Ilae Classification Of Seizure Type
Epilepsy is a variable condition, and it is therefore appropriate to devise a system of classification. The International League Against Epilepsy ILAE has been engaged on this task for over 40 years, proposing and then revising various systems. The classification most widely accepted is a classification of seizure type i.e. of the phenomenology of seizures rather than of epilepsies . Such a classification could be based on various criteria, for instance the cerebral region in which the seizure...
Meningitis and encephalitis
The risk of chronic epilepsy following encephalitis or meningitis is almost sevenfold greater than that in the population in general. The increased risk is highest during the first 5 years after infection, but remains elevated for up to 15 years. The risk is much higher after encephalitis relative risk RR 16.2 than bacterial meningitis RR 4.2 or aseptic meningitis RR 2.3 . The presence of early seizures i.e. during the acute phase of the infection greatly influences the risk of subsequent...
Renal stones and oligohydrosis
A striking difference that has been noted between Japanese studies and the US and European studies is the occurrence of renal stones. In pre-approval studies in Japan, only two patients 0.2 developed urinary stones, compared with a rate of 2.6 in the early studies in the USA and Europe. Table 3.27 Adverse events of zonisamide in double-blind placebo-controlled studies pooled data events occurred in more than 5 of patients. Table 3.27 Adverse events of zonisamide in double-blind...
Diazepam
Diazepam was the first benzodiazepine to be used in epilepsy. It is highly lipophilic, allowing rapid entry into the brain, but this high lipid solubility also results in rapid subsequent redistribution into peripheral tissues. It is 90 -99 bound to plasma proteins. The volume of distribution for the free component of diazepam i.e. the active, unbound fraction is 1.1 l kg. The initial half-life is 1 hour. Entero-hepatic circulation result in a second peak in blood levels 6 -8 hours after...
Epilepsy arising in the parietal and occipital lobes
Focal seizures arise from foci in these locations less commonly than from frontal, central or temporal lobe regions. The typical manifestations of the seizures are subjective sensory and visual disturbances Table 1.13 . Additional features are common owing to spread to adjacent cortical regions. Parietal lobe seizures typically comprise sensory manifestations. These may be tingling or a feeling of electricity which can be confined or march in a Jacksonian manner. Sensations of sinking, choking...
Polymicrogyria
The appearance of small and prominent gyri separated by shallow sulci is known as polymicrogyria. It can be diffuse or localized, and varies in severity as well as extent. The underlying cortex is invariably thickened, and can be un-layered or show an abnormal four-layered structure. The conditions may be a migrational defect in weeks 13 -18 of fetal life, or the result of ischaemia or perfusion failure between weeks 12 and 24 of fetal life. Epilepsy is the leading clinical feature, associated...
Periventricular nodular heterotopia
The presence of subependymal nodules of grey matter, located along the supralateral walls of the lateral ventricles is known as Periventricular nodular heterotopia synonym bilateral periventricular nodular heterotopia BPNH , subependymal nodular heterotopia SENH . The heterotopia is usually bilateral, although not always. It is much more common in females and conforms to X-linked dominant transmission. One mechanism may be X-chromosome inactivation. The condition is usually lethal in affected...
Neurofibromatosis type 1
Neurofibromatosis type 1 NF1 is a common, dominantly inherited genetic disorder, occurring in about 1 in 3000 live births. Almost half of all cases are new mutations. The mutation rate for the NF1 gene is about 1 in 10,000, amongst the highest known for any human gene. It is a large gene, and many different mutations have resulted in the clinical manifestations. Although the penetrance is essentially complete, the clinical manifestations are extremely variable. In NF1, the incidence of epilepsy...
Benign epilepsy with centrotemporal spikes BECTS
In this common childhood epilepsy syndrome p. 20 , therapy is gratifyingly straightforward and indeed drug treatment is not necessary in all cases. If attacks are infrequent or mild, regular therapy seems inappropriate, especially as some children have only a few attacks before the epilepsy remits. Tonic-clonic seizures carry greater risks than the partial attacks and may tip the balance towards therapy. The partial seizures, when frightening and distressing, can warrant treatment, even if they...
Pharmacopoeia
Use of antiepileptic drugs in different seizure types and syndromes. Partial and secondarily Tonic-clonic generalized tonic- seizures primary Absence Myoclonic West Lennox-Gastaut clonic seizures generalized seizures seizurestt syndromettt syndrometttt Reasonable clinical experience of effectiveness. At the time of writing, gabapentin, levetiracetam, pregabalin, tiagabine and vigabatrin are licensed only for use as add-on therapy in most countries. However, there is extensive published...
Rapid action and parenteral pharmacokinetics
Fast drug absorption is essential in the treatment of status epilepticus, and thus almost all drugs need to be administered intravenously. Midazolam is the only drug that is absorbed fast enough by the intra-muscular, intra-nasal or buccal routes. Diazepam and other drugs can be given rectally in out-of-hospital situations, but in hospital the intra-venous route is favoured. In order to act rapidly, the drugs need to cross the blood-brain barrier readily, and thus the drugs that are effective...
Articles in scientific journals 1
Adab N, Kini U, Vinten J, Ayres J, et al. 2004. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry, 75 1575-83. Adab N, Tudur SC, Vinten J, Williamson P, and Winterbottom J. 2004. Common antiepileptic drugs in pregnancy in women with epilepsy. Cochrane Database Syst Rev, 3 CD004848. American Academy of Pediatrics. Committee on Quality Improvement, Subcommittee on Febrile Seizures. 1999. Practice parameter long-term treatment of the child with simple...
Other vascular disorders
Cortical venous infarcts are particularly epileptogenic, at least in the acute phase, and may underlie a significant proportion of apparently spontaneous epileptic seizures complicating other medical conditions and pregnancy. Seizures also occur with cerebrovascular lesions secondary to rheumatic heart disease, endocarditis, mitral valve prolapse, cardiac tumours and cardiac arrhythmia, or after carotid endarterectomy. Infarction is also an important cause of seizures in neonatal epilepsy....
Suppression of subclinical epileptic activity
Antiepileptic drug therapy as a rule should be aimed at suppressing seizures and not the reduction of EEG activity. However, in selected situations, therapy can be targeted at EEG disturbances where these are considered to be having adverse clinical effects 'subclinical activity' . These include reduction of 3 Hz spike-wave paroxysms in children with absence seizures abolition of EEG changes in the Landau-Kleffner syndrome pp. 25-6 abolition of photosensitivity in photosensitive epilepsy...
Progressive myoclonic epilepsy PME
This is a rather specific phenotype, which can be caused by a variety of genetically determined neurological disorders Table 1.26 . In most parts of the world there are six common underlying conditions mitochondrial disorders, Unverricht-Lundborg disease, dentato-rubro-pallido-luysian atrophy DRPLA , Lafora body disease, neuronal ceroid lipofuscinosis, and sialidosis. The term progressive myoclonic epilepsy should be confined to those cases where the predominant clinical symptom is myoclonus....
Piracetam
Piracetam is a drug with an unusual clinical history Table 3.32 . It was developed in 1967 by the research laboratory of UCB-Pharma in Belgium and deployed in clinical practice as a 'memory enhancing drug'. Its efficacy in this role has been highly contentious and the drug has not been licensed for this indication, either in the USA or the UK, although it is widely used in other, particularly developing countries the manufacturers report over a million prescriptions . Recent controlled trials...
Inflammatory and immunological diseases of the nervous system
Epilepsy can be a complication of many inflammatory and immunological diseases affecting the central nervous system. The mechanisms of seizures can be due to the direct effect of immunological processes for instance in Rasmussen's encephalitis or an indirect effect due to vascular disease and cerebral infarction for instance in the cerebral vascul-itides . In many conditions the mechanisms are unknown. Seizures are the most common neurological complication of the inflammatory bowel diseases...
Precautions needed with parenteral benzodiazepines
Although benzodiazepines are the drugs of first choice for emergency therapy, they do carry a risk of respiratory depression, hypotension and cardio-respiratory collapse. In a well-controlled study in anaesthetic practice, for example, diazepam 10 mg was given intravenously to 15 patients and resulted in a drop in blood pressure of 10 mmHg or more in eight patients, a mean 28 decrease in ventilation, and a 23 decrease in tidal volume. The effects on cardiorespiratory function are as great or...
Nitrazepam
Nitrazepam is a benzodiazepine derivative with a nitro group at the 7 position of the benzodiazepine ring. Oral bioavailability is about 78 . Peak concentrations are reached in about 1.5 hours. Nitrazepam is 85-88 protein bound. The volume of distribution is 2.4 l kg, and is higher in the elderly. The plasma half-life is about 27 hours, but the drug is rapidly taken up into the CSF and brain tissue and the CSF elimination half-life is 68 hours. Nitrazepam is metabolized in the liver by...
Postvaccination encephalopathy
The possible role of vaccination particularly pertussis vaccination in causing a childhood encephalopathy and subsequent epilepsy and learning disability has been the subject of intense study, with contradictory claims. The UK National Childhood Encephalopathy Study found that children hospitalized with seizures and encephalopathy were more likely to have received diphtheria-tetanus-pertussis DTP vaccination in the previous 7 days than control children. However, the potential methodological...
The Reflex Epilepsies
The term reflex epilepsy is used to describe cases in which seizures are evoked consistently by a specific environmental trigger. In some cases the stimulus can be highly specific and in others less so. The term is not usually applied to patients whose seizures are precipitated by internal influences such as menstruation, nor to situations where the precipitating factors are vague or ill-defined e.g. fatigue, stress , nor to patients with existing epilepsy where seizures are more likely to...
Typical absence status epilepticus petit mal status
This occurs only in patients with idiopathic generalized epilepsy, usually as part of the subcategory childhood absence epilepsy, in which a history of absence status occurs in about 3 -9 . The attacks can recur, and can last for hours or occasionally days. The episodes are typically precipitated by factors such as menstruation, withdrawal of medication, hypoglycaemia, hyperventilation, flashing or bright lights, sleep deprivation, fatigue, stress, or grief. The principle clinical feature is...
Paraldehyde
Paraldehyde still has a minor role in premonitory stage given rectally, as an alternative to the benzodiazepines in situations where facilities for resuscitation are not available. Paraldehyde is rapidly and completely absorbed after IM injection or rectally. The risk of drug accumulation, hypotension or cardio-respiratory arrest is small, and seizures do not often recur after control has been obtained. Paraldehyde has been used for many years in status, and although there is wide experience in...
Myoclonic status epilepticus in coma
Myoclonic status epilepticus in coma is a well-recognized complication of the cerebral anoxia resulting from cardiorespiratory arrest typically after a myocardial infarction or cardiac surgery . It is characterized by spontaneous and stimulus-sensitive myoclonus usually occurring within 24 hours of the coma. To what extent this is really an 'epileptic' state, or is simply a sign of a severely damaged brain, is arguable. The patients generally have burst suppression on their EEGs, are deeply...
Cortical mapping
Cortical mapping of functionally important cortex is a vital function where neurosurgical procedures are planned in sensory, motor or speech areas, and is required to identify eloquent areas and thus avoid post-surgical neurological deficit. Techniques vary but all include the placement of grids over the proposed resection site, and the observation of the clinical effects of electrical stimulation of each cortical contact. Ictal and interictal EEG can be recorded at the same time. Mapping is...
Emergency antiepileptic drug therapy
This is needed in convulsive attacks if the convulsions persist for more than 10 minutes, recur rapidly or last longer than is customary for the individual patient. It is usual to give a fast-acting benzodiazepine. The traditional choice is diazepam, administered either intravenously or rectally. Intravenous diazepam is given in its undiluted form at a rate not exceeding 2-5 mg min, using the Diazemuls formulation. Because of the high lipid solubility of diazepam, injections given at a faster...
Rasmussens encephalitis
This is a rare progressive neurological disorder, of unknown cause, in which severe epilepsy co-exists with slowly pro gressive atrophy of one cerebral hemisphere. The condition usually begins in late childhood, but can start in adults and also in young children. Pathologically, there is severe atrophy of one hemisphere with histological evidence of perivascular lymphocytic infiltration, neuronal loss and microglial nodule formation. The pathological changes are strikingly unilateral, and where...
LandauKleffner syndrome
The Landau-Kleffner syndrome is a childhood epileptic encephalopathy in which persisting aphasia develops in association with severe EEG abnormalities and epilepsy Table 1.23 . It is an uncommon condition with a male predominance and usually without a family history. Onset occurs at between 18 months and 13 years, in most cases between 4 and 7 years. The aetiology and pathogenesis of the syndrome, if indeed these are unitary, are unknown. The condition develops in children who were previously...
Articles in scientific journals Tcj
Agathonikou A, Panayiotopoulos CP, Giannakodimos S, et al. 1998. Typical absence status in adults diagnostic and syndromic considerations. Epilepsia, 39 1265-76. Alldredge BK, Gelb AM, Isaacs SM, et al. 2001 A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med, 345 631-7. Erratum in N Engl J Med 2001, 345 1860. Aminoff MJ and Simon RP. 1980. Status epilepticus causes, clinical features and consequences in 98 patients. Am J Med,...
Pharmacokinetics
As there is no IV formulation, bioavailability measurements can be estimates only, but it appears that generally speaking between 75 and 85 of the drug is absorbed following oral ingestion. Absorption, however, can be slow and erratic, there is a marked intra-individual variation, and different formulations may have different absorption characteristics. It does not appear to make any difference whether the drug is taken before or after food. Peak levels are reached between 4 and 8 hours after...
Epilepsy arising in the central perirolandic region
The primary manifestations are motor or sensory Table 1.12 . The motor features can take the form of jerking, dystonic spasm, posturing or occasionally paralysis, Table 1.12 Partial seizures of central origin. Often no loss of consciousness simple partial seizure Contralateral clonic jerking which may or may not march Contralateral tonic spasm Posturing, which is often bilateral, and version of head and eyes Speech arrest and involvement of bulbar musculature producing anarthria or choking,...
Sialidosis
Sialidosis is less common than the other causes of progressive myoclonic epilepsy. There are at least two variants. All cases are inherited in an autosomal recessive manner. Type I sialidosis cherry-red spot myoclonus syndrome is due to N-acetyl neuraminidase deficiency, which results in defective cleavage, and thus accumulation, of oligosaccha-rides, typically with inclusion bodies with vacuolation. It has a juvenile or adult onset and is characterized by action myoclonus and an intention...
Pentobarbital
Pentobarbital is an alternative to thiopental, as barbiturate anaesthesia in the stage of refractory status epilepticus. It shares many of the characteristics of thiopental, but has the advantages of a shorter elimination half-life than thiopental, non-saturable kinetics, and no active metabolite. It is a stable compound and is unreactive with plastic. There is a surprising dearth of published information about its value, in spite of widespread use. Indeed, published trials have shown a...
Hypothalamic hamartoma and gelastic epilepsy
The hypothalamic hamartoma is a particular form of hamartoma. These are benign tumours, usually small and sometimes confined to the tuber cinerium. They are present in young children, and characteristically present with gelastic seizures, learning disability, behavioural disturbance, and later with precocious puberty. They are diagnosed by MRI scanning, but the lesions can be very subtle, especially if small, without mass effect, and isodense on both T1 and T2 sequences. Gelastic seizures are...
The Organization Of Epilepsy Surgery Care The Epilepsy Surgery Centre
It should be clear that epilepsy surgery is a specialized area which requires, for almost every patient, an input from specialists in different non-surgical areas for example neurology, neurophysiology, neuroradiology, neuropaediatrics, neurorehabilitation, neuropsychology and psychiatry. The input is needed to select suitable patients for surgery, to counsel patients adequately about the potential risks and benefits of surgery, and to follow-up patients after surgery. A full range of necessary...
Lidocaine
Lidocaine is a second-line drug for use in the stage of early status epilepticus only. It is given as a bolus injection or short IV infusion. The clinical effects and pharmacokinetics have been extensively studied in patients of all ages, and the drug is highly effective. The main disadvantage of lidocaine is that its antiepileptic effects are short-lived, and seizures are controlled for a matter of hours only. Lidocaine is thus useful only while more definitive antiepileptic drug treatment is...
Febrile seizures temporal lobe epilepsy and hippocampal sclerosis
A research area of great current importance, and intensive investigation, is the study of the undoubtedly strong genetic influences on febrile seizures and thus on hippocampal sclerosis and temporal lobe epilepsy TLE . Various strands of evid-ence exits. Families are reported with inherited TLE mesial and lateral TLE and also epilepsy with variable EEG foci . Four foci have to date been found in linkage studies of febrile seizures. In cohort studies, polymorphisms in the interleukin-1p gene...
Thiopental
Thiopental is, in most countries, the usual choice for barbiturate anaesthesia in the stage of refractory status epilepticus. It is a highly effective antiepileptic drug, with additional potential cerebral protective action. It reduces intracranial pressure and cerebral blood flow, and has a very rapid onset of action. Its principal metabolite is pentobarbital. The drug has a number of pharmacokinetic disadvantages including saturable kinetics, a strong tendency to accumulate, and a prolonged...
Generalised epilepsy with febrile seizures plus GEFS
This is a very heterogeneous form of epilepsy, inherited in an autosomal dominant fashion, with age-specific manifestations and variable penetrance about 60 in the original families . Febrile seizures are the most common feature, and seizures precipitated by fever tend to occur throughout childhood. Afebrile seizures of varying types, generalised tonic-clonic, myoclonic, atypical absence, and less commonly focal seizures, develop later in childhood. Status epilepticus can occur. The severity...
Benign partial epilepsy with centrotemporal spikes
Benign partial epilepsy with centro-temporal spikes BECTS also known as rolandic epilepsy or benign epilepsy with rolandic spikes is the most common 'idiopathic' epilepsy syndrome, accounting for perhaps 15 of all epilepsies Table 1.16 . The peak age of onset is 5-8 years and over 80 of cases have onset between 4 and 10 years. It is likely that the condition is the result of an age-related genetically determined neuronal hyperexcitability in the rolandic area, resulting in characteristic giant...
Autosomal dominant nocturnal frontal lobe epilepsy ADNFLE
This was the first 'pure epilepsy' in which the causal gene was found. Various mutations in the a4 and P2 subunits of the nicotinic acetylcholine receptor have been identified in families with this interesting condition. Typically, the condition is inherited in an autosomal dominant fashion with 75 penetrance. The patients suffer from purely nocturnal frontal lobe seizures sometimes many each night without daytime seizures and without other symptoms. The seizures are brief, lasting less than 1...
Magnetic resonance imaging MRI
MRI is undertaken in all patients undergoing evaluation for epilepsy surgery. Indeed, it is now the primary screening test for entry into a programme of pre-surgical evaluation. The imaging must be of an appropriate quality and tailored to the visualization of mesial temporal pathologies. Substandard MRI, for instance with wide inter-slice intervals or sequences with poor grey white differentiation, frequently fails to detect hippocampal sclerosis, which is then shown on better targeted...
Syndrome of electrical status epilepticus during slow wave sleep ESES
ESES continuous spike-wave of slow sleep CWES Table 1.22 refers to an epileptic encephalopathy characterized by the presence of generalized 1-3 Hz spike-wave discharges occupying 85 or more of the EEG of non-REM sleep. Of children with epilepsy, 0.5 show this EEG pattern. The condition is diagnosed during childhood 1-14 years with a peak age of onset between 3 and 5 years. About 30 of children showing this pattern have identifiable brain pathology such as previous meningitis or brain anoxia,...