Case Files Flashcards
Side effects of L-Dopa/carbidopa?
Long term use can lead to DYSKINESIAS following administration (on-off phenomenon)
Arrhythmias from increased peripheral formation of catecholamines
Non-medical ways to treat PD?
In patients that still have an excellent response to levodopa except for motor fluctuations and dyskinesias, surgical treatment that inhibits the subthalamic nucleus with high-frequency stimulation can provide excellent relief of the cardinal symptoms of disease. However, placement of a deep brain stimulation (DBS) appears to be the preferable surgical therapy.
In addition, inhibition of the ventrolateral thala- mus can be very effective for treatment of tremor
Which med is most likely to be able to help both relieve cardinal features of Parkinson disease as well as reduce drug-induced dyskinesias?
Amantadine can decrease the incidence of levodopa induced dyskinesia
List three dopamine agonists used to treat PD?
Bromocriptine
Pramipexole
Ropinirole
Selegiline is used to prevent the degradation of L-dopa by blocking COMT. T/F
False
Selegiline: inhibits MAO-B; blocks degradation of dopamine
Entacapone, tolcapone: inhibits COMT; prevents peripheral degradation of L-dopa
What would you take into consideration when starting a PD patient on a medication?
There is good evidence that starting treatment with a dopamine agonist rather than levodopa delays the onset of dyskinesias. Thus, those patients at high risk for developing dyskinesia probably should be treated initially with dopamine agonists.
Nongenetic causes of ataxia?
Trauma
Toxic/metabolic factors
Neoplasms
Autoimmune - e.g. Hypothyroidism
Clinical feature difference between AD and AR ataxias?
AR ataxias tend to have other body systems involved
Most common cause of tardive dyskinesia?
Chronic/LONG TERM exposure to central dopamine blocking agents, such as neuroleptic therapy.
What percentage of pts started on dopamine antagonists develop tardive dyskinesias?
1/3 eventually develop TD
Strongest risk factors for TD?
Female
Advanced age
Coexistent brain damage
How do you treat TD?
BEST: Prevention!
Increased dose of dopamine receptor blocking agents
Tetrabenazine and reserpine (selective depleter of catecholamine vesicles)
Mild sx: Benzos Baclofen Vitamin E Botulinum toxin
Pt has involuntary movements of mouth and face. How can you tell if its TD or focal dystonia?
Look for arching spasms of the back and neck = characteristic of tardive condition
Look for response to anticholinergics
- Might worsen sx if it’s TD
- Dystonia would respond to anticholinergic or dopaminergic meds
TD vs huntingtons?
TD is sometimes associated with more appendicular involuntary movements. As such, it can be confused with Huntington disease. The chorea of Huntington disease drifts in a random fashion around the musculature, whereas TD tends to be more stereotypic.
Most common cause of SCI in those younger than 10yo? Older than 10?
Younger than 10: MVC, falls
Older than 10: MVC, sports-related
Which is higher: nontraumatic SCI vs traumatic SCI?
Non-traumatic SCI is 3x-fold higher than traumatic
What causes central cord syndrome and how does it present? Why?
Trauma
Syringomyelia
Intra-axial neoplasms
Presents with a bilateral loss of pain and temperature sensation in the UPPER extremities as well as weakness in the same distribution but with preservation of fine touch.
Anatomically this is because the spinothalamic tract decussates immediately anterior to the central canal. Also, motor fibers traveling to the legs tend to run more laterally in the spinal cord and are therefore relatively spared.
Which blunt trauma patients get imaging? What kind of imaging?
In blunt trauma of patients older than 9 years of age, no spine imaging is necessary if they are alert, conversant, nonintoxicated, and have a normal neurologic examination without cervical tenderness.
If patients are younger than 9 years of age then imaging is recommended.
- Helical CT if looking for bony structures
- MRI if trying to visualize spinal cord
Which spinal nerves innervate the upper extremities?
C5-T1
What is spinal shock in relation to an acute SCI?
SCI –> loss of motor and sensory function below the level of the lesion, spinal cord transaction also results in LOSS OF AUTONOMIC FUNCTION –> spinal shock
Acute loss of descending sympathetic tone –> decreased systemic vascular resistance –> hypotension.
*If vagal output is intact then its unopposed influence can further lower vascular resistance and also result in a paradoxical bradycardia.
- In the context of spinal shock, aggressive fluid resuscitation is necessary to maintain perfusion pressure andprevent cord ischemia.
- The complete absence of deep tendon reflexes, superficial cutaneous reflexes, and rectal tone also suggests the presence of spinal shock.
- Finally, it is vital to remember to place an indwelling Foley catheter to empty the bladder because the patient will otherwise develop significant urinary retention and stasis.
SCI should get steroids to mediate inflammation-induced secondary injury. T/F
IV methylprednisolone is beneficial for adult patients with:
- incomplete acute spinal cord injury AND
- if administered within 8 hours of injury
- Otherwise it is controversial!
Superficial abdominal reflex?
Scratch the skin in all four quadrants around the umbilicus and watching for contraction of the underlying abdominal musculature.
- Stimulating above the umbilicus tests spinal levels T8 to T10
- Stimulating below the umbilicus tests approximately T10 to T12.
Classic presentation of epidural hematoma?
Injury/LOC –> Lucent period –> cranial to caudal pattern deterioration without neck stiffness
(Can also present as headache, vomiting, seizures)
Would NOT expect a lucent period in:
- Cerebral contusion
- Diffuse axonal injury
Epidural hematomas are more common than subdural hematomas. T/F
False
Epidural hematomas are HALF as common
Males outnumber females 4:1
What factors are associated with higher rates of mortality in those with EDH?
Mortality rate: 5–43%.
Higher rates are associated with:
- Both ends of the age spectrum (i.e., younger than 5 years of age and older than 55 years of age)
- Signs of more extensive anatomical (intradural lesions, increased hematoma volume)
- Clinical (rapid clinical progression, pupillary abnormalities, increased intracranial pressure [ICP], lower Glasgow Coma Scale [GCS]) involvement
- Temporal location.
*Mortality rates are essentially nil for patients not in coma preoperatively and approximately 10% for obtunded patients and 20% for patients in deep coma.
What is cushing’s response and what causes it?
Hypertension, bradycardia, bradypnea 2/2 increased ICP
- Expanding intracranial mass
Imaging choice for EDH? What findings?
CT w/o contrast Look for: - Mass that displaces brain away from skull - Smoothly marginated - Lenticular/biconvex homogenous density - Doesn't cross suture lines
Factors influencing outcome of EDH after surgical evacuation??
- Initial GCS, pupillary response, motor examination, and associated intracranial injuries seen on the CT scan.
A normal brain CT scan performed 1 hour after a closed head injury in the context of a relatively normal neurologic examination precludes development of epidural hematoma. T/F?
FALSE
An evolving epidural hematoma CAN OCCUR ANY TIME after the immediate injury.
- Repeat CT brain imaging is indicated if there is any change in the neurologic status of the patient.
Hallmarks of delirium?
Impaired concentration
Impaired attention
Fluctuating course
How are concussions classified?
- A grade 1 concussion involves no loss of consciousness and all symptoms resolve within 15 minutes.
- A grade 2 concussion involves no loss of consciousness but symptoms last longer than 15 minutes.
- A grade 3 concussion involves loss of consciousness for any period of time.
Most common cause of concussion in 5-14yo? Adults?
5-14yo: Sports and bicycle accidents
Adults: Falls, MVC
How does LOC occur in concussion (pathophys)?
Ascending reticular-activating system (ARAS) is a key structure mediating wakefulness
–> transient interruption of its function can be partly responsible for temporary LOC following head injury.
The junction between the thalamus and the midbrain, which contains reticular neurons of the ARAS, seems to be particularly susceptible to the forces produced by rapid deceleration of the head as it strikes a fixed object.
Which pts get imaging in regards to a concussion?
New Orleans Criteria (head CT if any are true):
(1) persistent headache
(2) emesis
(3) age: older than 60 years
(4) drug or alcohol intoxication
(5) persistent anterograde amnesia
(6) evidence of soft-tissue or bony injury above the clavicles (7) a seizure.
* Imaging is often recommended for children younger than 16 years of age because clear validated clinical criteria do not yet exist.
Return to play guidelines for concussions?
Grade 1 concussion:
- Should be removed from the game for at least 15 minutes and assessed at 5 minute intervals. If there was no loss of consciousness and the symptoms have resolved completely by 15 minutes (the definition of a grade 1 concussion) then the athlete can return to play.
Grade 2 concussion:
- Merits removal from the game for the remainder of the day. If the athlete’s neurologic examination is normal, he or she may return to play in 1 week.
Grade 3 concussion:
- Merits transport to an emergency room for evaluation and possible neuroimaging.
- Following this evaluation the patient’s neurologic examination should be repeated both at rest and after exertion.
- –If the examination is normal and the initial loss of consciousness was brief then the player can return after 1 week. If the loss of consciousness was more prolonged then 2 weeks are recommended.
What is post concussion syndrome?
Following a concussion, up to 90% of patients will continue to experience headaches and dizziness for at least 1 month.
- Irritability, depression, insomnia, and subjective intellectual dysfunction
- Fatigue, anxiety, and excessive noise sensitivity
- Unusually sensitive to the effects of alcohol
- Preoccupied with fears of brain damage
The peak of symptom intensity is generally 1 week after injury, and most patients are symptom free by 3 months.
BUT CAN STILL HAVE SX FOR UP TO A YEAR LATER
What helps distinguish a stroke and a transient ischemic attack?
Duration of symptoms
TIA: minutes to 1-2 hours, resolving within 24 hours
Stroke: Sx > 24 hours
The carotid arteries supply blood flow to _____
Frontal and parietal lobes
Most of temporal lobes and basal ganglia
The vertebrobasilar territory supplies blood flow to _____
Occipital lobes
Brainstem
Cerebellum
Thalami
What are the branches of the basilar artery?
PCA
Superior cerebellar
AICA
Pontine arterties
How should you address blood pressure in an ischemic stroke patient?
BP should not be lowered in the first few days of an ischemic stroke UNLESS EXTREMELY ELEVATED
As many as 20% of ischemic strokes have no discernible etiology despite a thorough diagnostic evaluation. T/F?
False; as many as 30%
Sources of cardioembolism that can cause an ischemic stroke?
Afib
Mechanical prosthetic valve
Acute MI
Low LVEF
Other than cardioembolism, other causes of ischemic stroke?
Large vessel atherosclerosis
- Can affect the carotid bifurcation, the major intracranial vessels, or the extracranial vertebral artery.
Small vessel strokes aka lacunar strokes
- Pure motor or pure sensory stroke associated with HTN/DM
Risk factors for stroke are similar to those of coronary heart disease and include elderly age, hypertension, smoking, diabetes, hyperlipi- demia, heart disease, hyperhomocysteinemia, and family history.
Clinical presentation of stroke that results from lesion from anterior circulation? Middle? Posterior?
Anterior:
- Aphasia (can’t use or comprehend words)
- Agnosia (loss of ability to recognize objects, persons, sounds, shapes, or smells)
- Apraxia (can’t execute or carry out purposeful movements)
Middle (left MCA)
- Aphasia
- Hemiparesis
- Gaze paresis
Posterior/vertebrobasilar:
- Diplopia
- Vertigo
- Crossed neurologic findings
- Homonymous hemianopia
What sx would raise suspicion for a hemorrhagic stroke?
HA
Decreased level of consciousness
Extreme elevations of hemorrhagic stroke
The symptoms of an intracerebral hemorrhage cannot be reliably distinguished from those of an ischemic stroke on clinical grounds alone. T/F
True
List three contraindications to t-PA.
What if pt has a contraindication?
Recent stroke
Active bleeding
H/o intracranial hemorrhage
*Not a candidate? Should be treated with ASPIRIN!
What is secondary stroke prevention?
IMPLEMENT RIGHT AWAY
Antiplatelet drugs
- Aspirin
- Clopidogrel, or
- Combination of aspirin and extended release dipyridamole
–> are the mainstays of stroke prevention treatment for most patients with ischemic stroke and TIA
Pt has a stroke and is discharged on which medication?
Long term antiplatelet therapy
*unless they have afib, long term warfarin
Risk factors for SAH?
Age (mean age is 50)
Female
Hypertension
Smoking
What chemistry change is frequently seen in those with SAH
Hyponatremia; correlating with:
- Increased ANP
- Cerebral salt wasting
- SIADH
ECG changes/complications from SAH?
QT prolongation
T wave inversion
Arrhythmias
What is a sentinel bleed?
Intermittent aneurysmal subarachnoid hemorrhage causing lesser headaches that precede the “worst headache” that occurs with rupture of the aneurysm.
Clinical complications of SAH?
(can occur days after ruptured aneurysm with SAH)
Vasospasm:
- Most alarming complication of aneurysmal subarachnoid hemorrhage in which irritation causes constriction of major cerebral arteries, vasospasm lethargy, and cerebral infarction
Acute communicating hydrocephalus:
- subarachnoid blood obstructs the subarachnoid granulations in the venous sinuses –> CT shows enlarged lateral, third, and fourth ventricles –> headache, vomiting, blurry and double vision, somnolence, and syncope.
Where are the locations of intracerebral aneurysms that cause subarachnoid hemorrhage
Subarachnoid hemorrhage is the underlying cause of approximately 10% of stroke
- Ruptured saccular or berry aneurysms account for up to 80% of nontraumatic SAH (=worst prognosis)
> 3/4 of intracerebral aneurysms arise in the anterior circulation. The most frequent sites of aneurysms are in:
- ACA (up to one-third of aneurysmal subarachnoid hemorrhages)
- followed by the bifurcation of the internal carotid artery with the posterior communicating artery
- THEN bifurcation of the internal carotid artery with the middle cerebral artery.
Risk factors for aneurysms?
- Chronic severe hypertension with diastolic blood pressure greater than 110 mmHg
- Liver disease
- Tobacco and alcohol use
- Vasculitides
- Collagen vascular disorders such as Marfan syndrome
- Infections (mycotic aneurysms)
- Oral contraception
What are some non-aneurysmal causes of SAH?
- Trauma
- AVM
- Cocaine or amphetamine use
What is the most sensitive imaging choice for SAH?
Head CT without contrast
- Sensitivity of CT is greatest 24 hours after the event with 50% still detectable after 1 week.
Next step in suspected SAH but CT is negative?
Negative head CT occurs in 10–15% of cases
Get LP and look for xanthochromnia
How is SAH graded?
Grade I
- Alert with mild headache and nuchal rigidity
- 5% chance of deteriorating with a 3–5% mortality risk.
Grade II
- Moderate-to-severe headache and nuchal rigidity
- 6–10% mortality.
Grade III
- Added confusion.
Grade IV
- Stupor and moderate hemiparesis.
Grade V
- Comatose with signs of severe increased intracranial
pressure
- Worst prognosis with 80% chance of deteriorating, 25–30% rebleeding rate, and 50–70% mortality. Delayed vasospasm is a calamitous complication that occurs in up to 20% of cases.
Mortality rates of SAH?
Up to 60% of patients die in the first 30 days
- 10% die instantly without warning.
Hospitalized? 40% die in first 30 days, with worsening of mortality to 50–80% with rebleeding.
How do you treat SAH?
Grade I and II: observe
Low grade and need to reduce rebleeding?
- Endovascular coiling > clipping
- Clipping should be performed in the first 48 hours after onset or be delayed for 2 weeks to avoid the window of greatest risk for vasospasm, especially with complicated high-grade cases.
Suspect ruptured aneurysm? Consider emergent conventional angiography
Mainstay medical tx:
Triple H therapy
- Hypertensive, Hypervolemic, Hemodilution –> to maintain cerebral perfusion
- Nimodipine (CCB) - prevents cerebral vasospasm
35yo woman admitted last week for SAH caused by a left MCA aneurysm. Today during rounds she appears much less alert. What happened?
Delayed vasospasm lethargy (and also acute hydrocephalus) can arise days after a ruptured aneurysm with subarachnoid hemorrhage.
Emergent neuroimaging should be performed to assess the need for angiography or ventriculostomy.
Pt has hyperacute onset of left hemiparesis 1 week after admission for a subarachnoid hemorrhage. What is the most sensitive imaging for detecting vasospasm induced ischemic injury?
Diffusion-weighted MRI
- More sensitive than CT for detecting hyperacute ischemic injury caused by vasospasm
How do carotid dissections present and what is it associated with?
Dissections can present with headache or thromboembolic cerebrovascular events.
Often associated with a Horner syndrome
Predisposing factors to spontaneous craniocervical dissection?
Fibromuscular dysplasia
EDS
Marfans
What is moyamoya disease?
- IDIOPATHIC
- NON-inflammatory
- Cerebral vasculopathy characterized by progressive occlusion of the large arteries at the circle of Willis.
*The characteristic moyamoya vessels refer to the small penetrating arteries that hypertrophy in response to chronic cerebral ischemia.
How are drugs related to stroke?
Cocaine and amphetamines are associated with both ischemic and hemorrhagic stroke.
H/p intravenous drug abuse should raise the suspicion of endocarditis and HIV disease.
Other rarer infectious etiologies of stroke include tuberculous meningitis and varicella zoster.
Coagulation disorders that predispose to stroke?
Malignancy, antiphospholipid antibodies, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden mutation, prothrombin gene mutation, and hyperhomocysteinemia.
Adult onset seizure is caused by ____ until proven otherwise
Tumor or stroke
In general seizures, the seizure usually has a focal onset. T/F?
True
right hand twitches, then right arm, then LOC
Treatment following the first seizure in adults alters the prognosis of epilepsy but not the relapse rate. T/F
False
Tx after first decreases relapse rate but NOT the prognosis
50% of patients with a single seizure with no known antecedent event will develop epilepsy. T/F?
False
10-25% will develop epilepsy
*Some neurologists will treat after first, some after 2 seizures
What is the most common inherited form of stroke disorder?
CADASIL
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
Start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 to 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and urinary incontinence.
A young soldier fainting during the military parade on a hot summer afternoon. Dx?
Orthostatic syncope
- Tilt table needed since orthostatics might not be enough when it happens in young healthy people
Causes of orthostatic syncope?
Elderly:
Hypovolemia
Increased venous pooling from prolonged rest
Polypharmacy (BB, loop, nitrate)
Autonomic system abnormality
- Diabetic neuropathy; interruption of the sympathetic reflex arc inhibits adequate adrenergic response to standing
Causes of autonomic failure that can lead to orthostatic syncope?
Diabetic neuropathy (most common) Amyloidosis Syphilis SCI Syringomyelia Alcoholic neuropathy Guillain-Barré syndrome
Orthostatic hypotension tx?
- Avoid hypovolemia, electrolyte imbalance, and excess alcohol intake.
- Increase salt intake
- Fludrocortisone or midodrine
- Elastic hose to enhance venous return
- Antiarrhythmics if applicable
First step in evaluating exertional syncope?
Echo
- Exertional syncope suggests cardiac outflow obstruction, mainly caused by aortic stenosis
What is a pseudoseizure and how can you tell?
- Resembles epileptic seizure but having purely psychological causes
- Lacks the EEG characteristics of epilepsy
- Patient may be able to stop it by an act of will.
Ex: four-extremity motor activity yet is wide awake and aware of his surroundings.
A 35-year-old man is suspected to have pseudoseizure. Next step in dx?
Video EEG (vs resting EEG) - 1-3% of pseudoseizure have true organic epilepsy
Risk factors for pseudoseizure?
Sexual abuse
Head Injury
*Asthma has been reported in 25% of pseudoseizure
Common vs classic aura?
Classic: Migraine with aura (A/V/smell/taste disturbances 5-30 min before pain)
Common: Migraine with no aura
Who gets migraines more commonly in children and in adults?
1: 1 ratio in children
3: 1 in adults female to male
Aura vs prodrome of migraine?
Prodrome (think more mental):
- Nonspecific phenomenon that can occur days but more often hours before the actual head pain.
- Depression
- Euphoria
- Irritability
- Increased urination, defecation, anorexia, or fluid retention.
- Often photophobia, phonophobia, and hyperosmia accompany the prodrome.
Aura (aura or prodrome can precede the actual head pain, but an aura is often associated with frank neurologic dysfunction usually transient in nature):
- Visual auras are the most common (scotomas, teichopsias, fortification spectra, photopsias, and distortion of images)
- Sensory auras such as numbness and tingling in a limb are second most common
- Aphasia and hemiparesis occur less often.
Describe the pain associated with migraines
Unilateral in 65%
Usually periorbital and can extend to cheek and ear; but can occur anywhere
Lasts 4-8 hours but can last for several days
Pulsating, throbbing
N/V/photophobia/phonophobia
What lab would you want to order in a 60+yo patient with new headache?
ESR
- Consider temporal arteritis
What is pseudotumor cerebri and is seen in which patients
Aka benign intracranial hypertension w/o evidence of a CNS malignancy
Sx: headaches often associated with visual disturbances.
Seen in female patients who are obese and often have menstrual irregularities.
Pain associated with acute glaucoma can begin after the use of _____
anticholinergic drugs
What are the four meds used in migraine abortive therapy?
Triptans
Ergotamine (when triptans fail)
Dihydroergotamine
Midrin (acetaminophen, dichloralphenazone, isometheptene mucate)
Contraindications to triptans?
H/o CAD
HTN
*If pt has hemiplegia or blindness as an aura, do not use triptans
How do triptans work? Side effects?
5-HT 1D agonist Use no more than 3 doses/24 hours Side effects - N/V - Numbness, tingling in fingers and toes
Common triggers of migraines?
Stress Excessive/too little sleep Physical activity Smoking Weather Smells - paint, fumes Caffeine withdrawal Food - chocolate, cheese, wine, citrus fruits, coffee, tea, tomatoes
When do you use prophylactic migraine meds?
At least 3 attacks per month OR
if acute therapy is not enough
Migraine prophylactic meds?
Anticonvulsants (topiramate, divalproex, and gabapentin; MOST FREQUENTLY USED, TOPIRAMATE!)
Beta-blockers (propranolol)
Verapamil
Antidepressants (duloxetine, amitriptyline, and nortriptyline)
2nd line:
- Methysergide maleate
- Lithium carbonate
- Clonidine
- Captopril
- MOAI
Major side effects of propanolol?
- Depression
- Fatigue
- Alopecia
- Bradycardia
- Cold extremities
- Postural dizziness.
Conditions that cause papilledema?
Meningitis Hydrocephalus Space occupying lesions Dural sinus thrombosis Pseudotumor cerebri *Presentation of HA with blurred vision and papilledema = medical emergency!
How do you define ICP?
> 200mm H2O or
>250mm H2O in obese
Typically, imaging in pseudotumor cerebri pts is normal. T/F
True
Imaging for increased intracranial pressure? What if its negative?
CT without contrast
- CT with AND without contrast will help determine if mass is tumor, hemorrhage, abscess, etc
- *MRI can be useful to r/o dural sinus thrombosis
If negative, do LP
Pseudotumor cerebri is associated with a normal LP. T/F
True
What is papilledema?
Disk edema from raised intracranial pressure; commonly bilaterally.
***inflammation, tumors, infections, ischemia can cause disk edema but papilledema refers to ICP
Sx of papilledema?
Visual dysfunction - transient visual obscuration or graying out/dimming of vision.
- Sudden visual loss from intraocular hemorrhage as a result of neovascularization from chronic papilledema
- Blurring and distortion of central vision
- Progressive loss of peripheral vision (often beginning in the nasal inferior quadrant)
- Loss of color perception
- Loss of central visual fields can occur later on
How to dx pseudotumor cerebri?
Dx of exclusion!
Requires the findings of:
- Increased intracranial pressure (papilledema)
- Nonfocal neurologic signs (except 6th nerve palsy)
- Normal imaging studies (except for slit-like ventricles)
- Normal CSF studies except for an elevated opening pressure
Pseudotumor cerebri sx?
HA*, dizziness, N/V
Transient visual obscuration
Tinnitus
Horizontal diplopia 2/2 CN VI palsy
HA is classically diffuse, worse in morning, worsens with valsalva
Most common exam abnormality is b/l disk edema
Pseudotumor cerebri risk factors?
Obesity
Recent weight gain
Female gender, especially in the reproductive age group
Menstrual irregularity
How do you treat pseudotumor cerebri?
Short term: High-volume LP at initial evaluation.
Long term: Acetazolamide (CA inhibitor to lower ICP)
If progressive visual loss ensues –> then create optic nerve sheath trations by cutting patches in the dura surrounding the optic nerve allowing the efflux of cerebral spinal fluid, which in turn reduces pressure.
CAN CAUSE BLINDNESS
If medical management is insufficient:
Lumbar-peritoneal shunt or VP shunt
What things can cause things that look like papilledema (since papilledema is optic disc swelling due to ICP)?
trauma, inflammation, tumors, infections, ischemia
Neuro exam findings of someone with pseudotumor cerebri?
normal except for visual loss (loss of color perception, loss of visual fields, transient visual obscuration) and a sixth nerve palsy
Where is the abducens nucleus and describe how it reaches the orbit
abducens nucleus is located in the lower dorsal pons.
- -> abducens nerve exits the pons ventrally and ascends in the prepontine cistern via the subarachnoid space
- -> then rises over the petrous apex of the temporal bone and enters the cavernous sinus laying between the carotid artery and V1
- -> through superior orbital fissure and into the orbit
How would you work up a suspected 6th nerve palsy?
ANA, ESR - inflammatory, vasculitis
Glycosylated hemoglobin - DM
CBC - infectious
MRI brain and orbits - vascular; aneurysms, mass lesions (sarcoid), demyelinating, neoplastic, traumatic
Diplopia is caused by _____. Binocular vs monocular?
Caused by lack of visual fusion
- Binocular diplopia (denotes double vision arising from mis- alignment of both eyes) –> think underlying primary neurologic problem
- Monocular diplopia –> think ophthalmologic disorder involving lens, cornea, vitreous humor, or iris.
*covering one eye resolves double vision in BINOCULAR but does not resolve in monocular
Pt with horizontal diplopia and says its worse with far vision. What muscle might be involved?
Diplopia worse on near vision?
- suggests a problem with the medial rectus
Diplopia worse on far vision and lateral objects?
- suggests a problem with the lateral rectus
Pt with vertical diplopia and says its worse with near vision. What muscle might be involved?
Vertical diplopia that worsens on near vision suggests a problem with either the INFERIOR oblique or SUPERIOR oblique.
Pt has a right CN IV lesion. What is their head doing?
Superior oblique intorts (top of eye towards nose) the eye + secondarily depress and abduct eye –> lesion? –> extort, deviate upward, and drift inward
May compensate by tilting head to the left
How to treat CN VI palsy?
Isolated and presumed ischemic-related?
- Observe for 1 to 3 months.
- Patching of the involved eye can help alleviate diplopia symptoms temporarily.
- Prism therapy can also be used.
- Maybe botulinum toxin
- All fail? Consider surgery
What is the red lens test and what is it used for?
Used for evaluating binocular diplopia
- Red lens is placed over an eye, most commonly the right eye, and the patient is asked to look at the nine positions of a cardinal gaze.
(1) image separation will be greatest in the direction of the weak muscle
(2) the image that is the furthest away from the midline is a false image and corresponds to the eye with impaired motility.
Other than the red lens test, how else can you evaluate binocular diplopia?
Alternate cover test
- Ask the patient to fixate on an object in each position of gaze. As the patient moves the eyes in each position, deviations in the eye as each one is alternately covered may be seen.
Describe the course of the facial nerve from the brainstem
The facial nerve emerges from the brainstem at the pons to traverse the cerebellopontine angle and then through the temporal bone.
- -> It emerges at the STYLOMASTOID FORAMEN to pass through the substance of the parotid gland and divide into branches that innervate the various parts of the face.
- Facial nerve passes through the MIDDLE EAR and TEMPORAL BONE
Facial paralysis associated with ________ suggests cerebellopontine angle and internal auditory canal disorders.
hearing loss and/or dizziness, vertigo, or imbalance
_____ is the most common cause of isolated facial paralysis in children
Acute otitis media
Otitis media and cholesteatoma can be associated with facial paralysis. T/F
True
What is a cholesteatoma
Benign tumor of epithelial debris that is produced when the squamous layer of the eardrum is trapped and cannot exfoliate properly. (cheesy epithelial debris in the ear canal or a pearly white tumor behind the ear drum)
- usually occurs in patients that have preexisting ear problems/hearing loss/foul-smelling purulent otorrhea.
- grows slowly and can be present for years without causing many symptoms –> neglected? –> can destruct ossicles, the inner ear or the facial nerve.
What are facial neuromas?
Schwannomas of the facial nerve (rare!)
- Benign tumors of the facial nerve that grow slowly and produce a slowly progressive (over several months, not days) form of facial paralysis.
- -> tumor in middle ear portion of facial nerve? –> conductive hearing loss!
- -> tumor in the internal auditory canal? –> sensorineural hearing loss!
Get audiogram and MRI with contrast, call neuro-otologist
Bilateral facial paralysis ddx?
Lyme disease
Guillain-Barré syndrome
Herpes zoster oticus (or Ramsay Hunt syndrome)
What is/causes Ramsay Hunt?
Reactivation of VZV in geniculate (sensory facial nucleus) –> vesicles in area of sensory distribution –> burning, painful
*Pain can linger for a year, despite resolution of active infection “postherpetic neuralgia”
How do you treat Ramsay hunt?
Anti-herpes virus medication for 7 to 10 days.
- Ganciclovir and valacyclovir (better oral absorption, less frequent dosing)
- Acyclovir (IV and for severe infections in severely immunocompromised; oral is poorly absorbed)
- Topical acyclovir can help speed healing of vesicles.
- Patients are contagious and can spread the virus to susceptible individuals as long as vesicles are present.
Facial paralysis?
- Steroids! Can reduce pain and improve chances of recovery but might risk worsening immunocompromised state –> dissemination of herpes to brain or eye
Hearing loss and vestibular symptoms can occur in patients with Ramsay Hunt syndrome. T/F
TRUE
Can produce ipsilateral sensorineural hearing loss and vestibular weakness
What is Bell Palsy? How to tx?
Facial nerve palsy, likely caused by viral (herpes simplex implicated and isolated)
High spontaneous recovery rate BUT
- Antiviral medications (ganciclovir or valacyclovir) and oral steroids have been shown to improve return of facial function compared to either medication alone or to placebo.
Bell Palsy can be treated with surgery. T/F
Surgery is only indicated for cases of facial paralysis where ENoG and EMG both show absence of facial function.
Patients with facial paralysis can develop loss of vision in the ipsilateral eye. T/F?
True
- because of the loss of the blink reflex and decreased lacrimation, the affected eye can dry out –> exposure keratitis –> loss of vision in the affected eye.
Ocular lubricant, call ophtho, f/u with PCP
The greater the weakness in Bell Palsy or Ramsay Hunt, the longer the recovery. T/F?
TRUE
An isolated facial nerve branch paralysis is caused by malignancy until proven otherwise. T/F
TRUE
By far the most common cause of acute facial weakness in adults is Bell palsy. T/F
TRUE This disorder is caused by reactivation of herpes simplex virus.
MS sx include hemiparesis. T/F
True, Hemiparesis INO Optic neuritis --> resulting in Marcus Gunn Bowel/bladder incontinence Relapsing and remitting course
What are the classes of MS and which one is most/least common?
Benign (20% of cases)
- Least severe
- Few, mild, early attacks
- Complete clearing of sx, minimal/no disability
2. Relapsing/Remitting MS (25%) - Frequent, early attacks
- Less complete clearing
- Long periods of stability
- Some degree of disability is usually present.
3. Secondary chronic progressive (40%) - Increasing attacks
- Fewer and less complete remissions after each attack.
- Can worsen for many years then level off –> moderate to severe disability
4. Primary progressive (15%) - MOST DISABLING
- Severe onset, slowly progressive
- NO clearing of sx
Moving to a non-temperate zone when youre younger than 15 decreases risk of developing MS. T/F?
True
Risk of MS is increased in individuals born or living in temperate zones
- BUT that people born or migrating to low-risk areas (i.e., nontemperate zones) prior to 15 years of age have decreased risk.
MS is related to genetic and environmental factors. T/F?
True
Other than diplopia, what is another sx resulting from brainstem compromise in MS pts (occurs in 1% of pts)?
Trigeminal neuralgia
- There are other causes but if young pt with trigeminal neuralgia, think MS
Facial Myokymia (wormlike movement of muscles that the pt feels but hard for observer to see) from orbicularis oculi muscles
What is Lhermitte sign?
Sensations of electricity running down their spine, sometimes extending into the limbs
What happens if a pt with MS takes a hot bath?
MS patients can experience sudden and transient neurologic deterioration if their body temperature is elevated. This can occur with fever, increased physical exertion, or taking a hot bath.
What kind of imaging do you get for MS pts? Where would you find the lesion?
- T2- weighted MRI (light up)
- Corpus callosum
- Periventricular regions
- BUT FLAIR IS BETTER –> provides increased sensitivity and specificity for MS white matter lesions
What CSF findings would support MS dx?
Elevated IgG index
Presence of oligoclonal bands
Increased myelin basic protein support the diagnosis.
MS is a clinical dx that does NOT need CSF or MRI. T/F
True
Imaging and CSF help confirm
MS DDx?
ADEM (post infectious) Guillain Barre Infections (syphilis, lyme, cat scratch, etc) Behcet Sarcoidosis SLE RA Bee/wasp/snake bite Postpartum optic neuritis Neuromyelitis optica Recurrent optic neuromyelitis with endocrinopathies
MS Treatment?
IV steroids, especially during acute attacks
Immunomodulating agents (given subq/IM; modifies course of MS)
- Interferon beta-1a
- Interferon beta-1b
- Glatiramer acetate (synthetic polypeptide of MBP)
- Mitoxantrone (an antineoplastic immunomodulatory agent, also has been shown to improve neurologic disability and delayed progression of MS in patients with worsening relapsing-remitting or secondary- progressive disease)
- Cyclophosphamide
- Methotrexate
- Cyclosporine
Steroids have shown to decrease future attacks in MS pts
False
No effect on future attacks and no effect on natural hx of disease
Earlier age of disease onset is usually associated with benign or relapsing remitting forms of MS.
True
Other than MS, in what other conditions can you find oligoclonal bands
SLE Neurosarcoidosis Subacute sclerosing panencephalitis SAH Syphilis CNS Lymphoma
The symptoms of MS seem to worsen with elevation of temperature or fever. T/F
True
What is acute disseminated encephalomyelitis?
ADEM is an acute, UNI-phasic syndrome (vs MS), probably caused by immune-mediated INFLAMMATORY DEMYELINATION.
It often is associated with - Postviral illness - Immunization - Vaccination "ADEM is VIP"
What is the hyperacute form of ADEM?
Acute necrotizing hemorrhagic encephalomyelitis (ANHE)
- Similar sx and cause
Sx of ADEM?
Multiple neurologic signs and symptoms (brainstem, spinal cord, cerebrum, optic nerves, and cerebellum)
- HA, N/V, confusion –> obtundation and coma
- Hemiparesis, hemisensory compromise
- Ataxia
- Optic neuritis
- Transverse myelitis
- Seizures, myoclonus
- Memory loss.
- Sx appear SUDDENLY 1-3 weeks after infection
The primary finding in ADEM is perivenular axonal damage. T/F?
False; primary finding is perivenular demyelination, with relative SPARING OF AXONS
How do you treat ADEM?
Supportive and symptomatic
- IV corticosteroids to shorten course
In the absence of a biological marker, how can you distinguish MS vs ADEM?
certain features are more indicative of ADEM and include:
- Viral prodrome or recent vaccination exposure
- Early-onset ataxia
- High lesion load on MRI, involvement of the deep gray matter, especially thalami
- Absence of oligoclonal bands.
ADEM is a multifactorial, involving genetics and environment. T/F
True
A CT or MRI done before a spinal tap is preferred when evaluating for meningitis. T/F?
True
MRI has better resolution but do CT if it’s faster
- Imaging will tell you exclude increased ICP caused by impaired CSF drainage or a space-occupying lesion (since increased ICP could lead to herniation and death) BEFORE doing an LP
What empiric abx would you want to use in a suspected meningitis?
third-generation cephalosporin such as ceftriaxone or cefotaxime
+ vancomycin, IV dexamethasone, IV acyclovir.
*give these AFTER blood and CSF (or even when there is a delay in doing an LP)
What is the latex particle agglutination test?
Test where an antibody or antigen coats the surface of latex particles (sensitized latex). When a sample containing the specific antigen or antibody is mixed with the milky appearing sensitized latex, visible agglutination is noted.
USED TO DETECT:
- Hib
- Strep pneumoniae
- Neisseria meningitidis A, B, and C soluble antigens
Most common cause of bacterial meningitis ? Viral meningitis?
Bacterial:
Neonate - ecoli, listeria, gbs
children - s. pneumo, hib, n meningitis,
60+ - s. pneumo, listeria, GNR
Viral:
Enterovirus
Typical first line to tx bacterial meningitis?
Penicillin G or
Ampicillin + 3rd gen cephalosporin
Add vanc if you don’t know susceptibility to S. pneumo
Ampicillin covers most ____. Ceftriaxone and Cefotaxime cover most ____
Ampicillin:
Pneumococcus
Meningococcus
Listeria
Cef:
Gram negatives
Ampicillin resistant H flu
Penicillin G is used to treat
gram negative cocci
gram positive bacilli
(gram negative bacilli is treated with 3rd gen cephalo or AGs)
Do you give IV corticosteroids in bacterial meningitis?
Pediatrics, YES
Adults, maybe.
- If it’s S. Pneumo meningitis, give!
Tx of viral meningitis?
Supportive
If HSV?
- IV acyclovir
- Might have residual headache with recovery
- Children might have sensorineural hearing loss
Suspect meningitis and there’s a maculopapular rash. Next step?
Chem 20 CBC INR Blood culture IV abx (penicillin G OR ampicillin) ---if no rash, start ceftriaxone/cefotaxime + vanc
A viral meningitis can have predominantly PMNs. T/F
True
In early viral, can have PMN predominance making it hard to tell if its viral or bacterial
What are the two most common sources of botulinum spores?
Honey
Soil contamination
CDC recommends that honey should not be given to ____
infants
Most common cause of foodborne botulism in the USA?
Home canned vegetables
*BUT INFANTILE BOTULISM IS THE MOST COMMON CAUSE OF BOTULISM IN THE USA
Clinical presentation of infantile botulism?
constipation hypotonia respiratory difficulties cranial nerve abnormalities hyporeflexia.
How many types of botulinum are there and which ones cause infantile botulism?
7 types, A-G
A and B cause infantile botulism
Mechanism of the botulinum toxin?
Toxins are produced and absorbed throughout the intestinal tract after colonization occurs.
- -> irreversibly binds to presynaptic cholinergic receptors at motor nerve terminals and is then internalized
- -> Inside the cell, the toxin acts as a protease, damaging membrane proteins
- -> inhibiting the release of acetylcholine and disrupting exocytosis.
- -> inhibition of acetylcholine release results in disruption of neurotransmission between the nerve and end plate on the muscle.
How do you test for infantile botulism?
The best way to test for infantile botulism is through stool samples via a mouse bioassay.
More than ____ of infants with botulism will eventually require mechanical ventilation.
70%
What finding is typical on MRI for HIV-associated dementia?
Diffuse cerebral atrophy
HAD ddx?
Cerebral lymphoma
Progressive multifocal leukoencephalopathy
CNS infections
Toxic metabolic states (thyroid, B12 deficiency, alcoholism, meds, illicit drug)
Metastatic malignancy
How do you treat HAD?
HAART
- protects against HAD and induces remission of HAD
What are the early sx of HAD?
Difficulty with concentration, attention, and slowness of thinking.
Forgetfulness
Increasing difficulty performing complex tasks.
Personality changes begin to appear such as apathy, social withdrawal, and quietness.
Tripping or falling along with poor handwriting are the more common motor symptoms.
–> as the disease progresses, the ataxia worsens and can become disabling. Myoclonic jerks, postural tremor, and bowel and bladder dysfunction can be present in the later stages of the disease.
–> at end stage of the disease are unable to ambulate, have incontinence, and are almost in a vegetative state.
Focal neurologic deficits tend to be absent in HAD. T/F?
TRUE
Early neuropsych testing can be normal in HAD. T/F?
True; however, as time progresses there is evidence of a subcortical dementia.
- difficulty in concentration, motor manipulation, and motor speed. Mild problems with word finding and impaired retrieval can be present.
Later neuro findings in HAD?
Hyperreflexia
Spasticity
Frontal release signs can be found.
- apraxia (inability to perform previously learned tasks) and akinetic mutism (severely decreased motor-verbal output) can develop.
Lhermitte’s sign can be seen in what conditions?
Suggests lesion to dorsal columns
- MS
- Transverse myelitis
- Behcets
- B12 deficiency
- Trauma
HIV-associated dementia is typically associated with _____ (sx). What if it’s mild HAD?
Forgetfulness
Difficulty concentrating
Slowness in thinking
Loss of coordination
Mild? May present with depression and anxiety
What is Creutzfeldt-Jakob disease?
Degenerative, fatal brain disorder.
Onset around 60yo, rapid course, death within 1 year
Early stage sx:
- Failing memory
- Behavioral changes
- Lack of coordination
- Visual disturbances.
- Progresses –> mental deterioration becomes pronounced, and involuntary movements, blindness, weakness of extremities, and coma can occur.
How is CJD categorized?
Sporadic CJD
- Most common
- Disease without any risk factors
Hereditary CJD
- 5-10%
- FamHx of disease and/or positive tests for genetic mutation
Describe disease course of CJD (symptoms)
CJD is characterized by rapidly progressive dementia. Initially:
- Problems with muscular coordination
- Personality changes
- Impaired memory, judgment, and thinking
- Impaired vision (diplopia, distorted vision, visual agnosia) –> may go blind
- Insomnia, depression, or unusual sensations.
- NO FEVER/FLU LIKE SX
- Often develop MYOCLONUS
- -> eventually lose ability to move/speak –> coma –> PNA, infections, death
What causes CJD?
Some organism that isn’t really a bacteria or virus
Difficult to kill
No genetic information (DNA or RNA)
Long incubation period before sx (up to 40 years)
Leading theory that CJD is caused by a prion
How is CJD spread?
Grafts of dura mater
Transplanted corneas
Implantation of inadequately sterilized electrodes in the brain
Injections of contaminated pituitary growth hormone derived from human pituitary glands taken from cadavers
Blood donors are disqualified if they have resided for more than 3 months in a country where BSE is common. T/F?
TRUE
Even though there is no evidence that blood from sporadic CJD people is infectious, prions can accumulate in the lymph node, spleen, tonsils!
How do you dx CJD?
No diagnostic test, RULE OUT OTHER CAUSES
Can get EEG (sensitivity and specificity of 66% and 74%)
- Periodic sharp wave complexes 1-2 Hz
LP
- Protein marker in CSF, 14-3-3 protein
- ONLY WAY TO CONFIRM DX IS A BRAIN BIOPSY OR AUTOPSY
Medications to control CJD?
NONE
No drug to cure or control CJD
Tx aimed at symptomatic
- Opiates for pain
- Clonazepam, valproic for myoclonus
Normal sterilization procedures such as cooking, washing, and boiling do not destroy prions. T/F
True
CHLORINE BLEACH FOR 1+ HOUR
AUTOCLAVE AT LEAST 1 HOUR at 132–134°C (269–273°F)
Lancinating pain with associated sensory ataxia, cranial nerve abnormalities, and impotence or bowel and bladder dysfunction is a classical presentation for ______
Tabes Dorsalis
- Need RPR or VDRL for dx
- RPR can have frequent false positives; confirm with CSF
CSF Findings in neurosyphilis ?
◆ Elevated CSF protein up to 200 mg/dL
◆ Lymphocytic pleocytosis
What is an Argyll Robertson pupil and where do you see it?
Small pupils that constrict when focusing but fail to constrict when exposed to bright light (accommodate but do not react)
Neurosyphilis MS DM Sarcoidosis Lyme Wernicke Encephalopathy
You suspect neurosyphilis but RPR and VDRL (sensitive) are negative. What next?
Serum study for Treponema pallidum-specific antibodies.
- FTA-ABS test (specific!)
- T. pallidum hemagglutination test (TPHA)
- Microhemgglutination assay-T. pallidum (MHA-TP)
Neurosyphilis has similar presenting sx as what other infectious causes? How do you tell them apart?
HIV or hepatitis B and C can present with very similar symptoms of sensory ataxia, cranial mononeuropathies, and pain.
Look at TYPE of pain:
- neurosyphilis: lancinating pain
- others: burning type
Syphilis is a risk factor for acquiring HIV. T/F
True
* and HIV patients with syphilis are at increased risk for developing neurosyphilis and may do so earlier than HIV-negative individuals
T. pallidum enters the central nervous system at the same time that individuals develop primary and secondary syphilis. T/F
T. pallidum enters the central nervous system at the same time that individuals develop primary and secondary syphilis. Pathogenic changes consist of endarteritis of ter- minal arterioles with resultant inflammatory and necrotic changes. In the central nervous system, T. pallidum causes meningeal inflammation, arteritis of small and medium-sized vessels with subsequent fibrotic occlusion, and even- tually direct neuronal damage.
Pathogenic changes caused by T. pallidum?
Endarteritis of terminal arterioles with resultant inflammatory and necrotic changes.
In CNS:
- -> causes meningeal inflammation
- -> arteritis of small and medium-sized vessels with subsequent fibrotic occlusion
- -> eventually direct neuronal damage.
What is the most common clinical exam finding of neurosyphilis?
Hyporeflexia (50%)
Also:
- Sensory impairment (48%)
- Pupillary changes (43%) including Argyll Robertson pupils
- Cranial neuropathy (36%)
- Dementia or psychiatric symptoms (35%)
- Positive Romberg test (24%).
When do stroke like sx present in someone with syphilis?
In pts with neurosyphilis, 5-7 years after initial infection, can have cerebrovascular and meningovascular disease –>
Ischemia along MCA and meningeal inflammation
What clinical syndromes are associated with neurosyphilis and what is the timing of each?
Syphilitic meningitis (1-2 years)
- Cranial mononeuropathies
- Hydrocephalus
- Focal hemispheric signs
Cerebrovascular and meningovascular disease (5-7 years)
- Can present as stroke in evolution
- MCA and meningeal inflammation
General paresis (10 years)
- Impairment of higher cortical function
- Dementia
- Frontotemporal encephalitis
- Cerebellar dysfunction
- Pyramidal tract dysfunction
- Features suggesting psychiatric illness
Tabes dorsalis (10-20 years)
- Lancinating pain
- Sensory ataxia
- Bowel/bladder dysfunction
- CN abnormalities
Gummatous neurosyphilis (anytime) Asymptomatic neurosyphilis (anytime)
EMG studies are normal in tabes dorsalis. T/F?
True
But absent H reflexes are common because damage to dorsal ganglion
If EMG is abnormal, doubt tabes dorsalis!
Tx of neurosyphilis?
High dose IV Penicillin G
- 2-4 million units q4h x 10-14 days
Allergy? Ceftriaxone + Doxy
Tx CNS toxo? Prophylaxis?
Pyrimethamine
- Selective DHF reductase inhibitor
- Must give folate with it
- Give with sulfadiazine (synergistic)
Significant edema?
- Dexamethasone
PPx:
- Bactrim; indicated for HIV+ with CD4
Clinical features of intracranial toxo?
Usually, the patient experiences a deterioration in mentation over days to weeks
- -> headaches, seizures, or cognitive impairment
- –> motor or sensory deficits can also be seen.
- T. gondii can also affect other organs such as the eyes or lungs.
Confusion, drowsiness, focal weakness, aphasia, and seizures later on in the course
Coma can ensue within days to weeks if no treatment is started
Radiculomyelopathy can occasionally be present
Other: ataxia, cranial nerve palsies, hemianopia, personality changes
How to dx CNS toxo?
T. gondii IgG and IgM titers.
*IgM antibody response = newly acquired toxoplasmosis.
However, antibody levels can be very low in AIDS patients.
- So if there are no signs of increased intracranial pressure, get LP
- -> CSF shows elevated protein T
- -> PCR CSF for T. gondii
CT or MRI
- MULTIPLE hypodense lesions in the white matter and occasionally in the basal ganglia with mass effect.
- Ring enhancing lesions
*Brain biopsy, revealing the organism, should only be performed if there is no response to empiric treatment within 2 weeks or if there is a solitary lesion and negative serological studies.
Where are the preganglionic cell bodies located responsible for constricting the pupil?
Edinger Westfall nucleus
midbrain; pretectal, edinger westfall, ciliary ganglion - postganglionic cell bodies –> sphincter muscle
Describe sympathetic innervation of pupillary dilation
Starts in ipsilateral posterolateral hypothalamus
–> terminates in the ciliospinal center of Budge-Waller (intermediolateral gray matter of cord segments C8–T2).
These preganglionic neurons (second-order) ascend in the SYMPATHETIC CHAIN
–> and synapse in the superior cervical ganglion.
These postganglionic neurons travel superficially on the internal carotid artery until reaching the cavernous sinus when the nerve joins the ophthalmic division of the trigeminal nerve and then enters the orbit with the nasociliary nerve to innervate the dilator muscle via the long ciliary nerves
An abnormally small pupil is a sign of a lesion in the sympathetic nervous sys- tem whereas a large pupil suggests a lesion affecting the parasympathetic nervous system. Parasympathetic dysfunction can occur from what 4 possibilities?
- ) Third nerve injury
- ) damage to the iris itself
- ) pharmacologic effects (atropine, scopolamine, etc.)
- ) damage to the ciliary ganglion or the short ciliary nerves.
Compression of the third nerve by the uncus of the temporal lobe or by a posterior communicating artery aneurysm presents with ______ (pupil response). What happens to EOM?
Unilateral dilation and unresponsiveness
EOM usually intact
Dysfunction of the ciliary ganglion or the short ciliary nerves gives rise to ______
TONIC PUPIL pupil
- Lose pupillary light reflex
- Slow constriction to prolonged near effort focusing (light-near dissociation)
- Redilation after constriction to near stimuli is slow and tonic.
Holmes-Adie syndrome tx?
Reassurance, benign condition
Holmes-Adie syndrome?
Unilateral or in some cases bilateral tonic pupils (unresponsive pupils)
- Impaired corneal sensation
- Absent or depressed deep tendon reflexes in the legs
- Idiopathic, more in younger females
- NORMAL PUPIL ACCOMMODATION ON NEAR OBJECT (vs impaired in third nerve palsy!)
Presents with:
- sudden blurring of vision, photophobia, or without symptoms as an incidental finding.
- Pain is not associated
How do you tell the difference between third nerve palsy and holmes adie?
Holmes-adie will have normal pupillary response on accommodation
Both have abnormal light response
What kind of sx would help you distinguish between menieres and labrynthitis?
Meniere’s:
- Classically with low pitched, roaring tinnitus (high pitched tinnitus is associated with high frequency sensorineural hearing loss)
- Aural fullness
- Duration of vertigo attacks are relatively short 20min-24 hours
Labrynthitis:
- N/V
- Tinnitus, hearing loss
- Duration of vertigo attacks 2-3 days
Facial EMG is performed and shows fibrillation potentials, which is a sign of lack of facial nerve INPUT/OUPUT?
Lack of facial nerve INPUT
EMG vs EnoG?
Electromyograph:
- Stick NEEDLES into muscles, pt performs muscle activity –> looks for cMAP, abnormal waves, or fibrillation potentials
- Can evoke potentials (e.g. blink reflex) via EMG
- Absence of motor unit potentials –> severe damage or loss of nerve continuity
Electroneurogram:
- Stimulates nerve via SURFACE ELECTRODES –> evokes a compound muscle action potential (cMAP)
- Each side is stimulated at the stylomastoid foramen, and the responses from muscle groups are measured and compared.
- Significant nerve damage is indicated by a 90% OR GREATER reduction in the cMAP.
Patients that present with facial paralysis AND hearing loss require evaluation by diagnostic imaging. T/F
TRUE
What is the cerebellopontine angle and what contents are in it?
Structure at the margin at the cerebellum and pons. (think sx of balance, facial nerve, hearing, etc) Contains: Facial nerve (CN VII) Vestibulocochlear nerve (CN VIII) Flocculus of the cerebellum Lateral recess of the 4th ventricle *Book says contains CN 5-11
Pathology: Vestibular schwannoma (acoustic neuroma) Arachnoid cyst Facial nerve tumour Lipoma/Cholesterol cysts Meningioma Glomus tumor (paraganglioma)
Most common tumor of cerebellopontine angle?
Vestibular schwannoma
Tx: Stereotactic radiotherapy (directed focus radiation beam to the tumor)
What is a glomus tumor and where is it found?
Found in cerebellopontine angle
AKA paraganglioma.
- Highly vascular tumor from neuroepithelial cells.
- Named after the structures they come from
- glomus tympanicum (middle ear), glomus jugulare (jugular vein), glomus vagale (vagus nerve), and carotid body tumor (carotid artery).
- A rule of 10%:
- 10% are bilateral
- 10% are familial
- 10% are malignant
- 10% produce a catecholamine-like sub- stance
What are meningiomas
- Usually benign; F > M
- Mesoderm origin, attached to dura
- Commonly located: along sagittal sinus, over cerebral convexities, cerebellopontine angle
- Gray, firm, sharply demarcated
- Uniform cells with roung/elongated nuclei
- Whorling pattern
- Slow onset of neuro deficit or focal seizure
- Homogenous contrast enhancement
Tx: surgical is optimal
Tx: resection is curative
*Small asymptomatic lesions in older patients can be observed.
What tests can be done to assess hearing (beyond the tuning fork)
Audiogram (sensori vs conductive + info on retrocochlear hearing loss)
ABR - auditory brainstem response (can further assess sensorineural hearing loss)
What three options should you at LEAST consider in managing tumors in the posterior fossa?
- Observation and serial imaging
- Stereotactic radiosurgery
- Conventional surgery
When is stereotactic radiosurgery indicated? Downsides of this? Side effects?
For tumors that are surgically inaccessible
Very effective in managing small-medium tumors (up to 3cm) –> shorter hospital stay and recovery
- Can’t use for meningiomas or epidermoids
- Can’t use when you need a pathologic specimen for dx
- Potential for continued growth
- Surgery following radiosurgery is more difficult and outcomes aren’t as good
radiation necrosis, seizures, headaches, nausea, hemorrhage
Auditory Brainstem Response (ABR) is the best test to evaluate sensorineural hearing loss. T/F
False
- MRI of internal auditory canals with gadolinium!
ABR can evaluate unilateral SN hearing loss BUT
- Low specificity for dx
- No info on pathologic cause
What is the next step in therapy in someone with suspected mets to the brain?
Corticosteroids- reduces edema and capillary permeability
Anticonvulsant- 40% of brain mets will have a seizure
Brain metastases are 10x more common than primary brain tumors. T/F
TRUE
What are the most common tumors that metastasize to the brain?
Lung 50% Breast 20% Melanoma 10% Unknown primary 10% Other (thyroid, sarcoma, etc)
66% of mets go to the brain parenchyma (others go to leptomeninges, calvaria, dura)
Most mets to the brain end up supratentorially. T/F
True
82% supratentorially
15% cerebellum
3% brainstem
Most brain mets are localized to the grey-white junction and ______
Arterial border zones (narrowed blood vessels, can trap tumor cells)
Brain met ddx?
Brain abscess Demyelinating diseases Radiation necrosis Cerebral vascular accidents Intracranial bleed Primary brain tumors
Approximately 60% of those without any known primary tumor that present with brain metastasis have a primary lung cancer. T/F
TRUE
MRI of the brain cannot diagnose the type of tumor in patients with unknown primary malignancy. T/F
True with one exception, MALIGNANT MELANOMA
- Hyperintense on T1-weighted
- Hypointense on T2-weighted
(lipoma also looks hyper on T1 and hypo on T2)
Pt with brain mets; who would benefit from surgery?
Improved survival and quality of life has been shown in patients with SINGLE LESIONS when they have been treated with whole brain radiotherapy and surgery.
- Presentation at younger age
- Absence of extracranial disease
- Increased time to developing brain mets
*Radiation therapy has been shown to decrease the mortality from neurologic dysfunction.
Complications from radiation therapy for brain mets?
Brain necrosis Brain atrophy Cognitive deterioration Leukoencephalopathy Neuroendocrine dysfunction
Brain mets favorable prognostic factors?
Pts with mets to infratentorial have worse prognosis than those with supratentorial mets. T/F
TRUE
Median survival for pts with single brain mets who receive all brain radiation + surgery?
10-16 months
Seizures is the most commonly found sx for brain tumors. T/F
False
Headache!
______ is the most common form of childhood epilepsy
Benign Rolandic epilepsy aka
Benign childhood epilepsy with centrotemporal spikes
Most common focal epilepsy in adults? Children?
Adults: temporal lobe epilepsy
Children: BRE
Benign Rolandic epilepsy is highly heritable w/ unclear inheritance pattern and has no known etiology. T/F
TRUE
Benign Rolandic epilepsy has an onset between ____
Onset between 3-13yo
Seizures stop before 20yo
Typical seizure presentation with BRE
Begins with unilateral FACE AND MOUTH sensorimotor manifestations
- Oral paresthesias + facial clonic and/or tonic activity are common
- Speech arrest
- Hypersalivation
Most benign rolandic epilepsy seizure activity is at night , soon after falling asleep or on awakening. T/F
TRUE
What are the three general categories of epilepsies?
Symptomatic
- Anatomical substrate is seen in association with region of seizure focus
Cryptogenic
- Seizure focuse without any obvious finding on neuroimaging
Idiopathic
- Known or presumed GENETIC etiology
- E.g. BRE since its highly heritable but unknown mode of inheritance
How do you diagnose BRE?
EEG and HISTORY
- ~ 30% of patients with BRE will have SHARP WAVES seen arising from the CENTROTEMPORAL region.
- frontal dipole and a prepotential, which aid in identifying these sharp waves as consistent with BRE.
- If both the history and the EEG are consistent with BRE then no further diagnostic workup needs to be undertaken.
- *If the history is consistent, but the EEG is unrevealing? Get another EEG
Tx of BRE?
Without tx until pt has 3+ seizures (since most outgrow seizures, few seizures, side effects of drugs)
First line:
Oxcarbazepine
Gabapentin
What is another idiopathic localization-related epilepsy syndrome similar to BRE?
Benign epilepsy of childhood with occipital paroxysms.
- Seizures in these patients begin with visual symptoms followed by psychomotor, sensorimotor, or migraine- like phenomena.
- EEG reveals OCCIPITAL SPIKES that go away with eye opening.
What is Miller-Dieker syndrome?
A severe lissencephaly phenotype secondary to deletion on chromosome 17p13.3 with agyria and characteristic dysmorphic features.
What is lissencephaly?
Smooth brain genetic malformation of the cerebral cortex in which abnormal neuronal migration during early neural development results in smooth cerebral surfaces with absent (agyria) or decreased (pachygyria) convolutions.
What is isolated lissencephaly sequence?
Milder phenotype compared to Miller- Dieker syndrome, with pachygyria and mild or absent dysmorphic features
- -AUTO-DOM mutations in the LIS1 gene on chromosome 17p13.3 OR
- X-LINKED mutations in the doublecortin (DCX) gene on chromosome Xq22.3.
LIS1 mutation? posterior-predominant pachygyria
DCX mutation? anterior-predominant pachygyria
Tx of Miller-Dieker lissencephaly?
Supportive with attention to:
- Epilepsy (multiple anticonvulsants)
- Poor feeding (feeding tube/gtube)
- Spasticity (steroids/prednisone and ACTH, muscle relaxants, PT)
Lissencephaly pts also have congenital cardiac and renal abnormalities that need to be closely monitored. T/F
TRUE
Most cases of Miller-Dieker are hereditary. T/F
False, most are caused by a DE NOVO CHROMOSOMAL DELETION
Why do you get genetic counseling in Miller-Dieker if most cases are caused by a de novo deletion?
Recurrence risk can be as high as 33% if a familial reciprocal translocation is determined!
- Do FISH analysis for the 17p13.3 deletion
- Consult genetics specialist
- Prenatal testing through fetal chromosome analysis by karyotyping, FISH, chorionic villus sampling, or amniocentesis
***Imaging for cerebral gyral malformations is more sensitive beyond 28 weeks of gestation.
What are the three hallmarks of Miller-Dieker?
Motor delay
Seizures
Microcephaly
Child presenting with mental retardation, motor delay, infantile spasms, and characteristic craniofacial dysmorphic features including microcephaly, short nose with upturned nares, and micrognathia. What condition should you consider?
Lissencephaly
What is the most common type of austism spectrum disorder? least common?
Most: Pervasive personality disorder-NOS
Least: Asperger
What parts of the brain causes ASD
Cause of ASD unknown but likely to involve:
- Frontal lobe (regulating emotion and behavior)
- Amygdala (mediating response to stress)
ASD is more common in boys. T/F
True, 4:1
How do you manage pts with autism?
- Appropriately structured educational environment.
- Max development of child’s potential
- Behavioral interventions
Meds? None that are approved by FDA but based on smaller studies, possibly: - SSRI
- Atypical antipsychotic
Autism is PROGRESSIVE/NON-PROGRESSIVE and a child that has not learned to speak by ___ years of age usually will not gain communicative ability.
NON-progressive
5 years
(degree of language impairment and intelligence ability usually predict outcome of eventual function)
A delay in gross motor skills arising prior to 1 year of age strongly suggests the diagnosis of _____
Cerebral palsy
The Denver Developmental Screening Test is used to assess ______
Which developmental spheres are impacted
Beta blockers can be used to treat neurogenic syncope. T/F
True
Suppresses overactive cardiac mechanoreceptors
Mechanism/what causes neurogenic syncope?
Inappropriate activation of a cardioinhibitory and vasoDEPRESSOR reflex
Causes:
- Micturition
- Deglutition (swallowing)
- Carotid sinus compression
- Sudden underfilling of the ventricle
- Heightened vagal tone.
What signs/sx do you look for in vertigo that will point to a peripheral or central cause?
Peripheral: tinnitus and hearing loss
Central: diplopia, dysarthria, or other symptoms of brainstem dysfunction
Examples of recurrent episodes of spontaneous vertigo? What about single prolonged episode of spontaneous vertigo? Positional vertigo?
Spontaneous single long episode:
- Vestibular neuronitis
- Labyrinthine concussion
- Lateral medullary or cerebellar infarction
Spontaneous recurrent episodes:
- Menieres (intermittent increase in endolymph)
- Perilymph fistula (pop)
- Migraine
- Posterior circulation ischemia
Hypercalcemia sx? When do sx start to occur?
Decreases membrane excitability
- Fatigue, lethargy
- Areflexia
- Coma, convulsions (severe)
Sx usually don’t occur until 14mg/dL or higher
Tay Sachs enzyme deficiency? Sx? Inheritance?
Deficient: Hexosaminidase
Developmental delay Mental retardation Seizures Blindness *Autosomal recessive
Gaucher disease sx?
Hepatosplenomegaly
Pancytopenia
Look for Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper)
53yo with asterixis, esophageal varices, splenomegaly and abdominal ascites. Pt likely to become altered. How do you know if its due to copper poisoning or impaired hepatic detoxification of blood?
Altered consciousness is more likely due to liver disease and NOT heavy metal poisoning
*Encephalopathy that occurs with chronic hepatic disease and portal HTN = portal-systemic encephalopathy; blood bypasses liver with toxins in it as portal hypertension develops
Most common change in brain in someone with long-standing hepatic disease?
Long standing hepatic disease –>increase in Alzheimer type II ASTROCYTES –> neuronal loss and necrosis –> profound encephalopathy
Vs purkinje cell damage from chronic alcoholism or hepatic insufficiency via alcohol toxicity/thiamine deficiency
Causes of hypertensive encephalopathy?
Several conditions may evoke blood pressure elevation:
- Sudden withdrawal of antihypertensive treatment
- Pheochromocytoma
- Eclampsia
- Acute nephritis
- Renal artery thrombosis
- Crises in chronic essential hypertension
- Cushing’s syndrome
“SPEAR CC”
Pt with mental status changes, seizures, vision difficulties. Abnormally high T2 signal in posterior cerebral white matter. Proteinuria and BP of 210/120. What does the protein of CSF look like?
- Most patients will have MODERATE increases in CSF protein
Think hypertensive encephalopathy
CSF protein is variable since HTN could cause intracranial hemorrhage
Diabetic neuropathy involves axonal degradation and usually improves with dialysis. T/F
TRUE
Restless leg syndrome is characterized by _____. How does it relate to akathisia?
Feeling of discomfort in the legs that is relieved by movement. Pulling, stretching, cramping feeling that starts primarily at night, shortly after pt lays down
Akathisia occurs mostly during the day
Tx of restless leg syndrome?
Possibly help: Dopamine agonists (pramipexole, ropinirole) Clonazepam Gabapentin L-dopa Opiates Exercise before bed *Avoid neuroleptics, CCB, caffein
Thiamine is water soluble and easily lost in dialysis. T/F
True;
Often replace B12 and thiamine in pts getting dialysis
Pathophysiology of pernicious anemia? Sx?
Autoimmune to parietal cells –> chronic gastritis –> no intrinsic factor produced –> poor B12 absorption
Look for
- Sensory ataxia
- Weakness
- Acroparesthesia, etc
Lab test to confirm B12 deficiency?
Methylmalonyl CoA
- B12 is a cofactor for methylmalonyl coa–>succinyl coa
- Methylmalonyl CoA is readily excreted in urine
Or look for elevated serum homocysteine
- B12 is a cofactor for homocysteine –> methionine (if disturbed, can’t make RBC precursors)
What areas of the CNS are affected by B12 deficiency? Sx?
Demyelination of:
- Dorsal columns
- Lateral corticospinal columns
- Spinocerebellar tracts
– ataxic gait, paresthesia, impaired vibration and positional sense
Someone has hyperreflexia and then develops clonus or hyporeflexia. What nutritional concern would you think of?
B12 deficiency because it affects corticospinal tracts (would expect UMN/hyperreflexia) but also affects peripheral nerves (would expect hyporeflexia)
Vision changes associated with chronic B12 deficiency?
Normal blind spot enlarges temporally to involve the central vision
*similar blind spot associated with alcohol and tobacco excess (tobacco-alcohol ambylopia) most likely 2/2 thiamine deficiency though
What is the triad of Wernickes encephalopathy?
Ataxia
Ophthalmoplegia
Confusion
- Treat with IV thiamine
Korsakoff syndrome?
- Irreversible memory loss, confabulation, personality change
Associated with periventricular hemorrhage/necrosis of mammillary bodies
How do you treat alcohol withdrawal?
High dose benzos, like chlordiazepoxide
Isoniazid interferes with B6 absorption and pts taking INH need B6 supplementation. T/F?
False
INH interferes with B6’s participation in metabolic pathways but YES, they need to be supplemented otherwise –> peripheral neuropathy, glossitis
Pt who presents with irritability, sleeplessness, fatigue, memory loss, anemia, dermatitis on face. Vegetarian diet. Dx?
Pellagra
Deficiency in niacin or it’s precursor (tryptophan)
Slow evolution of gait difficulty, bladder dysfunction, hyporeflexia, impaired position and vibration sense, anemia?
B12 deficiency
Look for hypersegmented PMNs on peripheral smear
Tocopherol deficiency?
Looks like B12 deficiency (but no megaloblastic, no hypersegmented pmns, or increased MMA levels)
- most obvious sx is ATAXIA
- spinocerebellar tract demyelination (ascending tract that gives information to cerebellum about muscle length and tension)
- polyneuropathy
- pigmentary retinopathy
- hemolytic anemia (look for elevated serum bilirubin), muscle weakness, acanthocytosis
Kwashiorkor?
Look for presentation of apathy, indifference to environment, little spontaneous movement, edema
MEAL Malnutrition Edema (2/2 decreased oncotic pressure) Anemia Liver (fatty)
Young female with h/o hemophilia who received blood transfusions x5 in past 7 years with sx similar to MS but unrevealing MRI?
AIDS Encephalopathy
HIV-1 associated subacute encephalomyelitis is comparable to MS findings
Labs:
- HIV-1 antibodies
- CD4/CD8 ratio (symptomatic AIDS have ratio
Pickwickian syndrome?
Aka Obesity Hypoventilation Syndrome
= obesity + hypersomnia + other sx like sleep apnea
- sleep attacks abate with cessation of smoking and weight loss
Herpes encephalitis in someone who is not immunodeficient usually presents with psychiatric sx. T/F
True;
Depression, irritability, labile affect are common
Tx for meningococcal meningitis?
IV Penicillin G early in course
12-15 million U daily divided into 4-6 doses
After significant head trauma the pt is at significant risk for ____
Seizure
- lowest threshold during sleep (may go unnoticed) or when sleep-deprived
EEG findings in hepatic encephalopathy?
Diffusely slow triphasic waves
What CSF finding is specific to hepatic encephalopathy. How does this happen?
Glutamine
Astrocytes use glutamate + NH3 (INCREASED) –> glutamine
Three main functions of cerebellum
Posture, tone, coordination
What is the rebound phenomenon/Stewart Holmes Test
Sign of cerebellar disease
Fail to relax bicep after passive resistance released (hit self)
Peripheral causes of nystagmus have the fast-phase beating towards the side of the lesion. T/F
False
Peripheral beats away
Central beats towards
What are the types of episodic ataxia and how do you treat it?
Type 1 (K+ channel mutation on Ch. 12)
- Ataxia + myokymia (muscle twitching that can’t move joint) + nystagmus
- Brought on by startle
- Brought on by change in posture, exercise
Type 2 (Ca2+ channel mutation on Ch. 14)
- Lasts hours-days
- Brought on by startle
- Brought on by fatigue
Tx:
Acetazolamide
Anticonvulsants
Friedreich ataxia?
AR; MOST COMMON INHERITED form of ataxia
GAA expansion in intron of Frataxin (iron binding protein) gene in Ch. 9
Degeneration of:
- Spinocerebellar tracts –> ataxia
- Posterior columns –> loss of vibration and light touch
- Lateral corticospinal –> loss of pain and T
- DRG neurons –> diminished DTR
Cerebellum is spared in Friedreich ataxia. T/F
TRUE
S/s of friedreich?
Look for:
- Areflexia
- Loss of vibration/position sense (falling all the time)
- Cardiomegaly
Cerebellar signs; dysarthria, ataxia, staggering gait, nystagmus, dysmetria
Hyporeflexia Cardiomyopathy/cardiomegaly Mental retardation Diabetes Scoliosis, pes cavus, pes equinovarus (club foot)
MRI findings of friedreich?
Spinal cord atrophy
Ataxia-telangiectasia is inherited. T/F? What is it?
TRUE
Triad: Ataxia, Angiomas, IgA deficiency
- Telangiectasia, ataxias
- Nystagmus
- Myclonic jerks, areflexia, distal sensory defects
- Thymic hypoplasia –> IgA and IgG2 deficiency –> recurrent pulmonary infections
- DMI
Next step in someone with progressive ataxia? Ataxia with weight loss?
CSF titers for infection (lyme, syphilis, etc)
Work up paraneoplastic syndrome antibodies
What are the three stabilizing systems to prevent vertigo?
Somatosensory
Visual
Vestibular
S/s of optic neuritis?
Decreased visual acuity Decreased color perception Eye pain Marcus Gunn pupil/rAPD - 2/3 will have normal fundus exam - 1/3 disk swelling
Autosomal recessive disease that involves autonomic system that is almost exclusively found in Ashkenazi Jews? Tx?
Riley–Day syndrome aka hereditary sensory and autonomic neuropathy type 3
Aka Familial dysautonomia
- Insensitivity to pain and temperature
- Inability to produce tears
- Poor growth
- Labile blood pressure
- corneal ulceration, absence of pupillary reactivity, poor temperature regulation, excessive perspiration
- dysphagia, recurrent vomiting
- absence of papillae of the tongue
Tx:
- None; symptomatic
Refsum disease is also known as _______. Sx?
Hereditary motor and sensory neuropathy Type 4
- — Autosomal recessive ↓ oxidation of phytanic acid, a branched-chain FA
- Retinitis pigmentosa presenting as night blindness often precedes the onset of neuropathy
- Thickened skin (ichthyosis)
- Sclerodactyly
- Cardiomyopathy
- Cataracts
Tangier disease is also known as ______. Sx?
Familial alpha-lipoprotein deficiency
—Severe deficiency of high-density lipoproteins (HDL)
○ Autosomal recessive.
○ Deposition of cholesterol esters in skin and organs, most commonly tonsils (ORANGE TONSILS) + mucous membranes.
○ Syringomyelic presentation includes wasting of hand muscles, loss of pain + temperature sensation
Acute intermittent porphyria sx?
○ Triad (in order):
1) abdominal crisis
2) psychosis (hysteria)
3) acute neuropathy (usually motor)
○ Asymptomatic between attacks. No skin lesions (vs. porphyria cutanea tarda)
○ Acute attacks: ↑ urine aminolevulinic acid and/or porphobilinogen (between attacks, too)
What is the enzyme deficiency in acute intermittent porphyria? Accumulated substances?
Enzyme: porphobilinogen deaminase
Porphobilinogen, δ-ALA
Cauda equina vs conus medullaris?
Incontinence in both
Cauda equina:
- Asymmetrical
- LMN
- Decreased reflexes
- NO babinski
Conus medullaris:
- Symmetrical
- Mixed UMN and LMN
- Hyperreflexive patellar (L2,3,4)
- Hyporeflexive achilles (S1)
- YES babinksi
Most common place for cervical spondylosis?
C6 and C7
Cervical spondylosis dx? Tx?
Xray of head and neck
- look for osteophytes, osteoporosis
MRI if red flags OR hasn’t resolved in 4-6 weeks
Tx (while natural healing):
- gabapentin
- pregabalin
- SSRI
- TCA
- Topiramate
S/s of cervical spondylosis?
- Reduced range of motion of neck (most common finding)
- Neck pain and associated occipital headache
- Spurling sign: ↑ radicular pain on neck extension and lateral bending ipsilateral to lesion
- Lhermitte sign: electrical sensation running down the back (like MS)
Thoracic outlet syndrome sx?
Compression of structures above 1st rib and behind clavicle in the interscalene triangle
Structures compressed:
● Brachial plexus (95%)
- C8 + T1 (most common)
–Pain/paresthesia in medial arm and digits 4 & 5
● Subclavian vein (4%)
● Subclavian artery (1%)
○ Five P’s: pain, paresthesia, paralysis, pulselessness, pallor, poikylothermia
Thoracic outlet syndrome dx? Tx?
- Duplex ultrasonography
- MRA
- Diminished radial pulse with provocation (92% sensitive)
OR - Chest X-ray showing cervical rib if congenital
Shoulder girdle exercises
Avoid provocative positions
Surgery IF signs of ischemia or intractable pain; resect rib or scalene muscle
Ddx for low back pain?
Mechanical spinal (97%) ● Lumbar strain (70%) ● Degenerative changes (10%) ● Herniated disk (4%) ● Spinal stenosis (3%) ● Compression fracture (4%) ● Spondylolisthesis (2%) (slipped disk) ● Spondylolysis (vertebral structural defect)
Nonmechanical spinal (1%) ●Neoplasia (0.7%) ● Infection (0.01%) ● Inflammation (0.3%) Ex. Ankylosing spondylitis
Visceral (2%) ● Pelvic organs (prostatitis, endometriosis) ● Renal disease (pyelonephritis, stone) ● Abdominal aortic aneurysm Gastrointestinal organs (pancreatitis, cholecystitis)
Myotonia congenita?
Cl- channelopathy –> myopathy
○ Weakness is better with exercise (not paradoxical myotonia)
○ Worse when sitting or cold.
○ All muscles are involved. Muscle hypertrophy may be pronounced (“little hercules”)
How to differentiate between benign and pathologic fasciculations?
Benign fasciculations will cease immediately with intentional movement
What is stiff person syndrome? Tx?
Motor neuron disease that resembles tetanus
● Waxing & waning muscle rigidity
● Autoimmune:
- Anti glutamic acid decarboxylase (GAD)
○ Anti-GAD AB’s also seen in DM type 1, celiac disase
○ Glutamic acid decarboxylase ↓, GABA ↓, spinal
interneuron inhibition of motor neurons ↓
● Treatment: baclofen, benzodiazepine, PE, IVIg
ALS has no sensory component. T/F
TRUE
Also spares oculomotor
*bowel and bladder sphincters also usually spared
How do you diagnose ALS? Tx?
Clinical
● Diagnosis: definite (3+), probable (2), possible (1)
- Bulbar, cervical, thoracic, and lumbosacral motor neurons
Tx:
Riluzole (decreases presynaptic glutamate release)
S/s of ALS?
○ Asymmetric weakness in legs or trouble chewing as first symptom
○ Dysarthria
○ Pseudobulbar affect: exaggeration of motor expressions of emotion - excessive laughing, crying
Pathophysiology of ALS?
○ Accumulation of lipofuscin in neurons and glia –> lateral sclerosis/ loss of fibers in corticospinal tracts –> muscle atrophy after denervation
***VERY SELECTIVE: upper and lower motor neurons only. Cognitive neurons intact.
Ddx for muscle pain/myopathy WITHOUT weakness? (aka serum CK, EMG, and muscle biopsy are normal)
Fibromyalgia Polymyalgia rheumatica (increased ESR; may have associated temporal arteritis. Tx: steroids; will treat both)
First sign of DuchenneMD? Inheritance? Labs?
Gower maneuver with onset around 3-5yo
X-linked due to framshift, deleted dystrophin gene
Serum CK: ↑↑ 20-200x (10,000 IU or higher) normal
Biopsy shows fat infiltration (pseudohypertrophy)
Duchenne treatment?
Corticosteroids, can slow progression for up to 3 years
Becker MD?
X-linked
In-frame mutation of dystrophin gene (vs duchenne)
- Weakness in first decade; may not be significant until 40s
CK elevations but not as much as Duchenne
Congenital muscular dystrophy is inherited in an autosomal dominant pattern. T/F
False
Autosomal recessive!
Myotonic dystrophy is inherited in autosomal dominant pattern. T/F
True
Type 1 vs Type 2 myotonic dystrophy?
Type 1: CTG repeat + distally weak
Type 2: tetranucleotide repeat + proximally weak
What is myotonic dystrophy?
Autosomal dominant disease –> prolonged contraction followed by slow relaxation.
○ Cardiomyopathy/arrhythmia, gonadal atrophy, cataracts, insulin resistence, mental retardation
Pts have “Hatchet-face” due to temoralis, SCM wasting. Frontal balding prominent.
Lab findings in myotonic dystrophy work up? CK, EMG, biopsy?
CK: can be normal.
EMG: myotonia.
Biopsy: selective atrophy of type 1 (slow twitch) muscle fibers.
Lacunar stroke effective right subthalamic nucleus would result in what kind of movement?
Hemiballismus (sudden, wild flailing of one arm +/- ipsi leg)
- CONTRAlateral so right lesion => left arm flailing
Athetosis results from a lesion found in the ____. What about chorea?
Both are basal ganglia
Sx other than chorea in Huntingtons? What neurotransmitter patterns do you expect to see?
- Choreiform movements
- Aggression
- Depression
- Dementia (sometimes initially mistaken for substance abuse)
Increased dopamine
Decreased GABA
Decreased ACh
[CAG repeats; Caudate loses ACh and GABA]
Neuronal death via NMDA-R binding and glutamate toxicity.
MRI findings in Huntingtons?
Atrophy of caudate nuclei with ex vacuo dilatation of frontal horns on MRI
Left frontal eye field is lesioned. What happens to gaze? PPRF lesion?
FEF lesion: eyes look towards lesion
PPRF lesion: eyes look away from lesion
Agraphia, acalculia, finger agnosia, left-right disorientation are signs of ______ (lesion)
Dominant parietal-temporal cortex lesion
Gerstmann syndrome
Dejerine-Roussy syndrome aka _____ is characterized by:
Thalamic pain syndrome (PARADOXICAL PAIN ASSOCIATED WITH DECREASED PAIN SENSITIVITY)
- Stroke causing damage to the thalamus.
- Usually in one hemisphere of the brain
- -> contralateral hemiparesthesia/hemianesthesia initial lack of sensation and tingling in the opposite side of the body.
Can have hemiHYPEResthesia
Posterior circulation strokes?
P1 syndromes
- midbrain, subthalamic, thalamic
- Claude’s syndrome (CN III palsy with contralateral ataxia )
- Weber’s syndrome (CN III palsy with contralateral hemiplegia)
- Hemibalismus if subthalamic nucleus involved
- Decerebrate rigidity if whole midbrain infarcted
P2 syndromes
- cortical temporal, occipital
- Unilateral: contralateral homonymous hemianopia with macula sparing
- Bilateral: cortical blindness (blind with intact pupillary reflex).
- ANTON’S (blind but adamantly says they can see)
- Peduncular hallucinosis: very realistic, often involves people and environments that are familiar to the affected individuals. Pts can rarely distinguish between the hallucinations and reality
- BALINT’S SYNDROME (persistence of visual image), usually watershed infarct after cardiac arrest:
- inability to perceive the visual field as a whole (simultanagnosia)
- difficulty in fixating the eyes (oculomotor apraxia)
- inability to move the hand to a specific object by using vision (optic ataxia)
Anterior circulation (from carotids) stroke?
● Middle cerebral artery
○ Complete: Hemiparesis (85% of ischemic), hemianesthesia, homonymous hemianopia, aphasia
○ Partial: any combination of above
○ Globus pallidus and putamen: parkinsonism and hemiballismus (if subthalamic nucleus infarcted)
● Anterior cerebral artery (proximal occlusion tolerated well because of collaterals but not distal)
- Abulia, paraparesis of lower extremities, urinary incontinence.
*Sensation is spared.
● Anterior choroidal artery(rare):
- Contralateral hemiplegia
- Hemianesthesia
- Homonymous hemianopia
Anterior limb of internal capsule stroke?
- Ataxia (frontopontocerebellar tract)
- Hemiparesis (corticospinal tract)
Posterior limb of internal capsule lacunar stroke?
Pure motor impairment (corticospinal)
No cortical / visual dysfunction
Thalamus VPL nucleus lacunar stroke?
Contralateral hemianesthesia/parasthesia
○ Also can have hemihyperesthesia. (Thalamic syndrome / Dejerine-Roussy disease)
Lacunar stroke of anterior pons (basis pontis)?
Contralateral dysarthria-clumsy hand syndrome
What is malignant hyperthermia?
Rare
Life threatening
Hereditary condition
Fevers, severe muscle contractions after inhaled anesthetics (except N2O) like halothane or muscle relaxants like succinylcholine
Tx: dantrolene
Patients eye has trouble moving medially and complains of difficulty walking down stairs.
CN IV problem
Superior oblique helps eye move down and medial
Raccoon eyes should suggest basilar skull fracture. What other signs would indicate this?
Battle sign
Hemotympanum
CSF rhinorrhea or otorrhea
______ is the most common cause of coma in the head-injured pt without an intracranial mass lesion.
Diffuse axonal injury
- Look for multiple hemorrhagic foci
- Shearing of axons in vulnerable areas : subcortical white, corpus collosum, upper brainstem
Demyelinating neuropathy like GBS is associated with what bacteria? What else is it associated with?
C. jejuni
HHV Mycoplasma Haemophilus influenzae Recent HIV infection Recent immunization
Other than baclofen, what other med can be given to treat spasticity?
Tizanidine
Centrally active alpha-2 agonist
doesn’t effect on strength
Possible causes of pseudotumor cerebri?
Large doses of vitamin A
Tetracyclines
Withdrawal from corticosteroids
What reflex would be impaired in someone with CN V lesion?
Corneal (V1 – VII)
Lacrimation (V1 – VII)
Jaw Jerk (V3 – V3)
Problems pts have with CN VII lesion? (other than facial droop)
Unable to close eyes (responsible for eyelid closing)
Hyperacusis (stapedius muscle paralysis)
Causes of CN X lesion other than stroke?
Aortic aneurysms
Tumors (e.g. apical/Pancoast lung tumors)
Look for recurrent laryngneal palsy, hoarseness
- Dysphagia
- Lack of gag or cough
Innervation of gag reflex?
Afferent: CN 9
Efferent: CN 10
Metabolic causes of peripheral neuropathy?
Diabetes (autonomic and sensory neuropathy)
Hypothyroidism
Uremia
Nutritional causes of peripheral neuropathy?
Deficiency of B12 B6 B1 (dry beriberi) E
Toxin/medication causes of peripheral neuropathy?
Lead (classic sx of foot/wrist drop; look for coexisting CNS or abdominal sx) Isoniazid Vincristine Ethambutol (optic neuritis) Aminoglycosides (esp CN 8)
Immunization/autoimmune causes of peripheral neuropathy?
GBS SLE PAN Scleroderma Sarcoidosis Amyloidosis
Traumatic causes of peripheral neuropathy?
Carpal tunnel syndrome
Pressure paralysis (radial nerve palsy in alcoholics)
Fractures
Infectious causes of peripheral neuropathy?
Lyme HIV Tick bite Diptheria Leprosy
How do you dx Myasthenia gravis?
Tensilon test
- Inject tensilon (edrophonium), short acting anticholinesterase inhibitor, and muscle weakness improves
- Nerve stimulation studies
- Look for thymomas (improve with removal of thymomas)
- Med tx:
- Long-acting anticholinesterase inhibitors (pyridostigmine, neostigmine)
Extraocular muscles are spared in LEMS but not in MG. T/F
TRUE; LEMS spares extraocular muscles, MG does not
Myasthenia gravis DDx?
- LEMS
- Organophosphate poisoning
- agricultural exposure, look for parasympathetic excess (SLUDGE) since it irreversibly inhibits AchE - Aminoglycosides in high doses
5 less common muscular dystrophies?
Beckers - X-linked recessive
Mitochondrial myopathies - ragged red fibers on biopsy, ophthalmoplegia often present
Myotonic dystrophy - AD; between 20-30yo, myotonia (can’t relax muscles), mental retard, baldness, testicular/ovarian atrophy
Fascioscapulohumeral dystrophy - AD; begins between 7-20yo; normal life expectancy
Limb-girdlge dystrophy - begins in adulthood
Metabolic ddx for disease that affects muscle and resembles muscular dystrophy?
Glucogen storage diseases (all auto recessive!)
Very Poor Carb Metabolism
Esp McArdle’s disease
- deficiency in glycogen phosphorylase
- weakness and cramping after exercise d/t lactic acid build up
Essential tremor usually affects both hands/arms.
True
Also can affect head and voice
(PD is unilateral, doesnt affect head)
What systemic damage can be caused by exertional heat stroke?
Rhabdo
Acute renal failure
DIC
What syndrome is associated with cluster headaches?
Horner’s
Look for pt waking up in the middle of night with pain, ptosis, miosis, anhydrosis
Sensitive and specific physical exam finding for an upper motor neuron lesion?
Pronator drift (UMN lesion causes weakness in supination and pronation dominates)
- NOT a sign of cerebellar dysfunction (balance and coordination)
Fetal hydantoin syndrome?
Dysmorphic newborn 2/2 anticonvulsants ESP phenytoin and carbamazepine
Presents with
- Small body size
- Microcephaly
- Digit/nail hypoplasia
- Hirsutism
- Cleft palate
- Rib abnormalities
Pt with parkinsonism + hypotension, impotence, incontinence, or other autonomic sx?
Multiple system atrophy AKA Shy-Drager syndrome (degenerative)
- Parkinsonism
- Autonomic dysfunction
- Widespread neurologic signs
Tx: focus on intravascular volume expansion (anti-parkinson drugs dont work)
NPH
Wet, wacky, wobbly
D/t DECREASED CSF ABSORPTION
- -> transient increases in ICP
- NOT permanent increases in ICP
GBS ddx?
Tick-borne paralysis (tick feeds for 4-7 days and releases neurotoxin)
- sx in HOURS (vs GBS which is more days to weeks)
- can be asymmetrical (vs GBS symmetrical)
- no autonomic dysfunction (vs majority of GBS do!)
- ascending paralysis, sx improve with tick removal
- no fever or sensory sx
- normal CSF
Botulism
MS patients do not experience peripheral neuropathy. T/F
True
MS is a strictly CNS disease
Sarcoidosis can look like MS. Why?
Early in sarcoidosis, it can look like MS, especially if s&s are traced to CNS origin
Sarcoid can have
- Optic atrophy/uveitis
- Facial nerve palsy (Bell)
(Sarcoidosis: immune-mediated widespread noncaseating granulomas, elevated serum ACE levels, elevated CD4/CD8)
Dx of thiamine deficiency?
Increased RBC transketolase activity following thiamine administration
Most common site of CNS atrophy associated with chronic alcoholism?
Superior vermis
- Loss of purkinje cells, atrophy of molecular layer after years/decades of drinking
- White matter in cerebellum is relatively unaffected
Triorthocresyl phosphate?
Damages both upper and lower motor neurons (causes SEVERE MOTOR POLYNEUROPATHY)
- Severe, likely permanent
- Death may occur within a few days after exposure
- Common in rat poisons, roach powders, other insecticides
- Look for anticholinesterase activity of poison: HA, vomiting, ab cramps, sweating, wheezing, twitching
How do you treat organophosphate poisoning?
Atropine (antimuscarinic) + Pralidoxime (regenerates AchE if given early)
Antidote for arsenic poisoning?
Dimercaprol (BAL)
Succimer
Penicillamine
Pt from underdeveloped country eating mostly rye?
Ergotism
- Ergot is a potent vasoconstrictor from rye fungus, contaminates bread
- Chronic ergot poisoning –> degeneration of posterior columns and dorsal roots –> peripheral neuropathy
Neurotoxin that can give secondary parkinsonism?
Manganese
- Manganese inhalation by miners produces clinical picture similar to Wilsons (hepatolenticular degeneration)
(Copper is Hella BAD; ceruloplasmin, cirrhosis, corneal deposits, carcinoma, hemolytic anemia, basal ganglia degeneration/parkinsonism, asterixis, dysarthria, dyskinesia, dementa)
- Parkinsonism is the most prominent feature
- May also develop axial rigidity and dystonia
Other drugs that can cause parkinsonism:
- Metoclopromide
- Phenothiazines
- Butyrophenones
Neuro findings in CO poisoning?
CarboxyHgb:
20%: confusion, headache
50%: coma, posturing, seizures
CHARACTERISTIC:
- DELAYED neurologic deterioration 1-3 weeks after initial event
- Extrapyramidal disorder with parkinsonism gait and bradykinesia
- Imaging shows classic hypodensities in globus pallidus bilaterally
Ciguatera food poisoning?
Acts on voltage gated Na channels
–> increased permeability to Na and increased excitability
Sx:
- abdominal discomfort, N/V, diarrhea
- neuro: paresthesia, HA, fatigue, ataxia, myalgias
- 80% TEMPERATURE REVERSAL
Tx:
IV mannitol
Lathyrism?
Think African, malnourished, with subacute spastic paraparesis and gait instability. Cognition, sensory, cerebellum intact.
- D/t excessive dietary reliance on chickling pea (L sativus)
- CNS damage to corticospinal and spinocerebellar tracts
GBS vs tick paralysis?
Tick paralysis:
- Normal CSF protein (unlike GBS)
- More rapid
- Affects more young children (and with long hair where tick can hide)
Atherosclerosis without history of HTN, DM, or hypercholesterolemia?
Ionizing radiation may cause accelerated atherosclerosis.
Hepatic encephalopathy with decreased alertness, irritability, tremor, ataxia will progress to ______ (neuro sx)
lethargy paranoia bizarre behavior dysarthria nystagmus pupillary dilatation
What is the most common form of retinal degeneration?
Retinitis pigmentosum
Lack of red reflex? White reflex?
(think of anything that opacifies the pathway of light transmission to retina)
- Intrauterine infections, CMV or rubella, causing congenital cataracts
White reflex?
- Disease behind the lens
- Like scar from retinopathy of prematurity or retinoblastoma
Toxin that can cause large central scotoma?
Methanol
- ACUTE vision change
- acidosis is life threatening
- Other drugs: INH, ethambutol, streptomycin can cause this but more subacutely/chronic
Visual changes in papillitis vs papilledema?
Papillitis (inflammation of optic head): visual loss is significant
Papilledema: inconsequential vision change/preserved
Tunnel vision vs concentric constriction?
Test pts size area of perception based on how far they are from the testing screen.
If the area perceived is gets bigger as the screen is moved away –> concentric constriction –> associated with optic atrophy may occur with neurosyphilis
If the area is the same as screen is moved away –> tunnel vision –> not a physiologic pattern of vision loss –> conversion, malingering (or spiraling of visual field where repeat testing of same part of visual field gets during the same exam gets successively smaller each time)
Defect in Marcus Gunn pupil?
Afferent defect
- Commonly in MS pts as a sequela of optic neuritis
- Damage to optic nerve reduces light perceived in affected eye (OPTIC ATROPHY)
Retinal microaneurysms (red dots located in largest numbers in the paracentral region) most occur with _____
diabetes
CN 3, CN 4, CN 6 palsy - which one is most common?
CN 6 is TWICE as common as CN 3
CN 6 is SIX times as common as CN 4
With lateral rectus weakness, the affected eye will remain inverted on attempts to look straight ahead
MLF lesion indicates a mesencephalic or pontine injury. T/F
TRUE
What is ocular bobbing and what causes it?
Rapid downward deviation of both eyes followed by slow upward conjugate eye movements
D/t damage to pons (like pontine glioma)
Immunosuppresion, headaches, increasing confusion and seizures. Difficulty seeing for several days and hypertensive to 180/100. PERRLA but difficulty reading and finding objects presented to him. Motor and sensory exam normal. T2 signal in occipital and parietal lobe. Dx?
PRES 2/2 immunosuppression (tacrolimus, cyclosporine)
CSF of normal pressure hydrocephalus is relatively normal. T/F?
TRUE
TCAs are used to treat postherpetic neuralgia. T/F
True
TCA like imipramine are better than analgesics to help pain
Sx of BPPV can occur with aspirin and ______
Aspirin
Phenytoin
Alcohol intoxication
