Classification of Seizures

1. Classification of Seizures

2. Why do we need to classify seizures? • Different seizures affect different parts of the brain • Different antiepileptic drugs are more effective with different seizures

3. Classification of Seizures • Partial Seizures - Simple partial - Complex partial - Partial Seizures with Secondary Generalization • Generalised Seizures - Absence Seizures (Petit Mal) - Atypical Absence Seizures - Generalized, Tonic-Clonic Seizures (Grand Mal) - Atonic Seizures - Myoclonic Seizures • Unclassified

4. Partial Seizures • occur within discrete regions of the brain • less than 2 minutes • If consciousness is fully preserved, the seizure is a simple partial seizure • If consciousness is impaired, the seizure is a complex partial seizure

5. Partial Seizures Simple Partial • cause motor, sensory or autonomic changes • precursors to complex partial seizure or tonic-clonic seizure • no alteration in consciousness • last a few seconds • changes in sensory sensation - déjà vu, flashbacks - somatic sensation (paresthesias) - vision (flashing lights or formed hallucinations) - equilibrium (sensation of falling or vertigo) - autonomic function (flushing, sweating, piloerection)

6. Partial Seizures Complex Partial • One of the most common types of seizures • focal seizure activity + transient impairment of the patient's ability to maintain normal contact with the environment • frequently begins with aura (simple partial seizure) • unable to respond appropriately to visual or verbal commands during the seizure • Lasts 2-3 minutes • The behavioral arrest is usually accompanied by automatisms • post-ictal confusion ranges from seconds up to an hour

7. Partial Seizures Partial Seizures with Secondary Generalization • partial seizures that spread involving both cerebral hemispheres leading to a generalized seizure • often difficult to distinguish from a primarily generalized tonic-clonic seizure

8. Generalized Seizures • arise from both cerebral hemispheres simultaneously

9. Generalized Seizures Absence Seizures (Petit Mal) • sudden, brief lapses of consciousness without loss of postural control • lasts for only seconds (<10s) • no aura • no postictal confusion • usually accompanied by subtle, bilateral motor signs such as rapid blinking of the eyelids • begins in childhood (ages 4 to 8) or early adolescence

10. Generalized Seizures Atypical Absence Seizures • have features that deviate from both the clinical and EEG features of typical absence seizures • usually is of longer duration (>10s) • less abrupt in onset and cessation • accompanied by more obvious motor signs (tonic, clonic or automatisms) • usually associated with diffuse or multifocal structural abnormalities of the brain

11. Generalized Seizures Generalized, Tonic-Clonic Seizures (Grand Mal) • the main seizure type in approximately 10% of all persons with epilepsy • most common seizure type due to metabolic derangements • with or without aura Tonic phase • tonic contraction of muscles throughout the body • loud moan or cry • lasts 10 to 20 s Clonic phase • superimposition of periods of muscle relaxation on the tonic muscle contraction • Respirations are impaired, secretions pool in the oral cavity, and the patient becomes cyanotic.

12. Generalized Seizures Generalized, Tonic-Clonic Seizures (Grand Mal) • Contraction of the jaw muscles • increased heart rate, BP, and pupillary size • Lasts 1-2 minutes Postictal phase • characterized by unresponsiveness, muscular flaccidity, and excessive salivation that can cause stridorous breathing and partial airway obstruction. • Bladder or bowel incontinence may occur • Last over minutes to hours

13. Generalized Seizures Atonic Seizures • sudden loss of muscle tone lasting 1 to 2 s • Consciousness is briefly impaired • usually no postictal confusion • A very brief seizure may cause only a quick head drop or nodding movement, while a longer seizure will cause the patient to collapse Myoclonic Seizures • sudden and brief muscle contraction that may involve one part of the body or the entire body • lasts 1 to 2 s. • A normal, common physiologic form of myoclonus is the sudden jerking movement observed just when you are falling asleep (hypnic jerk)

14. EPILEPSYSYNDROMES

15. Disorders in which the predominant feature is epilepsy • Evidenced to suggest a common underlying mechanism ( through clinical, EEG, radiological or genetic observations)

16. Three important syndromes: • Juvenile Myoclonic Epilepsy • Lennox-Gastaut Syndrome • Mesial Temporal Lobe Epilepsy Syndrome

17. Juvenile Myoclonic Epilepsy • Generalised seizure disorder • Unknown cause • Appears in early adolescence

18. Usually singular or repetitive bilateral myoclonic jerks • Most frequent in the morning after awakening; can be provoked by sleep deprivation • Unless severe, consciousness is preserved

19. Many experience generalised tonic-clonic seizures or absence seizures • Benign condition • Responds well to anticonvulsant medication, but complete remission is uncommon • Often a family history of epilepsy is present

20. 2. Lennox- Gastaut Syndrome • Triad • multiple seizure types (generalised tonic-clonic, atonic & atypical absence seizures) • an EEG showing slow (<3 Hz) spike-and-wave discharges and a variety of other abnormalities • impaired cognitive function

21. CNS disease or dysfunction as a result of: • developmental abnormalities • perinatal hypoxia/ ischemia • trauma • infection • Nonspecific response of the brain to diffuse neural injury • Poor prognosis (due to the underlying CNS disease and the physical and psychological consequences of severe, poorly controlled epilepsy)

22. 3. Mesial Temporal Lobe Epilepsy Syndrome • Complex partial seizures • Responds well to surgical intervention, refractory to anticonvulsants • Distinctive clinical, EEG and pathological features

23. History • febrile seizure • family history of epilepsy • early onset • Clinical observation • aura • behavioral arrest • complex automatism • unilateral posturing • postical disorientation, memory loss, dysphasia • Laboratory studies • EEG, PET & SPECT changes • MRI findings- hippocampal sclerosis

24. Causes of seizures & epilepsy

25. Imbalance of the normal excitatory and inhibitory mechanisms within the CNS • Three main factors involved with the occurrence of seizures or epilepsy

26. Three factors • Endogenous factors • a.k.a. predisposing factors • Influence the threshold for having a seizure • Presence of differences between individuals in the susceptibility for seizures • Examples include: • Genetic factors • Degree of development

27. Three factors (cont’d) • Epileptogenic factors • Conditions that have an extremely high likelihood in resulting in a seizure • Initiate epileptogenesis • Examples include: • Severe penetrating head trauma • Stroke • Infections

28. Three Factors (cont’d) • Precipitating factors • Speaks for itself • Examples include: • Intrinsic physiological processes • Psychological or physical stress • Sleep deprivation • Hormonal changes assoc with the menstrual cycle • Extrinsic processes • Toxic substances • Medications

29. Three Factors (summary) • Three factors interplay to emphasize the concept behind the many causes of seizures and epilepsy • Role in treatment • Predisposing  close f/up & aggressive diagnostic evaluation • Epileptogenic  estimation of recurrence & duration of therapy • Precipitating  removal > drug treatment

30. Causes According to Age • In clinical practice, classifying by age is important as it determines: • Incidence of seizures or epilepsy • Likely aetiologies of seizures or epilepsy

31. Neonatal & Early Infancy • Hypoxic-ischemic encephalopathy • Trauma • CNS infection • Congenital CNS abnormalities • Metabolic disorders • Born to mothers using neurotoxic drugs • Hypoglycaemia • Hypcalcemia • Inborn errors of metabolism • Idiopathic/Inherited forms of benign neonatal convulsions

32. Late Infancy & Early Childhood • Febrile seizures • Peak incidence between 18 to 24 months • Generalized tonic-clonic seizure during a febrile illness • Usually during first day of illness • Two types: • Simple • Complex

33. Late Childhood • Well-defined epilepsy syndromes • Temporal lobe epilepsy • Developmental disorders • Head trauma • CNS infection • CNS tumour

34. Adolescence & Early Adulthood • Head trauma • CNS infections • Brain tumours • Congenital CNS abnormalities • Illicit drug use • Alcohol withdrawal

35. Older Adults • Cerebrovascular disease • Trauma • CNS tumours • Degenerative diseases

36. Non-age Dependant • Metabolic disturbances • Electrolyte imbalance • Renal failure • Hepatic failure • Endocrine disorders • Hematologic disorders • Vasculitides • Medications & Abused substances

37. Mechanism of seizures in epilepsy

38. Partial Seizures Begins from a discrete region of the cortex which slowly spread to the neighbouring regions. Divided into two phases: • Seizure initiation phase • Seizure propagation phase

39. Seizure initiation phase Consists of 2 concurrent events occurring in an aggregate of neurons: • High frequency bursts of potentials relatively long-lasting depolarization of neuronal membrane, initially initiated by the influx of Ca2+ from the ECF which later cause the opening of voltage-dependent Na+ channels and Na+ influx. This results in generation of repetitive AP. Depending on cell type, either GABA or K+ channels will cause hyperpolarization. • Hypersynchronization Synchronized burst from sufficient number of neurons will produce spike discharges seen on the ECG.

40. Seizure propagating phase Spread of bursting activity normally prevented by 2 mechanism: • Intact hyperpolarization • inhibitory neurones Region of inhibitory surrounding When sufficient neurons are recruited loss of surrounding inhibition propagation of seizure activity into: • Contiguous areas thru local cortical connections • More distant areas thru long commisural pathways e.g. corpus callosum

41. Neuronal Excitability Can be affected by various factors: • Intrinsic to neuron Conductance of ion channels, response characteristics of membrane receptors, cytoplasmic buffering, 2nd messenger systems and protein expression • Extrinsic to neuron Amount or type of neurotransmitters present at synapse, modulation of receptors by ECF ions and temporal and spatial properties of synaptic and non-synaptic input • Non-neuronal cells Astrocytes, oligodendrocytes

42. Some explainable situations causing seizures • Domoic acid ingestion Analogue of glutamate ( main excitatory NT in brain) • Penicillin Antagonizes the effects of GABA at its recpetors reducing seizure threshold seizures!

43. Other precipitating factors of seizures- not well understood • Sleep deprivation • Alcohol withdrawal • Fever • Hypoxia • Infection

44. Epileptogenesis Transformation of normal neuronal network into one which is chronically hyperexcitable. Takes months to years between CNS injury and first seizure. Pathologic studies of hippocampus of patients with TLE shows that: • due to changes in neuronal network loss of neurons contributing to inhibition of neurons • Remaining neurons sprout in a way that increases the network excitability

45. Initial injury (very focal region) • local hyperexcitability • structural changes over time • seizures

46. Genetic causes of epilepsy Recent identification of genetic mutations associated with variety of epilepsy syndromes important conceptual advances. Found that many inherited idiopathic epilepsies are due to channelopathies (mutations affecting the ion channel fx.) Current challenge is to identify multiple susceptibility genes that underlie the more common forms of idiopathic epilepsies.

47. Mechanism Of Action of Antiepileptic drugs Generally blocks the initiation and spread of seizures. Mechanisms: • Inhibition of Na+ dependent AP in a frequency dependent manner • Inhibition of voltage gated Ca2+ channels • Decrease in glutamate release • Potentiation of GABA receptor function • Increasing the availability of GABA • Inhibition of T-type Ca2+ channels in thalamic neurons There are no ‘ anti-epileptogenic’ drugs available which helps prevent emergence of seizure formation following injuries

48. Adult Case 1

49. PERSONAL DETAILS • Patient Initials: NS • Registration Number: HPD 31667 • Age: 39 years old • Race: Indian • Gender: Female • Occupation: Caterer • Date of Admission: 26th April 2009 • Date of Clerking: 28th April 2009

50. CHIEF COMPLAINT Presented with 3 episodes of seizures 1 day before admission.