Ep-PAINE-nym



Huntington’s Disease

 

Other Known AliasesHuntington’s chorea

 

DefinitionAutosomal dominant condition caused by expansion of the cytosine-adenine-guanine (CAG) trinucleotide repeats in the HD gene located on short arm of chromosome 4p16.3 that encodes the protein huntingtin.

Image result for huntington's disease

Clinical SignificanceThis condition affects 4-15 in 100,000 peoples of European descent and is extremely rare in non-European lineage.  The classic manifestations of the disease include chorea, psychiatric illness, and dementia.  These symptoms begin very slow and are often missed for a period of time, but always progress to severe deterioration of neuromuscular function.  It is uncurable and treatment is directed towards support and planning of care.  Average length of survival after symptoms onset is 10-20 years

Image result for huntington's disease

History – Named after George Huntington (1850-1916), an American physician who received his medical doctorate from Columbia University in 1871 at the age of 21.  He came from a long line of physicians dating back to 1797, when his grandfather opened the family practice in East Hampton.  He took meticulous notes on the disease that bears his name from going on house calls with his father early in his childhood, as well as reading and transcribing notes from his father and grandfather.  He only published two papers in his career, the first of which was on this disease.  He read this manuscript before the Meigs and Mason Academy of Medicine in Middleport, Ohio in 1872 (just 1 year after graduating medical school) and received such acclaim that it was published in the Medical and Surgical Reporter of Philadelphia just 2 months later.  This paper was published in the German literature later that year and his name was forever attached to this disease.  Even William Osler read and commented on this paper in 1908 saying ” In the history of medicine there are few instances in which a disease has been more accurately, more graphically, or more briefly described.”

 

https://upload.wikimedia.org/wikipedia/commons/c/c7/First_page_of_the_article_%22On_Chorea%22_by_G._Huntington_Wellcome_L0005209.jpg


References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. Huntington’s Disease.  https://ghr.nlm.nih.gov/condition/huntington-disease
  7. Huntington G.  On Chorea.  Medical and Surgical Reporter of Philadelphia.  1972;26(15):317-321 [article]

#41 – Bell’s Palsy



***LISTEN TO THE PODCAST HERE***

 



Anatomy and Physiology of Cranial Nerve VII

Cranial Nerve VII (the facial nerve) is a mixed nerve (having both sensory and motor function) with:

  • Somatic afferents from the external auditory canal
  • Afferent fibers from taste receptors from the anterior 2/3rds of the tongue
  • Parasympathetic fibers innervating lacrimal, submandibular, and sublingual salivary glands
  • Motor fibers innervating the facial muscles

There are six (6) segments of the nerve after it emerges from the pons of the brainstem:

  1. Intracranial (cisternal)
  2. Meatal (from brainstem to internal auditory canal)
  3. Labyrinthine (internal auditory canal to geniculate ganglion)
    1. Lacrimal gland, nasal/palate, pterygopalatine ganglion
  4. Tympanic (geniculate ganglion to pyramidal eminence)
    1. Stapedius nerve
  5. Mastoid (pyramidal eminence to stylomastoid foramen)
    1. Chorda tympani à tongue, salivary glands, lingual nerve
  6. Extratemporal (stylomastoid foramen to post parotid branches)
    1. 5 major facial branches
      1. Temporal
      2. Zygomatic
      3. Buccal
      4. Mandibular
      5. Cervical


Definition and Epidemiology

Bell’s Palsy is an acute peripheral nerve palsy of unknown etiology and makes up almost half of such cases.  It is estimated that the annual incidence is around 20 patient per 100,000 population.  There is no race, geographic, or gender correlation., though there is some old data on increased risk during 3rd trimester of pregnancy.


Pathogenesis

Had been hotly debated for many years as to the cause of this condition and is generally considered to be caused by Herpes Simplex virus due to associated serologic evidence in effected patients.  Newer data has been published, but is not entirely conclusive.  Most agree that is due to some viral pathogen with herpes being the most common, but also implicating CMV, EBV, adenovirus, and coxsackievirus. Specifically, the signs and symptoms are a result of viral mediated inflammatory demyelination of the nerve.


Signs and Symptoms

Most common presentation is acute (over several hours) unilateral facial paralysis with:

  • Motor
    • Inability to close the eye
    • Eyebrow sagging with inability to wrinkle the forehead
    • Obliteration of the nasolabial fold
    • Dropping of the affected corner of the mouth
  • Sensory
    • Hyperacusis
    • Loss of taste on the anterior 2/3rd of tongue

Symptoms are progressive and usually reach peak involvement within 3 weeks of onset.  Patients should begin to have return of function within 2-4 months.


Diagnostic Studies

Bell’s palsy is a clinical diagnosis and diagnostic studies are generally not indicated unless the presentation is atypical, still progressing at 3 weeks, or there is no return of function by 4 months.  History of facial twitching or spasms preceding the paralysis raises suspicion of compressive neuropathy from tumor or mass.

  • Electromyography (EMG)
    • The most simplest of the electrodiagnostic tests that can be used to show action potentials on active volition.  Some degree of potential infers that the nerve is still intact and therefor, can improve.
  • Nerve Conduction Studies (NCS)
    • Supramaximal stimulation near the parotid gland with measured evoked potentials over the orbicularis oculi, nasalis, and lower facial muscles  can measure the degree of axonal loss.  Studies have shown >75% is the critical cutoff for low likelihood of full recovery.  Ideally, this should be performed within 2 weeks of symptom onset for a more accurate prognosis.
  • Facial Nerve Stimulation
    • Should be considered with 2 weeks of symptoms onset if surgical decompression is considered due to potential for reversibility.
  • Needle EMG
    • Utilized after 3 weeks to assess the degree of axonal damage and evidence of subclinical reinnervation for recovery
  • Imaging
    • High-resolution, contrast-enhanced CT (for bony pathology) or gadolinium-enhanced MRI (for soft tissue structures) of the brain, temporal bone, and parotid gland.
  • Lyme serology should be entertained in patients from endemic regions.

Severity Grading

The House-Brackman scale is the most common grading scale that uses objective criteria to score the severity, mark progression, and track return of function.


Treatment

Mainstay of therapy for Bell’s palsy is corticosteroids (for the inflammation) and antivirals (for the viral pathogens).  Current recommendations are:

  • Prednisone 60-80mg daily for 7 days
  • Valacyclovir 1000mg TID for 7 days
  • Within 72 hours of symptoms onset

 

Eye care should include artificial tears and an eye patch for sleeping.


Prognosis

Favorable prognosis if any recovery is seen within 21 days of symptom onset with data showing 71% with complete resolution, 13% with slight residual sequelae, and 16% with residual weakness, synkinesis, or contracture.  94% of patients with incomplete involvement have full resolution, while only 60% of complete involvement returned to normal function.



References

  1. Monkhouse WS. The anatomy of the facial nerve. Ear, nose, & throat journal. 1990; 69(10):677-83, 686-7. [pubmed]
  2. May M, Klein SR. Differential diagnosis of facial nerve palsy. Otolaryngologic clinics of North America. 1991; 24(3):613-45. [pubmed]
  3. Hilsinger RL, Adour KK, Doty HE. Idiopathic facial paralysis, pregnancy, and the menstrual cycle. The Annals of otology, rhinology, and laryngology. ; 84(4 Pt 1):433-42. [pubmed]
  4. Peitersen E. Bell’s palsy: the spontaneous course of 2,500 peripheral facial nerve palsies of different etiologies. Acta oto-laryngologica. Supplementum. 2002; [pubmed]
  5. Schirm J, Mulkens PS. Bell’s palsy and herpes simplex virus. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 1997; 105(11):815-23. [pubmed]
  6. Kennedy PG. Herpes simplex virus type 1 and Bell’s palsy-a current assessment of the controversy. Journal of neurovirology. 2010; 16(1):1-5. [pubmed]
  7. Morgan M, Nathwani D. Facial palsy and infection: the unfolding story. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1992; 14(1):263-71. [pubmed]
  8. Liston SL, Kleid MS. Histopathology of Bell’s palsy. The Laryngoscope. 1989; 99(1):23-6. [pubmed]
  9. Valls-Solé J. Electrodiagnostic studies of the facial nerve in peripheral facial palsy and hemifacial spasm. Muscle & nerve. 2007; 36(1):14-20. [pubmed]
  10. May M, Klein SR, Taylor FH. Indications for surgery for Bell’s palsy. The American journal of otology. 1984; 5(6):503-12. [pubmed]
  11. Gilden DH. Clinical practice. Bell’s Palsy. The New England journal of medicine. 2004; 351(13):1323-31. [pubmed]
  12. House JW, Brackmann DE. Facial nerve grading system. Otolaryngology–head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 1985; 93(2):146-7. [pubmed]
  13. Gronseth GS, Paduga R, . Evidence-based guideline update: steroids and antivirals for Bell palsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2012; 79(22):2209-13. [pubmed]
  14. Baugh RF, Basura GJ, Ishii LE, et al. Clinical practice guideline: Bell’s palsy. Otolaryngology–head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2013; 149(3 Suppl):S1-27. [pubmed]
  15. Schwartz SR, Jones SL, Getchius TS, Gronseth GS. Reconciling the clinical practice guidelines on Bell’s palsy from the AAO-HNSF and the AAN. Otolaryngology–head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2014; 150(5):709-11. [pubmed]
  16. de Almeida JR, Guyatt GH, Sud S, et al. Management of Bell palsy: clinical practice guideline. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2014; 186(12):917-22. [pubmed]
  17. Peitersen E. The natural history of Bell’s palsy. The American journal of otology. 1982; 4(2):107-11. [pubmed]

PAINE #PANCE Pearl – Neurology



Questions

 

  1. What is the popular scoring system for determining a patient’s need for anticoagulation to prevent stroke in atrial fibrillation?
  2. If you do start anticoagulation, what are some scoring systems to determine a patient’s risk for bleeding while on anticoagulation?

 

Image result for atrial fibrillation stroke

Image result for atrial fibrillation stroke

Answer to Neuro Question

19yo male is brought into the emergency department by EMS after getting into an altercation and getting knocked unconscious.  He unsure of how long he was out, but he came to once EMS arrived.  He denies any nausea, vomiting, or vision changes.  He is drowsy/lethargic with his eyes closed, but is arousable to voice.  He can carry on a conversation, but he needs frequent redirection and he does not know where he is.  While talking with him, the nurse starts an IV and he tries to swat her away with his opposite hand.

 

What is the classic score we use and what is his score?

The Glasgow Coma Scale (GCS) was first devised in 1974 and has been the predominant neurologic scoring system since.  It takes into account 3 main variables and each variable has a point score attached to it.  The maximum score is 15 and the minimum score is 3 (3T if intubated).

  • Eye opening
    1. 4 points – Spontaneous
    2. 3 points – To speech
    3. 2 points – To pain
    4. 1 point – None
  • Verbal Response
    1. 5 points – Oriented
    2. 4 points – Confused conversation
      1. Not sure where they are, or what their name is
    3. 3 points – Inappropriate words
      1. They speak real words, but they are not in context
    4. 2 points – Incomprehensible sounds
    5. 1 point – None
  • Motor Response
    1. 6 points – Obeys commands
    2. 5 points – Localizes to pain
      1. Crosses midline/clavicles to remove painful stimuli
    3. 4 points – Withdrawal to pain
      1. Moves extremity/head away from painful stimuli
    4. 3 points – Decorticate (flexor) posturing
    5. 2 points – Decerebrate (extensor) posturing
    6. 1 point – None

Our patient’s score is 3E + 4V + 5M = 12

How good is it?

The GCS was never designed to be used for acute injury.  It was created to monitor changes in neurologic status of patients in a neurosurgical unit and was not designed to have the 3 individual variables combined into one score.  Here are the important limitations of the GCS.

  • The GCS is NOT reliable
    1. It is made up of subjective elements that are open to the interpretation of each provider assessing the patient and has been repeated shown to have poor inter-rater reliability.
      1. One study showed only a 38% accuracy between raters and were 2 or more points off 33% of the time.
  • Providers CAN’T remember the scale
    1. It has too many elements and is regarded as too complicated to be easily, and rapidly applied to patients
    2. In 2003, it was discovered that 25% of British hospitals were using the original 12-point scale instead of the current 13-point scale without anyone noticing.
  • The GCS is only GROSSLY predictive
    1. It is not designed to predict outcomes of patients with acute neurologic injury.
  • The GCS is NOT equal to the sum of its parts
    1. The original creators vehemently opposed the summed total score because it assumes that each variable is equal to the others in terms of importance
      1. Example
        1. GCS of 4 with 1E + 1V + 2M = 48% mortality
        2. GCS of 4 with 1E + 2V + 1M = 27% mortality
        3. GCS of 4 with 2E + 1V + 1M = 19% mortality

Are there any other scoring systems out there?

The motor subscale of the GCS has been proven to be most predictive of outcomes in patients with neurologic trauma and injury.  This has led to debate about whether to do away with the other 2 subscales and use just the motor score (since it has been shown to close to linear in regards to survival).

Healy C. J Trauma. 2003.

Healy C. J Trauma. 2003.

But this is still 6 points and some argue can be further simplified.  One study broke down the 6-point motor subscale and found that only 3 of those were statistically important.  Those are:

  • Obeys commands
  • Localizes to pain
  • Withdrawal to pain or less

This new Simplified Motor Scale can be remembered by the acronym TROLL (Test Responsiveness: Obeys, Localizes, Less).  2 other simplified scores have also been created to help quickly determine neurologic status.  These are:

  1. AVPU
    1. Alert
    2. Responds to verbal stimuli
    3. Responds to painful stimuli
    4. Unresponsive
  2. ACDU
    1. Alert
    2. Confused
    3. Drowsy
    4. Unresponsive

There is another, although more complicated, score called the FOUR score, which has 4 components and stands for Full Outline of UnResponsiveness.  Unfortunately, it is even more complicated than the GCS (in the original study it was performed by neurologic specialists, not general practitioners) and it performed just as poorly in external validation studies as the GCS.

Wijdicks EF. Ann Neurol. 2005.

Wijdicks EF. Ann Neurol. 2005.

 

Bottom Line

GCS is essentially worthless clinically even when it is calculated correctly.  Simplified scores give just as much information, are easier to use, and are just as predictive. But….you will always be asked “what is the patient’s GCS”, in spite of the growing evidence against it.


References

  1. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81-4.
  2. Green SM. Cheerio, laddie! Bidding farewell to the Glasgow Coma Scale. Ann Emerg Med. 2011;58(5):427-30.
  3. Teasdale G, Jennett B, Murray L, Murray G. Glasgow coma scale: to sum or not to sum. Lancet. 1983;2(8351):678.
  4. Zuercher M, Ummenhofer W, Baltussen A, Walder B. The use of Glasgow Coma Scale in injury assessment: a critical review. Brain Inj. 2009;23(5):371-84.
  5. Healey C, Osler TM, Rogers FB, et al. Improving the Glasgow Coma Scale score: motor score alone is a better predictor. J Trauma. 2003;54(4):671-8.
  6. Gill M, Windemuth R, Steele R, Green SM. A comparison of the Glasgow Coma Scale score to simplified alternative scores for the prediction of traumatic brain injury outcomes. Ann Emerg Med. 2005;45(1):37-42.
  7. Mcnarry AF, Goldhill DR. Simple bedside assessment of level of consciousness: comparison of two simple assessment scales with the Glasgow Coma scale. Anaesthesia. 2004;59(1):34-7.
  8. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, Mcclelland RL. Validation of a new coma scale: The FOUR score. Ann Neurol. 2005;58(4):585-93.
  9. Fischer M, Rüegg S, Czaplinski A, et al. Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study. Crit Care. 2010;14(2):R64.

Neuro Question

19yo male is brought into the emergency department by EMS after getting into an altercation and getting knocked unconscious.  He unsure of how long he was out, but he came to once EMS arrived.  He denies any nausea, vomiting, or vision changes.  He is drowsy/lethargic with his eyes closed, but is arousable to voice.  He can carry on a conversation, but he needs frequent redirection and he does not know where he is.  While talking with him, the nurse starts an IV and he tries to swat her away with his opposite hand.

 

What is the classic score we use and what is his score?

How good is it?

Are there any other scoring systems out there?

 

#13 – Transient Ischemic Attacks



***LISTEN TO THE PODCAST HERE***



Epidemiology

  • Estimated to be 50-80 per 100,000, or 240,000 per year

Definition

  • Original
    • Neurologic deficits lasting for < 24 hours
      • Can still have permanent tissue injury
Picture1

Ay H. Ann Neuro. 2005;57(5):679-86

  • Consensus from American Heart Association and American Stroke Association
    • Transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia WITHOUT acute infarction
    • Benefits
      • Tissue damage can be seen on imaging (more objective)
        • Thus, encourages early neurodiagnostic tests

Pathophysiology

  • 3 main causes
    • Intrinsic, vessel abnormality
      • Atherosclerosis, lipohyalinosis, dissection, malformation, inflammation
    • Embolic from distal source
    • Inadequate cerebral blood flow
      • Decreased perfusion pressure or increased blood viscosity

Classifications

  • 3 main types
    • Large artery, low-flow
      • Brief (minutes to a few hours), recurrent, and sterotyped due to specific vessel it effects
        • Often due to stenotic internal carotid, middle cerebral, or vertebral-basilar junction
    • Embolic
      • Discrete, infrequent, prolonged (several hours) episode
    • Lacunar, small vessel
      • Stenosis of intracerebral penetrating vessels from middle cerebral, basilar, or vertebral arteries
      • HTN and DMII main culprits

Signs and Symptoms

  • All depends on the vessels being effected
  • 2 Global Regions
    • Anterior Circulation
      • Internal carotid arteries
        • Anterior cerebral artery (contralateral LE>UE weakness)
        • Middle cerebral artery (contralateral face/UE>LE)
    • Posterior Circulation
      • Vertebral arteries
        • Basilar artery (crossed deficits, ataxis, visual disturbances)
          • Cerebellar arteries (dizziness, N/V, visual disturbances)
        • Posterior cerebral artery (visual disturbances, contralateral hemiplegia)
UpToDate

UpToDate

  • Disabling symptoms that suggest stroke
    • Complete hemianopsia
    • Severe aphasia
    • Visual/sensory extinction
    • Any weakness limiting sustained effort against gravity
    • NIHSS ≥ 5
    • Inability to walk
    • Modified Rankin Score ≥ 1
    • Any deficit considered potentially disabling to patient or family

Stroke Mimics

  • Seizures
  • Migraine auras
  • Syncope
  • Peripheral vestibulopathies
  • Pressure/position related peripheral neuropathies
  • Metabolic derangements
    • Hypo/hyperglycemia, renal, liver, pulmonary

Initial Evaluation

  • Laboratory studies
    • BMP, CBC, NH4, LFT, PT/PTT/INR
  • EKG
  • Brain imaging
    • Preferred – Brain MRI with diffusion-weighted imaging
    • Suboptimal – Non-contrast head CT
    • CT perfusion scans becoming an option

ABCD2 Score

  • Used to estimate the risk of ischemic stroke in the first 48 hours after TIA
  • 2-day stroke risk
    • 0-3 – 1%
    • 4-5 – 4%
    • ≥ 6 – 8%
UpToDate

UpToDate

Admit or Outpatient???

  • Recommend admission for:
    • ABCD2 ≥ 3
    • ABCD2 ≤ 2 and unsure if work-up can be completed in 48 hours as outpatient
    • ABCD2 ≤ 2 and other evidence that this is caused by focal ischemia

Definitive Work-Up

  • Neuroimaging within 24 hours of symptom onset
    • Brain MRI with diffusion-weight imaging
  • Neurovascular evaluation
    • Preferred – 4-vessel catheter angiography
    • Options – CTA, MRA, CDUS, TCD
  • Cardiac Evaluation
    • Reasonable to perform if neurovascular work-up is negative
    • TTE if:
      • Patient ≥ 45 years
      • High suspicion of left ventricular thrombus
      • TEE is contraindicated
    • TEE preferred if:
      • Patient < 45 years without history of CVD
      • Patients with atrial fibrillation
      • Patients with mechanical valve
      • Patients with suspected aortic pathology
      • High pretest probability of cardiac embolic source
UpToDate

UpToDate

Secondary Stroke Prevention

  • Medical Management
    • Hypertension
    • Antiplatelet (ASA and clopidogrel)
    • Statins (intensive therapy)
    • Lifestyle modifications
  • Large artery disease
    • Carotid
      • Revascularization
        • Endarterectomy
        • Stenting
    • Extracranial vertebral
      • Angioplasty and stenting
    • Intracranial cerebral vessels
      • Intensive medical management
  • Small artery disease
    • Intensive medical management
  • Cardiogenic embolism
    • Atrial fibrillation
      • Lifelong anticoagulation
    • Myocardial infarction and left ventricular thrombus
      • Anticoagulation for at least 3 months
    • Mitral valve disease (prolapse, calcification)
      • Antiplatelet

Recent Study (video explanation)

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke (TIA Registry Investigators)

  • 4789 patients, 61 sites in 21 countries
  • Patients
    • ≥ 18 years and had a TIA or minor stroke in the last 7 days
      • Mean age – 66years
      • 70% had HTN and DM
      • 87% sought attention within 24 hours
    • Modified Rankin scale ≤ 1
  • Timeline
    • 2-day, 7-day, 30-day, 90-day, and 1-year (following for 5-years)
    • Followed median 27.2 months
  • Outcomes
    • Primary (composite)
      • Death from CV causes
      • Nonfatal stroke
      • Nonfatal ACS
    • Secondary
      • Individual components of primary
      • TIA recurrence
      • Death from any cause
      • Bleeding
  • Results
    • Primary
      • 2% incidence of major fatal or nonfatal CV events
      • Estimate of stroke risk was 5.1%
        • Highest in 1st 90-days
    • Patients with ABCD2 score ≤ 3 still had a 20% early recurrent stroke
    • Higher ABCD2 score, large artery atherosclerosis, and multiple infarctions on imaging are strong independent predictors of recurrent events
    • Risk of recurrent stroke was less than half of expected historical cohorts
      • Attributed to faster and more aggressive secondary prevention
Amarenco P. NEJM. 2016;374(16):1533-42

Amarenco P. NEJM. 2016;374(16):1533-42

Cottage Physician

Cottage Physician - 1893

Cottage Physician – 1893


References

  1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28-e292.
  2. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009;40(6):2276-93.
  3. Furie KL, Ay H. Initial evaluation and management of transient ischemic attacks and minor ischemic stroke.  In: UpToDate.  Waltham, MA.
  4. Ay H, Koroshetz WJ, Benner T, et al. Transient ischemic attack with infarction: a unique syndrome?. Ann Neurol. 2005;57(5):679-86.
  5. Quinn TJ, Dawson J, Walters MR, Lees KR. Reliability of the modified Rankin Scale: a systematic review. Stroke. 2009;40(10):3393-5.
  6. Levine SR, Khatri P, Broderick JP, et al. Review, historical context, and clarifications of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke. 2013;44(9):2500-5.
  7. Brott T, Adams HP, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864-70.
  8. Johnston SC, Rothwell PM, Nguyen-huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283-92.
  9. Johnston SC, Nguyen-huynh MN, Schwarz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006;60(3):301-13.
  10. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-236.
  11. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e576S-600S.
  12. Amarenco P, Lavallée PC, Labreuche J, et al. One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke. N Engl J Med. 2016;374(16):1533-42.