Transcript A beautiful mind

A BEAUTIFUL MIND
LECTURE 3 OF THE 6 PART MINI MED SCHOOL SERIES
DISCLOSURES
• I am a medical student
• This session is not intended to give you a diagnosis or
replace you seeing your health professional
OVERVIEW
• Discuss brain anatomy
• Focus on the relevance of the anatomy
• Talk about some of the common conditions affecting the nervous system
QUIZ
1.
What is the difference between the sympathetic and the parasympathetic
nervous system?
2.
3.
4.
What is the “pleasure” neurotransmitter?
What does DIAL it down mean?
How are Immodium and heroin similar?
FUN FACTS
• Brain is about 2% of the body weight, but uses about 20% of total energy
and oxygen
• Estimated 86 billion brain cells
• Prefrontal cortex is still developing until 25
• Brain has no pain receptors
BRAIN LAYERS – MENINGES
MENINGITIS
MOST VULNERABLE PART OF THE SKULL
CLINICAL IMPLICATIONS (EPIDURALS)
ORGANIZATION OF THE NERVOUS SYSTEM
AT THE CELLULAR LEVEL
NEUROTRANSMITTERS
• Either excitatory or inhibitory (by opening of different types of channels)
• Effect depends on the neurotransmitter and the circuit involved
OTHER PLAYERS (GLIA)
• Myelinating cells – Oligodendrocytes (CNS) and Schwann cells (PNS)
• Microglia – immune cells in the CNS
• Polydendrocytes – stem cells that can regenerate both glia and neurons
• Ependymal cells – secrete cerebrospinal fluid
• Astrocytes – maintain the extracellular environment and blood brain barrier
BLOOD BRAIN BARRIER
MYELIN (OLIGODENDROCYTES AND SCHWANN CELLS)
DEMYELINATING DISEASES
• Central nervous system
•
•
•
•
Multiple sclerosis
B12 deficiency
Tabes dorsalis
Progressive multifocal leukoencephalopathy
• Peripheral nervous system
• Guillain-Barre syndrome
• Charcot – Marie – Tooth disorder
MULTIPLE SCLEROSIS (MS)
• Autoimmune disease
• 1 in 2000 Canadians develop the disease
• Lower rates in tropical climates, probably due to higher levels of vitamin D
• Smoking increases risk
• Age of onset most commonly 20 – 40
• More common in females
• Some genetic component
MS PATHOLOGY
• Immune-mediated disease
•
•
•
•
T-cell activation and migration into the CNS
Inflammation
Demyelination
Neurodegeneration
• Demyelination leads to a conduction block
MS SYMPTOMS
• Numbness, visual disturbance, weakness, spasticity, double vision, impaired
gait, bladder dysfunction
• Acute/subacute onset followed by remission
• Uhthoff’s phenomenon – symptoms are worse in the heat (ex. hot shower)
RISK FACTORS
• Living in colder climates/low vitamin D
• 1 in 2000 vs 1 in 10000
• Type I diabetes
• Smoking
• Viral infection (EBV)
MS TREATMENTS
•
Glucocorticoids – reduce inflammation, suppress immune response. Short-term benefit
only
•
Interferon beta – signaling molecule that reduces activation of T-cells and reduces
inflammation
•
Glatiramer acetate – reduces T-cell activation, reduces inflammation and has
neuroprotective effects
•
•
Natalizumab – reduces the entry of T-cells into the CNS
•
Symptom treatment
Alternative treatments – oral cannabis extract or synthetic cannabinoids to treat
complications
FUNCTIONAL AREAS
DEMENTIA
• Alzheimer disease (60-80%)
• Vascular dementia
• Lewy body dementia
• Frontotemporal dementia
ALZHEIMER DEMENTIA
• Lifetime risk for a 65-year-old is 9% for males and 17% for females
• Increasing incidence with age
• Some genetic component
ALZHEIMER DEMENTIA
• Unclear etiology
• Some genetic component
• Pathology
• Extracellular beta amyloid deposits
• Intracellular neurofibrillary tangles
MESIAL TEMPORAL LOBE (HIPPOCAMPUS)
• One of the first areas affected in Alzheimer
Dementia
• Consolidation of short term memory into long term
ALZHEIMER SYMPTOMS AND SIGNS
• Loss of short term memory (most common first manifestation)
• Asking repetitive questions, misplacing objects
• Later signs
• Impaired reasoning
• Difficulty thinking of words
• Inability to recognize faces or common objects
RISK FACTORS
•
•
•
•
•
•
•
•
High LDL cholesterol levels
High blood pressure
Type 2 diabetes
Cerebrovascular disease
Traumatic brain injury
Obesity
Physical inactivity
Smoking (indirectly via its effects on cholesterol and blood pressure)
DIAGNOSIS IS CLINICAL
•
Gradual onset
•
•
•
Interview with the family
Impairment in memory plus one of
•
•
•
•
•
A lot of overlap
Executive function
Language
Learned motor skills
Recognition of objects
Impairment must be severe enough to interfere with work, social activities or
relationships
ALZHEIMER TREATMENT
• Risk factor management
• Cholinesterase inhibitor (Donepezil, Rivastigmine)
• Memantine (NMDA receptor antagonist)
• Vitamin E
• NOT RECOMMENDED
• Possibly slows cognitive decline, but some mixed results
• Associated with higher mortality especially cardiac mortality
ALZHEIMER PREVENTION
• Challenging mental activities (Attending these lectures counts!)
• Exercising (also slows decline)
• Reduces the accumulation of beta-amyloid
• Controlling your blood pressure
• Lowering cholesterol
• Diet rich in Omega-3 fatty acids
Pitkälä KH, Pöysti MM, Laakkonen M, Tilvis RS, Savikko N, Kautiainen H, Strandberg TE.
Effects of the Finnish Alzheimer Disease Exercise Trial (FINALEX)A Randomized Controlled
Trial. JAMA Intern Med. 2013;173(10):894-901. doi:10.1001/jamainternmed.2013.359
DEEP STRUCTURES
How do we know about the function
of each area?
MOVEMENT DISORDERS
• Cortex
• Basal ganglia
• Parkinson’s disease
• Huntington’s disease
• Cerebellar
• Pyramidal (final output pathway)
PARKINSON’S DISEASE (BASAL GANGLIA)
• Unknown etiology
• Average age of onset is 60 years
• Lifetime risk at 65 is <1%
PATHOGENESIS
• Degeneration of the Substantia Nigra
• Produces dopamine
• Subthalamic nucleus is also involved
• Apha-synuclein aggregating into Lewy bodies
BRAAK HYPOTHESIS
McCann, H., Cartwright, H. and Halliday, G. M. (2016), Neuropathology of αsynuclein propagation and braak hypothesis. Mov Disord., 31: 152–160.
doi:10.1002/mds.26421
SYMPTOMS
•
•
•
•
•
•
•
•
Pill rolling tremor
Rigidity
Slow movement/inability to initiate movement
Postural instability
Lack of facial expressions
Quiet speech
Loss of sense of smell + other autonomic symptoms
+ many more
RISK FACTORS
• Genetics
• History of traumatic brain injury
• Low levels of vitamin D
• Excess body weight
PROTECTIVE FACTORS
• Exercise = the only neuroprotective treatment for Parkinson’s
• Caffeine is associated with lower risk
• Smoking appears to be protective
• Alternative explanation – people who will develop Parkinson’s exhibit less reward
seeking behavior
TREATMENT
• Levodopa/carbidopa
• Dopamine agonists
• MOA – B inhibitors
• Amantadine
https://www.youtube.com/watch?v=Gg5M3J_FHXY
MENTAL HEALTH
• Anxiety
• Depression
• Often they are seen together and with other mental condition
• Not so fun fact: we have 50 000 thoughts per day, 70% of which are
negative
STIGMA
• Prejudice, avoidance, rejection
• Can perpetuate the cycle of negative thoughts, perceptions and behaviors
• Contributes to isolation
• Prevents people form seeking help
STOP STIGMA (CMHA)
• Ask yourself if what you hear
• Stereotypes people with mental health conditions (that is, assumes they are all alike
rather than individuals)?
• Trivializes or belittles people with mental health conditions and/or the condition itself?
• Offends people with mental health conditions by insulting them?
• Patronizes people with mental health conditions by treating them as if they were not as
good as other people?
• Speak up!
ANXIETY
• Normal, adaptive behavior
• Becomes maladaptive when out of proportion to the degree of threat
• Formally
• Panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized
anxiety disorder, posttraumatic stress disorder, obsessive compulsive disorder
• All can present with panic attacks
• Sweating, shortness of breath, racing heart, fear of loosing control
• Generalized anxiety disorder is the most common with 5-10% lifetime
prevalence
PREDISPOSING FACTORS
• Some genetic component
• Life trauma, extreme family environments
• Conditioned fear reaction
• Maladaptive beliefs
TREATMENTS
• Pharmacological
• Benzodiazepines
• Beta blockers
• SSRI (selective serotonin reuptake inhibitors)
• Cognitive behavioral therapy
CBT
• Looks at patterns of thoughts, feelings and behavior
• Seeks to change unhelpful patterns
• Focuses on developing coping strategies
• Works alone or in conjunction with medications
DIAL IT DOWN
•
•
•
•
D
•
Dunk your face
•
Intense exercise
I
A
•
Abdominal paced breathing
•
Let go of tension
L
DEPRESSION
• At least 1 in 10 of us will get depression at some time in our lifetime
• 40% will never seek help
SYMPTOMS
• Decreased mood or loss of pleasure in usual activities PLUS 3 OF
•
•
•
•
•
•
•
Weight gain or weight loss
Sleep changes
Psychomotor agitation or slowing
Fatigue or loss of energy
Guilt
Decreased concentration
Suicidality
BOTH FUNCTIONAL AND STRUCTURAL CHANGES
• Functional
• Monoamines (serotonin, norepinephrine, and dopamine)
• Gamma-aminobutyric acid (GABA)
• Glutamate
• Structural
• Increased ventricle to brain ratio
• Decreased size of the frontal lobe
• Decreased size of the hippocampus
RISK FACTORS
• Some genetic factors
• Childhood trauma
• Poor social relationships
• Negative thinking patterns
• Chronic diseases
• Medications (glucocorticoids)
TREATMENT
https://www.youtube.com/watch?v=PPbjK
3MmjL0
• Lifestyle
• Exercise
• Mindfulness
• Zinc supplementation
https://www.ted.com/talks/andres_lozano_parkinson_s_depress
ion_and_the_switch_that_might_turn_them_off (3:30 – 10:25)
• Pharmacologic
• SSRI (selective serotonin reuptake inhibitors)
• SNRI (selective serotonin norepinephrine reuptake inhibitors)
• Cognitive behavior therapy + other psychological therapies
• Deep brain stimulation + other
HOMEWORK
• Mindfulness video
• https://www.ted.com/talks/andy_puddicombe_all_it_takes_is_10_mindful_mi
nutes
BRAIN PROTECTION
• Mental stimulation
• Exercise
• Decreased incidence and severity of symptoms of anxiety and depression
•
As effective as pharmacotherapy and psychotherapy
• Improved memory and cognitive function
• New neuronal connections
• New neuron formation in Hippocampus
BRAIN PROTECTION
• Control your blood pressure, cholesterol and diabetes
• Diet
• B vitamins especially important for brain health
• Omega – 3
•
•
Associated with decreased cognitive decline in dementia
May be some benefit in depression
BRAIN PROTECTION
•
Caffeine
•
•
•
•
Seems to be protective in Parkinson’s and Alzheimer disease
Can both cause and relieve headaches
Can cause anxiety, insomnia, and panic attacks
Ginkgo biloba
•
•
•
•
Inconsistent evidence
Appears to slow progression of dementia, with no effect on development on dementia
Better than placebo at treating depression
No memory improvement
THINGS THAT ARE NOT RECOMMENDED
• St. John’s wort
• Some antidepressant effect
• Less effective than current treatments
• Many drug interactions
QUIZ ANSWERS
1.
What is the difference between the sympathetic and the parasympathetic
nervous system?
2.
3.
4.
What is the “pleasure” neurotransmitter?
What does DIAL it down mean?
How are Immodium and heroin similar?