Neuro Flashcards
Cinchonism (drug reaction)
Quinidine
Quinine
Parkinson-like Syndrome (drug reaction)
Antipsychotics
Reserpine
Metoclopramide
Seizures (drug reaction)
Isoniazid (B6 deficiency)
Bupropion
Imipenem/cilastatin
Enflurane
Tardive dyskinesia (drug reaction)
Antipsychotics
Metoclopramide
Neural development
Notochord induces overlying ectoderm to differentiate into neuroectoderm and form neural plate
Neural plate gives rise to neural tube and neural crest cells
Notochord becomes nucleus pulposus of IV discs in adults
Alar plate (dorsal) = sensory (same as SC)
Basal plate (ventral) = motor (same as SC)
Regional specification of developing brain
1) Forebrain (prosencephalon)
- Branches into Telencephalon - Cerebral hemispheres and lateral ventricles
- Also into Diencephalon - Thalamus and 3rd ventricle
2) Midbrain (mesencephalon) - Midbrain and Aqueduct
3) Hindbrain - Metencephalon and Myelencephalon
- Metencephalon - Pons, Cerebellum, Upper part of 4th ventricle
- Myelencephalon - Medulla and lower part of 4th ventricle
CNS/PNS origins
Neuroectoderm - CNS, neurons, ependymal cells (inner lining of ventricles, make CSF), oligodendroglia, astrocytes
Neural crest - PNS neurons, Schwann cells
Mesoderm - Microglia (like Macrophages)
Neural tube defects
Neuropores fail to fuse (4th week) causing persistent connection between amniotic cavity and spinal canal
Associated with low folic acid intake before conception and during pregnancy.
Increased alpha-fetoprotein (AFP) in amniotic fluid and maternal serum
Increased acetylcholinesterase (AChE) in amniotic fluid is a helpful confirmatory test (fetal AChE in CSF transudates across defect into amniotic fluid)
Spina bifida occulta
Failure of bony spinal canal to close, but no structural herniation.
Usually seen at lower vertebral levels. Dura is intact. Associated with tuft of hair or skin dimple at level of bony defect. Normal AFP
Menigocele
Meninges (but no neural tissue) herniate through bony defect
Meningomyelocele
Meninges and neural tissue herniate through bony defect
Anencephaly
Forebrain anomaly
Malformation of anterior neural tube leads to no forebrain, open calvarium.
Clinical findings: High AFP; polyhydramnios (no swallowing center in brain)
Associated with maternal type 1 diabetes.
Maternal folate supplementation lowers risk
Holoprosencephaly
Forebrain anomaly
Failure of left and right hemispheres to separate; usually occurs during weeks 5-6
May be related to mutations in sonic hedgehog signaling pathway. Moderate form has cleft palate/lip, most severe form results in cyclopia.
Seen in Patau syndrome and Fetal Alcohol Syndrome
Chiari II
Posterior fossa malformation
Significant herniation of cerebellar tonsils and vermis through foramen magnum with aqueductal stenosis and hydrocephalus.
Often presents with lumbrosacral meningomyelocele, paralysis below the defet
Dandy-Walker
Posterior fossa malformation
Agenesis of cerebellar vermis with cystic enlargement of 4th ventricle (fills the enlarged posterior fossa)
Associated with hydrocephalus, spina bifida
Syringomyelia
Cystic cavity (syrinx) within spinal cord (if central canal - hydromyelia)
Crossing anterior spinal commissural fibers are typically damaged first. Results in a “cape-like” bilateral loss of pain and temperature sensation in upper extremities (fine touch sensation is preserved)
Associated with Chiari malformations, trauma, and tumors
Syrinx = tube, as in syringe
Most common at C8-T1
Chiari I malformation - cerebellar tonsillar ectopia > 3-5mm; congenital, usually asymptomatic in childhood, manifests with headaches and cerebellar symptoms
Tongue development
1st and 2nd branchial arches form anterior 2/3 (thus sensation via CN V3, taste via CN VII)
3rd and 4th branchial arches form posterior 1/3 (thus sensation and taste mainly via CN IX, extreme posterior via CN X)
Motor innervation is via CN XII to hypoglossus (retracts and depresses tongue), genioglossus (protrudes tongue), and styloglossus (draws sides of tongue upward to create a trough for swallowing)
Motor innervation is via CN X to palatoglossus (elevates posterior tongue during swallowing)
Taste - CN 7, 9, 10 (solitary nucleus)
Pain - CN V3, 9, 10
Motor - CN 10, 12
Neurons
Signal transmitting cells of the nervous system. Permanent cells - do not divide in adulthoos.
Signal-relaying cells with dendrites (receive input), cell bodies, and axons (send output)
Cell bodies and dendrites can be seen on Nissle Stain* (stains RER)
RER is not present in the axon.
Injury to axon leads to Wallerian degeneration - degeneration distal to injury and axonal retraction proximally; allows for potential regeneration of axon (if in PNS)
Astrocytes
Physical support, repair, K metabolism, removal of excess nt’s, component of BBB, glycogen fuel reserve buffer. Reactive gliosis in response to neural injury.
Astrocyte marker = GFAP
Derived from neuroectoderm
Microglia
Phagocytic scavenger cells of CNS (mesodermal, mononuclear origin)
Activated in response to tissue damage. Not readily discernible by Nissl stain
HIV-infected microglia fuse to form multinucleated giant cells in CNS
Myelin
Increases conduction velocity of signals transmitted down axons - saltatory conduction of action potential at the nodes of Ranvier, where there are high concentrations of Na channels.
CNS - oligodendrocytes
PNS - Schwann Cells
Wraps and insulates axons: Increases space constant and Increases conduction velocity
Schwann cells
Each Schwann cell myelinates only 1 PNS axon
Also promote axonal regeneration. Derived from neural crest
Increased conduction velocity via saltatory conduction at the nodes of Ranvier, where there is a high concentration of Na channels
May be injured in Guillain-Barre Syndrome
Acoustic Neuroma - type of schwannoma. Typically located in internal acoustic meatus (CN8). If bilateral, strongly associated with neurofibromatosis type 2
Oligodendroglia
Myelinates axons of neurons in CNS. Each oligodendrocyte can myelinate many axons (~30). Predominant type of glial cell in white matter
Derived from neuroectoderm
“Fried egg” appearance histologically
Injured in MS, progressive multifocal leukoencephalopathy (PML), leukodystrophies
Free nerve endings
C - slow, unmyelinated fibers
Adelta - fast, myelinated fibers
Location: All skin, epidermis, some viscera
Senses: Pain and temp
Meissner corpuscles
Large, myelinated fibers; adapt quickly
Location: Glabrous (hairless) skin
Senses: Dynamic, fine/light touch, position sense
Pacinian corpuscles
Large, myelinated fibers; adapt quickly
Location: Deep skin layers, ligaments, joints
Senses: Vibration, pressure
Merkel discs
Large, myelinated fibers; adapt slowly
Location: Finger tips, superficial skin
Senses: Pressure, deep static touch (shapes, edges), position sense
Ruffini corpuscles
Dendritic endings with capsule; adapt slowly
Locations: Finger tips, joints
Senses: Pressure, slippage of objects along surface of skin, joint angle change
Peripheral nerve makeup
Endoneurium - invests single nerve fiber layers (inflammatory infiltrate in Guillain-Barre syndrome)
Perineurium (permability barrier) - surrounds a fascicle of nerve fibers. Must be rejoined in microsurgery for limb reattachment
Epineurium - dense connective tissue that surrounds entire nerve (fascicles and blood vessels)
Norepinephrine
Increased in anxiety
Decreased in depression
made in Locus Ceruleus (pons)
Locus ceruleus = stress and panic center
Dopamine
Increased in Huntington Disease
Decreased in Parkinson Disease
Decreased in Depression
Made in Ventral tegmentum and substantia nigra pars compacta (midbrain)
5-HT
Decreased in anxiety
Decreased in Depression
Made in Raphe nuclei (pons, medulla, midbrain)
ACh
Increased in Parkinson Disease
Decreased in Alzheimer Disease
Decreased in Huntington Disease
Made in Basal nucleus of Meynert
GABA
Decreased in anxiety
Decreased in Huntington Disease
Made in nucleus accumbens
Nucleus accumbens and septal nucleus - reward center, pleasure, addiction, fear
Blood Brain Barrier
Prevents circulating blood substances (bacteria, drugs) from reaching the CSF/CNS
Formed by 3 structures
1) Tight junctions between nonfenestrated capillary endothelial cells
2) Basement membrane
3) Astrocyte foot processes
Glucose and amino acids cross slowly by carrier-mediated transport mechanisms
Nonpolar/lipid-soluble substances cross rapidly via diffusion
A few specialized brain regions with fenestrated capillaries and no BBB allow molecules in blood to affect brain function (area postrema - vomiting after chemo; OVLT - osmotic sensing) or neurosecretory products to enter circulation (neurohypophysis - ADH release)
Infarction and/or neoplasm destroys endothelial cell tight junctions leading to vasogenic edema
Other notable barriers include:
Blood testis barrier
Maternal-fetal blood barrier of placenta
Hypothalamus
The hypothalamus wears TAN HATS
T = Thirst and water balance A = adenohypophysis control (regulates anterior pit) N = Neurohypophysis releases hormones produced in the hypothalamus H = Hunger A = Autonomic regulation T = Temperature regulation S = Sexual urges
Inputs (areas not protected by BBB): OVLT (Organum Vasculosum of the Lamina Terminalis; senses change in osmolarity), Area postrema (responds to emetics)
Supraoptic nucleus - makes ADH
Paraventricular nucleus - makes oxytocin
ADH and oxytocin - made by hypothalamus but stored and released by posterior pit.
Lateral area of hypothalamus
Hunger
Destruction leads to anorexia, failure to thrive (infants). Inhibited by leptin
“If you zap your lateran nucleus you shrink laterally”
Ventromedial area of hypothalamus
Satiety
Destruction (craniopharyngioma) leads to hyperphagia. Stimulated by leptin
“If you zap your ventromedial nucleus, you grow ventrally and medially”
Anterior hypothalamus
Cooling, parasympathetic
“Anterior/Cooling = A/C”
Posterior hypothalamus
Heating, sympathetic
Suprachiasmatic nucleus
Circadian Rhythm
“You need sleep to be charismatic”
Sleep physiology
Sleep cycle is regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN) of hypothalamus
Circadian rhythm controls nocturnal release of ACTH, prolactin, melatonin, NE: SCN triggers NE release to the pineal gland which releases melatonin
SCN is regulated by environment (light)
2 stages: REM and non-REM. Extraocular movements during REM sleep due to activity of PPRP (Paramedian Pontine Reticular Formation/Conjugate Gaze Center)
REM sleep occurs every 90 minutes, and duration increases throughout the night
Alcohol, benzos and barbs are associated with reduced REM sleep and delta wave sleep; NE also reduces REM sleep
Treat bedwetting (sleep enuresis) with oral desmopressin (ADH analog); preferred over imipramine bc of the latter’s adverse effects
Benzos are useful for night terrors and sleepwalking
Sleep stages
1) Awake (eyes open) - alert, active mental concentration
Beta (highest frequency, lowest amplitude) waves on EEG
2) Awake (eyes closed) - Alpha waves
3) Non-REM sleep
- Stage N1 (5%) - Light sleep - Theta waves
- Stage N2 (45%) - Deeper sleep; when bruxism occurs - sleep spindles and K complexes on EEG
- Stage N3 (25%) - Deepest non-REM sleep (slow wave sleep); When sleepwalking, night terros, and bedwetting occur - Delta waves (lowest frequency, highest amplitude)
4) REM sleep (25%) - Loss of motor tone, increased brain O2 use, increased and variable pulse and BP; when dreaming and penile/clitoral tumescence occur; may serve memory processing function - Beta waves
Thalamus
Major relay for all ascending sensory information except olfaction
VPL nucleus of thalamus
Input: Spinothalamic and dorsal column/medial lemniscus
Pain, temp; pressure, touch, vibration, proprioception
Destination: Primary Somatosensory cortex
VPM nucleus of thalamus
Input: Trigeminal and gustatory pathway
Face sensation, taste
Destination: Primary Somatosensory cortex
“Makeup goes on the face/ vpM”
LGN nucleus of thalamus
Input: CN II
Vision
Destination: Calcarine sulcus
“Lateral = Light”
MGN nucleus of thalamus
Input: Superior olive and inferior colliculus of tectum
Hearing
Destination: Auditory cortex of temporal lobe
“Medial = Music”
VL nucleus of thalamus
Input: Basal ganglia, cerebellum
Motor
Destination: Motor Cortex
Limbic System
Collection of neural structures involved in emotion, long term memory, olfaction, behavior modulation, ANS function
Structures include hippocampus, amygdala, fornix, mammillary bodies, cingulate cygrus
Responsible for the 5 F’s
Feeding Fleeing Fighting Feeling Sex
Osmotic demyelination syndrome (Central Pontine Myelinosis)
Acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness
Can cause “locked-in syndrome”
Massive axonal demyelination in pontine white matter secondary to osmotic changes
Commonly iatrogenic, caused by overly rapid correction of hyponatremia. In contrast, correcting hypernatremia too quickly results in cerebral edema/herniation
Correcting Na too fast:
From low to high you pons will die (osmotic demyelination syndrome)
From high to low, your brain will blow (cerebral edema/herniation)
Cerebellum
Modulates movement; aids in coordination and balance
Input:
1) Contralateral cortex via middle cerebellar peduncle
2) Ipsilateral proprioceptive information via inferior cerebellar peduncle from spinal cord
Output:
1) Sends info to contralateral cortex to modulate movement. Output nerves = Purkinje cells - deep nuclei of cerebellum - contralateral cortex via superior cerebellar peduncle
2) Deep nuclei (lateral to medial) - Dentate, Emboliform, Globose, Fastigial (Dont Eat Greasy Foods)
Lateral lesions - voluntary movement of extemities; when injured, propensity to fall toward injured (ipsilateral) side
Medial lesions - lesions involving midline structures (vermal cortex, fastigial nuclei) and/or flocculonodular lobe - truncal ataxia (wide-based cerebellar gait), nystagmus, head tilting
Generally, midline lesions result in bilateral motor deficits axial and proximal limb musculature
basal ganglia
Important in voluntary movements and making postural adjustments
Receives cortical input, provides negative feedback to cortex to modulate movement
Striatum = Putamen (motor) + Caudate (cognitive)
Lentiform = Putamen + Globus pallidus
Excitatory pathway - cortical inputs stimulate the striatum, stimulating the release of GABA, which disinhibits the thalamus via the GPi/SNr (increases motion)
Inhibitory pathway - cortical inputs stimulate the striatum, which disinhibits STN via GPe, and STN stimulates GPi/SNr to inhibit the thalamus (lowers motion)
Dopamine binds to D1, stimulating the excitatory pathway, and to D2, inhibiting the inhibitory pathway - increases motion
Athetosis
Slow, writhing movements; especially seen in fingers
Characteristic lesion: Basal ganglia (Huntington)
Writhing, snake-like movement
Chorea
Sudden, jerky, purposeless movements
Characteristic lesion: Basal ganglia (Huntington)
Chorea = dancing
Dystonia
Sustained, involuntary muscle contractions
Writer’s cramp; blepharospasm (sustained eyelid twitch)
Essential tremor
High-frequency tremor with sustained posture (outstretched arms), worsened with movement or when anxious
Often familial. Patients often self-medicate with EtOH, which lowers tremor amplitude
Tx = B-blockers, primidone
Hemiballismus
Sudden, wild flailing of 1 arm +/- ipsilateral leg
Characteristic lesion: Contralateral subthalamic nucleus (lacunar stroke)
Contralateral lesion**
Intention tremor
Slow, zigzag motion when pointing/extending toward a target
Characteristic lesion: Cerebellar dysfunction
Myoclonus
Sudden, brief, uncontrolled muscle contraction
Jerks; hiccups; common in metabolic abnormalities such as renal and liver failure
Resting tremor
Uncontrolled movement of distal appendages (most noticeable in hands); tremor alleviated by intentional movement
Characteristic lesion: Parkinson Disease
occurs at rest; “pill rolling tremor” of Parkinson
Parkinson Disease
Degenerative disorder of CNS associated with Lewy Bodies (composed of alpha-synuclein - intracellular eosinophilic inclusions) and loss of dopaminergic neurons (depigmentation) of substantia nigra pars compacts
Parkinson TRAPS your body T = tremor (pill-rolling tremor at rest) R = rigidity (cogwheel) A = Akinesia (or bradykinesia) P = Postural instability S = Shuffling gait
Huntington Disease
Autosomal dominant trinucleotide repeat disorder on chromosome 4
Symptoms manifest between ages 20-50; characterized by choreiform movements, aggression, depression, dementia (sometimes initially mistaken for substance abuse)
Increased dopamine
Decreased GABA
Decreased ACh
All in brain
Neuronal death via NMDA-R binding and glutamate toxicity. Atrophy of caudate nuclei with ex vacuo dilatation of frontal horns on MRI
Expansion of CAG repeats (anticipation)
Caudate loses Ach and Gaba (CAG)
Aphasia - general
higher order inability to speak (language deficit).
Dysarthria = motor inability to speak (movement deficit)
Broca aphasia
Nonfluent with intact comprehension and impaired repetition.
Broca area - inferior frontal gyrus of frontal lobe
Broca = Broken Boca
Wernicke aphasia
Fluent with impaired comprehension and repetition
Wernicke area - superior temporal gyrus of temporal lobe
Wernicke is wordy but makes no sense. Wernicke = what??
Conduction aphasia
Poor repetition but fluent speech, intact comprehension. Can be caused by damage to arcuate fasciculus
Can’t repeat phrases such as “No ifs, ands, or buts”
Global aphasia
Nonfluent aphasia with impaired comprehension
Arcuate fasciculus, Broca, and Wernicke areas affected
Transcortical motor aphasia
Nonfluent aphasia with good comprehension and intact repetition
Transcortical sensory aphasia
Poor comprehension with fluent speech and intact repetition
Mixed transcortical aphasia
Nonfluent speech; poor comprehension, intact repetition
Broca and Wernicke areas involved; arcuate fasiculus not involved
Bilateral amygdala lesion
Kluver-Bucy Syndrome - disinhibited behavior (hyperphagia, hypersexuality, hyperorality)
Associated with HSV-1
Frontal lobe lesion
Disinhibition and deficits in concentration, orientation, judgement; may have reemergence of primitive reflexes
Nondominant parietal-temporal cortex lesion
Hemispatial neglect syndrome (agnosia of the contralateral side of the world)
Dominant parietal-temporal cortex lesion
Agraphia, acalculia, finger agnosia, left-right disorientation
Gerstmann Syndrome
Reticular activating system (midbrain) lesion
Reduced levels of arousal and wakefulness (coma)
Mammillary bodies (bilateral) lesion
Wernicke-Korsakoff Syndrome - confusion, ophthalmoplegia, ataxia; memory loss (anterograde and retrograde amnesia), confabulation, personality changes.
Associated with thiamine (B1) deficiency and excesive EtOH use; can be precipitated by giving glucose without B1 to a B1 deficient patient.
Wernicke problems come in a CAN of beer = Confusion, Ataxia, Nystagmus
Basal ganglia lesion
May result in tremor at rest, chorea, athetosis
Parkinson, Huntington
Cerebellar hemisphere lesion
Intention tremor, limb ataxia, loss of balance; damage to cerebellum leads to ipsilateral deficits; fall toward side of lesion
“Cerebellar hemispheres are laterally located - affect lateral limbs”
Cerebellar vermis lesion
Truncal ataxia, dysarthria
“Vermis is centrally located - affects central body”
Subthalamic nucleus lesion
Contralateral hemiballismus
Hippocampus (bilateral) lesion
Anterograde amnesia - inability to make new memories
Paramedian pontine reticular formation lesion
Eyes look away from side of lesion
Frontal eye fields lesion
Eyes look toward lesion
Regulation of cerebral perfusion
Brain perfusion relies on tight autoregulation. Cerebral perfusion is primarily driven by P CO2 (P O2 also modulates perfusion in severe hypoxia)
Therapeutic hyperventilation (lowers P CO2) helps reduce ICP in case of acute cerebral edema (stoke, trauma) via vasoconstriction. Fainting in panic attacks due to reduce perfusion
Cerebral perfusion relies on a pressure gradient between mean arterial pressure (MAP) and ICP. Lower BP or higher ICP leads to reduced cerebral perfusion pressure (CPP)
CPP = MAP - ICP
If CPP = 0 there is no cerebral perfusion - brain death
Middle Cerebral Artery stroke
1) Motor cortex - upper limb and face
Contralateral paralysis - upper limb and face
2) Sensory cortex - upper limb and face
Contralateral loss of sensation - upper limb and face
3) Temporal lobe (Wernicke area); Frontal lobe (Broca area) - Aphasia if in dominant (usually left) hemisphere. Hemineglect if lesion affects nondominant (usually right) side
Anterior Cerebral Artery stroke
1) Motor cortex - lower limb
Contralateral paralysis
2) Sensory cortex - lower limb
Contralateral loss of sensation
Lenticulostriate artery stroke
Striatum, internal capsule - Contralateral hemiparesis/hemiplegia
Common location of lacunar infarcts, secondary to unmanaged HTN
Anterior Spinal Artery stroke
1) Lateral corticospinal tract - contralateral hemiparesis - upper and lower limbs
2) Medial lemniscus - reduced contralateral proprioception
3) Caudal medulla - hypoglossal nerve - Ipsilateral hypoglossal dysfunction (tongue deviates ipsilaterally)
Stroke commonly bilateral
Medial medullary syndrome - caused by infarct of paramedian branches of ASA and vertebral arteries
Posterior Inferior Cerebellar Artery (PICA) stroke
Lateral medulla - vestibular nuclei, lateral spinothalamic tract, spinal trigeminal nucleus, nucleus ambiguus, sympathetic fibers, inferior cerebellar peduncle
Vomiting, vertigo, nystagmus; reduced pain and temp sensation from ipsilateral face and contralateral body; dysphagia, hoarseness, reduced gag reflex; ipsilateral Horner Syndrome; ataxia, dysmetria
Lateral Medullary (Wallenberg) Syndrome - Nucleus ambiguus effects are specific to PICA lesions
“Don’t pick a (PICA) horse (hoarseness) that can’t eat (dysphagia)”
Anterior Inferior Cerebellar Artery (AICA) stroke
1) Lateral pons - cranial nerve nuclei; vestibular nuclei, facial nucleus, spinal trigeminal nucleus, cochlear nuclei, sympathetic fibers
Vomiting, vertigo, nystagmus, Paralysis of face, reduced lacrimation, salivation, lower taste from anterior 2/3 of tongue.
Ipsilateral reduced pain and temp of the face, contralateral reduced pain and temp of the body
2) Middle and inferior cerebellar peduncles
Ataxia, dysmetria
Lateral pontine syndrome = facial nucleus effects are specific to AICA lesions “Facial droop means AICA’s pooped”
Posterior Cerebral Artery stroke
Occipital cortex, visual cortex - contralateral hemianopia with macular sparing
Basilar artery stroke
Pons, medulla, lower midbrain, corticospinal and corticobulbar tracts, ocular cranial nerve nuclei, paramedian pontine reticular formation
Preserved consciousness and blinking, quadriplegia, loss of voluntary facial, mouth, and tongue movements
“Locked-in syndrome”
Anterior Communicating Artery stroke
Most common lesion is aneurysm. Can lead to stroke. Saccular (berry) aneurysm can impinge cranial nerves
Visual field defects
Defects are typically aneurysms, not strokes
Posterior Communicating Artery stroke
Common site of saccular aneurysm
CN 3 palsy - eye is “down and out” with ptosis and mydriasis
Lesions are typically aneurysm not strokes
Saccular (Berry) Aneurysm
Occurs at bifurcations in the circle of Willis. Most common site is junction of anterior communicating artery and anterior cerebral artery
Rupture (most common complication) leads to subarachnoid hemorrhage (“worst headache of my life”) or hemorrhagic stroke
Can also cause bitemporal hemianopia via compression of optic chiasm
Associated with:
1) ADPKD
2) Ehlers-Danlos
Other risk factors: advanced age, HTN, smoking, race (more in blacks)
Charcot-Bouchard microaneurysm
Associated with chronic HTN; affects small vessels (e.g. in basal ganglia, thalamus)
Central post-stroke pain syndrome
Neuropathic pain due to thalamic lesions. Initial paresthesias followed in weeks to months by allodynia (ordinarily painless stimuli cause pain) and dysesthesia
Occurs in 10% of stroke patients
Epidural hematoma
Rupture of middle meningeal artery (branch of maxillary artery) often secondary to fracture of temporal bone.
Lucid interval.
Rapid expansion under systemic arterial pressure leads to transtentorial herniation, CN 3 palsy
CT shows biconvex (lentiform), hyperdense blood collection not crossing suture lines. Can cross falx, tentorium
Subdural hematoma
Rupture of bridging veins. Slow venous bleeding (less pressure = hematoma develops over time)
Seen in elderly, alcoholics, blunt trauma, shaken baby (predisposing factors: brain atrophy, shaking, whiplash)
Crescent-shaped hemorrhage that CROSSES SUTURE LINES. Midline shift. Cannot cross falx, tentorium
Subarachnoid hemorrhage
Rupture of an aneurysm (such as berry/saccular aneurysm, as seen in Ehlers-Danlos, ADPKD) or arteriovenous malformation.
Rapid time course
Patient complains of “worst headache of my life (WHOML)”
Bloody or yellow (xanthochromic) spinal tap. 2-3 days afterward, risk of vasospasm due to blood breakdown (not visible on CT, treat with nimodipine) and rebleed (visible on CT)
Intraparenchymal (hypertensive) hemorrhage
Most commonly caused by systemic HTN. Also seen with amyloid angiopathy (recurrent lobar hemorrhagic stroke in elderly), vasculitis, neoplasm.
Typically occurs in basal ganglia and internal capsule (Charcot-Bouchard aneurysm of lenticulostriate vessels), but can be lobar
Ischemic brain disease/stroke
Irreversible damage begins after 5 minutes of hypoxia
Most vulnerable: hippocampus*, neocortex, cerebellum, watershed areas. Irreversible neuronal injury
Stroke imaging: Noncontrast CT to exclude hemorrhage (before tPA can be given). CT detect ischemic changes in 6-24hrs. Diffusion-weighted MRI can detect ischemia within 3-30 mins.
Histo features:
12-48hrs = red neurons
24-72 hrs = Necrosis + neutrophils
3-5 days = Macrophages (microglia)
1-2 weeks = Reactive gliosis + vascular proliferation
> 2 weeks = Glial scar
Hemorrhagic stroke
Intracranial bleeding, often due to HTN, anticoagulation, cancer (abnormal vessels can bleed).
May be secondary to ischemic stroke followed by reperfusion (increased vessel fragility)
Basal ganglia are most common site of intracerebral hemorrhage
Ischemic stroke
Acute blockage of vessels leads to disruption of blood flow and subsequent ischemia leading to liquefactive necrosis
3 types:
1) Thrombotic - due to a clot forming directly at site of infarction (commonly MCA), usually over an atherosclerotic plaque
2) Embolic - embolus from another part of the body obstructs vessel. Can affect multiple vascular territories. Examples: Atrial fibrillation; DVT will patent foramen ovale
3) Hypoxic- due to hypoperfusion or hypoxemia. Common during cardiovascular surgeries, tends to affect watershed areas
tx = tPA (if within 3-4.5 hr of onset and no hemorrhage/risk of hemorrhage). Reduce risk with medical therapy (aspirin, clopidogrel); optimum control of BP, blood sugars, lipids; and treat conditions that increase risk (AFib)
Ventricular system
Lateral ventricle goes to 3rd ventricle via right and left interventricular foramina of Monro
3rd goes to 4th via cerebral aqueduct (of Sylvius)
4th to subarachnoid space via:
- Foramina of Luschka (Lateral)
- Foramen of Magendie (Medial)
CSF is made by ependymal cells of choroid plexus; it is reabsorbed by arachnoid granulations and then drains into dural venous sinuses
Idiopathic intracranial HTN (pseudotumor cerebri)
Increased ICP with no apparent cause on imaging (hydrocephalus, obstruction of CSF outflow)
Patients present with HAs, diplopia (usually from CN 6 palsy), no mental status alterations
Papilledema seen on exam. Risk factors include being a woman of childbearing age, vitamin A excess, danazol. Lumbar puncture reveals higher opening pressure and provides HA relief.
Tx = weight loss, acetazolamide, topiramate, invasive procedures for refractory cases (repeat lumbar punctures, CSF shunt placement, optic nerve fenestration surgery)
Communicating hydrocephalus
Nonobstructive
Lower CSF absorption by archnoid granulations leads to higher ICP, papilledema, herniation (arachnoid scarring post-meningitis)
Normal Pressure hydrocephalus
Nonobstructive
Affects the elderly; idiopathic; CSF pressure elevated only episodically; does not result in increased subarachnoid space volume.
Expansion of ventricles distorts the fibers of the corona radiata leads to triad of urinary incontinence, ataxia, and cognitive dysfunction (sometimes reversible).
“Wet, wobbly, wacky”
Noncommunicating hydrocephalus
Obstructive
Caused by structural blockage of CSF circulation within ventricular system (stenosis of aqueduct of Sylvius; colloid cyst blocking foramen of Monro)
Ex Vacuo Ventriculomegaly
Hydrocephalus mimic
Appearance of increased CSF on imaging, is actually due to decreased brain tissue (neuronal atrophy) (e.g. Alzheimer, advanced HIV, Pick Disease)
ICP is normal; triad is not seen
Spinal nerves
There are 31 pairs of spinal nerves in total - 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal
C1-C7 nerves exit above the corresponding vertebra
C8 exits below C7 and above T1
All other spinal nerves exit below (L2 exits below 2nd lumbar vertebra for example)
Vertebral disc herniation - nucleus pulposus (soft central disc) herniates through annulus fibrosus (outer ring); usually occurs posterolaterally at L4-L5 or L5-S1
Spinal cord - lower extent
In adults, spinal cord extends to lower border of L1-L2 vertebrae. Subarachnoid space (which contains the CSF) extends to lower border of S2 vertebra. Lumbar puncture is usually performed between L3-L4 or L4-L5 (level of cauda equina)
Goal of lumbar puncture is to obtain sample of CSF without damaging spinal cord. To keep the cord “alive”, keep the spinal needle between L3 and L5.
Dorsal column
Ascending - it synapses then crosses
Pressure, vibration, fine touch, and proprioception
1) 1st order neuron = sensory nerve ending goes to cell body in DRG then enters spinal cord and ascends ipsilaterally in dorsal column
2) Synapse 1 = Ipsilateral nucleus cuneatus (upper body/arms) or gracilis (lower body/legs) in medulla
3) 2nd order neuron = Decussates in medulla then ascends contralaterally in medial lemniscus
4) Synapse 2 = VPL (thalamus)
5) 3rd order neuron = Sensory cortex
Spinothalamic tract
AKA “anterolateral system”
Ascending - it synapses then crosses
Lateral = Pain, Temperature Anterior = Crude Touch, Pressure
1) 1st order neuron = Sensory nerve ending (Adelta and C fibers) (cell body in DRG). Then enters spinal cord.
2) Synapse 1 = Ipsilateral gray matter (spinal cord)
3) 2nd order neuron = Decussates at anterior white commissure then ascends contralaterally
4) Synapse 2 = VPL (Thalamus)
5) 3rd order neuron = Sensory cortex
Lateral Corticospinal tract
Descending
Voluntary movement of contralateral limbs
1) 1st order neuron = UMN: cell body in primary motor cortex descends ipsilaterally (through internal capsule), most fibers decussate at caudal medulla (pyramidal decussation). Then they descend contralaterally
2) First synapse = Cell body of anterior horn (spinal cord)
3) 2nd order neuron = LMN: leaves spinal cord
4) Synapse 2 = NMJ (neuromuscular junction)
UMN vs LMN
1) Weakness = UMN or LMN
2) Atrophy = LMN
3) Fasciculations = LMN
4) Reflexes = Increased (UMN) or decreased (LMN)
5) Tone = Increased (UMN) or decreased (LMN)
6) Babinski = UMN
7) Spastic paralysis = UMN
8) Flaccid paralysis = LMN
9) Clasp knife spasticity = UMN
Lower = everything lowered (less muscle mass, less muscle tone, lower reflexes, downgoing toes)
Upper = everything up (tone, DTR, toes)
Fasciculations = muscle twitches
Positive Babinsky is normal in infants
Werdnig-Hoffmann Disease
Poliomyelitis and spinal muscular atrophy
LMN lesions only, due to destruction of anterior horns; flaccid paralysis
MS
Due to demyelination; mostly white matter of cervical region; random and asymmetric lesions, due to demyelination; scanning speech, intention tremor, nystagmus
ALS
Combined UMN and LMN deficits with no sensory or oculomotor deficits; both UMN and LMN signs.
Can be caused by defect in superoxide dismutase I
Commonly presents as fasciculations with eventual atrophy and weakness of hands; fatal
Riluzole treatment modestly increases survival by lowering presynaptic glutamate release
Complete occlusion of anterior spinal artery
Spares dorsal columns and Lissauer tract; Upper thoracic ASA territory is watershed area, as artery of Adamkiewicz supplies ASA below T8
Tabes Dorsalis
Caused by tertiary Syphilis. Results from degeneration (demyelination) of dorsal columns and roots - impaired sensation and proprioception, progressive sensory ataxia (inability to sense or feel the legs causes poor coordination)
Associated with Charcot joints, shooting pain, Argyll Robertson pupils
Exam will demonstrate absence of DTRs and (+) Romberg sign
Syringomyelia
Syrinx expands and damages anterior white commissure of spinothalamic tract (2nd order neurons) - bilateral loss of pain and temp sensation (usually C8-T1); seen with Chiari I malformations; can expand and affect other tracts
Vitamin B12 Deficiency
Subacute combined degeneration - demyelination of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts
Ataxic gait, parasthesia, impaired position and vibration sense
Poliomyelitis
Caused by poliovirus (fecal-oral transmission). Replicates in oropharynx and small intestine before spreading via bloodstream to CNS. Infection causes destruction of cells in anterior horn of spinal cord (LMN death)
Symptoms = LMN lesion signs: weakness, hypotonia, flaccid paralysis, fasciculations, hyporeflexia, muscle atrophy. Signs of infection: malaise, HA, fever, nausea, etc
Findings = CSF with high WBCs and slight elevation of protein (with no change in CSF glucose). Virus recovered from stool or throat.
Spinal muscular atrophy (Werdnig-Hoffman Disease)
Congenital degeneration of anterior horn of spinal cord leads to LMN lesion. “Floppy baby” with marked hypotonia and tongue fasciculations. Infantile type has median age of death of 7 months.
Autosomal recessive
Friedrich Ataxia
Autosomal recessive trinucleotide repeat disorder (GAA) on chromosome 9 in gene that encodes frataxin (iron binding protein)
Leads to impairment in mitochondrial functioning. Degeneration of multiple spinal cord tracts causes muscle weakness and loss of DTRs, vibratory sense, proprioception
Staggering gait, frequent falling, nystagmus, dysarthria, pes cavus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy (cause of death).
Presents in childhood with kyphoscoliosis
“Friedreich is fratastic (frataxin): he’s your favorite frat brother, always staggering and falling but has a sweet, big heart”
Brown-Sequard Syndrome
Hemisection of spinal cord. Findings:
1) Ipsilateral UMN signs below level of lesion (due to corticospinal tract damage)
2) Ipsilateral loss of tactile, vibration, proprioception sense below level of lesion (due to damage to dorsal column)
3) Contralateral pain and temp loss below level of lesion (due to spinothalamic tract damage)
4) Ipsilateral loss of all sensation at level of lesion
5) Ipsilateral LMN signs (flaccid paralysis) at level of lesion
If lesion occurs above T1, patient may present with Horner syndrome due to damage of oculosympathetic pathway
Landmark dermatomes
C2 = posterior half of a skull “cap”
C3 = high turtleneck shirt
C4 = low collar shirt
T4 = at the nipple - “T4 at the teat pore”
T7 = at the xiphoid process
T10 = at the umbilicus (important for early appendicitis pain referral)
L1 = at the inguinal ligament - “L1 = IL”
L4 = includes the kneecaps - “Down on ALL 4’s”
S2, S3, S4 = erection and sensation of penile and anal zones - “S2, 3, 4 keep the penis off the floor”
Clinical reflexes
Biceps = C5 nerve root
Triceps = C7 nerve root
Patella = L4 nerve root
Achilles = S1 nerve root
Reflexes count up in order:
S1,2 - “buckle my shoe” - Achilles
L3,4 - “kick the door” - Patellar
C5,6 - “pick up sticks” - biceps
C7,8 - “lay them straight” - triceps
L1,2 - “testicles move” - cremaster
S3,4 - “winks galore” - anal wink
Primitive reflexes
CNS reflexes that are present in a healthy infant, but are absent in a neurologically intact adult
Normally disappear within 1st year of life. These primitive reflexes are inhibited by a mature/developing frontal lobe. They may remerge in adults following frontal lobe lesions - loss of inhibition of these reflexes
1) Moro reflex - “Hang on for life” reflex - abduct/extend arms when startled, and then draw together
2) Rooting reflex - Movement of head toward one side if cheek or mouth is stroked (nipple seeking)
3) Sucking reflex - Sucking response when roof of mouth is touched
4) Palmar reflex - curling of fingers if palm is stroked
5) Plantar reflex - Dorsiflexion of large toe and fanning of other toes with plantar stimulation
“Babinski” - presence of this reflex in an adult, which may signify UMN lesion
6) Galant reflex - Stroking along one side of the spine while newborn is in ventral suspension (face down) causes lateral flexion of lower body toward stimulated side
Brain stem - dorsal structures
Pineal gland - melatonin secretion, circadian rhythms
Superior colliculi - conjugate vertical gaze center
Inferior colliculi - auditory
Parinaud Syndrome - paralysis of conjugate vertical gaze due to lesion in superior colliculi (stroke, hydrocephalus, pinealoma)
Cranial nerve nuclei
Located in tegmentum portion of brain stem (btw dorsal and ventral portions)
Midbrain = nuclei of 3,4
Pons = nuclei of 5,6,7,8
Medulla = nuclei of 9,10,12
Spinal cord = nucleus of 11
Lateral nuclei = sensory (aLar plate)
—– Sulcus Limitans —–
Medial nuclei = motor (basal plate
Cranial nerve and vessel pathways
Cribiform plate = 1
Middle cranial fossa = 2-6 - through sphenoid bone
- Optic canal = 2, ophthalmic artery, central retinal vein
- Superior orbital fissure = 3, 4, V1, 6, ophthalmic vein, sympathetic fibers
- Foramen Rotundum = V2
- Foramen Ovale = V3
- Foramen Spinosum = Middle meningeal artery
Posterior cranial fossa = 7-12 - through temporal or occipital bone
- Internal auditory meatus = 7,8
- Jugular foramen = 9, 10, 11, jugular vein
- Hypoglossal canal = 12
- Foramen magnum = spinal roots of 11, brain stem, vertebral arteries.
Cranial nerves
1) Olfactory = Smell - only one without thalamic relay to cortex (S)
2) Optic = Sight (S)
3) Oculomotor = Eye movements (SR, IR, MR, IO), pupillary constriction (sphincter pupillae: Edinger-Westphal nucleus, muscarinic receptors), accommodation, eyelid opening (levator palpebrae) (M)
4) Trochlear = Eye movement (SO) (M)
5) Trigeminal = Mastication, facial sensation (ophthalmic, maxillary, mandibular divisions), somatosensation from anterior 2/3 of tongue (B)
6) Abducens = Eye movements (LR) (M)
7) Facial = Facial movement, taste from anterior 1/3 of tongue, lacrimation, salivation (submandibular and sublingual glands), eyelid closing (orbicularis oculi), stapedius muscle in ear (note: nerve courses through the parotid gland, but does not innervate it) (B)
8) Vestibulocochlear = Hearing, balance (S)
9) Glossopharyngeal = Taste and somatosensation from posterior 1/3 of tongue, swallowing, salivation (parotid gland), monitoring carotid body and sinus chemo-and baroreceptors, and stylopharyngeus (elevates pharynx, larynx) (B)
10) Vagus = Taste from epiglottic region, swallowing, soft palate elevation, midline uvula, talking, coughing, thoracoabdominal viscera, monitoring aortic arch chem and baroreceptors (B)
11) Accessory = Head turning, shoulder shrugging (SCM, Trapezius) (M)
12) Hypoglossal = Tongue movement (M)
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Vagal nuclei
1) Nucleus Solitarius - Visceral sensory info (taste, baroreceptors, gut distention) - CN 7, 9, 10
2) Nucleus Ambiguus - Motor innervation of pharynx, larynx, upper esophagus (swallowing, palate elevation) - CN 9, 10, 11 (cranial portion)
3) Dorsal motor nucleus - Sends autonomic (parasympathetic) fibers to heart, lungs, upper GI - CN 10
Cranial nerve reflexes
1) Corneal
Afferent = V1 Ophthalmic (nasociliary branch)
Efferent = VII (temporal branch: orbicularis oculi)
2) Lacrimation
Afferent = V1 (loss of reflex does not preclude emotional tears)
Efferent = VII
3) Jaw jerk
Afferent = V3 (sensory - muscle spindle from masseter)
Efferent = V3 (motor - masseter)
4) Pupillary
Afferent = II
Efferent = III
5) Gag
Afferent = IX
Efferent = X
Common cranial nerve lesions
1) CN V motor lesion - jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle
2) CN X lesion - Uvula deviates away from side of lesion. Weak side collapses and uvula points away
3) CN XI lesion - Weakness turning head to contralateral side of lesion (SCM). Shoulder droop on side of lesion (trapezius)
The left SCM contracts to help turn the head to the right
4) CN XII lesion (LMN) - Tongue deviates toward side of lesion (“lick your wounds”) due to weakened tongue muscles on affected side
Cavernous sinus
Collection of venous sinuses on either side of pituitary. Blood from eye and superficial cortex goes to the cavernous sinus then to internal jugular vein
CN 3, 4, V1, 6 and sometimes V2 plus postganglionic sympathetic pupillary fibers en route to orbit all pass through cavernous sinus. Cavernous portion of internal carotid artery is also here.
Nerves that control extraocular muscles (plus V1 and V2) pass through the cavernous sinus
Cavernous Sinus Syndrome - presents with variable ophthalmoplegia, decreased corneal sensation, Horner syndrome and occasional decreased maxillary sensation. Secondary to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection. CN 6 is most susceptible to injury
Outer ear
Visible portion of ear (pinna), includes auditory canal and eardrum. Transfers sound waves via vibration of eardrum
Middle ear
Air-filled space with 3 bones called the ossicles (malleus, incus, stapes). Ossicles conduct and amplify sound from eardrum to inner ear
Inner ear
Snail-shaped, fluid-filled cochlea. Contains basilar membrane that vibrates secondary to sound waves.
Vibration transduced via specialized hair cells - auditory nerve signaling - brain stem
Each frequency leads to vibration at specific location on basilar membrane (tonotopy)
Low frequency heard at apex near helicotrema (wide and flexible)
High frequency heard best at base of cochlea (thin and rigid)
Hearing loss
1) Conductive - Rhinne abnormal (bone > air). Weber localizes to affected ear
2) Sensorineural - Rhinne normal (air > bone). Weber localizes to unaffected ear
3) Noise-induced - Damage to sterociliated cells in organ of Corti; loss of high frequency hearing 1st; sudden extremely loud noises can produce hearing loss due to tympanic membrane rupture
Cholesteatoma
Overgrowth of desquamated keratin debris within middle ear space; may erode ossicles, mastoid air cells causing conductive hearing loss
Facial lesions
1) UMN - lesion of motor cortex or connection btw cortex and facial nucleus. Contralateral paralysis of lower face; forehead spared due to bilateral UMN innervation
2) LMN - Ipsilateral paralysis of upper AND lower face
3) Facial nerve palsy - Complete destruction of the facial nucleus itself or its branchial efferent fibers (facial nerve proper)
Peripheral ipsilateral facial paralysis (absent forehead creases and drooping smile) with inability to close eye on involved side
Can occur idiopathically (Bell Palsy); gradual recovery in most cases
Associated with Lyme Disease, herpes simplex and (less common) herpes zoster (Ramsay Hunt Syndrome), sarcoidosis, tumors, diabetes
Tx = corticosteroids
Mastication muscles
3 muscles close jaw: Masseter, Temporalis, Medial pytergoid
1 opens: lateral pytergoid
All are innervated by trigeminal nerve (V3)
“It takes more muscles to keep your mouth shut”
Refractive errors
Common cause of impaired vision, correctible with glasses
1) Hyperopia - eye too short for refractive power of cornea and lens - light focused behind retina
2) Myopia - eye too long for refractive power of cornea and lens - light focused in front of retina
3) Astigmatism - abnormal curvature of cornea - different refractive power at different axes
4) Presbyopia - Age-related impaired accommodation (focusing on near objects), possibly due to decreased lens elasticity. Often necessitates “reading glasses”
Cataract
Painless, often bilateral, opacification of lens leading to decrease in vision.
Risk factors: Age,, smoking, EtOH, excessive sunlight, prolonged corticosteroid use, classic galactosemia, galactokinase deficiency. diabetes mellitus (sorbitol), trauma, infection
Glaucoma - general
Optic disc atrophy with characteristic cupping (thinning of outer rim of optic nerve head versus normal), usually with elevated IOP and progressive peripheral visual field loss
Open angle glaucoma
Associated with age, blacks, family history. Painless, more common in US
Primary - cause unclear
Secondary - blocked trabecular meshwork from WBCs (uveitis), RBCs (vitreous hemorrhage), retinal elements (retinal detachment)
Closed/Narrow angle glaucoma
Primary - enlargement of forward movement of lens against central iris (pupil margin) leads to obstruction of normal aqueous flow through pupil causing fluid build up behind iris, pushing peripheral iris against cornea and impeding flow through trabecular meshwork
Secondary - hypoxia from retinal disease (diabetes mellitus, vein occlusion) induces vasoproliferation in iris that contracts angle
Chronic closure - often asymptomatic with damage to optic nerve and peripheral vision
Acute closure - true ophthalmic emergency. Increased IOP pushes iris forward leading to angle closing abruptly. Very painful, red eye, sudden vision loss, halos around lights, rock-hard eye, frontal headache
Do not give Epinephrine bc of its mydriatic effect
Uveitis
Inflammation of uvea (iritis aka interior uveitis, choroiditis, aka posterior uveitis). May have hypopyon (accumulation of pus in anterior chamber) or conjunctival redness.
Associated with systemic inflammatory disorders (sarcoidosis, RA, juvenile idiopathic arthritis, HLA-B27 associated conditions)
Age related macular degeneration
Degeneration of macula (central area of retina). Causes distortion (metamorphopsia) and eventual loss of central vision (scotomas)
Dry (nonexudative, > 80%) - deposition of yellowish extracellular material in and beneath Bruch membrane and retinal pigment epithelium (“drusen”) with gradual decrease in vision. Prevent progression with multivitamin and antioxidant supplements
Wet (exudative, 10-15%) - rapid loss of vision due to bleeding secondary to choroidal neovascularization. Treat with anti-VEGF (vascular endothelial growth factor) injections (ranibizumab) or laser.
Diabetic retinopathy
Retinal damage due to chronic hyperglycemia. 2 types.
Nonproliferative - damaged capillaries leak blood causing lipids and fluid to seep into retina. This causes hemorrhage and macular edema. Tx = blood sugar control, macular laser
Proliferative - chronic hypoxia results in new blood vessel formation with resultant traction on retina. Tx = peripheral retinal photocoagulation, anti-VEGF (bevacizumab)
Retinal vein occlusion
Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis
Retinal hemorrhage and venous engorgement, edema in affected area
Retinal detachment
Separation of neurosensory layer of retina (photreceptor layer with rods and cones) from outermost pigmented epithelium (normally shields excess light, supports retina) - degeneration of photoreceptors - vision loss.
May be secondary to retinal breaks, diabetic traction, inflammatory effusions. Visualized on fundoscopy by the splaying and paucity of retinal vessels.
Breaks more common in patients with high myopia and are often preceded by posterior vitreous detachment (“flashes” and “floaters”) and eventual monocular loss of vision like a “curtain drawn down.”
Surgical emergency
Central retinal artery occlusion
Acute, painless monocular vision loss. Retina cloudy with attenuated vessels and “cherry-red” spots at fovea (center of macula)
Retinitis pigmentosa
Inherited retinal degeneration. Painless, progressive vision loss beginning with night blindness (rods affected first).
Bone spicule-shaped deposits around macula
Retinitis
Retinal edema and necrosis leading to scar. Often viral (CMV, HSV, HZV)
Associated with immunosuppression
Papilledema
Optic disc swelling (usually bilateral) due to increased ICP (secondary to mass effect).
Enlarged blind spot and elevated optic disc with blurred margins seen on fundoscopic exam
Miosis
Constriction, parasympathetic
1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN 3
2nd neuron: short ciliary nerves to pupillary sphincter muscles
Pupillary light reflex
Light in either retina sends a signal via CN 2 to pretectal nuclei in midbrain that activates bilateral Edinger-Westphal nuclei; pupils contract bilaterally (consensual reflex)
Result: illumination of 1 eye results in bilateral pupillary constriction
Mydriasis
Dilation, sympathetic
1st neuron: hypothalamus to ciliospinal center of Budge (C8-T2)
2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels)
3rd neuron: plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary nerve to pupillary dilator muscles. Sympathetic fibers also innervate smooth muscle of eyelids (minor retractors) and sweat glands of forehead and face
Marcus Gunn pupil
Afferent pupillary defect - due to optic nerve damage or severe retinal injury.
Decreased bilateral pupillary constriction when light is shone in affected eye relative to unaffected eye. Tested with “swinging flashlight test”
Horner Syndrome
Sympathetic denervation of face
Ptosis (slight drooping of eyelid: superior tarsal muscle)
Anhidrosis (absence of sweating) and flushing (rubor) of affected side of face
Miosis (pupil constriction)
Associated with lesion of spinal cord above T1 (Pancoast tumor, Brown-Sequard [cord hemisection], late-stage syringomyelia)
Any interruption results in Horner Syndrome
Ocular motility
CN 6 innervates LR
CN 4 innervates SO
CN 3 innervates the rest
LR6SO4
SO abducts, intorts, and depresses while adducted
CN 3 damage
CN 3 has both motor (central) and parasympathetic (peripheral) components.
Motor output to ocular muscles - affected primarily by vascular disease (diabetes mellitus: glucose becoming sorbitol) due to depressed diffusion of oxygen and nutrients to the interior fibers from compromised vasculature that resides on outside of nerve. Signs: ptosis, “down and out” gaze
Parasympathetic output - fibers on the periphery are 1st affected by compression (posterior communicating artery aneurysm, uncal herniation). Signs: diminished or absent pupillary light reflex, “blown pupil” often with “down and out” gaze
CN 4 damage
Eye moves upward, particularly with contralateral gaze and head tilt toward the side of the lesion (problems going down stairs, may present with compensatory head tilt in the opposite direction)
CN 6 damage
Medially directed eye that cannot abduct
Internuclear ophthalmoplegia
Medial longitudinal fasciculus (MLF): pair of tracts that allows for crosstalk between CN 6 and CN 3 nuclei. Coordinates both eyes to move in same horizontal direction. Highly myelinated (must communicate quickly so eyes move at same time). Lesions may be unilateral or bilateral (bilateral classically seen in MS)
Lesion in MLF = internuclear ophthalmoplegia (INO), a conjugate horizontal gaze palsy. Lack of communication such that when CN 6 nucleus activates ipsilateral lateral rectus, contralateral CN3 nucleus does not stimulate medial rectus to fire. Abducting eye gets nystagmus (CN 6 overfires to stimulate CN 3). Convergence normal.
When looking left, the left nucleus of CN 6 fires, which contracts the left lateral rectus and stimulates the contralateral (right) nucleus of CN 3 via the right MLF to contract the right medial rectus
Directional term (right INO, left INO) - refers to which eye is paralyzed
Dementia - general
A decrease in cognitive ability, memory, or function with intact consciousness
Alzheimer Disease
Most common cause of dementia in elderly. Down Syndrome patients have an increased risk of developing Alzheimer
Familial form (10%) associated with the following altered proteins:
1) ApoE2: lower risk
2) ApoE4: higher risk
3) APP, presenilin-1, presenilin-2: higher risk of early onset
Widespread cortical atrophy. Narrowing of gyri and widening of sulci.
Lower ACh
Senile plaques in gray matter: extracellular B-amyloid core; may cause amyloid angiopathy leading to intracranial hemorrhage; Amyloid-B synthesized by cleaving amyloid precursor protein (APP)
Neurofibrillary tangles: intracellular, hyperphosphorylated tau protein = insoluble cytoskeletal elements; number of tangles correlates with degree of dementia
Frontotemporal Dementia
Dementia, aphasia, parkinsonian aspects; change in personality
Spares parietal lobe and posterior 2/3 of superior temporal gyrus
Also called Pick Disease. Note the Pick bodies: silver-staining spherical tau protein aggregates
Frontotemporal atrophy
Lewy Body Dementia
Initially dementia and visual hallucinations followed by parkinsonian features
alpha-synuclein defect (Lewy Bodies, primarily cortical)
Creutzfeldt-Jakob Disease
Rapidly progressive (weeks to months) dementia with myoclonus (“startle myoclonus”)
Spongiform cortex
Prions (PrPc to PrPsc sheet [B-pleated sheet resistant to proteases])
Other causes of dementia
Multi-infarct (aka vascular, 2nd most common cause of dementia in elderly)
Syphilis
HIV
Vitamins B1, B3, or B12 deficiency
Wilson Disease
Normal pressure hydrocephalus
Multiple Sclerosis - general
Autoimmune inflammation and demyelination of CNS (brain and spinal cord). Patients can present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils), INO, hemiparesis, hemisensory symptoms, bladder/bowel incontinence
Relapsing and remitting course. Most often affects women in their 20s and 30s; more common in whites living further from equator
Charcot classic triad of MS is a SIN:
Scanning speech
Intention tremor (also Incontinence and INO)
Nystagmus
Multiple Sclerosis - Findings and Tx
Increased protein (IgG) in CSF. Oligoclonal bands are diagnostic
MRI is gold standard. Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with destruction of axons. Multiple white matter lesions separated in space and time.
Tx: slow progression with disease-monitoring therapies (B-interferon, natalizumab).
Treat acute flares with IV steroids.
Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABA b receptor agonists), pain (opioids)
Acute inflammatory demyelinating polyradiculopathy
Most common subtype of Guillain-Barre Syndrome
Autoimmune condition that destroys Schwann Cells causing inflammation and demyelination of peripheral nerves and motor fibers. Results in symmetric ascending muscle weakness/paralysis beginning in lower extremities
Facial paralysis in 50% of cases. May see autonomic dysregulation (cardiac irregularities, HTN, hypotension) or sensory abnormalities. Almost all patients survive; the majority recover completely after weeks to months
Findings: High CSF protein with normal cell count (albuminocytologic dissociation). Increased protein may cause papilledema
Associated with infections (Campylobacter jejuni, viral) causing autoimmune attack of peripheral myelin due to molecular mimicry, inoculations, and stress, but no definitive link to pathogens
Respiratory support is critical until recovery. Additional treatment: plasmapharesis, IV immunoglobulins
Acute disseminated (postinfectious) encephalomyelitis
Multifocal periventricular inflammation and demyelination after infection (commonly measles or VZV) or certain vaccinations (rabies, smallpox)
Charcot-Marie-Tooth Disease
Also known as hereditary motor and sensory neuropathy (HMSN)
Group of progressive hereditary nerve disorders related to the defective production of protein involved in the structure and function of peripheral nerves or the myelin sheath.
Typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches)
Krabbe Disease
Autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase
Buildup of galactocerebroside and psychosine destroys myelin sheath.
Findings = peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Metachromatic Leukodystrophy
Autosomal recessive lysosomal storage disease, most commonly due to arylsulfatase A deficiency
Buildup of sulfatides leads to impaired production and destruction of myelin sheath.
Findings = central and peripheral demyelination with ataxia, dementia
Progressive multifocal leukoencephalopathy
Demyelination of CNS due to destruction of oligodendrocytes. Associated with JC Virus.
Seen in 2-4% of AIDS patients (reactivation of latent viral infection). Rapidly progressive, usually fatal.
Increased risk associated with natalizumab, rituximab
Adrenoleukodystrophy
X-linked genetic disorder typically affecting males
Disrupts metabolism of very long chain fatty acids leading to excessive buildup in nervous system, adrenal glands, testes.
Progressive disease that can lead to long term coma/death and adrenal gland crisis
Partial (focal) seizures
Affect single area of the brain. Most commonly originate in medial temporal lobe. Often preceded by seizure aura; can secondarily generalize:
1) Simple partial (consciousness intact) - motor, sensory, autonomic, psychic
2) Complex partial (impaired consciousness)
Generalized seizures
Diffuse.
1) Absence (petit mal) - 3 Hx, no postictal confusion, blank stare
2) Myoclonic - quick, repetitive jerks
3) Tonic-clonic (grand mal) - alternating stiffening and movement
4) Tonic - stiffening
5) Atonic - “drop” seizures (falls to floor); commonly mistaken for fainting
Epilepsy
Disorder of recurrent seizures (febrile seizures are not epilepsy)
Status epilepticus
Continuous or recurring seizures that may result in brain injury. Variably defined as > 10-30 mins
Causes of seizures by age
Children - genetic, infection (febrile), trauma, congenital, metabolic
Adults - tumor, trauma, stroke, infection
Elderly - stroke, tumor, trauma, metabolic, infection
Differentiating headaches
Pain due to irritation of structures like the dura, cranial nerves or extracranial structures
1) Cluster HA
Unilateral
15min - 3hr, repetitive
Repetitive brief HAs. Excruciating periorbital pain with lacrimation and rhinorrhea. May induce Horner Syndrome. More common in males
Tx = 100% O2, sumatriptan
2) Tension HA
Bilateral
> 30mins (typically 4-6 hrs); constant
Steady pain. No photophobia or phonophobia. No aura.
Tx = analgesics, NSAIDs, acetaminophen; amitriptyline for chronic pain
3) Migraine
Unilateral
4-72hrs
Pulsating pain with nausea, photophobia, or phonophobia. May have “aura.” Due to irritation of CN 5, meninges, or blood vessels (release of substance P, calcitonin gene-related peptide, vasoactive peptides)
Tx = Abortive therapies (triptans, NSAIDs) and prophylaxis (propranolol, topiramate, Ca channel blockers, amitriptyline)
POUND = Pulsatile, One-day duration, Unilateral, Nausea, Disabling
Vertigo
Sensation of spinning while actually stationary. Subtype of “dizziness,” but distinct from “lightheadedness”
1) Peripheral vertigo - more common. Inner ear etiology (semicircular canal debris, vestibular nerve infection, Meniere disease). Positional testing leads to delayed horizontal nystagmus
2) Central vertigo - brain stem or cerebellar lesion (stroke affecting vestibular nuclei or posterior fossa tumor). Findings = directional change of nystagmus, skew deviation, diplopia, dysmetria. Positional testing yields immediate nystagmus in any direction; may change directions. Focal neurologic findings
Sturge-Weber Syndrome
A neurocutaneous disorder
Congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ectoderm) due to activating mutation of GNAQ gene.
Affects small (capillary-sized) blood vessels leading to port wine stain of the face (nevus flammeus, a non-neoplastic “birthmark” in CN V1/V2 distribution); ipsilateral leptomeningeal angioma leading to seizures/epilepsy; intellectual disability; and episcleral hemangioma causing increased IOP leading to earl-onset glaucoma
STURGE = Sporadic, port wine Stain; Tram track calcifications (opposing gyri); Unilateral; Retardation (intellectual disability): Glaucoma, GNAQ gene; Epilepsy
Tuberous sclerosis
A neurocutaneous disorder
HAMARTOMAS
H = Hamartomas in CNS and skin A = Angiofibromas M = Mitral regurgitation A = Ash-leaf spots R = cardiac Rhabdomyoma T = tuberous sclerosis O = autosomal dOminant M = Mental retardation A = renal Angiomyolipoma S = Seizures, Shagreen patches
Increased incidence of subependymal astrocytomas and ungual fibromas
Neurofibromatosis type 1 (von Recklinghausen disease)
A neurocutaneous disorder
Cafe-au-lait spots, Lisch nodules (pigmented iris hamartomas), cutaneous neurofibromas, optic gliomas, pheochromocytomas.
Mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of RAS) on chromosome 17. Skin tumors of NF1 are derived from neural crest cells
Von Hippel-Lindau disease
Hemangioblastomas (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum, spine; angiomatosis (cavernous hemangiomas in skin, mucosa, organs); bilateral renal cell carcinoma; pheochromocytomas.
List the adult primary brain tumors
1) Gliobastoma multiforme
2) Meningioma
3) Hemangioblastoma
4) Schwannoma
5) Oligodendroglioma
6) Pituitary adenoma
Glioblastoma multiforme
Adult
Common, highly malignant primary brain tumor with about 1 year median survival
Found in cerebral hemispheres. Can cross corpus callosum (“butterfly glioma”)
Stain astrocytes for GFAP
Histology = pseudopalisading pleomorphic tumor cells - border central areas of necrosis and hemorrhage
Meningioma
Adult
Common, typically benign primary brain tumor. Most often occurs in convexities of hemispheres (near surfaces of brain) and parasagital region. Arises from arachnoid cells, is extra-axial (external to brain parenchyma), and may have a dural attachment (“tail”).
Often asymptomatic; may present with seizures or focal neuro signs. Resection and/or radiosurgery
Histo = Spindle cells concentrically arranged in a whorled pattern; psammoma bodies (laminated calcifications)
hemangioblastoma
Adult
Most often cerebellar. Associated with von Hippel-Lindau syndrome when found with retinal angiomas. Can produce erythropoietin leading to secondary polycythemia
Histo = Closely arranged, thin-walled capillaries with minimal intervening parenchyma
Schwannoma
Adult
classically at the cerebellopontine angle, but can be along any peripheral nerve
schwann cell origin
S-100 (+)
Often localized to CN 8 leading to vestibular schwannoma. Resectable or treated with stereotactic radiosurgery
Bilateral vestibular schwannomas found in NF-2
Oligodendroglioma
Adult
Relatively rare, slow growing. Most often in frontal lobes. “Chicken wire” capillary pattern.
Histo = oligodendrocytes = “fried egg” cells - round nuclei with clear cytoplasm. Often calcified in oligodendroglioma
Pituitary adenoma - tumor qualities
Most commonly prolactinoma. Bitemporal hemianopia (shows normal visual field above, patient’s perspective below) due to pressure on optic chiasm
Hyper or hypopituitarism are sequelae
List the childhood primary brain tumors
1) Pliocytic astrocytoma
2) Medulloblastoma
3) Ependymoma
4) Craniopharyngioma
Pliocytic (low grade) astrocytoma
Childhood
Usually well-circumscribed. In children, most often found in posterior fossa (cerebellum)
May be supratentorial.
GFAP +
Benign, good prognosis
Rosenthal fibers - eosinophils, corkscrew fibers
Cystic + solid (gross)
Medulloblastoma
Childhood
Highly malignant cerebellar tumor. A form of primitive neuroectodermal tumor. Can compress 4th ventricle, causing hydrocephalus. Can send “drop metastases” to spinal cord
Homer-Wright rosettes. Solid (gross), small blue cells (histo)
Ependyoma
Childhood
Ependymal cell tumors most commonly found in 4th ventricle. Can cause hydrocephalus. Poor prognosis
Characteristic perivascular rosettes. Rod-shaped blepharoplasts (basal ciliary bodies) found near nucleus
Craniopharyngioma
childhood
Benign childhood tumor, may be confused with pituitary adenoma (both can cause bitemporal hemianopia).
Most common childhood supratentorial tumor
Derived from remnants of Rathke pouch
Calcification is common (tooth enamel-like)
Herniation syndromes
1) Cingulate (subfalcine) herniation under falx cerebri - can compress ACA
2) Downward transtentorial (central) herniation - Caudal displacement of brain stem leads to rupture of paramedian basilar artery branches causing Duret hemorrhages
Usually fatal
3) Uncal herniation - Uncus = medial temoral lobe. Compresses ipsilateral CN 3 (blown pupil, “down and out” gaze), ipsilateral PCA (contralateral homonymous hemianopia), contralateral crus cerebri at the Kernohan notch (ipsilateral paresis; a “false localization” sign)
4) Cerebellar tonsillar herniation into the foramen magnum - coma and death result when these herniations compress the brain stem
