Neurology Pathology

Arise from incomplete closure of the neuropores (openings at either end of the neural tube) --> persistent connection between amniotic cavity and spinal canal

Associated with low folic acid intake before conception and during pregnancy

Elevated α-fetoprotein (AFP) in amniotic fluid and maternal serum

Elecated AChE in amniotic fluid (confirmatory test)

• Types:
• 1. Spinia Bifida Occulta
• 2. Spina Bifida
•      -Meningocele
•      -Meningomyelocele
• 3. Anencephaly

Failure of bony spinal canal to close, but no structural herniation

Failure of posterior vertebral arch to close

Usually seen at lower vertebral levels

Dura is intact

Associated with tuft of hair or skin dimple at level of bony defect

• Meningocele
• -meninges (but not the spinal cord) herniate through spinal canal defect
• 

• Meningomyelocele
• -meninges and spinal cord herniate through spinal canal defect
• 

Malformation of anterior neural tube (failure of anterior neuropore to close)

• No forebrain, open calvarium, "frog-like appearance"
• 

• Elevated AFP
• Polyhydramnios: no swallowing center in brain, fetal swallowing of amniotic fluid is impaired

Associated with maternal DM1

Maternal folate supplementation decreases risk

• 1. Anencephaly
• 2. Holoprosencephaly

Failure of L and R hemispheres to separate

Usually occurs during weeks 5-6

Complex, multifactorial etiology, may be related to Shh pathway mutations

• Moderate form --> cleft lip/palate
• Most severe form --> cyclopia (cyclops)

• 1. Chiari II (Arnold-Chiari malformation)
• 2. Dandy-Walker

Congenital cerebellar tonsillar and vermian herniation through the foramen magnum (MBB: NOT vermis)

Aqueductal stenosis and hydrocephalus

Often associated with thoraco-lumbar myelomeningocele and paralysis below the defect

Agenesis of cerebellar vermis

Massively dilated 4th ventricle (fills the enlarged posterior fossa)

Associated with hydrocephalus and spina bifida

Cystic enlargement of central canal of spinal cord (syrnix = tube (syringe))

Crossing fibers of spinothalamic tract are typically damaged first (anterior white commissure)

"Cape-like" bilateral loss of pain and temperature in upper extremeties

Fine touch sensation is preserved

• Associated with Chiari I malformation
• Most common at C8-T1

• 
• Syrinx Expansion:
• 1. Anterior horn --> LMN syndrome
• 2. Lateral horn --> Horner syndrome

Degenerative loss of Dopaminergic neurons in the substantia nigra pars compacta of the basal ganglia

• Lewy Bodies:
• -α-synuclein (intracellular inclusion)
• 

• Depigmentation of the SN_PC
• 

• "TRAP"
• Tremor (pill rolling at rest, disappears with movement)
• Rigidity (cogwheel)
• Akinesia (bradykinesia, mask like face)
• Postural Instability (shuffling gait)

Degeneration of GABAergic (inhibitory) neurons in the caudate nucleus of the basal ganglia

Autosomal dominant disorder of trinucleotide repeats (CAG) in the huntingtin gene

Anticipation due to further expansion during spermatogenesis

CAG repeats: "Caudate loses Ach and GABA"

• Presentation (40yrs):
  Chorea
• Aggression
• Depression
• Dementia
• Athetosis
• *may be mistaken for substance abuse*

• 
• -Atrophy of striatal nuclei (caudate) (Neuronal death via NMDA-R binding and glutamate toxicity)
• -hydrocephalus ex vacuo
• -Huntingtin inclusions

*suicide is a common cause of death*

• 1. Hemiballismus
• 2. Chorea
• 3. Athetosis
• 4. Myoclonus
• 5. Dystonia
• 6. Essential tremor (postural tremor)
• 7. Resting tremor
• 8. Intention tremor

• Presentation:
• -sudden, wild flailing of arm +/- ipsilateral leg

• Lesion:
• -contralateral subthalamic nucleus (lacunar stroke)

"half of body ballistic"

• Presentation:
• -sudden, jerky, purposeless movements

• Lesion:
• -basal ganglia (Huntington's)

chorea = dancing

• Presentation:
• -slow, writhing movements
• -especially seen in fingers
• -"snake like"

• Lesion:
• -basal ganglia (Huntington's)

• Presentation:
• -sudden, brief uncontrolled muscle contraction
• -jerks, hiccups

*common in  metabolic abnormalities (renal and liver failure)

• Presentation:
• -sustained, involuntary muscle contractions
• -writer's cramp
• -blepharospasm (eyelid twitch)

• Presentation:
• -action tremor
• -exacerbated by holding posture/limb position

• -Genetic predisposition
• -patients often self medicate with ethanol (decrease tremor amplitude)

• Treatment:
• -β-blockers
• -primidone

• Presentation:
• -uncontrolled movement of distal appendages (most noticeable in hands)
• -tremor alleviated by intentional movement

• Lesion:
• -Parkinsons disease (substantia nigra) ("pill rolling")

• Presentation:
• -slow, zigzag motion when pointing/extending toward a target

• Lesion:
• -cerebellar dysfunction

• Presentation:
• -hyperorality
• -hypersexuality
• -disinhibited behaviour

• Lesion:
• -bilateraly amygdala

*associated with HSV-1

• -disinhibition
• -deficits in concentration, orientation and judgement
• -may have reemergence of primitive reflects

• -spatial neglect syndrome
• -agnosia of the contralateral side of the world

• -reduced levels of arousal and wakefulness
• -coma

Wernicke-Korsakoff Syndrome

-lesion of bilateral mammillary bodies

• TRIAD
• 1. Ophthalmoplegia (esp LR)
• 2. Ataxia (axial > appendicular)
• 3. Cognitive Syndrome
•      -memory loss
•      -confusion
•      -confabulation
•      -personality changes

Associated with thiamine (B1) deficiency and excessive EtOH use

Can be precipitated by giving glucose without B1 to a B1-deficient patient (glucose revs up metabolism and uses remaining B1)

Patients often have cognitive residua of basic amnesia syndrome

• -tremor at rest
• -chorea
• -athetosis

EG: Parkinson's disease

• -intention tremor
• -limb ataxia
• -loss of balance

Ipsilateral deficits ("fall to side of lesion")

"Cerebellar hemispheres are laterally located -- affect lateral limbs"

• -truncal ataxia
• -dysarthria

"Vermis is centrally located -- affects central body"

-contralateral hemiballismus

• -anterograde amnesia
• -inability to make new memories

• -eyes look away from side of lesion
• -loss of horizontal saccades toward side of lesion

(Involved in horizontal gaze and saccades)

-eyes look toward lesion

-Massive axonal demyelination in pontine white matter tracts

• Presentation:
• -acute paralysis
• -dysarthria
• -dysphagia
• -diplopia
• -loss of consciousness
• -"locked in syndrome"

• Commonly iatrogenic
• -caused by overly rapid correction of Na+ levels during hyponatremia

• Imaging:
• -T2 MRI with FLAIR shows increased signal in central pons

Aphasia: higher-order inability to speak (language deficit)

Dysarthria: motor inability to speak (movement deficit)

• 1. Broca's
• 2. Wernicke's
• 3. Global
• 4. Conduction

• Presentation:
• -non-fluent aphasia with intact comprehension
• -telegraphic speech

• Lesion:
• -Broca's area
• -inferior frontal gyrus of frontal lobe

"Broca's Broken Boca"

• Presentation:
• -fluent aphasia with impaired comprehension
• -"word salad"

• Lesion:
• -Wernicke's area
• -superior temporal gyrus of temporal lobe

• "Wernicke's is Wordy but makes no sense"
• "Wernicke's = What?"

• Presentation:
• -non-fluent aphasia with impaired comprehension

• Lesion:
• -Both Broca's and Wernicke's Areas

• Presentation:
• -poor repetition but fluent speech, intact comprehension

• Lesion:
• -arcuate fasciculus

Can't repeat phases such as "No ifs, ands or buts"

• -MCA
• -ACA
• -Lateral Striate Artery

• -ASA
• -PICA
• -AICA
• -PCA

• -AComm
• -PComm

• Area of Lesion:
• 1. Motor cortex: upper limb and face
• 2. Sensory cortex: upper limb and face
• 3. Temporal Lobe: Wernicke's area
• 4. Frontal Lobe: Broca's area

• Presentation:
• 1. Contralateral paralysis of upper limb and face
• 2. Contralateral loss of sensation of upper limb and face
• 3. Aphasia if in dominant (usually left) hemisphere
• 4. Hemineglect if lesion in nondominant (usually right) hemisphere

• Area of Lesion:
• 1. Motor Cortex: lower limb
• 2. Sensory Cortex: Lower limb

• Presentation:
• 1. Contralateral paralysis of lower limb
• 2. Contralateral loss of sensation of lower limb

• Area of Lesion:
• 1. Striatum/Internal Capsule

• Presentation:
• 1. Contralateral hemiparesis/hemiplegia

**common location of lacunar infarcts (secondary to unmanaged HTN)

• Area of Lesion:
• 1. Lateral corticospinal tract
• 2. Medial lemniscus
• 3. Caudal medulla (hypoglossal nerve)

• Presentation:
• 1. Contralateral hemiparesis of lower lmbs
• 2. Decreased contralateral proprioception
• 3. Ipsilateral hypoglossal dysfunction (tongue deviates ipsilaterally)

• Notes:
• -Stroke commonly bilateral
• -Middle Medullary Syndrome (infarction of paramedian branches of ASA and vertebral arteries)
• 

• Area of Lesion:
• 1. Lateral Medulla
• -vestibular nuclei
• -lateral spinothalamic tract
• -spinal trigeminal nucleus
• -nucleus ambiguus
• -sympathetic fibers
• -inferior cerebellar peduncle

• Presentation:
• -vomiting, vertigo, nystagmus
• -↓ pain and temperature to limbs/face
• -dysphagia, hoarseness, ↓ gag reflex
• -ipsilateral Horner's syndrome
• -ataxia, dysmetria (lack of coordination characterized by overshoot/undershoot)

• Notes:
• -Lateral Medullary (Wallenberg's) Syndrome
• -nucleus ambiguus effects are specific to PICA lesions

"Don't pick a (PICA) horse (hoarseness) that can't eat (dysphagia)"

• Area of Lesion:
• 1. Lateral Pons
• -cranial nerve nuclei
• -vestibular nuclei
• -facial nucleus
• -spinal trigeminal nucleus
• -cochlear nuclei
• -sympathetic fibers

2. Middle and inferior cerebellar peduncles

• Presentation:
• 1. Lateral Pons
• -vomiting, vertigo, nystagmus
• -paralysis of face, ↓ lacrimation, salivation, ↓ taste from anterior 2/3 tongue, ↓ corneal reflex
• -↓ pain and temperature in face
• -ipsilateral ↓ hearing
• -ipsilateral Horner's syndrome

• 2. MCP, ICP
• -ataxia
• -dysmetria

• Notes:
• -Lateral Pontine Syndrome
• -facial nucleus effects are specific to AICA lesions

"Facial droop means AICA's pooped"

• Area of Lesion:
• -occipital cortex
• -visual cortex

• Presentation:
• -contralateral hemianopia with macular sparing

• Area of Lesion:
• -common site of saccular (berry) aneurysm →
•  impingement on cranial nerves

• Presentation:
• -visual field defects

• Notes:
• -lesions are typically aneurysms, NOT strokes

• Area of Lesion:
• -common site of saccular (berry) aneurysm

• Presentation:
• -CNIII palsy (eye is "down and out" with ptosis and pupil dilation)

• Notes:
• -lesions are typically aneurysms, NOT strokes

-abnormal dilation of artery due to weakening of vessel walls

• 1. Berry Aneurysm
• 2. Charcot-Bouchard microaneurysm

• 
• Location:
• -bifurcations in the circle of Willis
• -most common site: bifurcation of the ACA

• Complications:
• -rupture (most common complication)
• -compression

• Rupture Presentation:
• -subarachnoid hemorrhage
• -"worst headache of life"

• Compression Presentation:
• -bitemporal hemianopia (optic chiasm)

• Associations:
• -ADPKD
• -Ehlers-Danlos syndrome
• -Marfan's syndrome

• Risk Factors:
• -advanced age
• -HTN
• -smoking
• -race (higher incidence in blacks)

• Location:
• -affects small vessels (ie: basal ganglia, thalamus)

• Associations:
• -chronic hypertension

• 1. Epidural Hematoma
• 2. Subdural Hematoma
• 3. Subarachnoid Hemorrhage
• 4. Intraparenchymal (hypertensive) Hemorrhage

• Pathophysiology:
• -rupture of middle meningeal artery (branch of maxillary)
• -often secondary to fracture of temporal bone
• -collection of blood between the dura and the skull

• Clinical Presentation:
• -lucid interval
• -rapid expansion under arterial circulation → transtentorial herniation/CNIII palsy

• Imaging:
• -CT shows lentiform, hyperdense blood collection (lens shaped)
• -does NOT cross suture lines (can cross falx, tentorium)

• Pathophysiology:
• -rupture of bridging veins
• -slow venous bleeding (less pressure → hematoma over time)
• -usually arises with trauma
• -collection of blood underneath the dura

• Epidemiology:
• -elderly (atrophy)
• -alcoholics (atrophy)
• -blunt trauma (whiplash)
• -shaken baby

• Imaging:
• -CT shows crescent-shaped hemorrhage
• -crosses suture lines
• -midline shift
• -cannot cross falx, tentorium

• Pathophysiology:
• -rupture of an aneurysm (berry: ADPKD, Ehlers-Danlos, Marfans) or an AVM

• Presentation:
• -rapid time course
• -"worse HA of my life"
• -bloody or xanthochromic spinal tap
• -nuchal rigidity

• Complications:
• -vasospasm 2-3 days after (due to blood breakdown) → treat with nimodipine
• -rebleed (visible on CT)

• Pathophysiology:
• -most commonly caused by systemic hypertension
• -also seen with amyloid angiopathy, vasculitis and neoplasm
• -typically seen in basal ganglia and internal capsule (Charcot-Bouchard aneurysm of lenticulostriate vessels)
• -can be lobar

• Presentation:
• -severe headache
• -nausea
• -vomiting
• -eventual coma

-irreversible damage begins after 5 minutes of hypoxia

• Most vulnerable areas of the brain:
• -hippocampus
• -neocortex
• -cerebellum (purkinje cells)
• -watershed areas

• Timecourse:
• -12-48 hours: Red dead neurons
• -24-72 hours: necrosis and neutrophils
• -3-5 days: macrophages
• -1-2 weeks: reactive gliosis and vascular proliferation
• ->2 weeks: glial scar

• Stroke Imaging:
• -bright on diffusion weighted MRI (visible in 3-30 minutes, lasts 10 days)
• -dark on non-contrast CT (visible in ~24 hours)
• -bright areas on CT indicate hemorrhage

• Types of Strokes:
• 1. Atherosclerosis
• 2. Hemorrhagic Stroke
• 3. Ischemic Stroke
• 4. Transient Ischemic Attack (TIA)

• Pathophysiology:
• -thrombi lead to ischemic stroke with subsequent necrosis

• Pathology:
• -cystic cavity with reactive gliosis

• Pathophysiology:
• -intracerebral bleeding
• -often due to: HTN, anticoagulation, cancer (abnormal vessels bleed)
• -may be secondary to ischemic stroke followed by reperfusion (vessels are fragile)

• Thrombotic Strokes:
• -rupture of an atherosclerotic plaque
• -usually develops at branch points
• -results in pale infarct in the periphery of the cortex

• Embolic Stroke:
• -due to thromboemboli
• -most common source is the L side of the heart (A Fib)
• -Other etiologies: carotid dissection, patent foramen ovale, endocarditis)
• -usually involves MCA
• -results in a hemorrhagic infarct

• Lacunar Strokes:
• -secondary to hyaline arteriolosclerosis (HTN or diabetes)
• -most commonly involve lenticulostriate vessels (off MCA)
• -small areas of cystic infaction
• -internal capsule: pure motor stroke
• -thalamus: pure sensory stroke
• 
  Treatment:
• -tPA within 4.5 hours (rule out R/O hemorrhage)

Brief, reversible episode of focal neurologic dysfunction typically lasting <1 hour

WITHOUT acute infarction (MRI is negative)

Deficits due to focal ischemia

• Communicating (Non-Obstructive)
• 1. Communicating hydrocephalus
• 2. Normal Pressure hydrocephalus
• 3. Hydrocephalus ex vacuo

• NonCommunicating (Obstructive)
• 1. Noncommunicating hydrocephalus

• Pathophysiology:
• -↓ CSF absorption by arachnoid granulations
• -can lead to an ↑ in intracranial pressure, papilledema and herniation

Eg: arachnoid scarring post-meningitis

• Pathophysiology:
• -increase in subarachnoid space volume but no increase in CSF pressure
• -increased CSF resulting in dilated ventricles
• -expansion of ventricles distorts the fibers of the corona radiata
• -usually idipathic

• Clinical Presentation (Triad):
• 1. Urinary Incontinence
• 2. Ataxia
• 3. Cognitive dysfunction (sometimes reversible)
• "Wet, wobbly and wacky"
• Treatment:
• -LP improves sx
• -ventriculoperitoneal shunting

• Pathophysiology:
• -increase CSF in atrophy
• -commonly seen in Alzheimers, advanced HIV, Pick's disease)

• Clinical Presentation:
• -intracranial pressure is normal
• -triad not seen

• Pathophysiology:
• -structural blockage of CSF circulation within the ventricular system

Eg: stenosis of the aqueduct of Sylvius

• -Weakness
• -Hyperreflexive
• -Increase tone
• -Babinski sign
• -Spastic paralysis
• -Clasp knife spasticity

"Upper MN = everything up (tone, DTRs, toes)"

• -Weakness
• -Atrophy
• -Fasciculations
• -Hyporeflexive
• -Decrease tone
• -Flaccid paralysis

"Lower MN = everything lowered (less muscle mass, tone, reflexes, down going toes)"

• Area Affected:
• -anterior horn cells

• Presentation:
• -LMN lesions only
• -flaccid paralysis

• Poliomyelitis:
• -poliovirus infection
• -GI → CNS by blood

• Werdnig-Hoffman Disease:
• -inherited degeneration of anterior motor horn
• -autosomal recessive
• -presents as "floppy baby"
• -death occurs a few years after birth

• Area Affected:
• -mostly white matter of cervical region
• -random and asymmetric lesions
• -due to demyelination

• Presentation:
• -scanning speech
• -intention tremor
• -nystagmus

• 
• "Lou Gehrig's Disease"

• Area Affected:
• -Anterior motor horn (LMN signs)
• -Lateral corticospinal tract (UMN signs)

• Presentation:
• -combined UMN and LMN deficits
• -NO sensory, cognitive or oculomotor deficits
• -commonly presents as fasiculations with eventual atrophy (progressive and fatal)
• **lack of cognitive deficits (Stephen Hawking)
• **lack of sensory impairment distinguishes ALS from syringomyelia

• Pathophysiology:
• -can be caused by defect in superoxide dismutase 1
• -most cases sporadic, in middle age adults

• Treatment:
• -Riluzole modestly increases survival by decreasing presynpatic glutamate release

• Area Affected:
• -spares dorsal columns and Lissauer's tract

• Pathophysiology:
• -complete occlusion of anterior spinal artery
• -upper thoracic ASA territory is a watershed area (artery of Adamkiewicz supplies ASA below T8)

• Area Affected:
• -dorsal columns
• -dorsal roots

• Pathophysiology:
• -caused by 3° syphilis
• -degeneration (demyelination) of dorsal columns and roots
• -leads to impaired sensation and proprioception with progressive sensory ataxia
• -inability to sense or feel the legs

• Associated Signs and Sx:
• -Charcot's joints (lack of sensation leads to repetitive microinjury to joints)
• -shooting pain
• -Argyll Roberston pupils (Prostitute's Pupils "accomodate but don't react")

• Exam Findings:
• -absence of DTRs
• -positive Romberg

• Area Affected:
• -anterior white commissure of spinothalamic tract (second order neurons)

• Pathophysiology:
• -cystic degeneration of spinal cord
• -arises with trauma or associated with Arnold-Chiari malformation
• -usually occurs at C8-T1
• -syrinx expansion can involve other tracts (LMN of anterior horn, Horner's Syndrome)

• Presentation:
• -sensory loss of pain and temperature with sparing of fine touch and position sense in the upper extremities
• -"cape-like"

"Subacute combined degeneration"

• Area Affected:
• -dorsal columns
• -lateral corticospinal tracts
• -spinocerebellar tracts

• Pathophysiology:
• -demyelination

• Presentation:
• -impaired position and vibration sense
• -paresthesia
• -ataxic gait

• Pathophysiology:
• -hemisection of spinal cord

• Presentation (below lesion):
• -ipsilateral UMN below lesion (corticospinal tract)
• -ipsilateral loss of tactile, vibration, and proprioception sense below lesion (dorsal column)
• -contralateral pain and temperature loss below lesion (spinothalamic tract)

• Presentation (at level of lesion):
• -ipsilateral loss of all sensation (at level of lesion)
• -ipsilateral LMN signs (flaccid paralysis) (at level of lesion)

**if lesion occurs above T1: patient may present with Horner's Syndrome (sympathetic ganglion)

• Pathophysiology:
• -caused by poliovirus (F/O transmission)
• -replicates in oropharynx and small intestine
• -spreads to the CNS via the bloodstream
• -infection causes destruction of the anterior horn cells (LMN)

• Symptoms:
• -LMN
• -weakness
• -hypotonia
• -flaccid paralysis
• -atrophy
• -fasciculations
• -hyporeflexia
• -muscle atrophy
• -signs of infection: malaise, HA, fever, nausea

• Findings:
• -CSF: ↑WBC, slight ↑ protein, Normal glucose
• -virus found in stool or throat

• Pathophysiology:
• -congenital degeneration of anterior horns of spinal cord → LMN lesions
• -autosomal recessive

• Presentation:
• -"floppy baby" syndrome
• -marked hypotonia, tongue fasciculations
• -infantile type: median age of death 7 months

• Pathophysiology:
• -autosomal recessive trinucleotide repeat disorder (GAA)
• -in frataxin gene
• -impairment in mitochondrial function

• Presentation:
• -staggering gait
• -frequent falling
• -nystagmus
• -dysarthria
• -pes cavus (high arches)
• -hammer toes
• -hypertrophic cardiomyopathy (cause of death)
• -presents in childhood with kyphoscoliosis

"Friedreich is Fratastic (frataxin): he's your favorite frat brother, always stumbling, staggering and falling"