UMEM Educational Pearls - Neurology

• Treating stroke patients older than age 80 with intravenous tissue plasminogen activator (IV-tPA) continues to be a controversial topic, primarily due to its perceived association with increased rates of intracranial hemorrhage (ICH).

• Reliable analysis of robust datasets from the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) has shown that, in fact, IV-tPA patients older than age 80:

             (1) do not have increased risk for clinically significant ICH,

             (2) have early clinical improvement similar to younger patients, and

             (3) have poor outcomes related to increased mortality (odds ratio 30% versus 12%), rather than

                   to higher rates of functional dependence (i.e. Modified Rankin Score 3 to 5). 

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Causes of Pulsatile Tinniitus 

• Pulsatile tinnitus, also known as objective tinnitus, results from altered blood flow or increased blood turbulence near the ear.  People other than the person experiencing the tinnitus are often able to hear this rhythmic, pulse-patterned noise.  
• While there are several benign causes of pulsatile tiniitus such as strenuous exercise, atherosclerosis, and ruptured tympanic membranes, there are only a few serious etiologies.
• It is important that the astute emergency provider be aware of and know the appropriate treatment for the following life-threatening and/or high morbidity-associated causes of pulsatile tinnitus:

1. Idiopathic intracranial hypertension (previously known as pseudotumor cerebri)
2. Carotid artery aneurysm
3. Carotid artery dissection
4. Vasculitis such as giant cell arteritis  

Lithium Toxicity

• Lithium toxicity is common and occurs in 75 to 90% of patients receiving long-term lithium therapy at some point during their management.  It most often results from inadequate renal excretion.
• Toxic patients typically present with mild side effects such as hand tremor, but other symptoms like weakness, delirium, rigidity, hyperreflexia, altered gait, seizure, and EEG changes may also result.
• While severe lithium toxicity typically correlates with elevated serum levels, not all patients with high lithium levels present with advanced symptoms, at least in the early stages; this is due to delayed distribution within tissues.  Similarly, patients with lower serum levels of lithium may present with advanced symptoms, if the drug has accumulated in the cerebrospinal fluid to a greater extent than it has the serum. 

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Contraindications to performing lumbar puncture (LP):

- INR > 1.4 or other coagulopathy

- Platelets < 50

- Infection at desired puncture site

- Obstructive / non-communicating hydrocephalus

- Intracranial mass

- High intracranial pressure (ICP) / papilledema (relative contraindication depending on etiology; especially a concern with intracranial mass lesion secondary to the increased risk of transtentorial or cerebellar herniation)

- Focal neurological symptoms/signs, decreased level of consciousness

- Partial / complete spinal block

- Acute spinal trauma

• Patient positioning is key when measuring opening pressure (OP) of cerebrospinal fluid (CSF) during lumbar puncture. 

• OP is only accurate when measured while the patient is completely horizontal and relaxed, in the lateral decubitus position (i.e. no neck flexion or extension, legs extended, no valsalva).  In order to achieve this, you may need to carefully place patient in a lateral decubitus position if they are initially sitting upright prior to dural puncture and/or be sure to have patient straighten their legs (i.e. abort fetal position) once ready to measure OP.

• Strictly speaking, normal range of CSF pressure is 8 to 21 cm, but obesity can increase it up to 25 cm and still be considered normal.  Thus, while the significance of measurements between 20 and 25 cm in obese patients may be unclear, levels above 25 cm are always abnormal.

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• Chemoprophylaxis should be given to those individuals who came into "close contact" with someone infected with meningitis due to meningococcal infection (i.e. Neisseria meningitidis).  It should be given as early as possible following the exposure; when there is a high index of suspicion, do not wait for culture results to give prophylaxis.
• Chemoprophylaxis is generally not indicated when the etiology is Streptococcus pneumoniae, and should be reserved for young children who have not received a Haemophilus influenzae type b (Hib) vaccination and immunocompromised close contacts when the etiology is Hib.
• While the definition of a "close contact" remains somewhat ambiguous, it generally refers to individuals who have had prolonged (>8 hours) contact while in close proximity (<3 ft) to the patient, or who have been directly exposed to the patient's oral secretions between one week prior to the onset of the patient's symptoms until 24 hours after initiation of appropriate antibiotic therapy.
• Standard regimens for antimicrobial prophylaxis include ciprofloxicin, ceftriaxone, and rifampin.  Adults typically require a single oral dose of 500 mg of ciprofloxicin or 250 mg of intramuscular (IM) ceftriaxone, while individuals under age 15 may receive a single dose of 150 mg of IM ceftriaxone.

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• Trigeminal Neuralgia (TN) presents with unilateral, lancinating head and facial pain, affecting one or more of Cranial Nerve V's divisions.

• The pain occurs in 1 to 5 second multiple attacks throughout the day.  Symptoms may remit and recur.

• TN is associated with trigger points, but lacks any associated focal neurologic deficit or abnormality.

• These characteristics will help distinguish TN from other sources of unilateral headache, such as migraines, cluster headaches, sinusitis, and glaucoma.

• There are a host of treatments for TN, including options such as medical management with anti-convulsants and/or muscle relaxants, surgical ablation, alcohol injection (induces numbness), glycerol injection (destroys affected part of nerve), balloon compression, and administration of electrical current.

• Medical management with analgesics and muscle relaxants is typically the most appropriate, first-line treatment in the emergency department.

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• Myasthenic patients who initially present in a stable fashion with normal ventilation and minimal dyspnea can decompensate rapidly.
• In Myasthenia Gravis, the body produces antibodies against native post-synaptic acetylcholine (Ach) receptors. Adding a paralytic that occupies the few remaining functional Ach receptors could significantly prolong general muscular dysfunction and the need for ventilatory support during a myasthenic crisis.
• If intubation is required, DO NOT administer neuromuscular blocking/paralytic agents such as succinylcholine or rocuronium, as these agents antagonize Ach binding receptors at the post-synaptic membrane of the neuromuscular junction.
• Studies have shown that the use of propofol and fentanyl, without any paralytic, provides sufficient analgesia and sedation to successfully complete a humane intubation in these cases.
  
   

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Note that yesterday's Neurology pearl should have read as follows -

Amongst others, diagnostic criteria for NMS includes:

Exposure to a dopamine ANTAGONIST (NOT AGONIST) or dopamine agonist withdrawal within past 72 hours.

Apologies for the type-o.

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• Neuroleptic Malignant Syndrome (NMS) is a life-threatening complication of anti-psychotic medication therapy.
   
• While NMS is rare (0.02 to 2.44% amongst those taking neuroleptic drugs), its associated mortality (up to 12%) and morbidity (i.e. rhabdomyolysis, pneumonia, seizures, renal failure, disseminated intravascular coagulation (DIC), respiratory failure) are severe.
   
• Historically, there has been little consensus about universally accepted diagnostic criteria for NMS, until an expert panel of various physician specialists recently convened and determined the following criteria:

           - Exposure to dopamine agonist or dopamine agonist withdrawal within past 72 hours
           - Hyperthermia
           - Rigidity
           - Mental status alteration
           - Elevated creatinine phosphokinase
           - Sympathetic nervous system lability (2 or more of the following: elevated blood pressure, fluctant blood pressure, urinary incontinence, diaphoresis)
           - Tachycardia and tachypnea
           - Negative work-up for infectious, metabolic, neurologic, or toxic etiologies.

• Treatment includes immediate withdrawal of any antipsychotic medication and is, otherwise, largely supportive.

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• Given the common need to treat conditions such as Clostridium difficile colitis, refractory bacterial vaginosis/trichomoniasis, and bacteremia/sepsis with prolonged courses of metronidazole, the astute clinician should be mindful of metronidazole-induced neuropathy as the possible etiology of numbness, tingling, and parasthesias in patients taking this medication.
• This is a rare, but serious side effect which is dose and duration dependent; doses of 1000 mg to 2400 mg for at least 30 days duration is typically required to cause neuropathy.
• The lower extremities are most commonly affected.
• In suspected cases, use of metronidazole should immediately be stopped; sometimes symptoms never completely resolve even after cessation of use, particularly in cases of prolonged oral therapy.

The onset of idiopathic seizures typically affects patients between ages 5 and 20. 

Therefore, be highly suspicious of a diagnosable etiology in patients who present with new onset seizure prior to age 5 or after age 20.

Common causes of such seizures include:

• Tumors or other structural brain lesions (i.e. intracranial hemorrhage)
• Traumatic brain injury
• Abrupt cessation of alcohol abuse
• Dementia ( i.e. Alzheimer's disease)
• Congenital brain defects
• Intra-partum brain injury
• Hypoglycemia or hyponatremia
• Renal or hepatic insufficiency
• Cocaine or amphetamine illicit drug use
• Abrupt cessation of benzodiazepines, barbiturates, analgesics (i.e. morphine, gabapentin), or sleeping pills
• Infection (i.e. brain abscess, meningitis, encephalitis, neurosyphilis, AIDS)
• Phenylketonuria (PKU) in infants

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• Phenytoin has a wide volume of distribtuion and is 90% bound to protein. 
• Only the unbound proportion is biologically active, and therefore, FREE levels of phenytoin should be checked to determine whether acute seizure activity is related to suboptimal levels or not. 
• Given these properties, patients with the following conditions are more likely to become phenytoin toxic:  neonates and the elderly (due to poor metabolism and low protein production); uremia, nephrotic syndrome, pregnancy, malignancy, malnutrition (due to low potein levels).

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• A simple febrile seizure (SFS) is generalized, tonic-clonic in type, and occurs in children between the ages of 6 months and 6 years of age, lasting less than 15 minutes and NON-recurring in a 24 hour period.
• According to the 1996 guidelines of the American Academy of Pediatrics (AAP) and based on the consensus that seizure is a common presenting symptom of bacterial meningitis, the following indications should be used to determine whether lumbar puncture (LP) is performed in patients presenting with SFS:

             --  6 to 12 months  >  "strongly consider" LP

              --  12 to 18 months  >  "consider" LP

              --  18 months and up  >  LP not routinely necessary; may consider after clinical assessment

              --   Any infant/child with recent antibiotic treatment plus SFS  >  "strongly consider" LP

• Despite these relatively outdated guidelines based largely on retrospective data, more recent literature suggests that serious bacterial infections such as meningitis are very rarely associated with simple febrile seizures, such that guidelines and practice paradigms may soon change.   

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• Procedural sedation consists of administering sedatives (i.e. midazolam, etomidate, propofol) or dissociative agents (i.e. ketamine) with or without opioid analgesics such as morphine and fentanyl.
• The widespread use of ketamine for procedural sedation may be limited by physician concern about unpleasant, vivid dreaming, hallucinations, and reactions after its administration known as recovery agitation.  This has been found to occur in 12 percent of cases and is seen less often in youth.
• In some instances, ketamine might be considered more ideal than other procedural sedation agents because it provides sedation, analgesia, and an amnestic-like dissociation between mind and body.
• Recent studies have shown that administering ketamine with a benzodiazepine such as midazolam significantly reduces the incidence of recovery agitation following procedural sedation; this alternative might therefore be considered when appropriate.
   

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• The benefit of IV alteplase (tPA) beyond the conventional window of 3 hours after onset of stroke symptoms was established by the randomized ECASS III Trial, which compared treating acute ischemic stroke with IV alteplase versus placebo, between 3 and 4.5 hours (median 4 hours).
• The study found a significantly more favorable outcome amongst participants who received alteplase (odds ratio 1.34, 95% CI 1.02 - 1.76).  The overall number needed to treat was 14.
• The standard exclusion criteria used in this study differed from those of others, and these characteristics must be taken into account when deciding which patients are eligible for treatment at up to 4.5 hours.
• Therefore, data from ECASS III can not be used to support treating at up to 4.5 hours in the following types of patients:

              -- Age > 80 years old

              -- NIH Stroke Scale > 25

              -- History of combination of previous stroke and diabetes

              -- On anticoagulation medication, regardless of INR

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• Seizure is very rarely associated with true ischemic stroke; the presence of seizure is, in fact, a  contraindication for administering t-PA in patients thought to have had a stroke.

• Thus, when patients present with an alleged stroke in the setting of seizure, be skeptical as to whether there truly was an ischemic stroke and do more investigating to ascertain a satisfactory conclusion.  In these cases, perhaps the patient suffered a hemorrhagic stroke, which is associated with seizure more often than is ischemic stroke.

• Post-seizure sequelae can present as focal neurologic deficit that mimics stroke (i.e. Todd's Paralysis), but note that these are generally associated with partial, not generalized, seizures.

• Finally, remember that patients who have had strokes in the past are at increased risk for having future strokes AND for developing a seizure disorder secondary to the focal area of brain tissue damaged by their prior stroke.  These patients, therefore, may present with a combination of true, new OR exacerbated, old stroke symptoms, with or without seizure.

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• Parkinson's Disease is a degenerative disorder of the central nervous system characterized by tremor and impaired muscular coordination due to deficient levels of intra-cerebral dopamine.
• Many of these patients experience motor fluctuations which consists of periods of being "on," which is when they experience a good or hyper response to their medication, and periods of being "off," which is when the parkinson's condition itself is exacerbated.  Differentiating between these two modes is important in terms of managment, but may be challenging.  
• "On time" typically presents with relatively normal or dyskinetic involuntary  ballistic movements, chorea, dystonia, or myoclonus.  These episodes are best treated by avoiding levodopa, carefully administering low-dose benzodiazepines, or perhaps amantadine(possibly effective).
• "Off time"typically presents with sometimes painful dystonia, intorsion of limbs, spasm, and stiffness, and often relates to a period wherein the effects of parkinson's medications such as levodopa are wearing off.   These episodes are best treated by gradually increasing dopamine agonist medication such as bromocriptine, pramipexole, and ropinirole, and likely admission to the hospital. 

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• Using the neurological examination to test coordination primarily assesses cerebellar function.
• The cerebellum is important for motor learning and timing of motor activity.  It fine-tunes agonist and antagonistic forces of muscle activity, simultaneously and sequentially, across multiple joints which results in smooth and purposeful movements.
• Cerebellar dysfunction causes deterioration of movements, with subsequent under-shooting and over-shooting of purposeful movement, also known as dysmetria.
• Deterioration of movement and dysmetria are precursors to the development of ataxia.

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