UMEM Educational Pearls - By Aisha Liferidge

** Fosphenytoin (Cerebyx) is a pro-drug of Phenytoin (Dilantin).

** Differences between fosphenytoin and phenytoin are primarily due to fosphenytoin being more water soluble.
 

Fosphenytoin versus Phenytoin:
•     Fosphenytoin  >  less risk for cardiac-related adverse effects (propylene glycol not required for solubilization)
•     Fosphenytoin >  lower risk of local skin and subcutaneous irritation during infusion 
•     Fosphenytoin > can be given intramuscularly
•     Fosphenytoin >  can be infused at a faster rate (20 mg/kg phenytoin equivalents (PE’s) load at a rate of 100 to 150   mg of PE’s/minute) due to its safer side/adverse effects profile.

• Phenytoin (Dilantin) should not be infused at a rate greater than 50 mg/minute, to a total of 20 mg/kg.

• Caution is encouraged while infusing due to the risk of inducing hypotension and cardiac arrhythmias, making cardiac monitoring during infusion mandatory.

• These adverse effects are partly related to the propylene glycol used to solubilize phenytoin.

• Additionally, the risk of local pain and injury, such as venous thrombosis and the purple glove syndrome, increases with rapid infusion rates.

• Exact definitions of status epilepticus vary. 

• Generally speaking, status epilepticus is defined as a single unremitting seizure that lasts longer than 5 to 10 minutes OR greater than one generalized clinical seizure with no interictal return to clinical baseline.

• While treatment with phenytoin and diazepam is often used for status, studies have shown that lorazepam use alone is more effective. 

• Chiari Malformations are congenital abnormalities wherein the cerebellum downwardly displaces into the spinal canal.
• This results in an increase in pressure and subsequent obstruction of CSF flow.
• Common symptoms associated with Chiari Malformations include:

              -  vertigo

              -  headache

              -  muscle weakness

              -  coordination abnormalities

              -  gait abnormalities

              -  visual abnormalities

• It is crucial to be familiar with and use  the NIH Stroke Scale (NIHSS) to objectively describe the extent of a stroke, in a language universal to all physicians, particularly our neurology colleagues.
• This validated tool consists of 15 items and the scale ranges from 0-42.  The higher the number, the worst the stroke.
• The NIHSS does not have to be memorized, but rather accessible for reference when needed.
• Studies have validated an abbreviated, 5-item NIHSS that has the same predictive performance as the 15-item scale.  This scale ranges from 0-16.
• While this abbreviated scale was created primarily for use in the prehospital setting, it can certainly be performed in the ED prior to rushing the patient off the CT for a head scan, in order to provide your neurologist with some objective information in a timely fashion.
• The NIHSS-5 assesses the following functions, in decreasing order of importance in terms of prognosis:

              --  motor function (right leg)

              --  motor function (left leg)

              --  gaze

              --  visual fields

              --  language

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• There is mounting evidence in favor of effectively treating migraine headaches with antiemetic dopamine antagonists such as metoclopramide (Reglan) and prochlorperazine (Compazine) as primary parenteral management.

• Diphenhydramine (Benadryl) can be administered simultaneously with such agents to prevent akathisia and dystonic reactions.

• Apart from the prophylactic effects of diphenhydramine, it may also play a synergistic role is actually treating the symptoms.

• A recent study (Friedman, et al) showed no significant difference in the efficacy or adverse events of treating migraine with 20 mg of metoclopramide plus 25 mg of diphenhydramine versus 10 mg of prochlorperazine plus 25 mg of diphenhydramine, although there was an insignificant trend in favor of prochlorperazine lowering the pain score to a greater degree.

• Note that the 20 mg dose of metoclopramide is higher than what is traditionally used in most emergency departments, but escalating the dose of up to 20 mg over a few hours may be more efficacious (the slower the administration and the simultaneous use of diphenhydramine decreases risk of dystonic reactions).

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-- Tourette Syndrome (TS) is an inherited neurological disorder characterized by repetitive involuntary movements and uncontrollable vocal sounds called tics.
-- Underlying defect is unknown; however, research suggests that it could be caused by abnormalities in serotonin and dopamine activity within the basal ganglia.
-- Associated behavioral problems include OCD, ADHD, anxiety, and depression.
 

Diagnostic criteria:

• Encephalomalacia, also known as cerebromalacia, is a softening of brain tissue that results from ischemia or inflammation, most typically due to vascular insufficiency or degenerative changes.

• On Brain CT, it appears as a darkened area and can be confused for cerebral edema due to acute ischemia (i.e stroke).

• Unlike edema, encephalomalacia on CT is often accompanied by:

                    ---  well defined, circular vacuoles

                    ---  presence of good gray-white matter differentiation in surrounding areas

                    ---  a lack of significant effacement or lost of sulcus definition

                    ---  a history of prior stroke or head injury

• Acceleration, deceleration, and rotational forces cause diffuse axonal injury (DAI).
• It is characterized by widespread shearing and retraction of axons during traumatic brain injury (TBI).
• DAI often results in coma and is associated with poor prognosis.
• In addition to cortical white matter injury, it often also involves the corpus callosum, basal ganglia, brainstem, and cerebellum.
   

tPA should NOT be used to treat ischemic stroke in the following instances:

• Platelet count < 100,000
• INR > 1.7 or PT > 15
• Heparin administration within past 48 hours with subsequent PTT above upper limits of normal

• Arteriovenous malformation (AVM) is a congenital defect of the circulatory system, comprised of a nest of blood vessels.
• AVM is typically detected incidentally during CT or MRI studies.
  
• Symptoms vary depending on the location of the AVM and the amount of hemorrhage, but can be as general as a seizure or headache.
• The following clinical symptoms commonly occur with AVM bleeds:
  

• Asterixis is a tremor of the wrist that occurs when the wrist is extended (dorsiflexed).
• It is also often referred to as a "flapping tremor" or "liver flap."
• Asterixis results from arrhythmic, interrruptions of voluntary muscle contraction resulting in brief lapses in posture.
• It is most often associated with hepatic encephalopathy that results from abnormal metabolism of ammonia to urea, causing brain cell damage.  The subsequent elevated levels of ammonia are due to liver failure.
• In addition to hepatic enephalopathy, asterixis can also be associated with the following conditions:

               -- azotemia

               -- cardon dioxide toxicity

              -- metabolic encephalopathies

              -- Wilson's Disease

• Anisocoria is when pupillary size is assymetric.

• Anisocoria suggests a lesion in the efferent fibers supplying the pupillary sphinter muscles.

• In order to localize the causative lesion, you must first determine which pupil is abnormal, the smaller one or the larger one.

• The smaller pupil is abnormal when the degree of assymetry is more pronounced in darkened settings.

• The larger pupil is abnormal when the degree of assymetry is more pronounced in bright light.

• Most studies suggest that the risk of aneurysm rupture significantly increases after the size of 7 mm.

• The risk of rupture is greater for posterior circulation aneurysms.

• Five-year risk of aneurysmal rupture based on size (for anterior and posterior circulation aneurysms, respectively):
  
  ---  7 to 12 mm --> 2.6 and 14.5%              

             ---- 13 to 24 mm --> 14.5 and 18.4%

• Cerebral aneurysms are usually not congenital, but rather often form over days, weeks, or months.  

• It is hypothesized that the critical size for rupture is smaller for newly formed aneuryms; thus, treat newly discovered aneurysms that were previously radiographically absent more proactively and cautiously.

• While hypertension and cigarette smoking are not thought to cause aneurysmal rupture, they do contribute to the problem;  Hypertensive smokers are at a 15-fold increased risk of SAH compared to non-hypertensive non-smokers.

• About 2% of the adult population have an asymptomatic cerebral aneurysm.

• Unruptured aneurysms can cause symptoms such as headache, visual acuity loss, cranial neuropathies (particularly thrid nerve palsy), pyramidal tract dysfunction, and facial pain; these are thought to be due to mass effect on the aneurysm.

• 20 to 30% of people with a cerebral aneurysm, have multiple aneurysms; Don't miss co-existing aneurysms on CTA or MRI. 

• The majority of intracranial aneurysms are located in the anterior circulation, most commonly in the Circle of Willis.

• When localizing aneurysm on CTA and MRI, common sites include: 

              ---  junction of the anterior communicating artery (ACOM) with the anterior cerebral artery (ACA)

              ---  junction of the posterior communicating artery (PCOM) with the internal carotid artery (ICA)

              ---  bifurcation of the middle cerebral artery (MCA)

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• Tramadol (Ultram) is an uncontrolled substance in the opiod family that binds mu receptors and is indicated for moderate to moderately severe pain.

• Tramadol lowers seizure threshold to < 1/100,000, likely related to its inhibition of neuronal re-uptake of serotonin and norepinephrine in the CNS.

• Concurrent use with SSRI's, TCA's, MAOI's, neuroleptics, other opiods, naloxone (when given for tramadol overdose) and alcohol exacerbates the risk of seizure onset.

• Tramadol-related seizure is independent of dose (i.e. can occur at starting dose of 25 mg), although brisk titration up to maintenance doses does increase seizure risk.
•  
•  To avoid triggering a seizure, tramadol should not be used in patients with the following conditions:

             --  seizure disorder

             --  alcohol withdrawal

             --  alcoholism

             --  drug withdrawal

             --  CNS infections

             --  metabolic disorder

             --  head trauma

• Don't forget to check for distal lower extremity neurologic deficit after knee injury, particularly when there is a direct blow to the popliteal fossa.
• The common peroneal and tibial nerves exit from the lateral and middle sections of the popliteal fossa, respectively.
• The common peroneal nerve wraps laterally around the fibula (where it's palpable), primarily supplying the lateral portions of the lower leg and foot.
• The tibial nerve primarily supplies the muscles of the posterior compartment of the lower leg (i.e. gastrocnemius, soleus, popliteus).
• Both the common peroneal and tibial nerve fibres branch into the sural nerve, which supplies the lateral foot.
• Common peroneal also splits into deep and superficial branches which supply the muscles of the anterior lower leg compartment and lateral lower leg compartment, respectively.  The deep branch also provides cutaneous innervation of the cleft between the great and second toes.

--  IN SUMMARY:

• Neurologic deficit of the posterior lower leg muscles likely = tibial nerve injury.
• Neurologic deficit of the anterior and lateral lower leg muscles likely =  peroneal nerve injury.
• Decreased sensation in the web space between the great and 2nd toes likely = (deep) peroneal nerve injury.
• Decreased sensation over the lateral dorsum of the foot likely = sural nerve injury.

*** Speaking of such deficits by naming the affected nerve distribution is particularly helpful when consulting orthopedists, neurologists, etc.

• The Sciatic Nerve is commonly injured during intramuscular buttocks injections as well as hip fracture dislocations and posterior dislocations.  In such instances, always confirm and document preserved sciatic nerve function.

• Sciatic nerve injury often results in foot drop due to decreased function of the hamstring, calf, and anterolateral lower leg muscles.

• Sciatic nerve injury may also cause loss cutaneous sensation over the calf , as well as the sole and lateral portions of the foot.

Top Reasons to call your Neurointerventionalist:

1. Vascular "blowouts" (i.e carotid tumor or trauma). 
2. Symptomatic dissections within 6 hours of onset (i.e. carotid or vertebral).
3. Ischemc Stroke with visible clot on CT angiogram outside of 3-hour IV tPA window.
4. Ischemic Stroke with visible clot on CT angiogram outside of 3-hour IV tPA window or with contraindication for tPA (i.e may be MERCI Device candidate).
5. Subarachnoid hemorrhage of aneurysmal origin.