CC: Seizure Disorder (Epilepsy)

If seizures are controlled but are accompanied by significant adverse effects,

a reduction in drug dosage can be attempted.

Migraine -- relevant background history features that help distinguish it from a seizure

food and environmental triggers of migraine, and its stronger family history

If seizures or intolerable side effects continue with a third drug or drug combinations,

the patient is formally medically refractory, and alternative treatments should be considered

Absence seizures

('petit mal') brief clouding of consciousness generally lasting less than 30 seconds and having minimal accompanying motor signs (e.g., axial stiffening, brief clonic movements of the mouth, or twitching of the eyelids) The prototypical accompanying EEG abnormality is a generalized spike and wave pattern. ---- In classic absence this is exactly at 3 Hz term atypical absence is used if this less than 3 Hz.

Worldwide incidence of SE is

10 to 60 per 100,000 person-years Even with optimal treatment in an intensive care environment, mortality remains high (~ 50% in refractory SE) Patients with a known diagnosis of epilepsy constitute only half of all cases of SE

Runaway activation (i.e., seizure) is prevented by

AHP and also surround inhibition, that limits spatial propagation of excitation. This is mediated by GABA-ergic inhibitory interneurons that synapse onto adjacent neurons.

Seizures result from

AHP and surround inhibition breakdown allowing continuously repetitive neuronal firing and spread of excitation beyond the initiating focus. Distant spread may occur incrementally through cortico-cortical U-fibers or directly via the major white matter pathways.

Generalized Seizure types

Absence Myoclonic Atonic Tonic-Clonic

Simple Partial Seizures

Clinical manifestations of a simple partial seizure vary depending on the location of the cortical electrical discharge

Presurgical investigations

Core investigations = brain MRI and EEG videotelemetry Interictal positron emission tomography and ictal single-photon emission computed tomography are useful supplementary imaging modalities Neuropsychological testing for assessing language and memory function is vital, and serves to both localize the epileptogenic area by assessing the type and degree of cognitive dysfunction, as well as predict the likely cognitive effects of the proposed cortical resection. psychosocial evaluation of always useful in exploring the patient's wider life circumstances, their degree and quality of social connectedness, and preparedness for surgery and life after surgery.

Most widely used system of seizure classification

International Classification of Epileptic Seizures --- developed by a task force of the International League Against Epilepsy In practical terms, classifying seizures is a form of neurological localization, indicating the brain area involve -- partial -- generalized also allows for the diagnosis of an epilepsy syndrome, by grouping seizure types known to occur together based on a combination of clinical and electroencephalographic (EEG) change accompanying each seizure type Alternative system based purely on subjective symptoms and objective signs ('semiology') has been proposed; this system is arguably better suited for everyday use, given that EEG is only rarely ongoing at the time the patient is seizing.

SE patients wo a previous epilepsy diagnosis --- due to

Intracranial infection fever (in children) metabolic upset (including alcohol withdrawal) structural brain lesions

American Academy of Neurology (AAN) issues practice parameters for the management of neurological conditions

Level A recommendations are backed by more than one randomized population-based trial Level U is when evidence is conflicting or lacking Levels B and C are intermediary. The current practice parameter issued by the AAN for investigating a first seizure assigns a Level B recommendation to EEG and neuroimaging (CT or MRI), and a Level U recommendation for all other investigations

Imaging

MRI is the neuroimaging modality of choice and should be offered to all patients. In an emergency, cranial computed tomography (CT) will identify the majority of immediately treatable causes of new seizures. routine EEG should be done at some point

Presurgical investigations --- intensive approach for precisely locating seizure onset zone

Occasionally, the patient's epilepsy warrants a more intensive approach with invasive EEG recording with intracerebral electrodes electrical stimulation mapping of eloquent cortex is usually also performed to identify those areas of cortex whose removal would result in loss of sensory processing, motor or linguistic ability.

Physical exam on epilepsy patients

Patients with uncomplicated epilepsy often have normal physical examination, reiterating the importance of information gathered from history in the patient encounter

Diagnosis - History

Questions regarding the overall tempo of the illness and the specific event itself are paramount, and should comprise a subjective and an objective account of each distinct type of episode identified patient's experience of the event should be taken rst: what they were doing just before it, whether they were awake, falling asleep, or arousing, whether they experienced a warning, how the event itself began and evolved as far as can be recollected, and whether incontinence, tongue biting, muscle ache, confusion or headache was noticed afterwards. eyewitness account should include whether the patient warned them or appeared unwell before the episode, showed impairment of consciousness or had abnormal movements dur- ing the event, how long the episode lasted, and whether the patient was confused or appeared to have trouble speaking afterwards inquiry should include sleep disruption, physical or mental stress, recent illness, previous medical history, medications or illegal drugs, and family history

Syncope -- workup & diagnosis

Routine cardiac workup - 12 lead EKG Holter monitoring chest X-ray echocardiography and referral to cardiology is indicated in patients presenting with repetitive syncope.

In a spike, excitation initiates

a corrective afterhyperpolarization (AHP) phase mediated by γ-aminobutyric acid (GABA) and voltage-dependent K+ channels returns the LFP to baseline to block further action potentials. The cycle then repeats itself at irregular intervals.

If the second drug fails,

a third may be introduced in similar fashion. chances of success markedly diminish with successive drug trials. seizure freedom in patients with partial and secondarily generalized seizures was achieved with the first drug selected in 47% of patients ---- used the older-generation anticonvulsants, including carbamazepine, phenobarbital, phenytoin, and primidone Newer trial w newer drugs --- another 13% of patients became seizure free with the second drug used, and only a further 4% became seizure free with the third drug or with combina- tions of drugs.

SE is catagorized in three stages:

according to the duration of seizures Currently, Class I evidence (i.e., from prospective randomized controlled trials) is available only for the first-line drugs used in Stage I SE (e.g., lorazepam) Nevertheless, there is agreement on an overall treatment algorithm, which is based on a rapid, progressive trial of successive intravenous agents, culminating in general anesthesia if seizures continue.

Mechanism for a chronic seizure tendency

alteration of network connectivity such as occurs in the hippocampus with mossy fiber sprouting and cell loss in the dentate gyrus and cornu ammonis This aberrant connectivity, which may itself be induced by seizures, fosters further seizures.

Felbamate

approved in 1993 efficacy as an anticonvulant being compromised by a significant chance of triggering a potentially life-threatening idiosyncratic systemic reaction.

Pverall age-adjusted incidence of acute symptomatic seizures (i.e., seizures triggered directly by antecedent cause)

approximately 40 per 100,000 person-years lifetime incidence is about 4% If childhood febrile seizures are included, the lifetime incidence rises to about 10%. The incidence of seizures is thus significantly different from that for epilepsy

Cumulative risk of recurrence after a single seizure in adults

approximately 40% over the first 2 years However, in the subgroup of patients with IEDs, the 2-year cumulative risk was 81%, compared with 39% in patients with other types of EEG abnormalities and 12% in those with normal EEGs. Abnormal imaging studies or a positive family history increases relapse risk, and seizures that occur more than 7 days after severe head injury are strongly associated with recurrence

Partial Seizures

arise from a delimited brain region where symptoms originate from, and remain in, a part of one cerebral hemisphere can be simple (no impairment of awareness), or complex (impaired awareness)

Morbidity of SE

arises from several interacting pathophysiologic mechanisms: neuronal injury and loss of cerebral autoregulation from excitotoxic damage cardiorespiratory compromise from autonomic hyperstimulation rhabdomyolysis, acidosis, hyperkalemia, and other systemic effects of continued seizures

Generalized epilepsies

associated with seizures in which both the clinical and EEG characteristics are bilateral and diffuse at onset (e.g. juvenile myoclonic epilepsy)

Migraine

aura of classic migraine produces evolving neurological symptoms that may instead suggest seizure Cortical spreading depression, the supposed mechanism for migrainous aura produces a symptom complex that evolves over several seconds or minutes. Seizure spread is more rapid. ensuing headache, though not always present, is a strong discriminant from seizure Headache can however occur as an isolated manifestation of seizures, most commonly in children with complex partial seizures. Distinguishing such seizures from migraine can be dif cult without the clarity of an adult history or a clear hemicranial presentation.

Myoclonic seizures

brief whole-body muscle contractions occurring singly or in clusters. range from subtle, such that only the patient notices them, to massive jerks. It is thought that consciousness is preserved during myoclonic seizures. The EEG pattern is a diffuse, bilaterally synchronous high-amplitude polyspike discharge, frequently maximal over the frontocentral brain regions.

Migraine -- EEG

can be surprisingly unhelpful in distinguishing migraine from seizure - focal slowing during migraine can be profound, though the typical, though not universal, paroxysmal change characterizing seizure is absent.

N-methyl-D-aspartate (NMDA) receptor

channel for several cations that requires the ligands glutamate and glycine for activation.

Starting a drug treatment

chosen drug is started as monotherapy dose is progressively increased (with the target dose and rate of increase determined by the specific drug and the clinical circumstances) until seizures are controlled, adverse effects develop, or the maximum dose is reached. If seizures are controlled in the absence of signi cant adverse effects, therapy has succeeded.

Migraine and seizures may

co-exist, such as in patients with vascular lesions.

Epilepsy Surgery

coinciding largely with the arrival of advanced brain imaging Community neurologists should refer patients for consideration of epilepsy surgery if the first few (3-4) drug trials fail. This may take as little as a year to establish in some patients.

After a tonic-clonic seizure...

comatose; consciousness gradually returns, though cognitive change (i.e., confusion, aggression, or mood changes) may persist for several hours. In the young, otherwise healthy patient, the immediate postictal phase may be as brief as 20 minutes the postictal phase lengthens if the patient has more than one seizure; is elderly, frail, cognitively impaired at baseline, or otherwise unwell.

Complex partial seizures of temporal lobe origin

commonly accompanied by automatisms, which are stereotypic motor acts. Oroalimentary automatisms are repetitive movements of the mouth, lips, tongue, and jaw: chewing, swallowing, and lip smacking. Hand (manual) automatisms are repetitive grasping or fumbling movements; the patient may reach and pull or pick at anything within reach.

Seizure

commonly understood to mean a convulsion More accurately, a seizure is a paroxysmal alteration in behavior in the domains of motor or sensory modalities or consciousness. A generalized convulsion is one type of seizure. Neurophysiologically, an uncontrolled, excessive, and hypersynchronous discharge of cortical neurons. With a few exceptions (some controversial) subcortical gray matter does not generate seizures.

Diagnosis -- basic laboratory studies

complete blood count --- WBC --- e.g. anemia and sickle cell cerebrovascular disease comprehensive metabolic profile including electrolytes, glucose, calcium, and magnesium. --- screens for most common metabolic triggers for acute seizures Blood or urine screening for drugs If the patient is already on anticonvulsants, serum levels should be considered

Convulsive syncope

consists of a faint followed by jerky movements The movements involve a few repetitions of whole-body myoclonus, generally lasting less than 30 seconds. The movements are thought to arise from disinhibition of brain stem structures from supratentorial ischemia.

Brain lesions commonly associated with intractable focal epilepsy in adults

cortical dysplasia low-grade tumors dysembryoplastic neuroepithelial tumor encephalomalacia (e.g., from previous stroke) vascular malformations

Neuronal hyperexcitability is due to

derangements of the fine balance between excitability and inhibition that characterizes the normal state, placing a neuron abnormally close to firing threshold

Most important part of the initial workup of a patient with paroxysmal neurologic symptoms

detailed history There is little dif culty in diagnosing a generalized seizure when the history is typical. However, other seizure types span a wide range of phenomena, and may be difficult to interpret for even those with experience. differential diagnosis in a newly presenting patient is wide, and the physician should be alert to both neurological and non-neurological seizure mimics.

Febrile patients presenting with seizure for the first time

do lumbar puncture

Monotherapy carries the advantages of

dosing simplicity, reduced cost and reduced adverse effects. However, if the use of two drugs in combination was successful and seizure control cannot be maintained after withdrawal of one of the drugs, dual therapy should be resumed.

Tonic-clonic ('grand mal') seizure --- EEG

during the initial phase of the seizure may show generalized paroxysmal fast activity ---- Typically this is obscured by muscle artifact in the tonic phase of the seizure clonic phase accompanied by a choppy pattern of intermittent generalized muscle artifact. There is postictal suppression of all rhythms, with a slow return of background activity.

Management of SE

early involvement of a neurologist

Management of SE

early treatment very important early involvement of a neurologist Intervention consists of general measures, specific measures for particular patients (e.g., blood culture, spinal fluid examination for suspected intra-cranial infection), supportive treatment, and the administration of antiepileptic drugs. Patients with a known diagnosis of epilepsy should have their normal anticonvulsants reinstituted promptly in addition to all other measures

Third-most common cause of neurological morbidity in the United States

epilepsy (after stroke & dementia) in the USA -- 61 per 100,000 -- lifetime prevalence of 1.65% --- Annual epilepsy-related costs to the nation are estimated in excess of $10b

Terminology

epilepsy and seizure are often used interchangeably. However, recurrent seizures are more accurately regarded as paroxysmal symptoms of the underlying condition of epilepsy. The epilepsy may be either a syndrome in itself or a consequence of other neurologic disease. Seizures do not always imply epilepsy: for example, childhood febrile seizures, or a single seizure in an adult from, say, metabolic disturbance, are regarded as acute symptomatic events. Epilepsy is only diagnosed on the basis of repetitive, unprovoked seizures. ---- commonly, this is when a patient presents with a second seizure without apparent cause.

Newer antiepileptic drugs

gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin and zonisamide. no evidence demonstrating improved efficacy of any of the newer agents over the old in reducing the seizure frequency advantages: different mechanisms of action, improved pharmacokinetics with less need for drug monitoring, fewer drug interactions, improved therapeutic ratios, decreased toxicity, and improved tolerability in special populations

Strategy of epilepsy surgery

identify whether a definite brain focus for the patient's seizures exists and whether it can be safely removed (i.e., without creating unacceptable neurologic deficit). ----- Open resective surgery

Diagnosis of SE

in an obviously convulsing patient with a corroborating history, it is straightforward always worth pausing to exclude pseudo-SE in a patient with nonepileptic seizures

Infection

increases the likelihood of seizure occurrence elevation in white blood cell count may follow seizures

Complex Partial Seizure

involve at least some loss of awareness and amnesia for the event, and normally indicate a temporal or frontal lobe location patient may stare or behave confusedly, and does not follow commands consistently There may be a period of postictal confusion or aphasia before the patient returns to interacting normally. The loss of awareness is likely due to simultaneous inactivation of language and memory mechanisms, and therefore pronounced in seizures of the dominant hemisphere.

Generalized Seizure

involve the whole brain both clinical and EEG manifestations reflect bihemispheric brain involvement may occur at the outset or may progress from a partial seizure Clinical symptoms vary from a pure staring spell (impaired awareness without major motor manifestions) to generalized motor activity.

When adding a second anticonvulsant to a patient's regime,

it is wise to choose one with a different mechanism of action than the one the patient is already on. significant fraction of epilepsy patients remain resistant to all current drug treatments

Treating SE

key to good outcome is early treatment includes prompt recognition of status epilepticus by primary care providers, caregivers, and emergency medical services personnel, as well as the administration of first-line drugs in the community.

3 main categories of epilepsy

localization-related generalized un-determined

Tonic-clonic ('grand mal') seizure

may be preceded by partial seizures, in which case they are referred to as secondarily generalized seizures. In the idiopathic epilepsies, they occur de novo begin with a tonic phase: loss of consciousness and stiffening of the axial musculature and extremities; can be accompanied by a sharp exhalation (causing the audible epileptic cry) and a period of apnea during which the patient may turn blue; Associated jaw clenching may cause a tongue bite. The tonic phase of the seizure generally lasts less than 30 seconds. clonic phase follows; it is characterized by repetitive muscle contraction and relaxation, normally lasting under 1 minute, after which urinary incontinence may occur

Inborn derangements

may be structural (cortical dysplasia causing abnormal network architecture) or originate in metabolic or chromosomal anomaly. Epilepsy genetics is a rapidly developing field, and a number of epilepsies have now been ultimately linked to mutations in ion channel or receptor genes

EEG during complex partial seizures

may show localized or more diffuse rhythmic changes Occasionally, a clear pattern emerges within a few seconds of onset that precisely localizes the seizing brain lobe. It is not uncommon however for EEG to be normal, obscured by artifact, or otherwise nonlocalizing. ------- This is typically the case in seizures of deep frontal lobe origin, where the little surface change there would be is obscured by movement artifact.

Status epilepticus (SE)

medical emergency continuous or repetitive seizures lasting 30 minutes or more, without intervening recovery of consciousness. Many experts advocate shortening this defining period to 10 minutes or less; for clinical purposes, continuous seizures for 5 minutes or longer constitute a practical definition of SE.

Spikes and seizures arise from

membrane hyperexcitability that allows repetitive action potentials ---- puts neuron closer to firing threshold Facilitated transmission between neurons via altered synaptic and network mechanisms allow propagation of these disturbances to distant brain regions.

CC and MST are considered when

more definitive resective surgery is precluded

Radiosurgery

non-invasive alternative achieved with targeted radiation from a gamma knife restricted presently to a few published series and centers possessing the requisite technology takes time to achieve its effect (>6 months) and appears to offers little by way of advantages for seizure or cognitive outcome. does not constitute a widespread realistic alternative to conventional surgery

Psychogenic nonepileptic seizures

nonorganic events mimicking epileptic seizures eventual diagnosis in 10-45% of all patients initially referred to comprehensive epilepsy programs. Females are more frequently affected than males. The psychiatric mechanisms are presumed to be dissociation and conversion. (not a type of malingering, genuine psych disease) There is a reported association with previous physical and sexual abuse.

Simple partial seizures involving the primary somatosensory cortex

numbness or paresthesias symptoms may remain isolated or evolve sequentially

Atonic Seizures

opposite of myoclonus: there is a sudden loss of postural tone; recovery is usually immediate. range in severity from a brief head drop with preserved axial muscle tone, to a whole body loss of tone, resulting in an abrupt fall, with risk of significant injury. The scalp EEG pattern is usually nonlocalizing. Concurrent EMG confirms the diagnosis with a corresponding transient dropout of activity.

Localization-related epilepsies

originate from a specific focus. A focus may be a circumscribed single lesion, such as old stroke, brain tumor, or vascular anomaly. The origin may also be multifocal (e.g., tuberous sclerosis) or diffuse (e.g., hypoxic- ischemic injury).

Multiple subpial transaction (MST)

palliative surgical procedure controversial; carried out routinely in only a few epilepsy centers employed when the seizure onset area is close to, or abuts, eloquent cortex. undercut the U-fibers that link the seizure onset area from adjacent cortex, leaving the descending white matter pathways intact. Results for seizure outcome and preservation of eloquent function are variable

Corpus callosotomy (CC)

palliative surgical procedure divide the corpus callosum (usually the anterior two-thirds, keeping the splenium intact), to prevent seizure propagation between the hemispheres employed principally to treat drop attacks, when it can be very effective. There is evidence that it also ameliorates other seizure types. Children and young adults tend to do better long term than older patients.

Differential Diagnosis

paroxysmal event may result from seizure, syncope, migraine, cerebral ischemia, movement disorder, labrynthine problems, sensory or cerebellar pathology, sleep disorder, metabolic imbalance, or psychiatric disturbance. Functional (nonorganic) cause is also common. Three of the more common conditions that may be confused with epileptic seizure are psychogenic nonepileptic seizures, syncope and migraine.

Epilepsy

pathologic brain state characterized by a spontaneous tendency to recurrent seizures

Epilepsy pathophysiology is thus understood via

perturbations of ion channel biophysics, recep- tor chemistry and network architecture. One or more of these produces an epilepsy, whose domain (focal or generalized), seizure propensity, and other behavioral characteristics depend on the details.

Before 1990, seven major anticonvulsants were available for the treatment of all forms of epilepsy:

phenobarbital phenytoin carbamazepine valproic acid primidone Ethosuximide and clonazepam also fell into this category but were used far more selectively. continue to be used; they have the advantages of familiarity, lower costs, established efficacy, long patient-year experience among physicians, and wide availability. However, limited utility of these older drugs in a large fraction of patients with epilepsy

EEG

presence of IEDs on EEG will support a diagnosis of epilepsy, though a normal EEG does not exclude the diagnosis. Approximately 50% of pa- tients with subsequently proven epilepsy will have visible IEDs on the first EEG, with more detected if the EEG is repeated, though there is little evidence of diagnostic bene t from further EEG testing if the first four studies are negative. Alternatively, some centers perform prolonged continuous (24h) recording at first presentation, which should theoretically offer the best diagnostic yield of IEDs.

Un-determined epilepsies

presence or absence of a focus is unknown are categorized as undetermined

Truly nonlesional epilepsy

presents great difficulty, and represents the biggest current challenge to curative epilepsy surgery

Simple partial seizures involving the motor strip

produce focal motor activity This activity can remain localized (e.g., twitching of one thumb) or spread to involve sequential body parts—the so- called Jacksonian march.

Simple partial seizures involving the special sensory areas

produce simple or complicated visual or auditory hallucinations, depending on whether primary or association areas are involved. Gustatory hallucinations, abdominal sensations, and autonomic symptoms (e.g., nausea, vomiting, pallor, flushing, diaphoresis, pupil dilatation, etc.) occur with involvement of the limbic structures or insula. Aphasia is common if the dominant temporal or lateral frontal cortex is involved.

Pseudo-SE

recognized by atypical, intermittent and neurologically inconsistent (e.g. jerky movements of one arm and the opposite leg) patterns of body movements and some response to pain and threat, though it requires experience to reliably distinguish the two. should also be suspected if there is an indifferent response to emergency anticonvulsant treatment.

Psychogenic nonepileptic seizures --- treatment

relies primarily on psychotherapy Anticonvulsants should be withdrawn A short history and good patient insight are favorable prognostic factors. Patients with a chronic course, multiple comorbidities,unfavorable psychosocial circumstances and inadequate insight do poorly and can be difficult to manage long term. Epileptic and nonepileptic seizures may coexist, adding to the complexity of these cases.

Nonconvulsive SE (NCSE)

requires a high index of suspicion and should be excluded with EEG in any patient in an unexplained altered mental status or coma. The lack of convulsions in this case leads to less morbidity and better outcomes than convulsive SE.

Voltage-gated Na+ channel

responsible for the large influx of this species at the upstroke of an action potential

Chronic refractory epilepsy

roughly 30% of the epilepsy population In the United States, this comprises a patient population of close to 1 million. The challenge of refractory disease has driven the development of newer anticonvulsant medications, provided impetus for epilepsy surgery, and widened the search for alternative treatments.

Definition of a spike

short-lived burst of synchronous neural firing causing a corresponding sharp rise followed by decay of local field potential (LFP). (also called interictal epileptiform discharges, IEDs) can be seen on the scalp EEG, and are the archetypal abnormality of epilepsy. Seizures are, to good approximation, spikes that propagate in time and space.

Psychogenic nonepileptic seizures --- EEG

should be referred for continuous video-EEG monitoring, which will usually clarify the diagnosis by recording the relevant paroxysmal episodes of abnormal movement or behavior Many of these have recognized patterns, though this is not always so the physician looks for physical behavior that is inconsistent with an epileptic seizure, rather than positively identifying a template nonepileptic spell. The EEG during the episode is normal.

Epilepsy syndrome

simple concept of a clinicopathologic entity characterized by one or more of the following: seizure type (or types), EEG appearance, age of patient at onset, family history, precipitating factors and severity. Attempting accurate syndromic diagnosis is informs medication choice, prognosis, and the appropriateness of surgical intervention.

Considerations when choosing the correct drug

specific seizure type and the epilepsy syndrome safety, efficacy, and potential adverse effects pharmacokinetic profile and interactions with other medications impact of a given drug on the patient's other medical conditions, and quality of life issues may be the main consideration in speci c patient groups (e.g., the elderly or those with mul- tiple comorbidities) Cost

If the area of cortex involved in a simple partial seizure is small,

the ongoing EEG can be normal In practice, this is only rarely the case; localized rhythmic change is usually seen.

Syncope

spells usually have a characteristic warning (i.e., lightheadedness, loss of vision, or muffled hearing) onset is gradual, and a precipitant is usually identified, except when syncope results from cardiac arrhythmia Typical features include occurrence with prolonged sitting or standing; dyspnea or palpitations before the loss of consciousness; diaphoresis or nausea before an episode; and chest pain or a feeling of warmth before an episode. Incontinence during the episode is rare. The tip of the tongue (usually not the side) may be bitten. Patients generally have minimal or no postictal confusion and somnolence, though autonomic symptoms may be prominent (e.g. nausea)

Diagnosis --- hallmark of epileptic seizures

stereotypy, duration (seconds to minutes, only rarely longer) and their relation to other aspects of the patient history

Acquired causes of epilepsy include

stroke, trauma, tumor, etc. that induce seizure-promoting changes of neuronal reorganization after injury.

A full systemic and neurologic examination should follow the history.

tailored to the relevant aspects of the history (e.g., postural blood pressure measurements for patients reporting paroxysmal orthostatic symptoms, the Hallpike maneuver for patients reporting positional dizziness; eye movement, cerebellar and sensory exam for patients describing intermittent unsteadiness).

Within the surgical population, most common cause of refractory focal epilepsy in adults

temporal lobe epilepsy associated with hippocampal sclerosis also the most amenable to surgical treatment

Treatment of temporal lobe epilepsy associated with hippocampal sclerosis

temporal lobectomy for epilepsy arising from unilateral mesial temporal sclerosis ----- results in freedom from seizures for 90% of patients A similarly favorable outcome can be expected for most epilepsies that result from focal lesions, provided that the lesion can be unequivocally demonstrated to generate the patient's seizures.

If seizure control cannot be achieved without significant adverse effects,

the drug is considered a failure and a second drug is chosen and the process repeated. If this is successful, an attempt may be made to withdraw the first drug.

Resting membrane and action potentials of neurons are largely governed by

the movements of sodium (Na+), potassium (K+), calcium (Ca++) and chloride (Cl-) ions. Their transmembrane traffic is governed by ion channels, which are proteins that change their conformation to allow or block throughput, depending on local voltage (voltage-gated) or presence of specific ligands (ligand- gated).

Excitatory influences are mediated by

the α-amino-3-hydroxy-5-methylisoxazole- 4-propionate (AMPA), NMDA and voltage-gated Ca++ channels

Most common type of generalized seizure

tonic-clonic ('grand mal') seizure

Migraine or Seizure? When diagnostic doubt persists, most clinicians will...

treat for migraine and assess response, rather than starting anticonvulsants it is important to avoid migraine agents that are also anticonvulsants, such as valproic acid or topiramate

Mortality for epilepsy patients

two to four times as high as in matched nonepileptic populations. The highest mortality and the lowest measures of quality of life are found in patients with chronic refractory epilepsy

SE patients with known epilepsy

usually the result of anticonvulsant withdrawal from poor compliance

Epilepsy surgery success rates

vary with epilepsy syndrome, as well as the technology and the human expertise deployed. reported a success rate of 66%

Management of Second Seizure

warrants treatment irrespective of investigative findings It is important to emphasize that committing a patient to treatment is effectively making a diagnosis of epilepsy, and the patient should counseled be appropriately.

Three main epilepsy classes are further subdivided according to

whether a definitive brain lesion is responsible (symptomatic), suspected (cryptogenic) or absent (idiopathic)

Management of First Seizure

whether to treat is controversial Most physicians would treat a first seizure in the setting of an epileptiform interictal EEG or relevant abnormal neuroimaging. If none such is found, routine practice is to not treat.

Complex partial seizures arising from the medial frontal or orbitofrontal brain regions

whole body stiffening, bicycling or other violent proximal limb movements (Automatisms can also occur in seizures in which consciousness is preserved.)