilepsy have about seizure control and medication effects, social issues play an important role in their everyday lives. Consensus conference on driver licensing and epilepsy: American Academy of Neurology, American Epilepsy Society, and Epilepsy Foundation of America. To drive or not to drive: the 3-month seizure-free interval for people with epilepsy [editorial]. Counselling for driving restrictions in epilepsy and other causes of temporary impairment of consciousness: how are we doing Epilepsy and motor vehicle driving-a symposium held in Quebec City, November 1998.
There is usually deviation of the eyes and of the head toward one side, and this may amount to rotation involving the whole body (sometimes actually causing the patient to turn around, even two or three times). The features are distorted; the color of the face, unchanged at first, rapidly becomes pale and then flushed and ultimately livid as the fixation of the chest by the spasms stops the movements of respiration. The eyes are open or closed; the conjunctiva is insensitive; the pupils dilate widely as cyanosis comes on. As the spasm continues, it commonly changes in its relative intensity in different parts, causing slight alterations in the position of the limbs. Epilepsia Partialis Continua Under this name have been described cases of simple partial seizures with focal motor signs without a march, usually consisting of clonic spasms, which remain confined to the part of the body in which they originate, but which persist with little or no intermission for hours or days at a stretch. The sudden loss of postural tone in the head and trunk may lead to injury by projecting objects. In the case of more prolonged atonic attacks, the slumping may be progressive in a rhythmic, successive relaxation manner. Postictal paralysis has been ascribed to neuronal exhaustion due to the increased metabolic activity of the discharging focus, but it may also be attributable to increased inhibition in the region of the focus, which may account for its appearance in nonmotor somatosensory seizures. The aura, of course, is the start, not the cause, of a seizure, as Erastus pointed out around 1580. The 1981 International Classification of Epileptic Seizures (3) defined the aura as "that portion of the seizure which occurs before consciousness is lost and for which memory is retained afterwards. Conventional usage further limits the word to the initial sensations of a seizure, without observable signs, that the patient is aware of and recollects. This definition specifically separates an aura from a focal motor seizure and is used in this chapter. To the extent that patients can clearly recollect such symptoms as shivering with piloerection at seizure onset, autonomic phenomena can be experienced as an aura. Less commonly, some patients with generalized epilepsy can experience stereotyped sensations before a generalized seizure.
Diseases
Some of the imaging strategies that may be employed to improve lesion detection are discussed in the following section. Increase in the magnetic field strength improves the signal-to-noise ratio and contrast-to-noise ratio thereby improving the detection of subtle lesions (46). This also illustrates the smallest of veins (because veins contain higher deoxygenated blood) in the submillimeter caliber in great detail. C, D: Subtle blurring of gray-white region on the banks of central sulcus (arrow), barely visible on the 1. Inversion recovery sequences can alleviate this effect but cannot be used when one attempts to compare with a contrast enhanced T1 image, as inversion recovery pulse interferes with visualization of contrast. Reducing the excitation flip angle improves gray-white contrast despite reduction in signal-to-noise ratio. Higher magnetic field strength also accentuates the susceptibility effects and this can cause artifacts. Recent studies report a 20% to 48% increase in detection of new or additional information by 3 T study compared to 1 to 1. Two of these three studies also used phased array coils and it is unclear whether the improved lesion detection rate was solely due to higher magnetic field strength. Limited coverage of cortex (and the resultant "tunnel vision"), overall increase in scan time, need for pre-imaging hypothesis, and decreased signalto-noise ratio for the deeper structures were major limitations precluding routine use of surface coils. Increased anatomical coverage by increase in the number of elements in the phased array coils has minimized the limitations of traditional surface coils. Though the differences appear robust, this study did not distinguish the effect of the higher field strength from the effect of surface coils. More research on the use of such coils is required to guide routine use of this technique in clinical practice. If the imaging voxels in the three-dimensional acquisitions are designed to achieve an equivalent length in all three imaging planes (isotropic data), the images can be reconstructed in any alternate plane without compromising the spatial resolution or fidelity when compared to the original images. On the other hand, if the voxels were too anisotropic, the reconstructed images will be noticeably degraded compared with the original data. In practice, data can only be "nearly" isotropic as patients will not routinely tolerate the length of time required to acquire truly isotropic data.
The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Comparison of the effectiveness of phenobarbital, mephobarbital, primidone, diphenylhydantoin, ethotoin, metharbital, and methylphenylethylhydantoin in motor seizures. A comparison of the effectiveness of primidone versus carbamazepine in epileptic outpatients. Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up. Depressive symptoms in epilepsy: prevalence, impact, aetiology, biological correlates and effect of treatment with antiepileptic drugs. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Phenobarbital-induced absence seizure in benign childhood epilepsy with centrotemporal spikes. Phenobarbital-associated bone marrow aplasia: a case report and review of the literature. Grand mal seizures and acute intermittent porphyria: the problem of differential diagnosis and treatment. Incidence of anticonvulsant osteomalacia and effect of vitamin D: controlled therapeutic trial. Its narrow therapeutic profile has limited its use to the treatment of childhood absence epilepsy. Some studies have also suggested a potential therapeutic effect in epileptic negative myoclonus (1). Antiepileptic Effects the presumed mechanism of action against absence seizures is reduction of low-threshold T-type calcium currents in thalamic neurons (11,12). The spontaneous pacemaker oscillatory activity of thalamocortical neurons involves low-threshold T-type calcium currents (13).
Pharmacokinetics of lamotrigine in patients with renal impairment: influence of hemodialysis. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy. Oral cyclosporine decreases severity of neurotoxicity in liver transplant recipients. Prophylactic fluconazole in liver transplant recipients: a randomized, double blind, placebo-controlled trial. However, allergic reactions, metabolically or genetically determined drug-induced illnesses, and idiosyncratic effects of drugs, while rare, may be life-threatening. The process begins with the disclosure to patients and family members of all information required for an informed decision delivered within the framework of risks and benefits. Regularly scheduled accumulation of hematologic data, routine serum chemistry values, and results of urinalysis creates an archive (2). Although these sources appear to define the standard of practice for many clinicians, they actually preserve observations about specific and well-defined groups of patients under close scrutiny during drug trials. Contrary to some clinical practices and these publications, evidence-based scientific criteria fail to support routine monitoring, and the resulting archival data rarely predict serious drug reactions. One study (5) of 199 children evaluated liver, blood, and renal function at initiation of therapy and at 1, 3, and 6 months. Screening studies repeated every 6 months disclosed no serious clinical reactions from phenobarbital, phenytoin, carbamazepine, or valproate. Abnormal but clinically insignificant results prompted retesting in 12 children (6%), and therapy was discontinued unnecessarily in 2 children. The authors concluded that routine monitoring provided no useful information and sometimes prompted unwarranted action. A second study (6) of 662 adults treated with carbamazepine, phenytoin, phenobarbital, or primidone failed to detect significant laboratory abnormalities during 6 months of monitoring and led to the conclusion that routine screening was neither cost-effective nor valuable for asymptomatic patients. Treatment of 480 patients with either carbamazepine or valproic acid in a double-blind, controlled trial also demonstrated the lack of usefulness of routine laboratory monitoring (7).
Syndromes
The molybdenum cofactor is essential for the proper functioning of the enzymes sulfite oxidase and xanthine dehydrogenase. A fresh urine sample shows positive results of a sulfite test and elevated levels of xanthine and hypoxanthine, coupled with depressed concentrations of uric acid. This array of chemical malfunction can arise from mutations in three molybdenum cofactors or in gephyrin. Mutations in sulfite oxidase are found in patients with isolated sulfite oxidase deficiency. There is no effective treatment, and prognosis for neurologic recovery and survival is poor. Neonatal Intoxications Lidocaine or mepivacaine inadvertently injected into the fetal scalp during local pudendal analgesia for the mother, cocaine, heroin (135), amphetamines, propoxyphene, and theophylline also may cause seizures. Neurocutaneous Syndromes Chronic Causes Cerebral Dysgenesis Some neonatal seizures result from long-standing disorders, such as cerebral dysgenesis, neurocutaneous syndromes, genetic disorders, or very early onset epilepsy. The identification of cerebral Among the neurocutaneous syndromes that may give rise to neonatal seizures is familial incontinentia pigmenti, a mixed syndrome of different mosaicisms (139). Perinatal inflammatory vesicles are followed by verrucous patches that produce a distinctive pattern of hyperpigmentation and finally dermal scarring. In contrast to the familial form, sporadic incontinentia pigmenti maps to Xp11 and is considered its "negative" pattern. Better known as hypomelanosis of Ito, its cutaneous lesions appear as areas of hypopigmentation. Linear sebaceous nevi are a family of disorders with distinctive raised, waxy, sometimes verrucous nevi on the scalp or face, associated with hemihypertrophy, hemimegalencephaly, and neonatal seizures (142). Epilepsy Syndromes of Early Infantile Onset In the 1970s, French neurologists coined the "fifth-day fits" (benign neonatal convulsions) to describe an electroclinical syndrome in which seizures unexpectedly arose between the fourth and sixth days of life (143). The seizures were usually partial clonic, often with apnea and status epilepticus.
No treatment is required, but clonazepam or other benzodiazepines have been suggested in children who demonstrate a large amount of benign myoclonic activity. Spasmodic Torticollis Spasmodic torticollis is a disorder characterized by sudden, repetitive episodes of head tilting or turning to one side with rotation of the face to the opposite side. The episodes may last from minutes to days, during which children are irritable and uncomfortable but alert and responsive. The etiology is unknown, although dystonia and labyrinthine imbalance have been proposed. The differential diagnosis includes congenital, inflammatory, and neoplastic conditions of the posterior fossa, cervical cord, spine, and neck in which the episodes of torticollis are sustained, lacking the usual on-and-off variability. An evaluation is necessary, but spasmodic torticollis usually subsides without treatment during the first few years of life. Wakefulness Jitteriness Neonates and young infants demonstrate this rapid generalized tremulousness, which in neonates may be severe enough to be mistaken for clonic seizures. The infants are alert, and the movements may be decreased by passive flexion or repositioning of the extremities. Although jitteriness may occur spontaneously, it is typically provoked or increased by stimulation. Prognosis depends on the etiology, and in neonates with severe, prolonged jitteriness may be guarded. Nevertheless, in 38 full-term infants who were jittery after 6 weeks of age, the movements resolved at a mean age of 7. Sedative agents may be used, but their adverse effects usually increase the irritability (11,12).
An imbalance of malignancies was observed with ocrelizumab; across both studies and through 96 weeks, neoplasms occurred in 0. 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. Among the ocrelizumab-treated patients that developed neoplasms, there were 2 cases of invasive ductal breast carcinoma, 1 case of renal-cell carcinoma, and 1 case of malignant melanoma. Rebif-treated patients with neoplasms included 1 case of mantle-cell lymphoma and 1 case of squamous-cell carcinoma in the chest. The proportion of patients with 20% worsening of the timed 25-foot walk confirmed at 12 weeks was 49% in ocrelizumab-treated patients compared to 59% in placebo-treated patients (25% risk reduction). Infusion-related reactions, upper respiratory tract infections, and oral herpes infections occurred more frequently with ocrelizumab vs placebo. Among the ocrelizumab-treated patients that developed neoplasms, there were 4 cases of breast cancer, 3 cases of basal-cell carcinoma, and 1 case in each of the following: endometrial adenocarcinoma, anaplastic large-cell lymphoma (mainly T cells), malignant fibrous histiocytoma, and pancreatic carcinoma. In the placebo group, 1 patient developed cervical adenocarcinoma in situ and 1 patient developed basal-cell carcinoma. Between the clinical cutoff date (July 24, 2015) and June 30, 2016, 2 additional cases of neoplasm (1 case of basal-cell skin carcinoma and 1 case of squamous-cell carcinoma) were detected during the open-label extension phase in which all patients received ocrelizumab.
The and auxiliary subunits for Cav channels are classified in three major families for each. There are Cav1 (L-type), Cav2 (P/Q-, N-, and R-type), and Cav3 (T-type) subunits and 2, and auxiliary subunits. Cav1 channels are typically localized postsynaptically in the somatodendritic regions and contribute to calcium signaling in response to action potential backpropagation, synaptic activity, and activity-dependent gene regulation. Cav2 channels are localized both pre- and postsynaptically with both axonal and somatodendritic expression. An important function for these channels is the regulation of presynaptic neurotransmitter release. Cav3 channels underlie a transient calcium current that activates at subthreshold potentials and is critical for the regulation of calcium flux at near resting membrane potential and also during action potentials. A number of the antiepileptic drugs mediate an anticonvulsant effect through altering the function of these channels (see Chapter 50). Mutations in the genes encoding Cav channels and their auxiliary subunits were first described in mice with naturally occurring mutations in these channels that were associated with generalized spike and wave activity (36). Subsequently, mutations in Cav channels associated with idiopathic epilepsy in humans have been described. Some are associated with a gain of function but others have effects on channel kinetics, trafficking, or decrease the underlying current. Subcellularly, these channels are localized presynaptically where they play a critical role in initiating neurotransmitter release. The channels are also localized in the somatodendritic regions where they modulate excitability of the postsynaptic membrane in neurons (26). Some kindreds with mutations in this gene express a phenotype that also includes epilepsy. There are different mutations described and functional characterization of some of them suggests that channel function is impaired in the mutant channel.
These are for constituents that have been demonstrated to interact in their own right, but which are prevalent in a number of herbal medicines, the most common example of this being the flavonoids. This structure allows us to assess the relevant data in one place, and cross-reference the reader as appropriate. Because so many herbs contain a multitude of these constituents it would not be possible to cover them in each plant monograph. The data on interactions are of widely varying quality and reliability, and this is even more the case when considering interactions between herbal medicines and conventional drugs. The best information comes from clinical studies carried out on large numbers of patients under scrupulously controlled conditions; however, with herbal medicines these are sparse. As with all our publications we undertake extensive literature searching, we consider guidance published by regulatory bodies and we aim to avoid citing secondary literature wherever possible. We have included them because they appear in other reference sources for interactions, but we have attempted to put their results and recommendations in perspective. The herbal medicines, dietary supplements and nutraceuticals selected for inclusion in this first edition were chosen on the basis of their popularity and/or because they have interaction reports associated them. Incidence of herbal medicines interactions the incidence of interactions between herbal medicines and nutritional supplements with conventional drugs is not yet fully known, and there is no body of reliable information currently available to draw upon when assessing the scale of any possible problem, or predicting clinical outcomes. In general, the lack of evidence may be due to under-reporting or unrecognised interactions, but there is also the possibility that many herbal medicines have a generally safe profile and do not interact significantly with drugs. Given the poor quality of information available it can be difficult to put the problem into perspective and in the absence of good evidence, speculation has taken its place. These have to be evaluated very carefully before advising patients as to the safety (or not) of combining herbal medicines with either other supplements or conventional drugs.
Nafalem, 39 years: When the ability to generate an ictus becomes more facile, this is thought to generalize to epileptogenesis. Tai Chi for Chronic Pain Conditions: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Ingvar, 24 years: Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co-varies with alkylamide content. Especially controversial is the detectability of spikes generated in the mesial temporal lobe.
References
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