BMS2046_Disorders of CNS_Part 1_v1.0_04 MAR 2024.pdf

BMS2046 Disorders of the Central Nervous System (CNS): Part 1 Dr Vikki Revell [email protected] Office: 03MA00 - Clinical Research Building, Manor Park Campus Overall Learning Outcomes Neurological and psychiatric disorders Prevalence Cost The Central Nervous System (CNS) Brain regions Cell type...

BMS2046 Disorders of the Central Nervous System (CNS): Part 1 Dr Vikki Revell [email protected] Office: 03MA00 - Clinical Research Building, Manor Park Campus Overall Learning Outcomes Neurological and psychiatric disorders Prevalence Cost The Central Nervous System (CNS) Brain regions Cell types CNS disorders Symptoms, Causes, Treatment(s) if available Part 1: Learning Outcomes Be able to define the most prevalent neurological and psychiatric disorders Have an understanding of the cost of brain disorders Within the Central Nervous System (CNS) be able to describe: The location and function of different brain regions The component cell types and their function Disorders of the brain Neurological illness Mental health conditions ~13% of global disease prevalence Neurological disorders Condition in the central or peripheral nervous system that affects its functioning Brain, spinal cord or nerves Structural, biochemical or electrical abnormalities Cause Genes Environment Bacterial or viral infections Traumatic injuries or accidents Neurological disorders > 600 known neurological conditions Four main categories: Sudden onset conditions e.g., stroke, traumatic brain injury, spinal injury, meningitis Intermittent and unpredictable conditions e.g., epilepsy, migraine Progressive conditions e.g., Parkinson’s disease, dementia, motor neurone disease Stable with changing needs e.g., Tourette’s syndrome, narcolepsy, cerebral palsy https://www.neural.org.uk Neurological disorders 14.7 million people in the UK are affected by neurological conditions https://www.neural.org.uk https://www.nationalbrainappeal.org/ Psychiatric disorders Mental health condition Causes significant distress or impairment of personal functioning Characterized by a combination of abnormal thoughts, perceptions, emotions, mood, behaviour and relationships with others 1 in 4 people will experience a mental health problem of some kind each year in England 1 in 6 people report experiencing a common mental health problem (like anxiety and depression) in any given week in England https://www.mind.org.uk/ https://www.mentalhealth.org.uk Mental health conditions Depression Anxiety Personality disorders Bipolar disorder Schizophrenia and other psychoses NHS Digital ONS, Nov 2022 Cost of mental health in Europe Direct costs All costs that are completely attributable to the use of a health care intervention or illness Direct medical costs Value of resources used in treatment, care and rehabilitation of a patient Medication Consumables e.g., needles, cannulas Staff costs Smith, Nature 2011 Cost of mental health in Europe Direct non-medical costs Transportation costs Caregiver time Equipment maintenance Insurance Heating and lighting Indirect costs Value of economic resource lost because of disease-related disability or premature mortality Smith, Nature 2011 2010 costs Total = €137, 476 million Indirect cost = €62, 346 million Direct healthcare = € 36, 036 million Direct non-medical = € 36, 077 million Fineberg et al, J Psychopharmacol 2013 Estimated annual prevalence of disorders in the UK: 2010 45 million diagnoses Fineberg et al, J Psychopharmacol 2013 Prevalence of mental health conditions https://www.mentalhealth.org.uk Summary of learning: Brain disorders comprise neurological conditions and mental health conditions Four main categories of neurological conditions Sudden onset; Intermittent and unpredictable; Progressive; Stable High economic burden Direct medical and care costs Indirect costs: disease-related disability or premature mortality Central Nervous System CNS = Brain + spinal cord Brain – 85 billion neurons Spinal cord – 100 million neurons Functions of the nervous system Sensory – detect internal and external stimuli Integration – process information and make decision Motor – effect an appropriate response Neurons Dendrites, cell body, axon Form complex networks Neurons Electrical excitability Convert stimulus into an action potential Action potential propagates along the axon Most are unable to undergo mitotic divisions Glial cells Support, nourish, and protect neurons Glial cells Astrocytes Protoplasmic – short branching processes, found in grey matter Fibrous – long unbranched processes, found in white matter Microfilament structure enables them to support neurons Maintain appropriate chemical environment for generation of nerve impulses May play a role in learning and memory Influence formation of neural synapses Glial cells Microglia Phagocytes Remove cellular debris, microbes and damaged nervous tissue Oligodendrocytes Form and maintain myelin sheath around CNS axons Myelin sheath = multilayered lipid and protein covering Insulate axons and increase speed of nerve impulse conduction Regions of the brain Brain =2% of total body weight Brain consumes ~ 20% of oxygen & glucose used by the body Need continuous supply of glucose Blood-brain barrier (BBB) Tight junctions - seal together endothelial cells of brain blood capillaries Thick basement membrane that surrounds capillaries Restricts access for substances in blood to enter brain Blood-brain barrier (BBB) Diffusion Lipid-soluble substances: O2, CO2, steroid hormones, alcohol, barbiturates, nicotine, caffeine Water Facilitated transport A few water-soluble substances, such as glucose Slow or no transport Ions very slowly Proteins and most antibiotics do not cross BBB Cerebrospinal fluid (CSF) Mechanical protection Shock-absorbing medium to protect brain and spinal cord Chemical protection Optimal chemical environment for neuronal signalling (action potentials and postsynaptic potentials) Circulation Allows exchange of nutrients and waste products between the blood and adjacent nervous tissue Cerebrum “Seat of Intelligence” Outer cerebral cortex – grey matter Cerebral white matter Cerebral Cortex 2–4 mm thick - billions of neurons arranged in distinct layers Associated with higher level processes Frontal lobes ‘Higher’ cognitive functions: decision-making, conscious thought, control of emotion and behaviour, language production Temporal lobes Memory, hearing, emotion and some aspects of language Parietal lobes Integrating sensory information and movement co-ordination Occipital lobes Visual processing Midbrain Superior colliculi Coordinate movements of head, eyes, and trunk in response to visual stimuli Inferior colliculi Coordinate movements of head, eyes, and trunk in response to auditory stimuli Substantia nigra Dopaminergic nucleus which has a critical role in modulating motor movement and reward functions Basal ganglia Deep cerebral nuclei Caudate nucleus, Putamen, Nucleus accumbens, Olfactory tubercle, Globus pallidus, Ventral pallidum, Substantia nigra, Subthalamic nuclei Motor function: initiation, coordination of movement, posture, tone Cognition, perception and emotional behaviours (including reward system) Brainstem Pons Relay signals from motor areas of cerebral cortex to cerebellum Respiratory regulation Brainstem Medulla oblongata Cardiovascular - regulates heartbeat and blood vessel diameter Respiratory - regulates breathing Vomiting, swallowing, sneezing, coughing, and hiccupping Reticular formation - consciousness and arousal Cerebellum Co-ordinates skilled movements Regulates posture and balance Evaluates how well movements initiated by motor areas in the cerebrum are actually being carried out Feedback to motor areas of cerebral cortex Cerebellum Damage to cerebellum can result in ATAXIA Loss of ability to coordinate muscular movements Abnormal walking movements, altered speech Hypothalamus Controls and integrates activities of autonomic nervous system Hormone production e.g., oxytocin and antidiuretic hormone (ADH) Regulates emotional and behavioural patterns Hypothalamus Feeding and satiety centres Thirst centres Suprachiasmatic nuclei (SCN) Regulation of body temperature Thalamus Relays sensory information to cerebral cortex Motor function: transmits information from cerebellum and basal nuclei to motor area of cerebral cortex Role in maintaining consciousness Limbic system Emotion, behaviour, long-term memory and olfaction Several components: Cortical areas Limbic lobe (frontal & temporal) Subcortical areas Amygdala, hippocampus Some thalamic nuclei Some hypothalamic nuclei Image: https://qbi.uq.edu.au/brain/brain-anatomy/limbic-system Limbic system Limbic system is unique to mammals: Species preservation Reproduction, instinctive behaviours Self-preservation Feeding behaviour, aggression Expression of fear Motivation Emotions Learning & memory Image: https://qbi.uq.edu.au/brain/brain-anatomy/limbic-system Neurotransmitters - monoamines Epinephrine/Adrenalin & Norepinephrine/Noradrenalin Excitatory NT (sympathetic nervous system) Hormone Produced in the adrenal glands Stress response Neurotransmitters - monoamines Dopamine Substantia nigra, ventral tegmental area & hypothalamus Excitatory, inhibitory & modulatory Reward, addiction, motivation & motor control Neurotransmitters - monoamines Serotonin Inhibitory NT Role: mood, emotion, appetite & digestion Precursor to melatonin - sleep Balances out excessive excitatory NT effects Neurotransmitters – amino acids GABA Gamma-aminobutyric acid Primary inhibitory NT Regulate anxiety, vision and motor control Low levels can cause irritability & anxiety Glutamate Most abundant NT in the CNS Excitatory NT Cognitive functions, memory and learning Summary of learning: Different regions of the brain are specialized for specific functions Disruption of specific regions will be associated with related symptoms The CNS is comprised of neurons and supporting glial cells (astrocytes, microglia, oligodendrocytes) Part 1: Learning Outcomes Be able to define the most prevalent neurological and psychiatric disorders Have an understanding of the cost of brain disorders Within the Central Nervous System (CNS) be able to describe: The location and function of different brain regions The component cell types and their function Some useful resources https://www.youtube.com/playlist?list=PLNZqyJnsvdMqFNFyHvMFrFnlXLosnw wB_ Glossary: http://www.dana.org/brainglossary/