5th year neurology lectures:Around 30 Lectures:

1. Dr. Mohammad Shaikhani: 8.1. Dr. Mohammad Shaikhani: 8.2. Dr. Mohammad Tahir: 7.2. Dr. Mohammad Tahir: 7.3. Dr. Rasul M.Hasan: 7.3. Dr. Rasul M.Hasan: 7.4. Dr. Akram Mahdawi: 7.4. Dr. Akram Mahdawi: 7.

5th year neurology lectures:1 lecture/week

every Saturday 8-9 AM.

My lectures:My lectures:2.2. Introduction 1: anatomy/physiology.Introduction 1: anatomy/physiology.3.3. Introduction 2: investigations of NS.Introduction 2: investigations of NS.4.4. Peripheral neuropathies.Peripheral neuropathies.5.5. Myopathies.Myopathies.6.6. Mysathenia gravis.Mysathenia gravis.7.7. Movement disorders & parkinsonism 1.Movement disorders & parkinsonism 1.8.8. Movement disorders & parkinsonism 2.Movement disorders & parkinsonism 2.9.9. Multiple sclerosis.Multiple sclerosis.

5th year neurology lectures:Introduction:

ANATOMY / PHYSIOLOGY:

Dr. Mohammad Shaikhani.Dr. Mohammad Shaikhani.

Assistant professor.Assistant professor.

M. B. Ch. B/ C.A.B.MM. B. Ch. B/ C.A.B.M

NS Cells The nervous system includes:The nervous system includes: 1.Neurons of different types.1.Neurons of different types. 2.Specialised blood vessels.2.Specialised blood vessels. 3.Ependymal cells lining the cerebral ventricles3.Ependymal cells lining the cerebral ventricles 4.Glial cells, of 3 types:4.Glial cells, of 3 types: A. Astrocytes: form the structural framework for the neurons & A. Astrocytes: form the structural framework for the neurons &

control their biochemical environment&their foot processes closely control their biochemical environment&their foot processes closely associated with the blood vessels to form BBB. associated with the blood vessels to form BBB.

B. Oligodendrocytes are responsible for the formation & B. Oligodendrocytes are responsible for the formation & maintenance of the myelin sheath, which surrounds axons &is maintenance of the myelin sheath, which surrounds axons &is essential for the rapid transmission of action potentials& myelin is essential for the rapid transmission of action potentials& myelin is also made by Schwann cellsalso made by Schwann cells . .

C. Microglia are blood-derived mononuclear macrophages. C. Microglia are blood-derived mononuclear macrophages.

GENERATION /TRANSMISSION OF NERVOUS IMPULSE Functioning of the NS by 2 physiological processes: Functioning of the NS by 2 physiological processes: 1.The generation of action potential with conduction down axons. 1.The generation of action potential with conduction down axons. 2.The synaptic transmission of impulses between neurons &/or 2.The synaptic transmission of impulses between neurons &/or

muscle cells. muscle cells. These processes depend upon the energy-demanding maintenance These processes depend upon the energy-demanding maintenance

of an electrochemical gradient across neuron cell membranes of an electrochemical gradient across neuron cell membranes effected by specialised ion channels in the membrane.effected by specialised ion channels in the membrane.

Synaptic transmission involves the release from a neuron of Synaptic transmission involves the release from a neuron of neurotransmitter molecules that bind to specific receptors on the neurotransmitter molecules that bind to specific receptors on the membrane of the receptor cell. membrane of the receptor cell.

These molecules alter either that cell's membrane potential via These molecules alter either that cell's membrane potential via effects upon ion channel permeability, or its metabolic function. effects upon ion channel permeability, or its metabolic function.

There are > 20 different neurotransmitters known to act at There are > 20 different neurotransmitters known to act at different sites in the NS, all potentially amenable to different sites in the NS, all potentially amenable to pharmacological manipulation. pharmacological manipulation.

GENERATION /TRANSMISSION OF NERVOUS IMPULSE The neuronal cell bodies are acted upon by synapses with large The neuronal cell bodies are acted upon by synapses with large

numbers of other neurons. numbers of other neurons. Each neuron therefore acts as a microprocessor, reacting to the Each neuron therefore acts as a microprocessor, reacting to the

influences upon it by changes to its cell membrane potential, influences upon it by changes to its cell membrane potential, causing it to be more or less ready to discharge an impulse down its causing it to be more or less ready to discharge an impulse down its axon(s). axon(s).

The synapsing neuron terminals are also subject to regulation by The synapsing neuron terminals are also subject to regulation by receptor sites on their pre-synaptic membrane, which modify the receptor sites on their pre-synaptic membrane, which modify the release of transmitter across the synaptic cleft. release of transmitter across the synaptic cleft.

The effect of some neurotransmitters is to produce long-term The effect of some neurotransmitters is to produce long-term modulation of metabolic function or gene expression rather than modulation of metabolic function or gene expression rather than simply to change the membrane potential. simply to change the membrane potential.

This effect probably underlies more complex processes in cognition, This effect probably underlies more complex processes in cognition, as long-term memory. as long-term memory.

Neurotransmission / neurotransmitters. (1) An action potential arriving at the nerve terminal depolarises the membrane & opens voltage-gated calcium channels. (2) Entry of calcium causes the fusion of synaptic vesicles containing neurotransmitters with the pre-synaptic membrane & release of the neurotransmitter across the synaptic cleft. (3) The neurotransmitter binds to receptors on the post-synaptic membrane to either (A) open ligand-gated ion channels which, by allowing ion entry, depolarise the membrane& initiate an action potential (4), or (B) bind to metabotrophic receptors, which activate an effector enzyme (e.g. adenylyl cyclase)& thus via the intracellular second messenger system modulate gene transcription, leading to changes in synthesis of ion channels or modulating enzymes. (5) Neurotransmitters are taken up at the pre-synaptic membrane

&/or metabolised.

NEUROTRANSMITTERS

Pesticide toxicity

injectionsBotulinum toxicity

Cataplexy

Anticholinergics, e.g. oxybutinin

Bladder control

Anticholinergics, e.g. hyoscine

Motion sickness

Huntington's chorea

Anticholinergics, e.g. benztropine, orphenadrine, procyclidine

Parkinson's disease

Peripheral acetylcholinesterase inhibitors, e.g. edrophonium, pyridostigmine

Myasthenia gravis

Central acetylcholinesterase inhibitors, e.g. donepezil, rivastigmine

Alzheimer's diseaseExcitatoryAcetylcholine

PharmacologyClinical relevanceEffectNeurotransmitter

Used therapeutically as i.m. botulinum toxin

MetoclopramideVomiting

AntipsychoticsSchizophrenia

Alzheimer's disease

dopamine agonistsParkinson's diseaseExcitatoryDopamine

Motor neuron disease

MemantineAlzheimer's disease

Memory

Epilepsy Aspartate

Cerebral ischaemiaExcitatoryGlutamate

DexamfetamineSleep disorders

TizanidineSpasticity

Multi-system atrophy

Amphetamines, sibutramineAppetite

(α-blockers)Bladder control

(β-blockers), (α-blockers)Cardiovascular control

AntidepressantsMood disorders

β-blockersMigraineExcitatoryNoradrenaline/adrenaline

UncertainInhibitoryHistamine

Startle syndromesInhibitory

BenzodiazepinesSpasticity

BenzodiazepinesAnxiety

vigabatrinEpilepsyInhibitoryGABA

Sleep

OndansetronVomiting

Pain

SSRI antidepressantsDepression

Pizotifen, triptansMigraineExcitatory(5-HT, serotonin)

Dynorphins

Morphine Enkephalins

Morphine Endorphins

MorphineOpioid peptides (> 20)

PainSubstance P

Melanocyte-stimulating hormone (MSH)

Adrenocorticotrophic hormone (ACTH)

Memory UncertainExcitatory/ inhibitoryNeuropeptidesVasopressin

FUNCTIONAL ANATOMY OF THE NERVOUS SYSTEM

Cerebral hemispheres

The cerebral cortex constitutes the highest level of nervous function, the anterior half dealing with executive ('doing') functions & the posterior half constructing a perception of the environment ('receiving/ perceiving'). Each cerebral hemisphere has four functionally specialised lobes. Many of the functions are lateralised. To which side depends on which of the two hemispheres is 'dominant', i.e. where language function is represented. In right-handed individuals this is almost always the left hemisphere while in left-handers either hemisphere may be dominant with about equal frequency

Cerebral hemispheres: frontal lobes

Concerned with executive function, movement & behaviour,it has: Primary. Supplementary motor cortex Specialised areas for eye movements, speech (Broca's area) & micturition control.

Cerebral hemispheres: Parietal lobes

Concerned with the integration of sensory perception. The primary sensory cortex lies in the post-central gyrus of the parietal lobe. Much of the remainder is devoted to 'association' cortex, which integrates the input from the various sensory modalities. The supramarginal/ angular gyri of the dominant parietal lobe form part of the language area. Close to these are regions dealing with numerical function. The non-dominant parietal lobe houses areas concerned with spatial awareness / orientation.

Cerebral hemispheres: Temporal lobes

Are the primary auditory cortex & primary vestibular cortex. On the medial side lie the olfactory cortex & parahippocampal cortex involved in memory function. Also contain many structures associated with the limbic system, including hippocampus & amygdala, involved in the processing of memory / emotions. The dominant temporal lobe also participates in language functions, particularly verbal comprehension (Wernicke's area). Music processing occurs in both temporal lobes, rhythm being processed on the dominant side& melody/pitch more on the non-dominant side.

Cerebral hemispheres: Occipital lobes

Are principally concerned with visual processing. The contralateral visual hemifield is represented in the primary visual (striate) cortex&areas immediately surrounding this are involved in the processing of specific visual submodalities as colour, movement or depth& the analysis of more complex visual patterns as faces.

Cerebral hemispheres: Basal ganglia

Collections of cells in the depths of the hemispheres deal with: Motor control (the basal ganglia). The appropriate attention to sensory perception (the thalamus). Emotion & memory (the limbic system). Control over internal bodily functions (the hypothalamus).

Cerebral hemispheres: ventricles

The cerebral ventricles contain the choroid plexus; producing CSF, which cushions the brain within the cranium. From the fourth ventricle the CSF leaves through foramina in the brain stem to circulate down around the spinal cord& over the surface of brain, where it is reabsorbed into the cerebral venous system.

The brainstem:

Containing: 1.All the sensory & motor pathways entering / leaving the hemispheres. 2.The nuclei of the cranial nerves: providing motor control to head muscles (including face / eyes) & some in the neck, along with coordinating sensory input from the special sense organs & the face, nose, mouth, larynx & pharynx. They also control autonomic functions including pupillary, salivary & lacrimal functions. 3.Nuclei projecting to the cerebrum& cerebellum.4. The reticular formation: predominantly involved in the control of conjugate eye movements, the maintenance of balance, cardiorespiratory control & the maintenance of arousal.

The SC:

Contains: 1.The afferent / efferent fibres arranged in functionally discrete bundles. 2.Collections of cells in the grey matter responsible for lower-order motor reflexes & the primary processing of sensory information, including pain.

The PNS:

The sensory cell bodies of peripheral nerves are situated in the dorsal root ganglia in the spinal exit foramina, whilst the distal ends of their neurons are invested with various specialised endings for the transduction of external stimuli into nervous impulses. The motor cell bodies are in the anterior horns of the spinal cord. Motor neurons initiate muscle contraction by the release of acetylcholine across the NMJ which results in change in potential in the muscle end plate. To increase the speed of impulse conduction, peripheral nerve axons are variably invested in myelin sheaths consisting of the wrapped membranes of Schwann cells& any peripheral nerve is made up of a combination of large, fast, myelinated axons (which carry information about joint position sense & commands to muscles)& smaller, slower, unmyelinated axons (which carry information about pain , temperature& autonomic function).

The Autonomic NS:

The unconscious neural control of the body's physiology is effected through the autonomic system. This innervates the cardiovascular/ respiratory systems, smooth muscle of GIT& glands throughout the body. The autonomic system is controlled centrally by diffuse modulatory systems in the brain stem, limbic system & frontal lobes, which are concerned with arousal & background behavioural responses to threat. The output of the autonomic system is divided functionally & pharmacologically into two divisions: the parasympathetic/ sympathetic systems.

The major anatomical components of the nervous system

The anatomy of the cerebral cortex.

CORTICAL LOBAR FUNCTIONS

Focal sensory seizuresContralateral hemisensory loss

DysphasiaLanguageCalculation

Parietal: dominant

Versive seizuresFocal motor seizures (Jacksonian march)Continuous partial seizures (epilepsia partialis continua)

Impaired smellContralateral hemiparesisFrontal release signs

DisinhibitionLack of initiationAntisocial behaviourImpaired memoryExpressive dysphasiaIncontinence

PersonalityEmotional controlSocial behaviourContralateral motor controlLanguageMicturition

Frontal

Positive phenomenaAssociated physical

signsCognitive/behaviouralFunctionLobe

Effects of damage

CORTICAL LOBAR FUNCTIONS

lower quadrantanopiaDressing apraxia

Contralateral homonymousConstructional apraxia

AgraphaesthesiaSpatial disorientation

Focal sensory seizuresContralateral hemisensory loss Astereognosis

Neglect of contralateral side

Spatial orientationConstructional skills

Parietal: non-dominant

CORTICAL LOBAR FUNCTIONS

Complex hallucinations (smell, sound, vision, memory)

Contralateral homonymousupper quadrantanopia

Receptive aphasiaDyslexiaImpaired verbal memory

Auditory perceptionLanguageVerbal memorySmellBalance

Temporal: dominant

CORTICAL LOBAR FUNCTIONS

Complex hallucinations (smell, sound, vision, memory)

Contralateral homonymous upper quadrantanopia

Impaired non-verbal memoryImpaired musical skills (tonal perception)

Auditory perceptionMelody/pitch perception Non-verbal memorySmellBalance

Temporal: non-dominant

CORTICAL LOBAR FUNCTIONS

Simple visual hallucinations (e.g. phosphenes, zigzag lines)

Homonymous hemianopia (macular sparing)

Visual inattentionVisual lossVisual agnosia

Visual processing

Occipital

NS Exam: