Main Scenario 6

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Myotomes and reflexes Nerve impulse physiology Neurotransmitters Nerve Anatomy Tracts Sensory and Motor How body feels pain Autonomic Nervous System Dermatome Anatomy of Bladder and Pelvis Faecal Continence Urinary Continence Micturition Reflex Neuropathic Bladder Disorders Urinary Incontinence Female Pelvis Differential Optic Atrophy • Multiple Sclerosis o Differential of sensory loss + hereditary causes (hereditary spastic paraplegia) – Paul o Differential of parasthesiae – Paul o Peripheral neuropathies – Paul o Radiculopathies – Paul o Neurological investigations – EMG, EEG, CT/MRI, LP, visual evoked potentials – Paul o Findings on CSF – Paul o Upper and Lower motor neurone problems – findings on examination – Paul o Synapses – lectures!!! – Paul o Spinal cord anatomy - Paul o Drugs for incontinence – other things e.g. pads, bladder retraining, catheters – Paul o Urinary tract infections and antibiotics – Paul o Psychosocial of incontinence of urine and faeces! He will smell!! - Paul o Gives up job – loss of role, loss of identity, loss of finances, benefits, loss of motivation, social isolation, depression etc etc etc!! – Paul • Beta Interferon • Chronic illness and physical disability • Financial Support • Reason for non attending clinics • Theory of planned behavior • Addressing health promotion • Antibiotics • Brain Anatomy

Myatomes and Reflexes

Discuss the mechanism of Action Potentials

Nerve Impulse •At rest (-70 mV) many K+ channels open, most Na+ channels closed; these Na+ channels are voltage regulated channels •2) As depolarization begins (we will discuss how this all begins in more detail in the next lecture), some Na+ channels open •3) Na+ concentration and electrical gradients are into cell, so Na+ starts to move into cell a) This causes more depolarization, which opens more Na+ channels b) Positive feedback loop established •4) At threshold (-50 mV) “all” Na+ channels are open a) membrane far more permeable to Na+ than K+ b) Na+ rushes in, and inside of cell becomes positive (+30 mV) •5) Two things help repolarize: a) Voltage-sensitive Na+ channels close at +30 mV b) K+ channels are also voltage-sensitive; when membrane voltage is +30, “all” K+ channels open; K+ rushes out of cell along both concentration and electrical gradient. c) Positive charges leaving with K+ repolarizes membrane. •6) K+ rushing out can take out too many positive charges = a slight hyperpolarization How is the gradient restored after an Action Potential has passed? 1) At completion, membrane potential restored, but concentrations of Na+ and K+ not. 2) Very few K+ and Na+ cross membrane during AP compared to total available, so concentration not changed much. 3) Na+/K+ ATPase pump. How are nerve impulses conducted across synapses? •Action Potential reaches axon terminals

•B) Action Potential triggers voltage-regulated Ca++ channels to open •C) Influx of Ca++ triggers fusion of synaptic vesicles with plasma membrane = synaptic release •D) Neurotransmitter diffuses across synaptic cleft and binds to a receptor on the postsynaptic membrane •E) Causes some change in the postsynaptic cell (usually a local change in membrane potential by opening an ion channel) For example activation of nicotinic Ach receptors is excitatory because it causes an influx of Na+ and depolarisation, activation of GABA receptors is inhibitory because it causes and influx of Cl- ions and hyperpolarization. •F) This generates an Excitatory Postsynaptic Potential (EPSP) by the following mechanism... 1 Neurotransmitter binds to receptor 2 Na+ channels open (or Ca++ channels) 3 Lots of Na+ in 4 With net influx of +, membrane depolarizes a little 5 Membrane is closer to threshold •G) Neurotransmitter is removed from synaptic cleft What are the inhibitory and excitatory neurotransmitters? •Release of excitory neurotransmitters from the presynaptic membrane opens channels in the postsynaptic membrane and leads to an increase in the concentration of sodium ions within the postsynaptic cell and a decrease in that of potassium ions. This leads to a 'depolarisation' of the postsynaptic cell, which is propagated further along the cell membrane by an action potential. •Inhibitory neurotrasmitters encourage the hyperpolarisation of the postsynaptic cell, making it less likely to generate an action potential. Neurotransmitter: Function: Synthesis by (enzymes): Acetylcholine: mostly excitatory: Choline acetyltransferase Bioactive amines: Dopamine: exitatory and inhibitory: Tyrosine hydroxilase Epinephrine: excitatory: Tyrosine hydroxilase and dopamine-b-hydroxilase Norepinephrine exitatory Tyrosine hydroxilase and dopamine-b-hydroxilase Serotonin exitatory Tryptophan hydroxilase Amino acids: Glutamate exitatory Metabolic amino acid Glycine mostly inhibitory Metabolic amino acid g-Aminobutiric acid (GABA) inhibitor Glutamate descarboxilase

How does the body feel pain? •All pain receptors are free nerve endings. There are mechanical, thermal and chemical pain receptors. They are found in skin and on internal surfaces such as periosteum and joint surfaces. Deep internal surfaces are only weakly supplied with pain receptors and will propagate sensations of chronic, aching pain if tissue damage in these areas is experienced. •Two main types of nociceptor, Aδ and C fibres, mediate fast and slow pain respectively. Thinly myelinated type Aδ fibres, which transmit signals at rates of between 6 to 30 metres per second mediate fast pain. This type of pain is felt within a tenth of a second of application of the pain stimulus. It can be described as sharp, acute, pricking pain and includes mechanical and thermal pain. Slow pain, mediated by slower, unmyelinated ("bare") type C pain fibres that send signals at rates of between 0.5 to 2 metres per second, is an aching, throbbing, burning pain. Chemical pain is an example of slow pain.

How is pain transmitted in the Central Nervous System? •There are 2 pathways for transmission of pain in the CNS. These are the neospinothalamic tract (for fast pain) and the paleospinothalamic tract (for slow pain).

•Fast pain travels via type Aδ fibres to terminate on lamina I (lamina marginalis) of the dorsal horn. Second order neurons of the neospinothalamic tract then take off and give rise to long fibres which cross the midline through the anterior commisure and pass upwards in the contralateral anterolateral columns. These fibres then terminate on the Ventrobasal Complex (VBC) of the thalamus. From here, third order neurons communicate with the somatosensory cortex. Fast pain can be localised easily if Aδ fibres are stimulated together with tactile receptors. •Slow pain is transmitted via slower type C fibres to laminae II and III of the dorsa horns, together known as the substantia gelatinosa. Second order neurons take off and terminate in lamina V, also in the dorsal horn. Third order neurons then join fibres from the fast pathway, crossing to the opposite side via the anterior commisure, and travelling upwards through the anterolateral pathway. These neurons terminate widely in the brain stem, with one tenth of fibres stopping in the thalamus, and the rest stopping in the medulla, pons and mesencephalon. Slow pain is poorly localized.

Autonomic Nervous System

Spinal outflow Position of ganglia

Parasympathetic Cranial nerves III, VII, IX, X Near or in target tissue

Primary neuro transmitter

ACh

Primary receptors at tissue

Ach Muscarinic Receptors (M1,M2,M3) Nitric Oxide (NO) vasoactive intestinal peptide (VIP)

Co-transmitters

Sympathetic Thoracic and Lumbar Near Spinal Cord (Paravertebral sympathetic chain) Mainly NA (Ach in sweat glands and the adrenal medulla) Adrenoreceptors (a1, a2, b1, b2, b3) ATP, neuro peptide Y

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Autonomic nervous system is divided into two main branches the parasympathetic and sympathetic nervous system. Peripheral portions of the ANS are made up of pre-ganglionic and post-ganglionic neurones Cell bodies of the pre-ganglionic neurones are located in the intermediolateral gray column of spinal cord or the homologous nuclei of the brain (cranial nerves) The axons of pre-ganglionic fibres are mostly myelinated, slow conducting type B fibres The axons post-ganglionic neurons are mainly unmyelinated C fibres In some instances these act in opposition to each other. Increased sympathetic increases heart rate, parasympathetic slows the heart rate. Some organs or tissues are innervated by one system (blood vessels only stimulated by sympathetic nervous system) There are a number of similarities between the two systems. Both generally feature a single synapse, found in the ganglia positioned between the spinal cord and the target organ or issue. The neurons that stretch between spinal cord and the ganglia are pre-ganglionic, those between the ganglia and target tissue are called the post ganglionic. The sympathetic nerve that supply the adrenal medulla are an exception to this rule as they do not feature ganglia. The cell bodies of the pre ganglionic neurons are founf in the ganglia, those of the post ganglionic are found in the tissue. The neurotransmitter released by pre ganglionic neurone at the ganglionic synapse is exclusively Ach. Which acts on nicotinic Ach receptors on the post ganglionic neruone to propagate the signal..

Enteric Nervous System • The third division of the autonomic nervous system which forms a comlex net around the viscera, with cell bodies embedded in the intramural plexuses of the intestinal wall. The GIT is innervated by the autonomic nervous system (sympathetic and parasymphathetic) which forms the extrinsic pathway. • The extrinsic pathway connects to the local nerve supply within the wall of the GIT (intrinsic pathway) • These two pathways interact and their main function is to fine tune the functions of the GIT. through release of a number of neuro peptides and transmitters other than NA and Ach (e.g. 5 hydroxytrypatmine, nitric oxide and ATP). • Parasympathetic input is from the vagus and pelvic nerves • Sympathetic inputs are from celiac, superior and inferior mesenteric, and hypogastric plexuses • Activation of parasympathetic stimulates • Whereas activation of sympathetic system inhibits motor and secretory actions of GIT • Sympathetic stimulation inhibits the muscularis externa but stimulates the muscularis mucosae and certain sphincters • There are two networks of nerve fibres and ganglions. These innervate the GIT from mouth to anus They are called intramural plexus Myenteric plexus (Auerbach’s plexus), Submucosal plexus (Meissner’s plexus) • Myenteric plexus is mainly motor and regulates GIT motility • In Hirschsprung’s disease is it is missing in some section, Leads to hypomotility and distension of that region • The submucosal plexus mainly control GIT secretion and blood flow, It also receives signals from the epithelium and stretch receptors in the gut wall, Utilises many neurotransmitters

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Reflex control of gut Afferents within the GIT provide the sensory inputs integrated at two levels, Local within the ENS and Central in the CNS, Send information back influencing GIT function

Ganglionic Synaptic Transmission in the autonomic nervous system • The events leading to transmitter release at the autonomic ganglia are indistinguishable than what is described above (neuromuscular synapse), Except!. That far less neurotransmitter is needed to stimulate an action potential in a neurone compared to a muscle. Equally the events at the Ach receptor are exactly the same Except! That depolaristaion results in propagation of the action potential in the post ganglionic neurone, instead of a muscle.

Synaptic Transmission at the post-ganglionic sympathetic nerve terminal

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Ach is the neurotransmitter released by post ganglionic parasympathetic nerves, but it acts upon Ach muscarinic receptors on the post synaptic membrane of the relevant tissue. Two date 5 sub classes of muscarinic receptors have been identified, only three have been well characterized 1. M1 receptors are found in the CNS autonomic and enteric ganglia (neural M1) and on parietal cells that secrete gastric acid (gastric M1) 2. M2 receptors (Cardiac) are found in the heart (primarily the atria) and on presynaptic neurons. 3. M3 glandular receptors are found on the exocrine glands, smooth muscle and the vascular endothelium. All muscarinic receptors are G-protein coupled Stimulation of M1 and M3 receptors activates G-protein coupled phospholipase C to generate IP3 and diacyglycerol, leading to cellular activation. Activation of M2 receptors inhibits G-protein coupled adenylate cyclase leading to reduced rate and force of contraction of the heart.

Autonomic Nervous System in regulation of blood volume

Anatomy of Bladder and Urogenital tract and Penis Levator Ani • Thin sheet like muscle forms the main component of pelvic floor. It gains attachment posteriorly inferior aspect of the body of the pubis,posteriorly to the ischial spine and laterally to the fascia covering attachments. Muscle fibres pass anteriorly, inferiorally and medially to interdigitate forming a midline raphe. This acts as a sling. 1. Anterior fibres form a sling around the urethra in the male or the vagina in the female by attaching medially to the perineal body. 2. Middle group of fibres form a sling around the recto anal junction attaching anteriorly to the perineal body, the deep part of the external anal sphincter and posteriorly to the anococcygeal body 3. Posterior or lateral group of fibres form the fascia over the obturator internus form a sling attachment to the anococcygeal body anteriorly and sacrum and coccyx posteriorly. • The levator ani 1. Supports the pelvic contents especially when intra abdominal pressure is raised as indefecation, pissing and parturition 2. Assists in voluntary continence of urine and faeces. 3. Assists in rotating the fetus in normal childbirth • Innervation is from the lower branches of the sacral plexus via the pudendal nerve and also directly from the sacral plexus.

Coccygeus • The small triangular muscle fills in a small defect in the pelvic floor posterior to levator ani. It passed from ischial spine and fans out attaching to the lateral aspect of the sacrum. It supports the actions of the levator ani, as it completes the muscular pelvic floor. Innervation of this small muscle is as pre levator ani. Peritoneal Cavity • The peritoneum is reflected from the body wall on to the surface of the various structures located within the pelvic cavity, creating several pouches.

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Pus will collect in these pouches. In the male peritoneum from the posterior wall of the pelvis covers the rectum, and lies on the upper surface of the pelvic diaphragm before reflecting anteriorly on the superior surface of the bladder. The rectovesical pouch. In the female this space is divided into two by presence of uterus and fallopian tubes. As the peritoneum passes along the pelvic diaphragm from the rectum it reaches the posterior aspect of the uterus. From here the peritoneum continues anteriorly on the superior surface of the bladder. It then passes upwards anteriorly onto superior surface of the bladder. Lateral to the uterus the peritoneum also passes inwards to cover the fallopian tubes to attach to the lateral pelvic wall and lateral aspect of the uterus, forming a peritoneal fold as the broad ligament. Posteriorly the pouch between the rectum and the uterus is known as the rectouterine pouch, whilst the anterior pouch between the uterus and bladder is known as uterovesical pouch.

Rectosigmoid Junction to Anal Sphincter • Sigmoid colon is variable in length and can pass cranially from the pelvic inlet before coming continuous with the rectum within the pelvic cavity at the level of the third sacral vertebra. • The rectum has a peritoneal covering only on the upper third of its anterior and lateral aspects. • Peritoneum covers only the anterior aspect of the middle third, while the lower third lies within the pelvic fascia between the peritoneum and levator ani and has no peritoneal covering. • The inferior third of the rectum is dilated to form the ampulla. Within the rectal cavity are mucosal folds meant to help in detecting shit and flatulence. • Anal canal is a continuation of the alimentary tract from the rectum passing through the pelvic diaphragm (levator ani) opening externally as the anus. • In passing inferiorly the anasl canal turns posteriorly forming a sharp bend in the GI tract. It is this bend that activation of the levator ani fibres will exaggerate and enhance faecal contininence.

Ureters • Enter the pelvic cavity anterior to the bifurcation of the common iliac vessels, which in turn lie anterior to the sacroiliac joints and remain retrop-peritoneal structures. • They descend on the posterior aspect of the pelvic cavity superficial to the branches of the internal iliac artery to the level of the pelvic floor at the ischial spine. At this point the ureters run anteriorly along the lateral aspect of the pelvic floor within the fascia that lies superior to levator ani and deep to the peritoneum covering the pelvic floor. • In this part of the course they are crossed by the uterine artery in the female and the vas deferens in the male. • Anteriorly they turn slightly medially to pass through the bladder wall to form the posterior corners of the trigone. • Through out their course they lie just deep to the peritoneum lining the pelvic cavity. Within the pelvic cavity, the ureters gain their blood supply from, superiorly, the gonadal artery and more distally the inferior vesical artery. Bladder • Is a hollow muscular structure lies in the anterior aspect of the pelvic cavity immediately posterior to the pubic bone, separated from the bone by the fat filled retro pubic space. • It has been designed as a distensible storage container for urin and delivered via the two ureters which can then be emptied through the urethra located in the bladder base. When empty is like a three sided pyramid, though when full it is oval in shape. • Projecting inferiorly from the apex of the bladder are three surfaces, two anterolaterally in contact with the pubic bone on each side of the pubic symphasis and a superior surface. The latter joins the two former surfaces and is thepart that distends as the bladder fills and is covereved with peritoneum. • Inferiorly each of the three sides is joined to form the narrow base.Within the base is a smooth triangular area (trigone) marked anteriorly by the opening of the urethra and posteriorly by the openings of the two ureters. It is the oblique passage of the ureter through the posterolateral aspect of the trigone that creates a one way valve allowing urine into the bladder but preventing reflux into the ureters. • Posteriorly the bladder is related to the rectum in the male and the uterus in the female. The base lies within the pelvic fascia, which thickens to form ligaments connecting the bladder neck to the pubic bone anteriorly, laterally to the pelvic walls and posteriorly to the rectum. In the female, while these ligaments attach the bladder to the cervicx posterriorly, the bladder is more mobile then in the male which is supported by the prostate gland. • When empty the bladder in the adult lies inferior to the pelvic brim, though in the young child it lies superior to the pubic bone. It is important to note that when the bladder is distended, it is possible to pass a needle just superior to the pubic symphasis, inserted in the midline, directly into the bladder. • Useful land mark is the peritoneal side of the anterior abdominal wall, seen in minimally invasive surgery, is the median umbilical ligament, a midline structure passing from the apex of the bladder superiorly to the umbilicus. It represents the obliterated urachus. This is a

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relatively bloodless area through which trocas can be inserted in minimally invasive bladder surgery. Innervation Bladder receives autonomic innervations from the pelvic plexuses. The sympathetic fibres descend from L1 and L2 segments of the sponal cord and pass via the pelvic plexuses to the bladder. They provide the motor supply to the internal urethral sphincter closing it and inhibit contraction of the bladder wall itself, allowing the bladder to fill up and distend. The parasympathetic fibres on the other hand make the internal sphincter relax and the bladder wall contract allowing the bladder to empty.

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The urethra • The wall of the bladder is formed of smooth muscle fibres and is thickened inferiorly in the bladder base around the proximal urethra to form the internal urethral (vesical) sphincter. • The urethra passes inferiorly from the bladder and in the male is S shaped and 20cm long, while female is only 2 cm long. Prostate gland • Cone shaped prostate gland lies within the pelvic fascia inferior to the badder. Its base is in contact with the bladder superiorly, whilst the apex is in contact with the levator ani inferiorly. This gland is a fibromuscular structure containing glandular tissue, divided into lobs by the fibrous septa and the two ejaculatory ducts. Benign enlargement of the median lobe of the two lateral lobe is common in middle aged men and presents with difficulty in starting and stopping voiding. Particularly common with enlargement of the median lobe as it surrounds the urethra. • In benign lesions it normally has a smooth surface with a vertical midline groove. However if enlarged and irregular shape it is more likely to be due to a malignant growth. • The gland is surrounded by a fibrous capsule or sheath , which is continuous superiorly with the fascia around the bladder neck. Inferiorly it lies on the supporting pubroprostatic ligaments, and posteriorly lie the seminal vesicles and rectum. • The blood supply is from the internal iliac arteries via the inferior vesical and middle rectal arterties. Surrounding the gland is a plexus of veins draining primarily to the internal iliac vein but also to the vertebral plexus of veins. It is the latter that is important in the spread of prostatic malignancy to the spine via this vertebral venous drainage to the internal iliac and sacral nodes

Male urethra • In the male the urethra descends inferiorly from the internal sphincter and immediately enters the prostate gland. This is known as the prostatic urethra and is approximately 3cm long and is widest part of male urethra. • On leaving the prostate gland the urethra passes between the anterior attachments of the right and left levator ani to enter the deep pouch of the perineum as the rather rigid membranous urethra. Here the internal urethral sphincter providing volunatary control of pissing surrounds the urethra (16cm long). The urethra turns 90 degrees is dilated and joined by the ducts of bulbourethral glands. Penile urethra transverses the corpus spongiosum travelling distally to the glands of penis. Just prior to urethral meatus it dilates to form navicular fossa. Female urethra • Shorter and straighter than males, approx 3cms long passing inferiorly between the pubocervical ligaments and between the anterior attachments of the right and left levator ani to pass into the deep pouch of the perineum. The external urethra surrounds this part before transversing the superficial pouch to open in the vestibule. • Clitoris lies anterior to the urethral meatus whils vagina runs posteriorly • Urethra gains blood supply from the inferior vesical artery or from the internal pudendaly artery wit corresponding venous drainage. Only the urethra within the syperficial pouch has lymphatic drainage to the groin where as the deeper parts of the urethra drain into the internal iliac nodes. Pudendal nerve provides the sensory innervations to urethral mucosa. Perineum • Diamond shaped area lies inferior to the pelvic floor and is bounded anteriorly to the pubic symphasis, anterolaterally by the ischial tuberosities, posterolaterally by the sacro tuberous ligaments and posteriorly by the coccyx. The perineum is further divided into the anal triangle.

Anal triangle • Anal triangle contains the anal canal with surrounding sphincters in the midline and on each side laterally, the two wedge shaped ischiorectal fossaa. Both fossae communicate with each other, anterior and posterior to the anal canal. • Each has a base the perineal skin, a medial laterall suface. The pelvic diaphragm in particular levator ani, forms the superomedial surface. These blend inferiorly with the external anal sphincter. The lateral surface is the fascia covering obturator internus. • Posteriorly space projects between the sacrotuberuous and sacrospinous ligaments to the space deep to glueteus maximus.

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To allow distension during shitting each space is full of fat. The inferior rectal nerve passes into the fossa via the lesse sciatc notch and crosses the fossa from lateral to medial to innervate the anal sphincters. These extensions and course of inferior rectal nerve are important in abcess formation of the fossa.

Uro genital Triangle • The urogential triangle is bounded anteriorly by the pubic symphasis, anterolaterally by the inferior aspect of each pubic bone, the intervening ischiopubic rami, and posteriorally the ischial tuberosities. The deep doundary is the pelvic diaphragm formed by the levator ani and the superficial boundary is the membranous fascia of the perineal skin attaching laterally to the ischiopubic rami. • The space is divided by into two by the urogential diaphragm. A layer of fascia attaching anterolaterally to the ischiopubic rami amd posteriorly to the membranous fascia, closing off the superficial pouch contains the from deeper structures. • In the male this superficial pouch contains the scrotal sac and the base of the penis. • In female the pouch is split into two by the vestibule, a space lying between the labia each of which contain part of the base of the clitoris.

Deep perineal Pouch • The urogenital pouch is split into deep and a superficial layer to form the deep perineal pouch between both layers. The deep pouch contains the important urethral sphincter, composed of skeletal muscle, forming a sphincter around the membranous urethra. • This important sphincter is innervated by a branch of the pudendal nerve and provides voluntary control of pissing. Also within the deep pouch lying posterior to the urethra is the depp transvers perineal muscle. In the male the bulbouurethral glands which secrete a lubricant lies within the deep pouch and their ducts pass inferiorly entering the superficial pouch posterior to the urethra. • These ducts drain into the posterior aspect of the urethral bulb.

Superficial perineal pouch • Developmentally the genital area commences with a common cleft similar to that seen in the female at birth. • On each side of cleft (vestibule) lying on the urogenital diaphragm are two columns of erectile tissue each covered with a thin layer of muscle. The more lateral column corpus cavernosum attaches on each side to the ischiopubic rami. They pass anteriorly to form the dorsal aspect of the shaft of the penis in the male or clitoris in the female. • Each column is covered proximally by the muscle ischiocavernosus, which twists round on to the dorsal aspect of the penis or clitoris. • The more medial structure the (corpus spongiosum) on either side of the vestibule cleft in the female are known as the vetibular bulbs and each is covered by skeletal muscle bulbospongiosis. • In the male the two columns come together and in so doing wrap around the urethra to form the single structure corpus spongiosum. • In so doing the bulbospongiosus muscles also come together forming a single muscle. • In female the skin covering the genital folds forms the labia in female, in male it fuses on developing penis. • The male corpus spongiuosom enlarges posteriorly to form the bulb of the penis and attaches securely to the superficial layer of the urogeintial diaphragm. Distally it is the coprpus spongiosum that will enlarge forming the glans of the penis. Or clit. • The glans is tethered to the skin covering it by a fold of mucosa, the frenululm, containing a small artery. • In both sexes the gland is supplied with sensory nerve endings carried in pudendal nerve. • The corpora are sponge like with autonomic innervations from pelvic plexi which closes venous drainage causing a stonking erection. • In male testes in superficial pouch. • In female it is the greater vestibular bulb within the superficial perineal pouch. These small apocrine glands secret into the vestibule itself. Male genital tract • Male reproductive system is represented by vas deferens and seminal vesicles.

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Testes lie within superficial perineal sac. Joining testes and the prostate is the vas deferens passing superiorly from the testis to traverse the inguinal canal, then descending on the internal aspect of the lateral wall of the pelvis to the posterior aspect of the prostate gland. 26th week the testes drop retroperitoneally form place of origin on posterior abdominal wall to the deep inguinal rings. On each side the fibromuscular gubernaculums forms a path for the process vaginalis to pass through the anterior abdominal wall to form inguinal canal. The testes descend into developing scrota where it is tethered to the lateral aspect of the genital cleft. Throughout descent the testes maintain blood supply from the aorta and the lymph drainage to nodes at the level of second lumbar vert alongside place of origin L2/L3. Preceded by the processi vaginalis the testis passes through the inguinal canal emerging at the superficial inguinal ring with three coats covering it and the trailing “tubular” structures. 1. Internal spermatic fascia from transversalis fascia 2. Cremasteric fascia and muscle from the internal oblique 3. External spermatic fascia from the external oblique After testis enters the scrotum, the inguinal canal normally contracts around the spermatic cord. Testis is now in scrotal sac lying in superficial perineal pouch and separated by median septum. It is surrounded by the extension of the peritoneal pouch known as the tunica vaginalis. The cremasteric muscle has the role of retracting the testis when surrounding temperature is low and relax when warm.

Spermatic Cord • Spermatic cord contains 1. Testicular artery (from the aorta) artery to the vas deferens (from the inferior vesical artery. (cremasteric artery) from the inferior epigastric artery. 2. The pampiniform plexus of veins 3. Lymph channels from testis and vas to the para-aortic nodes 4. Vase deferens 5. Sympathtic nerves from T10, genital branch of genitor femoral nerve and lying on not within the ilionguinal nerve • Oval shaped testes has complicated tubular structure and is covered with a tough fibrous coat the tunica albuginea.

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The epididyimis normally lies posteriorly and there is a serosal covering, the tunica vaginalis, within the second scrotal sac with a parietal layer deep to the skin and a visceral layer on the testis itself. Vas deferens approx 45cm long is a muscular tube, which at the deep inguinal ring descends lateral to the inferior epigastric vessels just deep to the peritoneum o nth lateral pelvic wall. It crosses the superficial external iliac vessels. The obutrator vessels and nerve and the vesical branches of the internal iliac artery before turning medially at the ischial spine. Running medially and inferior to the bladder it dilates forming the ampulla of the vas just prior to gaining acess to the posterior aspect of the prostate. Finally it is joined by a duct from the seminal vesicle to form the ejaculatory duct, which passes through the superior aspect of the posterior lobe of the prostategland. The seminal vesicle is a coiled blind sad lying posterior to the prostat, one on each side lateral to the ampulla of the vas. Each vesicle lies with pelvic fascia. The vesicle is designed to produce a secretion of rich in fructose to assist the nutrition of the sperm following ejaculation. Blood supply is from surrounding vesical vessels with autonomic innervations (sympathetic) via the pelvic (hypogastric) plexus, providing the necessary motor stimulus to propel spunk from the ejaculatory ducts.

Female genital tract • Ovary, fallopian tubes and the uterus lie in the bony pelvic cavity with the vag passing through the pelvic floor into the perineum between urethra anteriorly and the rectum/anal canal posteriorly. • Uterus is pear shaped muscular with criss cross of layers of smooth muscle fibers. Composed of body, capped superiorly by fundus and inferiorly by a narrow cervix. The cervix which projects into the vag has few muscle fibres and consists of mostly connective tissue and collagen. • Body of uterus normally angled anteriorly on the cervix and is anteflexed. • If uterus angled porsteriorly it is retroflexed leading to painful shagging. • At fundus of uterus the uterine fallopian tubes project laterally. • Lateral to uterus the peritoneum rises from the pelvic floor to cover both the uterus and the uterine tubes so forming the broad ligament which divides the rectovesical space into two spaces, the rectouterine posteriorly and uteroveiscal pouch aneteriorly. • Uterine wall has 3 layers. Each uterine tube lies within the medial 2/3 rds of the broad ligament. • Opening into the superolateral aspect of the uterine cavity the uterine part lies within uterine wall. • Lateral to the urehtrus the uterine tube narrows forming the isthmus, which dilates to form ampulla, which turns posteriorly to form the funnel shaped infundibulum. • Passing from infundibulum are the finger like fimbira, which wrap around the ovary attached to the posterior surface of the broad ligament. • Blood supply is via uterine artery from the internal iliac artery.

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In the pelvic floor deep to the peritoneum but superior to levator ani there thickenings of the connective tissue, the uterine ligaments.

External Genitalia • Develop in same way for both sexes up to end of seventh week when male and female features appear when proliferating mesenchyme produces a small raised area the genital tubercle anterior to cloacal membrane • Lateral to cloacal membrane labioscrotal swellings and urogenital folds develop and genitl tubercle becomes the phallus. • With formation of the urogenital sinus the cloacal membrane becomes known as urogenital membrane lying inthe urogenital groove. The urogential membrane then ruptures leaving a urogenital orifice. • Female Urethra and vag open into common cavity, the vestibule, which lies deeper in urogential orifice. • Oestrogen causes phallus to develop into clitoris and urogenital folds remain unfused, forming labia minora. The larger lateral labioscrotal folds fuse at the anterior to form the anterior labial commisure and mons pubis whilste unfused develop into the labia majora. • Male Testosterone from testes causes the phallus to elongate becoming the penis. The labioscrotal folds fuse to form the scrotum with the line of fusion the scrotal raphe. • Urethral groove located on undersurface of the penis. Urogenital folds form lateral wall. • Groove is lined with proliferation of endodermal cells forming urethral plate. • Fusion of the urogenital folds along the undersurface of the penis forms the spongy urethra and overlying ectoderm ruses forming the penile raphe, enclosing the urethra. • An ectodermal ingrowth develops at the tip of the glans of the penis forming a cellular ecotdoerm cord which canalises the joining the spongy urethra within the penis and creates an external urethral orifice. • Further proliferation produces the foreskin which remains adherent to the glans.

Cardiovascular system • •

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Arteries Anterior to sacroiliac joint on each side the internal iliac artery lies deep and slightly posterior to the ureter as it descends into pelvic cavity. The internal iliac then divides providing branches to pelvic viscera. 1. Middle and inferior rectal arteries to the rectum, anteriorly the vesical artery to the bladder. 2. Vesical artery to the bladder 3. In the female the uterine and vaginal arteries and in the male the prostatic arteries which are branches of the inferior vesical and middle rectal arteries. Key aspect is the arteries lie on the lateral aspect of the pelvic walls just deep to peritoneum yet superficial to obutrator internus laterally and the pelvic floor inferiorly. Inferior rectal artery a branch of the pudendal artery, supplies the lower third of the anal canal and anastomoses withthe superior rectal artery to supply the rectum and upper two thirds of the anal canal. In the female there is an anastomosis between the ovarian artery and the uterine artery along the superior aspect of the broad ligament superiorly. Inferiorly the uterine artery forms an anastamosis with the vaginal arteries from the internal iliac artery along the vaginal wall. Three branches from the internal iliac artery pass into the lower limb poseriorly the superior and inferior gluteal arteries passing through the greater sciatic notch and anterriorly the obturator artery passing through the obturator foramen inferior to the superior pubic ramus. Venus drainage of structures is by veins corresponding to the relevant artery to the internal iliac vain alongside the internal iliac artery. Key exceptions are 1. The rectum and upper two thirds of the anal canal draining into the portal vein and hence the liver before passing into inferior vena cava. 2. The left gonad to the left renal vein and the right gonad to the inferior vena cava. 3. Skin in the superficial perineal pouch to the femoral vein. Veins on the external surface of rectum drain to the internal iliac vein and communicate with with the inferior vesical veins. Important to note that veins draining to prostatic gland in the mal communicate with the veins in the spine, providing mechanism for vascular spread or prostatic tumours to vertebral bodies.

Lymphatics • Lymphatic drainage of the pelvic structures is initially to the internal iliac lymph nodes following the vascular supply and hence to common iliac and para aortic nodes. The perinueum drains to the internal iliac nodes except for: 1. The superficial structures within the superficial perineal pouch where the skin drains to the superficial inguinal lymph nodes, then to the deep inguinal nodes before passing to the external iliac nodes 2. The testis which drains directly to the para-aortic nodes 3. The lower third of the vagina to the inguinal group of nodes 4. The fallopian tube to either the internal iliac of the para aortic nodes. Peripheral nerves • The ventral rami from the fourth lumbar nerve to the 4th sacral nerve form the sacral plexus on each side located anterior to the sacrum on the surface of the piriformis.

• • • • •

• •

From the two plexi there are branches distributed within the pelvis to the pelvic wall muscles and branches pass through the greater sciatic notch to innervate structures within the perineum and the lower limb. The pelvic para sympathetic outflow leaves the spinal canal accompanying the ventral rami of the 2nd and 4th sacral nerves and passed through the sacral plexus to synapse within the hypogastric and pelvic plexi. All branches of sacral plexus leave through the greater sciatic notch. The pudendal nerve leaves the pelvis inferior to the piriformis and is the key nerve supplying structures within the perineum. It leaves the pelvis inferior to pirifformis and is the key nerve supplying structures within the perineum. It leaves the pelvis through the greater sciatic notch. The inferior rectal nerve bracnhc passes through the ischiorectal fossa from lateral to medial to supply the external anal sphincter providing voluntary control of anal continence. The pudendal nerve passes into the deep perineal pouch providing branches to the penis/ clitoris, external urethral sphincter (providing voluntary control of micturation) and to structures and skin of the superficial perineal pouch. Pudendal nerve provides a motor input to the sphincters and muscles of the perineum. Lower half of anal canal, skin covering the glans penis/clitoris. Skin on anterior third scrotum is supplied by the ilioinguinal and gastrofemoral nerves.

Autonomic Nerves • Pelvic autonomic nerves supplying pelvic structures are distributed through two pelvis, the hypogastric plexus and the pelvic plexi. The hypogastric plexus lies just inferior to the bifurcation of the aorta while the two pelvic plexi lie lateral to the rectum and anterior to the sacrum. • Input from sympathetic via sympathetic chain and parasympathetic outflow (sacral nerves 2,3, and 4) to both plexi. These autonomic branches are distributed to the pelvic viscera and to the colong from the splenic flexure to the anal canal. • Parasympathetic fibres in pelvis facilitate emptying of the visceral contents whilst those that lies lateral on pelvic walls pass anteriorly to supply the erectile tissue and are both involved in dilation within erectile tissue of both sexes. Internal bladder sphincter Anal sphincter

Erectile tissue Prostate Vas deferens Seminal vesicles Uterus

Sympathetic Inhibits muscle wall Motor to internal sphincter i.e. relaxes wall and closes internal sphincter allowing bladder to fill, also sensory to the bladder Post ejaculation facilitates emptying Stimulate smooth muscle fibres during ejaculation Motor for ejaculaton Motor for ejaculation (T12 andL1) Contraction of muscle, vasoconstriction

Parasympathetic Motor to muscle wall Inihbits internal sphincter, i.e. opens the internal sphincter and contracts wall to pass urine also sensory to the bladder Empties rectum/anal canal, reflexes and anal sphincters Glandular secretion Glandular secretion Vasodilation

Faecal Continence • Is produced through the action of the internal and external sphincters. The former is composed of smooth muscle (involuntary control) whilst the latter is skeletal muscle and

• •

therefore under voluntary control. The internal sphincter has deep fibres around the middle third which blend with the fibres of the levator ani, while the sphincter has superficial fibres attaching anteriorly to the perineal body and the anococcygeal body posteriorly. Sympathetic nerves cause contraction of the internal sphincter, while parasympathetic fibres from the hypogastric plexus cause the rectum to empty. The inferior rectal nerve, a branch of the pudendal nerve from the sacral plexus, supplies the external sphincter providing voluntary continence.

Urinary Continence • Micturation is an autonomic reflex under voluntary control. The bladder fills and gives the urge to micturate. It is controlled in the cerebellum. It influences the (Pontine Micturition Centre) which in turn controls the sacral micturition centre (SMC). • Normally bladder relaxes and fills with urine and the sphincter tone increases to prevent leakage. • During micturition perineal muscles and the external urethral sphincter relax. • The detrusor muscle contracts, (parasympathetic activity) • Urine flows out of the bladder. • Bladder distenstion stimulates bladder stretch receptors which stimulate afferent limb of voiding reflex and parasympathetic fibres of the bladder. • Higher stimulation of the pudendal nerve keeps the sphincter closed until its appropriate to urinate.

Micturition Reflex • As bladder fills many superimposed micuturition contractions appear as dashed spikes which are result of stretch reflex. • Sensory signals are sent from the bladder stretch reflexes are conducted to the sacral plexus then reflex back to the the bladder through parasympathetic nerves. • When bladder only partially full these contractions stop quickly Detrusor muscles stop contracting. As bladder fills contractions Are more frequent and cause greater contractions. • Once reflex begins it is self renegnerative and the cycle is repeated Again and again until bladder has strong degree of contraction. • After few seconds to minute the self regenerative reflex fatigues Permitting the bladder to relax. • So reflex is complete cycle of 1 progressive and rapid increase in pressure 2 period of sustained pressure 3 return of the pressure to basal tone of the bladder. If there has not been successful emptying of the bladder the nervous elements remain inhibited state for few minutes or an hour. Before starting again. Fuller the bladder the more powerful the reflex. • Once the micturition has become powerful enough it causes another reflex which pass through the pudendal nerves to the external sphincter to inhibit it. If this inhibition is more potent in the brain than the voluntrary constrictor signals to the external sphincter urination will occur. • Voluntary urination initiated by person voluntarily contracts abdominal muscles, increase pressure in the bladder, allows extra urine to enter the bladder neck and posterior urethra under pressure thus stretching their walls. This stimulates stretch reflex and simulataneoulsy inhbits the external urethral sphincter. Ordrinarily all urine is emptied with rarely more than 5-10 milliltres left. Abnormalities of Micturation • Atonic bladder caused by destruction of sensory nerve fibers. Micturition reflex cannot occure if the sensory fibres from the bladder to the spinal cord are destroyed this prevents stretch signals from bladder. Person loses bladder control. Instead of empyting periodically bladder fills to capacity and overflows a few drops at a time = Overflow incontinence. Causes include crush injury syphilis. • Automatic bladder If the spinal cord is damaged above sacral region but sacral region still intact typical micturation reflexes can still occur. Initirall reflexes are suppressed due to “bladder shock” from sudden loss of impulse from brain and cerebrum. If bladder emptied with catherisation to prevent over stretching of bladder the micturation reflex returns and grad increases then periodic bladder emptying occurs. • Uninhibited Neurogenic Bladder caused by lack of inhibitory signals from the brain. Frequent and uncontrolled micuration as result of partial damage to spinal cord which interrupts inhibitory signals. Facilitative impulses pass down all the time so the bladder keeps emptying whatever the level of urine. Neuropathic Bladder Disorders

• •

Epidemiology It may arise as a result of many clinical entities, the epidemiology is reflected by the underlying disorder. Pathology Neuropathic disorders of the bladder can arise entirely or as part of underlying disorder. Detailed clinical assessment is needed to locate site of structural lesion.

Location

Site of lesion

Causes

Celebrum

Above the pontine micturition centre Above sacral micturiation centre

CVA Dementia Parkinsons Spinal cord trauma Meningomyelocel e MS

Spinal cord

Clinical features Disrupted social awareness

Initially detrosur hyperreflexia then detrusor sphincter dyssnergia Spinal cord At or below sacral Areflexic micturition centre incompetent bladder Peripheral Distal to the Diabetes Areflexic bladder nerves spinal cord prolapsed disc with or without incompetence • Clinical Features Neuropathic disorders of the bladder can arise entirely or as part of the underlying disorder. A detailed clinical assessment is required to locate the site of any structural lesion, as voiding symptoms vary according to location of the lesion. And range fromm disrupted social awareness of voiding to a complete atonic bladder and incompetent sphincter. • Investigations Urea and electrolytes, urinanalysis which due to proneness to infection. Abdominal ultrasound. Pressure flow urodynamics. • Management Permanent indwelling catheter, keeps their bladder pressure at 0. Intermittent self catherisation for people who have good hand function. Transurethral sphincterotomy. Bladder augmentation. Which bivalves the bladder and uses a patch of bowel to cover the defect. • Prognosis Patients with neuropathic bladder secondary to spinal cord injury most commonly succumb either to obstructive renal failure or pneumonia. Urinary incontinence • Epidemiology The incidence of incontinence increases with age it affects up to 30% of the elderly community and 50% of those institutionalised. • Stress incontinence Loss of urine associated with raised intra abdominal pressure such as coughing or sneezing and laughing. Suggesting weakness in the pelvic floor musculature or sphincter weakness. Follows childbirth in women and neurological origin or prostatic or urethral surgery in men. • Pathology Incontinence may occur in several pathophysiological circumstances often the picture is mixed • Urgency Incontinence involuntarily loss of continence associated with extreme urgency. (detrusor overactivity)

• •

•

•

Continuous Is the involuntary loss of urine regardless of urgency or raised intra abdominal pressure. Could be complete sphincter deficiency. Overflow incontinence Occurs in men with chronic urinary retention. Bladder remains full and continence is maintained by virtue of the urethral resting pressure exceeding the bladder pressure. When bladder is overstretched an unstable contraction may occur overcoming the urethral pressure and the patient leaks. The leakage may occur at day or night (nocturnal enuresis) and a painless full bladder maybe palpable. Investigations Urinanalyiss dipstick urine for infection Frequency volume chart patient measures the volume of urine produced and the frequency, pad test pad is placed in underwear and weighed before and after exercise. Ultrasound, IVU, Cystoscopy, VCMG. Management Outflow obstruction =Transurethral resection of the prostat. Fistula with fistula repair. 1. Stress Incontinence = Pelvic floor exercises, Serotonin nor adrenaline reuptake inhibitors (duloxetine). Surgery is aimed at elevating the bladder to its intrabdominal location by suspending the bladder neck e.g. colosuspension, or providing urethral support. Urethral bulking agents. 2. Urge incontinence = Bladder retraining regimes. Patients are instructed to resist the urge to void and increase intervals between voiding. Voiding by the clock helps this giving patients target time to hold urine. 3. Anicholinergic medication = (e.g. oxybutinin and tolterodine) 4. Surgery for those who have extreme symptoms. Cysto distension, urinary diversion via and ileal loop may be appropriate. Or catheters for those who are no suited for surgery or do not wish to have it.

Female pelvis • For childbirth the female pelvis has to compromise mechanical efficiency concerning locomotion and safety in the passage of a baby through a bony ring. • In male pelvis the blade of the ilium is nearly vertical, giving a deep sided false pelvis whilst the sides of the true pelvis curve inwards creating a narrow pelvic outlet. • Female pelvic the blade of the ilium is flatter giving shallow false pelvic and sides of the true bony pelvis are more vertical opening the pelvic outlet. Female pelvis is to allow safe passage of fetus. 1. Lenghtening of superior pubic ramus 2. Opening of the subpubic angle 3. Ischial spines more vertical 4. Opening greater sciatic notch by increasing angulation between ischium and iliac articular surface. 5. Ala of the sacrum are longer Ilium articulating with fewer sacral vertebrae 2 and a half rather than 3.

Differential Diagnosis of Optic Atrophy

• • • •

Optic atrophy is a term used to describe and optic nerve which has lost substance, seen as a pale disc. Optic nerve once damaged cannot be regenerated. Atrophy can be unilateral or bilateral. Bilateral tends to be genetic. Symptoms are reduction of all parameters of visual function It may indicate chronic intracranial pathology or intraocular disease.

Clinical Features in Differential 1. Features of optic nerve dysfunction • Papilloedema is a swollen optic nerve head due to increased intracranial pressure associated with late loss of vision rather than acute. And has earlier transient blurring instead. • Altiduinal loss = Ischemia of the optic nerve head. • Arcuate scotoma= Glaucoma • Bitemporal Hemianopia = caused by chiasmal disease • Homonymous hemianopia= optic tract disease. 2. Underlying disease • Systemic hypertension, ischaemia (atherosclerosis, giant cell arteritis, diabetes), raised intracranial pressure, thyroid disease. Drugs related with benign intracranial hypertension such as ethambuanol. Optic atrophy due to alcoholism. Intraocular inflammation may lead to optic atrophy. 3. Associated findings

•

Raised intracranial pressure may cause sixth nerve palsy. This is a non localising sign. Proptosis indicates orbital disease. Flame haemorrhages = retinal vein occlusion.

•

Optic neuritis= rapid progressive loss of vision (acuity and colour) with pain on eye movement. Central scotoma and afferent pupil defect. Anterior Ischemic Optic Neuropathy (AION) =sudden onset sight loss unilateral at first, maybe preceded by transient episodes of vision loss. Afferent pupil defect. Haemorrhage cotton wool spots altiduinal sight loss. 2 Types • Arteritic : Caused by giant cell arteritis, Scalp tenderness, inflamm of arteries, jaw claudication, ESR and CRP. • Non Arteritic: No sign of inflammation and associated with athereo sclerosis, hypertension, smoking and diabtes mellitus

•

•

Psuedopapilloedema Swollen optic disc hypermetropia is the most common cause. Optic nerve drusen (hyaline bodies) is included.

•

Investigations Neuroimaging, Fluoroscein, Angiography, can help to distinguish true disc swelling from pseudopapilloedema and an ultrasound scan will demonstrate optic nerve drusen. Visual evoked response are used in assessment of patients with demyelination

Multiple Sclerosis MS epidemiology: • Occurs worldwide but is far more common in temporate climates. The prevalence increases in proportion to distance from the equator. This applies in northern and southern hemispheres. • In England at between 50 and 60 degrees latitiude, the prevalence is 60100/100 000. • 15/100 000 at the equator. Move from high to low prevalence prior puberty, the risk of developing disease takes on low prevalence area. If move after puberty risk of high prevalence is retained. • Occurs in young adults, the peak age of onset being between 20 and 30 years. F>M

Pathogenesis: • Suggestion of cytokines playing a critical role, in pathophysiology by regulating aberrant autoimmune responses and by mediating myelin damage. Genetic Factors • Increased familial incidence of MS with a relative of an affected individual having 20 increase risk of getting disease. Positive association with HLAA3, B7, B18, DR2 and DW2. Infection • Immune response suggests viral infection. Pathology • Areas of demyelination are found in the white matter of the brain and the spinal cord called plaques. The lesions lie in close relationship to postcapillary venules (perivenular) • Periventricular region of the cerebral hemispheres. • Corpus collosum • Brainstem and its cerebellar connections (medial longitudinal fasicululus). • Cervical cord • Optic nerves • Myelin destruction with preservation of the axons. Inflammatory infiltrate containing mononuclear cells and lymphocytes is found. Insterstitial oedema occurs in acute lesions. Remyelination is rare and the mechanism of functional recovery is uncertain. Clinical Features • Relapsing and remitting: with lesions occurring in different parts of the CNS at different times. This makes up 90% of cases initially. • Secondary progressive: when the disease starts with relapsing and remitting picture but eventually recovery from each successive relapse becomes less complete, causing residual progressive disability. Over half the patients presenting with relapsing remitting disease develop secondary progressive. • Primary progressive: In which there is little or no recovery from relapses, with a cumulative disability from the onset. Only 10% of patients with this form of disease. • 15 years after onset of symptoms, 30% of patients are still working and 40% still walking. Common Presentations • Optic Neuritis presents as sub acute visual loss, usually unilateral, with central scotoma and pain on ocular movement. Recovery is over few weeks. Lesion can be on optic nerve head (papillitis) or in the optic nerve behind the eye (retrobulbar neuritis). In the former , a pink swollen disc is seen, whereas in the latter the disc looks normal. • Following a attack, optic atrophy (pale disc) often develops. Optice neuritis maybe an isolated event it may occur simultaneously with a transverse myeltitis (Devic’s syndrome) or maybe be a for runner for MS as in 70% of cases!. • Brainstem Diplopia often due to internuclear opthalmaplegia, Nystagmus, Vertigo, Dysarthria, facial numbness + trigeminal nerve neuralgia as it affects the exiting fifth nerve and nucleus, dysphagia, ataxia, pyramidal signs, effort related fatigue.

•

Spinal cord lesions (myelopathy) Leadind to spastic paraparesis (thoracic cord) tetraparesis (cervical cord). Bladder symptoms common. Lhermittes symptom indicative of lesions within the spinal cord. • Symptoms and signs worse with heat (uthoffs phenomenon). • Differential diagnosis Bechets disease, CNS sarcoidosis, SLE, Optic neuritis= brainstem lesions and myelopathy. Investigations • MRI: Hyperintense lesions are seen on the T2 weighted images. Lesions enhanced with contrast. Does not distinguish between new and old lesions. • CSF: Lymphocyte pleocytosis maybe during relapses. Protein might be slightly elevated. Presence of oligoclonal bands “intense bands of staining for IgG on western blotting) in the CSF but not in serum is highly suggestive of MS. • Visual Evoked Potentials (VEPs) If demylination of optic nerve the conduction of visual images is delayed. Normal response takes 100 milliseconds. • Somatosensory evoked potentials (SSEPS) May detect delay in central pathways. • Brainstem auditory potentials (BAEPs) Measurements of BAEPS during auditory testing may detect brainstem lesions. Management Treatments for disease process • Anti-inflammatory treatment Steroid therapy, usually given IV as the methylprednisolone (high dose for 3 days) is the mainstay treatment used for severe acute relapses. May shorten relapses but does not effect outcome. • Interferon- B1a and 1b and glatiramer acetate are currently being used in selected patients those in relapsing and remitting disease. Patient must have 2 significant relapses within the past 2 years to qualify for treatment. Relapse rate is reduced by 30%. NICE says they are not cost effective when cost compared to QALY but still prescribed to individuals who benefit. Symptomatic Treatment Spasticity • Baclofen, dantrolene, diazepam, and tizandidine can be helpful. Do not reduce tone too much as some patients require increased tone to walk. • Bladders Dysfunction Oxybutinine, tolterodine), Intermittent self catheterisation or permanent urinary catheter maybe required. Intravesicel capsaicin also been known to help. Prevention and early treatment of UTIs is important because neuro signs plus symptoms can worsen with intercurrent infection. • Paroxysmal Spasms Some patients develop muscle spasms which maybe helped by carbamazepine or phenytoin. • Intention Tremor Clonazepam Other Demyelinating Diseases • Acute dissmeminated encephalomyelitis-ADEM: A central form of Guillan Barre syndrome presents following viral illnesses or vaccination. Progressive multifocal leuconcephalopathy (PML) caused by JC papovavirus infection, especially in HIV patients. Leucodystrophies Metachromatic leucodystrophy (disorder of arylsulphatase A enzyme) adrenoleucodystrophy (accumulation of very long fatty acids-VLCFAs)

SSPE Sub Acute sclerosing panencephalitis) this is a rare and delayed complication of measles virus infection. Vitamin B12 deficiency:- causes central demyelination. Central pontine myelinolysis (CPM) This is associated with too rapid a correction of sodium, in patients who are hyponatraemic and often have history of alcohol abuse.

Differential Diagnosis of Sensory loss – Lesions of the peripheral nerves – Mononeuropathy – • Sensory impairment of all modalities in the anatomical distribution • NB if is a mixed nerve will have accompanied weakness • Causes – trauma, surgery, prolonged compression e.g. carpal tunnel Multiple mononeuropathy – • Instead of one nerve affected, a number affected often different in geography • Sensory impairement of all modalities of the anatomical distribution • NB if is a mixed nerce will have accopmpanied weakness • Cause – Diabetes, Sarcoidosis, Vasculitis, leprosy, amyloidosis etc systemic disease Polyneuropathy – • Symmetrical impairment of all sensory modalities • Usually starts distally affecting hands and feet – glove and stocking • Reflexes diminished or lost , +/- muscle weakness • Causes – diabetes, alcohol abuse, b12 def, paraproteinaemia, drugs and heavy metals

Lesions of the Spinal cordTransection of the cord – • Bilateral impairment of all sensory modalities below that transaction (dermatonal Pattern) • Initially flaccid progessing to spastic paraplegia/tetraplegia • Cause – trauma ~ RTA, sports injury, Stabbing etc Lesions of the posterior spinal cord • Dorsal columns affected, spinothalamic and corticospinal spared • Bilaterally - Light touch, two point discrimination, vibration and proprioception affected • Motor, pain, temperature all spared unless lesion progresses • RARE – cause~ MS, spondylosis, prolapse disc Lesions of the Anterior cord • Spinothalamic and corticospinal tracts affected dorsal column spared • Bilateral impairment of pain temperature • Spastic para/tetraplegia below lesion • RARE cause~spinal artery occlusion, trauma, Hemisection of the Cord (brown-Sequard) • Light touch, two point discrimination, vibration below lesion on same side • Perception of pain and temperature below lesion on the opposite side • Cause – trauma, tumour, demyelination

Common causes of Sensory loss/parastheia – • Diabetes mellitus o Covered in more detail in another scenario • Syringomyelia o Rare- Progressive expansion of a fluid cavity in the spinal cord – o Causes: obstruction CSF flow caused by tumour or trauma o Presents as a central cervical cord lesion with slow progression can give cranial signs due to pressure o Treatment – drainage, decompression of the spinal cord, shunt insertion • Anterior spinal artery thrombosis o Clot blocks artery causing bilateral disruption of the corticospinal tract, causing motor deficits, and bilateral disruption of the spinothalamic tract • Subacute combined degeneration o Degeneration of the posterior and dorsal columns o Caused by patchy loss of myelin o Results in from b12 deficiency o Treated by b12 – full recovery • Multiple sclerosis o Covered else where • Alcoholic neuropathy o Most common neuropathy (30%), o slowly progressing starting distally with pain and parasthesiae o caused by alcohol as a toxin but alos associated vitamin deficiency o treatment cessation of alcohol thiamine therapy o tricyclics eg amitriptline for the pain •

Guillan-Barre syndrome o T Occurs 1-3 weeks post another infection o Present distal parasthesia and weakness with sensory loss moving proximally o Clincial diagnosisis aided by nerve conduction and CSF proteins o IV Immunoglobulins gold standard + management of paralysis o Recovery is gradual sometimes incomplete

Hereditary Causes • Fredricks ataxia o Autosomal dominant – GAA trinucleotide repeat o Progressive degeneration of the posterior column, corticospinal, dorsal and spinocerebellar tracts o Ataxia, dysarthria, neuropathy, pryamidal signs, pes cavus scoliosis cardiomyopathy, optic atrophy and diabetes all associated o Treatment is symptomatic – cardiac monitoring, pes cavus scoliosis etc •

Hereditary motor Sensory neuropathy (HMSN) or Charcot Marie tooth disease o Distal wasting of the limnbs slowly progressing, absent reflexes with sensory loss o Pes cavus and claw toe common, age of onset variable from 0 -50 o CMT 1 (commonest form) 5-15 onset, demyelinating neuropathy, onion bulb formation on micrsocopy o CMT II axonal neuroplasty 10 – 20 yrs onset o CMT III demyelination with gross hypertrophy and a raised CSF protein

Various other complex forms exist that have additional features eg optic atrophy, deafness and spastic paraperesis. Porphyria o A group of disorders characterized by overproduction of porphryins o Autosomal dominant manifesting as acute intermittent porphyria o Present like guillan barre diagnosed by urine screening fir porphobilinigen levels o Management is supportive, high carbohydrate diet, pain relief haematin infusion. o

•

Common peripheral neuropathy’s Nerve Median Nerve (Carpal Tunnel Syndrome)

Site of compression Carpal Tunnel in the wrist

Ulnar Nerve

Cubital tunnel at the elbow

Radial Nerve

Spiral groove of humerus

Common Peroneal Nerve

Neck of fibula

Aetiology

Presentation

Treatment

Often idiopathic, but sometimes seen in: 1) Hypothyroidism 2) DM 3) Pregnancy & obesity 4) Rheumatoid arthritis 5) Acromegaly 6) Amyloid 7) Renal dialysis patients 8) Trauma Follows ulnar fractures or prolonged / recurrent pressure.

Nocturnal tingling and pain in the hand (+/or forearm) followed by weakness of thenar muscles. Wasting of adbuctor pollicis and radial 3½ fingers. Tinnels and Phalen’s sign seen.

Wrist splint at night or a local steroid injection in the wrist. In pregnancy it is self limiting. Surgical decompression of the carpal tunnel is the definitative treatment.

Clawing of the hand due to wasting of ulnar innervated muscles develops (hypothenar muscles, interossei and medial 2 lumbricals) with sensory loss of the ulnar and 1 ½ fingers. Wrist drop and weakness of brachioradialis and finger extension follow.

Decompression and transposition of the nerve at the elbow may be necessary

Usually occurs during deep sleep or unconsciousness e.g. after an alcoholic binge (‘Saturday night palsy”) This can be injured by external pressure (coma, plaster, casts, carpet laying, leg crossing), trauma and entrapment

Foot drop and weakness of ankle eversion. A patch of numbness on the anteriolateral border of the shin or dorsum of the foot develops.

Most patients improve spontaneously. A lively splint is helpful in improving hand function during recovery. Depends on aetiology. A foot drop splint helps function.

in the fibular tunnel. Radiculopathy • Common frequent sites - lumbar spine and cervical spine • Common causeso TProlapse of disc o Spondylosis o Spinal Stenosis o Spondylolisthesis • Presents as pain radiating along affecged nerve root, weakness and reflex changes sensory loss Weak biceps/deltoid – weak elbow flexion and arm abduction + numbness over shoulders and down arm Weak supination of wrist and diminished supinator reflex + numbness down arm to thumb Weak extension of arm + numbness to middle and index fingers Weak finger flexion + numbness over ulnar border of hand Weakness of fine finger movements, Horner’s syndrome + numbness on inner arm Weak knee extension and hip adduction + Foot drop Foot drop •

C5 C6 C7 C8 T1 L3 L4 L5

Diagnosed based on history confirmed by radiography, MRI or CT

Red flags to consider - Infection or malignancy more likely: • Age - new back pain with patient over 50 years, or age under 20 years • Previous history of cancer (e.g. possible metastases) • Systemic (constitutional) symptoms, e.g. fever, chills, unexplained weight loss • Recent bacterial infection (e.g. urinary tract infection) • Intravenous drug abuse • Immunosuppressed patient • Pain that worsens when supine; severe night-time pain; thoracic pain IF infection or malignancy suspected – bloods, 2 week wait? Cauda equina• Compression of the cauda equina (below L2) • Causes: any lesion which compresses the spinal cord e.g infection, tumour, epidural haematoma or abscess • Symptoms: • Urinary and faecal incontinence (loss of sphincter tone and perianal sensation) • Saddle anaesthesia • Bilateral sciatica • Lower motor neurone weakness • Progressive motor weakness or gait disturbance • Treatment - surgical decompression within 48h to prevent neurological damage Neurology investigations – Bloods

TEST

Abnormality

Indicates

hb

Low – anaemia

MCV Neutrophils Lymphocytes ESR APT VIT b12 Folate Sodium Potassium Urea Creatinine glucose calcium LFTS Thyroid function

High - polycthaemia High Macrocyti High – neutrophilia Low – neutropenia high high high low low High/low High/low High (renal failure) High (renal failure) High Low high Deranged (alcohol disease) High Low

ANA dsDNA Rhuematoid factor Anti GM1 antibodies Cultures – blood or csf Viral serology VDRL (blood) Borrelia serology

Non specific neuro symptoms – fainting dizzy etc (chronic illness???) Predisposition to stroke and to chorea VIT B12 deficency (peripheral neuropathy, dementia) Meningitis or other infection Leukaemia, lymphoma Viral infection (transverse myelitis, Guillan Barre syndrome) Active inflammation – vasculitis , SLE SLE– fits confusion neuropathy Peripheral neuropathy, optic neuropathy Peripheral neuropathy, optic neuropathy Fits, weakness, confusion Paralysis Neuropathy confusion Neuropathy confusion Neuropathy seizures Confusion, coma, focal signs Tetany , seizures Neuropathy, confusion tremor Tremor confusion hyper relexia SLE – fits confusion neuropathy Sjorgens syndrome neuropathies SLE– fits confusion neuropathy Cervical spine subluxation, vasculitis, neuropathies Guillan Barre syndrome Septicaemia, meningitis, Guillan barre syndrome, vertrebral abscess etc Meningitis, encephalitis, shingles Primary syphilis ( false postives in SLE malaria) Lyme disease

EEG •

• • •

EEG measures the potentials generated by neurons and then compares to either a reference electrode or a neighbouring electrode trace should be symmetrical asymmetry is indicative underlying disorder Produces a trace like a ECG Used in Epilepsy, coma, encephalitis CJD. Can either support a diagnois, classify a seizure type, assess fro surgical intervention Invasive EEG is prolongedmonitoring from embedded electrodes prior to DBS for epilepsy

EMG (electromyography) and NCS (nerve conduction studies) • EMG is a needle inserted into the muscle and at rest it is silent but in abnormal muscle or denervation there is spontaneous activity at rest • NCS Two electrodes are placed on the body and one end is stimulated the other records the activity test the patency of the nerve, reduction in conduction in conduction velocity suggest demyelination, reduction in amplitude is suggestive of axonal loss • Are usually performed together and analyse the electrical activity and conduction of neuromuscular junction and lower motor neurones differentiates axonl and myelin loss • Determines cause of weakness, distribution of an abnormality, suggest type of myopathy, assessing baslines prior to surgeries e.g carpal tunnel, measure response to medical therapies

Evoked potentials (eps) • Electrodes are used to record responses centrally to periperhal stimuli Imaging of the nervous system All common modalities are used to image the nervous system – X-ray, CT, MRI, all with usual benefits and drawbacks

Lumbar puncture – • Insetion of a needle between the lumbar spinous process (L4,L5 to avoid cord entering the cauda) • Pressure is normally measured normal range is 50 – 180mm • CSF should be clear and colourless

• •

Test carried out include – biochemistry looking for proteins and oligoclonal bands, microbiology looking for PCR for TB, immunology and cytology Contraindicated in cases of suspected rasied ICP due to risk of coning or herniatio

Findings on Examination Site of lesion

Wasting

Tone

UMN LMN

none present

increased decreased

Neuromuscular Junction

Uncommon

Usually normal may be decreased

Muscle

From mild to severe

Decreased in proportion to wasting

Pattern of weakness Pyramidal pattern Individual or groups of muscle Bilateral and predominantly of proximal limb girdle Bilateral and predominantly of proximal limb girdle

Reflexes increased Decreased/abssent Usually normal

Decreased in proportion to wasting

Spinal Cord Anatomy – • Spinal cord runs from the brain stem to L2 where it becomes the Cauda Equina • It is thicker at the top and narrows toward the bottom as fibre leave it • Thirty one pairs of nerves are attached to the cord (anterior and posterior nerve roots • A section through the cord shows a butterfly shaped grey matter with 3 funiculi (anterior, lateral and posterior columns) of white matter • Gray matter has a small central canal • Axons travel in the grey matter • Then longtidinally in the white matter tracts

Plantar response extensor Flexor or absent flexor

Flexor

Pathways responsible for the transmission of sensation Dorsal Column• carries light touch, two point discrimination, vibration, proprioception • fibres ascend laterally and synapse in the gracile and cuneate lower medulla • pt complains of numbness, pins and needles, illusion of swelling, loss proprioception Spinothalamic Tract• carries pain, temperature, itch and tickle sensation • ascend 1-2 segments in Lissauers tract then synapse in dorsal horn carried contralateral in Spinothalamic tract synapse in the thalamus and terminate in the parietal cortex • pt compains of parasthesia, pain, injuries Pathways responsible for the transmission of Motor control Pyramidal tracts • Corticospinal Tract control of voluntary movement. • Fibres arise from the cell bodies in the cerebral cortex. passing through crus cerebri of the midbrain. • At medulla oblongata they form two prominent pyramids on the surface .In the caudal medulla • 75-90% of fibres dessucate and enter the contralateral lateral corticospinal tract in SC. • 10-25% of pyramidal fibres remain ipsilateral and enter the ventral corticospinal tract in sc. Extrapryamidal tracts Rubrospinal tract • Controls the tone of limb flexor • Originates in the midbrain in red nucleus proceeding ventromedially and cross in the ventral tegmental decussation after which they descend down the spinal cord. • Red nucleus receives cereballat input and as such is a non pyramidal control of tone and positon Vestibulospinal Tract • Controls tone of extensor muscles and posture

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Arise form the vestibular nuclei in the pons, medial portion goes ipsilaterally to control head and neck, lateral portion goes ipsilaterally to control trunk postion and posture Reticular spinal tract • Control muscles of the trunk and proximal limbs also functions in breathing • Arise in the pons and medulla terminate in the interneurons of the SC Tectospinal Tract • coordinates head and eye movements. is responsible for motor impulses that arise from one side of the midbrain to muscles on the opposite side of the body. • originates is the superior colliculus, which receives afferents from the visual nuclei. It projects to the contralteral side of the SC Spinocerebellar Tract • Carries info from muscle, tendons and tactile receptors to control posture and movement • Arise peripherally and terminate in the cerebellum • They decussate in enetering the SC and pass contralterally Synapses• Synapse is a junction between a neuron and it’s target cell • Synapses can be classified according to o Mode of transmission;  Electrical  Chemical o Location;  Axodendritic  Dendrodendritic  Axoaxonal  Axosomatic  Endplate/neuromuscular junction o Effects;  Inhibition  Excitation Electrical synapses • plasma membrane of the pre and post-synaptic neurones are closely apposed to form Gapjunctions • Information is transferred between the two neurones by direct current flow • Hence no neurotransmitter is involved • The current is carried across the gap (~2-3nm) via protein channels made of the protein Connexin • Six connexins form half a channel called a Connexon • Electrical synapses can be either reciprocal (both ways) or rectifying (one way) • They are found brain, heart, intestinal smooth muscles, lens cells and hepatocytes

Chemical Synapses• majority of the synapses in the body • membranes of the pre-synaptic and post-synaptic neurones are separated by a narrow synaptic cleft (~20-40nm wide). • Leads synaptic delay hence there are two types of chemical synapses  fast (~0.5ms delay) transmitter synthesised in the button e.g. ACH,  slow (>1ms delay) transmitter sythesised in cell body moved by axonal flow e,g, Vasopressin, oxytocin • The post-synaptic membrane contain many neurotransmitter receptors to ensure uptake • Neurotransmitter’s either destroyed by enzymes or reabsorbed into the pre synaptic neurones • Can have ionotropic(absortption sets off change in potential) or metabotropic (absorption caused a metabolic process) activity Treatment of incontinence – Women medical • lifestyle interventions - reduction in caffeine intake,reduce fluid intake at problem times i.e before bed BMI >30 weight loss • physical & behavioural therapies - pelvic floor exercise, bladder training • drug therapies o oxybutynin is an anticholinergic  Oxybutynin exerts direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle  Side effects - dry mouth, difficulty in micturition, constipation, blurred vision, drowsiness and dizziness o desmopressin is a synthetic replacement for antidiuretic hormone  which reduces urine production during sleep o Side effects - headaches, facial flushing, nausea, hyponatremia • hormone replacement therapy o Vaginal oestrogens for women with vaginal atrophy to rebulk the vagina wall Surgical options• Overactie bladder – scaral nerve stimulation, botulinum injections, augmentationcystoplasty • Stress incontinence – slings, artifical sphincter, rerouting Both – cathethrisation Men medical treatment • incomplete emptying o cholinergic agents - carbachol,bethanecol } been superseded by catheterisation o anticholinesterases distigmine bromide - inhibits the acetylcholine breakdown. It may be useful in the management of patients with an upper motor neurone neurogenic bladder • retention o alpha-blockers e.g. prazosin, indoramin - used to relax smooth muscle in benign prostatic hypertrophy resulting in an increase in urinary flow rate and an improvement in obstructive symptoms • detrusor instability o anticholinergics e.g. oxybutynin hydrochloride, flavoxate hydrochloride - result in increased bladder capacity by diminishing unstable detrusor contractions Men surgical treatment –

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Remove prostate treats BPH TURP Catheterisation o Self – a soft flexible tube is inserted the bladder emptied tube removed o Short term – catheter is temporarily inserted needs chainging depending on model 1-2 weeks o Long term catheter long term changed every 6 weeks o Supra pubic catheter for patients unsuitable for trans urethral version

General treatments – • Make life easier - bed near bathroom, easy access toilet, assess and ensure mobility. • Protective measures – Pads, self catetherisation, SRC cathether(infection risk) • Maintainence – laundry services, home care to change sheets, district nurse UTI • •

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Common infection caused by bacterial infiltration of the Urinary tract system Bacteria most often responsible are e.coli, proteus and enterobater from faeceal contamination Symptoms include – Dysuria,Frequency,Urgency,Cloudy offensive urine,Mild fever,Painful sexual intercourse Penile pain More common in women then in men (anatomy), people with SRC, following cystoscopy, pregnancy, diabetics, elderly dipstick testing - protein, nitrites and leucocytes then a UTI is suspected. MSU will be sent of for analysis and treatment commenced. Common antibiotics used are Trimetophrim 200mg bd po for 3 days (5 in men) Complications include pyleonephritis

Psycho social effects of incontinence – Common psychological effects: • Denial, sadness • Disappointment, shame • Anger, resentment at burden of needs • Stress, fatigue, depression • Low self-esteem - high self esteem allows person to tolerate criticism, rejection, looks of surprise, etc. • Body image • Relationships • Quality of life Stressors: • Uncertainty about the course of their disease • Need to accept and adjust to changes in mobility and function • Frustration – unable to do things they could do before + anger at reliance on others for help • Decreased income – due to time off work etc. • Debt • Having to readjust their life goals and expectations • Difficulties in maintaining social networks/relationships • Stigma associated with; disease, symptoms, consequences of disease e.g. unemployment, smell Particular effects on young adult: • May relationships gf/bf, parents/family • Awareness of being different • Change in how treated by family friends

• May lead to problems with body image, confidence and quality of life • Reserved, withdrawn, non-competitive, or over-achieve to compensate Practical considerations• Smell – almost unavoidabel • Mess – not bad with urinary, bad with faeces • Skin deterioration – urine is erosive of skin dermis • Stigma – there is a social issue of incontinence esp in one so young • Embarrassment – is not nice to be incontinent even for the most confident person • Cost – laundry, clothes, inco products(only basics provided by NHS) Physical Manifestations of psychological problems: • Insomnia/ excessive sleepiness • Increased pain perception (see top right) • Palpitations, tachycardia • Eating a lot/very little • Mood swings • Lethargy • Shortness of breath • Alcohol/drug dependence • Withdrawn behaviour • Impaired immune system – increased chance of and slow healing of infection Coping – why is it needed? • Severe illness presents challenges, e.g. changes in lifestyle, ADL, uncertainty re. future, treatment and hospitalisation. These challenges as well as the illness can act as stressors, and coping is how the patient manages these stressors • Coping strategies can be emotion focused [response modifying] or problem focused. [Action changing, problem solving] They can overlap and be interdependent. o In acute illness – may be good to use emotion focused o In chronic illness – emotion focused may be inappropriate as it may compromise selfmanagement. Problem focused is better – active management • Coping is influenced by;  Nature of incontinence:  Severity  Course: temporary/permanent  Cause: congenital or acquired (stage in life)  Personality traits  Social factors  Relationships – is going to make sex intimacy difficult  Work, hobbies - hard to maintain a working life or play sports  Cultural expectations Coping strategies • Problem solving: direct action, decision making, planning • Support seeking: social support, comfort/help seeking • Escape-avoidance: disengagement, denial, wishful thinking • Distraction: alternative activities • Cognitive restructuring: positive thinking, accommodation • Rumination: -ve thinking, self blame, worry, catastrophising • Helplessness: inaction, passivity, giving up • Social withdrawal: self isolation, concealment, stoicism • Emotional regulation: emotional expression, relaxation

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Information seeking: learning more, observation, monitoring Negotiation: compromising, prioritising, deal making Opposition: anger, blaming others, projection, reactance Delegation: maladaptive help seeking, complaining, self-pity

Beta Interferon Beta interferons There are three beta interferon products: Avonex and Rebif are interferon beta-1a products licensed only for the treatment of RRMS. Betaferon is interferon beta-1b and is licensed for the treatment of both RRMS and SPMS . • The beta interferons work by reducing the inflammatory process that characterises MS. Such inflammation usually precedes an MS relapse. However, the precise mode of action of these disease-modifying agents on immunological mechanisms remains uncertain. • The beta interferons commonly cause temporary influenzalike adverse effects in 50% , as well as injection site reactions and leucopenia. Less commonly, the use of the beta interferons is linked to depression. In addition, these agents, have antigenic effects and therefore may induce the development of antibodies, high titres of which have been observed in some patients. Theoretically, these antibodies may produce allergic reactions or bind to the drug molecule neutralising its effects. The significance of these antibodies on the effectiveness of the beta interferons is uncertain, as such effects have not been reported in clinical practice. • An estimated 1,750 people are currently prescribed beta interferons, which equates to 2.8%of all MS patients, or 3.3% of those with RRMS or SPMS. These percentages vary between health authorities. 3.6 The current annual cost per patient of the beta interferons in the UK is £7,259 (Betaferon), £9,061 (Avonex) or £9,088/£12,068 (lower dose/higher dose Rebif • The cost per patient of glatiramer acetate is £6,650 per year. • During 2000, NICE considered several models of the costeffectiveness of beta interferon and glatiramer acetate. There were problems with these models and so the Institute decided to commission a new model.After considering all of the evidence, including the views and experiences of patients, NICE has issued the following advice to theNHS in England and Wales. A recommendation to use these medicines cannot, presently,be justified, taking both benefits and costs into account.. Chronic illness and physical disability is disruptive of a person’s: • Social roles and relationships (including their occupational roles) • Self and identity • Daily routines and activities (including their leisure/ recreational activities) • Life plans or plans for the future • Biography (i.e. how they make sense of their changed ‘life story’) • Cause depression, social isolation, anxiety. Financial Support for Those Who Are Chronically, Seriously or Terminally Ill Diagnosis with a potentially fatal disease may have a severe economic impact on some individuals and families. Individuals are entitled to Disability Living Allowance which is fast tracked for the terminally ill. • Disability Living Allowance= <65 and need help with personal care and mobility

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Attendance Allowance= ≥65+ need help with personal care Incapacity Benefit= <65+unable to work because of illness or disability Low incomes may be entitled to; Housing Benefit and help with Council Tax Carer’s Allowance if>16years+spend ≥35 hours/week caring for a person who receives Attendance Allowance or Disability Living Allowance or Constant Attendance Allowance Disability Living Allowance Care Component Weekly rate Highest rate £62.25 Middle rate £41.65 Lowest rate £16.50 Mobility Component Weekly rate Higher rate £43.45 Lower rate £16.50 Social services provide social care services and equipment for the terminally ill. Family, friends, the respiratory team; nurses, social workers, hospital chaplains and doctors may provide sufficient emotional support. Additional support available via professional councilors are recommended from the British Association for Counseling and Psychotherapy. Free NHS help with medical and nursing care at home accessed via GPs including district or community nurse visits and community carer visits. Alternatively hospices+home care options for those with specialized needs. Reasons for non-attendance at clinics • Job • Cannot afford to get to hospital (peasant). • Lazyness • Depression • Shot dead • Injured • Denial of illness • Overslept • Physical Disability The theory of planned behaviour • This theory suggests the importance of intentions as predictors of future behaviour. • The intentions are motivational factors which indicate how hard people will try and how much effort they are willing to employ in order to carry out a behaviour. • Intentions are determined by ‘perceived control’; barriers to carrying out these actions; attitudes towards the action and others approval of the action. • Perceived control is a person’s assessment on their ability to carry out a behaviour, including thinking about barriers that may stand in their way. Those who believe in their ability (high perceived control) show greater persistence and effort in trying to succeed. • Attitudes towards the action are our overall evaluation of the behaviour and are similar to those of the health belief model. • If we value certain people’s opinions and if they are close to us, then their views will have an influence on our intentions. •

This model is useful, as by suggesting that beliefs produce behaviour through intentions, it provides an explanation for why many beliefs result in a decision to carry out an action. Also it enhances behavioural predictions, which health care

professionals can use to target advice, and it acknowledges the effect of social influence (e.g. approval of others) on behaviour. 5. Addressing health promotion The stage of change model is a useful guide for determining if people are ready for change 1) Precontemplation – an individual is not intending to change 2) Contemplation – lifestyle changes are under consideration and are an intention. 3) Preparation- small changes. 4) Action- actively engaging in new behaviours. 5) Maintenance stage- strategies are in place to reinforce the new behaviour. 6. What makes people carry out health related actions? When they believe • Their health is important • They are susceptible to a health threat which could have adverse consequences • The proposed action will be beneficial and does not have many costs • People who are important to the person approve of the action • They believe that they can carry out the action successfully. 7. How doctors can help people carry out health related actions (i.e. increasing perceived control) • Teach patients how to do something in order to gain an effective outcome (e.g. insulin use) • Encouraging them to believe in their own abilities (e.g. discuss how someone gave up smoking in the past) • Modelling a behaviour so that the person can watch it be carried out properly (e.g. video of someone using an inhaler). • Encourage practice of preparatory behaviours (e.g. discussing contraceptive use with partners) How doctors can help patients to change behaviours • Assess patient’s intentions to change i.e. their readiness and willingness to change. • Know patients concerns and expectations so can offer the right level of support. • Identify and breakdown barriers that will hinder change (e.g. a smoker going out with smoker friends) • Educate patient on ways to go about change, benefits of change. • Helping to set realistic goals • Involve supportive others • Refer to relevant support groups e.g. – NHS stop smoking • At the local government level by supporting community self help groups • A the national government level- e.g. by recommending a reduced level of alcohol that drivers should legally consume

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Summary of antibiotics Bacteriostatic: require input from the immune system. Effectiveness limited by Mean Inhibitory Concentration (MIC); Bacteriocidal: limited by Mean Bacteriocidal Concentration (MBC), often higher than the MIC; MIC= defined as the lowest concentration of antibiotic required to inhibit 90% of colonies of a particular organism; Bioavailability affects the MIC/MBI and is limited by: Amount of drug; Route of administration; Speed of uptake; Rate of clearance;

 Other factors influence choice and route on antibiotic include: Immune status: AIDS, Neutropenia; Organ: Infective endocarditis,Meningitis; Pregnancy; Age – children vs geriatric; Drug allergy; Abscess - pus binds antibiotic; Haematoma - RBC bind antibiotics; pH - Incr. or Decrease activity; Foreign body;  Remember, blood brain barrier can limit penetration of some antibiotics to the brain. Multiple antibiotics are often used, but antagonistic effects between drugs should be avoided.  β-Lactams: o Inhibit cell wall synthesis; o Competitively block transpeptidases, penicillin-binding proteins and peptidoglycan synthesis; o Only act on dividing bacteria; o Totally ineffective on the mycoplasmas that lack a cell wall; o Do not use a bacteriostatic agent followed by penicillin; o Resistance (β-Lactamase genes) now present in 30-60% E. coli & related species & in 5-20% of H. influenzae & gonococci; o β-Lactams include: Penicillin (poorly lipid soluble so only cross the blood-brain barrier when it is inflamed, eg in meningitis); Cephalosporins – broad spectrum bactericidal antibiotics, the latest generations of which are resistant to β-Lactamases. Used when people have adverse reactions to penicillin.  Glycopeptides: o Inhibit late stages of cell wall peptidoglycan synthesis at 2 stages; o Cannot penetrate gram-negative porins so gram-negative intrinsically resistant;  Aminoglycosides; o Bind to 30 S subunit of bacterial ribosomes; o Disrupt bacterial protein synthesis.  Tetracyclines: o Inhibit protein synthesis by preventing tRNA binding to ribosomes and modify ribosomal subunits pHdependent accumulation in cells;  Chloramphenicol: o Competitively inhibits transfer of tRNA-binding to 50S ribosomal subunit;  Macrolides: o Reversibly binds to 50S subunit and dissociates peptidyl-tRNA from ribosome.  Quinolones: o Block DNA replication resulting in cell death; o Effective but expensive + increasing resistance;  Imidazoles: o Under aerobic conditions form superoxide-damaging proteins, nuclear acids and lipids;  Sulphonamides: o Inhibitors of enzymatic activity (cell membrane function); o Well absorbed orally; o Effective against gram positive and some gram negative organisms, but rarely used alone;  Side effects of ABX: o Common side effects of antibiotics include upset stomach, diarrhea, and, in women, vaginal yeast infections; o Some side effects are more severe and, depending on the antibiotic, may disrupt the function of the kidneys, liver, bone marrow, or other organs. o Blood tests are used to monitor adverse reactions; o Some people who receive antibiotics develop colitis, an inflammation of the large intestine. The colitis results from a toxin produced by the bacterium Clostridium difficile, which grows unchecked when other antibacteria are killed by the antibiotics; o Antibiotics can also cause allergic reactions. Mild allergic reactions consist of an itchy rash or slight wheezing. Severe allergic reactions (anaphylaxis) can be life threatening and usually include swelling of the throat, inability to breathe, and low blood pressure.

Cerebrum: The largest and most highly developed part of the brain, composed of the two cerebral hemispheres, separated from each other by the longitudinal fissure in the midline. Each hemisphere has an outer layer of grey matter, the cerebral cortex, below which lies white matter containing the basal ganglia. >Connecting the two hemispheres at the bottom of the longitudinal fissure is the corpus callosum, a massive bundle of nerve fibres. >Within each hemisphere is a crescent-shaped fluid-filled cavity (lateral ventricle), connected to the central third ventricle in the diencephalon. >The cerebrum is responsible for the initiation and coordination of all voluntary activity in the body and for governing the functioning of lower parts of the nervous system. The cortex is the seat of all intelligent behaviour.

Cerebral Cortex Outermost layer of the cerebral hemisphere composed of gray matter. Divided into 2 hemispheres by the longitudinal fissure. Each hemisphere has 4 lobes: Frontal Lobe: Front part of the brain divided from the parietal lobe by the central sulcus. -Anterior portion: Prefrontal cortex. Important for higher cognitive functions such as behaviour and emotions and personality. -Posterior portion: Premotor and motor area. Nerve cells that produce movements are located in the motor areas in the form of a homunculus (different areas control movement of different parts of the body. The premotor areas serve to modify movements by interacting with the cerebellum and the thalamus. Parietal Lobe: Contains the primary sensory cortex which controls sensation (touch, pressure). Behind the primary sensory cortex is an association area controlling fine sensation) e.g. Judgment of texture, weight, size, shape). Higher function differs according to the side of the brain. In 99% right handed people and 60% of left handed people: -Damage to the right parietal lobe causes visio-spatial deficits (e.g. finding way round new or even familiar places) -Damage to eh left parietal lobe may disrupt a patient’s ability to understand spoken and/or written language. Temporal Lobe: region at the side of the brain at about the level of the ears. Allows smell and sound discrimination. Also helps sorting new information and believed to be responsible for short term memory. Function differs between the two hemispheres. In 99% right handed people and 60% left handed people -the right lobe is mainly involved in visual memory (i.e. memory from pictures and faces) -the left lobe is mainly involved in verbal memory (i.e. memory for words or names) Occipital Lobe: Back of the brain. Processes visual information. Responsible for visual reception and also contains association areas that help in visual recognition of shapes and colours Cerebellum: Helps coordinate movement (balance and muscle coordination). Damage may result in tremor, ataxia and/or nystagmus. This can interfere with a person’s ability to walk, talk, eat and perform other self care tasks. Basal Ganglia: Subcortical gray matter nuclei. Processing link between thalamus and motor cortex. Damage causes movement disorders. E.g. Parkinson’s disease

Thalamus: Processing centre of the cerebral cortex. Coordinates and regulates most functional activity of the cortex (except olfaction). Damage can result in thalamic syndrome in which there is spontaneous pain on the contra lateral side of the body. Hypothalamus: Integration centre of the autonomic nervous system (anterior hypothalamus- parasympathetic activity; posterior hypothalamus- sympathetic activity.) Concerned with regulation of body temperature and endocrine function Ventricular system: As the central canal of the spinal cord ascends into the brain stem it moves progressively in a dorsal direction, eventually opening out to form a shallow, rhomboid-shaped depression on the dorsal surface of the medulla and pons (the hindbrain portion of the brain stem) beneath the cerebellum. This is the fourth ventricle. > At the rostal border of the pons, the walls of the fourth ventricle converge, forming once again a narrow tube, the cerebral aqueduct. > The cerebral aqueduct dives into the substance of the brain stem running the length of the midbrain beneath the inferior and superior colliculi. > At the junction of the junction of the midbrain and forebrain, the aqueduct opens into the third ventricle, a slit like chamber, narrow from side to side but extensive in dorsoventral and rostrocaudal dimensions. > The lateral walls of the third ventricle are formed by the thalamus and hypothalamus of the diencephalon (an anatomical division of the forebrain, consisting of the epithalamus, thalamus (dorsal thalamus), hypothalamus, and ventral thalamus (subthalamus).)

> Near the rostal end of the third ventricle a small aperture, the interventricular foramen (foramen of Monro) communicates with an extensive chamber, the lateral ventricle, within each cerebral hemisphere. > The ventricular system is the site of CSF, which is secreted by the choroid plexus. Brain Stem: When viewed externally the massive cerebral hemispheres obscure many other structures but a medial sagittal section reveals most features of the basic brain and the brain stems can be seen clearly on both median sagittal and ventral views of the brain. > Consists of the medulla oblongata, pons and midbrain, each of which can be readily delineated >through the brain stem pass the ascending and descending nerve fibre tracts linking the brain and spinal cord which carry sensory information from, and permit movement of, the trunk and limbs. > Brain stem is also the origin and termination site of many of the cranial nerves. (Origin of cranial nerves IIIXII) > Within the brain stem also lie centres controlling respiration, BP, heart rate, digestion and level of consciousness. > The medulla oblongata is continuous caudally with the spinal cord and extends rostrally as far as the pons. Cranial Nerves: The brain receives sensory information from, and controls the activities of, peripheral structures, principally the head and neck. > Afferent and efferent nerve fibres run in 12 pairs of cranial nerves, which are identified by individual names and numbers. > Certain cranial nerves contain only sensory or motor nerve fibres but the majority like the spinal nerves contain a mixture. > The first two cranial nerves (I olfactory & II optic) attach directly to the forebrain and the rest attach to the brain stem >Within the brain stem lie a number of cell groupings called the cranial nerve nuclei which are the sites of termination of sensory fibres and the origin of the motor fibres that run in the cranial nerves

Cerebellum > The cerebellum is attached to the brain stem by a large mass of nerve fibres that lie lateral to the fourth ventricle on either side. It is split normally into three parts: the inferior, middle and superior cerebellar peduncles.

> These carry nerve fibres between the medulla, pons and midbrain, respectively, and the cerebellum. The largest cerebellar peduncle is the middle and it is the only one readily seen without further dissection. > The cerebellum consists of an outer layer of gray matter, the cerebellar cortex, surrounding a central core of white matter. > The cortical surface is highly convoluted to form a regular pattern of narrow, parallel fold or folia > The cerebellar white matter consists of nerve fibres running to and from the cerebellar cortex. > The white matter has a characteristic branching, tree-like arrangement in section as its ramifications reach towards the surface. > The cerebellum is concerned with the coordination of movement and operates at an entirely unconscious level. > Rostral to the pons is located the relatively small midbrain. On its dorsal surface can be seen the rounded eminences of the superior and inferior colliculi, beneath which runs the cerebral aqueduct.

Diencephalon > Rostral to the brain stem lays the forebrain, consisting of the diencephalon and cerebral hemisphere. The diencephalon and cerebral hemisphere on each side of the brain are to a large extent physically separate from their counterparts in the other side, although important cross connection do exist. > The diencephalon consists of four main subdivisions in a dorsoventral direction: the epithalamus, thalamus, subthalamus and hypothalamus. > The epithalamus is small and its most notable component on a sagittal section is the penial gland (pea-sized mass of nerve tissue attached by a stalk to the posterior wall of the third ventricle of the brain, deep between the cerebral hemispheres at the back of the skull. It functions as a gland, secreting the hormone melatonin. The gland becomes calcified as age progresses, providing a useful landmark in X-rays of the skull),

which lies midline immediately rostral to the superior colliculi of the midbrain. > The thalamus is by far the largest part of the diencephalon and it forms much of the lateral wall of the third ventricle. The thalamus plays an important part in sensory, motor, and cognitive functions and has extensive connection with the cerebral cortex > Little of the subthalamus can be seen. > The hypothalamus forms the lower part of the walls and floor of the third ventricle. It is a highly complex and important region because of its involvement in many systems, most notably the autonomic nervous system, the limbic system and neuro-endocrine system. > From the ventral aspect of the hypothalamus in the midline arises the infundibulum (pituitary stalk) to which is attached the pituitary gland. Coverings and blood supply > The brain and spinal cord are supported by the bones of the skull and vertebral column. Within these bony coverings the CNS is entirely ensheathed by three layers of membranes called the meninges. > The outermost membrane is the dura mater, a tough, fibrous coat that surrounds the brain and spinal cord like a loose fitting bag. > The spinal dura and much of the cranial are separate from the periosteum, which lines the surroundings bones. At certain locations however, such as the floor of the cranial cavity, the dura and periosteum are fused and the cranial dura is tightly adherent to the interior of the skull. > Two large sheets of dura project into the cranial cavity, incompletely dividing it into compartments. > The falx cerebri (a sickle-shaped fold of the dura mater that dips inwards from the skull in the midline, between the cerebral hemispheres) lies in the sagittal plane between the two cerebral hemispheres. Its free border lies above the corpus callosum (the broad band of nervous tissue that connects the two cerebral hemispheres, containing an estimated 300 million fibres). > The tentorium cerebelli is orientated horizontally, lying beneath the occipital lobes of the cerebral hemispheres and above the cerebellum. > The dura mater can be regarded as consisting of two layers. These are fused together except in certain locations where they become separated to form spaces, the dural venous sinuses, which serve as channels for the venous drainage of the brain.

> Important venous sinuses occur: on the floor of the cranial cavity, along the lines of the falx cerebri and tentorium cerebelli to the interior of the skull (superior sagittal sinus), and along the line of attachment of the falx cerebri and tentorium cerebelli to one another (straight sinus). > Beneath the dura lies the arachnoid mater, the two being separated by a thin subdural space. This arachnoid is a translucent, collagenous membrane that, like the dura, loosely envelops the brain and spinal cord. > The innermost of the meninges is the pia mater, a delicate membrane of microscopic thickness that is firmly adherent to the surface of the brain and spinal cord, closely following their contours. > Between the arachnoid and the pia is the subarachnoid space through which CSF circulates. > The brain is supplied with arterial blood by the internal carotid and vertebral arteries, which anastomose to form the circle of Willis on the base of the brain. > The spinal cord is supplied by vessels arising from the vertebral arteries, reinforced by radicular arteries derived from segmental vessels. > The arteries and veins serving the CNS run for part of their course within the subarachnoid space. > The meninges are supplied by a number of vessels, the most significant intracranial one being the middle meningeal artery, which ramifies extensively between the skull and dura mater overlying the lateral aspect of the cerebral hemisphere.

Anatomy of the spinal cord: The spinal cord lies within the vertebral canal of the vertebral column and is continuous rostrally with the medulla oblongata of the brain stem. > The spinal cord receives information from, and controls, the trunk and limbs which is achieved through 31 pairs of spinal nerves which join the cord at intervals along its length and contain afferent and efferent nerve fibres connecting with structures in the periphery. > Near to the cord, the spinal nerves divide into dorsal and ventral roots, which attach to the cord along its dorsolateral and ventrolateral borders, respectively. > The dorsal roots carry afferent fibres (neurones that convey impulses from sense organs and other receptors to the brain or spinal cord,), the cell bodes of which are located in the dorsal root ganglia (collection of nerve cell bodies and often synapses.) > The ventral roots carry efferent fibres with the cell bodies lying within the spinal grey matter. > Spinal nerves leave the vertebral canal through the intervertebral foramina, between adjacent vertebrae > Different rates of growth of the spinal cord and vertebral column during development result with the spinal cord in an adult not extending the full length of the vertebral canal but ending at the level of the intervertebral

disc between L1&L2. The lumber and sacral spinal nerves, therefore, descend in a leash-like arrangement called the cauda equina to reach their exit point > The spinal cord is approximately cylindrical in shape, containing at its centre a vestigial central canal > The separation of nerve bodies from nerve fibres gives a characteristic ‘H’ shape to the central core of grey matter that surrounds the central canal > Four extensions of the central grey matter project dorsolaterally and ventrolaterally towards the lines of attachments of the dorsal and ventral roots of the spinal nerves. These are the dorsal horns and ventral horns > The dorsal horn is the site of termination of many afferent neurones conveying impulses from sensory receptors throughout the body and is the site of origin of ascending pathways carrying sensory impulses to the brain. > The ventral horn contains motor neurones that innervate skeletal muscle. > In addition, at thoracic and upper lumber levels of the cord only, another, smaller, collection of cell bodies comprises the lateral horn which contains preganglionic neurones belonging to the sympathetic division of the autonomic nervous system. > The periphery of the cord consists of white matter that contains longitudinally running nerve fibres. These are organised into a series of ascending tracts, which carry information from the trunk and limbs to the brain, and descending tracts, by which the brain controls the activities of neurone sin the spinal cord. > The principal ascending tracts are the dorsal columns which carry fine touch and proprioception, the spinothalamic tracts, which carry pain, temperature, coarse touch and pressure and the spinocerebellar tracts, which carry information from muscle and joint receptors to the cerebellum. > Amongst the descending tracts, one of the most important is the lateral corticospinal tract, which controls skilled voluntary movement Sensory pathways Sensory information about the internal and external environment is carried to the CNS in afferent nerve fibres running in cranial and spinal nerves. > Sensory information can be classified under the headings of ‘special senses’ and ‘general senses. > The special senses are all carried in cranial nerves and comprise olfaction (I), vision (II), taste (VII&IX) and hearing and vestibular function(VIII). > The general senses include the modalities of touch, pressure, pain and temperature (relayed from exteroceptors in the skin and interoceptors in the viscera), and awareness of posture, and movement (from proprioceptors in joints, tendons and muscles). > General sensory information from the trunk and limbs is carried in spinal nerves; from the head it is carried in the trigeminal nerve (cranial V) > For all modalities in the category of general sensation, there is a sequence of three neurones between the sensory receptor located in the periphery and the perception of sensation at the level of the cerebral cortex. > The first neurone (1st order neurone) enters the spinal cord, or the brain stem, through a spinal nerve, or the brain stem, through a spinal nerve, or the trigeminal nerve, on the same side of the body as its peripheral nerve is located. > The cell body of the 1st order neurone is located in the dorsal root ganglion of a spinal nerve, or the trigeminal ganglion. > Within the CNS, the 1st order neurone remains ipsilateral and synapses upon the second neurone (2nd order neurone), the exact location of its termination dependent on the modality concerned. > The 2nd neurone has its cell body in the spinal cord or brain stem. Its axon crosses over (decussates) to the other side of the CNS and ascends to the thalamus, where it terminates. > The 3rd neurone in the sequence has its cell body in the thalamus and its axon projects to the somatosensory cortex, located in the parietal lobe of the cerebral hemisphere. > Sensory innervation is broadly divided into two pathways: the posterior columns (mediate fine touch and proprioception) and the spinothalamic tract (mediate pain and temperature sensation & crude sensation e.g. vibration) > Posterior columns: These fibres have their cell bodies in the dorsal root ganglia. Primary spinal afferents carrying proprioceptive information and discriminative (fine) touch ascend uninterrupted on the same side of the cord, forming the dorsal columns (fasciculus gracilis and fasciculus cuneatus). They terminate in the dorsal column nuclei (nuclei gracilis and cuneatus) located in the medulla. From here, 2nd order neurones decussate and ascend to the thalamus as the medial lemniscus. > Spinothalamic tract: Primary spinal afferents carrying coarse touch/pressure, pain and temperature information terminate near their level of entry into the cord. They synapse with 2 nd order neurones, the axons of which decussate within a few segments and thereafter form the spinothalamic tract. > Primary afferent neurones that enter the brain stem in the trigeminal nerve terminate ipsilaterally in the trigeminal sensory nucleus, one of the cranial nerve nuclei. From here 2nd order neurones decussate and ascend to the thalamus as the trigeminothalamic tract.

> 2nd order sensory neurones, of either spinal cord or brain stem origin, converge upon the same region of the thalamus (the ventral posterior nucleus), synapsing upon 3rd order neurones that project to the somatosensory cortex in the postcentral gyrus of the parietal lobe. > Throughout the central projections of the somatosensory system there is a high degree of spatial segregation of the neurones representing different parts of the body which is most dramatically demonstrated at the level of the cerebral cortex where the somatosensory area occupies a strip of cortex that extends from the medial aspect of the hemisphere (leg area) to the inferolateral aspect of the parietal lobe (head area).

Neurone: A component of the nervous system. A neurone is a nerve cell and all its processes. They have a role in the reception of stimuli and the conduction of nerve impulses. All neurones have a cell body, from which extend neurites (the various conduction pathways of the neurones). Neurites responsible for receiving information and conducting it towards the cell body are called dendrites. The single long neurite that conducts impulses away from the cell body is called the axon. Dendrites and axons are often referred to as nerve fibres The point of contact of one neurone with another is known as a synapse. Upper Motor Neurone: Originating from the brain and form descending tracts which control the activity of the lower motor neurones. The descending tracts are known as corticospinal and corticobulbar tracts. They originate from within the brain and their axons pass through the internal capsule and into the brain stem where most of them cross over to the other side of the cerebral cortex (thus motor control is contralateral). Corticobulbar fibres control the activity of motor neurones located in the cranial nerve nuclei, which innervate the skeletal muscles of the head and neck through the cranial nerves. Corticospinal fibres control activity of motor neurones in the spinal cord, which innervate the trunk and limb muscles. The point at which the corticospinal fibres cross over to the other side of the nervous system (at the ventral aspect of the medulla) is known as the decussation of the pyramids. Thus, the corticospinal tract is also know as the pyramidal tract. Corticobulbar and corticospinal/pyramidal pathways function to control voluntary, skilled movements. Extrapyramidal pathways are also involved in the control of movement, posture and tone; consisting of nuclei in the brain stem (vestibular & reticular nuclei), basal ganglia and subcortical nuclei located in the forebrain. Lower Motor Neurone: Directly innervate skeletal muscle. They have cell bodies in the grey matter of the spinal cord and brain stem. They form the final common pathway by which the nervous system controls movement

Neurone Types Unipolar: Typical sensory neurone. Cell body has a single neurite split into two branches; one proceeding to a peripheral structure and the other entering the central nervous system (CNS). Bipolar:Typical interneuron (link between the different neurones). Central cell body with two neurites branching from either end. Multipolar: Typical of a motor neurone. Multiple neurites arising from the cell body. Most neurones of the brain and spinal cord are of this type Pyramidal Cell: Found in the cerebral cortex, with a pyramid-shaped cell body, a branched dendrite extending from the apex towards the brain surface, several dendrites extending horizontally from the base, and an axon running in the white matter of the hemisphere

Structure of a Motor Neurone