Seizure Diagnosis, Pathophysiology and Management - Coursework Example

SEIZURE DIAGNOSIS, PATHOPHYSIOLOGY AND MANAGEMENT By Student’s name Code + Course Name Professor’s Name University/College Name City, State Date Introduction Seizures are usually a manifestation of neurological disturbances in discharge of neurons in the brain. Different brain areas can form the epicentre or origin of seizure. Their presentation vary depending on the type of seizure and the aetiology behind the seizure (Sun, Selassie & Pritchards 2014, p. P5). Common symptoms range from brief attention lapses and abnormal muscle movement to convulsions that can be prolonged (World health Organization [WHO] 2015). Seizures can occur at a frequency of once yearly to many episodes per day. Some seizures are more common in children than adults while others present more in adults than children but an individual from any age group can be affected (Buchhalter 2011, p. 113). If the seizures occur recurrently and they are unprovoked whether been from identifiable or unidentifiable causes, they are described as epilepsy (Beletsky & Mirsattari 2012, p. 1). About 50 million people in the world are estimated to be affected by epilepsy with more than 70% of the affected individuals originating from low and middle-income nations (WHO 2015). The prevalence is high among children and in older adults aged above 60 years (Beletsky & Mirsattari 2012, p. 1). In this paper, the diagnosis, pathophysiology and management of different forms of seizures shall be examined with consideration of the case study provided of a patient that has experienced an episode of seizure. The Seizure and its Differential Diagnosis The patient has experienced a seizure. To diagnose the type of seizure experienced by the patient requires sufficient history regarding the occurrence of the seizure and any other previous history that may be classified as a seizure, presence of precipitating factors or known aetiologies for seizures such as traumatic brain injury, tumours, strokes, or diseases affecting the brain, and some genetic syndromes (WHO 2015). Some of these aetiologies may be identified via use of computerised tomography (CT) scan of the brain or less commonly magnetic resonance imaging (MRI) but confirmation of a clinical diagnosis is aided by interictal electroencephalogram (EEG) abnormalities (Ho et al. 2013, p. 399; AlEissa 2015). Nevertheless, lack of EEG abnormalities is not an exclusion criteria for seizures or epilepsy. Based on the history, aetiologies, clinical presentation and findings on neuroimaging or EEG, diagnosis of seizures is possible. Generally seizures can be grouped into focal onset and generalised onset seizures. The former is further subdivided into simple focal, complex focal and secondarily generalised tonic clonic seizures (SGTCS) (Panayiotopoulos 2010, p. 29). Generalised onset seizures include tonic seizures, absence seizures, myoclonic seizures, clonic seizures, atonic seizures and primarily generalised tonic clonic seizures (PGTCS) (Panayiotopoulos 2010, p. 29-30). When these seizures happen on a more frequent basis such as at least two episodes of the seizures without there been any immediate provocation from any source, it is said to be epilepsy (AlEissa, 2015). Considering the patient in the provided case scenario, the seizure first presented with aura before it occurred as the patient reported having felt dizzy before collapsing (Ko 2015). The aura probably presented in form of a simple focal seizure as the patient had his consciousness preserved and he could remember the events prior to the seizure degeneration. After the first seizure the patient exhibited confusion and disorientation and he could not remember the events during the seizure increasing the likelihood that the seizure had aggravated to a complex focal seizure (Johannessen & Ben-Menachem 2006, p. 1702; N Acharya & J Acharya 2014, p. S18). This is supported by the fact that loss of consciousness or recollection of events during the ictal stage of the seizure is characteristic of complex seizures that may be of focal origin (Carroll, 2015). Postictal confusion is also a common occurrence in complex focal seizures. It is not clear regarding the patients’ symptoms during the seizure to inform more narrowed differential diagnosis of the seizure types. Nevertheless, since there was loss in consciousness as the patient could not remember ictal events, the seizure could have been a complex focal type. Depending on the presenting symptoms, the localisation of the hemispherical origin of the seizure is possible. If during the seizure, the patient was seen to perform automatism activities such as lip-smacking movements, chewing, muttering or mumbling words without decipherable meaning, or wondering around, then the complex focal seizure (CFS) can be identified to be of temporal origin (Panayiotopoulos 2010, p. 31). CFS of frontal origin may have presenting symptoms such as screams or loud cries heard from the patient or strange body movements kicking and cycling movements. Sometimes the focal seizure can progress to generalised seizures in which case they are referred to as secondary generalised seizures (SGS) (Carroll 2014). Fortifying the diagnosis of SGS requires the identification of symptoms of generalised seizures in patients who have just had a focal seizure. Such symptoms include rhythmic jerky movements and sudden tonic flexion or extension of the extremities. However, differentiating primary and secondary generalised seizures on the basis of the presenting history alone is not easy and an ictal EEG is a better confirmatory test for the diagnosis (Fisher, Scharfman & deCurtis 2014, p. 4-6; Staley & Dudek 2006, p. 199). In addition, it is not uncommon to find overlapping seizures such that differentiating them from the patient’s history is difficult. Therefore, the other types of generalised seizures such as clonic, atonic, tonic, and myoclonic seizures cannot be completely excluded from the differentials linked to the patient in the case scenario. Absence seizures can be ruled from the other differentials of seizures since the patient has exhibited aura symptoms in addition to postictal confusion, symptoms that are not usually observed in absence seizure (Guerrini & Barba 2013, p. 74). Furthermore, it rarely present in adults as they is predominantly in children and adolescents. Clonic seizure are characterised by jerky movements that are rhythmic in frequency and can be accompanied with changes in consciousness level (Panayiotopoulos 2010, p. 44). The lower and upper limbs can be simultaneously involved. These jerky movements may cause the patient to collapse which is a possible occurrence in this patient since he was reported to have collapsed too. Loss of consciousness experienced by the patient also augments the diagnosis of clonic seizure. Clonic seizures have also been shown to originate from a focal region as simple or complex focal seizures (Ko 2015). Therefore, based on this knowledge, the probability that the patient experienced a clonic seizure is enhanced since the initial presenting symptoms were characteristic of simple focal seizure that propagated into complex focal type of seizures. The patient might also have had tonic seizure when he recently collapsed and eight months ago when he fell from the stairs as reported by his daughter. Tonic seizures are characterised by flexion or extension of the extremities, trunk and the neck that sets in suddenly placing the patient at an increased risk of falls which is what may have happened to the patient in this cases study (Ko 2015). However, circumstances under which the seizure might have occurred can fortifying a diagnosis of tonic seizures since they are common just after a patient has fallen asleep and a few minutes after waking up (Panayiotopoulos 2010, p. 45). This may exclude the diagnosis of the second seizure the patient had in the presence of the paramedic been a tonic seizure because of a lack of relation to sleep. Another possible seizure differential is atonic seizure that is characterised by a transient deficit in postural tone causing the patient to fall if he was standing. This seizure type may sometimes occur as a continuation of myoclonic or tonic seizure which may complicate its diagnosis (Panayiotopoulos 2010, p 50). However, atonic seizures are predominant in patients who exhibit neurological abnormalities that are clinically significant (Panayiotopoulos 2010, p. 50). Therefore, a comprehensive neurological examination of the patient may ascertain the presence or absence of neurological abnormalities to aid in ruling out atonic seizure. Differentiating the various seizure types requires a thorough history and observation of the patient to identify the presenting symptoms prior to, in the course of and after the seizures to enable a more credible diagnosis. However, even with sufficient history it may be challenging to diagnoses a given seizure hence the need of an EEG to aid in identifying the discharges, spikes and lows experienced in the brain and relate with a specific kind of seizure. Pathophysiology of Seizures As mentioned earlier, seizure result from sudden alteration in the electrical activity of the cerebral cortex such that the balance between inhibitory and excitatory forces is impaired in favour of excitatory forces culminating in a net excitation in the cerebral cortex (Broomfield, Cavazos, & Sirven 2006, p. 1-3; Henry 2012, p. 1). The symptoms presented in the patient will depend on the affected region of the brain. The brain controls virtually every function of the body not excluding the advanced functions of the cortex. Therefore, if the motor or visual cortex is affected, the manifestation of the seizure shall be motor or visual related respectively. Similarly the involvement of the temporal lobe will manifest with psychic deja-vu phenomenon. The pathophysiology of generalised onset and focal onset seizures are different despite there been an overall increase in excitability of neurons (Broomfield, Cavazos & Sirven 2006, p. 4; Huff & Fountain 2011, p. 2). The difference between the two is in their synchronization mechanisms. Pathophysiology of Epileptic Seizures Seizures including focal seizures are epitomised by a cellular feature described as PDS or paroxysmal depolarization shift and the occurrence of interictal epileptiform spikes in an EEG (Henry 2012, p. 2). PDS appear as lengthened membrane depolarization resulting from generation of action potentials that are rapid and repetitive but without there been a refractory state. The duration of the membrane potential is longer than expected from typical excitatory postsynaptic potentials (EPSP) (Henry 2012, p. 2). The depolarization in a PDS sequence is initiated by extracellular calcium ions after their entry into the neuronal cells resulting in the opening of neuronal sodium channels that are voltage dependant causing depolarization and generation of multiple action potentials (Broomfield, Cavazos & Sirven 2006, p. 17). Normally, after the depolarization follows a significant after-hyperpolarization where the neuronal membrane becomes hyperpolarised past the normal resting potential. The hyperpolarization phase is substantially mediated by potassium channels that are calcium dependent though chloride ions influx and GABA receptors can also be implicated depending on the neuronal cell (Broomfield, Cavazos & Sirven 2006, p.17). During a seizure, PDS are generated from numerous neurons in synchronization resulting in the interictal spike seen on an EEG. In focal seizure, the spike originates from a specific hemispherical area of the brain. When the focal cortical neurons are sufficiently activated, the nearby neurons can be recruited. The surrounding inhibition and intact hyperpolarization are usually responsible for the preclusion of dissemination of the activity. However, sufficient activation enable activation of the nearby neurons through various mechanisms. First, with multiple action potentials and discharges, there is a rise in potassium ions extracellularly that in turn blunts the degree of hyperpolarizing outward potassium ion currents resulting in a depolarization of surrounding neurons; second, the influx of calcium ions results in its accumulation in the presynaptic terminals augmenting the release of neurotransmitter; thirdly, during depolarization some “N-methy-D-aspartate [NMDA] receptor” are induced to release the excitatory amino acid culminating in the influx of more calcium ions and activation of more surrounding neurons (Broomfield, Cavazos & Sirven 2006, p. 18). The result is a spread of the depolarising wave through the surrounding cortical connections and to further cortical areas by means of long association pathways leading to the formation of an epileptic seizure from an interictal spike. Mechanisms involved in the causation of seizures include decreased inhibition, diminished activation of GABA neurons and increased activation that may be caused by traumatic brain injury, febrile seizures and central nervous system infections (Vezzani 2014 p. 5). Inflammatory reactions resulting from some of these aetiologies result in the release of inflammatory cytokines that affect glial cells, astrocytes and other neuronal cells leading to a general increase in excitability of neurons (Vezzani 2014, p. 5). In additions, mutations have also been implicated in the overall increase in excitability of some neurons. Decreased Inhibition. GABA usually has inhibitory activity on cortical postsynaptic neurons through GABA-A chloride current that directly induces an “inhibitory postsynaptic potential [IPSP]”and GABA-B potassium current that inhibits activity at presynaptic afferent fibres by impeding release of neurotransmitter that causes its excitation (Ko 2015). Altered or mutated potassium or chloride subunits can impact on the likelihood of having a patient having seizures. Possible mechanisms for decreased inhibition include defective GABA-A and GABA-B inhibition and defective GABA neurons activation (Ko 2015). Mutations affecting the expression of the subunits of GABA-A receptor complex, that is, gamma, alpha and beta subunits have been implicated in focal onset seizures. In addition , alterations in the distribution of the subunits of the receptor complex has also been suggested to impair the permeability of GABA-A chloride channels derailing the GABA induced inhibitory activity (Ko 2015). On the contrary, GABA-B inhibition activity is mediated through potassium channels producing currents of longer duration relative to chloride currents. It is postulated that this long duration of activity associated with GABA-B potassium coupled channels is significant in the ictal to interictal progress of a seizure typical of focal onset seizures. Defective GABA neurons activation in the hippocampus, a brain region implicated in temporal lobe epilepsy, has been suggested to contribute to susceptibility to seizures (Broomfield, Cavazos & Sirven 2006, p. 5-6). Defective Activation of GABA Neurons. The GABAergic neurons are usually activated through a feedforward and feedback mechanisms in the hippocampal cells from excitatory neurons. Damage to this activation mechanisms impairs the GABA mediated inhibition of excitatory neurons. Furthermore, after traumatic injury to the brain, the mossy cells in the dentate gyrus of the hippocampus lose the ability to convey feedforward and feedback activation of the inhibitory GABAergic neurons. Synaptic reorganization after neuronal damage sometimes results in the formation of new synaptic contacts with excitatory cells more than with inhibitory cells leading to multiple excitatory circuitries that affects the inhibitory excitatory tone balance in the hippocampus worsening the propensity to seizures (Ko 2015). Increased Activation. This is mediated through increased NMDA receptor activation, and ephaptic interactions or recurrent excitatory collaterals that enhance interneurons synchrony or increase activation (Ko 2015). Glutamate, the predominant brain excitatory neurotransmitter acts through NMDA, AMPA and metabotropic receptor resulting in an EPSP (Broomfield, Cavazos & Sirven 2006, p. 4). While NMDA activation allows opening of both divalent and monovalent cations, AMPA activation leads to opening of only monovalent cations. It is presumed that in focal onset seizures and in epilepsy, NMDA receptors activation is increased (Ko 2015). In some genetically predisposed individuals, their NMDA receptors are activated faster and for a longer time than normal lowering the threshold for seizures. Ephaptic or non-synaptic interactions between excited and non-excited neighbouring pyramidal neurons may result in excitation of the latter. Recurent excitatory collaterals formed after losses of hippocampal mossy fibres as explained earlier also enhance the activation and synchrony of neurons. The seizures developing from such excitation have the potential to cause further damage to the hippocampus resulting in loop like increase in susceptibility and occurrence of seizures (Ko 2015). This mechanisms has been suggested to be implicated in the causation of intractable seizures of focal onset. Management of Epileptic Seizures The initial supportive management of a seizure in the pre-hospital environment involves ensuring that the victim is airways, breathing and circulation is intact (Australian Resuscitation Council [ARC] 2014, p. 1). The patient shall have to be kept free from danger including removal of any objects capable of secondarily injuring the patient while noting the time which the seizure began. The latter is significant in identifying some seizures since some such as status epilepticus can be prolonged for as long as 30 minutes and require urgent treatment (Dionisio et al., 2013, p. 740). In addition, the timing is significant in the management of a persisting seizure as is discussed below. The patient’s head should be protected and the patient should not be restrained. The patient should be laid down in a lateral position while making sure the airways are maintained (ARC 2014, p. 2). In addition, IV access should be ensured and blood sugars should be assessed to rule out hypoglycaemia. Antiepileptic medication should be prepared. If the seizure persist for more than five minutes anticonvulsant medications shall be necessary. Benzodiazepams are preferred at this stage because of their GABA-A target which are the initially expressed receptor in the early phase of the seizure (Dionisio et al., 2013, p. 742). They enhance the permeability of chloride ions in GABA-A receptors hyperpolarizing the membrane and decreasing its excitability. Midazolam is an appropriate choice at this stage because of its rapid entry in the CNS aiding in seizure abortion without causing excessive longer sedation (Ko 2015; Dionisio et al., 2013, p. 742). The primary treatment goal is to keep the patient seizure free with no adverse effects (N Acharya & J Acharya 2014, p. s20). Adverse effects from the pharmacological agents used in the management of seizures and refractoriness of some seizures are the major challenges facing management of epilepsy (Krauss & Sperling 2011, p. 14-15). Monotherapy is preferred because the patient is exposed to fewer drugs limiting the risk of adverse drug reactions unlike with multiple therapy. As the seizure progresses beyond 10 minutes the continued release of GABA results in stimulation of internalization of GABA-A receptors lessening the usefulness of benzodiazepams (Dionisio et al. 2013, p. 742). Therefore, other agents such as phenobarbitone are useful at this stage because of its prolonged agonistic activity at the GABA-A chloride channels and additional inhibition of NMDA neuronal excitatory activity. Other useful agents include valproate and Levetiracetam. If the seizure, progresses beyond 30 minutes, it is defined as status epileptticus requiring transport for management in the ICU to provide sustained observations and maintenance of the airways (Dionisio et al. 2013, p. 743-744). Conclusion Seizures may present in different ways with some having specific symptoms that aid in their diagnosis. However, the different seizure types may also present at the same time making it difficult to diagnose them hence the need for an EEG. The pathophysiology of seizure development and propagation informs the management of these seizures. The initial management is usually supportive but pharmacological agents are useful if the seizure persist. If status epilepticus develops, management of the patient from an ICU setup shall be necessary. References Acharya, JN & Acharya, VJ, 2014. Epilepsy in the elderly: special considerations and challenges. Annals of Indian Academy of Neurology, 17(Suppl 1), pp. S18-S26. AlEissa, EI, 2015. Firs adult seizure. 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