Neurological Diseases

1. June 27, 2011 Neurological Diseases

2. Brainstorm: Neurological Diseases

3. Neurological Disease Presentations • Sleep apnea • Schizophrenia • Paranoia • Psychological disease • Mad Cow Disease • Multiple Sclerosis • Cerebral Palsy • Dementia • Alzheimer’s Disease • Meningitis • Parkinson’s • Post-Partum Depression • Hysteria

4. Neurological Disease Presentations • 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

5. Case Study

6. Split My Brain The Case of Jerrod’s Seizures http://www.holah.co.uk/summary/sperry/

7. What’s Wrong With Jerrod? Symptoms Differential Diagnoses • Right arm twitching • Disorientation • Weakness • Episodes of blank staring • Head movements • No memory of episodes

8. 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

9. 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) EEG: Electroencephalography http://www.dizziness-and-balance.com/disorders/central/epileptic.html

10. 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: • 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

11. 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. MRI: Magnetic Resonance Imaging http://www.medicexchange.com/MRI/mr-spectroscopy-for-determining-gestational-age.html

12. MRI in Epilepsy On an MRI, an area of brain 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? 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.

13. Final Diagnosis: Rasmussen’s Encephalitis • What is Rasmussen’s Encephalitis? What causes it? • 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? • Anticonvulsant medications usually do not work. • Hemispherectomies are often required.

14. WARNING: THE NEXT SLIDE CONTAINS GRAPHIC IMAGES. IF YOU ARE SQUEAMISH TO THE SIGHT OF BLOOD, YOU MAY WANT TO CLOSE YOUR EYES NOW!

15. 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 Hemispherectomies http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=epilepsy&part=A783&rendertype=figure&id=A831

16. Which brain regions would be removed? Left temporal lobe Left frontal lobe Corpus Callosum What skills would Jerrod have trouble with after his surgery? Movement Sensory information Organized thinking and planning Language and Speech Jerrod’s Hemispherectomy http://my.clevelandclinic.org/epilepsy_center/services/epilepsy_surgery/hemispherectomy.aspx

17. 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? • 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.

18. 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? What Can We Do to Improve?

19. Brandi’s Miracle http://www.brandibinder.com/brandiartwork.html

22. Reading Circles

23. Neurological Disease Presentations

24. Therapeutic Approaches Emory ALS Study Progesterone & Brain Injury

25. Phantom Nose Experiment http://www.imagesdisney.com/images/5-images-pinocchio-g.jpg

26. 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…

27. Neuroplasticity

28. True or False? FALSE The brain is static, unchanging, and set before you start school.

29. 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: • Learning • Memory • Response to injury • How can we study plasticity?

30. 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

31. Answer: Habituation • What does this mean? • After repeated stimulations, the Aplysia becomes less responsive to the stimulus. • Can you think of an every-day example in your life? • 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.

32. What Other Responses Might Aplysia Show? • Sensitization • What does this mean? • 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. • This withdrawal will continue even after the tail shock is stopped. • In more general terms, sensitization is an increased response to a stimulus.

33. 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

34. Neurological Mechanisms? • Habituation: • Do you think this is a result of stronger or weaker synaptic transmission? • Answer: Weaker (known as synaptic depression) • Sensitization: • 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…?

35. How Does Plasticity Affect Function?

36. 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!

37. 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.

38. 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.

39. Neurogenesis

40. 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: • Granule Cell Layerof the Olfactory Bulb • Dentate Gyrusof the Hippocampus http://www.iop.kcl.ac.uk/departments/?locator=622&context=872

41. 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?

42. Subventricular Zone 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. 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.

43. Why Do We Need Neurogenesis? The Journal of Neuroscience. 2006 May; 26(22):5888 -5893. Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus. Bruel-Jungerman E, Davis S, Rampon C, and Laroche S. • We don’t know! • Possibly involved in learning: • 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.