Thalamocortical myoclonus

The following sections about thalamocortical myoclonus was excerpted from Eplilesy textbook on 2013/02/16
Thalamocortical myoclonus or idiopathic generalized epileptic myoclonus represents the common type of myoclonus in various epileptic syndromes. Myoclonia are often spontaneous, predominantly arrhythmic and axial with varying severity, and associated chronologically with an EEG pattern of diffuse polyspikes or (poly) spike-and-wave discharges. A hyperexcitable cortex is thought to be driven diffusely and synchronously by ascending subcortical inputs that trigger the paroxysmal events. As a consequence, muscles from both sides are activated, and muscles innervated by the cranial nerves are involved through a rostrocaudal manner.
Electrophysiologically, SEP usually does not show giant SEP, and C-reflex may be recorded at rest. A negative peak of the generalized spike (30–100 msec duration) precedes the jerk (<100 msec duration) by 20 to 75 msec. The latency of the spike is relatively longer, and the temporal relationship is looser than in that of cortical myoclonus. The underlying mechanism of the thalamocortical myoclonus is still uncertain. The myoclonus of benign myoclonic epilepsy of infancy, myoclonic-astatic epilepsy, and JME belongs to this category.
Myoclonus observed in patients with Dravet syndrome is not straightforward: Patients may exhibit massive myoclonus combined with a generalized spike-wave (rarely in infancy, mostly in childhood), and erratic myoclonus, particularly during episodes of myoclonic status, in which the patient is drowsy with diffuse slow wave activity and few spikes. The generator remains unidentified.

Cortical myoclonus

The following sections about cortical myoclonus was excerpted from Eplilesy textbook on 2013/02/16
Cortical myoclonus reflects impulses that originate in the sensorimotor cortex and travel down the brainstem. Cortical myoclonus is typically seen in progressive myoclonus epilepsy. Muscles involved tend to be distal more than proximal and flexor more than extensor, and to involve more the face and upper extremities than the rest of the body. Cortical myoclonus is more commonly encountered in a multifocal form, presenting with multifocal spike discharges. If myoclonus is triggered by stimuli, the term cortical reflex myoclonus is used. If myoclonus occurs periodically, the term epilepsia partialis continua is used. The neurons in the sensorimotor cortex may be primarily hyperexcitable, or may be driven by abnormal inputs from the neurons of other brain parts. Therefore, cortical myoclonus occasionally is called fragmented epileptic convulsion.
In patients with cortical reflex myoclonus, the cortical components of median-nerve SEP showed abnormally large amplitude. Usually, the initial peaks (N20/P22) are not large, and the following components become higher. This giant SEP is thought to indicate hyperexcitability of the sensorimotor cortex. Abnormally large evoked potentials were also reported by photic stimulation.
When the peripheral nerve is stimulated, the stimulus goes up the spino-thalamo-cortical tract and, after excitation of the pyramidal neuron, it goes down the cortico-spinal tract, resulting in muscle contraction (long-loop reflex). In normal subjects, long-loop reflex can be recorded only when subjects maintain muscle contractions. In patients with cortical reflex myoclonus, however, this reflex can be recorded even while resting (C-reflex). The latency of C-reflex for median nerve stimulation is about 40 to 45 msec, which is almost double of the latency of N20 to the median nerve stimulation. When the C-reflex is recorded from the contralateral limbs to the stimuli, the latency delay is about 10 msec to the ipsilateral limbs, which corresponds to the traveling time of the transcallosal pathway. This stimulation-locked muscle contraction is believed to share the same underlying mechanism with cortical reflex myoclonus.
Some EEG correlates are time-locked to cortical myoclonus. However, because of the relatively smaller amplitude of the EEG spikes in comparison with the background activities, the physiologic correlates of myoclonus can only be detected by using jerk-locked (EEG or magnetoencephalograhic [MEG]) averaging (JLA of jerk-locked magentic field [JLF]) or coherence analysis method. In JLA, EEGs are averaged with respect to the EMG onset, to reduce the non–time locked background EEG activities. Positive peak of the EEG spikes is 15 to 20 msec prior to the myoclonus for the upper limbs, and 25 to 40 msec for the lower limbs. Spikes are located around the contralateral primary motor cortex.
As such, cortical reflex myoclonus is caused by hyperexcitability of the primary sensorimotor cortex. However, because giant SEPs are not always present in patients with cortical reflex myoclonus (as in dentatorubral-pallidoluysian atrophy [DRPLA]), some other pathophysiologic mechanisms may exist.
In Lennox-Gastaut syndrome (LGS), myoclonus is rare and disclosed only in those cases with a cortical lesion affecting the rolandic area; thus, myoclonus appears to be produced by a secondary generalization of focal cortical myoclonus. They also present with arrhythmic, distal small focal jerks, leading to the individual tiny finger movements unaccompanied by premyoclonic potentials on JLA that Wilkins et al. proposed to call minipolymyoclonus. Brown et al. indicated that the major role of facilitation of inter- and intra-hemispheric spread of cortical myoclonic activity is through trans-callosal or intrahemispheric corticocortical pathways in producing generalized or bilateral myoclonus. Therefore, bilateral jerks may not be synchronous in patients with cortical myoclonus.

Stereotypies

The following paragraph was taken from textbook "Neurology and clinical neuroscience" on 2013/02/05:
Stereotypies are repetitive, rhythmical, and invariant motor behaviors, without an apparent purpose or function, that can vary from simple motor behaviors such as rocking or hand waving to extraordinarily complex acts and rituals. They are one of the defining features of autism and are common in patients with mental retardation. Stereotypies are seen in adults with lesions or disorders affecting the frontostriatal circuit running between the dorsolateral frontal cortex and the head of the caudate nucleus. Frontotemporal dementias commonly manifest with stereotypic behaviors resulting from degeneration of the dorsolateral prefrontal cortex. Stimulant medications can produce complex stereotypies through a dopaminergic effect on the basal ganglia. Other repetitive motor behaviors such as compulsive behaviors and tics are seen in patients with Gilles de la Tourette syndrome and obsessive-compulsive disorder, both of which are considered to be associated with basal ganglia pathology. Of importance is that stereotypies, compulsions, complex tics, mannerisms (unusual or pathological styles of performing goal-directed activities, such as a bizarre gait and unusual ways of greeting people), and habits can often be difficult to distinguish purely on the basis of subjective observation. The context and history of the motor phenomena provide important diagnostic information.

Postictal state of seizure

The following paragraph was taken from UpToDate on 2013/01/23:

Postictal state —Manifestations typically include confusion and suppressed alertness; focal neurologic deficits may also be present. The postictal state may last from seconds to minutes to hours, depending upon several factors including which part(s) of the brain were affected by the seizure, the length of the seizure, whether the individual was on AEDs, and age.
As an example, young adults with partial seizures of frontal lobe origin may have postictal states that last only several seconds, while elderly patients with secondarily generalized seizures may have postictal confusion and sleepiness that persists for as long as several days to a week, particularly if there is underlying brain dysfunction. If a person had a CPS or a convulsion, his or her level of awareness gradually improves during the postictal period, much like a person waking up from anesthesia after an operation.
The ictal and postictal manifestations are different between complex partial seizure and generalized tonic-clonic seizure:
1. Complex partial seizures typically last less than three minutes and may be immediately preceded by a simple partial seizure. Afterward, the patient enters the postictal phase, often characterized by somnolence, confusion, and headache for up to several hours. The patient has no memory of what took place during the seizure other than, perhaps, the aura.
2. A generalized tonic-clonic seizure (also called grand mal seizure, major motor seizure, or convulsion) is the most dramatic type of seizure. It begins with an abrupt loss of consciousness, often in association with a scream or shriek. All of the muscles of the arms and legs as well as the chest and back then become stiff. The patient may begin to appear cyanotic during this tonic phase. After approximately one minute, the muscles begin to jerk and twitch for an additional one to two minutes. During this clonic phase the tongue can be bitten, and frothy and bloody sputum may be seen coming out of the mouth. The postictal phase begins once the twitching movements end. The patient is initially in a deep sleep, breathing deeply, and then gradually wakes up, often complaining of a headache.
End Note: please remember the following sentence…
In some cases, the postictal symptoms may be the presenting clinical feature, when the seizure itself is very brief and/or unwitnessed.

Difference between temporal and frontal lobe seizure

The following paragraph was taken from UpToDate on 2013/01/23:
Temporal lobe epilepsy
Complex partial seizures are the most common manifestation of mesial TLE. About one-third of patients have secondarily generalized tonic-clonic seizures in addition to complex partial seizures or as their primary seizure type. Only a few patients with mesial TLE develop status epilepticus. Distinctive characteristics of mesial TLE seizures include the following:
1. An “aura” (a simple partial seizure with sensory symptoms) occurs in most patients, often with features that are relatively specific for TLE, including a rising epigastric sensation (often likened to a "roller coaster" sensation), and psychic or experiential phenomena, such as deja vu, jamais vu, or fear. Auras of taste and smell are less common but are also relatively specific for TLE. Auras can occur in isolation as a simple partial seizure or can precede a complex partial seizure. In either case, patients with mesial TLE usually recall the seizure aura.
2. Complex partial seizures usually manifest with a behavioral arrest and staring and last between 30 and 120 seconds. The patients are generally unaware and unresponsive during this period. Occasionally, such patients present with amnestic attacks, but more detailed questioning or observation of the seizures reveal the presence of olfactory hallucinations, other seizure auras, or ictal automatisms.
3. Automatisms are common, occurring in about 60 percent of complex partial seizures of mesial TLE. These are repetitive, stereotyped, purposeless movements. In TLE, they are typically mild, involving the hands (picking, fidgeting, fumbling) and mouth (chewing, lip smacking).
4. Lateralizing features can occur during as well as after a partial complex or secondary generalized seizure. Unilateral automatisms are usually ipsilateral to the seizure focus, while dystonic posturing almost invariably occurs on the contralateral side. Head deviation at seizure onset is usually ipsilateral to the seizure; when it occurs later, it is contralateral. This later head turning also has a more forceful, involuntary appearance and is so-characterized as "versive" (a seizure characterized by sustained, forced conjugate ocular and cephalic and/or truncal deviation). Contralateral clonic activity is relatively unusual. Lateralizing findings in the setting of mesial temporal sclerosis should be interpreted with some caution, as many of these patients have bilateral, independent seizure foci.
5. Less commonly observed behaviors associated with a temporal lobe seizure include ictal speech and vocalizations, affective behaviors (laughing, crying or fear), hypermotor behaviors usually associated with frontal lobe seizures, and so-called "leaving behavior" (walking or running away).
6. Postictal confusion usually lasts minutes, but may be complicated by psychosis. Postictal hemiparesis can occur contralateral to the seizure focus, and postictal aphasia can occur with a seizure emanating from the dominant hemisphere. Nose-wiping, performed by the hand ipsilateral to the focus of seizure onset, is a common postictal event in mesial TLE. Postictal wandering is not specific to TLE, but is seen more often with temporal compared to extratemporal seizures.

Frontal lobe epilepsy
Common characteristics of frontal lobe seizures are short duration (<30 seconds) and predilection for occurrence during sleep. The latter is particularly true for frontal lobe complex partial seizures and supplementary motor seizures. Differentiating nocturnal seizures from parasomnias can be challenging; one study suggests that it is not uncommon for the two to co-exist.

Seizure clusters and status epilepticus (whether partial, complex partial, or generalized) are also more common in frontal lobe epilepsy than with TLE. A postictal state may be brief or absent. Secondary generalization of frontal lobe seizures was at one time thought to be more common than in mesial TLE, but systematic comparisons suggests that this has a similar incidence in both.

Frontal lobe seizure types include:
1. Complex partial seizures are often characterized by hypermotor behaviors (proximal limbs, tonic). These can produce bizarre-looking episodes that may be mistaken for psychogenic nonepileptic seizures.
2. Other features that suggest complex partial seizures of frontal rather than temporal lobe origin include bicycling automatisms as well as pelvic thrusting and other sexual automatisms. Tonic posturing and head and eye deviation (version), usually contralateral to the side of the seizure focus, can occur in some patients. Vocalizations are also very common.
3. While seizure auras are common in frontal lobe epilepsy, they are less ubiquitous than in mesial TLE, and the sensation is often ill-described and typically does not include epigastric phenomenon. Fear and anxiety occur as seizure auras in both TLE and frontal lobe epilepsy.
4. Consciousness may be more preserved in frontal lobe complex partial seizures compared with TLE. Patients often report recall of ictal events even though they are not able to respond, but the accuracy of this reporting is not certain.
5. Focal motor seizures involving the primary motor cortex will produce hemiclonic activity in the contralateral face, arm, or leg. Seizures may be quite focal (isolated to one limb or face) or may spread (or march) to adjacent areas (ie, Jacksonian seizure). Hemiclonic activity is more common in complex partial seizures of frontal origin than with those in TLE.
6. Supplementary motor area seizures typically produce stereotyped asymmetric tonic movements. One example is the "fencing posture," in which the head and eye deviate to the contralateral side, with extension of the contralateral arm and flexion of the ipsilateral arm. The most prominent tonic activity occurs contralateral to the seizure focus. Brief superimposed clonic movements or vocalizations may also occur. Speech arrest may accompany seizures arising from the dominant hemisphere. There may be a somatosensory aura. Despite bilateral tonic movements, consciousness is often preserved unless there is secondary generalization.
7. So-called frontal absence seizures manifest with staring, trance-like states. These seizures originate from the frontopolar or medial frontal regions. These seizures are more prolonged than other seizure types, often lasting several minutes, sometimes hours, or even days.
8. Secondary generalization may occur after any of the above initial ictal manifestations. A minority of patients have secondary generalized seizures that occur without preceding complex partial or motor symptoms.

TIA (limb-shaking) or seizure in elderly

The following paragraph was taken from UpToDate on 2011/12/07:
Transient ischemic attacks (TIAs) may be mistaken for seizures, but they may also induce seizures.

Brain ischemia produces reduced neural activity and "negative" symptoms such as hemiparesis or hemisensory loss. In contrast, seizures usually cause "positive" symptoms from neural overactivity. So called "limb-shaking" TIAs may represent a source of diagnostic confusion in this regard. This somewhat unusual manifestation of cerebral ischemia typically occurs in the setting of high-grade carotid stenosis.

Certain symptoms, such as aphasia, can occur in TIA or seizure. While an isolated episode of aphasia is more likely to be a TIA than a seizure, aphasic seizures are well described. In general, ictal aphasia is progressive, developing over minutes from dysphasia to paraphasic errors, and culminating in a global aphasia. In contrast, TIA symptoms develop abruptly and typically do not evolve. Although TIA is commonly considered as a cause for confusional episodes, confusion is rarely a manifestation of TIA.

Chronic, recurrent stereotyped events are much more likely to be seizure than TIA. Transient loss of consciousness only should not be diagnoed as TIA. However, since syncope can rarely occur in association stroke, care should be exercised in the evaluation of patients with syncope and limb weakness which can actually be Todd's paralysis after a seizure of no witness.

Dialeptic seizure or syncope in elderly

The following paragraph was taken from UpToDate on 2012/12/07:

Complex partial seizure was the most common seizure type in older patients; 38.3 percent of patients experienced complex partial seizures. In contrast to younger patients, complex partial seizures in older adults are more often extratemporal, usually frontal, in origin, and therefore have an "atypical" clinical presentation. Classic descriptions of seizure aura, such as deja vu and olfactory hallucinations, are uncommon. Patients may instead report antecedent symptoms that are atypical and nonspecific, such as vaguely localized paresthesias, dizziness, and muscle cramps. Observers often note episodic confusion, sleepiness, or clumsiness rather than motor manifestations such as tonic or clonic movements, or automatisms. Postictal states are frequently more prolonged in elderly patients, particularly if there is underlying brain dysfunction.

Because of the "atypical" symptomatology, elderly patients with seizures may be frequently misdiagnosed. In a study, VACS#428, 73.3 percent of patients ultimately diagnosed with epilepsy had a different referral diagnosis. These included altered mental status, confusion, blackout spells, memory disturbance, syncope, dizziness, and dementia. In another series, transient ischemic attack (TIA), depression, and metabolic or psychiatric disorders were also among the initial misdiagnoses. Misdiagnosis is more common in patients with partial complex and partial simple seizures than with generalized tonic-clonic seizures. Despite the known association of seizures and cerebrovascular disease, a history of stroke or TIA was associated with a 1.7-year delay to diagnosis. Similarly, comorbid dementia can obscure the recognition of seizures.

How about syncope? The following description is an extract from Adam’s Neurology:

Description of symptoms, as with other predominantly subjective states, is often ambiguous. The patient may refer to the experience as light-headedness, giddiness, dizziness, a "drunk feeling," a weak spell, or, if consciousness was lost, a "blackout." Careful questioning may be necessary to ascertain the exact meaning the patient has given to these words. In many instances the nature of the symptoms is clarified by the fact that they include a sensation of faintness and then a momentary loss of consciousness, which is easily recognized as a faint, or syncope. This sequence also informs us that under certain conditions any difference between faintness and syncope is only one of degree. These symptoms must be clearly set apart from certain types of epilepsy, the other major cause of episodic unconsciousness, and from disorders such as cataplexy, transient ischemic attacks (TIAs), "drop attacks," and vertigo, which are also characterized by episodic attacks of generalized weakness or inability to stand upright, but not by a loss of consciousness.

The clinical manifestations of fainting attacks vary to some extent, depending on their mechanisms and the settings in which they occur. The most common type of faint—namely, vasodepressor or vasovagal syncope conforms more or less to the following pattern. The patient is usually in the upright position at the beginning of the attack, either sitting or standing. Certain subjective symptoms, the prodrome, mark the onset of the faint. The person feels queasy, is assailed by a sense of giddiness and apprehension, may sway, and sometimes develops a headache. What is most noticeable at the beginning of the attack is pallor or an ashen-gray color of the face; often the face and body become bathed in cool perspiration. Salivation, epigastric distress, nausea, and sometimes vomiting may accompany these symptoms, and the patient tries to suppress them by yawning, sighing, or breathing deeply. Vision may dim or close in concentrically, the ears may ring, and it may be impossible to think clearly ("grayout").

This serves to introduce the common faint that is known to all physicians and most laypersons. However, if there is no such typical presentation, it is challenging to different syncope or faint from dialeptic seizure in the elderly. Seizures are the probable cause of 5 to 15 percent of apparent syncopal episodes. They can mimic syncope when the seizure is atypical and not associated with tonic-clonic movements, the seizure is not observed, or a complete history cannot be obtained. A careful clinical history is important in distinguishing syncope from epilepsy. Important features are not always volunteered and must be specifically solicited.
Features that distinguish syncope from seizures are discussed further on.

Differential diagnosis:

Syncope in an elderly patient can be accompanied by incontinence, and recovery is often slow, mimicking a postictal state. In addition, some patients with syncope present with myoclonic or other involuntary movements that are suggestive of a seizure but are actually due to cerebral hypoxia.
One distinguishing feature is recovery of consciousness. Patients usually wake up quickly after a syncopal event. Prolonged confusion or lethargy lasting several minutes or longer favors seizure.

Clinical setting - Epileptic seizures and syncope arising from cardiac arrhythmias can occur in any setting and are usually unprovoked. Vasovagal syncope tends to occur in the setting of a strong emotional or painful stimulus, but may also occur with more subtle stimuli, including a hot environment. Reflex syncopes occur with specific stimuli (eg, micturition, cough). Events in the setting of exertion suggest syncope related to structural cardiac disease. Except when caused by a cardiac arrhythmia, it is unusual for syncope to occur when patient is supine.

Warning symptoms (aura, prodrome) - In vasovagal syncope, a prodrome of presyncope is the rule. These patients may note lightheadedness, warmth, nausea, and a gradual fading or tunneling of binocular vision. In contrast, symptoms of olfactory hallucinations or deja vu suggest a seizure aura. However, not all epileptic seizures include a seizure aura. Cardiogenic syncope typically occurs without warning.

Associated symptoms - Pallor and diaphoresis strongly suggest syncope. However, it is unusual for syncope to be associated with tongue biting, head or eye turning to one side, or hypersalivation; these suggest epileptic seizure. Urinary incontinence can occur in both seizures and syncope.
Symptoms occurring in association with syncope can point toward a specific cause. As examples, dyspnea may suggest an acute pulmonary embolism; angina frequently indicates an underlying cardiac cause; a history of focal neurologic abnormalities favors a neurologic origin; and urinary and/or fecal incontinence suggest, but do not prove, a seizure.


Motor activity - While motor activity during an episode of unconsciousness often suggests a seizure diagnosis, brief motor activity, including tonic extension of the trunk and limbs or several clonic jerks, can occur in uncomplicated syncope. The severity of convulsive symptoms in syncope varies from subtle signs that are often overlooked to more dramatic symptoms that mimic an epileptic seizure. Relatively few bystanders witnessing syncopal attacks report convulsive symptoms, but clinicians systematically observing attacks (eg, during tilt table testing, invasive cardiac electrophysiologic testing, blood drawing) describe convulsive symptoms in up to half of patients. Convulsions (in syncope) are more likely to occur with more prolonged and more severe cerebral hypoperfusion.
Electroencephalography (EEG) recordings during syncopal events usually demonstrate generalized slowing followed by high voltage frontal delta activity [15,16]. Flattening of the EEG can follow if cerebral hypoperfusion persists. It is at this stage that nonepileptic, seizure-like movements are most often described. It has been suggested that these movements may represent a brainstem-release phenomenon.

The combination of seizure-like motor activity in the setting of syncope is sometimes referred to as convulsive syncope. While these convulsions are common in syncope, a true epileptic seizure ("anoxic seizure") is rare, except in susceptible people or those with prolonged cerebral ischemia.