• Intracranial hemorrhage (ICH) can expand for the first 24 hours after onset.
• Peak ICH expansion occurs at 6 hours.
• REMEMBER:  The heads of patients with ICH should be elevated (~30 degrees) for at least 24 hours after the onset of bleeding to decrease the extent of expansion.  This is a simple, but too often neglected, clinical measure that potentially offers great benefit to the patient.

• A recent retrospecitve study of over 830 patients with suspected or confirmed benzodiazepine overdose from the Florida State Poison Center Database showed that only 0.7% experienced subsequent seizure or seizure-like acitivity (i.e. dystonia, muscle rigidity) after flumazenil administration.
• This study was conducted by emergency physicians from the University of Florida at Jacksonville where flumazenil is apparently often used as an antidote for benzodiazepine overdoses.
  

Show References

• Myasthenia Graves (MG) is a chronic, autoimmune disorder which causes voluntary (skeletal) muscle weakness.
• In MG, antibodies block, destroy, or alter acetylcholine receptors at the neuromuscular junction (NMJ), which impedes nerve conduction to the muscle.
• The hallmark of MG is weakness, classically of the muscles controlling bulbar function, mastication, neck movement, and facial expression, that worsens with activity and improves with rest.
• A true MG crisis ensues once respiratory muscles weaken to the point of requiring assisted ventilation. Such a medical emergency can be triggered by fever, infection, or an adverse reaction to medication.
• Edrophonium chloride (or Tensilon) can be administered intravenously to confirm the diagnosis of an MG attack. This drug increases levels of acetylcholine at the NMJ and temporarily relieves the symptoms of an MG.
• Assisted ventilation, plasmpharesis, and high dose IV immune globulin can all be used to treat an acute MG crisis.
• MG can chronically be controlled with anticholinesterase agents such as neostigmine and pyridostigmine, as well as immunosuppressives such as prednisone, cyclosporine, and azathioprine. Thymectomy is also a surgical treatment option.

• Animal models have shown that neuroprotectants, including free radical trapping agents, decrease injury after ischemic stroke.

• NXY-059 is a promising neuroprotective agent that was studied in the SAINT I and II trials.

• SAINT I showed that NXY-059 used within 6 hours of ischemic stroke resulted in significant improvement in the primary outcome measure of reduced disability at 90 days.

• SAINT II was done to confirm the results of SAINT I with a larger study population, but unfortunately did not show any significant difference in mortality between NXY-059 and placebo.  There was also no difference in adverse reactions, however.

• More research is needed to determine the best neuroprotective agent to be used acutely for ischemic stroke.

• The future of emergency treatment of ischemic stroke will likely include such agents, to be administered by emergency physicians.

• The risk of symptomatic intracerebral hemorrhage after use of IV tPA for acute stroke is 6% (within 36 hours of administration).

The NINDS tPA Stroke Study Group.  "Intracerebral Hemorrhage after Administration of Intravenous tPA for Ischemic Stroke."  Stroke.  1997; 28:  2109-18.

• The Dix-Hallpike Maneuver is performed to help diagnose/rule out benign positional vertigo, a condition attributed to floating (canalithiasis) or fixed (cupulolithiasis) otoconial debris within the posterior semicircular canal of the ear.
• To perform, turn the patient's head 45 degrees to one side and then rapidly but carefully recline them backwards to a supine position, preferably with the head hanging partially off the bed (i.e. at a position about 10-20 degrees inferior to that of the rest of the body).  Next, perform the maneuver by turning the patient's head 45 degrees to the other side.
• If nystagmus is induced, the test is positive.  Note the following five characteristics of the nystagmus:  (1)  latency, (2)  direction, (3)  fatigue (i.e. extinguishes with repetitive maneuvers), (4)  habituation (i.e. duration), and (5)  reversal upon sitting upright.
• Note that the Dix-Hallpike Maneuver described here is the diagnostic version, not the one performed therapeutically, the latter of which is also helpful. 

• Nystagmus which results from gaze (i.e. extraocular motion) in a particular direction, is detected by asking the patient to look at a target object 20 to 30 degrees to the right or left of their midline (i.e. when looking straight ahead) for 20 seconds.
• If gaze nystagmus is present, the eye will beat towards the intended direction of gaze.
• The ability to maintain eccentric gaze is a function of the brainstem and midline cerebellum, particularly the vestibulocerebellum. 
• Gaze nystagmus is attributable to a central process, typically due to drugs (i.e. sedatives, anti-epileptics), alcohol, CNS tumors, or cerebellar degenerative syndromes.

Be sure to perform a thorough head and neck examination in the dizzy patient, as the etiologic source is often due to ear, nose, and throat pathology, such as structural abnormalities, some of which may even signal a more widespread process

Such common physical examination findings may include the following:

• cerumen impaction
• otitis media with effusion
• chronic otitis with otorrhea
• chronic sinusitis with nasal airway obstruction
• orophayrngeal findings consistent with sleep apnea
• congenital abnormalities of the pinna, external auditory canal, and face may suggest labyrinthine involvement

• Romberg testing is an important component of the neurological examination which assesses proprioception (i.e. sense of joint position/balance) which is a function of the dorsal columns of the spinal cord.

• A Romberg test is performed by asking the patient to stand erect with their feet together and arms/hands at their side.  You first ask the patient to stand this way with their eyes open for 1 minute and then with their eyes closed for 1 minute.

• A positive Romberg test results if the patient exhibits clear swaying or even falling ONLY when their eyes are closed.  This suggests that the patient's ataxia is sensory in nature (i.e. dorsal columns), rather than cerebellar.

• Patients with cerebellar ataxia will typically loose their balance and sway even with their eyes open.

• Classic neurological abnormalities associated with a positive Romberg test include tabes dorsalis (neurosyphilis) and sensory peripheral neurpathy, among others.

• Be sure to cautiously standby while performing this test in order to protect the pateint should they fall.

• The brainstem is the lower extension of the brain that connects the brain to the spinal cord.

• Neurological functions located in the brainstem include those necessary for survival (breathing, digestion, heart rate, blood pressure) and for arousal (being awake and alert).

• Most of the cranial nerves come from the brainstem.  The brainstem is the pathway for all fiber tracts passing up and down from peripheral nerves and spinal cord to the highest parts of the brain.

• Remember that it is important to check a patient's peripheral vision when concerned about stroke, and when performing a neurological exam in general.
• Recognizing grossly abnormal peripheral vision often suggests the presence of various types of visual field cuts and helps localize a stroke lesion.
• When performing a general, very gross examination for peripheral vision abnormalities:

1. It is sometimes helpful to ask the patient to cover the eye that you are NOT checking for abnormality at the time.
2. Ask the patient to look straight ahead.
3. Ask the patient to tell you when they are able to see the long, narrow object (i.e. your finger, a pencil, etc.) that you slowly move forward into their view, starting from the point where the finger tips of the patient's laterally abducted arm would be (i.e. the object begins at a distance approximately equal to the patient's arm length).
4. Using this axis of reference, normal peripheral vision should occur at 45 degrees or less.

• Dihydroergotamine (DHE) is an older medication approved for the treatment of intractable migraine and cluster headaches.  Many of our Neurology colleagues still use this drug and its administration could start while the patient is 
  in the ED.
  
• Intranasal forms have become popular (i.e. Migranal).  Intramuscular and subcutaneous administration are also possible.
  
• The typical intravenous dose is 0.25 to 1 mg IV push over 2-3 minutes q 6 hours for 24 to 72 hours.
  
• DHE use is contraindicated in the following patients: 
  
  >    Patients concurrently on a protease inhibitor or macrolide antibiotic because of increased risk of life- threatening peripheral ischemia (**Black Box Warning**) 
  >    Patients with a hypersensitivity to ergot alkaloids 
  >    Patients with increased risk of developing vasospastic events 
  >    Patients who are concurrently taking vasoconstrictors 
  >    Patients who are pregnant or nursing 
  >    Patients with hemiplegic or basilar migraines
  
• Monitor for the following potential adverse reactions, which are typically related to vasoconstriction/spasm
  and warrant immediate abortion of the drug’s administration: 
  
  >    Myocardial infarction (check ECG's)
  >    Arrhythmia (place on cardiac monitor)
  >    Stroke (regular neuro. checks)
  >    Hypertension (check often) 
  >    Ischemia (monitor for clinical signs/symptoms) 
  
  
  
  
  -- Diener HC, Kaube H, Limmroth V. A practical guide to the management and prevention of migraine. Drugs. 1998;56(5):811-824.
  -- Fisher M, Gosy EJ, Heary B, Shaw D. Dihydroergotamine nasal spray for relief of refractory headache: A retrospective chart review. Curr Med Res Opin. 2007;23(4):751-755.
  -- http://www.aetna.com/cpb/medical/data/400_499/0462.html
  -- http://www.rxlist.com/cgi/generic/dihyergmes.htm
  
   

• Transient Neurological Attack (TNA) = attacks of sudden onset consisting of focal or non-focal neurological deficit, lasting no longer than 24 hours.
• Examples of TNA include TIA (when the deficit is focal), global amnesia, acute confusion, and syncope without a known cause.
• Patients who experience non-focal TNA are at higher risk for major vascular diseases and dementia than those without TNA.

Bos, et al.  "Incidence and Prognosis of Transient Neurologcial Attacks, " JAMA, pgs. 2877-85.  Dec. 26,  2007.

Johnston.  "Transient Neurological Attack:  A Useful Concept?," JAMA, pgs. 2912-13.  Dec. 26, 2007

• Neurologic manifestations are often the first, yet most insidious, signs of uremia (i.e. electrolyte abnormalities due to renal insufficiency).

• Signs and symptoms of uremic encephalopathy range from normal to comatose.  Some specific examples include dysarthria, pruritus, restless legs, mental status abnormality, myoclonic jerks, tetany, seizure, confusion, asterixis.

• Elevated PTH and calcium levels have been shown to particularly correlate with uremic encephalopathy.

• Elevated BUN levels tend to correlate with the degree of decreased level of consciousness.

• Ammonia levels are not typically elevated with uremic encephalopathy unless there is simultaneous liver disease.

• The treatment is dialysis.

http://www.emedicine.com/neuro/topic388.htm

• Of the 700,000 annual strokes in the U.S., 200,000 are recurrent.

• Risk of recurrent stroke is reported to be:

              -->  11.5% at 1 week

              -->  6-15% at 1 month

              -->  18.5% at 3 months

• Risk of stroke following TIA is reported to be:

              -->  8% at 1 week

              -->  11.5% at 1 month

              -->  17.3% at 3 months

• Due to the significant risk of stroke recurrence and new stroke after TIA, many of which lead to permanent disability, death, and health care costs, it is imperative that due diligence be given to proactively and thoroughly working stroke/TIA patients up in a timely fashion after the initial event. 

• Secondary prevention, such as smoking cessation, weight management, alcohol consumption moderation, tight glucose control, and anti-platelet therapy, should also be encouraged.

Thom, et al.  AHA Statistics Committee and StrokeStatistics Subcommittee.  Heart Disease and Stroke Statistics-2006 Update.  Circulation 2006; 113:e85-151.

Sacco, et al.  Predictors of Mortality and Recurrence after Hospitalized Cerebral Infarction in an Urban Community:  the Northern Manhattan Stroke Study.  Neurology 1994;44:626-34.

Coull, et al.  Population Based Study of Early Risk of Stroke after Transient Ischaemic Attack or Minor Stroke:  Implications for Public Education and Organisation of Services.  BMJ 2004;328:326.

• Consider cervical artery dissection as the source of stroke in patients younger than age 40.
• About 20% of such strokes are due to carotid artery or vertebral artery dissections.
• Of these, internal carotid artery dissections are the most common.
• These patients often present with a triad of neck and head pain, Horner's syndrome, and pulsatile tinnitus.
• MRI/MRA is the best non-invasive diagnostic modality for arterial dissection.  Angiography may needed for confirmation.

Selim M, Caplan LR. Carotid Artery Dissection.  Current Treatment Options Cardiovascular Medicine.  2004; 6:  249-253.

Stapf C, Elkind MS, Mohr JP.  Carotid Artery Dissection.  Annual Review Medicine.  2000; 51:  329-47.

Schievink W. Spontatneous Dissection of the Carotid and Vertebral arteries.  NEJM.  2001; 344:  898-906.

• Less than 10% of sarcoidosis cases affect only the nervous system.
• In such cases, granulomas form within nervous tissue and usually only occurs when there is significant systemic involvement.
• Most sarcoid exacerbations affecting the nervous system are not recurrent. 
• Manifestations of neurosarcoidosis include:
  • 1)  Mononeuropathy - Cranial nerve dysfunction most common     (Heerfordt  syndrome = uveitis, fever, parotid gland inflammation, and facial nerve palsy).
  • 2)  Peripheral neuropathy - Sensation and/or motor dyusfunction
  • 3)  Central Nervous System -  Hypothalamus/pituitary gland, cerebral cortex, cerebellum, spinal cord (rare)

• Note that the use of steroids within 8 hours of injury for SCI is not routinely practiced worldwide and was initially based on a controversial study, the National Acute Spinal Cord Injury Study (NASCIS I & II).

• The approved methylprednisolone dose is 30 mg/kg IV bolus over 15 min, followed by 5.4 mg/kg/h over 23 h; begin IV infusion 45 min after conclusion of bolus.
  

Bracken MB, Shepard MJ, Collins WF, et al: A randomized, controlled trial of
methylprednisolone or naloxone in the treatment of acute spinal-cord injury.
Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med
1990 May 17; 322(20): 1405-11. 

• IA lytics for stroke emerged to increase the 3-hour window for treatment.

• IA tPA may also be indicated for:

              --  candidates with severe neurological deficits (NIHSS score > 10)

              --  candidates with a recent history of major surgical procedures

              --  candidates with occlusion of major cervical or intracranial vessels

• Early IA lytic trials utilized urokinase and tPA, usually within a 6-hour window, though some reports extended the window to 12 hours for posterior circulation ischemic strokes.

• Studies have shown that THERE IS NO SIGNIFICANT DIFFERENCE IN RECANALIZATION RATE, SYMPTOMATIC HEMORRHAGE, AND NIHSS FOR IV PLUS IA LYSIS VERSUS IA LYSIS ALONE.

Zaidat OO, Saurez JL, Santillan C, et al.  "Response to intra-arterial and combined intravenous and intra-arterial thrombolytic therapy in patients with distal internal carotid artery occlusion."  Stroke 2002, 33:  1821-1826.

Bellolio MF, et al.  "Stroke Update 2007:  Better Early Stroke Treatment (BEST)," Emergency Medicine Practice, Augst 2007, Volume 9, Number 8.

• 325 mg of aspirin should be given within 48 hours of symptom onset in ischemic stroke; while its good form to give it when appropriate while the patient is still in the ED, per recent guidelines, it is not imperative.

• Aspirin should not be given to stroke patients who will receive tPA.

• Prior administration of aspirin is not a contraindication to giving tPA, however.

• If dysphagia and/or aspiration risk is suspected, give 300 mg of aspirin per rectum.

2007 AHA and ASA Guidelines for the Early Management of Adults with Ischemic Stroke and Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults.