Dissociative Seizures

Introduction

Psychogenic Non-Epileptiform Seizures is a real disease. These events probably represent a subconscious dissociative physical response to distressing internal emotional stimuli. These attacks may look like epileptic seizures but are not truly caused by altered electrical activity in the brain but happen due to a reaction to adverse life experiences, trauma, loss or bereavement. Patients with PNES do not have a focal lesion, but rather have dysfunction that is distributed across a wide array of limbic and cortical substrates modulated by several key endocrine signals. The production of seizure-like symptoms is not under voluntary control, meaning that the person is not faking. Interestingly, about 5-20% of people with PNES also have epilepsy.

Other Terminologies

• Pseudoseizures - Use of this particular terminology is discouraged
• Functional Seizures
• Dissociative Seizures
• Non-Epileptiform Attack Disorder 

No single historical feature or combination of features is diagnostic of PNES. PNES are distinct from Epileptiform seizures as they do not show any abnormal electric discharge from the brain. The definitive test to diagnose PNES is Video EEG. Features that may suggest PNES are:

• Same frequency but variable amplitude throughout the seizure
• Recall of events
• Pelvic thursting
• Forced eye closure
• Episodes >2min

Treatment of PNES

1. Adequate communication and education with the patient/family
2. Continued neurological follow-up to safely withdraw anticonvulsant medications
3. Address comorbid psychiatric diagnoses - CBT/Antidepressants/Antipsychotics (Haloperidol/Olanzapine)

Further Reading
https://www.epilepsy.com/article/2014/3/truth-about-psychogenic-nonepileptic-seizures

Posted by:

              

     Lakshay Chanana

     

     ST4 Trainee

     Royal Infirmary of Edinburgh

     Department of Emergency Medicine

     Edinburgh

     Scotland

     @EMDidactic

Febrile Seizures

Simple Febrile Seizures 

Generalized tonic-clonic seizure that last <15 minutes with fever 38°C in a child 6 months to 5 years of age that occurs only once in a 24-hour period. Simple febrile seizures tend to occur within the rst 24 hours of a febrileillness. If the seizure occurs > 24 hrs after the onset of fever as in this case, the index of suspicion for a serious bacterial illness should be heightened. Anticonvulsant therapy is not recommended for simple febrile seizures since side effects outweigh the minor risks of seizure recurrence. No dedicated seizure workup is required for simple febrile seizures. The workup should focus on looking for the source of the fever, and the approach should be the same as if the child had only the fever with no seizure. However, lumbar puncture should be strongly considered in children who presnet with signs or symptoms suggestive of intracranial infection or those who are unimmunized. 

The height of fever does

not correlate with seizures; however, the rapidity of the rise in temperature is thought to correlate with the occurrence of seizures.

Complex febrile seizures 

Seizures with fever that last >15 minutes, that recur within a 24-hour period, are focal or generalised, or occur in children <6 months or >5 years of age without any signs of serious infection. The distinction between simple versus complex febrile seizures is important, as complex febrile seizures may indicate a more serious underlying disease process and warrant a workup. Meningitis should always be on thedi erential diagnosis in a child with complex febrile seizures. 

Having a febrile seizure does not mean that a child will develop epilepsy. Risk of epilepsy is approximately 2% after a simple febrile seizure and 5% after a complex febrile seizure (compared with 1% in the general population)

When working up, routine tests include FBC, CRP, Blood Cultures, Urine Analysis, Electrolytes and LP should be considered if:

• Post-ictal >1 hr
• Signs of meningitis
• Irritable
• ALready on Antibiotics
• Unvaccinated
• Complex Partial Seizures

Although antipyretics are indicated in children with fever, there is no evidence that antipyretics can prevent subsequent febrile seizures.

Admission and discharge depends on parental comfort, well/sick looking child but consider admission for the following groups: 

• Complex febrile seizures 
• A child with a febrile fit who is less than 18 months of age 
• The child with no serious clinical findings but who is recently/currently taking antibiotics 
• Children who do not have a clear focus of infection 

References:

• Provisional Committee on Quality Improvement, Subcommittee on Febrile Seizures:practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. Pediatrics 97: 769, 1996.
• Subcommitte on Febrile Seizures, American Academy of Pediatrics: Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics 127: 389, 2011.
• Kimia AA, Capraro AJ, Hummel D, et al: Utility of lumbar puncture for first simple febrile seizure among children 6 to 18 months of age. Pediatrics 123: 6, 2009. [PMID: 19117854]
• SteeringCommitteeonQualityImprovementandManagement,SubcommitteeonFebrile Seizures: Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics 121: 1281, 2008.
• https://cks.nice.org.uk/febrile-seizure#!scenario

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

New Onset Seizures in ED

Seizure is an episode caused by inappropriate electrical discharge from neurone due to imbalance between glutaminergic (excitatory) and γ-aminobutyric acid (inhibitory) activity whereas Epilepsy implies a fixed, more excitatory condition of the brain with a lower seizure threshold. The term epileptic does not refer to an individual a known or reversible cause of seizures.

Types of seizures:

Generalised Seizures: Generally caused by simultaneous activation of the entire cerebral cortex, or originating from a focus and then leading to secondary generalisation. 

Generalized tonic-clonic seizures (grand mal) are the most dramatic type of the generalised seizures where the patient suddenly becomes rigid (tonic phase), trunk and extremities are extended, and the patient falls to the ground. This is followed by rhythmic (clonic) jerking of the trunk and extremities. Patients may appear cyanotic when seizing due to apnea. There is often h/o bowel or bladder incontinence. Following the attack, patient remain in an unconscious state for few minutes. Consciousness returns gradually, and postictal confusion, myal- gias, and fatigue may persist for several hours or more.

Absence seizures (petit man): Classic absence seizures occur in school-age children and are often attributed by parents or teachers to daydreaming or inattention. Brief, generally lasting only a few seconds. Patients suddenly develop altered consciousness but no change in postural tone. They appear confused, detached, or withdrawn, and current activity ceases. They may stare or have twitching of the eyelids. They may not respond to voice or to other stimulation and may exhibit involuntary movements or lose continence. The attack ceases abruptly, and the patients typically resume previous activity without post-ictal symptoms. Similar attacks in adults are more likely to be minor complex partial seizures and should not be termed absence. 

Focal Seizures are more likely to be secondary to a localized structural lesion of the brain. The electrical discharges begin in a localized region of the cerebral cortex and then get secondarily generalised. In simple partial focal seizures, the seizure remains localized, and consciousness and mentation are not affected. In contrast, in complex partial seizures consciousness is affected. Focal seizures are regarded as focal seizures from treatment standpoint. 

Consider developing common protocols between ED and Neurology to expedite management in this subset of patients. 

Key Questions:

• Differentiate between seizure or syncope (Get collateral history if possible) 
• Preceding aura? Sudden v/s Gradual onset ? 
• Focal, Generalised, Focal with secondary generalisation
• Duration, Post ictal confusion, Aura, Any h/o Trauma 
• Past h/o fits (Ask frequency, last follow up, medications, compliance, changes in dose or stressors - sleep deprivation, strenuous activity; infection; electrolyte disturbances; and alcohol or substance use or withdrawal)
• Co-morbidities 
• Medications, Recreational Drug use

Examination:

• Blood Glucose
• Tongue Bite
• Look for other injuries (Head/Spine Injury, Shoulder dislocation)
• Focused Neurological Examination - transient focal deficit following a focal seizure may be seen (Todd’s paralysis)

Investigations

• Known seizure disorder presenting with a single unprovoked seizure -> blood glucose level and AED levels
• New onset seizures -> Blood Glucose, Metabolic profile, Ca, Mg, pregnancy test, and urine tox screen. Seizure driven lactate abnormalities usually clear within 30 minutes 
• LP - in cases of fever, immunocompromised, suspected SAH 
• Obtain imaging (Non-Contrast CT Head) in cases of new onset seizures OR a change in seizure pattern, persistent deficits, fever, recurrent episodes. Because many pathologies may not be evident on initial CT, a follow-up MRI with EEG is frequently done as outpatients 
• Do radiographs or imaging of Spine/Shoulder or other relevant injuries as indicated 

Treatment

• Read more on Status Epilepticus and active seizure management here
• Give Loading dose if already on AEDs and there is h/o being non-compliant
• Adjustment of medication should always be made after discussing with a Neurologist
• Outpatient treatment with AEDs in new onset fits should always be started in liaison with Neurologist 
• Arrange timely follow up and Safety Net (Instruct discharged patients not to to take precautions to minimize the risks for injury from further seizures. Swim, drive, work with hazardous tools or machines, and working at heights)

Patients with provoked (secondary) seizures due to an identifiable underlying condition often require admission and should generally be treated to minimize seizure recurrence

Take Home:

• Differentiate between seizure and other similar pathologies (Migraine, Pseudofits, Syncope)
• Arranging follow up and safety netting is crucial
• Change in AEDs to starting new AEDs should always be done in liaison with Neurologist 

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

  

Posterior Reversible Encephalopathy Syndrome (PRES)

Introduction

Posterior Reversible Encephalopathy syndrome PRES (also known as reversible posterior leukoencephalopathy syndrome) is a constellation of clinical and radiological findings which presents with rapid onset headache, seizures, altered consciousness, and visual disturbances. 

It strongly associated with with renal disease, vascular and autoimmune diseases, immunosuppressive medications, and organ transplantation. Nearly 3/4 patients with PRES are hypertensive, but others may have normal or only mildly elevated blood pressure.

Pathophysiology

Failure of Cerebral Autoregualtion, endothelial injury, disruption of blood brain barrier leading to Vasogenic edema is a proposed mechanism. However, the exact pathophysiology remains unclear. 

Diagnosis 

Prompt recognition of PRES is important to prevent permanent damage due to ongoing cerebral ischemia. Having a high index of suspicion is important. PRES must be added to our routine list of differentials of Posterior Circulation Stroke, SAH, Cerebral Venous Thrombosis. Focal neurologic deficits are uncommon in PRES and Seizures are the most common presentation. 

It is reasonable to start with CT Head in the Emergency Department to rule out other CNS Catastrophes. However, MRI is a better tool to diagnose PRES. Magnetic Resonance Imaging recordings showing white matter abnormalities without infarction. Classical MRI findings of vasogenic edema involving bilateral parietal-occipital lobes. 

PRES appears to be a misnomer as the syndrome is not always reversible, and it may not be localised to either the white matter or the posterior regions of the brain. Atypical features— including hemorrhage, asymmetrical changes, isolated involvement of the frontal lobes, and cortical lesions are common.

Management

• Rapid withdrawal of the trigger (Eclampsia, Drugs)
• Prevent Seizures
• Aggressive blood pressure management 

Take Home:

• PRES should be considered in patients who present with seizures, altered consciousness, visual disturbances, or headache, particularly with acute hypertension.
• PRES has been associated with chronic and acute kidney disease, solid organ transplantation, and use of immunosuppressive drugs.
• Typical MRI findings include reversible, symmetrical, posterior subcortical vasogenic edema.
• If recognized and treated promptly, the rapid-onset symptoms and radiologic features usually fully resolve within days to weeks.

References:

• Hinchey J, Chaves C, Appignani B, et al.  A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(8):494-500
• Hobson, E. V., Craven, I., & Blank, S. C. (2012). Posterior Reversible Encephalopathy Syndrome: A Truly Treatable Neurologic Illness. Peritoneal Dialysis International : Journal of the International Society for Peritoneal Dialysis, 32(6), 590–594. http://doi.org/10.3747/pdi.2012.00152
• Fugate, J. E., Claassen, D. O., Cloft, H. J., Kallmes, D. F., Kozak, O. S., & Rabinstein, A. A. (2010). Posterior Reversible Encephalopathy Syndrome: Associated Clinical and Radiologic Findings. Mayo Clinic Proceedings, 85(5), 427–432. http://doi.org/10.4065/mcp.2009.0590
• https://radiopaedia.org/articles/posterior-reversible-encephalopathy-syndrome-1

Author:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

                    

Status Epilepticus - Rapid Review

Background

Status Epilepticus (SE) is the second-most frequent life-threatening neurological emergency after stroke that bears considerable risks of morbidity and mortality. SE requires emergent, targeted treatment to reduce patient morbidity and mortality but the treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. Rapid control of seizures is fundamental to the emergency treatment of SE. Adverse effects may include systemic problems arising from seizures (e.g., impaired ventilation, pulmonary aspiration, and metabolic aberrations) or due to direct neuronal cellular injury from excitotoxicity. 

Definition and Classification

• SE is defined as 5 min or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures
• SE is further classified as either convulsive SE (convulsions that are associated with rhythmic jerking of the extremities) or non-convulsive SE (seizure activity seen on EEG without the clinical findings associated with convulsive SE)
• Refractory SE (RSE) should be defined as SE that does not respond to the standard treatment regimens, such as an initial benzodiazepine followed by another AED. Although some experts consider failure of the first drug i.e. BZD to terminate seizure as RSE.

Rationale for changing the traditional 30 minutes definition to 5 minutes 

Animal data suggests that permanent neuronal injury may occur before the traditional definition of 30 min of continuous seizure activity have passed. Evidence also demonstrates that seizures that do not cease in 5-10 minutes are less likely to terminate without intervention (Pharmacoresistance).

  

Pathophysiology

In short - excess excitation and reduced inhibition. However, the failure of inhibitory processes is increasingly thought to be the major mechanism leading to SE.

Excitatory neurotransmitters: Glutamate, NMDA

Inhibitory neurotransmitters: GABA

Most seizures terminate spontaneously within several minutes but with continuing seizures, inhibitory GABA receptors are internalized in clathrin coated vesicles and at the same time, excitatory N-methyl-d-aspartate (NMDA) receptors may be mobilized to the membrane. This receptor trafficking results in a decreased inhibitory control and increased excitation that may lead to continuing status epileptics. The internalization of GABA receptors may explain the clinical finding that benzodiazepines are less effective as seizure durations increase.

Possible Etilogy

• AED Non-Compliance
• Stroke 
• Hypoxic injury, Traumatic Brain Injury
• Drugs and Toxins (eg, cocaine, theophylline, INH)
• Withdrawal (Opioid, BZD, Barbiturates, Alcohol)
• Electrolyte abnormalities 
• Renal Failure, Liver Failure
• Neoplasms
• CNS infections (eg, meningitis, brain abscess, encephalitis)
• Autoimmune Encephalitis

Management 

All patients need a 

• Fingerstick glucose
• Vital signs monitoring
• Head computed tomography (CT) scan is required for most
• Order laboratory test: blood glucose, complete blood count, basic metabolic panel, calcium (total and ionized), magnesium, AED levels. 
• Continuous electroencephalograph (EEG) monitoring

Consider these based on clinical presentation

• Brain magnetic resonance imaging (MRI)
• Lumbar puncture (LP)
• Comprehensive toxicology panel including toxins that frequently cause seizures (i.e. isoniazid, tricyclic antidepressants, theophylline, cocaine, sympathomimetics, alcohol, organophosphates, and cyclosporine)
• Other laboratory tests: liver function tests, arterial blood gas, AED levels, toxicology screen (urine and blood), and inborn errors of metabolism.

The treatment of convulsive SE should occur rapidly and continue sequentially until clinical seizures are halted. The goal of treatment is to stop the seizures (both clinical and electrographic) as soon as possible. The initial treatment strategy includes simultaneous assessment and management of airway, breathing, and circulation (obtain IV access, administer O2, and securing the airway as needed), seizure abortive drug treatment, screening for the underlying cause of SE, and immediate treatment of life-threatening causes of SE (e.g., meningitis).

Benzodiazepines are the drugs of choice. Lorazepam is the drug of choice for IV administration and Midazolam is the drug of choice for IM administration. Early intubation is advisable if continuous intravenous AEDs are necessary. 

Options for RSI meds include Propofol and Ketamine and this is a scenario where you might consider skipping the paralytics. If you are using them, beware of succinyl choline induced hyperkalemia in prolonged seizures or a chronic neurological illness. If you are using Rocuronium, get the continuous EEG to pick convulsions in a paralysed patient. 

The diagnostic labs are selected depending on the patient’s history and physical examination. Not every diagnostic study is required in every patient. For instance, a lumbar puncture is needed if there is any suspicion of a central nervous system (CNS) infection, but may not be required if patients gives a history of AED non-compliance.

Dosing and Considerations when using second and third line agents 

Dosing of continuous infusion AEDs for RSE should be titrated to cessation of electrographic seizures or burst suppression.

                                                                                                                                                   

                     

Propofol comes with issues like severe hypotension and propofol related infusion syndrome. Midazolam appears to be safer and less hypotensive. Be prepared to start a vasopressor drip to maintain blood pressure or switch to ketamine.

Alternative therapies: Reserve these therapies for patients in RSE

• Ketamine (3 mg/kg IV followed by an infusion of at least 1 mg/kg/hr up to 10 mg/kg/hr.)
• Hypothermia
• Inhales Anesthetics (Isoflurane)
• Ketogenic Diet
• Steroids, ACTH
• Immunomodulation (IVIG or Plasma Exchange)
• Electroconvulsive therapy
• Vagus Nerve Stimulation
• Repetitive Transcranial Magnetic Stimulation
• Surgical Management

     Medications are more likely to terminate seizures when given closer to the seizure onset and they decrease in effectiveness as seizure duration increases, most likely related to changes in the neuronal gamma aminobutyric acid (GABA) receptor subunit composition as a function of time. 

Rationale for using Ketamine 

There is growing evidence that increasing refractoriness to treatment is partly the result of progressive impairment of GABA mediated inhibition as a result of internalization of GABA receptors under conditions of sustained excitability. Due to this internalisation  , GABAergic drugs dare less likely to work for sustained SE. There is also evidence for increased numbers of N-methyl-D-aspartic acid (NMDA) receptors at the synaptic membrane that results in increased sensitivity to excitatory neurotransmitters. The rationale behind using Ketamine is an attempt to antagonise the excitatory NMDA system as GABAergic system is impaired. 

Take Home

• Seizure onset to drug delivery time is more important then debating which BZD works better. Be aggressive while treating SE because pharmacoresistance develops over minutes.
• Never forget that NCSE can present as coma and maintain a low threshold for obtaining a bedside EEG. 
• Ketamine is definitely an option for refractory status epilepticus. 

Further Reading:

1. Shinnar S, Berg AT, Moshe SL, Shinnar R. How long do new-onset seizures in children last? Ann Neurol 2001;49:659-64. 
2. Gaspard N, Foreman B, Judd LM, et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multi-center study. Epilepsia. 2013;54(8):1498-1503. doi:10.1111/epi.12247.
3. Treatment of Refractory Status Epilepticus: Literature Review and a Proposed Protocol Nicholas S. Abend, MD and Dennis J. Dlugos
4. Glauser, Tracy, et al. "Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society." Epilepsy Currents 16.1 (2016): 48-61.
5. Rossetti, Andrea O., and Thomas P. Bleck. "What's new in status epilepticus?." Intensive care medicine 40.9 (2014): 1359.
6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731413/pdf/nihms481665.pdf
7. Emergency Medicine Practice - Evidence Based Medicine - Clinical Decision Making In Seizures And Status Epilepticus 
8. Lowenstein, Daniel H., and Brian K. Alldredge. "Status epilepticus." New England Journal of Medicine 338.14 (1998): 970-976.
9. www.neurocriticalcare.org
10. Brophy, Gretchen M., et al. "Guidelines for the evaluation and management of status epilepticus." Neurocritical care 17.1 (2012): 3-23.

Other FOAMed thoughts on Status Epilepticus: 

http://www.pharmacyjoe.com/status-epilepticus-management-tips-for-the-pharmacist/

http://emcrit.org/podcasts/status-epilepticus/

http://crashingpatient.com/medical-surgical/seizures-status-epilepticus.htm/

http://lifeinthefastlane.com/ebm-status-epilepticus/

http://first10em.com/2015/11/16/status-epilepticus/
http://emlyceum.com/2014/12/09/seizure-answers/