Table 8.4 Interactional and linguistic features which can help in the differentiation of ep ileptic seizures and psychogenic non-epileptic seizure (PNES) Feature Epilepsy PNES Subjective seizure symptoms Volunteered, detailed Avoided, no detail Formulation work Extensive Practically absent Seizure suppression attempts Volunteered Not mentioned Gaps in consciousness Exact description Little description Metaphors Seizure as independently acting agent, patient often depicted as \200\230victim \200\231 o f the seizure Seizures as a place or space, which patients travel through Seizure labels No resistance to use of \200\230medical \200\231 labels (e.g. \200\230seizures \200\231, \200\230grand mal \200\231 for episodes) Resistance to the use of \200\230medical \200\231 labels (e.g. seizure). Preference of lay terms ( \200\230 \201 t \200\231, \200\230blackout \200\231) oxford textbook of epilepsy and epileptic seizures 86 prove diagnostic, particularly if the history is vague or the epi- sodes are dif \201 cult to describe. This is particularly useful for epi- sodes that occur from sleep, the rarer p aroxysmal dyskinesias, and also PNES. after the episodes. In particular, speci \201 c questions should be asked about whether th ere was a likely or even possible trigger for the episodes. In the active, high-achieving t eenager (most often female) with PNES, a relatively common trigger is a new activity or pur suit that proves to be the \200\230 \201 nal straw \200\231; rather than appearing to fai l at this activity, the child becomes sick and is therefore unable to par- ticipate \200 \224 and not just in this new activity but everything else. PNES is a common manifestation of this behavior. Clearly, most of the history will be obtained from the child \200\231s pa rents or carers but it is crucial to always ask the child themselves about any aspects of t he episodes. Even young children may be able to provide valuable information that may actua lly con \201 rm the nature of the paroxys- mal episodes. If the parent or carer has not ac tually witnessed the child \200\231s episodes then it is important to obtain information fr om those who have observed them. This may include contacting or talking with another family member, friend, schoolteacher, or other individuals, such as a swimming pool attendant or lifeguard. The sort of information \200\224 and how it is given to the doctor \200\224 th at may suggest an adult is experiencing PNES, may similarly be heard from a mother who is f abricating her child \200\231s \200\230seizures \200\231 with the child being a victim of M nchhausen syndrome by proxy. Investigations Interictal tests Interictal tests are greatly overrated in the differential diagnosis of TLOC. \200\230Brain tests \200\231 are often normal in patients with epilepsy , \200\230cardiac tests \200\231 are often normal in patients with syncope. In the series of 158 consecutive outpatients cited previously, interictal EEG only changed the diagnosis in one patient. Neuroimaging revealed a relevant abnormality in 12/43 scanned (27.9 % ) ( 1 1 ). Electroencephalography The EEG is a very useful test in the classi \201 cation of the epil epsy syndrome, but the role of the EEG in the initial diagnosis of patients who have experi enced a TLOC is controversial. There is a risk of non-experts overinterpreting the diagnost ic signi \201 cance of non-speci \201 c EEG changes ( 13 ): in one study such changes wer e seen in 55 % of adults with a clinical diagnosis of epilepsy but also in 45 % of people w ho had experienced syncope ( 15 ). Another study found non-speci \201 c EEG changes in 18 % of adults with PNES ( 64 ). Examination Ictal examination The observation and examination of a patient during a seizure is rarely possible, especially in patients \201 rst presenting with seizures. However, t he observation of closed eyes during the seizure, resisted eye opening, gaze avoidance, ret ained pupillary light re \202 ex, semi- purposeful movements, responsiveness to tickle or corneal re \202 ex, and normal plantar responses would be very helpful and support a diagn osis of PNES rather than epilepsy ( 59 , 60 ). Examination \201 ndings during a faint may include abnormalities of heart rhythm and hypotension. The examination soon after a GTCS m ay show evidence of a severe (typically lateral) tongue bite, bruising or skel- etal injury , and petechial hemorrhages around the eyes or in the conjunctiva. As in adults, the EEG is an often over-used investigation in chil- dren. In view of the nor mal maturation of the EEG, which ranges from preterm through infancy and early childhood to the adult pattern by 12 \200\22314 years, there is an even greater danger of misinter- pre ting children \200\231s EEGs. It is of concern that in the UK, approxi- mately half of the clinicians who routinely report pediatric EEGs have not received formal training in pediatr ic electroencephalog- raphy ( 65 , 66 ). In addition, many pediatricians continue to believ e that the EEG is a \200\230diagnostic test \200\231 for epilepsy and hold on to the erron eous belief that the child \200\231s paroxysmal episodes cannot be epileptic if the EEG is normal and conversely that the episodes must be epileptic if the EEG is abnormal. Interictal examination Interictal examination \201 ndings in patients with epilepsy may p ro- vide a clue to the underlying pathology (e.g. focal central nervous system dysfunction, neurocutaneous syndromes, intracranial space occupation). Patients with syncope may have a postural blood pres- sure drop, a cardiac murmur or arrhythmia. However, in one con- secut ive case series of 158 adult patients attending a TLOC clinic, physical examination \201 ndings did not contribute to the diagnosis in a single case ( 11 ). A brief screen for adve rse life events and psy- chiatric morbidity may yield potential aetiological factors in pat ients with PNES ( 61 ), although rates of adverse life events and mental illness are also h igher in patients with epilepsy and patients with refractory syncope than in the general po pulation ( 62 , 63 ). Neuroimaging Neuroimaging is never a diagnostic test for epilepsy, and even if abnormal doe s not necessarily mean that the patient \200\231s paroxysmal episodes are epileptic. Howeve r, neuroimaging should be carried out in all patients with suspected epilepsy to exclude un derlying pathology (with the exception of those with a clear history and typical EEG change s of idiopathic generalized epilepsy). In one study, nearly 30 % of MRI scans in adults wit h a clinical diagnosis of epilepsy showed abnormalities, but abnormalities were also seen i n 4 % of MRI scans in patients with syncope ( 12 ). One study described abnormalities in 27 % of adults with PNES ( 67 ). As the quality of MRI scans improves, the risk of identifyin g non-speci \201 c changes and misinterpreting these as potential causes of epileptic seiz ures is likely to increase. Examination in children The examination \201 ndings in children, both interictally and ic tally, will generally be similar to those described in adults. Young chil- dren will often be distressed following a GTCS and will usually sleep; this is unlikely if the child has ex perienced a syncopal attack or a PNES. Increasingly, parents will attend the \201 rst new patient appointment with a video of their child \200\231s episodes which may In children with early-onset seizures (speci \201 cally myoclonic, tonic, or focal seizure s and infantile spasms), or in adolescents aged older than 14 years with a new focal epilep sy, neuroimaging is also mandatory and may identify an underlying structural lesion, includ ing cortical dysplasia, a neuronal migration abnormality, neurocutaneous disorders, and, ra rely (in contrast to adults), a tumor. CHAPTER 8 differential diagnosis of epilepsy 87 Cardiac investigations Electrocardiography (ECG) is recommended in all adults present- ing with TLOC because it is risk free and will identify patients with abnormal cardiac conducti on syndromes which can imitate epilep- tic seizures or PNES (such as the long QT-syndrome) ( 68 ). It also helps to stratify patients into those with possible cardiac syncope who sho uld be investigated further and those with neurovasogenic/ unexplained syncope in whom furt her cardiological tests are unlikely to yield an explanation for the TLOC ( 69 ). there is a history of heart disease, if syncope was exercise-related or occurred from the s upine position, if there is a shorter history of attacks, and an absence of pre-syncopal sy mptoms ( 18 ). The diag- nostic evaluation of neurovasogenic syncope can be limited to the exclusion of risk factors for cardiac syncope by means of the patient \200\231s history and a routine ECG test. If in doubt, tilt-table test- ing can be helpful ( 80 ). A diagnosis o f CSH can be established by performing carotid sinus massage under blood pressure and ECG m onitoring. Patients with possible cardiac syncope need to be investigated further with echo cardiography, and prolonged ECG recordings (possibly using implantable loop recorders which can continue to monitor the patient for intermittent arrhythmias for over 18 months) ( 71 ). One study showed that cardiac syncope may be under-recognized in seizure clinics and sho uld always be con- sidered as a possible diagnosis in patients whose apparently epilep- tic seizures fail to respond to antiepileptic drugs ( 9 ). Cardiac arrhythmias are an uncommon cause of TLOC or \200\230drop attacks \200\231 (tonic or atonic seizures) in children under 10 years of age. However, an ECG should always be und ertaken wherever there is a history of events that seem to be closely related to vigorous e xercise or a sudden shock or startle. If the ECG is normal but the level of suspicion of a cardiac cause remains high, children should be referred for a formal cardiac opinion. Psychogenic attacks Psychogenic non-epileptic seizures PNESs are episodes of altered moveme nt, sensation, or experience resembling epileptic seizures but not associated with ictal el ectrical discharges in the brain ( 81 ). Attacks are interpreted as a dissocia- tive or con version response to distress in the current diagnostic manuals ( 82 \200\22384 ). In the IC D-10 (International Statistical Classi \201 cation of Diseases and Related Health Problems , 10th revi- sion), PNESs are described as involving \200\230partial or complete loss of t he normal integration between memories of the part, awareness of identity and immediate sen sations, and control of bodily move- ments \200\231 ( 84 ). Most PNESs are characterized by impairment of con- sciousness, collapse, and shaking of the limbs lasting for several minu tes ( 81 ). A number of biographical, psychological, physiolog- ical, sociological, and \201 nancial factors including trauma and neglect in earlier life, adverse life events in a dulthood, personality pathol- ogy, and inadequate coping skills can predispose to, precipit ate and perpetuate PNESs ( 85 ). PNESs often occur in the context of comorbid psychopatholo gy. Most PNESs are not considered to be under patients \200\231 volitional control although the distinction from attacks occurring in the context of factitious disorder or malinger- ing is dif \201 cult ( 86 ). Ictal tests Tests which observe attacks themselves (such as video-telemetry, ambulatory EEG , prolonged ECG, tilt-table tests or even home video recordings) are much more speci \201 c in the differential diagno- sis of TLOC than interictal tests ( 70 \200\22372 ). However, these tests are also much less sensitive and rarely help in patients \201 rst presenting with seizures. Tests which use different forms of symptom provoca- tion may increase the y ield of time-limited brief outpatient proce- dures. Photic stimulation and hyperventilation lead to a small increase in the yield of routine EEG examination for epileptiform EEG chan ges, but (in combination with suggestion) provoke a typi- cal PNES in around 50 % of adult patients ( 73 ). Like syncope, PNES may also be provoked by tilt-table examinations ( 74 ). Suggestion during a routine EEG rarely induces or provokes a PNES in children. Video-EEG ma y prove diagnostic in differenti- ating epileptic seizures from PNES or parasomnias but cle arly only if the child experiences their habitual episodes during the record- ing. Ambulato ry EEG is less useful than video-EEG, \201 rst because of considerable movement artifact or \200\230equipment failure \200\231 (both of which are common in this age group) and sec ond because there is no video-footage of the clinical events. Where there is a high index o f suspicion of fabricated seizures (M nchhausen by proxy), inpa- tient video-EEG telemetry is the investigation of choice. Dissociative disorders There are other, non-convulsive manifestations of dissociation (disr uption in the usually integrated functions of consciousness, memory, identity, or perceptio n) which can be mistaken for epilep- tic seizures. Simple partial seizures may involve feel ings of deper- sonalization or derealization which can also occur as isolated dissociative symptoms in the absence of epileptic discharges in the brain ( 87 ). A dissociative etiolog y is more likely if these symptoms are related to stressful events, if there is a history o f other dissocia- tive phenomena and if there are no associated symptoms of epilepsy (such as olfactory hallucinations, d j vu or jamais vu experience) or investigation \201 ndi ngs making epilepsy more likely ( 88 ). Complex partial seizures or transient epileptic amn esia may be dif \201 cult to distinguish from dissociative amnesia. Both may be characteri zed by decreased recall of autobiographical knowledge although only the latter typically in volves the lack of recollection of traumatic events. Complex partial (non-convulsive) statu s epilepticus may only be distinguishable from brief periods of dissociative fugue (unexpec ted travel away from home or place of daily activities with Differential diagnoses of epilepsy Syncope Syncope is a sudden, transient, self-limited los s of consciousness, usually leading to falling. The onset of syncope is relatively rapid, a nd the subsequent recovery is spontaneous, complete, and rela- tively prompt. The underlyin g mechanism is transient global cere- bral hypoperfusion ( 75 ). Syncope can be related to a range of triggers and mechanisms (Table 8.2 ) ( 76 ) . A diagnosis of \200\230syncope \200\231 is therefore incomplete and must be combined with a determina- tion of the likely underlying mechanism. The most important dis- tinction is that between re \202 ex or neuro vasogenic (60 \200\22370 % ) and cardiac causes (10 \200\22320 % ) ( 69 , 77 , 78 ). Caroti d sinus hypersensitiv- ity (CSH) causes a particular form of neurovasogenic syncope in whic h hypotension and/or cardiac inhibition are triggered by stim- ulation of the carotid baror eceptors in the neck. CSH is particularly common in older patients ( 79 ). Cardiac syncope is more likely if oxford textbook of epilepsy and epileptic seizures 88 Hyperventilation Hyperventilation is de \201 ned as breathing in excess of the metabolic n eeds of the body, eliminating more carbon dioxide (CO 2 ) than is produced, and resulting i n respiratory alkalosis. The reduction in blood CO 2 levels produces vasoconstriction and s econdary hypoxia in the brain. Clinically, hyperventilation is associated with perioral and acral paraesthesiae, stiffness, clumsiness, dysarthria and carpo- pedal spasms. Symptoms a re usually bilateral but can only mani- fest on one side. If maintained for long enough, hy perventilation can cause syncope or provoked epileptic seizures ( 89 ). It can link anxiety with physical and cognitive symptoms, which can easily be mistaken for epileptic seizures. Diagnostic confusion with epilepsy is particularly likely when sensory and motor symptoms are unilat- eral. Several studies suggest that cerebral anxiety networks are par- ticularly sensitive to carbon dioxide \202 uctuations in patients with panic disorder. The diagnos is of hyperventilation related attacks is made more likely by elevated scores on the Nijmeg en Hyperventilation Questionnaire ( 90 ), or the provocation of typical symptoms during a h yperventilation tests (maintaining a respira- tory rate of 30/minute for 4 minutes). lack of recall of identity) because of other signs or symptoms sug- gestive of epilepsy (su ch as automatisms or incontinence), because there are more de \201 nite epileptic seizures at other times, or because patients carried out more complex social or other activities, w hich are unlikely to have been completed in complex partial status epi- lepticus. Panic disorder Panic disorder is characterized by unpredictable, recurrent attacks of sever e anxiety not restricted to any particular situation or cir- cumstance. Dominant symptoms v ary but sudden onset palpita- tions, chest pain, choking, dizziness, feelings of unreality (depersonalization/derealization) are common. Almost invariably patients have a secondary f ear of dying, losing control, or going mad. Attacks last for minutes or longer. Many patien ts develop an urge to leave the situation in which the attack has occurred. Similar circums tances may be avoided in the future. In between attacks most patients are relatively asympt omatic although a degree of anticipatory anxiety (fear of further attacks) is common. Impai rment of consciousness is not a feature of panic attacks ( 84 ), although it may be dif \201 cult to draw a line between feelings of unreality and more profound symptoms of dissoc iation (and PNES). Panic symptoms can also occur as a result of epileptic dis- charges, for instance in the amygdala and other parts of the limbic system. Table 8.5 lists a number of features, which can help in the differentiation of panic disorders and focal epilepsy. Sleep disorders Parasomnias The diagnosis of paroxysmal nocturnal events often represents a clinical challenge, with the distinction between nocturnal epilepsy and non-epileptic slee p-related disorders causing the greatest Table 8.5 Differential diagnosis of panic attacks and ictal anxiety caused by focal epilept ic seizures (from Schoendienst and Reuber, 2007) Primary panic attack Focal epileptic seizure with ictal anxiety Clinical features Consciousness Alert May progress to impairment Duration 5 \200\22310 minutes 0.5 \200\2232 minutes Automatisms Very rare Common with progression to CPS Nocturnal attacks Occur from state of wakefulness May wake patient up Subjective symptoms D j vu, hallucinations Very rare > 5 % Depressive symptoms Common, severity associated Not uncommon, severity not associated Anticipatory anxiety Very common Can occur but not common Relation to \200\230normal \200\231 anxiety No clear subjective difference between \200\230normal \200\231 fear and panic states Clear difference between \200\230normal \200\231 and ictal fear Investigations Interictal EEG Usually normal Often abnormal Ictal EEG Usually normal Usually abnormal (may be normal in SPS) MRI of temporal structures Usually normal Often abnormal Linguistic and interactional features in the history Anxiety symptoms as a topic Usually volunteered Not volunteered without prompting Anxiety symptoms Discussed extensively Volunteered quickly Self-initiated as a topic Frequent use of formula ic expressions Are described as focused on particular objects Discussed sparingly Hesitant disclosure Often not discussed without prompting Apparently di f \201 cult to describe, descriptions characterized by high formulation effort. Ictal fear is described as non-speci \201 c untargeted anxiety. CHAPTER 8 differential diagnosis of epilepsy 89 dif \201 culties. Epileptic seizures of frontal lobe origin often occur during sleep (non- rapid eye movement (NREM) light sleep). Some patients only have sleep-related epileptic sei zures and ful \201 l the cri- teria for nocturnal frontal lobe epilepsy (NFLE). NFLE is mo st likely to be confused with NREM arousal parasomnias. NREM arousal parasomnias are paroxy smal behaviors without conscious awareness, usually arising from NREM deep sleep. They have a broad spectrum of clinical manifestations ( 91 \200\22393 ). In clinical prac- tice the NREM arousal disorders are subdivided into three main forms: confusional arousals, sleep wa lking (somnambulism), and sleep terrors (pavor nocturnus). Common underlying mechanisms are believed to be responsible and patients may display features of several subtypes (sometime s also associated with obstructive sleep apnoea). The motor patterns observed during these events such as wandering, semipurposeful automatisms, and motor agitation may be seen also in epileptic seizures, and furthermore most descrip- tions of arousal disorders in the lite rature are not based on video- EEG or polysomnography recordings ( 93 ). A simple questionn aire has been developed to help with this particular differential diagno- sis (the Frontal Lobe Epilepsy and Parasomnias (FLEP) scale) ( 94 ). A subsequent study based on the systema tic semiological evalua- tion of video-EEG recorded parasomnias and NFLE seizures in 44 pat ients (120 events) has provided further evidence ( 95 ). Sixty- nine elemental semiological features were identi \201 ed and cluster analysis was applied to the data set. Elemental clinical features strongly favoring a diagnosis of parasomnias included crying or sobbing, waxing and waning pattern, interactive behavior, failure to wake after the event, prolonged duration ( > 2 minutes), and indistinct offset. In contrast, bicycling movements, thrashin g, grunting, grimacing, and dystonic posturing clearly favored NFLE. On the basis of this d ata set the authors developed a diag- nostic classi \201 cation tree based on video featur es only, which cor- rectly classi \201 ed 94 % of the events (Fig. 8.2 ). This may be usef ul not only in the assessment of video-EEG monitoring data, but also in assessing home vide o recordings. underlie a hypothesis that the disorders may have a common path- ogenic background ( 96 , 9 7 ). Narcolepsy Narcolepsy is a disorder of the regulation of sleep and wakefulness ( 98 ), most ly starting in adolescence. Patients have excessive day- time sleepiness (EDS) with or with out irresistible sleep attacks and fractionated nocturnal sleep. They may also have episode s with sleepiness or \200\230micro-sleeps \200\231 with automatic behavior. These epi- sod es may be mistaken for absences or complex partial seizures with ambulatory automatisms, bu t typically patients come round from \200\230micro-sleep \200\231 refreshed and not confus ed or tired. Most narcolepsy patients also have cataplexy (70 % ) which is characterized by a sudden los s of postural muscle tone, and may result in sudden falls with retained consciousness. The episodes are provoked by intense emotions, speci \201 cally laughter or anger, and may las t seconds to several minutes. Cataplectic attacks may be both partial and complete. The par tial attacks are usually very short, most often affect the jaw and the face and the return of muscle function is abrupt ( 99 ). The episodes of cataplexy are some- times misdiagnosed as either focal or \200\230drop \200\231 (atonic or astatic) epi- leptic seizures. Other symptoms of narcolepsy include hallucinations and/or paralysis when falling asleep or on wa king. The diagnosis of narcolepsy rests on clinical ground supported by sleep investiga- ti ons (polysomnography followed by a multiple sleep latency test). Auxiliary laboratory tests can help differentiating between patients with or without cataplexy (almost all patients o f Western European ancestry with narcolepsy and cataplexy are HLA DQB1 * 0602 posi- tive an d have low cerebrospinal \202 uid hypocretin-1 values) ( 98 ). Taking a careful history r evealing the disabling EDS as well as the other symptoms will clarify the diagnosis. Movement disorders Paroxysmal dyskinesias Paroxysmal dyskinesias (PDs) are a group of rare hyperkinetic movement disorders characterized by brief intermittent dyskinetic movements. T he clinical features of the involuntary abnormal The similarities between features seen in parasomnias and NFLE as well as the fact that the disorders not uncommonly may coexist Yes NFLE Is there a discrete offset to the event (as opposed to a gradual emergence of full consciou sness)? Yes Yes NFLE Does the patient remain prone/supine, (i.e. does not sit, stand or walk during the episode) ? Does the patient clearly arouse fully (i.e. to normal wakefulness) at the end of the episod e? No Parasomnia No Yes NFLE Is there versive head turning dystonic posturing during the event? No Parasomnia No Fig. 8.2 Chi-squared automatic interaction detector tree analysis. Figure taken from Derry et al. ( 95 ) showing a diagnostic classi \201 cation tree, based on video features only. This algorithm correctly identi \201 ed 94 % of the 120 nocturnal events in the study. NFL E, nocturnal frontal lobe epilepsy. oxford textbook of epilepsy and epileptic seizures 90 Transient ischaemic attacks Whereas most epileptic seizures are characterized by predomi- n antly \200\230positive \200\231 ictal features (e.g. excessive movement, sensory, visual, or auditory hallucinations), most transient ischaemic attacks (TIAs) involve \200\230negat ive \200\231 features (e.g. weakness, loss of sensation, loss of speech). TIAs are rarely a ssociated with impairment of con- sciousness. However, especially in elderly patients with a history of cerebrovascular disease, it is not uncommon that focal seizures are mistaken f or TIAs even though loss of consciousness is clearly described. In the case of brief attack s of sensory symptoms or apha- sia without loss of consciousness it may be more dif \201 c ult to differ- entiate between an epileptic or vascular origin, although epileptic seizures are usually of shorter duration. Limb-shaking TIAs pose a particular diagnostic challenge. Limb-shaking is a speci \201 c clinical feature of TIA that has been associated with a hi gh-grade stenosis or occlusion of the internal carotid artery. Limb-shaking is charac- teri zed by brief, jerky, coarse involuntary movements involving an arm or a leg ( 107 ). In a s tudy of the clinical characteristics of limb- shaking in 34 affected individuals the attack s were shown usually to last less than 5 minutes and were often accompanied by paresis of t he involved limb. The symptoms were often precipitated by spe- ci \201 c circumstances tha t may lower cerebral blood \202 ow in patients with occlusion of the internal carotid art ery (e.g. rising or exercise) ( 108 ). Other aspects that have been described as helpful in the dif- ferential diagnosis from focal seizures are lack of involvement of the face or tr unk, absence of a march of symptoms, and of epilepti- form activity on EEG ( 109 ). movements include dystonia, chorea, athetosis, ballism, or combi- nations of these symptoms ( 100 ). PD can occur in isolation or in association with epilepsy. Age of onset is usuall y below 20 years and there is often a family history although there are also sporadic cases . The attacks are brief, they may be uni-or bilateral, there is usually no loss of consciou sness, and neurological status is typically normal between attacks. The most common type of PD is paroxysmal kinesigenic dyskinesia where the attacks are triggered by sudden voluntar y movements. In a study of 121 affected individuals the mean delay from seeking medical adv ice to correct diagnosis was 4.8 years and alternative diagnoses given included epilepsy, p sycho- genic seizures, tics, anxiety, and malingering ( 101 ). As in epilepsy, diagnosis is based mainly on a carefully taken history. However, it may be dif \201 cult for both the person but also, where the patient is a child, for their carers to accurately describe the movements. In this situation video-footage of the episodes may prove diagnostic. The moveme nt disorder in the genetic condition glucose transporter (GLUT1) de \201 ciency may also b e misdiagnosed as epilepsy; how- ever, it is also important to appreciate that both epileps y and a movement disorder may occur simultaneously in this condition. Myoclonus Myoclonus is a clinical sign that may be found in a number of different diseases, as an epileptic phenomenon or related to non- epileptic motor system disorders. Myoclonus is de \201 ned as sudden brief muscle jerks. The duration of movements is rarely longer th an 100 msec and it is usually a positive phenomenon, resulting in synchronized muscle contr actions. Negative myoclonus con- sists of a sudden brief loss of muscle tone which can be d emon- strated by loss in electromyography activity. Myoclonic jerks can occur with dysfunct ion in cortical, brainstem, or spinal motor systems and may also be psychogenic ( 102 , 103 ). Most causes of myoclonus are symptomatic, including posthypoxic or toxic- metabolic sta tes, storage disease and neurodegenerative disor- ders. In an epidemiological study from Mi nnesota, US, the annual average incidence of myoclonus of any cause was 1.3 cases per 100,0 00 person-years ( 104 ). Symptomatic myoclonus was the most common aetiological category (7 2 % ), followed by epileptic myoclonus (17 % ) and essential myoclonus (11 % ). Migraine There are clinical similarities between migraine with visual aura and occipital ep ilepsy with simple partial seizures (especially when these seizures are followed by a posti ctal headache which may be indistinguishable from migraine). However, several studies have also identi \201 ed diagnostically helpful differences ( 110 ): migrainous auras are more likely to start in the center of the visual \201 eld, spread outwards over the course of minutes, and involve one hemi \201 eld. Epileptic auras tend to start in the periphery, mo ve, split, or spread (possibly to the whole visual \201 eld) over the course of seconds. Although other visual phenomena are possible, migrainous auras are more likely to be black and white and produce linear patterns ( 111 ). Most elementary visual auras caused by epile ptic seizures involve colorful rounded forms. Migraines also tend to be less fre- quent tha n epileptic seizures. Both can be associated with tempo- rary blindness although this is mo re likely to affect the whole visual \201 eld in epilepsy than migraine. Other clinical p ointers to epilepsy include symptoms of spread of the ictal discharges to other parts of th e brain (including secondary GTCS), ictal gaze deviation or interictal visual \201 eld de fects ( 112 ). It is recognized that elementary visual hallucinations (and ictal visual los s) can also be a manifesta- tion of seizures primarily originating in the temporal lobes ( 113 ). Given the large number of possible causes of myoclonus, it is essential to take a good hist ory including age of onset, family his- tory, the character of myoclonus, precipitating fac tors, and pres- ence of associated symptoms and signs. The physical examination can give im portant clues. Myoclonus at rest indicates a spinal or brainstem cause, whereas action-indu ced myoclonus points to a cortical origin. Electrophysiology is very helpful in detecting t he level of origin of myoclonus ( 105 ). In epilepsy, myoclonus may occur as one component of a sei- zure, as the only seizure manif estation, or as one of multiple sei- zure types within an epileptic syndrome. Epileptic myo clonus is accompanied by a generalized ictal epileptiform electroencephalo- graphic dischar ge, but the myoclonus itself may be generalized, segmental, or focal ( 106 ). Myoclonus can appear in the generalized epilepsy syndromes (e g juvenile myoclonic epilepsy), symptomati c generalized epilepsies and the progressive myoclonic epilepsies (as in PME, e.g. Unverric ht \200\223Lundborg disease) but can also occur in focal epilepsy, often from a frontal foc us. Basilar migraine may also be mistaken for epilepsy. In this form of migraine neurological s ymptoms suggest primary involvement of the brain stem. Basilar migraine can cause loss of c onsciousness preceded by vertigo, tinnitus, hypo-acusis, and bilateral visual symptoms ( 11 4 ). However, attacks of basilar migraine tend to develop more slowly than epileptic seizur es and last longer. The symptoms listed here may also be associated with other brainstem si gns unlikely in epileptic seizures (such as ataxia or diplopia). Clinical cases in which ep ileptic seizures seem to develop out of typical migraines also exist ( \200\230migralepsy \200\231). The etiology of myoclonus tends to be easier to determine if it occurs as one part of a syn drome than if myoclonus appears in isolation. CHAPTER 8 differential diagnosis of epilepsy 91 Transient global amnesia The syndrome of transient global amnesia (TGA) is de \201 ned by a sudden onset of an anterograde and retrograde amnesia lasting up to 24 hours. The memory impairment consists of a profound reduction of anterograde and a milder reduction of retrog rade epi- sodic memory, including executive functions and recognition (for references see ( 115 ). Typically patients recover (although they do not tend to retrieve memories of the p eriod of amnesia) and a recent meta-analysis including 25 studies could not \201 nd long- term differences in cognitive performance between patients and healthy controls ( 116 ). Mo st attacks occur in people aged 50 \200\22370 years and occurrence below the age of 40 is r are, as is recurrence. There is, however, some evidence of association between younger pati ents and history of migraine and a case series of \201 ve patients with TGA who had previ ously successfully undergone temporal lobe resec- tion for epilepsy suggests that epilepsy surgery in the temporal lobes may increase the vulnerability for TGA ( 117 ). of consciousness (including symptomatic GTCS), odd behavior, speech dif \201 culties, and incoordination. There are several other endocrine disorders, which can cause episodic symptoms such as \202 ushing, tachycardia, tremor, and anx- iety and which may be mistaken for simple partia l seizures espe- cially of temporal lobe origin ( 83 ). These include carcinoid syndrome, s ystemic mast cell disease, phaeochromocytoma, med- ullary carcinoma of the thyroid, pancrea tic islet-cell tumors, renal cell carcinoma \200\224 or even menopausal hypo-oestrogenaemi a. In children and adolescents, hypocalcaemia may also induce symp- toms that mimic seizure s, typically tonic or focal seizures; unfortu- nately, hypocalcaemia may also cause genuine epileptic seizures, although this is typically in young infants. Common differential diagnoses in children Many of the conditions seen in adults and describ ed in this chapter also occur in children and particularly children over 10 years of age. C ardiac arrhythmias resulting in drop attacks tend to occur in older children ( > 12 years o f age) and TIAs are extremely uncom- mon. PNES is less commonly seen in children and is rar e under 9 years of age. The most common \200\230seizure \200\231 type in PNES is tonic \200\223 clonic-like followed by atonic-like seizures (drop or \200\230swoon \200\231-type seizures). Paroxysmal movement disorders, including simple or complex motor tics and stere otypies are relatively common and are often misdiagnosed as focal or myoclonic seizures. Pa rasomnias are a common phenomenon in children, and particularly arising from NREM-sleep res ulting in night terrors or rhythmic body- rocking or head-banging behaviors. Self-grati \201 cation is a common and normal behavior in infants and young children and may per- sist well into late childhood, although by this stage children are much more self-conscious and it is unlikely to be witnessed. However, the behavior may continue to be manifest in publi c places in children with learning difficulties or autism. Self- grati \201 cation is more likely to be seen when the child is bored or relaxed; speci \201 c situations include in a busy classroom or when watching television. Children can either assume dystonic or tonic postures with crossing of their legs or, less frequently, clonic move- ments of their legs usually in association with rhythmic rocking of the body and facial \202 ushing. They may also appear to be \200\230absent \200\231 and unresponsive although they can usually be d istracted out of them, but usually only temporarily. Predictably, these characteris- tic fe atures may lead to a diagnosis of absence, complex partial sei- zure, or, rarely, tonic sei zures. Precipitating factors described for TGA include physical exer- tion, emotional or psycholog ical stress, pain, medical procedures, and sexual intercourse. The diagnosis is primarily c linical, using the following criteria ( 118 ): 1 ) anterograde amnesia witnessed by an obse rver; 2 ) no clouding of consciousness or loss of personal identity; 3 ) cognitive impairme nt limited to amnesia; 4 ) no focal neurological or epileptic signs; 5) no recent history o f head trauma or seizures; and 5 ) resolution of symptoms within 24 hours. The exact pathop hysiology of TGA is not clear although a number of neuroimaging studies have shown mesiotem poral abnormalities (for references see ( 119 )). The main differential diagnostic problem in relation to epilepsy concerns transient epilept ic amnesia \200\224 TEA. This is a recently delineated neurological condition occurring in middle age and presenting with amnesic attacks ( 120 ). Butler described a series of 50 pa tients with TEA with detailed clinical and EEG data ( 121 ). They found that their patients with TEA had a mean onset of 62 years, similar to TGA. The amnesic episodes were rather mo re fre- quent (median 12/year) and shorter than TGA, although in general longer than epilep tic seizures (median duration 30 \200\22360 minutes), and transient amnesia was the most pr ominent feature of the epi- sodes. The amnesic attacks were characterized by mixed antero- grade and retrograde amnesia, sometimes with repetitive questioning. Epileptiform activity on EEG was present in 37 % of the patients and some patients had features indicative of foc al epi- lepsy, e.g. olfactory hallucinations, oral automatisms, or brief peri- ods of unres ponsiveness. However, epilepsy was the initial specialist diagnosis in only 12 of 50 cases. Forty of the 50 patients described persistent memory dif \201 culties. Importantly, attac ks ceased on anti- convulsant medication in 44 of 47 treated patients. Attacks com- monly o ccurred on waking, a helpful diagnostic clue. Less common differential diagnoses in children There is a wide range of other maturational (and therefore normal) phenomena but also a number of uncommon or rare non-physio- logical conditions that may be misdiagnosed as epilepsy, and usu- ally as myoclonic, tonic, or comp lex partial seizures (see Fig. 8.1 ). Fabricated or \201 ctitious illness (also known as M nchhausen syn- drome by proxy ( 124 , 125 )) is a relatively uncommon but almost certain ly under-recognized phenomenon and represents a form of child abuse or \200\230non-acciden tal injury \200\231. Syncope and seizures are the most common presentation of this conditio n. The parent, most often (but not invariably) the mother, fabricates a history that her ch ild is experiencing seizures. Less commonly, this fabrication is more sinister in that the parent is actively doing something to the