20. Clinical correlations


·          CNS infection routes: SSS, cavernous sinus

·          severe headache after spinal tap : subnormal CSF pressure

·          arachnoid granulations calcify with age

·          yellow CSF (protein, neoplasm); IgG in CSF (MS); cloudy CSF (bacterial meningitis)




Areas affected



Subarachnoid hemorrhage

- rupture of vessels within subarachnoid space

- most common: aneurysm (berry/saccular) rupture at Circle of Willis

- other causes: exertion, trauma, angiomas


- sudden severe headache

- nuchal rigidity

- decreased consciousness


Hydrocephalus (CSF)


1.         Dandy Walker Formation (hindbrain, cyst development)

2.         Arnold Chiari Formation (brainstem displacement)


- newborns: head enlarges (brain damage possible)

- children/adults: brain herniations and death

- adults: usually secondary to brain tumor



1.         increased CSF production

2.         reduced CSF reabsorption (blockage/cong. absence of villi)



destroy some choroid plexus

Cerebral edema (H2O)

1. vasogenic edema (extracellular, increased capillary permeability)

2. cytotoxic edema (intracellular)

3. interstitial edema (CSF à periventricular areas)





viral, bacterial


- severe (gradual) headache (referred from V, C1-3)

- nuchal rigidity

- decreased consciousness

- adhesions (pia and arachnoid)

- hearing loss, mental retardation, death

- high fever

- irritability

- lethargy

- twitching

- vomiting

- photophobia



1. uncal herniations (temporal lobe à tentorial incisure)


reticular system

- decreased consciousness

- pupillary dilation (ipsilateral)

à tonsillar herniations


2. tonsillar herniations (cerebellum)


- medullary compression (reticular formation: breathing, consciousness, HR, etc.)

- unconscious


Head injury

1. base of skull (most life-threatening): CSF from nose

2. shearing during child birth

3. epidural hemorrhage (endosteal+meningeal, endosteal and bone): side blow (middle meningeal artery), affects Area 4

4. subdural hemorrhage: superior cerebral veins à SSS; front blow, shaken baby syndrome


meningeal bleeding (vessels assoc. with bone)

contusion = brain bruise

concussion: disruption of brain function


Dementia pugilistica

petechial hemorrhages

contrecoup injury (head stabilized by neck muscles)

extrapyramidal motor system

- frontal lobe: thinking, memory are affected

- cerebellum

                        - ataxia (lack of limb coordination)

                        - dysarthria (lack of coordination of articulation muscles)

- occipital: visual problems

- Parkinson’s syndrome: extrapyramidal motor system

- Alzheimer’s



Broca’s: expressive/motor aphasia

Area 44,45

inability to express thought as language


conduction aphasia

arcuate fasciculus

inability to relate language heard to language produced

Wernicke’s: receptive aphasia

Area 22

inability to comprehend language

alexia, agraphia: reading, writing aphasia

Area 39, 40

inability to read/write language


somatosensory agnosias

Areas 2,5



visual agnosias

Areas 18,19


prosopagnosia: inability to match face with identity

Areas 20,21


touch agnosia

higher order to 3,1,2




higher order to 3,1,2

inability to discriminate size, shape, texture



higher order to 3,1,2

inability to recognize letters and numbers drawn on the palm


Multiple Sclerosis

autoimmune: oligodendrocytes in CNS

separated in time and space

oligodendrocytes (global CNS)

white matter only

- chronic CNS disease

- Disseminated neurological disorder

- White matter surrounding lateral ventricles is most common

- astrocyte scars

- exacerbations and remission

- paresthesias, optic symptoms, weakness

- sensory and motor

- unilateral optic neuritis (optic disk swelling)

- trigger identification

- physical therapy

- tricyclic or anti-depressants

- corticosteroids (does not alter progression)


acute inflammatory: Schwann cells in PNS

- follows flu, vaccination

Schwann cells (global PNS)

- paresthesia, weakness

- weakness usually ascends from legs to trunk to arms


Pituitary tumor


pituitary (below optic chiasm)

Decreased libido


Genital atrophy

Diabetes insipidus


Fetal Alcohol syndrome

Dendritic spines fail to mature

dendritic spines (global)




12-20 weeks of gestation (neuronal mitotic activity)

18-24 months: axonal growth, glia mitosis


- microencephaly

- dendritic architecture

- axon and synapse change



“disorder of the synapse”

unmasking of prefrontal areas




Alzheimer’s disease


1. Neo-cortex

- Area 28 (entorhinal cortex)

2. Limbic system

- Hippocampus

- Amygdala

3. Reticular System

- Nucleus basalis of Meynert (basal forebrain)

- Nucleus Locus Coeruleus (pons)

- Raphe Nuclei

- paranoia, dementia, incontinence, memory loss

- loss of autobiography (hippocampus)

- loss of learned fear, anger (amygdala)

- reward system (Nucleus basalis of Meynert)

(Nucleus Coeruleus)

- regulation of cerebral blood flow

- selective attention

- sleep/wake cycles and REM


II Lesions


Optic nerve

Ipsilateral vision loss


Optic chiasm

bilateral temporal heminopsia


Optic tract

homonymous contralateral heminopsia


Geniculocalcarine tract

homonymous contralateral heminopsia

- can be caused by damage to internal capsule (supplied by MCA)


Meyer’s loop

homonymous superior contralateral quadrantopsia

- no macular sparing, supplied by MCA


Area 17

- scotomas

- macular sparing possible if PCA compromised


Optic neuritis

inflammation of optic nerve (viral, syphilitic, etc.)


more common in women than men (20-50 yo)

ocular pain on eye movement

central vision loss

altered color vision

afferent pupillary defect

optic disk swelling



hardening of lens


difficulty with near vision



increased CSF pressure (hydrocephalus, space-occupying lesion, edema)




optic disk swelling

hypertension, optic neuritis




Shaken Baby Syndrome



lethargy, stupor, unresponsiveness


retinal hemorrhage (different colors/ages)


subdural hematomas à tonsillar herniations

macular scarring, retinal detachment, optic atrophy



Pupillary light reflex


II à pretectum à EW à III (PS) à ciliary ganglion


Vestibulo-oculomotor reflex


overcome by dizziness


Acoustic reflex


VIII à V (tensor tympani), VII (stapedius)


accommodation reflex


involves III: two medial rectus, pupillary constrictor muscles, ciliary muscles


sucking and swallowing reflexes


tractus solitarius (V) à XII


jaw jerk reflex


massater (V3) à mesencephalic nucleus (V) à motor nucleus (V3) mastication


corneal reflex


cornea (V1) à orbicularis oculi (VII)  [direct and consensual components]



disturbance of vestibulo-oculomotor reflex


slow phase, fast phase (COWS)


Benign paroxysmal positional vertigo



vertigo in certain positions



infection of labyrinth





normal hearing


Meniere’s disease

onset: 40’s

overproduction/under-resorption of endolymphatic fluid


fluctuating/periodic symptoms

1.         periodic vertigo (irregular intervals)

2.         fluctuating tinnitus

3.         fluctuating unilateral sensory-neural hearing loss



aminoglycosides (streptomycin, gentamycin, neomycin)




sensory-neural hearing loss

1. head trauma

2. vascular compromise (there is no collateral circulation)

3. Meniere’s disease

4. DM

5. Viral/bacterial infection

6. Hereditary and congenital abnormalities




acoustic schwannoma

vestibular schwannoma


cerebello-pontine angle

unilateral sensory-neural hearing loss

unilateral tinnitus, disequilibrium, vertigo, nausea (non-fluctuating: distinguishes from Meniere’s)

à affecting VII (facial weakness) à V (numbness), IX, X, or cerebellum


herpes zoster (shingles)

viral infection


(often: V1)

dermatomal distribution

(corneal ulcerations if V is affected)


syringomyelia (spinal cord)

syringobulbia (medulla)

dysraphic condition

- ventral gray and white commissures

- lateral spinothalamic system

- (anterior spinothalamic system: not important)

- bilateral

- most common: cervical enlargement (à analgesia of hands, arms, shoulders)

- loss of pain and temperature sensation

- “keep burning my hands”


ventrolateral spinal lesions


complete hemisection = Brown-Sequard Syndrome

ventrolateral part of spinal cord

Brown-Sequard: hemisection

- lateral spinothalamic system

- contralateral loss of pain and temperature below lesion level

- ipsilateral loss at level of lesion


thalamic syndrome

damage to VPL (supplied by PCA)


- complete contralateral loss of somatic sensation

- after a few weeks: sensations à abnormal (dysesthesia/central severe pain: induced by fine touch)


tabes dorsalis

wasting of dorsal columns (tertiary syphilis)

dorsal columns



Friedreich’s ataxia

autosomal recessive spino-cerebellar disease (chromosome 9)

mitochondrial protein (frataxin)

dorsal and/or lateral column degeneration

ataxia (cerebellum)

loss of fine touch and proprioception (dorsal column)

motor paralysis (lateral corticospinal tract)


subacute combined degeneration

chronic demyelination dorsal and/or lateral columns (vitamin B12 deficiency ß autoimmune pernicious anemia, vegans)

dorsal column: degeneration

lateral column: corticospinal tracts, dorsal spino-cerebellar

(sometimes: cerebrum is affected à dementia)

loss of position sense, fine touch, proprioception



demyelinating disorders

MS of IC (proprioceptive)




lesions of postcentral gyrus


Area 3,1,2


pain still felt (at level of thalamus) but unable to localize

2-point discrimination loss


lesions of Areas 5 and 7


parietal cortex (Areas 5 and 7)

right side à contralateral (left) neglect (has contralateral and ipsilateral, left side: only contralateral)

memory loss


III oculomotor ophthalmoplegia



1. lateral strabismus

2. ptosis (drooping of eyelid)

3. pupil dilation

4. diplopia


IV lesions



vertical diplopia


V: Tic douloureux (= trigeminal neuralgia)





VI lesions



horizontal diplopia


medial medullary syndrome

strokes of medial medullary branches of vertebral artery

1. XII (ipsilateral tongue deviation)

2. medial lemnisicus (contra. loss of fine touch/proprio.)

3. pyramid-cortico-spinal tract (contralateral hemiplegia)



lateral (Wallenberg or PICA) medullary syndrome

strokes of PICA

VIII, IX, X, spinal V, Horner’s syndrome (sympathetic), ataxia, cochlear nuclei, lateral spinothalamic tract



UMN lesion


motor! (above anterior horn cell)

Groups of muscles

No atrophy

Increased muscle tone, spasticity, reflexes

Babinsky sign

Clonus may be present



LMN lesion


motor! (anterior horn cell)

single muscles


decreased muscle tone, reflexes



decorticate à decerebrate lesions



decorticate: motor lesion above RN

decerebrate: motor lesion below RN, above vestibular nuc

seen with tonsillar herniation



RNA virus


gray matter

large neurons (e.g. anterior horn cells: L2-L3)

S3-S4 are almost always spared

LMN signs (flaccid paralysis)

histologically: chromatolysis/dispersion of Nissl substance

can have bulbar poliomyelitis


Brown-Sequard syndrome

hemisection of spinal cord



- ipsilateral LMN signs at hemisection level

- ipsilateral UMN signs below hemisection level

- ipsilateral fine touch and proprioception at and below level

- contralateral loss of pain and temperature below lesion level

- ipsilateral loss at level of lesion



unknown etiology

scarring (hardening) of motor neurons

superoxide dismutase (chromosome 21) or sporadic



(anterior horn cells, pyramidal cells and Betz cells, cranial)

- LMN and UMN signs (spastic paralysis: wasted limb)

- wasting of small muscles first (hands)

- fasciculations

- sensation and intellect intact


Parkinson’s disease


1.         idiopathic

2.         Enephalitic (Spanish Flu)

3.         CVA

4.         CO poisoning

5.         Tertiary Syphilis

6.         Toxic substances?


- substantia nigra: pars compacta (melanin containing: dopamine) à decreased thalamic output

- direct pathway: inhibited

- indirect pathway: increased

± dementia

Parkinsonian (cogwheel) rigidity

Akinesia (reptilian stare)



Increased muscle tone (firm and tense): hypertonia

Impaired posture

Autonomic disturbances (inc. sebaceous, salivation, coolness in extremities)


Huntington’s chorea

autosomal dominant (chromosome 4)


caudate and putamen (small cells of)

degeneration of prefrontal cells (depression)

à butterfly ventricles



depression (highest rate of suicide of any neurological disorder: 10%)


Sydenham’s chorea

children with rheumatic fever

EXTRAPYRAMIDAL (basal ganglia)

chorea (with full recovery)





subthalamic nucleus (shuts off indirect pathway)

most severe movement disorder known



torticollis (cervical muscle: most common)

belpharsospasm (orbicularis oculi)

spasmodic dysphonia (vocal)

Writer’s cramp


Lentiform nucleus?

muscle hypertrophy


Cerebellar Lesions

1. Trauma (contre coup)

2. Infections (Kuru)

3. Vitamin deficiency (Vitamin E) à cerebellar degeneration

4. Friedreich’s ataxia (cerebellar afferents and efferents – not cortex; Chromosome 9, frataxin protein, early onset, areflexia, Babinski sign, reduced vibratory sense, “uncoordinated adolescentà scoliosis)

5. Alcoholism (Purkinje cells: anterior lobe of cerebellum, inferior olive, mammillary bodies, peripheral neuropathy)

6. Carcinoma (paraneoplasia)

7. Tay-Sachs (=amaurotic familial idiocy, Jews of East European ancestry, neuronal storage disease: lipid accumulation: GM2 gangliosides, retinal ganglion cells blindness, neocortex mental retardation, Purkinje cells ataxia; macular cherry red spot on fundus exam; hypotonia leading to spasticity)

8. Tonsillar herniation

9. CVA’s


CEREBELLAR (midline)

ipsilateral (head and eye)

problems with stance and gait (broad-based stance)

titubation (rhythmic tremor of body or head)

truncal ataxia (extensor tone greater)

cerebellar “nystagmus” (connections to III, IV, VI)


CEREBELLAR (lateral)

ipsilateral (distal musculature)


lack of proprioceptive sense

dysarthria (speech ataxia): problem with articulation

dysmetria (timing is off): test with finger to nose


ataxic gait (alcohol has effect)

intention tremor

cerebellar “nystagmus”


Dysraphic States

1. Anencephaly

2. Encephalocele

3. Spina bifida

4. Syringomyelia




Non-dysraphic States

1. Hydrancephaly

2. Porencephaly

3. Agenesis of corpus callosum





1. Microencephaly

2. Macroencephaly

3. Polymicrogyria

4. Lissencephaly




Cerebral Palsy

(symptom complex, not a specific disease)

Risk factors: maternal mental retardation, hyperthyroidism, seizures

During: obesity, C-section, older age, estrogen use

1. cortex

2. extrapyramidal

3. cerebellum


May be: monoplegic, diplegic, hemiplegic, quadriplegic

* association with epilepsy

* may have normal cognition



1. Hypotonic (low muscle tone)

2. Spastic (increased resistance to passive movement)

3. Athetoid (slow writhing movements)

4. Dystonic (persistent abnormal posture with increases with movement)

5. Combination (abnormal tone with abnormal posture)



Experimental/Clinical Data


Prefrontal lobotomy

blunted affect

feel pain (but no longer care


Stimulation of cingulate gyrus

surprise reaction


Stimulation of septal nuclei

intense pleasure


Large temporal lobe lesions (including amygdala)

= Kluver-Bucy syndrome

-           hypersexual activity

-           place things in the mouth

-           decreased emotional affect

-           visual agnosias (prosopagnosia)

-           contralateral superior quadrantopsia (Meyer’s loop)

-           loss of amygdala à lose learned fear (PTSD, panic attacks)

-           Patient HM (anterograde memory loss), Phineas Cage (personality change)


Wernicke-Korsakoff’s syndrome

starvation (Thiamine=Vitamin B1 deficiency)

memory: Papez circuit (hypothalamus: mammillary bodies)

psychosis: thalamus (DM)

ataxia: inferior olive and cerebellar cortex

nystagmus: brainstem lesions

Wernicke’s encephalopathy

psychosis (delirium)


confabulatory anemia

extraocular palsy



Horner’s syndrome

(seen as part of PICA (Wallenberg) syndrome)

loss of sympathetic innervation to face






Hirschsprung’s Disease

congenital failure of enteric plexus development in distal colon


loss of peristalsis, fecal retention

distention of proximal colon


Pure Autonomic Failure (PAF)

unknown etiology


postural hypotension


bladder dysfunction

defective sweating


Multiple System Atrophy (MSA)



PAF symptoms+bradykinesia, rigidity, ataxia, nystagmus (cerebellar signs)



(overload or impairment of heat-dissipating mechanisms)

1. ANS

2. dehydration

cerebellum (etc.)

- heat exhaustion symptoms: flu-like (headache, nausea, vomiting, dizziness)

- CNS symptoms: confusion, delirium, ataxia, coma, seizure

- hyperthermia (core temperature > 41° C

- (uncoupling of oxidative phosphorylation >  42° C)

- first part of the CNS to be affected: cerebellum



- retention of dendritic spines

- sensitive to environmental influences (sleep position, smoking, etc.)

reticular formation (respiratory centers)

6000-7000 infants/year

≠ apnea

occurs exclusively at 1-7 months (critical: 2-4 months)