NEUROLOGIC (7%) Flashcards
AVM = ARTERIOVENOUS MALFORMATION
AVM = bad or abnormal formation between arteries and veins
Normal Physiology
- arteries carry oxygenated blood to tissues
- arteries branch into arterioles which branch into capillary beds where O2 and CO2 are exchanged
- veins then carry oxygen-rich blood back to heart
The pressure in arteries is HIGH
- the pressure decreases as blood moves from arteries to capillaries, and even lower pressure in veins
- capillaries dampen the arterial flow a bit to prevent high pressures in the veins (not equipped to handle high pressures)
AVM
⦁ entire capillary bed (and arterioles) = MISSING
⦁ the group of arteries directly links up to the group of veins
⦁ the vessels in AVM can start to tangle and form a NIDUS (“nest”)
AV FISTULA = when artery vessel –> vein
- when a single artery branches directly into single vein
in AVM, the arteries and the veins are therefore in HIGH SYSTOLIC BLOOD PRESSURE, because there are no capillaries to dampen the pressure
- the AVM Nidus can then expand in size and put pressure on surrounding tissue and surrounding capillaries –> prevent other tissues from getting enough blood flow (ischemia)
- the high pressure causes vessels to dilate
- causes veins to THICKEN –> FIBROSIS
Vessel walls are weakened and stretched out from high pressures –> can eventually lead to ANEURYSM or RUPTURE
- can be a small bleed –> forms a clot
- may not have any symptoms, but would still ideally want to treat that AVM as it is at risk for rupture again, and potentially with a much more severe bleed
CAUSE OF AVMs
- not well understood
- thought to be congenital - some sort of vessel growth dysfunction during embryonic or fetal development
- may be genetic
RISK FACTORS
- Males
- Family hx of AVM
- ** OSLER - WEBER - RENDU disease ** = Also known as Hereditary hemorrhagic telangiectasia syndrome = autosomal dominant disorder - causes blood vessel disorder all over the body
LOCATION
- AVMs can form anywhere in the body
⦁ MC location = ** brain + spinal cord + lungs **
The posterior branches of the MIDDLE CEREBRAL ARTERY are the most common arteries affected by the arteriovenous malformations.
at risk for RUPTURE
- drug use can cause AVMs to rupture
In >50% of patients with AVM, hemorrhage is the first symptom.
Symptoms due to bleeding include loss of consciousness, sudden and severe headache, nausea, vomiting, incontinence, and blurred vision, amongst others.
Drug use is a risk factor for AVM rupture (and this is hinted at in the question “there is redness around the nares bilaterally.”
Impairments caused by local brain tissue damage on the bleed site are also possible, including seizure, one-sided weakness (hemiparesis), a loss of touch sensation on one side of the body and deficits in language processing (aphasia).
Minor bleeding can occur with no noticeable symptoms. Following the bleed’s cessation, most AVM victims return to normal, after the blood vessel has had time to repair itself. In this patient, however, there is evidence of brainstem herniation (fixed, dilated pupil) so the prognosis is very poor.
SYMPTOMS
o ** BRUIT ** as blood rushes through AVM
- person can often hear it themselves if AVM is in brain
o If AVM ruptures in brain, can either be a microbleed, but if severe blood loss = SAH
- AVMs in brain are usually single
- SUBARACHNOID HEMORRHAGE –> can cause neurological symptoms
⦁ headache
⦁ seizure
⦁ if affects hippocampus –> can affect memory
⦁ if affects basal ganglia –> can affect movement
Brain AVMs usually present between the ages of 10 and 40 years.
In about half of all brain AVMs, intracranial HEMORRHAGE is the FIRST SIGN
Brain AVMs underlie 1 to 2 percent of all strokes, 3 percent of strokes in young adults, and 9 percent of subarachnoid hemorrhages
o If AVM ruptures in spinal cord = can damage nerve fibers
⦁ sensory disturbances
⦁ muscle weakness
⦁ paralysis in parts of body controlled by those nerves
o if AVM ruptures in lungs = can lead to
⦁ SOB
⦁ hemoptysis
WASTED WORK to have blood flow from heart –> AVM –> back to heart
- oxygen is NOT going to tissues capillaries, and blood is just rerouting back to the heart
- over time, heart has to work harder –> HEART FAILURE
DIAGNOSIS
⦁ ** ANGIOGRAPHY ** = gold standard
⦁ CT
⦁ MRI
- MC SIGN OF BRAIN AVM = BRAIN HEMORRHAGE **
- others = headache, epilepsy, neurologic symptoms
Spetzler-Martin grading system is used for preoperative risk-stratification of brain arteriovenous malformations
TREATMENT
⦁ most AVMs are treated regardless of if symptomatic or not - due to potential for complications
= SURGICAL EXCISION
o Radiosurgery = 1st alternative for non-surgical candidates = laser AVM to close off malformation
o Endovascular Embolization = adjunct - catheter used to obstruct the vessels in AVM
- Radiotherapy = used in patients who are not surgical candidates
⦁ symptomatic treatment for headaches / seizures
Patient will present as → a 63-year-old illiterate female with a history of right motor partial seizures and generalization since the age of 23 years arrives at the emergency room due to acute right hemiparesis. Neurological examination reveals a right hemiparesis, right tactile and pain hypoesthesia, poor fluency, temporal and spatial disorientation, and a Mini-Mental State Examination score of 5 points (one for immediate memory, two for naming, one for repetition, and one for commands).
TENSION HEADACHES
Primary Headaches (90%) = Tension, Migraine, Cluster Secondary Headaches (4%) = meningitis, SAH, intracranial HTN, hypertensive crisis, acute glaucoma
TTH = Tension Type Headache
TTH = MC type of primary headache
mean age of onset = 30’s, peaks in 40’s
TTH = more common in women
Thought to be due to mental stress. Have peripheral activation or sensitization of myofascial nocireceptors (pain receptors) that migrate through pain pathways in CNS
Tension headaches lead to steady, pressure-like pain with a bilateral distribution.
Tension headaches are characterized by a tightening feeling of the head and scalp, with pain potentially extending down the posterior neck and into the shoulders. The pain is frequently present on both sides of the head at the same time. The pain is typically mild to moderate, but may be severe.
SYMPTOMS
⦁ * mild to moderate intensity *
⦁ BILATERAL
⦁ non-throbbing (non-pulsatile) - unlike migraine
⦁ DULL, TIGHT, BAND-LIKE/TIGHT CAP
⦁ Muscle tenderness in head/neck/shoulders
⦁ Poor concentration
described as a constant pressure, as if the head were being squeezed in a cap
The pain can radiate from the lower back of the head, neck, eyes, or other muscle groups in the body
Typically affects the head bilaterally.
They usually occur for a DURATION > 30 minutes, typically last 4-6 hours
Causes constant daily headache
Muscle tenderness in head/neck/shoulders
Poor concentration
PRECIPITATING FACTORS ⦁ stress/mental tension ⦁ fatigue / lack of sleep ⦁ eye strain ⦁ bad posture ⦁ hunger ⦁ lack of caffeine ⦁ ** Not worsened with activity (unlike migraines) ** ⦁ ** No nausea, vomiting, or focal neurologic symptoms (no photophobia / phonophobia) - unlike migraines **
EPISODIC vs CHRONIC TTH
o Episodic tension headaches are usually associated with stress. Episodic = < 15 days / month
o Chronic tension headaches are usually associated with contracted muscles. Chronic = 15+ days / month
DIAGNOSIS
⦁ clinical
TREATMENT
⦁ **1ST LINE = NSAIDS
- ibuprofen/naproxen, or APAP (acetaminophen)
⦁ 2nd line = caffeine + 1st line
- caffeine can help increase effectiveness of NSAIDS / acetaminophen, but due to increase in SE, is reserved until patient has failed 1st line analgesic monotherapy
⦁ 3rd line = migraine meds if CI to 1st line (stomach ulcers, renal/liver failure, pregnant), or if not working = Triptans, TCAs (Elavil - Amytriptyline*), BBs, etc
- can try muscle relaxers as well
Triptan SE = nonischemic chest pain + distal paresthesias = don’t give in stroke / CVD / uncontrolled HTN / pregnancy
- higher chance of success with smoking cessation
- use relaxation techniques, massage, avoid high-stress, get good sleep, improve posture/sleep posture, avoid eye strain/corrected vision
ACUTE TREATMENT OF TTH (ER SETTING)
⦁ Ketorolac (Toradol) 30mg IM
If using OTC meds to treat TTH = need to taper off; abruptly stopping could cause rebound HA
- Medication-overuse headaches must be avoided by limiting use of abortive agents to no more than 2 days/week. TCAs can help with analgesic rebound headaches
- also to avoid gastritis from chronic NSAID use
PROPHYLAXIS
⦁ Amitriptyline - use with caution due to SE
Patient will present as → a 25-year-old female presents with a headache. She describes the headache as a tightening, band-like quality on both sides of his forehead. It is non-throbbing, but feels like a “tight cap.” She denies phonophobia or photophobia, nausea, or vomiting. On physical exam, you note pericranial muscle tenderness.
CLUSTER HEADACHE
More common in men (4x MC)
Predominantly occurs in young + middle-aged men
Trigeminal Hypothalamic Pathway
Cluster headaches are differentiated from trigeminal neuralgia by the duration of pain
- trigeminal neuralgia = shooting pain that typically lasts about 1 min
- cluster headache = lasts anywhere from 15min - 3hrs
Clusters of attacks separated by periods of remission
Symptoms usually remain on the same side / location during a cluster attacks
SYMPTOMS
⦁ RECURRENT* headaches that cluster together
⦁ typically last < 2 hrs (45-90 min)
⦁ Have 1 every other day to 8x/day x 6-8+ weeks
⦁ **UNILATERAL
⦁ PERIORBITAL/TEMPLE PAIN
⦁ Pain = Excruciating, sharp, searing, stabbing
⦁ Eye/Nose symptoms = Ipsilateral rhinorrhea, lacrimation, periorbital pain, nasal congestion, conjunctival injection*
⦁ ** Awakens patients from sleep **
Cluster headaches characteristically occur around the same time each day, often in the early hours of the morning
Can be worse at night = often wakes patients up from sleep
Attacks usually occur in series (cluster periods) lasting for weeks or months separated by remission periods usually lasting months or years. However, about 10–15% of patients have chronic symptoms without remissions
HORNER’S SYNDROME
= ptosis, miosis, anhidrosis (miosis = constriction)
The duration of cluster headaches are, on average, 15 min - 3 hrs.
many patients sit + rock back/forth or pace - active
Patients often pace, rubbing their heads to try to alleviate the pain
TRIGGERS ⦁ alcohol ⦁ stress ⦁ glare ⦁ ingestion of specific foods
The exact etiology of cluster headaches is unknown, but triggers may include stress, allergens, alcohol, and the vasodilator nitroglycerin.
DIAGNOSIS
⦁ MRI* (or CT) to rule out pituitary adenoma
TREATMENT
⦁ 1ST LINE = OXYGEN
- nonrebreather mask or cannula in upright position
- 6-10 L (pance) or 12-15L/min (ppt/picmonic) x at least 15 min (just think 15L/min x 15 min!)
- sometimes oxygen is enough
⦁ 2nd line = Triptans (cause vasoconstriction)
- Can try Oxygen + Sumatriptan (SQ) 6mg
- Sumatriptan 6 mg SQ: max 12 mg/24 hr with at least 1 hour between injections (max = 2 doses in 24hr period with 1 hr in between)
or
- Sumatriptan nasal spray: 20 mg. May repeat in 2 hours, max dose 40 mg/24 hr (max = 2 doses in 24hr period with 2 hrs in between)
Triptan SE = nonischemic chest pain + distal paresthesias = don’t give in stroke / CVD / uncontrolled HTN / pregnancy
- Other options = Ergotamines (vasoconstriction) or intranasal lidocaine
PROPHYLAXIS
⦁ CCB - VERAPAMIL 240mg QD
- Other prophylactic meds = verapamil, ergotamine, lithium, methysergide, prednisone, topiramate and other corticosteroids, indomethacin, beta blockers, TCAs, and SSRIs
SUMMARY
Cluster headache is a neurological disorder characterized by recurrent, severe headaches on one side of the head, typically around the eye. There are often accompanying autonomic symptoms during the headache such as eye watering, nasal congestion and swelling around the eye, typically confined to the side of the head with the pain. The are typically treated with inhaled oxygen and sumatriptans.
Patient will present as → a 45-year-old man comes to your office with a 4-week history of recurrent headaches that wake him up in the middle of the night. The headaches have been occurring every night and have been lasting approximately 1 hour. The headaches are described as a deep burning sensation centered behind the left eye. The headaches are excruciating (he rates them as a 15 on a 10-point scale) and are associated with watery eyes, “a sensation of heat and warmth in my face,” nasal discharge, and redness of the left eye.
MIGRAINE HEADACHE
Migraine = Severe headache, usually associated with Nausea, Vomiting and Light sensitivity
Neuronal Dysfunction: The trigeminal nerve becomes more susceptible to stimulus/more sensitive to irritating agents and increased pain reception
- Trigeminal nerve innervates blood vessels –> causes vasodilation –> HA
⦁ Migraines = affect women more than men
⦁ MC age = adolescent / early adults
⦁ Can be genetic (familial)
MC Type of Migraine = MIGRAINE WITHOUT AURA
TRIGGERS
⦁ ** MC = STRESS/EMOTIONAL STRESS (80%) **
Other triggers = ⦁ hormonal variation (estrogen)/OCPs ⦁ not eating ⦁ weather ⦁ sleep disturbances ⦁ diet (MSG, chocolate, cheese)
4 PHASES OF MIGRAINES
1) PRODROMAL PHASE
- occurs in 60% of patients with migraines
- Symptoms occur 24-48hrs before headache onset
- Symptoms = euphoria, depression, irritability**
- Can also have food cravings, constipation, neck stiffness, yawning
2) MIGRAINE AURA (classic)
- only occurs in 25% of patients with migraines
- Lasts < 1 hour
- start to feel HA coming on during aura
- Involves Positive and Negative symptoms
o POSITIVE
⦁ visual (bright lights, see shapes/objects)
⦁ auditory (tinnitus/noises)
⦁ sensory (burning / pain / paresthesias)
⦁ motor (twitches / muscle jerks)
o NEGATIVE ⦁ loss of vision ⦁ loss of hearing ⦁ loss of feeling ⦁ inability to move a part of the body
- *MC Aura symptoms = Visual (positive and/or negative)
- see bright lights, shapes/objects or have loss of vision - particularly in peripheral field just lateral to point of fixation)
- Visual usually followed by sensory aura
During aura, serotonin levels increase -> vasoconstriction
3) MIGRAINE HEADACHE
⦁ can last anywhere from 4-72 hours
⦁ Usually UNILATERAL, but can be bilateral.
⦁ Localized
⦁ PULSATILE/THROBBING
⦁ Can experience NAUSEA / VOMITING / PHOTOPHOBIA / PHONOPHOBIA
⦁ Worsens with activity
- worse with physical activity, stress, lack or excess sleep, alcohol, specific foods, OCPs/menstruation
During migraine, serotonin levels decrease-> vasodilation
4) POSTDROMAL PHASE
- patients often feel drained or exhausted
- Some report mild elation or euphoria
- Sudden head movement causes pain in the location of antecedent headache
DIAGNOSIS OF MIGRAINE
- neuroimaging only done with atypical features / red flags:
⦁ “Worst” headache of my life / thunderclap HA (SAH)
⦁ “New” headache - new (>40) - never had HA before
⦁ Any neurological symptoms (confusion, AMS, papilledema, seizures)
⦁ previous HAs were different
TREATMENT
- treatment for migraines should be administered as early as possible
- earlier administration improves efficacy
⦁ 1st line = NSAIDS / ASA / APAP (just like tension)
- Ibuprofen / Naproxen / Ketorolac / APA / ASA
- different OTCs may have different efficacy, so several should be tried before escalating treatment
Triptans = 1st line if moderate to severe migraine, or if NSAIDS have failed
- IV fluids and put patient in dark/quiet room can help
⦁ 2nd lineTRIPTANS (Sumatriptan/Imitrex)
- Triptans = first line after NSAIDS have failed
- DON’T give triptans with hemiplegic or brainstem aura
- SE of triptans = chest tightness due to vasoconstriction + distal paresthesias
Sumatriptan is a 5-HT1B/1D agonist in the cranial arteries. The drug binds to serotonin receptors in the brain, which triggers vasoconstriction, inhibits trigeminal activation (thought to be the cause of migraine pain)
Can try adding NSAIDS or caffeine to triptans
2nd line = or Ergotamines
MOA of triptans + ergotamines = serotonin 5HT-1 agonists ==> vasoconstriction
- SE = chest tightness from constriction
- CI = CAD / PVD / CVD / stroke / uncontrolled HTN / hepatic or renal disease / pregnancy
⦁ 3rd line = IV Phenothiazines: Metoclopramide, Promethazine, Prochlorperazine
= Dopamine blockers
- Indication = antiemetics for N/V
- ** Give with BENADRYL ** to prevent EPS / dystonic reactions / parkinsonism symptoms due to decreased dopamine
IF PREGNANT = can only give ACETAMINOPHEN
American Academy of Neurology (AAN) and AHS have also recommended RIBOFLAVIN (B2) + MAGNESIUM to help reduce migraine frequency and headache days
PROPHYLAXIS
⦁ BB (propranolol)*** or CCB
⦁ TCAs (Elavil)
⦁ Anticonvulsants (valproic acid, Topamax)
- triptans = not indicated for prophylaxis
Patient will present a → a 25-year-old female comes to your office with a 3-year history of recurrent headaches that have gotten worse during the past year. These headaches occur approximately twice per week. Before the headache, nausea, and severe vomiting begin, she experiences a “type of odd visual feeling or sight—flashing lights, almost like a pattern in front of my eyes.” Headaches usually lasts 24 to 36 hours. It is throbbing in nature and often “switches from one side to the other”. She needs to be in a dark room and finds noise bothersome when she has these headaches.
INTRACRANIAL HEMORRHAGE
4 types of Intracranial Hemorrhages ⦁ epidural hematoma ⦁ subdural hematoma ⦁ subarachnoid hemorrhage ⦁ intracerebral hemorrhage
EPIDURAL HEMATOMA
Dura Mater = outermost protective layer of the brain
Epidural = outside the dura
Epidural hemorrhage = bleeding above the dura mater
- bleeding between dura mater + skull
ANATOMY
- the brain is protected by MENINGES = 3 thin layers of tissue that cover the brain and spinal cord
1) dura mater = outerlayer
2) arachnoid mater = middle layer - subarachnoid space - houses CSF
3) pia mater = inner layer
Pia + arachnoid mater = leptomeninges
- between leptomeninges = subarachnoid space, which houses CSF (cerebrospinal fluid)
CSF = clear / watery fluid that is pumped around the spinal cord and brain that functions to provide nutrients as well as cushion them from impact
The dura mater has 2 layers: external + internal
the internal dura mater lies above the arachnoid mater
- subdural space = between internal dura mater + arachnoid mater
the external dura mater adheres to the inner surface of the skull
the 2 layers of the dura mater travel together, expect at meningeal folds, which help to divide sections of the brain
CAUSES OF EPIDURAL HEMORRHAGE
⦁ ** MC cause = HEAD TRAUMA **
- the meningeal arteries are protected by the skull, but can be damaged by serious head trauma
- MC site = PTERION = site where frontal, temporal, parietal, and sphenoid bones join
- this site is located right above the MIDDLE MENINGEAL ARTERY
MC site of skull fracture = TEMPORAL BONE = the most commonly affected in patients with skull fractures following blunt head trauma
- ** MC ARTERY = MIDDLE MENINGEAL ARTERY ***
- runs through foramen spinosum
Actively bleeding artery = hemorrhage
Collection of blood that results = hematoma
Once a meningeal artery is torn, blood will pool between the skull and the external layer of the dura mater ==> epidural hemorrhage / hematoma
The blood cannot cross the suture lines where the dura mater adheres, so appears as a BICONVEX or LENTICULAR shape
If blood accumulates slowly, there may be a “lucid interval” in which several hours pass before onset of symptoms
A LARGE epidural hematoma on one side can cause a “MIDLINE SHIFT” = displacement of the whole brain towards the opposite side of the skull
A LARGE epidural hematoma can also cause an increase in intracranial pressure –> can also cause brain to shift or herniate
Epidural hematoma can also cause
⦁ Supratentorial herniation = where the cerebrum is pushed against the skull or the tentorium (houses the cerebellum)
==> can compress arteries that lead to the brain –> Ischemic stroke!
⦁ Infratentorial herniation = cerebellum is pushed against the brainstem
==> can compress part of the brainstem –> can affect consciousness / respiration / heart rate
Both supratentorial + infratentorial herniation can be lethal!
SYMPTOMS OF EPIDURAL HEMORRHAGE
⦁ ** MC = LOSS OF CONSCIOUSNESS after head trauma - due to concussion **
slow epidural bleed
⦁ may have lucid interval - where patient improves temporarily right after initial trauma, but then deteriorates as hematoma grows
Lucid interval initially = the brain is initially able to compensate for the extra intracranial volume through redistribution of the blood and cerebrospinal fluid
⦁ Headache ⦁ Dizziness ⦁ Nausea / Vomiting ⦁ Focal neurological symptoms: such as muscle weakness or sensory deficit, depending on location ⦁ ** Ipsilateral pupil dilation **
BASILAR SKULL FRACTURES are closely associated with epidural hematomas = because the middle meningeal artery and vein run beneath the pterion, a relatively weak area of the skull where the frontal, parietal, temporal, and sphenoid bones meet.
⦁ clear rhinorrhea
⦁ “halo sign”
⦁ raccoon eyes = periorbital ecchymosis
⦁ battle sign = bruising behind the ears
⦁ deficits in CN 3 / 4 / 6
PHYSICAL EXAM
- assess pupillary response: Expansion of a hematoma can increase intracranial pressure and lead to an ipsilateral dilated pupil
- assess GCS scale
GCS < 8 confers a risk of ~80% of poor prognosis. Having multiple pathologies on CT scan confers a poorer prognosis
-
** CUSHING’S TRIAD ** = signifies increased ICP
1) bradycardia
2) widened pulse pressure (systolic rises steeply, diastolic decreases or remains normal)
3) irregular respirations (often irregular and deep = Cheyne stokes or apneic)
Cushing’s Triad =
1) bradycardia
2) widened pulse pressure
3) irregular respirations
DIAGNOSIS
⦁ CT without contrast
- appears as hyper-dense mass (super white)
- ** BICONVEX or LENTICULAR SHAPED ** = elliptical shape
- epidural hematomas DO NOT cross suture lines
⦁ or MRI
Lumbar puncture is contraindicated if increased intracranial pressure is suspected, such as in epidural hematomas, because it can cause herniation of the brain through the foramen magnum, compressing the brainstem and leading to respiratory arrest
TREATMENT
Due to its rapid expansion, an epidural hematoma is a neurosurgical emergency requiring drainage.
⦁ craniotomy - part of bone removed in order to remove blood accumulation below
⦁ burr hole - to drain fluid and relieve pressure
if ICP continues to be elevated, but post-op and normal vitals = HYPERVENTILATION via mechanical ventilation can serve to temporarily decrease an elevated ICP (only lasts 1-24 hours)
⦁ can also try hypertonic saline (not NS!)
⦁ can try elevating the head of the bed 30 degrees (reverse Trendelenburg)
⦁ mannitol = preferred diuretic in increased ICP (would not use Lasix as monotherapy, but in conjunction to mannitol)
⦁ aggressive mechanical cooling can be attempted if increased ICP and patient has a fever
Once hyperventilation no longer serves to decrease the ICP, the respiratory rate should be adjusted so that the patient’s PaCO2 returns to normal.
Patients classically present with a lucid interval after TBI, followed by LOC in an epidural hematoma
** stem will have patient start to feel fine, then HA **
Epidural hematoma will present with → transient loss of consciousness from an injury, then lucid period followed by increasing drowsiness, headache and unilateral (contralateral) weakness
SUBDURAL HEMATOMA
Subdural = below the outermost protective layer of the brain (dura mater)
Subdural hemorrhage = bleeding between the inner and outer layers of the dura mater
= VENOUS BLEEDING (bridging veins)
ANATOMY
- the brain is protected by MENINGES = 3 thin layers of tissue that cover the brain and spinal cord
1) dura mater = outer layer
2) arachnoid mater = middle layer - subarachnoid space - houses CSF
3) pia mater = inner layer
Pia + arachnoid mater = leptomeninges
- between leptomeninges = subarachnoid space, which houses CSF (cerebrospinal fluid)
CSF = clear / watery fluid that is pumped around the spinal cord and brain that functions to provide nutrients as well as cushion them from impact
The dura mater has 2 layers: external + internal
- internal dura mater lies above the arachnoid mater
- subdural space = between internal dura mater + arachnoid mater
the external dura mater adheres to the inner surface of the skull
the 2 layers of the dura mater travel together, except at meningeal folds, which help to divide sections of the brain
The subdural space plays a major role in venous blood drainage in the brain
Subarachnoid space has numerous arteries that supply oxygen to the brain. The blood drains into superficial cerebral veins (bridging veins) that also sit in the subarachnoid space –> travel through the arachnoid mater –> subdural space –> penetrate the inner layer of the dura mater to drain into dural venous sinuses = located between the 2 layers of the dura mater
eventually this blood in the dural venous sinuses drains into the internal jugular vein –> heart
CAUSE OF SUBDURAL HEMORRHAGE
due to rupture of the bridging veins –> hemorrhage
⦁ Head trauma (MC)- falls or shaken baby syndrome (babies have thin-walled bridging veins)
⦁ brain atrophy (elderly = brain shrinks in size –> bridging veins are stretched across a wider space
⦁ alcohol abuse (veins become thin-walled)
⦁ coup-contracoup (acceleration / deceleration injury - whiplash)
Acute subdural hemorrhage = associated with trauma
Chronic subdural hemorrhage = associated with mild trauma, cerebral atrophy, elderly, and alcoholism.
- once a bridging vein is torn, blood pools into the subarachnoid space
- since the bridging vein is under low pressure, the bleeding can be slow –> DELAYED onset of symptoms = may develop over days to weeks as hematoma gradually expands
o Acute subdural hematoma = symptoms in 1-3 days = hyperdense
o Subacute subdural hematoma = symptoms in 4days - 2 weeks = isodense
o chronic subdural hematoma = > 2 weeks = hypodense
Hematoma can compress the brain and cause INCREASED ICP (intracranial pressure)
Large subdural hematoma on one side of the brain can cause MIDLINE SHIFT
Increased intracranial pressure can also cause brain to herniate
o Supratentorial herniation = brain pushed against the skull or the tentorium
- can compress the arteries that nourish the brain –> ischemic stroke
o Infratentorial herniation = cerebellum pushed against the brainstem
- can compress brain stem which controls consciousness / heart rate / respirations
SYMPTOMS
⦁ LOC (at injury or in days / weeks as it increases in size)
⦁ Headaches
⦁ Nausea / Vomiting
⦁ Neurological symptoms: muscle weakness / sensory problems / etc
Chronic subdural hematomas present in the elderly after trauma with mental status changes, hemiparesis, headache, CN III or VI palsy, hemianopsia, and papilledema. Elderly patients on anticoagulation such as warfarin can develop subdural hematomas after even minor trauma.
-
** CUSHING’S TRIAD ** = signifies increased ICP
1) bradycardia
2) widened pulse pressure (systolic rises steeply, diastolic decreases or remains normal)
3) irregular respirations (often irregular and deep = Cheyne stokes or apneic) - no fever (98.6 or 37)
Cushing’s Triad =
1) bradycardia (< 60)
2) widened pulse pressure
3) irregular respirations (likely elevated)
DIAGNOSIS
⦁ CT without contrast
- Acute = hyperdense mass (more white than surrounding brain tissue)
- Chronic = hypodense mass (less white than surrounding brain tissue)
- Acute-on-Chronic = old bleed formed hematoma, then started to re-bleed (mixed hyper + hypodense)
- CRESCENT SHAPE / CONCAVE
Subdural hemorrhage = between 2 layers of dura mater - between outer and inner dura mater
- therefore subdural hematomas follow the contour of the brain –> CRESCENT SHAPE
- DOES CROSS SUTURE LINES (unlike epidural)
- do NOT perform LP - with increased ICP, can cause herniation
- Guidelines suggest urgent surgical evacuation if the ICP is consistently >20 mmHg.
TREATMENT
⦁ CRANIOTOMY = preferred surgical treatment of subdural hematoma
⦁ small subdural hematomas = burr hole drilled into brain, drained via catheter
- burr holes = shown to have more complications and lower efficacy than craniotomy
⦁ large subdural hematomas = craniotomy - part of bone is removed in order to drain blood below
GCS of 8 or less = Intubate
Midline shift >5 mm suggests that surgical intervention may be beneficial for the patient, but minimal shifting may be corrected medically.
if ICP continues to be elevated, but post-op and normal vitals = HYPERVENTILATION via mechanical ventilation can serve to temporarily decrease an elevated ICP (only lasts 1-24 hours)
⦁ can also try hypertonic saline (not NS!)
⦁ can try elevating the head of the bed 30 degrees (reverse Trendelenburg)
⦁ mannitol = preferred diuretic in increased ICP (would not use Lasix as monotherapy, but in conjunction to mannitol)
⦁ aggressive mechanical cooling can be attempted if increased ICP and patient has a fever
Have a high clinical suspicion for subdural hematoma in an elderly patient with history head trauma and altered mental status.
Subdural hematoma will present as → an elderly patient with a history of multiple falls who is now presenting with neurological symptom
“CRESCENT SHAPE”
also usually from trauma, like epidural hematoma, but no lucid interval
symptoms just develop slowly
Subdural hematoma will present as → an elderly patient with a history of multiple falls who is now presenting with neurological symptom
INTRACEREBRAL HEMORRHAGE
Intracerebral hemorrhage will present as → an abrupt onset of a focal neurologic deficit that worsens steadily over 30 to 90 minutes, altered level of consciousness, stupor, or coma. Headache, vomiting and signs of increased ICP
GLASGOW COMA SCALE (GCS)
out of 15 total points
minimum = 3 maximum = 15
EYE = Eye Opening (4) ⦁ 4 = spontaneous ⦁ 3 = to voice ⦁ 2 = to pain ⦁ 1 = none
VERBAL = verbal response (5) ⦁ 5 = normal conversation ⦁ 4 = disoriented conversation ⦁ 3 = words, but noncoherent ⦁ 2 = no words, only sounds ⦁ 1 = none
MOTOR = motor response (6) ⦁ 6 = normal ⦁ 5 = localized to pain ⦁ 4 = withdraws to pain ⦁ 3 = decorticate posture - an abnormal posture that can include rigidity, clenched fists, legs held straight out, and arms bent inward toward the body with the wrists and fingers bend and held on the chest = flexed arms at chest ⦁ 2 = decerebrate - an abnormal posture that can include rigidity, arms and legs held straight out, toes pointed downward, head and neck arched backwards = extended arms at sides ⦁ 1 = none
Using the Glasgow Coma Scale Generally, brain injury is classified as:
⦁ Severe: GCS 3-8 (You cannot score lower than a 3)
⦁ Moderate: GCS 9-12
⦁ Mild: GCS 13-15
If the patient’s GCS score drops to 8 or below (severe), immediate action would be required; specifically, endotracheal intubation.
ex: patient opens his eyes when his name is called, but has no verbal or motor response to painful stimuli =
3 + 1 + 1 = 5
ex: opens his eyes to pain, responds to speech with incoherent, isolated words, and tries to avoid a painful pinch to his nail-bed by pulling away from it.
2 + 3 + 4 = 9
BACTERIAL MENINGITIS
Inflammation of the meninges caused by bacteria
Meninges = 3 protective layers around the brain + spinal cord ⦁ dura mater = outermost ⦁ arachnoid mater = middle - subarachnoid space ⦁ pia mater = innermost
Meningitis = specifically inflammation of the 2 inner meninges, also called the Leptomeninges
Between the leptomeninges = subarachnoid space where CSF is located
CSF = clear / watery fluid that is pumped around the spinal cord and brain that functions to provide nutrients as well as cushion them from impact
CSF WBC count = up to 5 (no RBCs)
In 1 deciliter of CSF ⦁ 70% lymphocytes ⦁ 30% monocytes ⦁ remaining few = PMNs - PMNs (polymorphonuclear leukocytes = granulocytes = basophils + neutrophils + eosinophils) ⦁ proteins (15-50 mg) ⦁ glucose (45-100 mg) = about 2/3 of glucose found in same volume of blood ⦁ Pressure: 80-200 mmH20 = 5-20 mmHg
TOTAL AMOUNT OF CSF IN BODY = about 150mL
- is constantly replenished
- 500mL produced each day
- excess is reabsorbed into blood
For any nutrients to enter or leave the CSF = must go through tightly-regulated BBB (blood-brain barrier)
BBB = blood vessels in the brain
- endothelial cells in these blood vessels are so tightly bound to one another that they prevent leakage and only allow certain molecules to slip through them
Meningitis = NOT the inflammation of the brain itself (encephalitis), but the inflammation of the 2 inner leptomeninges surrounding the brain + spinal cord
Both can occur together, however, which is called meningoencephalitis
CAUSES / TRIGGERS OF MENINGITIS
⦁ autoimmune disease (lupus)
⦁ adverse medication reaction (intrathecal therapy - med injected directly into CSF)
- Intrathecal / immunocompromised = most associated with fungal meningitis
⦁ ** MC = INFECTION **
HOW IS INFECTION TRANSMITTED TO CSF + MENINGES
1) Direct spread
- pathogen gets into skull or spinal column and then penetrates the meninges, eventually getting to CSF
- sometimes the pathogen goes through overlying skin or up through nose
- MC = anatomical defect that allows pathogen through
⦁ congenital = Spina bifida
⦁ acquired = skull fracture - CSF leaking through sinuses
2) Hematogenous spread
- pathogen spreads through blood and through endothelial cells that make up BBB, and into CSF
- either by binding to surface receptors or finding area of damage in BBB
Once pathogen is in CSF ==> can start multiplying!
small amount of WBCs in CSF –> release cytokines –> recruit more WBCs –> may end up with thousands of WBCs in 1 microliter of CSF
> 5 WBCs = enough to signify meningitis
DIAGNOSIS FOR BACTERIAL MENINGITIS
- Opening Pressure (80-200 mmH2O / 5-20 mmHg) = Increased > 200 mmH20 / > 5-20 cm
- CSF appearance = Turbid
- Glucose levels (50-80) = decreased (< 40)
- Protein levels (18-58) = increased (>200)
- WBC count (0-5) = increased (100 - 100,000)
- PMNs (1%) = predominantly neutrophils (> 80%/ > 90%)
- gram stain positive
The additional immune cells attract more cells to the area –> start causing local destruction as they try to control the infection
Bacteria + Virus = usually cause acute meningitis
Fungi = usually cause chronic meningitis
BACTERIAL CAUSES
- MC overall bacterial cause = STREP PNEUMO
o < 1 month
⦁ MC = Group B strep (strep agalactiae) = 70% (gram positive cocci)
⦁ Listeria monocytogenes* (gram positive rod)
⦁ E. coli (gram negative rods)
⦁ strep pneumo (gram positive diplococci)
- Tx = Ampicillin (covers listeria) + Cefotaxime or Aminoglycoside (also used in 1-3 months old)
o 1 month - 18 years
⦁ MC = Neisseria meningitidis (petechial rash) (gram negative diplococci)
⦁ strep pneumo* (gram positive diplococci)
⦁ h. flu
- 1-3 months old = Ampicillin (covers listeria) + Cefotaxime or Aminoglycoside
- > 3 months - 18 = Ceftriaxone + Vanco
o 18 - 50 y/o
⦁ MC = Strep pneumo (gram positive diplococci)
⦁ Neisseria meningitidis (petechial rash) (gram negative diplococci)
⦁ listeria monocytogenes (gram positive rod)
⦁ h. flu
- Tx = Ceftriaxone + Vanco
o > 50 y/o
⦁ Strep pneumo (gram positive diplococci)
⦁ listeria monocytogenes (gram positive rod)
- Tx = Ampicillin + Ceftriaxone +/- Vanco
Tick-borne: Borrelia burgdorferi (lyme dz) meningitis
** start empiric antibiotics immediately! - don’t wait for LP **
SYMPTOMS
- CLASSIC TRIAD OF MENINGITIS SYMPTOMS
⦁ headache
⦁ fever / chills (95%)
⦁ nuchal rigidity (neck stiffness)
OTHER SYMPTOMS
⦁ photophobia
⦁ phonophobia
⦁ N / V
Can develop AMS / Seizures
** start empiric antibiotics immediately! - don’t wait for LP **
DIAGNOSIS
o Physical Exam
⦁ ** KERNIG’S SIGN ** = laying on back, lift 1 leg up, flexed at 90 at the knee. Slowly straighten the leg out at the knee to where leg is straight up –> back pain!
⦁ ** BRUDZINSKI SIGN ** = laying flat on back, patient flexes head forward –> causes patient to automatically bend both legs at the knee with feet still touching floor
o CT to rule out mass effect BEFORE getting LP
o LUMBAR PUNCTURE = ** definitive diagnosis **
- needle penetrates into subarachnoid space, take CSF
- analyze pressure / WBCs / Protein / Glucose
⦁ neutrophils
⦁ decreased glucose (< 45)
⦁ increased protein (> 200)
⦁ increased CSF pressure (>5-20mmHg) (> 200mmH20)
⦁ turbid color / cloudy
** start empiric antibiotics immediately! - don’t wait for LP **
** gold standard for diagnosis = LP - CSF BACTERIAL CULTURE ** (takes a few days, but is definitive)
- if suspect particular cause = can test for that
⦁ western blot - for TB
⦁ thin blood smear - for malaria
BACTERIAL TREATMENT
- depends on underlying cause
o < 1 month (MC = group B strep)
- Tx = Ampicillin (covers listeria) + Cefotaxime (also used in 1-3 months old)
o 1 month - 18 y/o (MC = Neisseria)
- 1-3 months = - Tx = Ampicillin (covers listeria) + Cefotaxime
- > 3 months = - Tx = Ceftriaxone + Vanco
o 18 - 50 y/o (MC = strep pneumo
- Tx = Ceftriaxone + Vanco
o > 50y/o (MC = strep pneumo)
- Tx = Ampicillin + Ceftriaxone +/- Vanco
POST-EXPOSURE PROPHYLAXIS
⦁ Cipro 500mg PO x 1 dose
⦁ Alternative = Rifampin 600mg PO q12h x 2 days
Patient presents as → a 34-year-old man who is brought by his wife because she believes her husband is very ill. The patient initially had a headache that progressed to neck stiffness and an inability to look at bright lights. His temperature is 103.1° F, blood pressure is 134/82 mmHg, and respirations are 20/min. Extreme pain is elicited upon flexion of the patient’s neck and the patient’s legs.
ASEPTIC MENINGITIS = non-bacterial meningitis = viral / fungal / TB
Inflammation of the meninges NOT caused by bacteria, but caused by virus / fungus / TB / etc.
Meninges = 3 protective layers around the brain + spinal cord ⦁ dura mater = outermost ⦁ arachnoid mater = middle - subarachnoid space ⦁ pia mater = innermost
Meningitis = specifically inflammation of the 2 inner meninges, also called the Leptomeninges
Between the leptomeninges = subarachnoid space where CSF is located
CSF = clear / watery fluid that is pumped around the spinal cord and brain that functions to provide nutrients as well as cushion them from impact
CSF WBC count = up to 5 (no RBCs)
In 1 deciliter of CSF ⦁ 70% lymphocytes ⦁ 30% monocytes ⦁ remaining few = PMNs - PMNs (polymorphonuclear leukocytes = granulocytes = basophils + neutrophils + eosinophils) ⦁ proteins (15-50 mg) ⦁ glucose (45-100 mg) = about 2/3 of glucose found in same volume of blood ⦁ Pressure: 80-200 mmH20 = 5-20 mmHg ⦁ WBC count (normal) = up to 5
TOTAL AMOUNT OF CSF IN BODY = about 150mL
- is constantly replenished
- 500mL produced each day
- excess is reabsorbed into blood
For any nutrients to enter or leave the CSF = must go through tightly-regulated BBB (blood-brain barrier)
BBB = blood vessels in the brain
- endothelial cells in these blood vessels are so tightly bound to one another that they prevent leakage and only allow certain molecules to slip through them
Meningitis = NOT the inflammation of the brain itself (encephalitis), but the inflammation of the 2 inner leptomeninges surrounding the brain + spinal cord
Both can occur together, however, which is called meningoencephalitis
CAUSES / TRIGGERS OF MENINGITIS
⦁ autoimmune disease (lupus)
⦁ adverse medication reaction (intrathecal therapy - med injected directly into CSF)
- Intrathecal / immunocompromised = most associated with fungal meningitis
⦁ ** MC = INFECTION **
HOW IS INFECTION TRANSMITTED TO CSF + MENINGES
1) Direct spread
- pathogen gets into skull or spinal column and then penetrates the meninges, eventually getting to CSF
- sometimes the pathogen goes through overlying skin or up through nose
- MC = anatomical defect that allows pathogen through
⦁ congenital = Spina bifida
⦁ acquired = skull fracture - CSF leaking through sinuses
2) Hematogenous spread
- pathogen spreads through blood and through endothelial cells that make up BBB, and into CSF
- either by binding to surface receptors or finding area of damage in BBB
Once pathogen is in CSF ==> can start multiplying!
small amount of WBCs in CSF –> release cytokines –> recruit more WBCs –> may end up with thousands of WBCs in 1 microliter of CSF
> 5 WBCs = enough to signify meningitis
DIAGNOSIS FOR VIRAL MENINGITIS
- Opening Pressure (5-20cm) = NORMAL or mild increase = < 200mmH20
- CSF appearance = Clear
- Glucose levels (50-80) = normal
- Protein levels (18-58) = normal or mild increase
- WBC count (0-5) = slight increase (10-300)
- Predominantly LYMPHOCYTES
- gram stain = negative
DIAGNOSIS FOR FUNGAL + TUBERCULOSIS MENINGITIS
- Opening Pressure (5-20cm) = Normal or mild increase
- CSF appearance = Fibrin webs
- Glucose levels (50-80) = decreased
- Protein levels (18-58) = increased
- WBC count (0-5) = slight increase (10-200)
- Predominantly LYMPHOCYTES
- gram stain = negative
- ** beta-D-glucan *** = approved blood test to detect systemic fungal infection
The additional immune cells attract more cells to the area –> start causing local destruction as they try to control the infection
Bacteria + Virus = usually cause acute meningitis
Fungi = usually cause chronic meningitis
o VIRAL CAUSES
⦁ Enterovirus = MC (MC = Echovirus, Coxsackie)
⦁ Arboviruses (arthropod borne viruses - via insects)
⦁ HSV
⦁ HIV
⦁ Mumps
o FUNGAL CAUSES
⦁ Cryptococcus
⦁ Coccidioides
- mainly affect immunocompromised
Cryptococcus neoformans is an opportunistic fungus that most commonly causes meningitis in HIV patients.
SYMPTOMS
- CLASSIC TRIAD OF MENINGITIS SYMPTOMS
⦁ headache
⦁ fever / chills (95%): fever > 38C (100.4F)
⦁ nuchal rigidity (neck stiffness)
OTHER SYMPTOMS
⦁ photophobia
⦁ phonophobia
⦁ N / V
Viral symptoms not as intense as bacterial meningitis symptoms
- Viral meningitis = associated with NORMAL cerebral function - not commonly associated with focal neurological deficits or seizures (no AMS / Seizures)
DIAGNOSIS
o Physical Exam
⦁ ** KERNIG’S SIGN ** = laying on back, lift leg to be flexed at 90 at hip. Slowly straighten the leg at the knee to where leg is straight up –> back/neck pain!
⦁ ** BRUDZINSKI SIGN ** = laying flat on back, passive flexion of head/neck forward –> causes patient to automatically bend both legs at the knee = flex both knees + hips
⦁ In babies look for a bulging fontanelle
- 1) CT scan to rule out intracranial mass BEFORE LP
- 2) LP - CSF analysis
Virus =
⦁ Lymphocytes
⦁ normal glucose
⦁ mildly elevated protein
o PCR = most accurate test = will detect viral genetic material to find out if patient has specific virus
- can be used to find specific causes, such as HIV, enteroviruses, HSV, TB, etc
TREATMENT = supportive care ⦁ antipyretics ⦁ IV fluids ⦁ antiemetics ⦁ IV acyclovir if HSV
PROGNOSIS = good
usually self-limiting, lasts about 7-10 days
- increased fatality in neonates
Patient presents as → a 34-year-old man who is brought by his wife because she believes her husband is very ill. The patient initially had a headache that progressed to neck stiffness and an inability to look at bright lights. His temperature is 103.1° F, blood pressure is 134/82 mmHg, and respirations are 20/min. Extreme pain is elicited upon flexion of the patient’s neck and the patient’s legs.
SUBARACHNOID HEMORRHAGE
2 main types of Stroke
⦁ Hemorrhagic stroke
⦁ Ischemic stroke
Hemorrhagic stroke = when an artery ruptures and bleeds within the brain
Ischemic stroke = when an artery gets blocked
2 types of Hemorrhagic strokes
⦁ Subarachnoid hemorrhage
⦁ Intracerebral hemorrhage
Intracerebral hemorrhage = bleeding within cerebrum
Subarachnoid hemorrhage = bleeding between pia mater and arachnoid mater
SUBARACHNOID HEMORRHAGE
- can be lethal!
- bleeding that pools between the arachnoid mater and the pia mater –> increased ICP
- prevents enough blood from flowing into the brain
BLOOD SUPPLY OF THE BRAIN
- brain receives blood from the left + right INTERNAL CAROTID ARTERIES as well as the left + right VERTEBRAL ARTERIES
- left + right vertebral arteries come together to form the BASILAR ARTERY ==> branches provide blood flow to the cerebellum + brainstem
- the basilar artery also branches into the right + left POSTERIOR CEREBRAL ARTERIES which provide blood to the occipital lobe and part of the temporal lobe + thalamus
- the left + right carotid arteries flow into the left + right MIDDLE CEREBRAL ARTERIES which provide blood to the lateral portions of the frontal / parietal / temporal lobes of the brain
- the left + right carotid arteries also branch into the left + right ANTERIOR CEREBRAL ARTERIES which provide blood to the medial portions of the frontal + parietal lobes
CIRCLE OF WILLIS = right/left internal carotid arteries + middle cerebral arteries + anterior cerebral arteries + anterior communicating artery + posterior cerebral arteries + posterior communicating arteries
- allow blood to get to various parts of the brain if blockage occurs
CAUSES OF SUBARACHNOID HEMORRHAGE ⦁ 1) MC = Berry Aneurysm - rupture - can rupture with increased ICP - Marfans = predisposed to aneurysms - MC aneurysm in brain = berry aneurysm of anterior cerebral arteries
The most common site of saccular aneurysm rupture causing subarachnoid hemorrhage is at the junction of the anterior communicating artery and anterior cerebral artery.
⦁ 2) Trauma
⦁ 3) AVM
- lack of capillaries between artery + vein = replaced by abnormally tangled vessels that directly connect high pressures of arteries with veins that are not built for high pressures –> rupture
Once SAH is occurring –> starts putting pressure on skull, nearby tissues and compressing nearby blood vessels
- less blood is flowing downstream to rest of brain
- healthy tissue can die with direct pressure + lack of oxygen within a few hours
- another complication = blood vessels sitting in a pool a blood can start to vasoconstrict (VASOSPASM) **
- if this occurs in the circle of willis = will reduce blood flow to brain –> further ischemic injury
Subarachnoid hemorrhage has an increased risk of developing communicating or obstructive hydrocephalus.
SYMPTOMS ⦁ sudden onset of severe "THUNDERCLAP" HEADACHE - worst headache of my life ⦁ may have LOC ⦁ Nuchal rigidity (neck stiffness)*** ⦁ photophobia*** ⦁ N / V** ⦁ vision changes ⦁ confusion / delirium
Subarachnoid hemorrhage (SAH) patients will commonly report having another sudden, severe headache one to three weeks prior. These are known as “sentinel headaches” and are thought to be caused by a minor hemorrhage.
DIAGNOSIS ⦁ CT FIRST without contrast*** = if CT negative but high suspicion => ⦁ LP - Xanthochromia (RBCs) - Increased CSF (ICP)
TREATMENT
⦁ Emergent surgery! - coiling or clipping of aneurysm
- supportive = bed rest / lower ICP / adjust BP
- CCB (*Nicardipine or Nimodipine) - can help prevent vasospasm from setting in
UPPER MOTOR NEURON LESION VS LOWER MOTOR NEURON LESION
o UPPER MOTOR NEURON LESION (UMN) ⦁ spastic paralysis or spastic muscle tone ⦁ no dis-use atrophy or slight atrophy ⦁ INCREASED DTRs ⦁ Positive BABINSKI sign
EXAMPLES OF UPPER MOTOR NEURON LESION ⦁ CVA ⦁ Cerebral Palsy ⦁ MS ⦁ Brain or spinal cord injury
o LOWER MOTOR NEURON LESION (LMN) ⦁ flaccid paralysis or flaccid muscle tone ⦁ severe atrophy ⦁ absent DTRs ⦁ plantar reflex = down-going
EXAMPLES OF LOWER MOTOR NEURON LESION ⦁ Guillain Barre ⦁ Bell's Palsy ⦁ Cauda Equina ⦁ Botulism ⦁ Poliomyelitis
