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)

Disease	Etiology	Areas affected	Symptoms	Treatment
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)	Non-communicating 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	shunt
	Communicating 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)
Meningitis	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
Herniation	1. uncal herniations (temporal lobe à tentorial incisure)	III (LMN) 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
Aphasias	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
Agnosias	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
	astereognosis	higher order to 3,1,2	inability to discriminate size, shape, texture
	agraphesthesia	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)
Guillain-Barre	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 Obesity Genital atrophy Diabetes insipidus
Fetal Alcohol syndrome	Dendritic spines fail to mature	dendritic spines (global)
malnutrition	12-20 weeks of gestation (neuronal mitotic activity) 18-24 months: axonal growth, glia mitosis		- microencephaly - dendritic architecture - axon and synapse change
schizophrenia	“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
Presbyopia	hardening of lens		difficulty with near vision
Papilledema	increased CSF pressure (hydrocephalus, space-occupying lesion, edema)
optic disk swelling	hypertension, optic neuritis
Shaken Baby Syndrome			lethargy, stupor, unresponsiveness brusing retinal hemorrhage (different colors/ages) papilledema subdural hematomas à tonsillar herniations macular scarring, retinal detachment, optic atrophy
Reflexes	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]
Nystagmus	disturbance of vestibulo-oculomotor reflex		slow phase, fast phase (COWS)
Benign paroxysmal positional vertigo			vertigo in certain positions
Labyrinthitis	infection of labyrinth	labyrinth	dizziness vertigo nausea 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
vestibulotoxicity	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	DRG (often: V1)	dermatomal distribution (corneal ulcerations if V is affected)	anti-viral
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)	VPL	- 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 (dementia)
demyelinating disorders	MS of IC (proprioceptive)	IC	contralateral
lesions of postcentral gyrus		Area 3,1,2	contralateral 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		III	1. lateral strabismus 2. ptosis (drooping of eyelid) 3. pupil dilation 4. diplopia
IV lesions			vertical diplopia
V: Tic douloureux (= trigeminal neuralgia)		V
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 SPASTIC PARALYSIS WITH BABINSKI
LMN lesion		motor! (anterior horn cell)	single muscles atrophy decreased muscle tone, reflexes FLACCID PARALYSIS
decorticate à decerebrate lesions		CORTICOSPINAL decorticate: motor lesion above RN decerebrate: motor lesion below RN, above vestibular nuc	seen with tonsillar herniation
polio	RNA virus	CORTICOSPINAL 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	CORTICOSPINAL	- 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
ALS	unknown etiology scarring (hardening) of motor neurons superoxide dismutase (chromosome 21) or sporadic	CORTICOSPINAL UMN and LMN (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	etiologies à INCREASED INHIBITORY OUTPUT 1. idiopathic 2. Enephalitic (Spanish Flu) 3. CVA 4. CO poisoning 5. Tertiary Syphilis 6. Toxic substances?	EXTRAPYRAMIDAL - substantia nigra: pars compacta (melanin containing: dopamine) à decreased thalamic output - direct pathway: inhibited - indirect pathway: increased	± dementia Parkinsonian (cogwheel) rigidity Akinesia (reptilian stare) Bradykinesia Dyskinesia Increased muscle tone (firm and tense): hypertonia Impaired posture Autonomic disturbances (inc. sebaceous, salivation, coolness in extremities)	L-Dopa
Huntington’s chorea	autosomal dominant (chromosome 4)	EXTRAPYRAMIDAL caudate and putamen (small cells of) degeneration of prefrontal cells (depression)	à butterfly ventricles chorea paranoia depression (highest rate of suicide of any neurological disorder: 10%)
Sydenham’s chorea	children with rheumatic fever	EXTRAPYRAMIDAL (basal ganglia)	chorea (with full recovery)
Ballismus	lesions	EXTRAPYRAMIDAL subthalamic nucleus (shuts off indirect pathway)	most severe movement disorder known
Dystonia	torticollis (cervical muscle: most common) belpharsospasm (orbicularis oculi) spasmodic dysphonia (vocal) Writer’s cramp	EXTRAPYRAMIDAL 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 adolescent” à 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) hypotonia lack of proprioceptive sense dysarthria (speech ataxia): problem with articulation dysmetria (timing is off): test with finger to nose dysrhythmokinesia 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
Dysplasias	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 Types: 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) nystagmus confabulatory anemia extraocular palsy ataxia
Horner’s syndrome	(seen as part of PICA (Wallenberg) syndrome)	loss of sympathetic innervation to face	ptosis miosis anydrosis flushing
Hirschsprung’s Disease	congenital failure of enteric plexus development in distal colon	ANS	loss of peristalsis, fecal retention distention of proximal colon
Pure Autonomic Failure (PAF)	unknown etiology	ANS	postural hypotension impotence bladder dysfunction defective sweating
Multiple System Atrophy (MSA)		ANS	PAF symptoms+bradykinesia, rigidity, ataxia, nystagmus (cerebellar signs)
Heatstroke	(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
SIDS	- 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)