1. More On Multiple Sclerosis MS destroys oligodendrocytes in the CNS  demyelinating autoimmune disease –Pathogenesis not fully understood (mix of genetics and environment) Some remyelination occurs, but after repeated attacks, a scar-like plaque begins to form around the damaged neurons Life expectancy same as unaffected individuals http://en.wikipedia.org/wiki/Multiple_sclerosis node of Ranvier nucleus soma axon myelin sheath oligodendrocyte (CNS) dendrite axon terminal

2. Loss of upper and lower motor neurons  progressive muscle weakness, atrophy (wasting away), and spasticity –Upper motor neurons: connect motor region of brain to neurons in spinal cord (NT=glutamate) –Lower motor neurons: connects brain stem and spinal cord to muscle fibers (NT in neuromuscular junction=acetylcholine) –These motor neurons cannot regenerate once lost Patient loses ability to control voluntary movement –Cognitive function usually unaffected –Sensory nerves remain functional (reason unknown) Cause and pathogenesis largely unknown –Family inheritance accounts for 5-10% of cases Life expectancy is 3-5 years from symptom onset –Death typically from respiratory failure Treatment with Riluzole –Inhibits release of glutamate from presynaptic neurons by blocking sodium channels  blocks Ca 2+ influx  indirectly prevents stimulation of glutamate receptor on postsynaptic neuron More On ALS

3. Case study 1: strychnine poisoning Case description –Martha cleaned up a rat poison spill in her barn –Later complained of severe muscle pains and jaw stiffness –Treated in ER diazepam (controls muscle spasms) quite room (prevent seizures due to sensory stimuli) IV fluid (maintain hydration) Bicarbonate (alkalinized urine) Lab findings –Strychnine found in urine and plasma –High creatine kinase and myoglobin levels (indicates muscle damage)

4. Case study 1: continued Discussion –Renshaw cells (interneurons) found in gray matter of spinal cord Receive excitatory stimulation from motor neurons in spinal cord As a feedback mechanism, Renshaw cells send out inhibitory signals to those excitatory motor neurons to dampen muscle contraction –Strychnine acts as an antagonist to the glycine (inhibitory NT) receptor Renshaw cell feedback loop does not function  lowers threshold for motor neuron firing  involuntary muscle contraction  muscle spasms and severe pain Can be fatal if diaphragm is involved –Diazepam (i.e. valium) muscle relaxing effects likely due to inhibition of voltage-gated sodium channels, thus slowing synaptic transmission

5. Case study 1: continued Discussion cont… –Damage to muscle tissue (rhabdomyolysis) results in myoglobin release in blood Can damage nephrons of kidney and lead to acute renal failure Myoglobin= oxygen carrier in muscle cells –IV fluids to dampen kidney damage –Bicarbonate to alkalinize urine, which prevents dissociation of myoglobin to toxic metabolites (ferrihemate=form of myoglobin at low pH, causes vasoconstriction)

6. Case study 2: ischemic stroke Case description –George (68 yrs old) abruptly stopped speaking and slumped to his left during breakfast one morning –Reached hospital within 35 minutes of onset –Examined in ER Blood pressure 130/90 (is this high or low?) Hadn’t taken his Warfarin medication (anticoagulant) in 4 days Lab findings –Prothrombin (blood clotting) time: 14 seconds (high/normal) –Blood glucose: 112 mg/dl (normal) Extreme high or low blood glucose symptoms can mimic a stroke –CBC (complete blood count): normal Infection can cause neurological symptoms

7. Case study 2: continued Discussion –Hemorrhagic or ischemic?? Warfarin medicine: increases concern of hemorrhagic stroke But most strokes are ischemic  opposite treatment –CT scan Can distinguish between the two Showed hypodensity (anatomy is less dense than surrounding tissue  less blood flow) in middle cerebral artery –What type of stroke was it? –What would be an appropriate treatment?

8. Botulinus Toxin Reference http://www.turkjbiochem.com/2007/141-144.pdf