How Do We Evaluate, Treat, and Disposition New Onset Seizure Patients?

1. How Do We Evaluate, Treat, and Disposition New Onset Seizure Patients? KHALID MBAYA (M.D) SUPERNUMERARY REGISTRAR JOINT DIVISION OF EMERGENCY MEDICINE UNIVERSITIES OF STELLENBOSCH AND CAPETOWN

2. A 25 years old female, known RVD +Ve not yet on ARVs, with CD4 counts of 95, is reffered from MDHS to GFJ on 24/01/2010 .Reason for referral is to do CT scan of brain because the patient had an episode of seizure followed with confusion few hours ago. The patient was given a stat dose of Ceftriaxon 2gm at MDHS before transfer to GFJ.

3. Questions • Why the patient was given Ceftriaxon 2gm? • What do you think was the diagnosis of this patient in the mind of referring doctor? • What reasons could probably made him to request CT of brain? -Afraiding of herniation of intracranial mass if he does LP? -Formality? Standard of care? -To confirm diagnosis?

4. The patient arrived at GFJ hospital on 25/01/2010 at 00h30. Vitals: B.P 108/75 mmhg, Pulse 88/min Temperature 35.5°C, Hb 8.4 Vx 7.7 Collateral from the mother: The patient had a fit in the morning and was unable to to talk for about 5minutes.she peed on herself.After that episode the patient remained confused untill they arrived at the day hospital. The patient is not known to be epileptic and was scheduled to start ARV clinic next day. On examination: The patient looks calm, oriented to TPP. Normal physical and systemic findings. Blood was drawn for EUC and FBC, and results was: Na 135, K 4.6, WCC 7.6, Hb 10.9, Platelets 561. Due to normal neurological findings, LP was done and 10mm3 of clear fluid under moderate pressure drawn and sent to the lab. Results were obtained just before the morning ward rounds. Poly 0, lymph 0, Eryth 72, gluc 3.6, indian ink –ve, culter pending.

5. 24/01/2010 at 0800 W/R with int.medicine consultant Dr.Nyo: -Why did you do LP? That is very dangerous -Since the LP results are normal, and patient looks fine, plans are as follow: 1.Descharge the patient to come back the next day for CT brain. 2.Start anti epileptic, Epilim 500mg b.d. The patient was then descharged early in the morning.

6. The same day after being discharged, at 16h00 the patient is brought back by her mother. She reports that the patient has become confused again, she is agitated, over talkative and talks abusive languages. She even beats her children unnecessarily. No fits were observed. • On arrival the patient started moving around the beds talking to each patient and some time intimidating them. • Vital signs were taken and found to be normal. • On examination, the patient was anxious, increased pressure speech, over talkative but oriented to TPP. Physical and systemic findings were normal. • The patient was given Diazepam 10mg iv and slept the whole night quietly.

7. 25/01/2010 08h00, Ward round with Dr.Aboo. -The patient looks calm, normal vital findings. • Who did the LP? And why? Somebody must have told him. These are Americans books confusing people. • This patient has toxoplasmosis, why not on bactrim? Plan: Do CT scan now. • Forms filled and signed for requesting CT of brain. • Results: CT Machine is not working. Patient booked for CTB on 05/02/2010. The patient was discharged with the following treatment: • Bactrim 4tabs b.d x 1/12 • Epilim 300mg b.d x 1/12 • Panado 1gm t.d.s x 1/52 • To start ARVs at local hospital

8. Questions • Bearing in mind the bureaucrats and difficultness of getting CT scan done in our hospitals -what could have been done to this patient if LP had not been done? 1.Treat her as Menengitis (Bacteria?Viral? Criptococcus?) until CTB done to confirm toxoplasmosis? 2.Treat her as Toxoplasmosis until CTB done to exclude it, then do LP to find for menengitis? 3.Treat her as Menengitis and Toxoplasmosis until CTB then LP done to exclude either.

9. Key Clinical Questions • What are the key components of the history and physical in a patient with a first time seizure? • What laboratory tests are indicated in this patient in the ED? • Does this patient need a neuroimaging study in the ED? • Which patients with new onset seizures should be started on AEDs in the ED? • Which patients with new onset seizures need to be admitted to the hospital? • Is it safe to LP before CT brain?

10. Recommendations • Class A: None specified. • Class B: • Perform a lumbar puncture either in the emergency department or after admission in patients with a first time seizure with HIV disease following a head CT. • Determine a serum glucose and electrolytes on patients with first time seizure with no co-morbidities who have returned to their baseline. • Obtain a pregnancy test if a woman is of child bearing age. • Perform a Neuroimaging of the brain in the emergency department on patients with a first time seizure. If Neuroimaging of the brain is not available in the emergency department, discuss the risk of recurrence with the patient and the patient’s primary physician and either admit the patient to the hospital or make arrangement for an outpatient evaluation.

11. Recommendations • Class C: • Patients with a first time seizure who have a normal neuroimaging of the brain, normal serum glucose and sodium, and normal neurologic examination can be discharged from the ED with outpatient follow-up. • Patients with a first time seizure who have a normal neurologic exam, normal neuroimaging of the brain, normal serum glucose and sodium, and no co-morbidities do not need to be started on an antiepileptic drug (AED) in the ED.

12. New Onset Seizures • 5% - 6% of the population will have at least one seizure during their lifetime • Diagnostic work-up in the ED depends on the clinical exam and co-morbidities • Etiologies of first time adult seizures (age group dependent and co-morbidity dependent (eg HIV): • Chronic alcohol consumption (30-60 year olds) • Cerebral vascular insults (>60 year old)

13. What laboratory tests are indicated in the ED evaluation of a patient with a new onset sz? • ACEP Clinical Policy. Ann Emerg Med 1997; 29:706 • Patients with a normal exam and no co-morbities: Glucose level, electrolytes, and pregnancy test • Consider a drug of abuse screen • Patients with co-morbidities require more extensive testing • CPK and prolactin levels are of limited value in the ED

14. Lumbar Puncture • A LP in the ED is not indicated if the patient: • Is not immunocompromised • Has returned to baseline • Has no fever or meningeal signs • There are no cases reportedof meningitis presenting as a simple tonic clonic seizure • Postictal pleocytosis (>5 polys in the CSF) has been reported in 2 - 18% of patients who have had a GTCS

15. Neuroimaging: Head CT and MR • Three per cent to 41% of patients with a first time seizure have an abnormal head CT • Imaging is dependent on the urgency of the evaluation and patient stability • Literature interpretation depends on outcome measure used

16. Neuroimaging in New Onset Seizures • ACEP, AAN, AANS, ASNR. Practice Parameter: ED neuroimaging in the seizure pt. Ann Emerg Med 1996; 27:114-118. Evidence based practice guideline • Emergent CT for patients with altered mental status, trauma, focal exam, immunocompromise, fever, co-morbitidity • Patients who are alert with a nonfocal exam can have an outpatient study • Focal abnormalities on CT are reported in up to 40% of patients with new onset seizures; up to 20% have non-focal exams • MRI is better than CT in detecting subtle lesions (e.g., hippocampal sclerosis) but impact on care is controversial • GF JOOSTE HOSPITAL CLINICAL GUIDELINES 2010: pg 46 APROACH TO FISRST SEIZURE: -Hiv+ve or suspected, awake, no focal signs, no papilloedema, no meningism= CT scan within 1 week, LP if no contraindication. pg 50: Urgent scan (within 48hrs)= First time seizure in HIV positive patients if a lumbar puncture is normal (L.P’s should only done if no focal signs)

17. Treatment and Disposition • Decision to admit or to initiate AED treatment depends on the risk of recurrence • Etiology and EEG are the strongest predictors • Recurrence risk in the first 24 hours is up to 23% in patients with a focal lesion and 9% in patients with a first time seizure of undetermined etiology(Tardy: study has many flaws) • No prospective studies exist; no outcome studies

18. Treatment and Disposition • Management must be coordinated with a neurologist or primary care provider • Patients needing immediate AED treatment can be loaded with intravenous phenytoin or valproic acid • Decision to admit depends on the assessed risk of recurrence, patient compliance and social circumstance

19. Areas in need of future research • Prospective study investigating laboratory testing in patients with new onset seizures • Prospective study of neuroimaging in new onset seizures and impact on outcome • Prospective study on seizure recurrance within 72 hours in patients with new onset seizure and no etiology identified in the ED • Prospective study on risk stratification in the ED and implementation of AED therapy

20. Definitions • Level A recommendations. Generally accepted principles • for patient management that reflect a high degree of clinical • certainty (ie, based on “strength of evidence Class I” or • overwhelming evidence from “strength of evidence Class • II” studies that directly address all the issues). • Level B recommendations. Recommendations for patient • management that may identify a particular strategy or • range of management strategies that reflect moderate clinical • certainty (ie, based on “strength of evidence Class II” • studies that directly address the issue, decision analysis • that directly addresses the issue, or strong consensus of • “strength of evidence Class III” studies). • Level C recommendations. Other strategies for patient • management based on preliminary, inconclusive, or conflicting • evidence, or, in the absence of any published literature, • based on panel consensus.

21. Related articles or researches • 1. DeLorenzo R, Hauser W, Towne A, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996; 46:1029-1035. This is an important prospective study that used a strict definition of status epilepticus involving 204 events. The authors report a projected annual incidence of status epilepticus of 50 per 100,000 population, with an overall mortality of 22%; 3% for children and 26% for • adults. According to the study, over one half of patients presenting to the ED in status epilepticus had no prior seizure history. Mortality in patients with status epilepticus is linked to the duration of the seizures and the underlying etiology • 2. American College of Emergency Physicians. Clinical policy for the initial approach to patients presenting with a chief complaint of seizure who are not in status epilepticus. • Ann Emerg Med 1997; 29:706-724. • This clinical policy is currently under revision. In essence, it is a formal consensus document that provides general guidelines for approaching the patient who has had a seizure. The policy recommends that patients with a first time seizure have, at a minimum, a set of electrolytes, a glucose level, and a pregnancy test if a female of child-bearing age. Therapeutics are not addressed. • 3. Turnbull T, Hoek T, Howes D, Eisner D. Utility of laboratory studies in the emergency department patient with a new onset seizure. Ann Emerg Med 1990; 19:373-377. • This is a prospective study of 136 patients with new onset seizures seen over a four-year period; it is not clear if these were consecutive patients (though doubtful thus introducing selection bias into the study). All patients had an evaluation of electrolytes, BUN, Cr, CBC, glucose, calcium, and magnesium. 11 cases of laboratory abnormalities were discovered, only two of which (patients with hypoglycemia) were not suspected. The authors conclude that, with the exception of serum glucose, serum analyses are of low yield in patients with new onset seizures who have normal physical exams and no co-morbidities. • 4. Pesola G, Westfal R. New onset generalized seizures in patients with AIDS presenting to an emergency department. Acad Emerg Med. 1998; 5:905-911. • This is a retrospective review of 26 AIDS patients with new onset seizures which were compared to 120 non-HIV patients. Four of the HIV patients were found to have treatable lesions that were not suggested by clinical findings. This study supports the need for a CT and a LP in HIV patients with new onset seizures.

22. 5. Tardy B, Lafond P, Convers P. Adult first generalized seizure: etiology, biological tests, • EEG, CT scan, in an ED. Amer J Emerg Med. 1995; 13:1-5. • This is the only study that specifically looks at seizure recurrence within 24 hours of presentation. It suffers from its retrospective design with probable selection bias. Of 247 patients, alcohol and acute stroke were the most common etiologies identified. 5 patients were hypoglycemic, 4 were hyponatremic, 3 had calcium or sodium abnormalities. 85 patients had a focul lesion on head CT; 32% had an EEG with a focal abnormality. Seizure recurrence was 19% in the first 24 hours; when alcohol and focal lesions were excluded, the rate dropped to 9%. Unfortunately, a complete data set is not provided to allow for an of predictors that might enable the clinican to risk stratify patients. • 6. Henneman P, DeRoos F, Lewis R. Determining the need for admission in patients with • new-onset seizures. Ann Emerg Med 1994; 24:1108-1114. • This is a retrospective review of 333 adult patients with new onset seizures. The authors conclude that patients needing admission can be predicted by a standardized medical evaluation in the ED though unfortunately the retrospective study design did not allow for a standardized evaluation to have been performed. A complete data set on patients is not provided making it difficult to support some of the conclusions made by the authors. • 7. American College of Emergency Physicians, American Academy of Neurology, • American Association of Neurological Surgeons, American Society of Neuroradiology. • Practice Parameter: Neuroimaging in the emergency patient presenting with seizure • (Summary Statement). Ann Emerg Med 1996; 27:114-118. • This is an important practice guideline that all emergency physicians should be familiar with. The guideline was a joint collaboration between ACEP and the AAN and the AANR. An evidence-based approach was taken to formulate recommendations. The three societies jointly recommended that a neuroimaging study could be obtained as an outpatient if the patient the neurologic exam was normal and no predisposing co-morbidites, eg malignancy, are identified.

23. COMPUTED TOMOGRAPHY OF THE HEAD BEFORE LUMBAR PUNCTURE IN ADULTS WITH SUSPECTED MENINGITIS.R0DRIG0 HASBUN, M.D., JAMES ABRAHAMS, M.D., JAMES JEKEL, M.D., AND VINCENT J. QUAGLIARELLO, M.D • Background: In adults with suspected meningitis clinicians routinely order computed tomography (CT) of the head before performing a lumbar puncture. • Methods :We prospectively studied 301 adults with suspected meningitis to determine whether clinical characteristics that were present before CT of the head was performed could be used to identify patients who were unlikely to have abnormalities on CT. The Modified National Institutes of Health Stroke Scale was used to identify neurologic abnormalities.

24. Results • Of the 301 patients with suspected meningitis, 235 (78 percent) underwent CT of the head before undergoing lumbar puncture. In 56 of the 235 patients (24 percent), the results of CT were abnormal; 11 patients (5 percent) had evidence of a mass effect. The clinical features at base line that were associated with an abnormal finding on CT of the head were an age of at least 60 years, immunocompromise, a history of central nervous system disease, and a history of seizure within one week before presentation, as well as the following neurologic abnormalities: an abnormal level of consciousness, an inability to answer two consecutive questions correctly or to follow two consecutive commands, gaze palsy, abnormal visual fields, facial palsy, arm drift, leg drift, and abnormal language (e.g., aphasia). None of these features were present at base line in 96 of the 235 patients who underwent CT scanning of the head (41 percent). The CT scan was normal in 93 of these 96 patients, yielding a negative predictive value of 97 percent. Of the three misclassified patients, only one had a mild mass effect on CT, and all three subsequently underwent lumbar puncture, with no evidence of brain herniation one week later.

25. Conclusions • In adults with suspected meningitis, clinical features can be used to identify those who are unlikely to have abnormal findings on CT of the head. (N EngI J Med 2001;345:1727-33.)

26. Questions ?