Neurology: First and Second Day

The study of nervous system anatomy, physiology, and pathology, as well as the treatment of its
disorders

All of us will face the effects of nervous system problems (or already have) in ourselves, our
friends and family, and/or in our professional lives.
Former President Reagan
Now the personality, intellect and behavior America was once familiar with is lost to Alzheimers
disease a plight faced by 4,000,000 Americans.
This stroke survivor is going through rehab. There are over 4,000,000 U.S. stroke survivors living
with varying degrees of disability due to some disruption of normal blood supply to regions of brain.

Traumatic Brain Injury (TBI)

~3,000,000 cases

Evaluation of an Infants Seizures

~2,000,000 Americans live with epilepsy

Michael J. Fox - just 1 of the at least 500,000 Americans with Parkinsons Disease
Richard Pryor
Two of the ~300,000 Americans suffering from multiple sclerosis (MS)
Christopher Reeves
Loss of bodily movement, sensation, and even normal breathing due to damage to a region of the
spinal cord no bigger than your little finger. There are about 200,000 survivors of spinal cord injury in
the US.

Laura Downey (left) has just been diagnosed with Huntingtons Disease. Like 30,000 others she faces
a gradual deterioration of motor control, cognitive functioning, personality and emotional control. There
is a 50/50 chance that her daughter has also inherited the disease-producing gene.

Stephen Hawkins
The mind of a great physicist trapped in an almost unmoving body due to amytrophic lateral
sclerosis (ALS). There are ~25,000 cases of this tragic condition also known as Lou Gehrigs disease)

Baby Tom had a hemispherectomy - half of his cerebrum was removed to control seizures.

Relating Brain Anatomy or Function to Psychological Disorder

Ongoing longitudinal study of the gradual loss of cortex in childhood schizophrenia
Brain Less Active in Depression
Decreased Cortical Activity in ADHD
 The cingulum is one brain region which appears to malfunction in obsessive-compulsive disorder.
Some desperate patients have received a cingulotomy to try to treat their disorder

More and more mental disorders are being recognized as disorders associated with distinctive
nervous system changes.
Recent studies suggest therapies, both medical and psychological, bring about changes in brain
function.

We also learn about the nervous system to better understand NORMAL or even exemplary nervous
system functioning:

Michel Flatley (Lord of the Dance) has been clocked at 35 taps per second. It is his nervous system
commanding his performance.
An Olympic gymnast is just one example of the precision, timing, & coordination provided by the
nervous system
Whoever your favorite composers or performers, they owe their music to the nervous system.
Feats of mind - creative or scientific - also products of the brain.
In a community of ~100,000 (like Cedar Falls/Waterloo), youll find, on average:
Over 2000 will suffer from migraines.
There will be over 500 with
back pain.
Over 350 will have experienced a herniated disc.
Over 250 will have
cerebral palsy.
Over 130 will be experiencing serious aftereffects of a concussion
(post-concussive syndrome)
Over 80 will suffer from shingles (herpes zoster)
Over 80 will have problems with their peripheral nerves
(peripheral neuropathy)
Over 80 will have brain tumors.
Over 70 will have been born with a congenital malformation of their nervous system
(like spina bifida)
Over 15 will have an infection of the brain (encephalitis) or meninges (meningitis)
Over 250 will be born with
Down Syndrome.
Over 300 will suffer from Menieres Disease.
ALL will be making continuous use of their nervous systems for all aspects of mental activity and
behavior, as well as to regulate bodily functioning.
Over 800 individuals with traumatic brain injuries
Over 250 will suffer from dementia.
Over 650 who have had strokes (cerebrovascular accidents)
Over 200 will suffer from Parkinsons Disease.
Over 60 will have
multiple sclerosis.
Over 50 will have a spinal cord injury.
Over 30 will have Lou Gehrigs Disease (ALS)
Over 650 will experience epileptic seizures.

Some Basic Neuroanatomy

Parts of the Neuron
Gray & White Matter
Brain areas with a high concentration of neuron cell bodies/dendrites look darker (gray matter)
and function like information processors receiving and combining/processing input
Areas with lots of myelinated axons appear lighter (white matter) and function like cables
connecting regions
A group of neuron cell bodies = nucleus (in CNS) or ganglion (in PNS)
A group of axons = tract or pathway (in CNS) or nerve (in PNS)

Cortex is Gray Matter

White Matter Under Cortex
CNS vs PNS
Central Nervous System (CNS): brain and spinal cord
Peripheral Nervous System (PNS): all the nerves outside of the brain & cord

5 levels of spinal cord

Cross Section of Cord
Dermatomes Related to the 31 Pairs of Spinal Nerves
5 Chunks of Brain
Book Fig. 1.10 and 1.12
5 Vesicles in Embryonic Brain
Brainstem
Triune Brain
Midline View of Brain
Limbic System
Basal Ganglia
Central Sulcus and Lateral Fissure; Precentral Gyrus and Postcentral Gyrus
Lobes
Motor Cortex & Somatosensory Cortex
Ventricles

Protection of the CNS

1. Bones
2. Meninges &
 3. Cerebrospinal Fluid (CSF) do a good job under normal everyday conditions.

The Meninges
3 layers of connective tissue enclosing brain & spinal cord
Starting from the outside, the layers are:
1. dura mater (tough mother)
Actually has 2 layers which run close together in most locations
a. outer layer is anchored to skull bone in certain places
b. inner layer forms folds that partition skull cavity into compartments
i. one between R & L hemispheres: falx cerebri
ii. one between occipital lobe & cerebellum:tentorium cerebelli
Spaces between layers at those folds form dural venous sinuses for blood leaving brain
Falx cerebri (picture) divides upper portion of skull into right and left compartments can
also see the tentorium cerebelli between occipital lobe and cerebellum, separating
lower compartment of skull from upper area of skull
2. arachnoid mater(spiderlike)
Thinner layer loosely enclosing CNS
Space beneath arachnoid is filled with cerebrospinal fluid (CSF)
Spider-like filaments cross this subarachnoid space to the inner most layer of meninges,
the pia mater
Blood vessels supplying brain are also travel in the subarachnoid space (SAS)
3. pia mater(tender matter)
Very thin layer that tightly follows brain surface
Contains lots of small capillaries supplying blood to the CNS

Clinical Applications
Dural partitions (Falx cerebri & tentorium cerebelli) play a significant role in brain damage related
to head injuries as well as brain damage resulting from increased intracranial pressure.
Meningioma- ~15% of brain tumors arise from the meninges
Meningitis infection/inflammation of the meninges (well come back to this shortly)

The Ventricular System and Cerebrospinal Fluid (CSF)

Reminder of Tube Shape of Early CNS easy to see it is a fluid filled tube (not so easy to see in adult
brain)

Side & Frontal Views of Ventricles

Lateral Ventricles in the Hemispheres

Lateral Ventricles From Above

n These are the canals of the cerebral hemispheres or telencephalon

3rd Ventricle in Diencephalon

Interventricular foramen links lateral ventricles to 3rd ventricle
Sagittal Section Thru vertically oriented 3rd Vent. On midline of diencephalon
n Connects to skinny cerebral aqueduct, the canal of the midbrain

4th Ventricle in the Hindbrain

Choroid plexus located in ventricles continuously produces CSF, replacing the ~125-150 ml several
times/day
Circulation of CSF

Arachnoid Granulations Allow CSF Re-absorption into dural sinus blood

Meningitis (inflammation of meninges)

n Can be caused by bacteria, virus, fungus, or reaction to chemicals/drugs
n Headache, fever, stiff neck, irritability, photophobia, nausea, possible seizures or altered mental state,
rash
n Bacterial meningitis can progress very rapidly and is a medical emergency (up to10% death rate).
Several different common bacteria if they gain access to the CNS can cause it (Haemophilus influenzae
B (Hib), Streptococcus pneumoniae, Neisseria meningitidis (the cause of the meningococcal meningitis in
the news)

Meningitis continued
n Inflammation/swelling can lead to lasting deficits in 20-30% (impaired hearing, vision or movement,
retardation, epilepsy, hydrocephalus), especially in neonatal cases or if treatment is delayed
n Viral meningitis is generally less serious
n Meningitis more common in young and adults with special risk factors.

Tests
n CT scan can show swollen meninges
n Lumbar puncture (spinal tap) to identify infection
n Kernigs sign
n Brudzinkis sign

n Bacterial meningitis treated with antibiotics

n Now vaccines for 2 varieties available: Hib and Meningococcal (Menimmune for Neisseria strains A,C,Y))
No vaccine for for the strain B most often striking

Meningococcal Vaccination
Spinal
Meninges
n Spinal cord ends at the top of the L2 vertebra.

Needle Enters Via Intervertebral foramen

Needle Enters Subarachnoid Space

Epidural Anesthesia

Spinal or Intrathecal Anesthesia

(into subarachnoid spac

Hydrocephalus
n Excessive CSF (enlarged ventricles)
Noncommunicating hydrocephalus an obstruction prevents flow of CSF thru ventricles
Communicating hydrocephalus CSF not reabsorbed normally
Rarely a tumor may cause excess production
n In an infant, the head can expand, but in adult intracranial pressure (ICP) rises.

Enlarged Ventricles

Enlarged Skull (bones not yet fused in infants)

Implanted Shunt to Drain CSF

3rd Venticulostomy

Normal Pressure Hydrocephalus

n Occurs in older (60+) individuals
n Show 3 symptoms:
Dementia
Gait (walking) problems (hesitation, slowness)
Incontinence
n Scan shows enlarged ventricles but CSF pressure is now in normal range
n Symptoms improve with shunting/removal of some CSF
n
n Sometimes ventricles enlarge because of loss of adjacent brain tissue (e.g. in Huntingtons,
schizophrenia) rather than a CSF problem

Some Other CNS Infections

n Viral
Rabies
Creutzfeld-Jakob Disease
Encephalitis
n Fungal (most often Candida albicans)
Usually in immune-compromised individuals
Infections continued
n Parasitic Infections
Neurosyphilis
Lyme Disease (from ticks)
Brucellosis (from cattle)

Traumatic Brain Injury (TBI)

Head Injury
8 million/yr in US, 1.5 million serious, .5 million hospitalized, 100,000 die, 90,000 disabled, 2,000 end up
vegetative
More Head Injury Stats:
l 2-3x more males than females
l peak ages 18-24 & over 75
l 20% of those who die from head injuries dont have a skull fracture; skull fracture is not a good
predictor of outcomes unless it is depressed
l in 2/3 death results from excessive movement of the brain in skull
Causes of Head Injuries
l 50% in motor vehicle accidents
l 21% in falls
l 12% assaults & violence
l 10% in sports/recreational accidents
l 7% other
Sports Injuries
l About 300,000 sport-related head injuries a year in US (9% serious)
l Sports involved (from most frequent)
Equestrian
Boxing
Football, soccer, rugby
Bicycling
Martial arts; auto racing
Hockey

Types of Injuries
l Concussion - transient neurologic dysfunction (altered consciousness or LOC) but no damage visible
l Closed head injury (CHI)-skull intact; brain injured by excessive movement
l Contusion - bruising of brain (surface blood vessels broken, tissue swells)
l Penetrating injury or laceration - brain tissue torn or punctured (by bullet, bone fragment)

Focal Damage to Frontal Lobes

Floor of Skull
Coup-Contrecoup Injuries
Damage in CHIs
l at point of impact (coup)
l opposite point of impact (contrecoup)
l where brain presses or is pulled against skull or dural partitions
l where tissue is stretched, twisted or sheared -rapid deceleration causes diffuse axonal injury &
petechia (pinpoint hemorrhages)
l tissue compressed by intracranial pressure (blood, swelling) or fracture
Coup-Contrecoup Injuries
Increased Intracranial Pressure
l No extra room in skull for blood, swelling
l Increased intracranial pressure presses on brain causing symptoms, damage, and possible herniation
l Signs: change in consciousness, pupils, breathing, motor function, headache, vomiting, seizures,
personality, papilledema
Head Injury Related Bleeding
l Epidural/extradural hematoma - most often after a blow to side of head damages meningeal arteries.
May appear lucid after initial signs of concussion but then rapidly decline (1-2 hr) - drowsiness,
hemiparalysis, 1 pupil may dilate. Emergency surgery to relieve growing pressure before brain
herniates.
Head Injury Related Bleeding (cont.)
l Subdural hematoma - front/back blow causes slower bleed over days/wks
l Intracerebral hematoma - bruising of brain can cause internal bleeding (most often frontal or
temporal)
Hematomas
Epidural Hematoma
Subdural Hematoma
Craniotomy to Remove Hematoma
Herniation Due to Pressure
l midline shift past falx cerebri
l medial temporal lobe past tentorium, causing pressure on midbrain
l cerebellum/medulla thru foramen magnum, causing pressure on medulla
l herniation can quickly cause coma and death

Diffuse Axonal Injury

Petechial Hemorrhages
Gunshot Thru Brain
Basal or Basilar Skull Fracture
l Sometimes visible surface of skull may be intact but injury has cause hairline fractures of the bottom
of the skull
l Fracture may tear dura or may injure the bones of the facial sinuses or auditory canal
l Signs: Racoons eyes, Battles sign, otorrhea, rhinorrhea
Battles Sign

Possible Head Injury Sequelae

l post-traumatic amnesia (PTA) or milder memory difficulties
l focal losses (e.g cognitive, personality, motor etc.)
l meningitis if head was opened
l post-traumatic epilepsy
l coma

Coma & Related States

l Coma total unconsciousness (eyes closed, cant be aroused, no response to pain)
l Persistant vegetative state eye opening and periodic wakefulness, eye movements, grimaces,
grasping/groping,withdrawal from pain, but no real awareness
l Locked-in syndrome consciousness but almost complete paralysis due to brainstem damage
Prevention
l wear seatbelts; use infant seats
l avoid motorcycles; wear helmits
l dont drink excessively (& dont drive)
l beware of hazardous falls; use ladders appropriately
l beware of assault situations; projectiles
CHIs Vary in Severity (see Iverson link)
l Head Trauma with little or no injury
l Uncomplicated Mild Head Injury
l Complicated Mild Head Injury
l Moderate Head Injury
l Severe Head Injury
l Catastrophic Head Injury
Neuron
Neuron
Multipolar Neuron
Synapse

Best Known Neurotransmitters

n Acetylcholine (ACh)
n Norepinephrine (NE)
n Dopamine DA)
n Serotonin or 5-Hydroxytryptamine (5HT)
n GABA
n Endorphin
Acetylcholine (ACh)
n neurons using ACh are known as cholinergic neurons. Examples:
n motor neurons
n parasympathetic neurons
n many CNS neurons (in cortex, basal ganglia, hippocampus, brainstem)
n acetylcholinesterase breaks down ACh
Norepinephrine (NE)
n aka noradrenaline
n transmitter of symnpathetic synapses to organs and glands
n also found in many CNS neurons (RF, hypothalamus)
n action terminated by reuptake
n closely related to DA (catecholamines) and both related to 5HT (monoamines)
Dopamine(DA)
n primarily known as a CNS transmitter
n transmitter in basal ganglia, limbic system & frontal cortex & parts of hypothalamus that control
pituitary
n action terminated by reuptake
Serotonin (5HT)
n primarily known as CNS transmitter
n found in neurons of brainstem associated with sleep & pain suppression, & in limbic system
n action terminated by reuptake
GABA
n best known inhibitory transmitter
n widely distributed in CNS
n seems necessary to keep neuron activity in check
Neuromuscular Junction
Myasthenia Gravis: A Neuromuscular Disease
n abnormal muscle fatiguibility & weakness
n progressive, usually affects muscles of head 1st
n autoimmune disease attacking ACh receptors on muscles

Patient Asked to Look Up

Ptosis (drooping of eyelid)

n Maybe Sleepy had MG
MG Tests
n Intravenous administration of Tensilon (edrophonium), a short-acting anti-cholinesterse, usually
produces brief improvement
n Nerve conduction studies show normal conduction; electromyogram shows normal muscle response
which decreases with each response
n Chest xray may show thymoma
MG Treatments
n Decrease the attack by the immune system:
immunosuppressant drugs
thymectomy
plasma exchange to remove antibodies
n Increase ACh levels with an anti-cholinesterase drug (prevents normal breakdown of ACh, prolonging
it ability to stimulate remaining ACh receptors)
Botulinum Toxin
n Toxin produced by bacteria Clostridium botulinum or its spores, incredibly potent, easily absorbed
from GI tract, and then distributed by blood everywhere except CNS
n Intereferes with the release of ACh, causing paralysis & autonomic effects
n Selective injections of botulinum toxin now used to treat excess muscle contraction (spasticity)

Action of Botulinum Toxin

Black Widow Spider Venom
Neurons and Glia
Glial Cells (supporting cells)
n 5-10X more numerous than neurons
n make up about half of brain weight
n several distinct types
n growing evidence of multiple roles that glia play
Astrocytes (most common)
n separate synapses
n form a limiting membrane on outside of CNS
n surround CNS capillaries adding to blood-brain barrier
n transfer materials to & from neurons
n produce growth factors
n clean up excitatory transmitter glutamate
n may even communicate?
n can multiply to form scar tissue or tumors
Astroglia or Astrocyte
Oligodendrocytes
n the other large glial type (macroglia)
n form myelin sheaths on CNS neurons
n form thin coat on unmyelinated ones
n produce nerve growth factor
n Schwann cell is the PNS counterpart

Myelin Sheaths
Cross-section of Nerve
Axons Within Nerve
Microglia
n small glia which are mobile phagocytes
n Recent evidence suggests they play a key role in neurodegenerative diseases - activated microglia
may attack neurons in AIDS, Alzheimers, MS, etc.
n contribute to scar tissue formation
Ependymal Cells
n line the ventricles/canals
n participate in CSF production
n have cilia to help circulate CSF
n may transport materials between CSF & neurons
Glia Clinical Notes
n 60% of brain tumors are gliomas
n multiplying of glia to form scar tissue (gliosis) can irritate nearby neurons: important cause of focal
epilepsies
Multiple Sclerosis: Another Autoimmune Disease
n Immune system attacks miscellaneous myelin sheaths in CNS, causing demyelination in 250,000 in US
(2/3 are women)
n Where myelin is lost, hard plaques of scar tissue (glia & immune cells) form
n Symptoms depend on which neurons lose myelin but always multiple symptoms (clinically diagnosed)
n Periodic attacks (days) & then remissions (months) which progress
Loss of White Matter in MS
Demyelination Seen in MRI
What Causes MS?
n More common in northern climates
n For some reason B-cells attack oligodendrocytes, T-cells attack certain myelin proteins that resemble
a virus.
n Illness activating immune system can aggravate the disease
n Less common in Blacks, Asians, Native Americans and shows some tendency to run in families (role of
genetics). Identical twins have 30% concordance.

MS Treatment Approaches
n Avoid stress & illness; treat the specific symptoms
n Steroids & other immunosuppressant drugs to shorten attacks
n New meds: beta-interferon, methotrexate
Consider this:
n Youve recently had the flu or some other infection (60%), or youve had a vaccination. You notice
some tingling & numbness in your feet & your legs seem to be getting weaker (60% cant walk). Over a
period of hours (or up to 2 weeks) the weakness & loss of ability to move moves up your body. If it gets
high enough you may not be able to breathe (20-30%) swallow, or speak & may have bilateral facial
paralysis. 5% die
Guillain-Barre Syndrome
n Rapid ascending, usually symmetrical PNS demyelination
n Loss of motor function most obvious; some numbness & back pain possible
n Can be a medical emergency- 25% need artificial respiration
n Probably a temporary autoimmune disorder; majority have recently had an infection or vaccination
n Some begin recovery within weeks, others months. 70-80% full recovery
GBS

Brain Tumors or Neoplasms

n Usually due to abnormal growth of tissues /cells other than neurons
~15-20% Meningiomas - benign, encapsulated growth of meninges
~60% Gliomas - infiltating, usually malignant multiplication of glial cells
Most common astrocytoma
Most dangerous glioblastoma multiforme
Acoustic Schwannoma/neuroma - covering on 8th cranial nerve grows
~10-30% metastatic tumors (originate outside the brain, e.g. in lungs, breasts)
Brain Tumors continued
n Most tumors occurring in adulthood are supratentorial (in cerebral hemispheres)
n Most tumors in children are infratentorial (below tentorium, in brainstem). The single most
common is a medulloblastoma.
n Tumor problems: compression of brain area, infiltration, increased ICP, sometimes may impair CSF
flow or endocrine controls.
Meningitis
n Can be caused by bacteria, virus, fungus, or reaction to medications
n Headache, fever, irritability, stiff neck, photophobia, nausea, possible seizures or altered cognition
n Bacterial meningitis can progress very rapidly so is a medical emergency
n Viral meningitis is generally less serious
n Inflammation/swelling can lead to lasting deficits in 20-30% (impaired hearing, retardation, epilepsy)
Tests
n Lumbar puncture to identify infection
n Kernigs sign
n Brudzinkis sign
Some Other CNS Infections
n Viral
May be pantropic (general infections of many tissues like mumps or herpes) or neurotropic (specific
affinity for nerves).
Example: viral encephalitis many varieties (St. Louis, Equine, HIV) virus spreads to brain itself with
high risk of mortality or disability
Common forms spread from animals to humans by mosquitos
Rabies a neurotropic infection
n Virus is picked up by nerve endings at the site of the bite & slowly(2 weeks-6 months) travels to CNS
via retrograde transport. If the virus reaches the CNS before vaccination it is invariably fatal.
n Symptoms may appear in 2 forms: furious rabies - hyperexcitable, irritable, muscle pain and spasms,
may viciously bite at anything, or dumb rabies - lethargy progessing to paralysis & coma
Creutzfeldt-Jakob Disease
n Progressive dementia and cerebellar ataxia
n In past most cases caused by exposure to tissue (cornea or dura transplants, human growth hormone
injections, contamination from previous brain surgery on infected patient). A few (5-10%) cases are
familial
n Long incubation period
n Caused by tiny abnormal proteins (prions) which are very resistant to inactivation
Bovine Spongiform Encephalopathy (BSE)
n Related animal diseases transmitted even through eating feed containing tissue from infected (mad
cow disease)
n 1996 evidence that BSE could cause a type of CJD in humans
n 1/2001 FDA recommends banning blood donations from those who lived in BSEcountries

n BSE identified in these countries

Fungal (most often Candida albicans)

n Usually in immune-compromised individuals
Infections continued
n Parasitic Bacterial Infections
Syphilis
Lyme Disease (from ticks)- untreated can cause arthritis and neurological problems like
Bell's palsy - facial muscle droop
meningitis
encephalitis
tingling of extremities
trouble with concentration *
memory loss *
extreme fatigue *

Tick Bite
Bulls Eye Rash
Nervous System Development see pages 4-7
Images
Inner Cell Mass of Blastocyst
Inner cells form 3 layers
Neural Plate Develops Groove Neural Folds
Grow Closer And Closer to form Neural Tube
Neural Tube & Neural Crests
Tube Closed by 4th Week Seen in cross-section
Formation of the Neural Tube, seen from above
Vesicles Form at Head End
Neural Tube Bends or Flexes
Inside the Tube: Alar & Basal Plates
Migration of Neurons
Each step must occur properly for normal development
Formation of the neural tube
Cell proliferation
Cell migration & differentiation
Growing of neural connections
Apoptosis or selective cell death or "pruning"
Myelination of axons and continued formation of synapses
Neural Crest Cells Become:
Sensory ganglia & incoming sensory nerves
Autonomic ganglia & nerves to organs
Parts of endocrine system related to NS (e.g. adrenal medulla)
Parts of eye and ear; some smooth muscles
Peripheral glial cells; pigmented cells
Neural Tube Defects (NTD)
Closure of the neural tube normal induces the normal development of spinal column, skull &
overlying skin. If closure does not occur normally, nervous system may remain exposed ("open
NTD"). In other cases the neural tube may not be exposed to the surface ("closed NTD"), but
the spinal vertebrae and skin surrounding the spine may not be completely normal.
Improper Closing of the Anterior Neuropore (~ 25 days )
Anencephaly forebrain & its coverings fail to develop.
Baby has a flattened, open skull.
With only hindbrain & midbrain structures intact, survival is brief (hours-days).
Anterior NeuroporeFails to Close Properly
Sometimes the forebrain develops but the skull does not fuse completely.
As a result part of the brain (often the occipital region) may bulge out of the opening.
This is encephalocele.
Improper migration of cells can cause abnormal development of brain areas, especially cortex
Much More Common: Improper Closing of PosteriorNeuropore(~27 days)
Spina bifida ("open spine")
May be so minor you don't know you have it ("spina bifida occulta"), or
may be so severe it causes death or disability
Has been linked to diet (insufficient folic acid), geography, and drugs, temperature, and illness
during pregnancy, age of mom, and does tend to run in families.
3 Types of SpinaBifida
Prenatal Diagnosis
Open NTDs are associated with elevated levels of alpha-fetoprotein in mother's blood and
amnionic fluid (~16-18 weeks)
Some NTDs are visible on ultrasound Some experimental surgeries to repair spinal
abnormalities in utero
Healthy Sonogram
Signs of Anencephaly
Signs of SpinaBifida
Cerebral Palsy (500,000 in US) aka Static Encephalopathy
Not a single disease or disorder but a category of nonprogressive motor impairments that result
from faulty brain development or early brain damage.
Specific motor symptoms vary, as does severity and presence of other disabilities.
Once thought to be primarily the result of difficult labors/birth injuries but majority of cases
due to genetic, developmental, intrauterine factors.
(see study guide and CP website)
Autism
Developmental disorder with the following key features:
Impaired social interactions
Impaired verbal & nonverbal communication
Impaired cognition (unable to imagine, impaired imitation)
Restricted repertoire of activities and interests; often show repetitive and stereotyped behavior
patterns
Once thought to be due to poor parenting
Growing evidence that autism results from an interaction between abnormal genes and
environmental factors very early in development (in most cases).
Improper development of the neural tube at the pons/medulla junction (area of 7th &
8thcranial nerves & cerebellum) at 20-24 days as well as other congenital malformations of
cerebellum, hippocampus, corpus callosum. Improper migration and apoptosis
Environmental factors: rubella, alcohol, valproate, thalidomide, PKU, & others
Fetal Alcohol Syndrome
Most common variety of drug-related faulty development, causing underdevelopment,
distinctive physical features as well as nervous system impairments. Also affects cell division,
migration and apoptosis.
FAS Facial Features
Spinal Cord Vocabulary
Foramen magnum
Segments of cord
Conus medullaris
Cauda equina
Filum terminale
Cervical and lumbar enlargements
Spinal reflexes

White matter columns

Long tracts of cord
Gray matter dorsal, ventral & lateral horns
Dorsal and ventral roots
Dorsal root ganglia
Vertebrae & intervertebral disks
Intervertebral foramina
 Meninges of Cord
Spinal Roots and Nerve
How Sensory Input Enters Cord

Dermatomes

Ascending Tracts or Pathways

Afferent" tracts carrying sensory input up cord from body to brain

Basic Organization of Ascending Somatosensory Pathways

A series of 3 neurons is needed to get the message from body surface to cortex:
First-order neuron: carries input from skin to CNS (dendrites are sensitive to external stimulus, soma
is in dorsal root ganglia, axon enters CNS & synapses on 2nd neuron)
Second-order neuron: axon of 2nd cell crosses to the opposite side of CNS & carries input up to the
thalamus. Also sends a branch to the reticular formation to arouse us.
Third order neuron: Thalamus neuron relays input to the cortex.

Key Pathways Mediating Conscious Sensations

Dorsal column pathway discriminative (detailed, fine) touch, proprioception (limb position/motion sense), &
vibration. This tract is needed for us to feel & precisely locate light touch & do 2 point discrimination,
stereognosis & graphesthesia.
Spinothalamic pathways pain, temperature and gross touch
The Sensory Exam

White Matter Columns in Cord (see Fig. 8.13)

Dorsal Column Pathway (Fig. 8.14)
Spinal Tracts

What happens if you suffer damage to or deterioration of the dorsal column pathway?
Irritation of Sensory Receptors
As sensory receptors deteriorate, they may malfunction before they stop functioning causing
paresthesia or dysesthesia.
E.g. in tabes dorsalis shooting, lancinating, electrical-like or cramp-like pains occur, and in peripheral
neuropathy unpleasant abnormal tingling, burning, tightness, & pins & needles paresthesias occur.
Youve experienced temporary paresthesias when your arm or leg falls asleep; also one of the early
signs of carpal tunnel syndrome

Sensory Ataxia
Gait (walking) problems related to loss of proprioception following degeneration of dorsal columns
and/or dorsal roots.
Watches feet while walking, feet tend to slap down; shows a positive Rombergs sign (person
sways and is unsteady if asked to stand with eyes closed)
Some of the causes:
 Syphilis Tabes dorsalis
Vitamin B-12 deficiency
Peripheral neuropathy (e.g. as seen in diabetics and alcoholics)
Multiple sclerosis
Romberg Test
Tabes Dorsalis (see study guide)

Astereognosis
Another symptom of dorsal column damage
Without fine discriminative touch person cannot identify objects or textures by touch
Example: Can happen in MS if dorsal column loses its myelin

Spinothalamic Pathway (Fig 8.15)

Pain, temperature and gross touch

Pain Chemicals

What will happen to an individual who has irritation of

or damage to the lateral spinothalamic pathway?
Have you had chicken pox?

If so, about 20% of you are likely to develop Shingles sometime later in your life.

Shingles (aka Herpes Zoster)

(1 million cases/yr in US)
After chicken pox the virus (Varicella zoster) lies dormant in dorsal root ganglia.
It may re-activate if your immune system is weakened or stressed, or as you get older (most
common after 50-60).
The first sign is tingling, burning or shooting pains, usually in a single unilateral dermatome.
A few days later a pox-like painful rash develops in that dermatome, lasting 4-5 weeks.

Herpes Zoster or Shingles

Treatment
Antiviral drugs like acyclovir can shorten the attack & decrease complications if taken when the first
signs appear.
Antiinflammatory pain relievers may be necessary.
Zostrix (capsaicin) cream applied to unbroken skin also relieves pain by decreasing the supply of
Substance P in pain receptors.
Now experimenting with boosting immunity with chicken pox vaccination.

Pain Perception
Recall the woman whose pain responses were being tested in the video
Electrode implanted in her calf, stimulating nerve of spinothalamic pathway
She perceived the pain as coming from her foot, not her calf
 Referred Pain we often experience pain from organs as if it were coming from the surface of body

The Gate Control for Pain

Ramachandrans
Mirror Box Therapy for Phantom Limb Pain

Descending Pain
Suppression Pathway

Another disorder affecting the spinothalamic pathway: Syringomyelia

Enlarged CSF filled cavity within cervical spinal cord, most often associated with Chiari malformation
(cerebellum bulging thru foramen magnum)
Cavity compresses and damages nearby tissue (like hydrocephalus of cord)
Cape anesthesia, loss of pain & temp sensation from hands, weakness if ventral horns damaged
If severe, operate on malformation or shunt.

Syringomyelia
MRI of Cavity

Descending Motor Pathways

Pathways from brain carrying motor commands down to lower motor neurons

Lower Motor Neurons (LMNs)

Neurons whose axons synapse on skeletal muscle fibers (to stimulate contraction)
aka alpha motor neurons
aka final common path
majority are in ventral horns of cord
some are in the brainstem (cranial nerve motor neurons)

Motor Units
Motor unit = a single LMN + the extrafusal muscle fibers it synapses on
Some motor units are small (axon synapses on just a few fibers); some motor units are
large (axon synapses on ~1000 fibers).
 All fibers of a motor unit would be stimulated by neurotransmitter (ACh) release at the same
time.
All movements depend on LMNs.

Spinal Anatomy and Physiology

Spinal Nerves
Myotomes
Muscle and tissue of the body innervated by spinal nerve roots
Key myotomes
Arm extension: C-5
Elbow extension: C-7
Small finger abduction: T-1
Knee extension: L-3
Ankle flexion: S-1
Upper Motor Neurons(UMNs):
The brain cells that send motor commands down to the LMNs.
UMNs are the source of the descending motor pathways
Damage to UMNs affects motor function/control because there is a loss of commands to the
LMNs

The Corticospinal or Pyramidal Pathway

Most direct route for UMNs to influence LMNs (Cortex to LMN)
Evolutionarily recent, largest in man
Most important for fine, precise, rapid, skilled voluntary movements of small motor units
(e.g. hands, facial muscles)
Big body muscles receive more input from other extrapyramidal motor pathways

Spinal Reflexes
Spinal cord is not just a cable between brain and body. Segments of cord also have local
functions relatively independent of the brain.
Monosynaptic stretch reflex
Multisynaptic withdrawal or flexor reflex
Multisynaptic withdrawal plus crossed extensor reflex

Stretch Reflex

Muscle Fibers Depend on Their Innervation

Muscle fibers that lose their LMN show:
no reflexive contraction (so no muscle tone)
no voluntary contraction
 This is called flaccid paralysis
atrophy of the muscle fibers over time
These are symptoms of LMN damage

Poliomyelitis
Viral infection causing a summer cold/flu like illness in most, but which, in some, infects
LMNs most often those controlling the lower limbs.
If those neurons die, the muscle fibers in their motor units will be paralyzed, show no
reflexes and will atrophy.
Example of LMN Damage:
Polio Induced Paresis(weakness)
& Paralysis
Muscle Atrophy
Cause by loss of LMNs due to polio

Other Descending Tracts:

Extrapyramidal Motor Pathways
Rubrospinal pathway to regulate tone of flexors in limbs for locomotion & to organize
repetitive movements that involve the flexors (e.g. walking, running, crawling)
Vestibulospinal pathway to stimulate extensors (antigravity) for standing, posture
Tectospinal pathway for reflexive motor reactions to visual stimuli
Reticulospinal pathway to regulate muscle tone by modulating the stretch reflex
Corticospinal path modulates activity of these tracts as well as spinal reflexes

Babies Are Born With Pre-Programmed Reflexes

Upper Motor Neurons Modulate Muscle Tone Via Gamma Motor Neurons
Gamma motor neurons (the other motor neurons) do not go to the extrafusal fibers that
move us.
They synapse on intrafusal muscle fibers inside stretch receptors/muscle spindle receptors.
Tensing these little fibers makes stretch receptors more sensitive.
UMN also can inhibit stretch reflex to allow movement, so we are not stiff statues.

Symptoms of UMN Damage

Reflexes and muscle tone still present and, in fact, intensified hyperreflexia
Voluntary control impaired
Spastic paralysis (excess muscle tone & loss of voluntary control of movement)
No denervation induced atrophy (LMNs are okay)
Reflex Changes After UMN Damage
hyperactive stretch reflex, particularly in anti-gravity muscles
too much muscle tone (hypertonia or spasticity)
clonus (rapid repetitive response to stretch)
altered Babinski & cremasteric reflexes after corticospinal damage
Normal vs. Positive Babinski

Clonus
Without descending modulation from brain, stretch reflex leads to repetitive contractions
 UMN Syndromes
UMN damage above red nucleus decorticate posture with arms flexed, hands fisted (upper
picture)
UMN damage between red nucelus and vestibulospinal & reticulospinal tracts decerebrate posture

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrigs Disease

Fatal progessive loss of LMNs as well as corticospinal pathway (UMNs). Several genes involved.
Onset most often in late 50s-early 60s; more men affected
70% will die within 5 years (eventually cannot swallow, breathe)

ALS Symptoms
First symptoms usually muscle cramping & twitching, with feelings of fatigue & weakness in
a limb
Loss of LMNs causes weakness, paralysis, loss of reflexes & atrophy in affected muscles.
Loss of UMNs causes spasticity (muscle stiffness, cramping from too much tonus).
Combination of UMN + LMN symptoms at multiple levels is fairly diagnostic
New treatments : riluzole (Rilutek) slows progression a little but research on gene therapy or
stem cell implants probably critical
Spinal Cross section
Cross-Sections
See Figure 8.8 or the figures included in the lecture I emailed you
Notice 1) the difference in the amount of white matter in the upper vs lower cord
2) Size of ventral horns (which reflects # of LMNs at each level
You should be able to recognize the level of these sections

Spinal Cord Injuries (SCI)

~10,000/yr in US; 50% disabled
Today about 10% die (used to be 90%)
Estimated 500,000 survivors, 200,000 in wheelchairs
About 2/3 are under 30; 82% are males
Causes of SCIs
Similar pattern to head injury data:
~45% in motor vehicle accidents
~22% in falls
~16% due to violence
~13% in sports
Must assume those with head injuries have spinal injury too until we know otherwise.

What Damages Cord?

Can have SC concussion or contusion
Overstretching or twisting of cord (like a CHI)
Fracture or dislocation of vertebrae causing laceration or compression of cord
Penetrating injury (e.g. bullet)
Vascular problem causing infarct
SCIWORA - spinal cord injury without radiographic abnormality
 Location of Damage
Cervical vertebrae most fragile & likely to fracture
Most mobile parts of spine (C5-C6, T12-L1, C1-C2) most likely to dislocate or overstretch
Cervical injuries - quadriplegia
Lumbar injuries - paraplegia
Can also have incomplete injuries

Consider the anatomy and function of the pathways we have discussed and where each crosses the
midline:
Dorsal column pathway
Spinothalamic pathway
Corticospinal pathway

Use That Info to Predict the Impairments In This Case (10 pt)
John has suffered a bullet wound to the right half of the spinal cord at the thoracic level. Draw out
the various pathways to decide what will and wont John be able to feel with each of his 4 limbs. What
will and wont he be able to move normally? Will any muscles show denervation atrophy? Will any
muscles show hyperreflexia & spasticity? Explain your answer.

Autonomic Nervous System (ANS)

Nerves supplying organs, glands and blood vessels
Function automatically, unconsciously
Help maintain the internal milieu of body, meeting its moment to moment needs
AKA visceral nervous system

Sympathetic Division - arouses body in response to stress/increased demands

Increase HR & BP
Increase respiration
Dilate blood vessels to heart
Increase blood flow to muscles
Release adrenaline
Release stored energy (glycogen)
Dilate pupils
Sweat to cool body
Decrease blood to skin
GI tract slows down; mouth dry

Parasympathetic Division - serves non-emergency, body maintenance functions, conserving &

replenishing body reserves

Decreases HR & BP
Slows breathing
Lubricates mouth, eyes
Stimulates digestion and storing energy
 Constricts pupil
Responsible for elimination

Sending an autonomic message requires a 2 neuron sequence

Sympathetic Nerves
leave CNS at thoracic or lumbar levels (thoracolumbar system)
preganglionic neurons are SHORT, traveling to just outside the spinal column to a chain or trunk
of sympathetic ganglia.
postganglionic neurons are long, traveling rest of the way to body organs, glands, & vessels.
almost all release NE as their transmitter (except those to sweat glands)
Sympathetic nerves usually respond in unison.

Parasympathetic Division
leave CNS from the brain or from sacral cord (craniosacral).
preganglionic neurons are LONG and go all the way out to body organs to reach ganglia.
postganglionic neurons are short, going from those ganglia to nearby organ/gland cells.
All release ACh.
Parasympathetic nerves tend to operate individually, as needed.

Parasympathetic ganglia are near to organs and are not all interconnected.

CNS-ANS Interaction
The hypothalamus, brainstem reflex centers, & even frontal lobe centers help to coordinate &
control ANS activity.
Some autonomic reflexes are spinal reflexes & can function independent of the brain.
Spinal injuries can damage:
descending voluntary control pathways (ANS UMNs)
damage the LMNs of the ANS, causing loss of reflex responses

Autonomic Dysreflexia
(can occur after spinal shock wears off)
Cervical or upper thoracic spinal injury disrupts normal feedback between sympathetic &
parasympathetic nerves.
Bladder/bowel distension/irritation, skin irritation, uterine contractions, or air temperature changes
can provoke uninhibited autonomic discharges (sym. below injury, parasym. above) with dangerous
hypertension.
Signs: intense headache, sweating

Raynauds Disease
Over-reaction of sympathetic nerves to peripheral blood vessels to cold causing intense vasoconstriction,
pallor, cyanosis and pain in fingers.

Raynauds Induced Gangrene

Spinal Shock
 Immediately following a spinal injury the cord below injury may go into shock and show little or
no function for a period of time. As the shock wears off, reflex functions (and perhaps some degree of
other functions) will return.

ANS Afferents
Autonomic nerves also carry sensory fibers from organs to CNS
These play a role in autonomic reflexes as well as our conscious awareness of some bodily functions
Localization of autonomic sensations is imprecise (e.g. referred pain phenomena)

Drug Manipulation of ANS

Drugs which act like NE or make NE more available will produce sympathetic effects (asthma
inhalers, amphetamine, cocaine are some sympathomimetics).
Drugs which block NE receptors will decrease sympathetic function ( e.g. alpha or beta blockers).
Drug Manipulation
Drugs which act like ACh can be used to stimulate parasympathetic function.
Drugs which block ACh receptors will decrease parasympathetic function (e.g. atropine, tricylic
antidepressants).
The Cerebellum
Anatomy of the Cerebellum
2 hemispheres with vermis in between
Very folded cerebellar cortex
Underlying white matter & deep nuclei
Deep nuclei are the output pathway
Massive cerebellar peduncles (axon bundles to and from cerebellum) connecting to brainstem

Primitive Cerebellum in Blue

Evolution of Cerebellum
Oldest part is the flocculonodular lobe - it gets input from the vestibular system (Vestibulocerebellar
path)
Next: the region around the vermis gets proprioceptive & cutaneous input via spinal cord
(spinocerebellar tr.)
Most recent region the hemispheres- get input from cortex via the pons (corticopontocerebellar
path)
All input goes to cerebellar cortex; all output is from the deep cerebellar nuclei
Loop-like feedback to each of those sources of input

Mode of Functioning
Totally unconscious
Computer-like feedback loops
Moment-to-moment adjustments
Ipsilateral in its control (right side of cerebellum related to movements of right side of body)
Cerebellum Is Needed For:
Fluid coordination of movements
Synergy/cooperation between muscles
 Precise timing & targeting of movements
Appropriate force & muscle tone
Cerebellum is storing these details during motor learning
Automatic adjustments to changing conditions & to maintain balance
Symptoms of Cerebellar Damage
Asynergia - loss of fluid coordination & cooperation between muscles; movements jerky & disjointed
Dysmetria - poor targeting of movement; over- or under-reach
Cant do finger to nose test
Intention tremor while targeting movements (see clip)
Dysarthria/Dysphonia - slurred, uncoordinated speech & speech volume
Lateral lesion- affects ipsilateral limbs
Symptoms of Cerebellar Damage
Disturbed balance (cant balance on 1 foot; walk heel-to-toe)
Gait ataxia wide-based, staggering walk, may shuffle,veer to side, may fall
Poor muscle tone (hypotonia)
Adiadochokinesia/Dysdiadochokinesia - cant rapidly alternate movements
http://www.neuroexam.com/36.html
Nystagmus-jerky, oscillating eye movements (see dbnystag. clip)
Midline lesion most likely to cause gait, posture, balance problems - Romberg test
http://www.neuroexam.com/37.html

Test for Dysdiadochokinesia

Medulloblastoma
A cerebellar tumor usually originating in the vermis, which then presses down on the brainstem
Accounts for ~1 in 20 brain tumors (1 in 5 in kids). 2/3 cases occur before age of 15 (median age = 5-6)
Symptoms: Falling, nausea & vomiting, double vision, headache, eventually trouble moving. If its
located on midline child will tend to fall forward or backward

Other Causes of Cerebellar Damage

Strokes or tumors affecting cerebellum
Demyelination due to MS
Genetically based degenerative disorders (e.g. Friedrichs ataxia caused by degeneration of
spinocerebellar tracts)
Alcoholic cerebellar atrophy. Cerebellum can also be damaged by some anticonvulsants or
chemotherapy.

Extrapyramidal Motor System

Descending extrapyramidal paths receive input from other parts of motor system:
From the cerebellum
From the basal ganglia or corpus striatum

Basal Ganglia or Striatum

Caudate & putamen get input from cortex, thalamus & substantia nigra, a midbrain motor area
They send commands to globus pallidus which sends them on to the motor portions of thalamus &
brainstem
 Very interconnected system with lots of feedback loops

Basal Ganglia or Striatum

Interconnected set of nuclei (gray matter) buried within the cerebral hemispheres that have
primarily motor functions
Best known components:
Caudate nuclei (tail shaped nuclei)
Putamen (seashell)
Globus pallidus (pale globe)
Functions
The basal ganglia are important for:
Initiating or starting motor programs often multiple programs at once
Inhibiting undesired movements; terminating voluntary movements

Parkinsons Disease
(paralysis agitans or shaking palsy)
About 1% of those over 50 have PD (~ 1,000,000 total in US; 55,000 new cases/yr; 90% cases occur
after age 60)
Progressive deterioration of major DA input to basal ganglia- the nigrostriatal pathway from
substantia nigra to the striatum
We lose about 4% of those DA neurons/decade, but those with PD have accelerated loss (70% or
more gone)
Results in difficulty initiating movements & tremor
The nigrostriatal path sends DA messages from the substantia nigra to the basal ganglia.
Classic PD Symptoms
Worsening bradykinesia & akinesia
Rigidity; clumsiness, decreased postural stability so tends to fall
Pill-rolling tremor-at-rest
Reduction in movement is also seen in lack of facial expression & blinking; shuffling walk without
assoc. arm movements; soft, halting, monotone voice; slow blinks; small writing; feeling stuck or frozen
Possible Causes
Environmental toxin of some sort (industrial heavy metals, pesticides, free radicals currently under
study)
Genetics (especially in those who get PD at an early age)
Brain trauma may increase your risk
Treatments
Increase DA production with l-dopa/carbidopa (Sinemet)
Problems: l-dopa induced dyskinesias and loss of effectiveness over time
Others: DA agonist (bromocriptine/Parlodel or pergolide/Permax, or newer, better Mirapex, Requip)
or DA releasor (amantadine/Symmetrel)
Eldepryl/Deprenyl (selegiline) to decrease DA breakdown and slow loss of neurons
 Anti-ACh drugs (Artane, Cogentin) can help restore chemical balance of basal ganglia

When Drug Therapy Fails

When drug effectiveness declines, exp. options include:
Pallidotomy; thalamotomy (Michael J. Fox)
Deep brain (thalamic) stimulation
Transplant of DA producing cells

Parkinsons Disease Update

Although PD is thought of as a motor disorder, the decline in DA also produces cognitive and
emotional changes in some
bradyphrenia (cognitive slowing); decreased attention
frontal lobe symptoms (disinhibition of behavior, poor judgment and planning)
Major depression
Full-blown dementia in ~50% (associated with neuropathological sign called Lewy bodies)
PD treatment, on the other hand, can produce hallucinations and other symptoms of psychosis
Impairment of the Inhibitory Functions of the BG
Dyskinesias involuntary movements
Chorea (dance-like) quicker irregular movements
Athetosis slower writhing, twisting movements
Dystonias abnormalities of excessive muscle tone
Huntingtons Disease
Transmitted by a dominant gene on chromosome 4 (about 30,000 US cases with 150,000 at risk kids)
Deterioration of striatum produces involuntary chorea, athetosis & other motor difficulties
Cortical deterioration causes progressive & debilitating dementia, aggressiveness, mood swings,
depression, psychosis
Death due to health complications in 15-20 yrs
Huntingtons Disease
Bad gene has excess CAG repeats (more than 36-250 instead of usual 29 or fewer) resulting in an
abnormal form of protein known as huntingtin.
The more repeats, the earlier symptoms appear.
# of repeats can increase across generations, especially in kids inheriting gene from father
Brain damage may be due to decrease in normal protective huntingtin + adverse effects of abnormal
protein on critical growth factors keeping cells alive.
Also looking at effects on excitotoxins & glucose metabolism.
Treatments for HD
Genetic testing to identify presence of the gene
Involuntary movements may be decreased by DA blockers (antipsychotics)
New drugs being tried to delay progression:
Rilutek (riluzole), Neurontin (gabapentin) decrease glutamate transmission
Rapamycin (transplant drug) speeds elimination of abnormal protein
Growth factor supplementation being studied
 Experimentation with brain cell transplants/surgeries is underway
Tourette Syndrome
Another *hereditary BG disorder characterized by involuntary movements
Multiple motor tics - simple tics of face or limbs and/or more organized complex tics (touching,
grimacing, pinching, poking, adjusting, hitting, jumping, kissing, throwing, gestures) plus:
Phonic or vocal tics - both simple (throat-clearing, coughing, hiccuping, grunting, yelping) and/or
complex tics (actual words, coprolalia, echolalia, palilalia, assuming different voices, talking to oneself in
different voices)
Seems to affect frontal lobe- BG connection that is important for our ability to inhibit actions
Tourette Syndrome
40% report sensory tics uncomfortable sensations that may be a reason for some of the
involuntary movements
Some degree of suppressibility, but individual experiences increased tension until tic is released
Pattern of tics changes & waxes & wanes with changes in stress, anxiety, fatigue.
Treated with DA blockers (antipsychotics). Milder tics may respond to NE agonist clonidine.
Majority experience decreased tics as adults.
Link with Other Disorders
~50-60% also suffer OCD (others estimate that up to 90% experience some involuntary touching
compulsions, ritualistic behaviors, intrusive thoughts)
~50-90% show evidence of ADHD as well; first signs of GTS are usually impulsive, hyperactive
behaviors (before tics appear)
About 30% have learning disabilities, emotional lability, rage, aggressiveness; 40-50% depressed
Evidence suggests a single gene with sex-linked, varied forms of expression of disinhibition
50-73% concordance in identical twins vs 8-22% in fraternal twins

Treatment of Epilepsy
Anticonvulsants
Dilantin (phenytoin)
Tegretol (carbamazepine)
Depakene (valproic acid)
Depakote (divalproex)
phenobarbital
Valium (Diazepam)
Ativan (lorazepam)
Clonopin (clonazepam)
Neurontin (gabapentin
Mysoline (primidone)
Zarontin (ethosuximide)
Good control achieved in about 75%
(anticonvulsants are also used for other purposes)
Treatment Alternatives
Surgical removal of epileptic focus
Select cases may benefit from strict high fat ("ketogenic) diets to alter brain chemistry
Avoid possible triggers (stress, fatigue, flashing lights, alcohol, excess caffeine, fever,
hyperventilation, hypoglycemia)
Frontal Lobes (~1/3 of cortex)
Motor control
Higher cognitive or executive functions
Self-regulation (behavioral inhibition, sensitivity to social cues, conscience)
Initiative
Anatomy
The frontal lobe is heavily interconnected with:
basal ganglia & other components of the motor system
all other lobes of cortex
limbic system
Beyond Motor Planning
Frontal lobe has evolved from being the main motor planner/organizer to a higher level
behavioral/strategic planner/organizer.
Provides us with a mental model, considering options, selecting behaviors based on context,
feedback, stored knowledge; adapting to the situation
What are executive functions?
Forming goals, considering consequences
Considering response alternatives
Choosing / initiating goal-directed behaviors
Self-monitoring your responses
Correcting/modifying behavior as necessary
Persistence despite distraction
Causes of Frontal Damage
traumatic brain injury
neoplasms (tumors)
vascular lesions (stroke)
degenerative diseases that affect frontal pathways (Alzheimers, Parkinsons, Huntingtons,
Picks disease, Lewy body disease) and cause dementia
Effects of Frontal Damage
Decreased consideration of alternative strategies/behaviors; reduced flexibility
Decreased spontaneity, initiative, may appear lazy, unmotivated
Knowledge/intelligence may seem intact (e.g. IQ) but its not used to generate strategies or solve
problems efficiently
Decreased Inhibition
Problems inhibiting incorrect/ineffective responses & switching to a new strategy
Perseverates; not responsive to feedback or changes in environment
Violates rules, expectancies; takes risks
Emotionally reactive
Decreased social inhibitions as well; disinhibited personality; impulsive
Decreased Temporal Memory
Impaired memory for order, recency, contextual info
Could affect problem-solving, planning and impair systematic, organized behaviors
Possible Personality and Emotional Changes
Lack of tact & restraint, immature, coarse,lack of social graces, inappropriate sexual behavior,
increased motor activity. More common after orbitofrontal or right frontal damage; called
"pseudopsychopathic"
Another Possible Personality Change
Apathetic, indifferent, loss of initiative, lack of emotion or somewhat depressed, little verbal
output ("apathetic-akinetic mutism). Most common after cingulate damage or left frontal
damage; called "pseudodepression"
Some Neuropsych Tests Used
Wisconsin Card Sorting Test; Stoop Test
Word Fluency Test; Design Fluency Test
Visual Search Test
Motor stength, speed and sequencing
test for aphasia, anosmia
The Parietal Lobe Regions
Primary and secondary somatosensory cortex
Multimodal association cortex
Lurias View of Sensory Processing Deficits
Primary sensory cortex damaged: Impairment of basic sensory awareness
Secondary sensory cortex damaged: Agnosia (modality-specific impairment of recognition of
what is sensed.
Tertiary (association) cortex damaged: Deficits in integrating that sensory input with other
modalities, memory, language, etc.; difficulties using/applying sensory information
Lateralization of Parietal Functions
Left parietal: sensory & integrative processing important for normal language and math
Right parietal: sensory & integrative processing related to the use of spatial information in
perceptual, cognitive & motor behaviors
Left Parietal Damage
Anomia: not able to name things
Alexia: not able to read
Agraphia: not able to write
Acalculia: loss of math abilities
Impaired grammar
Impaired left/right discrimination
Right Parietal Damage
Contralateral sensory neglect
"Constructional" apraxia-cant assemble, build, draw, construct because of visuomotor/spatial
impairment
Dressing apraxia (other ideomotor apraxias - left parietal)
Poor map reading/drawing
Impaired ability to recognize unfamiliar views of objects
Tests For Parietal Function
2 point discrimination (tactile sensation)
Seguin-Goddard Form Board (tactile recognition)
Golin Incomplete Figures; Mooney Closure Test (complex visual perception)
Semmes test of extrapersonal orientation
Kimura box test (motor learning)
Temporal Lobe Regions
Auditory area - superior temporal gyrus (primary & secondary auditory cortex)
Complex association cortex - middle & inferior temporal gyri (links audition-vision-memory
system)
Limbic region - medial temporal cortex (personality?) & amygdala (emotion) & hippocampus
(memory storage process)
Effects of Temporal Damage
Auditory impairment; word deafness; Wernickes aphasia
Visual agnosias; prosopoagnosia; impaired selective attention
Impaired storage of new memories; possible loss of long-term memories
Emotional & personality changes
Limbic Memory Regions
Essential for the storage of new memories
hippocampus
mammillary bodies and medial thalamus
Remembering emotional aspects
amygdala
Areas affected by Alzheimers disease
hippocampus and surrounding cortex, amygdala, nucleus basalis of Meynert
Temporal Lobe Epilepsy
Complex partial epilepsy (psychomotor)
Typically epilepsy is not associated with mental illness, but TLE is (~45% vs 10% have
psychiatric symptoms, changes in affect & personality. Other types of temporal lobe pathology
may also affect these aspects of behavior.
Emotional & visceral aura; rubbing and oral movements; hallucinations & disordered thought
Temporal Lobe Personality
Data on TLP is not consistent but these are some of the qualities that may be associated with
TL abnormalities:
humorlessness; paranoia; feel threatened
overemphasis on details/minutiae; verbose
egocentric, "sticky" personality, sense of destiny
religiosity, focus on good vs evil
aggressive outbursts (temporal lobe pathology has been found in brains of several mass
murderers and has been used as a defense by others)
Limbic System & Aggression
Abnormalities in hypothalamus or amygdala can also cause outbursts of rage or violence.
Rage in rabies associated with viral infection of hippocampus/amygdala
Amygdalectomy is a psychosurgery that has been used to treat episodic dyscontrol (attacks of
rage)
Brocas Aphasia
damage to frontal lobe language area
patient not articulate, not fluent
speech slow, difficult, & much reduced
comprehension relatively intact, but
comprehension of grammatical words, devices, and endings is impaired
production of sign impaired in the deaf
Wernickes Aphasia
temporal lobe language area damaged
speech is fluent, but nonsensical
reduced comprehension of language
confusion of phonemes
comprehension of sign language ok
Dyslexia
less lateralization
more likely to be bilateral or reversed
often small brain abnormalities
altered visual attention/perception
Williams Syndrome
excellent language abilities
impaired visual/spatial abilities
low overall IQ, less cortical development
Blood Supply to the Brain
2 Internal carotid arteries on either side of the neck
2 Vertebral arteries on either side of the spinal column, join to form a single basilar artery on
anterior surface of brainstem
All interconnected at the "circle of Willis"
Stroke or Cerebrovascular Accident
Death or damage of some portion of the CNS due to disruption of normal blood supply to that
area
Area of damaged/dead cells is called the infarct.
500,000/year in US
2 Main Varieties
ischemic stroke - obstruction of artery deprives the tissue beyond that point of its supply of
oxygen & energy ("ischemia" refers to a localized decrease in blood supply)
hemorrhagic stroke - artery ruptures causing both intracerebral bleeding & failure to supply
blood to tissues beyond that point
Common Treatable Risk Factors
Hypertension (high blood pressure)
Cigarette smoking; alcohol abuse
Hyperlipidemia (high fats & cholesterol)
Heart disease
Diabetes
Symptoms of Stroke
Depend on particular blood vessel affected and the site and extent of brain damage
Large Vessel Stroke
Blockade of a major artery by an embolus (a traveling clot or bit of matter carried by
bloodstream until it lodges in a vessel too small for it to pass thru. If a person suffered a stroke
due to a lodged embolus, we would say they had suffered an "embolism".)
Common sources of emboli
Heart problems (atrial fibrillation, enlarged heart, heart valve problems, damage due to heart
attack)
Atheroma (fatty deposits in arteries)
Large Vessel Stroke
Blockade of a major artery by a thrombus (a clot that forms within an artery - usually because of
atherosclerosis
Aspirin or other anticoagulant therapy can lessen the risk of clots
Small Vessel Stroke
Occlusion of small vessels produces a smaller area of ischemia and infarction
Small infarct are often called "lacunae"
Common locations: internal capsule, basal ganglia, thalamus, pons.
Really small lacunar strokes may go un-noticed.
Hemorrhagic Stroke
Intracerebral hemorrhage in basal ganglia, thalamus, pons, or cerebellum related to
hypertension, smoking, alcohol, cholesterol, stimulant abuse or anticoagulants.
Causes stroke symptoms + risk of increased intracranial pressure & herniation due to
hematoma.
Subarachnoid Hemorrhage
SAH may be due to head injury
primary SAH due to ruptured aneurysm
Symptoms: sudden severe headache, nausea & vomiting, fainting
Headache, pain behind eyes & stiff neck may precede SAH
Risks - rebleeding, hydrocephalus, ischemia from vasospasm
CT scan or spinal tap to show blood
Other Stroke Terms
Transient Ischemic attack - short-term disruption of blood supply to region with reversal of
symptoms within minutes to hours.
Reversible ischemic neurologic deficit (RIND)- resolves within 24 hrs.
Stroke in progress or in evolution - increasing symptoms of stroke
Limbic Memory Regions
l Essential for the storage of new memories
hippocampus
mammillary bodies & medial thalamus
l Emotional aspects of memory-
Amygdala
l Long term memories spread thru-out cortex

Effect of Damage to Limbic Memory Regions

l Hippocampal damage problems storing new declarative memories (semantic & episodic)
l Mammillary bodies & medial thalamus damage- memory difficulties of Korskaoffs syndrome
l Damage to selective areas of cortex may lose specific long term memories (like the names for
things or the color of things)
l
Dementia:
More Than Memory Loss
l Cognitive deficits (in memory, reasoning, understanding, language, organization of behavior) not due
to clouded consciousness
l Impaired social/occupational functioning
l Decline from previous level of functioning
l Over 100 causes; about 30% of dementias are reversible (due to endocrine problems, vitamin
deficiency, medications, CSF pressure, etc.)

Most Common
Dementias

l ~50% Alzheimers Disease

l ~10%-25%? Dementia with Lewy Bodies & PD
l (up to 40% those with AD also have Lewy bodies)
l 15% Vascular dementia e.g. multi-infarct dementia
l (seen in those with risk factors of stroke)
l 5-7% Picks Disease or fronto-temporal lobe dementia
l Other diseases causing dementia (AIDS, Huntingtons, Creutzfeld-Jakob)
Dementia with Lewy Bodies
l About 30% of Parkinsons disease patients develop dementia. In about of these cases it is Lewy
Body Dementia, in the others it is Alzheimers.
l Fluctuating cognitive function, visual hallucinations, extrapyramidal signs

Picks Disease or Fronto-temporal lobe Dementia

l 70% show unilateral degeneration, often in dom. hemisphere; microscopic Pick bodies
l Loss of restraint & personality changes before memory problems & disorientation; spatial abilities
preserved

l Folstein mini mental status exam for quick assessment

Blood Supply to the Brain (see 7.2)

l 2 Internal carotid arteries on either side of the neck
l 2 Vertebral arteries on either side of the spinal column, join to form a single basilar artery on
anterior surface of brainstem
l All interconnected at the circle of Willis

Internal Carotid Arteries

Vertebral Arteries

Circle of Willis or Circulous Arteriosus

Major Cerebral Arteries (see 7.4)

Medial View

PCA Vascular Distribution

MCA and Penetrating arteries

Angiogram (aka arteriogram)

Dural Sinus (Superior Sagittal)

Dural Sinuses (see 7.8)

Jugular Veins

Stroke or Cerebrovascular Accident (CVA)

l Death or damage of some portion of the CNS due to disruption of normal blood supply to that area
l Area of damaged/dead cells is called the infarct.
l 500,000/year in US

2 Main Varieties
l ischemic stroke - obstruction of artery deprives the tissue beyond that point of its supply of
oxygen & energy (ischemia refers to a localized decrease in blood supply)
l hemorrhagic stroke - vessel ruptures causing both intracerebral bleeding & failure to supply
blood to tissues beyond that point

Embolism

Suffering an Embolism

Thrombosis
Unhealthy blood vessels promote clot formation.

Thrombosis

Fatty Plaques in Vessels

Carotid Stenosis (narrowing)

Internal Carotid Stenosis
Before & after balloon angioplasty
Common Treatable Risk Factors
1. Hypertension (high blood pressure)
2. Cigarette smoking; alcohol abuse
3. Hyperlipidemia (high fats & cholesterol)
4. Heart disease
5. Diabetes
Treatments
Anticoagulants to decrease risk of future clots
Clot-busters like urokinase to break up a new clot
Medications to control brain swelling
Drugs under investigation to control neurotransmitter aftereffects of stroke
Preventative surgeries (angioplasty, endarterectomy)

Other Stroke Terms

1. Transient ischemic attack (TIA)- short-term disruption of blood supply to region with reversal of
symptoms within minutes to hours.
2. Stroke in progress or in evolution - increasing symptoms of stroke over time. If stroke is caught early
the progression of brain damage may be halted.
3. Multi-infarct or vascular dementia

Hemorrhage
Intracerebral Hemorrhage (ICH) / Hemorrhagic Stroke
 Most often due to the rupturing of a small blood vessel (e.g. the penetrating arteries supplying
basal ganglia, thalamus, pons, or cerebellum)
Major risk factor : hypertension
Others: smoking, alcohol or stimulant abuse, or use of anticoagulants.
Accounts for 10-15% of strokes; often lethal

Intracerebral Hemorrhage
Circle of Willis
Berry Aneurysm

Arteriovenous Malformation
Congenital malformation where arteries connect directly to veins in a little nest of vessels. These
malformations may rupture.
Subarachnoid Hemorrhage
Although SA bleeding may follow head injury,
primary SAH is usually due to the rupture of an aneurysm or AVM
o Symptoms:
sudden severe headache,
nausea & vomiting, fainting,
signs of meningeal irritation like stiff neck & photophobia,
possible seizure,
LOC
CT scan or spinal tap to show blood
Possible after effects-
o rebleeding,
o hydrocephalus,
o ischemia from vasospasm

Circle of Willis Aneurysm

Subarachnoid Hemorrhage

Clipping an Aneurysm

Non-Surgical Treatment
Insert platinum coil into aneurysm to obstruct blood from entering

Warning Signs
Sudden weakness or paralysis or numbness of lower face, arm, leg on one side
Sudden difficulty speaking
Sudden visual problems (blurring,loss, double)
Sudden severe headache
Unexplained dizziness, unsteadiness, falls especially with 1 of above signs

Symptoms of Stroke
Depend on particular blood vessel affected and the site and extent of brain damage
 o Large vessel strokes (e.g. one of the cerebral arteries) affect multiple areas
o Small vessel or lacunar strokes more limited may even go un-noticed until you have several
Patterns of Stroke Deficits
o MCA Contralateral motor & sensory problems of upper body, aphasia (L), neglect
o ACA Prefrontal symptoms, incontinence, motor & sensory problems in opposite leg
o PCA- Cortical blindness; visual agnosias
o Basilar brainstem symptoms: nystagmus, vertigo, eye control probs,dysphagia, dysarthria,
ataxia, possible locked-in syndrome

Small Vessel Stroke

Occlusion of small vessels produces a smaller area of ischemia and infarction
Small infarcts are often called lacunae
Common locations:
o internal capsule,
o basal ganglia,
o thalamus,
o brainstem.
Really small lacunar strokes may go un-noticed.