Amyloid plaques - extracellular accumulation of beta amyloid 1-42

not seen in FTD

concentrated in the hippocampus/parahippocampal gyrus/parietal lobe, which corresponds w/ memory loss and visual-spatial deficits

Neurofibrillary tangles - intracellular accumulation of hyperphosphorylated tau strands

also seen in FTD

tau is a normal protein that anchors microtubules, allowing neurons to maintain their axons' structural integrity

Loss of cortical neurons causes significant brain atrophy

Premild/mild cognitive impairment - short-term memory loss (more than expected with normal aging)

Mild - short-term memory loss, mild visual-spatial difficulty, some trouble finding words, but otherwise independent (lasts about 5 years)

Moderate - may become delusional or agitated, with sundowning, hypersexuality due to amydala damage, and trouble with language (lasts about 3 years)

Severe - gait apraxia from frontal cortex loss, feet "stuck to floor", grasp reflexes, language loss, bedridden and needs total care, trouble swallowing

Total duration from diagnosis is normally about 10 years

Primary family member (3x)

Inherited genetic mutation (amyloid precursor genes or presenilin)

APOE4 genotype (increases susceptibility, but doesn't directly cause AD)

Head trauma

Age

Female

Copper

Mild Cognitive Impairment

Diabetes - insulin is responsible for removing small soluble amyloid proteins before they develop into plaques

Hypertension

Down's Syndrome (amyloid protein is located on chromosome 21)

1) misidentification by family as normal aging

2) social skills can mask early changes

3) denial or lack of insight by patient

4) reluctance to report symptoms due to stigma

5) lack of screening tools

1) ADL

2) Clinical Dementia Rating

3) MMSE (insensitive to early disease, but useful to track deterioration)

4) MRI > CT, but more expensive and neither is useful for early diagnosis (ventricles + sulci enlarged from atrophy, and anterotemporal horn enlarged due to hippocampal atrophy)

5) PET - very expensive, may show loss of metabolism in frontal/parietal/temporal lobes, but may not

6) SPECT - less expensive but also less sensitive than PET

7) Pittsburgh B Compound (PIB) is a marker for amyloid protein in PET, but is not a great marker since many normal people have amyloid as well

Masked facies/can't look up - Parkinsonism

Have problems with behavior + judgement, but no memory problems

Autosomal dominant inheritance

Problem can be in chromosome 17 (tau protein, progranulin) or chromosome 3

In FTD with ALS, the TDP-43 protein is abnormal

Just supportive and symptomatic treatment for now:

1) cholinesterase inhibitors and memantine

2) antidepressants + atypical antipsychotics are helpful for managing symptoms

3) there are some amyloid busters going into trials now

LAND - lethargy, ataxia, nystagmus, and dysarthria

Hepatocerebral degeneration - cirrhosis of the liver, dementia (mental slowness, apathy, inattention, or memory impairment), movement disorders, hyperreflexia, Babinski's sign

Tremor (morning shakes)

Agitation

Anorexia

Nausea/Vomiting

Insomnia

Tachycardia

Hallucinosis (25%) - auditory or visual

Seizures (rum fits) - tonic/clonic, often multiple, but not difficult to control

Seizures can cause head trauma with plaque jaune (old cerebral contusions w/ yellow gold discoloration from resiudal hemosiderin), or intracranial hemorrhages like subdural or lobar hematomas

Delirium tremens - hyperautonomia, delirium w/ psychosis)

No seizures

Chronic alcoholic hallucinosis - auditory and unpleasant

Toxic tremor

Can be fatal due to infection, cardiovascular collapse, trauma, or pancreatitis, among others

Needs to be managed in the ICU with high-dose benzodiazepines and beta blockers, fluid management, and antibiotics

Ataxia, confusion, and ophthalmoparesis (CN VI palsy)

Acute thiamine deficiency, so need to give thiamine before giving glucose supplemented with thiamine

Neuronal loss, gliosis, and petechial hemorrhage in the periaqueductal gray

Most symptoms are at least partially reversible, but can be fatal

Memory deficits/peripheral neuropathy/ataxia

Apathy, poor insight, confabulation (patient makes things up but doesn't realize we can tell he is making things up)

Bilateral degeneration of dorsomedial thalamic nuclei

Usually irreversible

Aka cerebellar parenchymal degeneration

Degeneration of the superior, anterior vermis that is very noticeable on imaging

Purkinje cell loss causes gait ataxia

Requires a chronic alcoholism > 10 years and a nutritional deficiency

More common in middle-aged men (40-60)

Gradual onset over weeks to months

Midline ataxia that is often exacerbated by peripheral neuropathy commonly associated with alcoholism, but there is no limb ataxia

Can be reversible or at least stabilize with abstinence and better nutrition

All symptoms can stabilize and possibly reverse with abstinence and proper nutrition

Stocking glove syndrome - primarily sensory and very painful

Mononeuropathies - individual peripheral nerves become more susceptible to trauma (i.e. peroneal at knee, ulnar at elbow, radial at wrist, etc.)

Rhabdomyolysis - breakdown of muscle that injuries the kidneys and is painful; causes proximal weakness with tenderness in hips/shoulders

Caused by hyponatremia, which can be caused by giving 3x saline too aggressively

In response to hyponatremia, the brain can try to correct too rapidly and cause white matter destruction in the brainstem

Leads to "locked in" syndrome, where the patient is completely paralyzed everywhere except the eyes, but is fully awake and aware

Brain consumes disproportionate amount of body's oxygen since it derives almost all of its energy from oxidative phosphorylation

Glutamate and other excitatory amino acids - can selectively kill neurons

Activated microglia

Amyloid plaques + Tau tangles - plaques may cause damage due to catalyzing the Fenton reaction

Effective in mice, but not shown to have any effect in humans

Memantine - may have a modest beneficial effect for Alzheimer's patients by partially blocking NMDA receptors, reducing overexcitation and any subsequent oxidative damage

Vitamin E, Vitamin C, memantine

Mainly want to improve omega-3 to omega-6 ratio by eating fish

Mixed reports of effectiveness

Other anti-inflammatories: NSAIDs, curcumin

Change in sense of taste or smell

Difficulty chewing/swallowing/digesting food

Cells may not be as efficient in utilizing energy
Appetite control systems in brain can malfunction, causing extreme eating disorders

Difficulty preparing meals

Forgetting to eat a meal after cooking it

Nerve cell death can steal ability to feel hunger or thirst

Plaques and tangles - may actually be protective against oxidative damage, since oxidative stress drops after appearance of plaques and tangles

If this is true, then the true cause of Alzheimer's Disease may be oxidative damage and inflammation

Acetylcholine levels are lowered in Alzheimer's Disease, so some drugs (i.e. Aricept) focus on boosting ACh levels

Want to increase folic acid and B vitamins while reducing homocysteine levels

Exercise is the only proven way to slow Alzheimer's progression

Have antioxidant and anti-inflammatory properties

Curcumin - yellow curry spice that may be partly responsible for India's much lower rates of Alzheimer's Disease

Red wine - moderate consumption of resveratrol, the polyphenol in red wine, may be associated with a lower incidence of Alzheimer's Disease

Gingko - in addition to polyphenol effects, also improves brain circulation

After head trauma, should be given 1 year to improve

Regulated by alpha neurons, with excitatory input (glutamate/aspartate) from muscle spindle afferents and inhibition from the basal ganglia and cerebellum (GABA)

Flexors and internal rotators more heavily affected, so patients will be flexed at elbows + wrists, stand on their toes, and have knees and hips flexed and internally rotated

Measured by Ashworth scale (1-5, where 1 = normal and 5 = rigid in flexion or extension)

Physical exam is best done with patient lying down

Contractures - permanent shortening of muscle or tendon that does not improve with treatment

Some children rely on involuntary contractions of spasticity to supplement weak voluntary contractions in order to function - for them, treatment of their spasticity may not be necessary

Baclofen - works on GABA receptors in the spinal cord and causes drowsiness, ataxia, and confusion

Diazepam - works on GABA receptors in the brain and spinal cord and causes lethargy and tolerance

Dantrolene - works on the sarcoplasmic reticulum and causes weakness, diarrhea, and a rash

Tizanidine - alpha-2 agonist at interneurons and afferent terminals that decreases the release of ACh and causes drowsiness, hypotension, and dizziness

Alcohol or phenol can be used, but they permanently damage neurons and can cause muscle necrosis in addition to being painful on injection

Instead, injection of botulinum toxin is used for focal spasticity and works by blocking the release of ACh from presynaptic storage vessels by preventing membrane fusion

Single dose starts working in 2 hours, peaks at 4 hours, and wears off by 8 hours

Can use < 1% of concentration of oral dose, so very few systemic side effects

Can be used anytime once the child is big enough for the pump to fit

Battery lasts for 4-5 years

Side effects include listlessness, trunk/neck hypotonia, and urinary hesitancy

Overdose causes profound hypotonia and lethargy, and is treated with physostigmine and intubation/LP to draw off drug

Complications (infections, etc.) more frequent in pediatric patients that adults

May contribute to development of scoliosis, but since scoliosis is part of the natural history of cerebral palsy, this is not certain

Very effective therapy that improves pain, mental health, psychosocial status, and the amount of parental care needed

Motor (ventral) rhizotomy is only indicated for uncontrollable hyperkinetic movement disorders

Sensory rhizotomy, however, can be effective in the treatment of spastic diplegia

Examine the L2-S1 roots

First, separate dorsal roots from ventral roots

Then, stimulate each root one by one - if normal, should only be a single, brief muscle contraction followed by relaxation

In abnormal roots, however, there is a tetanic contraction that spreads to other muscle groups -> cut them

Reduces spasticity in upper and lower extremities

Usually done in children (ages 4-8) who are still capable of ADLs

Physical/occupational therapy post-surgery is at least as important as the surgery itself

Females > Males

4-72 hours

Unilateral, throbbing, worsened by movement, moderate to severe (at least 2)

Nausea, vomiting, photophobia + phonophobia (at least 1)

Aura - transient disturbances (i.e. flashing lights) preceding a migraine by 60 minutes or less

Most migraineurs do NOT suffer an aura

Females > males

Episodic or chronic

30 minutes to 7 days

Nonthrobbing, mild to moderate pain, not worsened by movement, bilateral (at least 2)

No nausea, vomiting, or photophobia and phonophobia

Unilateral

Males > females

30-120 minutes

1-8/day, especially at night

Pain is excruciating

Tumor

Trauma - concussive headache can look like migraine, but won't respond to migraine medications

Analgesic rebound - most common reason for a daily headache problem, and can be more powerful than a prophylactic medication

Sinusitis - rare

Subarachnoid hemorrhage

Meningitis and other infections

Migraines are often mistaken for sinus headaches because of referred pain from the trigeminal nerve

Caused by activation of trigeminal nucleus caudalis (TNC) due to vasodilation of dural blood vessels causing release of cGRP that is picked up by the nearby afferent fibers of CN V

Activation of the TNC can also result in activation of cranial parasympathetic fibers leading to lacrimation, rhinorrhea, and congestion that can cause sinus-like symptoms in migraine

Diagnosis of acute sinusitis requires purulent nasal discharge and pathologic sinus findings on imaging

Chronic sinusitis is NOT a cause of headache unless it relapses into the acute stage

Diet

Sleep deprivation or excess

Hormonal changes

Weather

Environmental factors

Physical exertion

Stress + anxiety

Head trauma

Taken after attack has begun to relieve pain/disability and prevent progression

Nonspecific (medication does NOT directly target cause of migraine) - NSAIDs, combination analgesics, neuroleptics/antiemetics, corticosteroids

Specific - ergotamine/DHE, triptans

Triptans are effective in migraine with or without aura

Should try medication in at least 2 separate attacks before giving up on it

Triptans and NSAIDs are synergistic

Want to take treatment as early in attack as possible

Nonpharmacologic treatments - cold compress, rest, quiet

Use a maximum of 2-3 times/week

Best when attacks are infrequent or when preventive medications cause problems or if adherence to preventive medication is difficult

53% of migraineurs meet criteria (in terms of disability and frequency) for preventive therapy, but < 5% actually use it

Anticonvulsants

Antidepressants

Beta-blockers

NSAIDs

Serotonin antagonists

Neurotoxins (Botox)

Angiotensin inhibitors

ACh inhibitors

Nociceptive - noxious peripheral stimuli

Heat pain receptors are distinct from cold ones

Normally, pain is conveyed by small myelinated A-delta and unmyelinated C fibers, but in injury A-beta fibers can be rerouted to play a role in activating pain fibers

Capsacin - a TRPV1 receptor agonist that burns the receptor out from overexcitation, providing pain relief

Inflammatory - due to release of cytokines that lower the pain threshold

Neuropathic - due to nerve damage

Non-neuropathic, non-inflammatory - due to abnormal brain processing

Heightened dorsal horn excitability due to increased peripheral nociceptor activity

Reduced threshold for dorsal horn neuron activation

Increased receptive field of dorsal horn neurons

Increased response of dorsal horn neurons to the same level of painful stimulation

Mechanisms - NMDA receptor activation, altered gene expression, decreased inhibition, microglial activation, and changes in thalamic/somatosensory cortex

The brain regions involved in pain processing (amygdala, thalamus, prefrontal cortex) are also responsible for emotional processing, so chronic pain can easily cause depression

Decompressive surgery can work very well

However, sometimes, the nerve will be permanently damaged or altered and pain will persist following surgery

In this case, implantation of a spinal cord stimulator that produces a tingling, non-painful sensation can help to distract the brain away from the painful stimuli

A clinical manifestation of an abnormal and overly excited/synchronized population of cortical neurons

The result of either an excess of excitation or a lack of inhibition

Can be due to excitatory axonal sprouting, loss of inhibitory neurons, loss of the excitatory neurons that drive inhibitory neurons, or ion channel defects

Epilepsy is a tendency toward repeated seizures that are unprovoked by any systemic or acute neurologic insults

Congenital - born with a malformed or disorganized brain; the most common cause of epilepsy in the US

Genetic - born with an ion channel defect that destines the patient to develop seizures; a rare cause

Acquired - from trauma, stroke, bleeding, lupus, encephalitis, meningitis, etc.; anything that causes an imbalance in excitation and inhibition can cause epilepsy

High temporal resolution but poor spatial resolution

Summation of excitatory and inhibition postsynaptic potentials from the neurons that happen to be perpendicular to the surface of the skull (mostly the pyramidal cells from layer 5)

Poor sampling since most of the brian is NOT organized in this orientation

Interictal spikes and paroxysmal depolarization shifts - spontaneous, abnormal depolarizations that can be recorded in epileptic patients in their post or pre-ictal state

Prevalence equivalent to lung cancer in men or breast cancer in women

Most prevalent neurologic disorder affecting people of all ages

Two distinct spikes in prevalence - at birth (congenital) and over 60 (acquired)

Most common cognitive impairment is memory loss

Sudden unexpected death in epilepsy (SUDEP) - a severe seizure occurs which generates apnea and/or a cardiac arrhythmia that spikes NE/EPI levels by 40x

SUDEP accounts for 7-17% of death in epilepsy patients

Overall, epileptic patients have a 2-3x increased mortality than the general population

Somatosensory symptoms - i.e. aura

Deja vu - memory structures of the temporal lobe become hyperexcited

No amnesia

Very brief

A simple partial that spreads enough to alter awareness

May start with deja vu, but soon alters to staring or unresponsiveness or loss of speech

< 2 minutes

Can be amnesic

Automatisms - subtle but very telltale movements such as lip smacking or fidgeting

Starts as a simple partial, but spreads all over the brain

Convulsive (tonic/clonic) seizures

Variable symmetry, intensity, and duration of tonic and clonic phases

1-3 minutes

Post-ictal confusion and somnolence, with or without a transient focal deficit

Autosomal dominant with incomplete penetrance

Brief staring spells (3-20 seconds) with impairment of awareness

Sudden onset and resolution

Can be provoked by hyperventilation

Onset generally between 4 and 14

Often resolves by age 18

Normal development/intelligence

EEG shows generalized 3 Hz spike-wave discharges

Brief staring spells (5-30 seconds), with variably reduced responsiveness

Gradual onset and resolution over a few seconds

Not provoked by hyperventilation

Onset generally after age 6

Often found in children with a global cognitive impairment

Generalized slow spike-wave complexes (< 2.5 Hz)

Often also have tonic/atonic seizures

Tends to be more resistant to medications

Brief, shock-like jerking of a muscle or muscle group

Bilaterally synchronous

< 1 second

Need to differentiate from benign, non-epileptic myoclonus (i.e. while falling asleep)

Generalized 4-6 Hz polyspike-wave complexes

Symmetric, tonic muscle contraction of extremities, waist, and neck

2-20 seconds

Sudden attenuation with generalized low-voltage fast activity or generalized polyspike-wave

Sudden loss of postural tone

Can result in sudden falls or, if milder, just sudden head drops/jaw drops

Consciousness usually impaired

Lasts seconds and rarely for > 1 minute

Sudden diffuse attenuation for a generalized polyspike-wave

Loss of consciousness and post-ictal lethargy/confusion

30-120 seconds

Tonic phase - stiffening/falling, associated with an ictal cry

Clonic phase - rhythmic extremity jerking

Generalized polyspikes

Childhood onset

Slow spike-wave EEG

Can have tonic, atypical absence, atonic, and other seizure types

Mental retardation

Myoclonic episodes in infancy/early childhood

Occurs between 6 months and 5 years

Simple - < 15 mins, generalized, at most 1/day

Complex - > 15 mins, focal, can have multiple/day

Boys > girls

Nocturnal oropharyngeal simple partial seizures with or without secondary generalization

Extremely benign and goes away after a few years

Asymptomatic - CEA if stenosis > 60%

Symptomatic - CEA if stenosis > 70%

Aspirin is sufficient if stenosis < 50%

CEA and stenting have similar long-term efficacy and safety

CEA has lower risk of stroke, but higher risk of MI

In younger patients, stenting seems to work better

Aspirin - blocks COX-2

Dipyrimadole - blocks phosphodiesterase

Clopidogrel - blocks ADP receptors

Aspirin + clopidogrel should NOT be taken together due to increased risk of hemorrhage

Estimated by finding CT slice with widest and longest area of hemorrhage

Count the number of total slices with hemorrhage

Volume = (W * L * H)/2

Presentation of Intracerebral Hemorrhage

Supratentorial - contralateral weakness/numbness, speech + visual disturbances

Cerebellar - headache, nausea/vomiting, vertigo, sudden ataxia/dysarthria

Brainstem - impaired consciousness, bilateral cranial nerve signs

Elderly patient with dementia or memory loss and NO history of hypertension

Presents with lobar hemorrhage that is heterogeneous and not round

Diagnostic test is Congo red stain looking for amyloid

Bilateral occlusion of the carotids as they come up into the brain

The brain compensates for this slow ischemia by creating lots of small collaterals around the occlusions which can bleed as you get older

Presents with worst headache of life - ruptured aneurysm

Frequently misdiagnosed in ER as a migraine

Sentinel headache - a milder headache that precedes the rupture by several weeks, caused by minor leaks from the aneurysm

50% mortality, 30% die before getting to hospital

Risk of re-rupture is 4% in first 24 hours, but rises to 50% over next 6 months

Non-focal neurologic deficits

Head CT can miss 10-15% of the time - more sensitive acutely

If CT is negative but presentation looks like aneurysm, get a LP and look for xanthochromia in the CSF (yellow tint due to presence of bilirubin from ruptured old RBC's - takes 6-8 hours for the bilirubin to show up since it has to be metabolized from released heme)

Mirror aneurysm - 15% chance, so should check

Vessel walls thin dramatically once they enter the skull, which makes aneurysms more common

Most feared complication of a subarachnoid hemorrhage

Begins on day 4, peaks at day 7, and subsides by day 21

Can be prevented with nimodine

Delayed cerebral ischemia when blood vessels constrict

Can also be treated by inducing hypertension to force blood into brain or with a balloon angioplasty to force vessel open

Abnormal within first 45 mins compared to 6 hours for CT

DWI is the gold standard - measures diffusion of water

In infarction, cells are ischemic, so depletion of ATP causes failure of Na+ and K+ pumps, allowing interstitial water to flow into the cells

Once water gets inside, it is trapped there -> therefore there is less diffusion in infarcted areas

DWI is bright with low diffusion and dark with high, so infarcted areas will be bright

Mean transit time (MTT) - average time required for blood to flow from major cerebral artery supplying a given area of brain to the major cerebral vein draining that area

Cerebral blood volume (CBV) - volume of blood in a given area of brain

Cerebral blood flow (CBF) = CBV/MTT

Sodium channel - lengthen the refractory period

Calcium channel - blocking them prevents neurotransmitter release from presynaptic terminals since the release is triggered by depolarization caused by influx of Ca2+

Glutamate antagonists - works in theory, but so many side effects that there are no drugs on the market that actually use this mechanism

GABA activation - increased synthesis of GABA, increased release of GABA, or increased reuptake of GABA by increasing the activity of GABA-transaminase, which converts GABA to glutamate to be shipped from astrocyte back to presynaptic neuron

GABA functions by hyperpolarizing neurons by opening Cl- channels, so increasing GABA will decrease neuronal activity, which is good for controlling seizures

Partial, tonic/clonic, status epilepticus
Highly protein bound

Liver enzyme inducer

Non-sedating

Blood levels important since metabolism is easily saturated at higher dosage levels

Interferes with learning, so not good for children

Gingival hyperplasia + excess/abnormal body hair growth

Teratogen - fetal hydantoin syndrome

Partial or tonic/clonic

Metabolized by liver

Highly protein bound

Liver enzyme inducer

Sedating

Antidepressant activity

Spina bifida (10x)

Small risk of aplastic anemia (5-8x)

Partial (less effective than phenytoin or carbamazepine), tonic/clonic, absence (if ethosuximide doesn't work), tonic, atonic, clonic

Highly protein bound

Non-sedating

Inhibits metabolism of other antiseizure medications, especially phenobarbital

Liver toxicity, especially those under 2 or over 60 - carnitine given simultaneously can decrease liver damage

Safe to use with children

Spina bifida (20x)

Partial, tonic/clonic, absence (if ethosuximide doesn't work), tonic, atonic, clonic

Rash development indicates severe toxicity, so immediately discontinue use

No good for children under 16

Introducing slowly minimizes risk of rash

First line treatment for absence seizures

Non-sedating and fairly safe if given in multiple doses

Use with caution in patients with renal disease

Drug of choice for infants with febrile seizures since it is easily absorbed and has sedative effects

Physically addictive, so need to wean off slowly

Can adversely affect cognitive function

Can occasionally cause sexual impotence

Partial and tonic/clonic

Excreted by kidneys

Drink lots of water to avoid kidney stones

Can cause metabolic acidosis and/or decrease effectiveness of oral contraceptives

Partial seizures only

Stabilizes quickly - steady state achieved in 2 days

One of the fastest-growing drugs in terms of usage

Pregabalin - eliminated by kidneys, replaced gabapentin due to better side effects

Zonisamide - drink water to prevent kidney stones, used in children/adults > 16 YO

Diuretic

Used for catamenial epilepsy (seizures caused by the high estrogen levels present at the start of the menstrual cycle)

Rapid tolerance develops, so not useful for chronic, daily seizures

IV diazepam

Then switch to phenytoin (slower-acting but longer-lasting)

Resuscitation should be available since diazepam is a cardiovascular/respiratory depressant

Rectal form of diazepam available that can be administered at home

After 1 hour, if no response, switch to phenobarbital

If that also fails, switch to propofol

All antiseizure meds are somewhat teratogenic

Maintain treatment, but go to a single drug at as low as dose as possible

Phenobarbital/phenytoin can cause vitamin K deficiencies, so babies whose mothers are on those drugs should get vitamin K IV shortly after birth

Ethosuximide - extremely high protein binding, so 90% gets into breast milk, so mothers on this drug should not breastfeed

Seizure prophylaxis (levetiracetam)

Vasospasm prevention (nimodine/MgSO4)

Antihypertensives

Clipping - young, healthy, distal aneurysm

Coiling - old, not as healthy, proximal aneurysm

Mediated by the reticular activating system, a poorly localized network of cells in the rostral brainstem and diencephalon

Uses dopamine systems for motor planning, norepinephrine systems for arousal/attention, and serotonin systems for sleep, thermoregulation, and pain

Thiamine

Naloxone - opioid antagonist for drug-induced coma

Flumazenil - benzodiazepine antagonist for drug-induced coma

Glucose

Cheyne-Stokes - non-localizing, caused by damage to respiratory centers

Hyperventilation - caused by metabolic acidosis, either peripheral or central

Apneustic breathing - slow, prolonged breath in, then a period of no breathing, then repeat; localizes to the pons

Cluster breathing - localizes to the pons/cerebellum

Ataxic breathing - shallow, hyperventilating breaths for a while, then a no time with no breathing or very shallow breathing; localizes to the medulla/cerebellum

Gaze deviation away from hemiparesis - hemispheric lesion

Gaze toward hemiparesis - pontine/cerebellar lesion

Downward gaze - midbrain/tectal lesion

Roving eyes - bilateral hemispheric lesion

Ocular bobbing - bilateral pontine damage

Saccadic eye movements - if eyes move and follow a moving object, patient is NOT in a coma

Reactive pupils with absent corneal reflex and doll's eye reflex - metabolic coma

Fixed, large pupils - midbrain

Pinpoint eyes that are unreactive - pontine

Oculocephalic reflex (aka doll's eye or ball-bearing eyes) - when head is quickly turned to side, eyes will move to keep looking in original direction - a sign of bilateral hemispheric dysfunction

Oculovestibular reflex (aka cold calorics) - inject ice water into ear with head tilted upwards; if eyes drift to cold ear, brainstem is intact and only the hemispheres are out

Decorticate (flexor) posturing - cortex out but brainstem intact

Decerebrate (extensor) posturing - brainstem out

Eyes open but person completely unresponsiveness

Brainstem and primitive reflexes remain intact, but there is no evidence of awareness or consciousness

Odds of recovery after 30 days in a coma - 50% if traumatic, 15% if not

Recovery after 12 months is extremely rare

In hypoxic/ischemic coma, patients who were destined to recover pretty much did so within 3-4 weeks

No cerebral function - no reaction to stimuli, no posturing, but deep tendon reflexes and primitive movements (back arching, Babinski) are allowed

No brainstem functions - Unresponsive pupils, no oculocephalic or oculovestibular reflex, no corneal reflex or facial movements, no cough/gag reflex

No spontaneous respiration in response to hypercarbia (apnea test)

Untreatable cause of death must be established

Confirmatory testing is not required and should not be performed unless the clinical testing is conflicting or insufficient to prove brain death

Expressive language = Brodman's area 44 = posterior end of third frontal gyrus (orbital gyrus)

Receptive area = Brodman's areas 41, 42, and 39 = posterior third of the superior temporal gyrus/inferior parietal lobe (angular gyrus)

Broca's - no speech, no writing, no repetition, but can understand; gait apraxia due to loss of communication to muscles despite intact muscle strength

Wernicke's - no understanding, no writing, no repetition, but can talk

Conductive - loss of communicating fibers between Broca's area and Wernicke's area; may miss a few words or say the wrong word, but generally able to communicate

Global aphasia - loss of Broca's AND Wernicke's areas; can't do anything; due to large hemispheric stroke

Transcortical motor - loss of Broca's area subcortex; same as Broca's except repetition is preserved

Transcortical sensory - loss of Wernicke's area subcortex; same as Wernicke's except repetition is preserved

Aprosody - loss of language area in non-dominant hemisphere; loss of ability to express or perceive emotional subtext of language

Tissue looks pale due to presence of water that makes the stain less effective

Pink cytoplasm, pyknotic nuclei (irreversible condensation of the chromatin prior to necrosis), influx of neutrophils and edema

Hypoglycemia looks similar to hypoxia

Subacute - influx of macrophages and reactive astrocytes

Remote - cystic lesion with a ring of gliosis and some macrophages within the lesion

Angiitis/Vasculitis of large vessels - Giant cell arteritis or Takayasu's arteritis

Moyamoya disease

Arterial dissection

Fibromuscular dysplasia

Hyperhomocysteinemia

NF1: autosomal dominant, chromosome 17, cafe-au-lait spots, neurofibromas, axial/inguinal freckling, optic glioma, Lisch nodules

NF2: autosomal dominant, chromosome 22, neurofibroma, Schwannoma, meningioma, glioma, lenticular opacity

Tubular sclerosis: autosomal dominant, chromosome 9 or 16, cortical tubers (gliotic neurons), Ash leaf spots, Shagreen patches (elevated, uneven skin), cardiac rhabdomyoma, subependymal giant cell astrocytoma

Sturge-Weber: 100% sporadic, unilateral port-wine stain, glaucoma, occipitoparietal calcification tracks