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Neurological Diseases
June 27, 2011
Brainstorm: Neurological
Diseases
Neurological Disease Presentations
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Sleep apnea
Schizophrenia
Paranoia
Psychological disease
Mad Cow Disease
Multiple Sclerosis
Cerebral Palsy
Dementia
Alzheimer’s Disease
Meningitis
Parkinson’s
Post-Partum Depression
Hysteria
Neurological Disease Presentations
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Mad cow disease (prion disorders): Juan
Parkinson’s: Vivian
Huntington’s: Paige
ALS: Chloe
Meningitis: Hannah
Encephalitis Lethargica: Krystal
Lyme Disease: Stephanie
Polio: Ime
Rabies: Melissa
Stroke: Kyle
Transient Ischemic Attack: Leandra
Migraines: Karla
Brain tumors/cancers: Brad
Chronic pain disorders: Allie
Sydenham’s Chorea: Ice
Sturge-Weber: William
Lesch-Nyhan Disease: Maria
West Nile: Varun
Case Study
Split My Brain
The Case of Jerrod’s Seizures
http://www.holah.co.uk/summary/sperry/
What’s Wrong With Jerrod?
Symptoms
 Right arm twitching
 Disorientation
 Weakness
 Episodes of blank staring
 Head movements
 No memory of episodes
Differential Diagnoses
Possible Diagnosis: Epilepsy
 What is Epilepsy? What causes it?
 Two or more unprovoked seizures
 Occurs with over-excitation of neurons
 Exact cause of this over-excitation is often unknown
 What type of seizures does Jerrod have?
 Partial Seizures: Occur when only one half of the brain (a
hemisphere) is involved in the seizure
 Very short, usually characterized by
muscle twitches or spasms
 Patient often does not remember
the seizure.
http://news.bbc.co.uk/2/hi/health/7378178.stm
EEG: Electroencephalography
 Uses electrodes & wires
attached to the
patient’s head to
measure electrical
activity of neurons in
the brain
 During seizure activity,
EEG shows a change in
the rhythm and
frequency of brain
activity waves (shown as
a spike)
http://www.dizziness-and-balance.com/disorders/central/epileptic.html
What Medications Can We Try?
 Anticonvulsants help reduce seizures by either decreasing
the activity of over-excited neurons, or by preventing the
seizure from spreading to multiple brain regions.
 Examples:
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Tegretol (Carbamazepine)
Klonopin (Clonazepam)
Valium (Diazepam)
Neurontin (Gabapentin)
Lamictal (Lamotrigine)
Keppra (Levetiracetam)
Dilantin (Phenytoin)
Depakene (Valproic Acid)
http://www.shorvon.eu/books_hoet_2nd.htm
MRI: Magnetic Resonance Imaging
 For an MRI, the patient lies
down inside of a large round
tube that contains several
powerful magnets.
 The MRI uses these magnets
and radiofrequency signals to
rearrange the atoms in the
brain and capture an image of
the brain.
 Different types of tissues will
cause different rearrangements
of atoms. These differences
cause some areas to look
lighter, while others are darker.
http://www.medicexchange.com/MRI/mr-spectroscopy-for-determining-gestational-age.html
MRI in Epilepsy
 On an MRI, an area of brain
Diagnosis and staging of Rasmussen's encephalitis by serial MRI and histopathology.
Bien, C; Urbach, H; Deckert, M; Schramm, J; Wiestler, O; Lassmann, H; Elger, C
Neurology. 58(2):250-257, January 22, 2002.
damage or decay shows up
as a different color than
surrounding areas.
 In epilepsy, this is most
often the region where the
seizures occur.
 How does knowing where
the seizures are occurring
help the doctor?
Final Diagnosis: Rasmussen’s Encephalitis
 What is Rasmussen’s Encephalitis? What causes it?
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Inflammatory disease that is limited to only one hemisphere of
the brain
The inflammation causes damage to the brain (atrophy), which
leads to the symptoms.
Symptoms include frequent seizures, motor difficulties, speech
problems
Likely an autoimmune disease
 How can we treat Rasmussen’s Encephalitis?
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Anticonvulsant medications usually do not work.
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Hemispherectomies are often required.
WARNING:
THE NEXT SLIDE CONTAINS GRAPHIC
IMAGES. IF YOU ARE SQUEAMISH
TO THE SIGHT OF BLOOD, YOU MAY
WANT TO CLOSE YOUR EYES NOW!
Hemispherectomies
 Removal of a portion of
the brain where the
seizure is localized
 Usually also includes
cutting of the corpus
callosum
 Stops the spread of the
seizure by severing the
connections in the brain
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=epilepsy&part=A
783&rendertype=figure&id=A831
Jerrod’s Hemispherectomy
 Which brain regions would
be removed?
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Left temporal lobe
Left frontal lobe
Corpus Callosum
 What skills would Jerrod have
trouble with after his surgery?
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Movement
Sensory information
Organized thinking and planning
Language and Speech
http://my.clevelandclinic.org/epilepsy_center/se
rvices/epilepsy_surgery/hemispherectomy.aspx
Jerrod’s Recovery & Prognosis
 What sort of rehabilitation might he need?
 Physical Therapy
 Occupational Therapy
 Speech Therapy
 With a lot of work, a positive attitude, and an excellent
team of healthcare professions, Jerrod can make a strong
recovery. How?
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In children, the brain is still very adaptable. With training, the
right side of Jerrod’s brain should be able to take over some of
the functions previously performed by the left side.
What Can We Do to Improve?
 What challenges should researchers and
doctors focus on in the future to
improve life for Jerrod?
 Is there anything can we do to prevent
Rasmussen’s encephalitis altogether?
Brandi’s Miracle
http://www.brandibinder.com/brandiartwork.html
Reading Circles
Neurological Disease
Presentations
Therapeutic Approaches
Emory ALS Study
Progesterone & Brain Injury
Phantom Nose Experiment
http://www.imagesdisney.com/images/5-images-pinocchio-g.jpg
Phantom Nose
 In the experiment, the subject sits in a chair blindfolded,
with an accomplice sitting in front of him, facing the same
direction. The experimenter then stands near the subject,
and with his left hand takes hold of the subject's left index
finger and uses it to repeatedly and randomly tap and
stroke the nose of the accomplice, while at the same time,
using his right hand, he taps and strokes the subject's nose
in precisely the same manner, and in perfect synchrony.
After 30-40 seconds of this procedure…
Neuroplasticity
True or False?
 The brain is static, unchanging, and set before you start
school.
How Can Your Brain Change?
 We know already that lots of changes occur to the brain
during development.
 But it still continues to change once you are an adult! This is
called plasticity.
 Necessary for:
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Learning
Memory
Response to injury
 How can we study
plasticity?
The Aplysia
 Neuroplasticity was first
studied sea slugs, or aplysia,
by Eric Kandel.
 If you lightly touch the gill of
an Aplysia, it will show a
reflexive gill withdrawal.
 What do you think would
happen if you applied the
stimulus repeatedly?
http://sandwalk.blogspot.com/2008/12/nobel-laureate-eric-kandel.html
Answer: Habituation
 What does this mean?
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After repeated stimulations, the Aplysia becomes less responsive to
the stimulus.
 Can you think of an every-day example in your life?
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Typically, when you get dressed in the morning, you initially feel
the fabric of your clothes against your skin, but you quickly adjust
to this so that stop noticing it.
 In more general terms, habituation is a decreased response to a
stimulus.
What Other Responses Might Aplysia Show?
 Sensitization
 What does this mean?
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Generalizing the negative response caused by an unpleasant
stimulus to other, neutral stimuli.
 In Aplysia, if the gentle touch is paired with a tail shock, the
Aplysia will once again withdraw their gill.
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This withdrawal will continue even after the tail shock is stopped.
 In more general terms, sensitization is an increased response to
a stimulus.
Habituation vs. Sensitization
 During a storm at night, a close lightning strike frightens you.
Additional lightning strikes increase your fear and apprehension. Have
you been habituated or sensitized to the lightning?
 Listen carefully for sounds. Is there a clock ticking? Birds outside the
window? Rain on the roof? The hum of your computer? Had you been
habituated or sensitized to them?
 A small child is tickled for several minutes by an older sibling. Later
attempts to tickle the child will elicit strong laughter as the older sibling
just begins to touch the child. Has the small child been habituated or
sensitized to the tickling?
http://www.ablongman.com/html/psychplace_acts/cc/habit.html
Neurological Mechanisms?
 Habituation:
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Do you think this is a result of stronger or weaker synaptic transmission?
Answer: Weaker (known as synaptic depression)
 Sensitization:
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Do you think this is a result of stronger or weaker synaptic transmission?
Answer: Stronger (known as synaptic potentiation)
 Remember these from our discussion of learning and memory…?
How Does Plasticity Affect Function?
What About Injury?
 Think back to our discussion of topographical
mapping.
 If the hand is topographically mapped so that each
finger maps to a different region of somatic sensory
cortex…what happens if a finger is lost through
injury?
 Plasticity allows the adult cerebral cortex to remap
itself!
Reorganization
 Functional Re-mapping also occurs in visual, auditory, and
motor cortices.
 Is this re-mapping restricted to changes due to injury?
Neuroscience. 2nd edition.
Purves D, Augustine GJ, Fitzpatrick D, et al., editors.
Sunderland (MA): Sinauer Associates; 2001.
No!! There’s More Than One Way to
Functionally Re-Map!
 Functional Re-mapping can also occur in response to repetitive
behaviors (think: Aplysia gill withdrawal).
Neuroscience. 2nd edition.
Purves D, Augustine GJ, Fitzpatrick D, et al., editors.
Sunderland (MA): Sinauer Associates; 2001.
Neurogenesis
What is Neurogenesis?
 Can our brains produce new neurons?
 YES! Our brain produces new neurons through a process called
neurogenesis.
 Occurs in only 2 known places in the brain:
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Granule Cell Layer
of the Olfactory Bulb
Dentate Gyrus
of the Hippocampus
http://www.iop.kcl.ac.uk/departments/?locator=622&context=872
What Sort of Neurons Are Made By Neurogenesis?
 Neurogenesis is mostly responsible for making
local neurons or interneurons.
 These neurons do not go far!
 But….if adult neurons cannot divide to create new
neurons, where do these new neurons come from?
Subventricular Zone
 Found in the cortical
hemispheres and the
hippocampus, the SVZ
keeps some neural stem
cells around in the adult
brain.
 These stem cells are able to
divide and give rise to new
neurons.
Popp A, Urbach A, Witte OW, Frahm C (2009).
"Adult and embryonic GAD transcripts are
spatiotemporally regulated during postnatal
development in the rat brain". PLoS ONE 4 (2):
e4371. doi:10.1371/journal.pone.0004371. PMC
2629816. PMID 19190758.
http://dx.plos.org/10.1371/journal.pone.0004371.
Why Do We Need Neurogenesis?
 We don’t know!
 Possibly involved in
learning:
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Rodent studies show that
animals that exhibit synaptic
potentiation also show
increases in neurogenesis.
 May or may be important
for effective response to
antidepressant medications.
The Journal of Neuroscience. 2006 May; 26(22):5888
-5893. Long-Term Potentiation Enhances
Neurogenesis in the Adult Dentate Gyrus. BruelJungerman E, Davis S, Rampon C, and Laroche S.