UMEM Educational Pearls - Neurology

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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FILE RESEND. This was tested via email and will hopefully work. I apologize for errors - Dlemkin (webmaster)

What is the diagnosis? (DON'T LOOK DOWN AT THE ANSWER)

50 year-old male prisoner s/p assault, + LOC

CT shows right-sided traumatic subarachnoid hemorrhage

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• The National Institute of Health Stroke Scale (NIHSS) is a well-validated, highly reproducible tool that is widely used to measure neurologic deficit and as a scoring system for stroke intervention.
• This scale is heavily weighted toward recognizing deficit due to anterior circulation strokes, however, while that due to posterior circulation strokes receives fewer points.
• One study found that nearly 1% of patients with MRI-confirmed acute ischemic stroke patients scored zero points on the NIHSS, and that the majority of these were posterior strokes.  These types were more likely to present with truncal ataxia (most commonly), headache, vertigo, and nausea.
• Take home points:  (1) The NIHSS should not replace a thorough neurological examination.  (2) Consider posterior stroke as the source of persistent symptoms in patients with an NIHSS score of zero. 

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• While seizure patients are often treated with common antiepileptics such as phenytoin and levetiracetam, those with severe refractory disorders may be treated with less frequently used medications such as felbamate.
• Felbamate is reserved as monotherapy or adjunctive therapy for refractory, partial seizures in adults with or without secondary generalized seizure, and as adjunctive therapy for children with partial and generalized seizures due to Lennox-Gastaut Syndrome (condition that causes seizures and developmental delay).
• In patients who present to the ED on felbamate, consider checking a CBC with differential and liver function tests, as it can cause aplastic anemia (relatively rare but 30% fatal) and liver damage (rare but 40% fatal), respectively.
• Signs and symptoms of aplastic anemia include:  fever, sore throat, chills, other signs of infection, bleeding, easy bruising, extreme fatigue, weakness, or lack of energy.
• Signs and symptoms of liver failure include: nausea, extreme fatigue, unusual bleeding or bruising, lack of energy, anorexia, right upper quadrant pain, jaundice, or flu-like symptoms.

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• Ischemic strokes often present as lacunar infarcts, wherein flow along the deep penetrating vessels of the middle cerebral artery is compromised.
• These strokes typically present with either purely motor or purely sensory neurologic deficit, in an ipsilateral pattern, often striking parts of the basal ganglia.
• Lacunar infarcts may present in a mild manner and carry the best prognosis for recovery relative to other types of ischemic stroke.

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• Lhermitte's phenomenon is a transient, sensory symptom which likens an electric shock that radiates down the spine or into the limbs.

• The sensation is triggered by neck flexion.  The frequency with which they occur varies and the slightest movement of the head or neck may trigger it.

• This phenomenon occurs most frequently with multiple sclerosis, but can also be seen with other lesions of the cervical cord, including tumors, disc herniation, post-radiation myelopathy, and following trauma.

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• Transverse Myelitis (TM) is the development of grey and white matter inflammation of the spinal cord, which can result in demyelination.
• Hallmark characteristics of this condition include: (1) isolated spinal cord (not brain) dysfunction, and (2) the lack of associated cord compression.
• TM can be acute or subacute, such that it progresses over the course of hours to several days.  Nearly half of cases will reach its maximal deficit within 1 to 10 days of onset.
• The diagnosis of TM is primarily based on the history and physical examination findings.  MRI of the spinal cord and myelography are often used as diagnostic adjuncts.
• This condition typically presents with paresthesias, back pain, and ascending leg weakness.
• Febrile illnesses often serve as a precursor; one series found this to be the case in 37% of complete TM cases.
• While steroids are sometimes administered over the first several days of illness to decrease inflammation, there is no cure for TM and treatment is largely supportive in nature. 

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• Patients with multiple sclerosis (MS), the most common autoimmune, inflammatory, demyelinating neurological condition, often present to  the emergency department with their first episode of symptoms and for treatment of future exacerbations.
• While the diagnosis of MS is ultimately made based on clinical findings such as visual abnormalities, sensory and motor complaints, gait abnormalities, and fatigue, use of brain MRI and cerebrospinal fluid (CSF) studies may be helpful in making the diagnosis.
• Brain MRI findings that are suggestive of MS include ovoid-shaped, demyelinated plaques often situated in periventricular regions and near the corpus callosum.  Seventy to 95% of MS patients will have an abnormal brain MRI.
• CSF findings suggestive of MS include oligoclonal IgG banding and is discovered in 85 to 95% of cases.

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• Any patient presenting with an acute onset of dizziness described as a spinning sensation should be thoroughly assessed for cerebellar stroke, as these often present in such a manner, prior to assuming that the source is simple vertigo.

• Cerebellar strokes, whether due to infarct or hemorrhage, typically present with ataxic gait, abnormal Rhomberg, dysmetria with finger-to-nose and heel-to-shin testing, and nystagmus.

• In addition, the dizziness associated with cerebellar strokes should be less reproducible and extinguishable than that due to simple vertigo.

• In terms of imaging, remember that CT scanning is not the preferred radiologic modality for evaluating the cerebellum and posterior aspects of the brain; the thickness of the posterior skull tends to create significant artifact and distortion. If suspicion warrants, MRI should therefore be pursued.

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