Tutorial for New-Extern “Survival Neurology”Surat Tanprawate, MD, MSc(London), FRCP(T) Division of Neurology, Chiang Mai University “เมือมีเรืองยาก หากหลีกไมได้ จงเขาใจมัน” ่ ่ ่ ้ Neurology extern should know • Medical coma and • Acute stroke • Tonic-clonic seizure and status epilepticus confusional state COMA and ACUTE CONFUSIONAL STATE Wakefulness and ascending reticular activating system(ARAS) >> level << drowsiness stuporous semi-coma coma VARIOUS STATE OF CONSCIOUSNESS Delirium Acute confusional state 2 component of consciousness: arousal and awareness coma, vegetative state, minimally conscious state, and locked-in syndrome. Practical approach • History taking • • • as the patient can not talk, then ask their relative or witness underlying disease is important (DM, atherosclerotic risk, HIV) symptoms before and during coma(neurological complain) clinical classification • • • Physical examination evaluate location and cause evaluate severity coma with localizing sign coma without localizing sign but with meningeal sign coma without both localizing and meningeal sign “GCS” “CPOMR” coma with seizure “CPOMR” can help us to localize the lesion ARAS is located mainly at the brainstem, and both hemisphere • • • Conscious: drowsy, stupor, semi-coma, coma Pupil: dilate, constrict, response to light, uni-bilateral abnormality Ocular movement: doll’s eye, eye deviation, nystagmus, ocular bobbbing Respiratory pattern: • The pupil Parasympathetic control Sympathetic control Pupillary pattern “Doll’s eye” “Oculocephalic reflex” “Vestibulo-ocular reflex” Loss of VOR indicates brainstem dysfunction Motor response and Posture in coma Decorticate posturebilateral flexion of the upper limbs and extension of the lower limbs, usually the consequence of an diencephalic lesion(late) Decerebrate rigiditybilateral upper and lower limb extensor posture, usually the consequence of bilateral mid-brain lesions the Respiratory pattern Cheyne-Srokes Central neurogenic hyperventilation Apneusis Clustering breathing Ataxic breathing Where is it? COMA Localizing sign-no Meningeal sign-yes Severe meningitis or CT with CM in bacterial meningitis Meningitis with complication; hydrocephalus, vasculitis, infarct CT without CM in SAH Encephalitis Subarachnoid hemorrhage - CT Brain with contrast - Lumbar puncture MRI Brain in viral encephalitis Non-structural lesion caused coma • Exogenous- drug, toxin (lead, thallium, cyanide, methanol, CO), addict substance (heroin, amphetamine) • Endogenous- metabolic; Ca, Na, glucose, hypoxemia, hypercapnia, hypothyroid ::: internal toxin; uremia, hepatic encephalopathy These causes are reversible; if no localizing sign; lab screen first Glucose, CBC with Plt, BUN, Cr, Elyte, Ca, Mg, PO, Oxygen sat Keep in Extern’s Mind Alter mental state 1. Ask history; if obvious history suggest cause, treat immediately (hypoglycemia in DM patient, toxin ingestion) 2. Restore vital signs (Oxygen, BP)...then taking lab (glucose immediately, and other basic lab) 3. Physical exam: “CPOMR” + “Meningeal sign” -) if coma with no both focal or meningeal sign: metabolic, toxic, drug, diffuse intracranial lesion, SAH, brain stem stroke, stroke with brain herniation -) if coma with meningeal sign; do CT brain emergency -) if coma with focal sign; do CT brain emergency -) if coma with sign suggesting to seizure: start AED Case exercise • A woman with sudden coma • complain vertigo, and then sudden coma • C=coma, P=pupil 1.5 mm, O=multidirectional nystagmus, and ocular bobbing, M=quadriplegia, R=apneustic breathing • GCS=E1VTM1 QuickTime™ and a H.264 de compressor are need ed to see this picture. Hypodensity lesion at pons and bilateral cerebellum : Basilar artery thrombosis Delirium, Acute confusional state - good wakefulness - impair orientation - fluctuation of consciousness (usually occur at night) - broader cause than coma Cause of delirium - intracranial cause: stroke, cerebritis, etc. - extracranial cause: e’lyte imbalance, deoxygenation etc. - multiple medical/surgical condition Please aware of aphasia that may mimic delirium QuickTime™ an d a Motion JPEG OpenDML decompressor are need ed to see this p icture . Sensory aphasia Acute stroke when we suspect stroke • when the patient has sudden neurological deficit; symptoms depend on where is the brain is involved • • • • • weak, numb brain stem sign cerebellar sign cortical sign alter mental state Stroke can be... Ischemic 75% TOAST classification • Large-artery atherosclerosis(emboli/thrombosis) Cardioembolism(high-risk/mediumrisk) Hemorrhagic (25%); subarachnoid, intracerebral • • • • Small-vessel occlusion(lacune) Stroke of other determine etiology Stroke of undetermined etiology HP Adams, Jr, BH Bendixen, Stroke 1993;24;35-41 TOAST, Trial of Org 10172 in Acute Stroke Treatment. Anterior vs Posterior circulation Condition that mimic stroke “Acute brain attack” ABCD, Neuro sign w/u stroke mimicker; specially hypoglycemia in DM, postseizure EKG IV NSS, Lab (CBC plt, PT, PTT, INR, BUN/Cr/elyte clinical stroke within 2-4.5 hours Activate Fast tract for rt-PA CT Brain non-contrast emergency CT Brain normal or evidence of acute ischemic stroke IV rtPA if indicated CT brain, non-contrast Hemorrhagic stroke • สามารถทาไดรวดเร็ว ใช้เวลาน้อย วินิจฉัยภาวะเลือดออกในสมองเฉียบพลันไดโดยมี sensitivity ้ ้ เกือบ 100% Minor or subtle signs : loss of lentiform nucleus, loss of insular ribbon, loss of gray-white differentiation and sulcal effacement Ischemic stroke Standard treatment in acute ischemic stroke • • • • IV rtPA within 3 hrs : NNT=10 (now 3-4.5 hrs) Stroke unit : NNT = 30-40 ASA within 48 hrs : NNT 140 Early decompressive surgery for malignant MCA infarction : NNT =2 for death prevent ขอบงชีในการให้ยาละลายลิม ้ ่ ้ ่ เลือด • • • • อาการเขาไดกับโรคหลอดเลือดสมอง ้ ้ ขาดเลือด อาการทางระบบประสาทไมไดหายเอง ่ ้ อาการทางระบบประสาทไมน้อยเกินไป ่ เช่น มีอาการชาอยางเดียว ่ สามารถให้การรักษาไดทันภายในเวลา ้ 3-4.5 ชัวโมง ่ Anti-coagulant in acute ischemic stroke • • ยาที่ใช้ : heparin IV drip , LMWH (enoxaparin) SC อาจพิจารณาให้ใน acute ischemic stroke กรณีตอไปนี้ ่ • • • • • Extracranial carotid or vertebral dissection Cerebral venous sinus thrombosis Unstable large vessel infarction Cardioembolic ทีพบ clot ในหัวใจ ่ Arterial dissection First case rt-PA in CM QuickTime™ an d a YUV420 codec decompressor are need ed to see this p icture . 5 Min QuickTime™ an d a YUV420 codec decompressor are need ed to see this p icture . 25 Min QuickTime™ an d a YUV420 codec decompressor are need ed to see this p icture . Brain herniation • Subfalcine (A) • Uncal (B) • Central (C) • Extradural (D) • Tonsillar (E) Herniation syndrome Treatment IICP • • • ให้นอนยกศี รษะและส่วนบนของรางกายสูง 20-30 องศา ่ จัดทาผูป่วยให้หลีกเลียงการกดทับของหลอดเลือดดาทีคอ ่ ่ ่ ้ (Jugular vein) • • พิจารณาให้ osmotherapy: Mannitol* 0.25-0.5 g/kg ทางหลอดเลือดดาใน 20 นาที 46 ครังตอวัน ้ ่ หรือ 10% Glycerol 250 ml ทางหลอดเลือดดาใน 30-60 นาที วันละ 4 ครัง ้ หรือ 50% Glycerol 50 ml ทางปากวันละ 4 ครัง ้ และ/หรือ Furosemide 1 mg/Kg ทางหลอดเลือดดา • • Treatment IICP • • • • หลีกเลียงการให้ hypotonic solution ่ หลีกเลียงภาวะขาดออกซิเจน พิจารณาใส่ทอ ่ ่ ช่วยหายใจในกรณีทมการหายใจผิดปกติ ี่ ี Hyperventilation เพือให้ Pco2 30-35 ่ mmHg มีประโยชนในการลดความดันในสมอง ์ ในช่วงสั้ น ๆ กอนผาตัด ่ ่ ไมควรให้ steroid ่ Hemicraniectomy in malignant MCA infarction Keep in Extern’s mind Stroke 1. when the sudden neurological deficit occur; suspect stroke...every case 2. check time and onset (eligible for rt-PA??) and exclude mimicker cause (hypoglycemia, seizure) 3. if within 4.5 hours; call resident/neurologist “activate FAST TRACT” can request CT brain emergency 4. check v/s, assess severity, check and follow up neurological signs Seizure and status epilepticus Seizure or Not seizure • Seizure mimicker • pseudo-seizure • convulsive syncope • movement disorder: myoclonus, • hypnic jerk chorea, paroxysmal dyskinesia QuickTime™ an d a decompressor are need ed to see this p icture . Identify cause of seizure • Acute processes • • • • • • Stroke Metabolic disturbances CNS infection Trauma Chronic processesPreexisting epilepsyEthanol abuseOld CVARelatively long-standing tumors Drug Toxicity Hypoxia Status Epilepticus How to define status... • The Epilepsy Foundation of • continuous seizure > 30 minutes • > 2 seizures with impaired consciousness America’s Working Group on SE (1993) New proposed definition of SE • Status Epilepticus Cooperative Study group (1998) • Lowenstein DH (1999) • SE > 5 minutes • SE > 10 minutes Classification of status epilepticus 1.Generalized convulsive status epilepticus 2.Non-convulsive SE 3.Simple partial SE (Treiman 1980) 1. Overt 2. Subtle 3. Electrical generalized generalized generalized convulsive SE convulsive SE convulsive SE Generalized convulsive status epilepticus (Treiman 1980) Complication of SE • Acidosis • Cerebral edema • Hypoglycemia • Other: arrhythmia, hyperthermia, hyperkalemia, DIC, rhabdomyolysis, myoglobinuria, renal failure Management of SE What should we do? • Evaluate ABCD, and check basic lab, intubation or oxygen therapy if indicate • Clarify: is it seizure?? • If seizure is not stop; consider AEDs • Complete general, and neuro-exam • Brain imaging if indicate Key • treat early as possible • step up AED is depended on stage of SE • add on therapy is needed • monitor EEG regularly, even if no obvious seizure Define stage of the status epilepticus • Pre-monitory status(0-5 min) • Early status(5-30 min) • Established status(30-60 min) • Refractory status(>60 min) Drug used • diazepam, phenytoin(Dilantin), valproic acid(Depakine), levetirazetam(Keppra) • Phenobarbital, propofol, midazolam, thiopental • Topiramate(feed) drug use depend on stage of status stage of status Premonitory (0-5 min) AED treatment Diazepam (i.v. bolus) Early (5-30 min) Diazepam (i.v. bolus) followed by phenytoin (iv load) or sodium valproate (i.v. loading) or levetiracetam (i.v.) Established (30-60 min) half dose i.v. load of previous drug, if seizure don’t stop, load another drug Refractory ( > 60 min) Propofol (i.v.), or midazolam (i.v.), or thiopental (i.v.) or phenobarbital (i.v.) or topiramate (feed) Diazepam • diazepam 10 mg (2-5mg/min) • max 10 mg per dose • can be repeated 2 doses Phenytoin • • • • Vial: 250 mg/5 ml/vial • 0.9% NaCl (don’t use infusion pump) starting dose: 20 mg/kg (rate < 1 mg/kg/min) maintenance: 5-8 mg/kg/day e.g. weight 50 kg • Dilantin 1000 mg+0.9%NSS 100 cc iv drip in 20 min. then Dilantin 100 mg+0.9%NSS 100 cc iv drip in 15 min Valproic acid • • • • Vial: 400 mg/4 ml/vial • 0.9% NaCl or 5% Dextrose starting dose: 20-30 mg/kg (rate < 50 mg/min) maintenance: 1-2 mg/kg/hr (max 60 mg/kg/day) e.g. weight 50 kg • Depakine 1000 mg+0.9%NSS 100 cc iv drip in 30 min. then Depakine 100 mg/hr (10 cc/hr) warning: hepatotoxicity Midazolam • Vial: 1 mg/ml/vial, 5 mg/ml/vial, 15mg/ 3ml • 0.9% NaCl or 5% Dextrose/w • • • starting dose: 0.1-0.3 mg/kg bolus (rate < 4 mg/min) maintenance: 0.05-0.4 mg/kg/hr e.g. weight 50 kg • Midazolam 5 mg iv bolus then + Midazolam (1:1)iv drip 5 cc/hr (0.1 mg/kg/hr) Levetiracetam (Keppra) • • • • • Vial: 500 mg/5 ml 0.9% NaCl or 5% Dextrose/w 100 ml starting dose: 2,000-4,000 mg/kg in 15 min maintenance: 10-30 mg/12 hr e.g. weight 50 kg • Keppra 2000 mg iv in 15 min then 1000 mg iv q 12 hour Propofol • Vial: 10 mg/ml • 5% Dextrose/w • • • starting dose: 2 mg/kg bolus maintenance: 5-10 mg/kg/hr e.g. weight 50 kg • Propofol (2:1) iv 100 mg then 250 mg/hr Consult ดมยา is required Thiopentone • • • Vial: 1 g/vial starting dose: 100-250 mg in 20 min then 50 mg q 23 min until seizure stop maintenance: 3-5 mg/kg/hr Consult ดมยา is required Phenobarbital • Vial: 200 mg/4 ml in sterile water 10 ml • 5% Dextose • • starting dose: 20 mg/kg (rate < 100 mg/min) maintenance: 1-4 mg/kg/day Topiramate for SE • Clinical trial: 500 mg every 12 hours noso/orogastric feed for 2 days then 150 mg-750 mg every 12 hours • Effective dose: 300-1600 mg/day Monitoring • Tapering off AED • seizure stop > 24 hours • Burst suppression on EEG > 24 hours • Slow tapering off AED • if seizure recur, increase AED dose enough to control seizure Keep in Extern’s Mind Seizure 1. Seizure or not seizure: history, neuro exam 2. Identify cause, ABCD management 3.Start AEDs if seizure tend to be recurrent 4. if seizure is going to be status; need to be quick, and follow up the status epilepticus guideline therapy download slide at... openneurons