EEG patterns of status

CONVULSIVE PATTERNS

Primary generalized tonic-clonic status epilepticus

Electrographically, the seizures characteristically begin with a flattening of the normal background rhythms, followed by generalized low voltage fast activity or polyspikes that increase in amplitude and decrease in frequency until these patterns become obscured by muscle and movement artifact. As the seizure clinically moves into the clonic phase, the EEG characteristically shows a checkerboard type pattern of muscle artifact corresponding to the rhythmic jerking movements observed clinically. During breaks between seizures, the EEG shows diffuse suppression of cerebral activity.

Generalized myoclonic status epilepticus

The EEG in myoclonic status epilepticus may show generalized, bisynchronous polyspikes, spikes, or sharp waves preceding and time-locked with the clinical myoclonus, superimposed on a diffusely slow and suppressed background. A burst-suppression pattern may also be seen. Of note, due to the accompanying muscle activity associated with the myoclonic movements, discerning true epileptiform activity from muscle artifact can often be challenging. In this case, the use of a short-acting paralytic agent may aid in determining if the myoclonus is cortically generated or whether it originates lower down the neuro-axis (ie, brainstem, spinal cord, or peripheral site). Ultimately, this determination may be difficult without simultaneous EEG and electromyography (EMG) with jerk-locked back-averaging techniques.

Generalized clonic status epilepticus

The EEG typically shows generalized, synchronous spikes or spike wave complexes time-locked with the clinical movements.

Generalized tonic status epilepticus

Tonic seizures have a propensity to cluster and are more common during non–rapid eye movement (REM) sleep. The electrographic appearance of tonic seizures consists of moderate to high amplitude, frontally predominant, generalized 10-25 Hz spikes, sometimes termed generalized paroxysmal fast activity (GPFA). A second ictal tonic EEG pattern consists of an abrupt, generalized attenuation or flattening of the background EEG activity (to < 5-10 µV) that can be the sole manifestation of the ictal activity or can precede the development of the 10-25 Hz generalized spikes.

Generalized atonic status epilepticus

Atonic seizures are common in patients with Lennox-Gastaut syndrome and are a prominent feature in patients with myoclonic-astatic epilepsy of Doose. The ictal EEG during atonic seizures typically shows either generalized polyspike-and-wave or generalized slow-spike-and-wave (SWS) activity, followed by diffuse, high-amplitude, generalized slow waves maximal over the central head regions.

Simple partial status epilepticus

The ictal EEG in simple partial status epilepticus may show any of a range of patterns from focal spikes, polyspikes, spike and waves, suppression, or focal rhythmic discharges of any frequency to a completely normal background without evidence of ictal activity. Because approximately 6 cm2 of synchronously firing cortex must be involved for EEG to detect ictal activity, it should not be surprising that many focal seizures will be beyond the resolution of scalp EEG, because the ictal focus is too small, too distant, or unfavorably oriented in relation to the electrodes (ie, originating deep in a sulcus) to be detected by scalp recording.

In such instances when the focal seizures cannot be detected by scalp recording, functional imaging modalities such as cerebral positron emission tomography (PET)—which measures cerebral glucose metabolism—or single photon emission computed tomography (SPECT) scanning—which measures regional cerebral blood flow—may be helpful in confirming the diagnosis. If such studies are performed during ongoing clinical signs or symptoms, increased local glucose metabolism or regional cerebral blood flow would verify the suspected seizure focus.

Complex partial status epilepticus

Because a significant amount of cortex (ie, >6 cm2) is typically involved to produce impaired consciousness, complex partial seizures will have an ictal correlate on EEG. The ictal footprint is variable and may consist of focal spikes, polyspikes, spike waves, suppression, or focal rhythmic discharges of any frequency.

NONCONVULSIVE PATTERNS

Typical absence status epilepticus

The classic EEG finding in typical absence status epilepticus is generalized 3 Hz spike-and-wave activity (range 2.5-4 Hz). However, generalized polyspike-and-wave may also be seen. The intradischarge frequency is classically constant but may vary over the course of the seizure.

Atypical absence status epilepticus

In contrast to typical absence seizures, in atypical absences, the onsets and offsets are clinically less abrupt and distinct and the seizures are longer in duration (lasting up to minutes). Additionally, changes in tone are more prominent than in typical absence seizures. The ictal EEG shows slow (< 2.5 Hz) generalized spike-and-wave complexes that may be more irregular and asymmetric than what is classically seen in typical absence status epilepticus.

Nonconvulsive SE with Partial Onset

Primary criteria

An electrographic or nonconvulsive seizure may be demonstrated by any electrographic pattern lasting at least 10 seconds and satisfying any 1 of the following 3 primary criteria:

*Repetitive generalized or focal spikes, sharp-waves, spike-and-wave, or sharp-and-slow wave complexes at a frequency of 3 or more per second.

*Repetitive generalized or focal spikes, sharp-waves, spike-and-wave, or sharp-and-slow wave complexes at a frequency of 3 or less per second AND one of the secondary criteria below.

*Sequential rhythmic, periodic, or quasi-periodic waves at 1 or more per second and unequivocal evolution in: (1) frequency (increasing or decreasing by at least 1/sec), (2) morphology, or (3) location. Of note, evolution in amplitude alone is not sufficient to meet the criteria for evolution. Additionally, change in sharpness of the waveform without other change in morphology is also not adequate to qualify as evolution of morphology.

Secondary criteria

An electrographic or nonconvulsive seizure may be additionally demonstrated by significant improvement in the patient’s clinical state or the appearance of previously-absent normal EEG patterns (such as a posterior dominant rhythm or sleep transients) temporally coupled to the acute administration of a rapidly-acting antiepileptic drug such as a benzodiazepine. Of note, resolution of the suspected ictal pattern without clinical improvement or the appearance of previously absent normal EEG patterns would not satisfy the secondary criteria.

When rhythmic, periodic, or quasi-periodic electrographic patterns fail to fulfill these criteria in an obtunded or comatose patient who lacks other clinical signs of seizure activity, the diagnosis of nonconvulsive status epilepticus becomes more difficult and controversial. Patterns such as lateralized periodic discharges (LPDs, formerly termed PLEDs); bilateral, independent periodic discharges (BIPDs, formerly termed BIPLEDs); generalized periodic discharges (GPDs, formerly termed GPEDs); and stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) represent ambiguous but potentially ictal patterns whose clinical significance and management remain controversial topics.

From 

http://emedicine.medscape.com/article/1138728-overview#a1

Basics of TMS

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890546/

A good review.

Dose of Lacosamide

Dosing: Adult (Uptodate)

Partial onset seizure:

Monotherapy: Oral, IV:

Initial: 100 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability.

Alternative initial dosage: Loading dose: 200 mg followed approximately 12 hours later by 100 mg twice daily for 1 week; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability. Note: Administer loading doses under medical supervision because of the increased incidence of CNS adverse reactions.

Maintenance: 150 to 200 mg twice daily. Note: For patients already on a single antiepileptic and converting to lacosamide monotherapy, maintain the maintenance dose for 3 days before beginning withdrawal of the concomitant antiepileptic drug. Gradually taper the concomitant antiepileptic drug over ≥6 weeks.

Adjunctive therapy: Oral, IV:

Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability.

Alternative initial dosage: Loading dose of 200 mg followed approximately 12 hours later by 100 mg twice daily for 1 week; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability. Note: Administer loading doses under medical supervision because of the increased incidence of CNS adverse reactions.

Maintenance dose: 100 to 200 mg twice daily (maximum: 400 mg daily)

Status epilepticus, refractory (off-label use): IV: 200 to 400 mg followed by a daily maintenance dose of 200 to 600 mg daily in 2 divided doses (Albers, 2011; Goodwin, 2011; Kellinghaus, 2011; NCS [Brophy, 2012]). Note: Although the Neurocritical Care Society recommends administration of the initial dose at a rate of 200 mg over 15 minutes, others have administered doses of up to 400 mg IV push over ≤5 minutes without apparent harm (Goodwin, 2011; Kellinghaus, 2011; NCS [Brophy, 2012]).

How do seizures stop? A review

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738747/

This is an interesting article from Fred Lado and Solomon Moshe, which reviews literature on mechanisms for seizure termination.

How does a status epilepticus become super refractory?

http://brain.oxfordjournals.org/content/134/10/2802

This question is obviously crucial to successful management. It is a common clinical experience that the more severe the precipitating insult (for instance, in status epilepticus after trauma infection or stroke), the more likely is the status epilepticus to become super-refractory. However, super-refractory status epilepticus also occurs frequently in previously healthy patients without obvious cause.

In all these cases, the processes that normally terminate seizures have proved insufficient (for review, see Lado and Moshe, 2008). At a cellular level, one of the most interesting recent discoveries has been the recognition that receptors on the surface of axons are in a highly dynamic state, moving onto (externalization), away from (internalization) and along the axonal membrane. This ‘receptor trafficking’ intensifies during status epilepticus, and the overall effect is a reduction in the number of functional γ-aminobutyric acid (GABA) receptors in the cells affected in the seizure discharge (Arancibia and Kittler, 2009; Smith and Kittler, 2010). As GABA is the principle inhibitory transmitter, this reduction in GABAergic activity may be an important reason for seizures to become persistent. Furthermore, the number of glutaminergic receptors at the cell surface increases, and the reduction in the density of the GABA receptors is itself triggered it seems by activation of the glutaminergic receptor systems. Why this should happen is unknown, and from the epilepsy point of view is certainly maladaptive. This loss of GABAergic receptor density is also the likely reason for the increasing ineffectiveness of GABAergic drugs (such as benzodiazepines or barbiturates) in controlling seizures as the status epilepticus becomes prolonged (Macdonald and Kapur, 1999). It has also been repeatedly shown that the extracellular ionic environment, which can change in status epilepticus, may be an important factor in perpetuating seizures, and the normally inhibitory GABA(A)-mediated currents may become excitatory with changes in extracellular chloride concentrations (Lamsa and Taira, 2003).

Other cellular events might also be important. Mitochondrial failure or insufficiency may be one reason for the failure of seizure termination and cellular damage and mitochondrial processes are involved in cell necrosis and apoptosis (Cock et al., 2002). Another category of disease triggering persistent status epilepticus is inflammatory disease (Tan et al., 2010), and inflammatory processes may be important in the persistence of status epilepticus. The opening of the blood–brain barrier almost certainly plays a major role in the perpetuation of seizures, due to a variety of possible mechanisms (Friedman and Dingledine, 2011), and this may be especially the case in status epilepticus due to inflammation (Marchi et al., 2011). This may explain the benefits of steroids in the therapy of status epilepticus. Leakage of the blood–brain barrier will also lead to higher potassium levels and excitation (David et al., 2009). No genetic mechanism has been identified to explain the failure of seizure termination although massive changes in gene expression occur within minutes of the onset of status epilepticus.

At a systems level, it has been suggested rather fascinatingly and counter intuitively that status epilepticus results from a failure to synchronize seizure activity (Schindler et al., 2007a, b; Walker, 2011), and that the lack of synchrony somehow prevents seizure termination.

These mechanisms influence strategies for therapy. However, often overriding is the importance of establishing cause of the status epilepticus, for emergency therapy directed at the cause may be crucial in terminating the episode (for review of the influence of aetiology on prognosis, see Neligan and Shorvon, 2011).

Spinal cord section

Joint position and vibration sense in the cord

http://www.ncbi.nlm.nih.gov/pubmed/2926427

Hankey GJ, Edis RH. The utility of testing tactile perception of direction of scratch as a sensitive clinical sign of posterior column dysfunction in spinal cord disorders. J Neurol Neurosurg Psychiatry. 1989 Mar; 52(3): 395-8.

Classical beliefs about the functions of the dorsal columns of the spinal cord have been attacked following recent evidence that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. There is evidence that the one specific function of the dorsal columns is for the transmission of information concerning the direction of tactile cutaneous movement. Thirty normal controls, 43 patients with spinal cord disorders and 10 patients with functional disorders were examined prospectively using an easily administered "direction of scratch" protocol. Interpretation of the direction of a 2 cm vertical tactile cutaneous movement over the lower limbs was found to be accurate in normal controls and grossly inaccurate in patients with functional disorders, exceeding the error rate of guessing. Detection of direction of 2 cm scratch was moderately impaired in 11 of 13 patients with spastic paraparesis and preserved sensation to all other modalities and 23 of 24 patients with spastic paraparesis and impaired proprioception and/or vibration sensations. Direction of 2 cm scratch, proprioception and vibration sensations were preserved in the three cases with anterior spinal cord syndromes. It is proposed that tactile perception of direction of 2 cm scratch over the lower limbs is a sensitive sign of posterior column function which can be usefully incorporated into the clinical sensory examination in the evaluation of spinal cord disorders.