Transcript File - The Brain for not-so

Recall the neuronal circuitry change in PD
Normal
Parkinson’s
Risk Factors for Parkinson’s Diseases (PD)
 Age
 Incidence 1% >60 years of age, only 0.01% <45 years of age
 Genetics
 More men than women (2:1) – could be genetic, could be hormonal
 15 -25 % of patients have a relative with PD (suggestive of genetic factor)
 Several mutations associated with PD (but is only a minority of cases)
 α-Synuclein mutation – “causative” gene
 LRRK2 mutations – “associated” gene (i.e., risk factor)
 “parkin” gene mutation  juvenile onset (no Lewy bodies, so not typical PD)
 Environmental?
 Earliest identified risk factor was use of well-water
 At least two pesticides (rotenone and paraquat) associated with increased risk
 Intravenous drug use in some cases…
Parkinsonism – Symptoms and Signs like PD, but another cause
Encephalitis lethargica (“Von Economo’s Disease)
Great NOVA show
PD - Prognosis
 PD is chronic and progressive, but quite variable
 Many treatments available or under investigation (more about that in Week 8)
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Drugs, but side-effects can be limiting
Surgery - not without risks
Electrical simulation of the brain - not without risks
Cell implants (e.g., stem cells) – still under investigation
 No cures available yet
 Caffeine may be protective
 Smoking associated with lower PD risk (NOT suggesting it is healthful overall!)
Drugs for PD
 DA-releasing cells are lost – so just give DA?
 DA does not cross the “blood-brain barrier” (BBB)!
 An anatomical and physiological “barrier” between the blood
and the CNS
 DA has unwanted peripheral effects
 Arvid Carlsson: give the “precursor” of DA? (L-DOPA)
 Crosses BBB – good!
 But is converted into DA peripherally – side effects.
 “Sinemet”
 L-DOPA + carbidopa, a drug that blocks conversion of
L-DOPA into DA and that doesn’t cross the BBB
(blood)
(brain)
Electrical Stimulation – for PD
 Electrode = insulated wire
 Electrodes are implanted through a hole in the skull into specific brain
regions
 Stimulation is achieved by pairs of electrodes used to pass electrical
current to modulate the activity nearby
 Often called “Deep Brain Stimulation’ (DBS)
Deep Brain Stimulation for Parkinson’s Disease
Normal
Parkinson’s
Cell Implant Therapy - PD
 DA-releasing cell implant therapy for PD
 From adrenals
 From fetal embryonic cells
 Much less successful in man than in animal models.
 Difficult procedure, cells tend to die, like the Substantia Nigra cells before them
 May need at least 100,000 embryonic cells to get benefit (equivalent to 3-5
embryos)
 Stems cell implants – promising, but not yet ready for clinical trials
 “Gene implant therapy”
 Use a virus to infect cells and turn them into DA-releasing cells
 Good safety profile
 Moderate success in a minority of patients
 Though in a minority, benefit is enduring
Epilepsy
 Disorder of “neuronal firing”, characterized by “seizures”
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“Hypersynchrony”- starts in one area disrupting its function, and can spread to other areas
Causes strange sensations, uncontrollable movements, loss of consciousness.
Sometimes generalized seizures are preceded by the experience of an “aura”
Chronic condition; seizure durations and frequency of occurrence vary widely
 Many causes:
 Trauma, tumor, genetics, neonatal hypoxia, error in normal development, systemic disease…
 Important to control because seizures can grow in severity (“kindling effect”)
 Epileptic events can get more intense each time they are triggered
Epilepsy – having “seizures”
Representative EEG
Of Generalized
Seizure
Focal Seizure
Types of Epilepsy
 Simple partial
 Partial Complex
 Primary generalized
 Absence
Surgical treatment – e.g., epilepsy
 The brain itself has no “pain sensors” (free nerve endings, nociceptors)
 There are nociceptors on the tissues surrounding and protecting the brain,
and on blood vessels in those structures.
 Often done while patient is awake to identify areas to not disturb (e.g.,
involved in vision, speech, movement)
Brain surgery for epilepsy
 Usually used for:
 Drug-resistant, dire cases
 Partial onset seizures
 Usually either:
 Resection of seizure focus (“trigger zone”)
 Correction of a “structural problem” (e.g., circulatory abnormality)
 Cutting fibers along which the seizure spreads
 E.g., copus callosotomy = “split brain”
Drugs: Epilepsy – just getting there is not always enough
 Seizures are caused by neuronal hypersynchronicity/hyperactivity
 The challenge is how to prevent hyperactivity without interfering with
normal activity
 This is why many anticonvulsants exhibit “use-dependence”
Drugs for Epilepsy - Use-Dependence
Electrical stimulation of neuron
Action potentials
(time )
No drug
With drug
Ketogenic Diet for Epilepsy
 used primarily to treat difficult-to-control (refractory)epilepsy in children.
 Children with a focal lesion (a single point of brain abnormality causing the
epilepsy) who would make suitable candidates for surgery are more likely to
become seizure-free with surgery than with the ketogenic diet.[10][31]
 Long-term use of the ketogenic diet in children increases the risk of slowed or
stunted growth, bone fractures and kidney stones.[6
Neurofeedback
 Like Biofeedback (e.g., for reducing blood pressure”, but feedback is dependent on
modulating specific features of real-time EEG
 Like “brain training” only based on EEG rather than behavior
 “Technologically-assisted meditation”?
 The ultimate in individualized medicine?
 Is diagnosis by brain function rather than by symptoms
 It is well-established that one can modulate EEG this way…
 BUT, clinical efficacy is not well established for most of the claims.
 Best evidence is in ADHD…
Some things that are good for every neuro/psych disorder
 Sufficient good quality sleep
 Good quality nutrition
 Physical exercise
 Meditation / relaxation
 Mental exercise (not just “use it”, but “push it”)
 Drug dosing optimization
 Dose, time of day, with or without food, avoid “food/drug interactions”
 Being your own best advocate
 Read, surf, go to meetings, participate in trials…ask questions!