Epilepsy

Up todate info on epilepsy classification Signs and Symptoms and management
Included are also EEG findings

1. 1 Seizures & Epilepsy: BY ORIBA DAN LANGOYA, MBCHB V & KUSEMERERWA MABLE, MBCHB V Supervisor: Dr. Kaddu Mark

2. 2 Outline Definition Etiology Classification Differential Diagnosis Treatment of Epilepsy

3. 3 Definition of Seizures Is a paroxysmal event due to abnormal excessive or synchronous neuronal activity in the brain. Seizures are usually unpredictable Seizures usually brief ( < 5 minutes) and stop spontaneously Convulsion , ictus, event, spell, attack and fit are used to refer to seizures. Epilepsy is the tendency to have recurrent seizures.

4. Epilepsy Epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process. This implies that a person with a single seizure, or recurrent seizures due to correctable or avoidable circumstances, does not necessarily have epilepsy. Using the def of epilepsy as 2 or more unprovoked seizures, the incid of epilepsy is ~0.3–0.5% in diff popn throughout, and the prev of epilepsy has been estimated at 5–30 persons per 1000 . Nonepileptic seizures (NES) are sudden changes in behavior that resemble epileptic seizures but are not associated with the typical neurophysiological changes that characterize epileptic seizure

5. 5 Etiology of Seizures Seizures are either provoked or unprovoked Provoked Seizures: Triggered by certain provoking factors in otherwise healthy brain Metabolic abnormalities (hypoglycemia and hyperglycemia, hyponatremia, hypocalcemia, Hypomagnesium, Non ketotic hyperglycemia, Uremia, Hypoxia, Hyperthyroidism, Dialysis disequilibrium syndrome, Porphyria, hypocalcaemia) Alcohol withdrawal Acute neurological insult (infection, stroke, trauma) Illicit drug intoxication and withdrawal Prescribed medications that lower seizure threshold (theophylline, TCA) High fever in children Unprovoked Seizures: Occur in the setting of persistent brain pathology

6. 7 Etiology of Epilepsy Any process that alters the structure (macroscopic or microscopic) or the function of the brain neurons can cause epilepsy Processes that lead to structural alteration include; Congenital malformation Degenerative disease Infectious disease Trauma Tumors Vascular process Inborn errors of metabolism In majority of patients, the etiology is proposed but not found In elderly , vascular, degenerative and neoplastic causes are more common compared to younger adults.

7. CLASSIFICATION OF SEIZURES The International League against Epilepsy (ILAE) Commission on Classification and Terminology, 2005–2009

8. General Principles A fundamental principle is that seizures may be either focal or generalized . Focal seizures originate within networks limited to one cerebral hemisphere. Generalized seizures arise within and rapidly engage networks distributed across both cerebral hemispheres. Focal seizures are usually associated with structural abnormalities of the brain. In contrast, generalized seizures may result from cellular, biochemical, or structural abnormalities that have a more widespread distribution .

9. FOCAL SEIZURES A rise from a neuronal network either discretely localized within one cerebral hemisphere or more broadly distributed but still within the hemisphere . They can be described as focal seizures with or without dyscognitive features . Focal seizures can also evolve into generalized seizures . Focal Seizures Without Dyscognitive Features FS can cause motor , sensory, autonomic, or psychic symptoms without impairment of cognition . Three additional features of focal motor seizures are worth noting. Ie, phenomenon, described by Hughlings Jackson and known as a “Jacksonian march, localized paresis (Todd’s paralysis), E pilepsia partialis continua

10. Focal Seizures Without Dyscognitive Features Focal seizures may also manifest as changes in somatic sensation ( e.g., paresthesias), V ision (flashing lights or formed hallucinations), Equilibrium (sensation of falling or vertigo ) A utonomic function ( flushing, sweating, piloerection) Temporal or frontal cortex may also cause alterations in hearing, olfaction, or higher cortical function (psychic symptoms ) This includes the sensation of unusual, intense odors (e.g., burning rubber or kerosene) or sounds (crude or highly complex sounds), or an epigastric sensation that rises from the stomach or chest to the head

11. An EEG shows the first 10 seconds of FS discharge, with 5-Hz rhythmic theta activity in channels recorded in the right temporal scalp

12. Focal Seizures with Dyscognitive Features May also be accompanied by a transient impairment of the patient’s ability to maintain normal contact with the environment. Inability to respond appropriately to visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase S eizures frequently begin with an aura (i.e., a focal seizure without cognitive disturbance ) The start of the ictal phase is often a sudden behavioural & marks the onset of the period of impaired awareness . The behavioral arrest is usually accompanied by automatisms , which are involuntary , automatic behaviors that have a wide range of manifestations. Eg. chewing , lip smacking, swallowing, or “picking” movements of the hands

13.   Interictal EEG in localization-related epilepsy.

14. P atient is typically confused following seizure, & transition to full recovery of consciousness may range from seconds up to an hour. Exams immediately following the seizure may show an anterograde amnesia or, in cases involving the dominant hemisphere, a postictal aphasia. The range of potential clinical behaviors linked to focal seizures is so broad Detailed EEG is required .

15. EVOLUTION OF FOCAL SEIZURES TO GENERALIZED SEIZURES FS can spread to involve both cerebral hemispheres and produce a GS, usually of the tonic- clonic . Observed frequently following FS arising from a focus in the frontal lobe Often difficult to distinguish from a primary generalized-onset tonic- clonic seizure. The focal onset is not clinically evident and may be established only through careful EEG analysis . Distinguishing btn these 2 entities is extremely important, B ecause there may be substantial differences in the evaluation and treatment of epilepsies associated with focal versus generalized seizures

16. GENERALIZED SEIZURES GS are thought to arise at some point in the brain but immediately and rapidly engage neuronal networks in both cerebral hemispheres Several types of GS have features that place them in distinctive categories and facilitate clinical diagnosis . Typical Absence Seizures Atypical Absence Seizures Generalized, Tonic-Clonic Seizures Atonic Seizures Myoclonic Seizures

17. Typical Absence Seizures TAS are xterized by sudden , brief lapses of consciousness without loss of postural control . Typically lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion . Absence seizures are usually accompanied by subtle, bilateral motor signs such as rapid blinking of the eyelids, chewing movements, or small-amplitude, Clonic movements of the hands TAS are associated with a group of genetically determined epilepsies with onset usually in childhood (ages 4–8 years) or early adolescence and are the main seizure type in 15–20% of children with epilepsy.

18. TAS Cont . The seizures can occur hundreds of times per day, but the child may be unaware of or unable to convey their existence. Often subtle, pay attention to often unexplained “daydreaming” and a decline in school performance recognized by a teacher The EEG hallmark of typical absence seizures is a generalized, symmetric, 3-Hz spike-and-wave discharge that begins and ends suddenly, superimposed on a normal EEG background . Periods of spike-and-wave discharges lasting more than a few seconds usually correlate with clinical signs. Hyperventilation tends to provoke these electrographic discharges and even the seizures themselves

19. Absence seizure. The 3-Hz spike and wave pattern of absence epilepsy

20. Atypical Absence Seizures D eviate both clinically & electrophysiologically from typical absence seizures. Eg. The lapse of consciousness is usually of longer duration and less abrupt in onset and cessation , The seizure is accompanied by more obvious motor signs that may include focal or lateralizing features The EEG shows a generalized, slow spike-and wave pattern with a frequency of ≤2.5 per second, as well as other abnormal activity . Usually associated with diffuse or multifocal structural abnormalities of the brain The seizures are less responsive to anticonvulsants

21. Generalized, Tonic-Clonic Seizures Generalized-onset tonic- clonic seizures are the main seizure type in ~10% of all persons with epilepsy . They are also the most common seizure type resulting from metabolic derangements The seizure usually begins abruptly without warning. The initial phase of the seizure is usually tonic contraction of muscles throughout the body. Tonic contraction of the muscles of expiration and the larynx at the onset will produce a loud moan or “ictal cry.” Respirations are impaired, secretions pool in the oropharynx, and cyanosis develops. Contraction of the jaw muscles may cause biting of the tongue .

22. Generalized, Tonic-Clonic Seizures Enhancement of sympathetic tone leads to increases in HR, BP, and pupillary size. After 10–20 s, the tonic phase of the seizure typically evolves into the clonic phase. Produced by the superimposition of periods of muscle relaxation on the tonic muscle contraction . The periods of relaxation progressively increase until The end of the ictal phase, which usually lasts no more than 1 min The postictal phase is characterized by unresponsiveness, muscular flaccidity Patients gradually regain consciousness over minutes to hours.

23. Generalized, Tonic-Clonic Seizures Patients subsequently complain of headache, fatigue, & muscle ache. The EEG during the tonic phase of the seizure shows a progressive increase in generalized low-voltage fast activity, followed by generalized high-amplitude, polyspike discharges . In the clonic phase, the high-amplitude activity is typically interrupted by slow waves to create a spike-and-wave pattern . The postictal EEG shows diffuse slowing that gradually recovers as the patient awakens There are a number of variants, pure tonic & Pure clonic seizure Usually associated with specific epileptic syndromes having mixed seizure phenotypes , such as the Lennox- Gastaut syndrome (discussed below).

24. Atonic Seizures Characterized by sudden loss of postural muscle tone lasting 1–2 s. Consciousness is briefly impaired, but there is usually no postictal confusion . A very brief seizure may cause only a quick head drop or nodding movement, whereas a longer seizure will cause the patient to collapse . The EEG shows brief, generalized spike-and-wave discharges followed immediately by diffuse slow waves that correlate with the loss of muscle tone . Similar to pure tonic seizures, atonic seizures are usually seen in association with known epilepsy syndromes.

25. Myoclonic Seizures Sudden and brief muscle contraction that may involve one part of the body or the entire body. Physiological form is the sudden jerking movement observed while falling asleep Pathologic myoclonus is most commonly seen in association with metabolic disorders, degenerative CNS diseases , or anoxic brain injury. Myoclonic seizures are considered to be true epileptic events because they are caused by cortical (versus subcortical or spinal) dysfunction . The EEG may show bilaterally synchronous spike-and-wave discharges synchronized with the myoclonus Myoclonic seizures usually coexist with other forms of generalized seizures but are the predominant feature of juvenile myoclonic epilepsy

26. CURRENTLY UNCLASSIFIABLE SEIZURES Not all seizure types can be designated as focal or generalized Epileptic spasms are such an example. These are xterized by a briefly sustained flexion or extension of predominantly proximal muscles, including truncal muscles. EEG in these usually shows hypsarrhythmias, which consist: Of diffuse, giant slow waves with a chaotic background of irregular , multifocal spikes and sharp waves . Epileptic spasms occur predominantly in infants and likely result from differences in neuronal function and connectivity in the immature versus mature CNS

27. EPILEPSY SYNDROMES Are disorders in which epilepsy is a predominant feature , and T here is sufficient evidence (e.g., through clinical, EEG, Radiologic , or genetic observations) to suggest a common underlying mechanism. JUVENILE MYOCLONIC EPILEPSY Is a generalized seizure disorder of unknown cause that appears in early adolescence. U sually xterized by bilateral myoclonic jerks that may be single or repetitive. Seizures are most frequent in the morning after awakening and can be provoked by sleep deprivation . Consciousness is preserved Many patients also experience GTCS, and up to one-third have absence seizures. Respond well to appropriate anticonvulsant medication . There is often a family history of epilepsy, and genetic linkage

28. LENNOX-GASTAUT SYNDROME O ccurs in children and is defined by the following triad: M ultiple seizure types (including GTCS, atonic, and atypical absence seizures ); An EEG showing slow (<3 Hz) spike-and-wave discharges & a variety of other abnormalities; Impaired cognitive function in most but not all cases . LGS is assoc with CNS disease or dysfunction from a variety of causes, including de-novo mutations Developmental abnormalities, perinatal hypoxia/ischemia, trauma, infection , and other acquired lesions. The multifactorial nature of this syndrome, nonspecific response of the brain to diffuse neural injury . Poor prognosis due to the underlying CNS disease

29. MESIAL TEMPORAL LOBE EPILEPSY SYNDROME MTLE is the most common syndrome associated with focal seizures with dyscognitive features. An epilepsy syndrome with distinctive clinical, electroencephalographic , and pathologic features High resolution MRI can detect the xteristic hippocampal sclerosis that appears to be essential in the pathophysiology of MTLE Recognition of this syndrome is esp important because it tends to be refractory to tx with anticonvulsants but responds well to surgical intervention .

30. DIAGNOSIS Laboratory screening – the following are necessary in evaluation of a first seizure Serum electrolytes, glucose, magnesium, calcium, CBC, RFTs, LFTs, TFTs and toxicology screen Prolactin – prolactin concentration rises shortly generalized tonic clonic seizures. Sample is drawn 10 to 20 minutes after the event and compared with the baseline drawn atleast six hours before. Lumbar puncture – Incase of suspected infectious process or metastatic cancer. It may be misleading since prolonged seizures may result in pleocytosis . Electroencephalogram Neuroimaging- MRI and CT scan. 50% of patients regardless of age have normal neuroimaging studies.

31. MANAGEMENT Goals for treatment C ontrolling seizures, A voiding treatment side effects Maintaining or restoring quality of life The optimal treatment plan is derived following , A ccurate diagnosis of the patient's seizure type(s ) Objective measure of the intensity and frequency of the seizures A wareness of medication side effects , Evaluation of disease-related psychosocial problems A ntiepileptic drugs (AEDs ) Patients should have knowledge about available AEDs including their mechanisms of action, pharmacokinetics, drug-drug interactions, and adverse effects.

32. Differential Dx of seizures

33. Management cont’d Treatment depends on the type/class of seizures e.g. partial or generalized seizures When to start AEDs Immediate antiepileptic drug (AED) therapy is usually not necessary in individuals after a single seizure, particularly if a first seizure is provoked by factors that resolve . AED therapy should be started in patients who are at significant risk for recurrent seizures, such as those with remote symptomatic seizures . AED treatment is generally started after two or more unprovoked seizures, because the recurrence proves that the patient has a substantially increased risk for repeated seizures, well above 50 percent. AED therapy is not necessarily life-long.

34. 36 Treatment of Established Epilepsy First Line Approved Anti-Epileptic Drugs (AEDs) Second Line (intractable epilepsy) Epilepsy Surgery Vagus Nerve Stimulation Therapy Experimental Therapy AEDs Implanted Devices

35. Selection of AED

36. STATUS EPILEPTICUS Series of seizures occur without the patient regaining awareness between attacks over a period of 30 min. Mostly it refers to recurrent tonic clonic seizures (major status). It’s a life-threatening medical emergency. Partial motor status is clinically obvious. It’s precipitated by abrupt withdrawal of anticonvulsant drugs, the presence of a major structural lesion or acute metabolic disturbance.

37. ETIOLOGY  Some of the more common predisposing factors include : Antiepileptic drug noncompliance or discontinuation Withdrawal syndromes Acute structural injury (e.g. , brain tumor or cerebral metastasis, stroke, head trauma, subarachnoid Remote or longstanding structural injury Metabolic abnormalities Chronic epilepsy; status epilepticus may represent part of a patient's underlying epileptic syndrome Mortality rates for adults with first episode is about 20%. Mortality rate for patients with cerebral anoxia is about 69 to 81%. Mortality is due to metabolic stress of repeated convulsions

38. The End DAN & MABLE, MBchB V