Neurology/Neurosurgery
13.1 Acute Serotonin Syndrome
Cause: MAO inhibitors (Hypericum perforatum, aka St. John’s Wort, is a weak MAO inhibitor), SSRIs (selective serotonin reuptake inhibitors), and non-selective 5-HT receptor agonist/antagonist, specifically meta-Chlorophenylpiperazine (m-CPP) (Psychiatry Res 1998;79:207) as leading causes, with increased likelihood when combined with meperidine (Acad Emerg Med 1999;6:156), dextromethorphan, venlafaxine (Neurol 1998;51:274), bromocriptine, levodopa, buspirone, lithium, cocaine, amphetamines, ecstacy (Ann EM 1998;32:377), tramadol (J R Soc Med 1999;92:474), or other serotonergic drugs (Med J Aust 1998;169:523). Equivocal data for combination with sumatriptan (Ann Pharmacother 1998;32:33).
Epidem: Not uncommon, with symptoms occurring within hours or days when increasing the dose of or adding a serotonergic drug; in approximately 14-16% of pts who are seen for SSRI overdose (J Toxicol Clin Toxicol 2004;42:277).
Pathophys: Increased activity at the post-synaptic serotonin receptors in the brain (Ped Emerg Care 1999;15:440).
Sx: Agitation, anxiety, shakiness, nausea.
Si: Mental status changes; tremors; seizures; autonomic instability with tachycardia or dysrhythmias, diaphoresis, hyperthermia,
HT, diarrhea, salivation, rigidity, dysarthria, ataxia, myoclonus, hyperreflexia, or localized neuro signs or deficits.
HT, diarrhea, salivation, rigidity, dysarthria, ataxia, myoclonus, hyperreflexia, or localized neuro signs or deficits.
Crs: Most recover within 24 hr; this may be a difficult diagnosis when confounded with drugs of abuse—have a high index of suspicion.
Cmplc: Rhabdomyolysis with subsequent myoglobinuria; fatalities rare but possible.
Diff Dx: NMS, drug abuse, or withdrawal (including serotonin withdrawal syndrome), malignant hyperthermia, meningitis, encephalitis, heat stroke, MAO inhibitor interactions, acute lethal catatonia, central anticholinergic crisis that responds to iv physostigmine, thyroid storm.
Lab: Clinical diagnosis when other etiologies excluded—CBC with diff; metabolic profile with Calcium and Magnesium; UA with myoglobin; CPK; aldolase; panculture if suspect infectious etiology; TSH if suspect endocrine source; consider LP.
Emergency Management:
Hold all meds, especially serotonergic agonists—listed above, also avoid codeine.
Iv fluids; sodium bicarbonate drip, if rhabdomyolysis (p484). Consider norepinephrine (p 51) if persistent hypotension.
Consider serotonin antagonists such as cyproheptadine 0.5 mg/kg per day divided into q 4-6 hr dosing at a maximum dose of 32 mg/d—usually 4-8 mg po each dose (Ped Emerg Care 1999;15:325; J Emerg Med 1998;16:615); may elect to try olanzapine 10 mg sl (J Toxicol Clin Toxicol 2004:725) or chlorpromazine 50-100 mg im (J Psychopharm 1999:100).
13.2 Acute Stroke Syndrome/Cerebral Vascular Accident (CVA)
Cause: Cerebrovascular accident classified according to 3 groups, and all types associated with HT and smoking (Jama 1999;281:1112)
Thrombotic CVA due to atherosclerosis (Cerebrovasc Dis 2000;10:102), which can be thought of to have the same risk factors for atherosclerosis as seen in those with coronary artery disease (for risks, Acute Coronary Syndrome see p7); hypotension—this may be transient and physiologic as seen in sleep; homocystinuria; crack cocaine abuse; migraine; high-dose estrogen birth control pills; arteritis caused by radiation, collagen vascular diseases (Lupus 1997;6:420; Arthritis Rheum 1998;41:1497), drug use, including ethanol in males (Alcohol 1999;19:119); infection leading to venous thrombosis or carotid occlusion; trauma to carotid or head that may cause spasm—associated with hx migraines; hematologic causes such as polycythemia, sickle cell disease (Blood 1998;91:288), TTP, DIC, dysproteinemias. Associated with homocystinuria, crack cocaine use, anabolic steroids (Neurology 1994;44:2405) and immediate post-partum period.
Embolic CVA due to proximal arterial atherosclerotic plaque; left-sided cardiac lesion as seen in SBE, left atrial myxoma, or clot (mitral stenosis or mitral valve billowing, prosthetic valve, sustained or intermittent atrial fibrillation (J Am Coll Cardiol 2000;35:183),
post-MI mural thrombus); paradoxical embolus from right heart, fat emboli, or venous system if patent intracardiac (foramen ovale—40% of pts < 55 yr of age with CVA have this open) right-to-left shunt. Associated with homocystinuria.
Subarachnoid CVAs due to aneurysm or AV malformation; associated with ethanol use in females (Alcohol 1999;19:119).
Thrombotic CVAs comprise 34% of all CVAs in large vessel type, and 19% of all CVAs in lacunar CVAs; 3% are pts < 40 yr of age.
Embolic CVAs comprise 31% of all CVAs, with 5 times increased incidence in atherosclerotic Afib, and 17 times increase in rheumatic Afib. 35% lifetime increased incidence in Afib, ¾ are embolic. For those with non-valvular Afib, use of warfarin with INR of 2 or greater leads to beneficial pt impact on frequency of ischemic CVA and the morbidity and mortality associated with ischemic CVA episodes (Nejm 2003;349:1019).
Subarachnoid hemorrhages comprise 7% of all CVAs and 1% of all adults have aneurysm. 2% of all with subarachnoid bleed and aneurysm have polycystic kidneys; associated with iv cocaine use; sometimes familial; sometimes with Ehler-Danlos syndrome, Marfan syndrome, and Type I neurofibromatosis.
Intraparenchymal bleeds comprise 9% of all CVAs.
Increased risk of hemorrhagic CVA (both types—subarachnoid and intraparenchymal) with use of phenylpropanolamine (Nejm 2000;343:1826).
Higher risk if previous CVA, especially if patent foramen ovale or atrial septal aneurysm (Nejm 2001;345:1740)
Increased risk of CVA with white matter lesions on MRI and increased more if coincident retinopathy (Jama 2002;288:67).
Black Americans with 2 times risk for intracerebral hemorrhage compared to whites (Neurol 1999;52:1617).
Neurologic syncope of any cause associated with approximately 3 times higher risk for CVA (Nejm 2002;347:878)
Possible Southeastern U.S. stroke belt (Am J Med Sci 1999;317:160).
Increased risk with either surgical or radiotherapy of pituitary adenoma (Int J Radiat Oncol Biol Phys 1999;45:693).
Livedo reticularis may be noted on physical exam in those with CVA who have antiphospholipid syndrome (Sneddon’s syndrome) (J Eur Acad Dermatol Venereol 1999;12:157).
Systemic respiratory infections associated with an increase in vascular events in the first 3 d of illness—this is not seen with immunizations (Nejm 2004;351:2611).
Pathophys: Thrombotic CVAs usually affect a watershed area in anterior circulation or vertebral basilar syndrome. Hypertension is a marker for stroke risk, but CVAs in these patients is a multifactorial issue, genetically determined (Cardiologia 1999;44:433). Hyperglycemia linked to delay in calcium recovery in ischemic stroke (J Cereb Blood Flow Metab 1992;12:469), and degree of hyperglycemia linked to size of infarct (Schweiz Arch Neurol Psychiatr 1993;144:233) and worse outcome (Stroke 1993;24:1129). Increase in superoxide dismutase (Life Sci 1994;54:711) in ischemic stroke, perhaps secondary to oxygen radicals causing problems.
Sx:
Embolic: Very abrupt onset; seizures occasionally.
Subarachnoid bleed: Severe headache of sudden onset which is frequently preceded by milder sentinel headache, nausea, vomiting, possible loss of consciousness, possible neck and back pain.
Intraparenchymal bleed:
Cerebellar with ataxia, headache, vomiting, nausea.
Cerebral with decreased level of consciousness, sudden onset headache, nausea, vomiting.
Si: Lateralized neurologic findings (see Table 13.1).
Carotid occlusion or significant stenosis may be elucidated with flow reversal through the supraorbital artery that one feels, and then occludes the facial artery as it wraps anterior to the inferior border of the mandible just anterior to the angle of the jaw—if lose pulse, then flow is reversed.
Thrombotic and Embolic with specific occlusion patterns:
Middle cerebral: Face and arm motor; expressive aphasia (Broca’s).
Carotid watershed: Parietal aphasias, weakness arm > face > leg.
Posterior cerebral: Homonymous hemianopsia, hemisensory loss, memory loss.
Lateral medullary plate syndrome—posterior inferior cerebellar artery: Ipsilateral pain and temperature loss on face, contralateral for rest of body, hoarseness, swallowing dysfunction, Horner’s, singultus (hiccups/hiccoughs), ipsilateral cerebellar signs.
Subarachnoid bleed: HT, stiff neck, Parinaud’s sign—upward gaze paralysis; subhyaloid retinal hemorrhage.
Intraparenchymal bleed:
Cerebellar: Awake, alert even with ophthalmoplegias; acute hypotonia; conjugate gaze paresis, skew deviation.
Cerebral: Motor and always sensory deficits; 13% have seizure within 48 hr.
Brain stem: Early loss of consciousness; brain stem signs including involvement of cranial nerves V, VII, VIII, IX, X, XI, XII; quadriplegia.
Crs: Non-hemorrhagic CVAs with 15% 30-d mortality; hemorrhagic CVAs with worse prognosis if large putaminal or thalamic bleed with HT, whereas subcortical, cerebellar, and pontine bleeds without correlation to blood pressure (Stroke 1997;28:1185). Separate risk factors for those treated with TPA for ischemic strokes, with worse in-hospital mortality corresponding with increasing age and altered mental status (Jama 2004;292:1831); also increased risk for worse outcome in those with elevated blood glucose, later time in administration of thrombolytic within the 3-hr window, and in those with cortical involvement (Jama 2004;292:1839).
Cmplc: Pulmonary emboli, aspiration pneumonia, UTIs, post-stroke depression, possible conversion of non-hemorrhagic CVA to hemorrhagic CVA; increased ICP.
Transient ischemic attack (TIA) (Ann EM 2004;43:592)— CVA symptoms that last less than 24 hours, with anterior circulation symptoms including amaurosis fugax; and posterior circulation symptoms including bilateral blindness, diplopia, and quadriplegia. Carotid bruit correlates poorly with symptomatic disease. Risk of subsequent CVA is 8% in first mon, 5% per yr for 3 yr, 3% per yr thereafter. 41% will die of MI. Risk factors of (1) patient age > 60 years; (2) diabetes mellitus; (3) episode lasting > 10 min; (4) weakness during the episode;
and (5) speech impairment during the episode convey a prognostic risk of CVA within 90 days by the following conversion (Jama 2000;284:2901):
0 risk factors with 0% risk
1 risk factor with 3% risk
2 risk factors with 7% risk
3 risk factors with 11% risk
4 risk factors with 15% risk
All 5 risk factors with 34% risk
Reversible ischemic neurologic deficit (RIND)—lasts longer than 24 hr, but less than 72 hr.
Migraine headache
Metabolic abnormality, such as hypoglycemia
Seizure, with Todd’s paralysis
Multiple sclerosis
Benign vertigo
Tumor
Carotid artery dissection or vertebral artery dissection (Nejm 2001;344:898)
Segmental mediolytic arteriopathy in young patients with CVA (Cardiovasc Surg 1994;2:350).
Table 13.1 NIHSS Scoring System | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Scoring System:
Median score of those treated in NINDS trial was 14, with low of 1 and high of 37—would suggest treating those with moderate deficits (score of 10-20), and not those with mild or severe deficits based on this trial.
Lab: CBC with diff; PT/PTT; metabolic profile including immediate glucoscan; EKG—cardiac markers if abnormal:
X-ray: Consider CXR; head CT without contrast—contrast given if lesion noted, except bleed because may elect to do angiography if bleed noted; although, may elect to perform CT angiography source images to offer prognostic data for regional blood flow and thus may determine risk of infarct growth (Stroke 2002;33:2426). CT has traditionally held the provence of better for acute bleeds, but MRI almost as good—MRI better for chronic bleeds or strokes that are undergoing transformation to hemorrhagic, but may miss a SAH (Jama 2004;292:1823). CT ability and readings moving toward delineating area and size of ischemia to correlate thrombotic vs embolic—still being developed (Stroke 1992;23:1748) and perhaps no significance of early ischemic changes in re: TPA use (Jama 2001;1:2830). MRI will determine ischemic CVAs within hours whereas CT will show in days. MRI or MRA for AVM evaluation.
US: Consider emergent carotid studies. Echocardiogram, if embolic source entertained. Leg studies, if paradoxical embolus suspected.
LP: LP if not anticoagulated and high suspicion for subarachnoid bleed, CT will miss up to 3-10% of these (Acad Emerg Med 1996;3:16; Ann EM 1998;32:297).
Emergency Management:
Airway; O2, only if hypoxia—is widely overused (Arch IM 2002;162:49).
Control/resuscitate blood pressure (Stroke 1998;29:1504); this is controversial and a “double-edged sword”—if hypertensive, get systolic BP around 180 mm Hg, since the hypertensive response is to maintain flow to the brain, which may be experiencing local edema, but even relative hypotension may decrease cerebral perfusion; if hypotensive, get systolic BP > 110 mm Hg to maintain flow to brain.
Four baby ASA chew and swallow (Stroke 2000;31:1240); no benefit of warfarin over ASA (Nejm 2001;345:1444).
Unfractionated heparin iv with weight-based protocol or low molecular weight heparin (LMWH) sc, no help for CVA in progress, but perhaps help in 6-mon survival—when to anticoagulate is the difficult decision— (Cochrane Database Syst Rv 2000;2) vs (Cochrane Database Syst Rv 2000;2). With Afib, controversy of ASA vs LMWH (Lancet 2000;355:1205).
Limit blood draws/procedures if possible if considering thrombolytics (Nejm 1995;333:1581). Complete NIHSS stroke scale as outlined under “Scoring System” in this chapter (Stroke 1999;30:2347).
The decision to perform thrombolysis should be made within 3 hr of symptom onset, BP < 185/110 with minimal pharmacologic help, no mild or dense deficits, and moderate deficits should not be improving. Should have no recent major surgery or dental work within 2 wk, no recent trauma, no gi bleed, and no history of cancer. Relative contraindications are those associated with embolic phenomenon, such as Afib, carotid stenosis, prosthetic valve, DVT with suspected patent foramen ovale, etc. Use TPA, not other agents—TPA 0.9 mg/kg give as a 10% bolus, and 90% over next 60 min, approximately 6% chance of bleed into CVA (Stroke 1997;28:2109).
If suspect increased ICP because of large CVA, supine was the best position for cerebral blood flow knowing that this does increase the ICP (Stroke 2002;33:497).
Equivocal data of Glucose-Insulin-Potassium (GIK) for those with mild to moderate hyperglycemia (Stroke 1999;30:793).
Permissive hypothermia is currently investigational (Stroke 1998;29:2461; Neurol 1997;48:762; Lancet 1996;347:422; J Neurosurg 2000;92:91)
and has numerous side effects (Int J Dev Neurosci 2003;21:353). See Head Trauma (p269).
Transcranial Doppler US augmentation with TPA use for those with ischemic strokes is investigational (Nejm 2004;351:2170).
Neither treating hyperhomocysteinemia with folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12) (Jama 2004;291:565) nor screening for antiphopholipid syndromes for prognostic information (including response to ASA or warfarin) (Jama 2004;291:576) is warranted at this time.
Magnesium does not change morbidity/mortality (Lancet 2004;363:439)—positive EMS FAST-MAG study with many limitations (Stroke 2004;35:e106).
Consult primary physician/neurologist.
Hemorrhagic CVAs:
Consult neurosurgery.
Control of systemic HT does not influence cerebral flow unless pt made hypotensive (Crit Care Med 1999;27:965), but better BP control with better morbidity and mortality outcomes (Stroke 1995;26:21). Consider use of nitroprusside, clonidine, labetalol, or ACE inhibitors.
Consider recombinant activated factor VII (rFVIIa) at 40 µg/kg, 80 µg/kg or 160 µg/kg dose—given within 4 hr of onset of intracerebral bleed, may reduce morbidity/mortality from 69% to approximately 50% in the first 24 hr and at 90 d reduce the mortality from 29% to 18%—this is at the expense of increased (from 2% to 7%) rate of serious thromboembolic disease (Nejm 2005;352:777).
Consider nimodipine 60 mg po q 4 hr for 21 d—prevents arterial spasm.
Hypertonic saline as effective as mannitol, and neither influences cerebral blood flow (Neurosurgery 1999;44:1055, 1063).
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