Integration II Flashcards
A 76-year-old man with a history of hypertension, diabetes, and smoking presents with sudden-onset of severe right face, arm, and leg weakness. The patient’s wife brings him to the emergency room within 3 hours of his symptoms. A CT scan of the head is normal. A CTA of the head and neck shows mild atherosclerosis of both carotid arteries but no vascular occlusion. Which of the following best describes initial steps in management of this patient based on the most likely diagnosis?
Allow blood pressure to autoregulate, prepare to give intravenous tPA
A 75-year-old woman develops sudden weakness and numbness of the left arm and left leg. On examination, she has a left pronator drift and 4 / 5 strength in the left arm and leg. Her left big toe goes upward when stroking the bottom of the foot. She has loss of sensation to both vibration and pinprick in her left arm and her left leg. Her right side is completely normal. A CT scan is performed in the emergency room and shows a faint hypodensity. Which of the following is the most likely explanation for her symptoms?
Ischemic stroke affecting the right internal capsule
A 58-year-old man wakes up in the post-anesthesia care unit after repair of a rupture abdominal aortic aneurysm. He cannot move either of his legs. On examination, he has no movement in either of his legs. He cannot feel pinprick through his abdomen or either leg, but he can identify whether his great toe is moving up or down and both sides. What testing would you perform first?
MRI of the cervical and thoracic spine
Remember! The nerves that innervate the feet are “lumbar” in origin and exit the spine in the lumbar region, BUT, their cell bodies are in the cervical and thoracic spine, and that is what we are interested in here.
Technically, prospopagnosia can be produced by. . .
. . . a lesion in either temporal lobe
Clostridium botulinum’s neurotoxin makes muscles ___.
Clostridium tetatni’s neurotoxin makes muscles ___.
Clostridium botulinum’s neurotoxin makes muscles flaccid.
Clostridium tetatni’s neurotoxin makes muscles tense.
Adult botulism course
- Classically contracted from undercooked smoked fish or home-canned vegetables
- Patients remain afebrile
- First develop bilateral cranial nerve palsies, commonly with diplopia and dysphagia
- This is followed by generalized muscle weakness
- Weakness progresses to sudden respiratory paralysis and death
- Patients must immediately be treated with antitoxin, as this only neutralizes unbound toxin. Intubation and ventilatory support is critical until respiratory muscles resume activity.
Infantile botulism course
- Classically acquired following ingestion of honey or corn syrup
- Prodrome of constipation
- Eventually develops generalized hypotonia
- Treated with supportive care in NICU and IV human botulism immunoglobulin
Tetanus course
- Classically acquired from puncture wound from object contaminated with spores (spores from feces or soil)
- Inhibition of inhibitory neurons causes diffuse, deregulated muscle contraction
- On clinical exam, this is characterized by risus sardonicus (uncomfortable looking “smile” from forced facial muscle contraction) and opisthotonus (posture caused by contraction of all back muscles)
- High mortality
Temporal lobe epilepsy
Type of focal epilepsy that can present more like acute, episodic anxiety. Always on the differential for panic disorder or agoraphobia.
Corticospinal tract at all layers of spine and brainstem
Anterolateral tract at all layers of spine and brainstem
Dorsal column tract/medial lemniscus at all layers of spine and brainstem
Identify the important midbrain regions
- Anterolateral tract also in green on original diagram
- Note that the trochlear nerve nucleus is just below this level in the same location as the occulomotor nucleus, but its nerve fibers decussate and exit posteriorly rather than staying ipsilateral and exiting anteriorly as the occulomotor nerve does.
Identify the important pontine structures
Major nerves entering/exiting the medulla
Identify the important medullary structures
Reflexes to test at each brainstem level
- Medulla: Gag reflex
- Pons: Corneal reflex
- Midbrain: Pupillary reflex
Which cranial nerve isn’t really a nerve, but we call it one anyway?
Cranial nerve II, the optic nerve
It is actually an extension of the brain itself: it does not have a nucleus, and its myelin is supplied by schwann cells (like the rest of the CNS), not oligodendrocytes (like the PNS).
This is why the optic nerve/tract are affected in MS, a central pathology, and why it is not affected in Gullian Barre despite most of the other cranial nerves being involved.
What differentiates tardive dyskinesia (acquired from long term antipsychotic use) from the dyskinesia of huntington’s?
Tardive dyskinesia tends to involve abnormal mouth movements, where as huntington’s or other hemiballismus is more limb based.
Patient with hx seizures describes that seizures onset with a “rising sensation” from the stomache and dejas vus
These are both common features of temporal lobe seizures, and likely correlate with mesial temporal sclerosis.
Psychiatric conditions with the highest risk for suicide
- Borderline personality disorder
- Schizophrenia spectrum disorders
- Anorexia nervosa
Passive death wish
Statements like “I wish I would go to sleep and not wake up”
Still an increased risk for suicide, but this does not count as suicidal ideation.
If someone screens + for suicidal ideation, you always have to ask about:
- Firearms
- Non-suicidal self injury
- Previous suicide attempts
-
Suicide plan (how to go about it)
- and associated Acts of Furtherance (buying a gun, drafting a will, writing a letter, etc)
- Suicidal intent (conviction that you will do it)
Quick, classic test for myasthenia gravis
If the patient has ptosis, put an ice pack on their eye for a couple minutes.
If they have myasthenia, it might just go away!
Very specific for myasthenia gravis.
PNS lesions tend to produce ___ more often than CNS lesions.
PNS lesions tend to produce positive symptoms more often than CNS lesions.
Ex, pain, tingling sensation
Mnemonic for cerebellar damage signs
-
DANISH
- Dysdiadikinesis
- Ataxia
- Nystagmus
- Intention tremor
- Slurred speech
- Hypotonia
Cavernous Sinus diagram
Location of the superior cervical ganglion
Caudal pons diagram
Rostral pons diagram
Antiplatelets vs anticoagulants
Which antiepileptics are safest during pregnancy?
The newer AEDs, levetiracetam and lamotrigine.
These drugs have a 95% CI including the reference rate for malformations in an untreated population. They still may have slightly increased risk relative to no antiepileptic at all, but no study as of yet has had sufficient power to demonstrate or refute this.
What types of malformations are seen in the children of pregnant women treated with antiepileptics?
Mostly neural tube, oral cleft, and cardiac malformations.
Antiepileptic master diagram
Main advantage of levetiracetam and gabapentin as antiepileptics
- Cause few to no hypersensitivity reactions (ex, SJS)
- Do not induce or inhibit hepatic enzymes
Supplements that interact with anti-epileptics
Gingko biloba or St John’s wort can interact with hepatically metabolized antiepileptic drugs, and is a contraindication
Status epilepticus protocol table
Status epilepticus field medicine
In the first stage (early status epilepticus), buccal midazolam has become an important out-of-hospital treatment option
Epilepsy is considered to be resolved for individuals who . . .
Epilepsy is considered to be resolved for individuals who either had an age dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure free for the last 10 years and off anti-seizure medicines for at least the last five years
5-hydroxytryptamine
Another name for serotonin!
This is why the serotinin receptors are the 5-HT family
Varicosities
Varicosities are projections at the end of neurons that release neutrotransmitters. However, unlike synapses, varicosities release the neutransitters large amounts of neutransmitter into the extracellular space with no discrete “junction” that becomes saturated.
This establishes a concentration gradient of the neutransmitter in a cloud surrounding the varicosities.
Serotonin and norepinephrine are primarily released from varicosities, not synapses.
Serotonin regulation
Norepinephrine regulation
Why are the older MAOi’s no longer first-line? What must a patient do if they want to take an older MAOi?
- Older MAOi’s also inhibit the degradation of dietary tyramine, a catecholamine present in processed meats, aged cheese, and red wine
- This may lead to tyramine toxicity, a syndrome characterized by hypertensive crisis, headache, tachycarcia, nausea, cardiac arrhythmia, and stroke
- For this reason, if a patient wants to take a MAOi, they must adopt a tyramine-free diet
- Newer MAOi’s are reversible inhibitors, where as the older ones are irreversible. So, newer MAOi’s can be displaced by large amounts of tyramine, and as such do not cause tyramine toxicity.
First-line therapy for OCD
Clompiramine
a TCA
Adverse effects of TCAs
TCAs have quinidine-like effects on the heart, and may cause bundle branch block or first-degree AV block. They are contraindicated in patients with preexisting cardiac problems and require regular ECG monitoring.
For this reason, they are also cardiotoxic if taken in high doses, and so should not be used in patients with high risk of suicidality
Apart from this TCAs also have anticholinergic effects, and may cause N/V, anorexia, dry mouth, blurred vision, confusion, constipation, orthostatic hypotension. and urinary retention
Non-depression uses of TCAs
Useful in chronic somatic pain disorders, including migraines
Adverse effects of SSRIs
- Diminished libido and decreased sexual function
- GI distress
- When administered with MAOi, may cause serotonin syndrome:
- Rare but serious syndrome of hypothermia, muscle rigidity, myoclonus, and rapid fluctuations in mental status and vitals
- Abrupt withdrawal causes SSRI-discontinuation syndrome:
- Characterized by anxiety, dysphoria, GI flu-like symptoms, insomnia, depersonalization, and frank suicidality
Bupropion uses and contraindication
- Useful for patients for whom sexual side effects of other antidepressants are a particular concern
- Lowers the threshold for seizures, and so is contraindicated in individuals with history of seizure or epilepsy, or conditions which may secondarily predispose to seizure (electrolyte abnormalities, eating disorders)
Etiology and treatment rationale for migraines
- Migraines are believed to be caused by cerebral vasodilation and subsequent activation of small pain fibers
- As such, serotonin agonists, which act as cerebral vasoconstrictors, are effective in abortive treatment
- Ergots and triptans are such serotonin agonists at the 5-HT1R
The 5-HT4 and 5-HT3 Receptors
- Serotonin receptors present in the GI tract that mediate the critical effects of serotonin on GI motility
- 5-HT4 agonists such as Cisparide induce gastric motility by stimulating the gastric myenteric plexus
- 5-HT4 antagonists induce intestinal motility and are effective in treating constipation-episodes in IBS
- 5-HT3 antagonists decrease serotinergic tone in the intestine, and result in reduced motility. These are effective in treating diarrhea-episodes in IBS
“Mood stabilizers”
- Lithium
- Valproic acid (antiepileptic)
- Carbemazepine (antiepileptic)
- 2nd generation antipsychotics
Inositol depletion hypothesis of lithium action
Lithium inhibits the association of crucial cation cofactors with the dephosphorylases involved in degrading IP2 to free inositol. This degradation is required for PIP2 regeneration and maintenance of the phosphotidylinositol signaling pathway.
Additionally, lithium inhibits de-novo synthesis of phosphatidylinositol from glucose-6-phosphate, and new phosphatidylinositol cannot be imported from the rest of the body since it is not able to permeat the blood-brain barrier.
Thus, lithium causes a gradual depletion of usable PIP2 and leads to inhibition of phosphotidylinositol signaling in the brain. Ultimately, this leads to a reduction in central adrenergic, muscarinic, and serotinergic signaling. It is proposed that this is lithium’s mechanism of action in treating mania.
GSK3 inhibition hypothesis of lithium action
Recent studies indicate that lithium blocks glycogen synthase kinase 3 (GSK3) activity. GSK3 is a key enzyme involved in regulating the WNT signaling pathway, which controls adult neurogenesis and is a regulator of multiple neuroplasticity mechanisms.
Growing pharmacologic and genetic evidence supports this as a likely mechanism in lithium’s antimanic and antidepressant activity.
Acute lithium intoxication
- Lithium has a very narrow therapeutic range
- Excessive lithium causes a syndrome of N/V, diarrhea, renal failure (from nephrogenic DI induction), neuromuscular dysfunction, ataxia, tremor, confusion, delirium, and seizures
- Medical emergency that may require dialysis
Lithium and NSAIDs
NSAIDs increase the reabsorption of lithium and may thus induce lithium intoxication. As such, these drugs are contraindicated.
Triptan contraindications
- Since they cause serotinergic vasoconstriction, they are contraindicated in CAD
Cranial nerve skull foraminae
Anatomic relationship of the facial and abducens nerves
Apoplexy
unconsciousness or incapacity resulting from a cerebral hemorrhage or stroke.
Chorda tympani
- Conveys special sensory and glandular innervation functions of the facial nerve and separates from the motor fibers prior to the major divisions of the facial nerve along the corner of the mandible
What pharmacologic agents do we use for preventing future ischemic attacks in a patient who presents with TIAs?
An antiplatelet medication
Usually we do not perscribe an anticoagulant concurrently for initial presentation.
Why don’t we give aspirin to children under the age of 16?
Risk of Reye’s syndrome
Acute encephalopathy and fatty liver – quite fatal
If a patient must take aspirin for antiplatelet properties but also has osteoarthritis or other condition requiring regular NSAID use, they should be instructed to . . .
. . . take a higher dose of aspirin, but don’t take NSAIDs concurrently with aspirin.
Ethosuximide is the drug of choice for absence seizures, but . . .
. . . it ONLY works for absence seizures.
So if a patient with absence seizures also has tonic-clonic seizures, they will need a different antiepileptic.
Gingival hyperplasia is a common side effect of ____.
Gingival hyperplasia is a common side effect of phenytoin
SJS management
Phenelzine vs selegiline
Phenelzine is a nonselective MAO inhibitor whereas selegiline is a selective MAOB inhibitor.
As such, phenelzine is used as an antidepressant while selegiline is used to treat Parkinson’s and Parkinson’s Plus syndormes.
Treating migraines
FDA Pregnancy Safety Categories
Tracts in the brainstem
Bell’s phenomenon
Inability to close eye on ipsilateral side. Sign of lower motor neuron involvenment for facial nerve -> Bell’s palsy
Very common in pregnancy.
