Nervous System Pathophysiology PDF

NERVOUS SYSTEM & IT’S PATHOPHYSIOLOGY DR. LSK School Of Nursing 1  Your Nervous System is the most complicated and fragile system… It tells all your other systems what to do… 2  Objectives By the e...

NERVOUS SYSTEM & IT’S PATHOPHYSIOLOGY DR. LSK School Of Nursing 1  Your Nervous System is the most complicated and fragile system… It tells all your other systems what to do… 2  Objectives By the end of the topic, the students should be able to:  List all the bones covering the nervous system State the basic functions of the nervous system (NS) Basic Brain pathophysiological areas Outline and explain the divisions and structures of the NS Describe the developmental and microscopic anatomy of the NS Explain the organization of neurons and how they connect/communicate List all the part of Central and Peripheral NS State the functions of the different parts/structures in the CNS & PNS Discuss the pathophysiology related to Nervous System 3 Introduction to skull and brain. Which cranial Nerve is responsible?  RECAP:Skull Part of Axial Skeleton Cranial bones = cranium Enclose and protect the brain Attachment for head + neck muscles Facial bones =framework of face Form cavities for sense organs Opening for air + food passage Hold teeth Anchor face muscles  Cranial and Facial Bones Facial – 14 Cranial - 8 Mandible Frontal Maxilla (2) Occipital Zygomatic (2) Sphenoid Nasal (2) Ethmoid Lacrimal (2) Parietal (2) Palatine (2) Temporal (2) Vomer Inf. Nasal Conchae(2)  Bones of Skull Flat bones: thin, flattened, some curve Sutures: immovable joints joining bones Calvaria = Skullcap =Vault Superior, Lateral, Posterior part of skull Floor = Base Inferior part of skull 85 openings in the skull Spinal cord, blood vessels, nerves Foramina, meatus, canal, and fissure  Cranial Fossae Created by bony ridges Supports, encircles brain 3 Fossae Anterior Middle Posterior All the bones visible from this view are the cranial bones!!  Basic Functions of NS coordinating or control centre for all body activities orientation of the body to internal and external environments assimilation of experiences requisite to memory, learning, and intelligence 1 1 Basic areas of the brain for pathophysiology Divisions of the NS 14 15  Structures of the NS Central NS: composed of brain and spinal cord contains grey and white matter covered by bone and meninges Peripheral NS: composed of nerves, ganglia and nerve plexuses Autonomic NS: Sympathetic and parasympathetic Meninges (meninx): fibrous membranes covering the CNS include: Dura mater, Arachnoid and Pia mater (DAP) Cerebrospinal fluid (CSF): clear, watery medium that surrounds and maintains homeostasis in the CNS 16  Skull Dura mater Arachnoid mater Pia mater Gray mater White mater 17  Cont’d Neuron (Nerve cell): structural and functional cells of the NS types: motor, sensory and intermediate Nerve: bundle of nerve fibres Nerve plexus: convergence or network of nerves Somatic motor nerve: nerve that innervates skeletal muscle Autonomic motor nerve: nerve that innervates smooth and cardiac muscles and glands 18  Cont’d Ganglion: cluster of neuron cell bodies outside the CNS Nucleus: cluster of neuron cell bodies within the CNS Tract: bundle of nerve fibres interconnecting regions of the CNS 19  Development of the NS appears in the early 3rd week of development dorsal streak/neuroectoderm appears along the length of the embryo later thickens to form a neural plate neural plate sinks and the edges of it thicken and form neural grooves and fold neural fold later fuses along the midline and forms the neural tube 2 0  Cont’d by 4th week, the neural tube exhibits three anterior dilations or primary vesicles: Prosencephalon (forebrain) Mesencephalon (midbrain) Rhombencephalon (hindbrain) by 5th week, the neural tube undergoes further development and subdivides into five secondary vesicles: Prosencephalon (forebrain): Telencephalon – cerebral hemispheres and lateral ventricles Diencephalon – thalamus, hypothalamus and 3rd ventricle Mesencephalon – midbrain and cerebral aqueduct Rhombencephalon (hindbrain): Metencephalon – pons, cerebellum and upper portion of 4th 21 ventricle Myelencephalon – medulla oblongata and lower portion of 4th ventricle  Telenceph alon Prosenceph Diencepha alon l oOnpti Mesenceph c alon vesicle Metencephal Rhombenceph on alon Myelencephal on Spinal cord 22  Microscopic anatomy of NS Nervous tissue: Neurons Neuroglia or glia cells 23  Neurons signal direction d e n d r i t e s myelin sheath synaptic terminal dendrite → c → cell body axon synapse e 24 l l  Neuroglia/glia cells Astrocytes Oligodendroc ytes Microglia 25  Classification of Neurons Structural classification: Multipolar: many processes arising from cell body found in brain and spinal cord Bipolar: two processes (from each end of cell body) found in ear, eyes, nose Unipolar: single process extends from cell body found outside of brain and spinal cord 26  Cont’d Functional classification: Sensory neurons – afferent: unipolar or bipolar Motor neurons – efferent: multipolar Interneurons/intermediate neurons: multipolar 27  How are neurons connected? Synapse: functional connection between the axon terminal (synaptic knob) of a presynaptic neuron and a dendrite of a postsynaptic neuron. Synaptic communication – nerve cells release the signal (neurotransmitter) which binds to receptors on nearby cells 28  Synapse AXO N The synapse - What is where the this in action the happens membr The next cell’s ane? Transpo rt plasma protein membrane 3 0  Synap Point of setransmission impulse between neurons; impulses are transmitted from pre-synaptic neurons to post-synaptic neurons Synapses usually occur between the axon of a pre-synaptic neuron & and a dendrite or cell body of a post-synaptic neuron. At a synapse, the end of the axon is 'swollen' and referred to as an end bulb or synaptic knob. Within the end bulb are found lots of synaptic vesicles (which contain neurotransmitter chemicals) and mitochondria (which provide ATP to make more neurotransmitters). Between the end bulb and the dendrite (or cell body) of the post-synaptic neuron, there is a gap commonly referred to as the synaptic cleft. So, pre- and post-synaptic membranes do not actually come in contact.  That means that the impulse cannot be transmitted directly. Rather, the impulse is transmitted by the release of chemicals called chemical transmitters (or neurotransmitters).  Neurotransmitters Acetylcholine: transmit signal to skeletal muscle Epinephrine (adrenaline) & norepinephrine: fight-or-flight response Dopamine: affects sleep, mood, attention & learning lack of dopamine in brain associated with Parkinson’s disease excessive dopamine linked to schizophrenia Serotonin: affects sleep, mood, attention & learning 3 3  The Brain 4 Parts Cerebrum *Diencephalon Brain Stem Midbrain Pons Medulla Cerebellum Gray matter surrounded by White matter w/outer cortex of gray matter Meninges: 3 membranes around brain and spinal cord Made of Connective tissue Functions Cover, Protect CNS Enclose, protect blood vessels supplying CNS Contain CSF 3 Layers Dura Mater (external) Arachnoid Mater (middle) Pia Mater (internal)  Cerebral features Gyri: elevated ridges “winding” around the brain Sulci: small grooves dividing the gyri Central sulcus: Divides the Frontal Lobe from the Parietal Lobe Fissures: Deep grooves, generally dividing large regions/lobes of the brain Longitudinal fissure – divides the two Cerebral Hemispheres Transverse fissure – separates the Cerebrum from the Cerebellum Sylvian/lateral fissure – divides the Temporal Lobe from the Frontal and Parietal Lobes 3 6  Gross anatomy of the spinal cord extends from C1 – L1/2 covered by 3 layers of meninges terminates at L1/2 (conus medullaris) Dura extends to S2 surrounds by CSF – subarachnoid space has 31 pars of spinal nerves has cervical and lumbar enlargements 37  Cont’d Conus medullaris: terminal portion of the spinal cord Filum terminale: fibrous extension of the pia mater; anchors the spinal cord to the coccyx Denticulate ligaments: delicate shelves of pia mater; attach the spinal cord to the vertebrae Spinal nerves: 31 pairs attach to the cord by paired roots Cervical nerves are named for inferior vertebra All other nerves are named for superior vertebra Cervical and lumbar enlargements: sites where nerves serving the upper and lower limbs emerge Cauda equina: collection of nerve roots at the inferior end of the vertebral canal 38 Cont’d Meningeal layers: Dura mater Arachnoid mater Pia mater 39 MEMBRANES - COVER THE CNS 3 IN ALL Protective coverings 1. DURA MATTER –PACHYMENINX 2. ARACHNOID 3. PIA 2 & 3 also called LEPTOMENINGES 4 0 Meninges Dura mater Arachnoid mater Pia mater 41 Cranial Dura Mater Bone Endoste al Sinus Meninge al 42 43  MENINGEAL LAYER INFOLDS TO GIVE 4 SEPTAE FALX CEREBRI TENTORIUM CEREBELLI FALX CEREBELLI DIAPHRAGMA SELLA Septae restrict displacemen t of brain associated with acceleration & deceleration 4 , when head 4 is moved  Falx Cerebri– the sickle Occupies the longitudinal fissure between cerebral hemispheres. Superior sagittal runs in its upper fixed margin. Inferior sagittal sinus in its lower concave free margin. Straight sinus along its attachment to tentorium cerebelli. 45  Tentorium Cerebelli– the tent Covers the superior surface of the cerebellum. Supports occipital lobes of cerebral hemispheres. The opening accommodates the brainstem. Midbrain passes through the tentorial notch. 46 Falx Cerebelli A small midsagittal septum below the tentorium. Partially separates cerebellar hemispheres 47  Diaphragma Sella Roofs over the pituitary fossa. Perforated by the infundibulum of the pituitary. 48  VENTRICULAR SYSTEM CAVITIES INSIDE THE BRAIN CONTAINING CSF LATERAL VENTRCLES CEREBRAL HEMISPHERES 3RD VENTRICLE DIENCEPHALON 4TH VENTRICLE RHOBENCEPHALON 4 9 INTRACRANIAL VENOUS SINUSES 5 0  DURAL VENOUS SINUSES Superior sagittal (SS sinus S) Inferior sagittal sinus Straight sinus Transverse sinus Sigmoid sinus Occipital sinus Cavernous sinus Superior petrosal 51 sinus Inferior petrosal  Cranial nerves CN I: Olfactory - Sensory CN II: Optic - Sensory CN III: Oculomotor - Motor CN IV: Trochlear - motor CN V: Trigeminal - Sensory and motor CN VI: Abducens - Motor CN VII: Facial - Sensory and motor CN VIII: Vestibulocochlear (auditory) - Sensory CN IX: Glossopharyngeal - Sensory and motor CN X: Vagus - Sensory and motor CN XI: Accessory (spinal accessory) - Motor CN XII: Hypoglossal - Motor 52  Names of cranial nerves Ⅰ Olfactory nerve Ⅱ Optic nerve Ⅲ Oculomotor nerve Ⅳ Trochlear nerve Ⅴ Trigeminal nerve Ⅵ Abducent nerve Ⅶ Facial nerve Ⅷ Vestibulocochlear nerve Ⅸ Glossopharyngeal nerve Ⅹ Vagus nerve Ⅺ Accessory nerve Ⅻ Hypoglossal nerve  Classification of Sensory cranial nerves: contain only afferent cranial (sensory) fibers nerves ⅠOlfactory nerve ⅡOptic nerve Ⅷ Vestibulocochlear nerve Motor cranial nerves: contain only efferent (motor) fibers Ⅲ Oculomotor nerve Ⅳ Trochlear nerve ⅥAbducent nerve Ⅺ Accessory nerv Ⅻ Hypoglossal nerve Mixed nerves: contain both sensory and motor fibers--- ⅤTrigeminal nerve, Ⅶ Facial nerve, ⅨGlossopharyngeal nerve ⅩVagus nerve Sensory cranial nerves N. Location of cell Cranial Terminal Main body and axon exit nuclei action categories Ⅰ Olfactory cells Cribrifom Olfactory Smell (SVA) foramina bulb Ⅱ Ganglion cells Optic Lateral Vision (SSA) canal geniculate body Ⅷ Vestibular Internal Vestibular Equilibri ganglion(SSA) acoustic nuclei um meatus Cochlear Cochlear Hearing ganglion (SSA) nuclei  Motor cranial N. nerves Nucleus of origin and axon categories Cranial exit Main action Ⅲ Nucleus of oculomotor Superior orbital Motor to superior, inferior (GSE) fissure and medial recti; inferior obliqus; levator palpebrae superioris Accessory nucleus of Parasympathetic to sphincter oculomotor (GVE) pupillea and ciliary muscl Ⅳ Nucleus of trochlear Superior orbital Motor to superior obliquus nerve (GSE) fissure Ⅵ Nucleus of abducent Superior orbital Motor to lateral rectus nerve (GSE) fissure Ⅺ Nucleus of accessory Jugular foramen Motor to sternocleidomastoid nerve (SVE) and trapezius Ⅻ Nucleus of hypoglossal Hypoglossal canal Motor to muscles of tongue nerve( GSE) Mixed cranial nerves  SUMMARY OF THE CRANIAL Nerve NERVES Components Location of Nerve Cell Cranial Exit Main Action(s) Bodies Olfactory Special Olfactory epithelium Foramina in Smell from nasal mucosa of roof of (CN I) sensory (olfactory cells) cribriform plate of each nasal cavity and superior sides ethmoid bone of nasal septum and superior concha Optic (CN Special Retina (ganglion cells) Optic canal Vision from retina II) sensory Oculomotor Somatic Midbrain Motor to superior rectus, inferior (CN III) motor rectus, medial rectus, inferior oblique, and levator palpebrae superioris muscles; raises superior eyelid; turns eyeball superiorly, inferiorly, and medially Superior orbital Visceral Presynaptic: midbrain fissure Parasympathetic innervation to motor Postsynaptic: ciliary sphincter of pupil and ciliary muscle; ganglion constricts pupil and accommodates lens of eye Trochlear Somatic Midbrain Motor to superior oblique that assists (CN IV) motor in turning eye infero-laterally (or inferiorly when adducted)  CON’ Location of Nerve Nerve T Trigeminal Components Cell Bodies Cranial Exit Main Action(s) (CN V) Ophthalmic Superior orbital Sensation from cornea, skin of (CN V1) fissure forehead, scalp, eyelids, nose, and mucosa of nasal cavity and paranasal sinuses Maxillary Foramen rotundum Sensation from skin of face over (CN V2) General maxilla, including upper lip, Trigeminal ganglion maxillary teeth, mucosa of nose, sensory maxillary sinuses, and palate Mandibular Foramen ovale Sensation from skin and over side (CN V3) of head mandible including lower lip, mandibular teeth, temporomandibular joint, mucosa of mouth and anterior two thirds of tongue Branchial Pons Motor to muscles of mastication, motor mylohyoid, anterior belly of digastric, tensor veli palatini, and tensor tympani Abducent Somatic motor Pons Superior orbital Motor to lateral rectus that turns (CN VI) fissure eye laterally  CON’ Location of Nerve Cell Nerve Facial T Components Branchial motor Bodies Pons Cranial Exit Main Action(s) Motor to muscles of facial (CN VII) expression and scalp; also supplies stapedius of middle ear, stylohyoid, and posterior belly of digastric Special sensory Geniculate ganglion Internal acoustic meatus; Taste from anterior two facial canal; stylomastoid foramen thirds of tongue and the palate Visceral motor Presynaptic: pons Parasympathetic Postsynaptic: innervation to pterygopalatine ganglion; submandibular and submandibular ganglion sublingual salivary glands, lacrimal gland, and glands of nose and palate Vestibuloc ochlear (CN VIII) Vestibular Special sensory Vestibular ganglion Vestibular sensation from semicircular ducts, utricle, and saccule related to Internal acoustic meatus position and movement of head Cochlear Special sensory Spiral ganglion Hearing from spiral organ  Location of Nerve Nerve Components Cell Bodies Cranial Exit Main Action(s) Glossopharyngeal Branchial Medulla Motor to (CN IX) motor stylopharyngeus to assist with swallowing Visceral motor Presynaptic: Parasympathetic medulla innervation to parotid gland Postsynaptic: otic ganglion Visceral Superior ganglion Jugular foramen Visceral sensation sensory from parotid gland, carotid body and sinus, pharynx, and middle ear Special Inferior ganglion Taste from posterior sensory third of tongue General Inferior ganglion Cutaneous sensation sensory from external ear  Location of Nerve Cell Nerve Components Bodies Cranial Exit Main Action(s) Vagus (CN X) Branchial motor Medulla Motor to constrictor muscles of pharynx (except stylopha-ryngeus), intrinsic muscles of larynx, muscles of palate (except tensor veli palatini), and striated muscle in superior two thirds of esophagus Visceral motor Presynaptic: medulla Parasympathetic innervation to smooth Postsynaptic: neurons in, muscle of trachea, bronchi, digestive tract, on, or near viscera and cardiac muscle of heart Visceral sensory Superior ganglion Visceral sensation from base of tongue, Jugula pharynx, larynx, trachea, bronchi, heart, r esophagus, stomach, and intestine to left forame colic flexure n Special sensory Inferior ganglion Taste from epiglottis and palate General sensory Superior ganglion Sensation from auricle, external acoustic meatus, and dura mater of posterior cranial fossa Spinal accessory (CN XI) Somatic motor Spinal cord Motor to sternocleidomastoid and trapezius Hypoglossal (CN XII) Somatic motor Medulla Hypoglossal Motor to intrinsic and extrinsic muscles of canal tongue (except palatoglossus) *The traditional cranial root of the accessory nerve is considered here as part of the vagus nerve (CN X); the spinal accessory nerve (CN XI) as listed here refers only to the traditional spinal root of the accessory nerve.  Summary of Cranial Nerve Lesions Nerve Type(s) and/or Site(s) of Lesion Abnormal Findings CN I Fracture of cribiform plate Anosmia (loss of smell); cerebrospinal fluid rhinorrhea CN II Direct trauma to orbit or eyeball; fracture Loss of pupillary constriction involving optic canal Visual field defects Pressure on optic pathway; laceration or intracerebral clot in the temporal, parietal, or occipital lobes of brain CN III Pressure from herniating uncus on nerve; Dilated pupil; ptosis; eye turns down and out; fracture involving cavernous sinus; pupillary reflex on the side of the lesion will aneurysms be lost CN IV Stretching of nerve during its course around Inability to look down when eye is adducted brainstem; fracture of orbit CN V Injury to terminal branches (particularly Loss of pain and touch sensations; CN V2) in roof of maxillary sinus; paraesthesia; masseter and temporalis muscles pathological processes affecting trigeminal do not contract; deviation of mandible to side ganglion of lesion when mouth is opened CN VI Base of brain or fracture involving Eye falls to move laterally; diplopia on lateral cavernous sinus or orbit gaze  Nerve Type(s) and/or Site(s) of Lesion Abnormal Findings CN VII Laceration or contusion in parotid region Paralysis of facial muscles; eye remains open; angle of mouth droops; forehead does not wrinkle Fracture of temporal bone As above, plus associated involvement of cochlear nerve and chorda tympani; dry cornea; loss of taste on anterior two thirds of tongue Intracranial hematoma (stroke) Forehead wrinkles because of bilateral innervation of the frontalis muscle; otherwise paralysis of contralateral facial muscles CN VIII Tumor of nerve (acoustic neuroma) Progressive unilateral hearing loss; tinnitus (noises in ear) CN IX Brainstem lesion or deep laceration of Loss of taste on posterior third of tongue; loss neck of sensation on affected side of soft palate CN X Brainstem lesion or deep laceration of Sagging of soft palate; deviation of uvula to neck normal side; hoarseness owing to paralysis of vocal fold CN XI Laceration of neck Paralysis of sternocleidomastoid and superior fibers of trapezius; drooping of shoulder CN XII Neck laceration; basal skull fractures Protruded tongue deviates toward affected side; moderate dysarthria (disturbance of articulation)  Oculomotor paralysis Abducent nerve injury PAIN PATHWAY Pain Pathway Explanation  Lateral spinothalamic tract – carries the sensory modalities of pain and temperature Anatomically, the pathway is divided into three: First, second and third orders neurones  The first-order neurones arise from the sensory receptors in the periphery. They enter the spinal cord, synapse at substantia gelatinosa of the spinal cord  The second-order neurones carry the sensory information from the substantia gelatinosa to the thalamus.  After synapsing with the first-order neurones, these fibres decussate within the spinal cord and then form two distinct tracts: Crude touch and pressure fibres – enter the anterior spinothalamic tract. Pain and temperature fibres – enter the lateral spinothalamic tract.  The third-order neurones carry the sensory signals from the Clinical Correlate of the Pathway Anterolateral System  Injury to the anterolateral system will produce an impairment of pain and temperature sensation. This sensory loss will be contralateral (the spinothalamic tracts decussate within the spinal cord).  Brown-Séquard syndrome refers to a hemisection (one-sided lesion) of the spinal cord. This is most often due to traumatic injury and involves both the anterolateral system and the DCML pathway: DCML pathway – ipsilateral loss of touch, vibration and proprioception. Anterolateral system – contralateral loss of pain and temperature sensation Neurological Disorders and Dr. LSK Limbic system  NEUROLOGICAL DISORDERS Neurological disorders are caused as a result of structural, biochemical or electrical abnormalities in the brain The common neurodegenerative diseases. Parkinson’s disease Epilepsy Dementia Alzheimer’s disease Parkinson’s disease and part of the brain Corticospinal tract: Pathway for Normal movement  PARKINSON’S DISEASE General Considerations Th e second most common progressive neurodegenerative disorder The most common neurodegenerative movement disorder Symptoms and neuropathology are well characterized Pathogenesis of PD is not clear May be multifactorial and heterogeneous in etiology  PARKINSON’S DISEASE Classical Clinical Features Resting Tremor Cogwheel Rigidity Bradykinesia Postural Instability  PARKINSON’S DISEASE Associated Clinical Features/ Non-Motor Drooling Dysphagia Autonomic dysfunction Depression Dementia Loss of olfactory function  PARKINSON’S DISEASE Descriptive Epidemiology  Prevalence: 10 million people worldwide  for individuals < 40 years of age 1%  for individuals > 60 years of age 2%  for individuals > 85 years of age 5% Men > Women  PARKINSON’S DISEASE Environmental Factors Many epidemiology studies Rural living / agricultural work Cigarette smoking, coffee drinking MPTP (mitochondrial complex I inhibitor) Pesticides/herbicides (rotenone, paraquat, dieldrin) Heavy metal (iron, manganese) Hydrocarbon solvents Diet  PARKINSON’S DISEASE Cigarette Smoking Apar t from age, the most consistently reported epidemiologic finding is an inverse association with cigarette smoking 50% decreased risk among smokers; inverse dose-response relationship  PARKINSON’S DISEASE Caffeine Consumption Prior coffee, tea, and noncoffee caffeine consumption is consistently associated with a reduced risk of PD There is the inverse dose-response relationship Five-fold reduction in risk of PD in those who drank coffee/day Risk reduction benefits men more than women Caffeine antagonizes adenosine A2A receptors in the striatum Blockage or inactivation of A2A receptors are known to protect against excitotoxic and ischemic neuronal injury Adenosine A2A antagonists significantly reduce the MPTP-induced nigrostriatal lesions Therefore, caffeine may protect against dopaminergic toxicity via its antagonistic action at the A2A receptor  PARKINSON’S DISEASE Diet Parkinson’s disease risks associated with dietary iron, manganese, and other nutrient intakes (Powers, et al., Neurology 2003). A high intake of iron, especially in combination with high mananese intake, may be related to risk for PD. No strong associations were found for either antioxidants or fats Dietary folate deficiency and elevated homocysteine level  PARKINSON’S DISEASE Genetic Factors PD may be multifactorial in etiology with genetic contributions Familial cases are relatively rare (5-10%) The younger the age of symptom onset, the more likely genetic factors play a dominant role Mitochondrial DNA (complex I) defects At least ten single gene mutations identified Ubiquitin-proteasome system  PARKINSON’S DISEASE Alpha-Synuclein Small flexible monomeric protein of 140 a.a. Abundantly expressed in CNS Presynaptic protein of unknown normal function Lewy bodies and Lewy neurites found in PD contain aggregates of α-synuclein Mutations cause autosomal dominant PD Although mutations are extremely rare, it is the first gene identified to cause familial PD  PARKINSON’S DISEASE Pathogenesis Mitochondrial system Oxidative stress Alpha-synuclein Environmental factors (rotenone, etc.) Treatment for Parkinson's disease Medications E.g Levodopa Surgery. Deep brain stimulation Complementary and supportive therapies include diet, exercise, physical, occupational, and speech therapy.  EPILEPSY Epilepsy is a disease where a person tends to have recurrent seizures. Seizures are caused by abnormal nerve signals in the brain and can cause a variety of symptoms. According to the International league against epilepsy (ILAE), epilepsy is a disorder of the brain defined by any of the following conditions: At least two unprovoked (or reflex) seizures occur more than 24 hours apart. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures occur over the next 10 years. Diagnosis of epilepsy syndrome.  Types of Seizures 1. Generalized seizures – that affect both sides of the brain. These occur without warning and hence are commonly associated with injuries. a)Tonic-clonic seizures patient can have sudden onset jerking/shaking with stiffness/ tightening of the whole body, which can be associated with b)Tonic seizures: In a tonic seizure, the patient's body may suddenly become stiff. If they are standing, they often fall and develop injuries. c)Atonic seizures: In an atonic seizure (or 'drop attack'), the patient's muscles suddenly relax and become floppy. If they are standing, they often fall, usually forwards, and may injure the front of their head or face.  TYPE S a. Tonic-clonic seizures- The patient can have sudden onset jerking/shaking with stiffness/ tightening of the whole body, which can be associated with ◦ Cry out. ◦ Loss of consciousness. ◦ Fall to the ground. ◦ Passage of urine or stools. ◦ Tongue bite ◦ Excessive salivation from mouth  ◦ Up rolling of eyes ◦ Pale skin colour ◦ Difficult breathing The person may feel tired, confused, or sleepy and may have headaches after a generalized tonic-clonic seizure. This state is called 'post-ictal' (after-seizure) state. They may or may not remember the seizure afterward. d) Myoclonic seizures: Myoclonic means' muscle jerk'. Myoclonic seizures are brief but can happen in clusters (many happening close together in time), and often happen shortly after waking. These are the prominent seizure types in "juvenile myoclonic epilepsy." Muscle jerks are not always due to epilepsy (for example, some people have them as they fall asleep) e) Absence of seizures: This is generally seen in children and young adults. The patient can have rapid blinking of eyes; the patient may seem confused or look like they are staring at something that is not there. 2.Focal seizures: In this type of seizure, abnormal activity starts in just one area of the brain. In this type of seizure, there can be: ◦ muscle twitching, or abnormal jerking of one limb ◦ abnormal sensation over some part of the body ◦ the feeling of strange taste or smell. Patients with focal seizures may become confused or be unable to respond to questions for up to a few minutes. The focal seizure begins in one part of the brain but can spread to both sides of the brain. In such cases, the person first has a focal seizure that is followed by a generalized seizure. Some people experience strange sensations before a seizure known as aura. The aura can be: ‘Rising' feeling in the stomach or Déjà vu (feeling like you have 'been here before) Getting an unusual smell or taste; A sudden intense feeling of fear or joy; A strange feeling like a 'wave' going through the head; A sensation that an arm or leg feels bigger or smaller than it is; or Visual disturbances such as colored or flashing lights Hallucinations (seeing something that is not there). Once the patient starts recognizing the aura, they can identify it as a warning they get before seizure occurrence. ETIOLOGY What are the causes of epilepsy? Epilepsy can occur due to many causes that lead to brain damage. In 60- 70% of cases, no cause is found. The causes may be different for different age groups. These include: Difficult birth causing low oxygen supply to the brain of the newborn. Head injuries Brain tumors Genetic conditions where other family members can also be affected. Eg. Tuberous sclerosis. Brain infections Stroke ETIOLOGY What can precipitate seizures in epilepsy patients who are already on treatment? Missing medication doses. Lack of sleep (a common cause of seizures in patients with juvenile myoclonic epilepsy) Fever Intake of other drugs that cause seizures Heavy alcohol intake  INVESTIGATIONS Patients with epilepsy may have to undergo a variety of investigations. These include: Computed tomography (CT) scan or Magnetic resonance imaging (MRI) scan- The images can help identify tumours, strokes, or abnormalities in brain structure. An electroencephalograph (EEG) records the electrical activity in the brain. It helps confirm seizure activity, determine the type of seizure, and identify the part of the brain involved in it. Video recording may be used with EEG to record the seizure. Blood investigations may also be required. CSF laboratory test can be used as well  WHEN TO REFER A PATIENT WITH EPILEPSY TO A HIGHER CENTER? Patients with epilepsy can generally be managed well at primary care facilities. However, in the circumstances discussed below, patient should be referred to a higher centre The epilepsy is not controlled with medication within 2 years despite good compliance. Management is unsuccessful after two drugs are given inadequate doses. Patients with epilepsy experience unacceptable immediate or long- term side-effects from medication.  There is a unilateral structural lesion on CT or MRI brain. There is psychological and/or psychiatric co-morbidity. Seizures are associated with other symptoms like declining school performance, behavioral disturbances, difficulty in walking, frequent falls, visual disturbances, etc. Patients with a strong family history of seizures.  MANAGEMEN T Although seizures can be frightening to see, they are not usually a medical emergency. Usually, the seizures are self-limiting and stop within 1 to 2 minutes. Once the seizure stops, the person recovers and goes back to normal after some time. Pharmacotherapy There are multiple drugs known as antiepileptic drugs that can be used to treat epilepsy. However, 30% of patients are not controlled with medications. These patients can have drug- refractory epilepsy. What is the duration of treatment In patients with epilepsy, discontinuation of antiepileptic treatment can be considered after two to three seizure-free years. However, the duration of treatment is individualized and depends on many factors like cause of epilepsy, seizure type, patient's occupation. Surgery Brain surgery can be done in some eligible patients with drug-refractory epilepsy. Medications are mostly continued even after surgery.  NON- PHARMACOLOGICA L INTERVENTION All non-pharmacological interventions are used in addition to pharmacological therapy. These include: Diet therapy: The ketogenic diet and modified Atkin’s diet are usually used in patients with drug-resistant epilepsy. The ketogenic diet is a high-fat, low- carbohydrate diet that is typically implemented with a 3:1 or 4:1 fat to carbohydrate/protein ratio by weight. Modified Atkin’s diet focuses more on carbohydrate restriction. Patients limit their daily intake of net carbohydrates to 10 to 20 grams per day indefinitely. Fat to protein and carbohydrate ratios is closer to 1:1.  DOSE AND SIDE EFFECTS OF THE COMMON DRUGS USED IN MANAGEMENT Medication OF EPILEPSY Dose Common side-effects Sleepiness, swollen Phenytoin 5 mg per kg gums, rash, Poor coordination or balance. Sleepiness, rash, poor coordination or balance, Carbamazep 10-20 mg per kg double vision, decreased ine blood cell count, decreased sodium level in blood. Sleepiness, weight gain, hair loss, decreased Valproate 20-40mg/kg blood cell counts, birth defects in the newborn of a pregnant women patient taking valproate  Medication Dose Common side-effects 5 mg/kg (Use half of this dose with slow titration if patient is Lamotrigine on valproate) Rash Very slow up titration not more than 25 mg per week increase Clobazam 0.2 to 0.5 mg per kg Sleepiness Levetiracetam Mood and behaviour changes 10-40 mg/kg  Alternative therapies: Yoga, exercise, and music therapy have been tried in patients with epilepsy. Though these can be advised to patients with epilepsy, these cannot be relied upon for epilepsy control. GENERAL PRECAUTIONS TO PREVENT INJURIES General precautions to prevent seizures: a) Do not skip medications b) Adequate sleep for at least 8 hours c)Early treatment of fever  GENERAL PRECAUTIONS TO PREVENT INJURIES Precautions to prevent seizure-related injuries a)Do not drive- Driving is not permitted in patients with epilepsy as per Indian laws. b)Avoid swimming- Patients should avoid swimming or should be supervised while swimming. Patients with frequent seizures should not swim to avoid drowning. Taking a shower in running water is better than with a bucket full of water to avoid drowning if a seizure occurs during bathing. c)The patient should avoid going at height alone. d)Patients with frequent drop attacks can be given a helmet to avoid head injuries.  FOLLOW UP CARE, FREQUENCY AND FOLLOW UP ASSESSMENT AT PRIMARY CARE LEVEL Since epilepsy is a chronic disease, long-term follow-up is required. Generally, in a patient with well-controlled epilepsy 3-6 monthly follow up is adequate. In other epilepsy patients, a more frequent follow-up should be done. During each follow-up visit: Ask for the last seizure episode Ask for the compliance Ask if the patient had any reaction/side effects to the drug (especially if a new drug is introduced). Ask for sleep duration  Preferably patients should maintain the seizure diary to record all this information. Patients immediate relative/ witness of the seizures should be interviewed for the seizure episodes. Ask for use of any alternate medications. In females, the drug changes may be required before conceiving, proper counselling is needed for this issue. Patients with well controlled epilepsy, who remain seizure free for > 3 years can be considered for tapering the drug dose. During tapering, the patient should be informed about the risk of breakthrough seizures with drug tapering.  WHAT NOT TO DO IN THE EVENT OF A SEIZURE? 1 2 3 Do not hold Do not put them down. Do not make anything to eat This can lead to them smell or drink in injuries and shoes or onions their mouth. fractures.  DEMENTIA Dementia is a syndrome – usually of a chronic or progressive nature – in which there is deterioration in cognitive function (i.e. the ability to process thought) beyond what might be expected from normal ageing (WHO). It affects- Memory Thinking Orientation Comprehension Calculation Learning capacity Language Judgement and social interaction Potentially Non- Modifiable Factors RISK Genetic factors FACTORS Illiteracy Hearing Loss Diabetes Hypertension Obesity Modifiable Smoking Factors Depression Physical Inactivity Social Isolation Stroke  SIGNS AND SYMPTOMS Stages of Dementia Sign & Symptoms Early The early stage of  forgetfulness 1 stage/ dementia is often overlooked,  losing track of the time Mild Demen because the onset  becoming lost in familiar places tia is gradual  becoming forgetful M of recent As events and people's 2 i names d dementia, d progresses to the  becoming lost at home l middle stage, the  having increasing e signs and difficulty with symptoms communication st become clearer a and more  needing help with personal care g restricting.  experiencing behaviour changes, e including wandering and repeated / questioning. Moder  SIGNS AND SYMPTOMS Stages of Dementia Sign & Symptoms The late stage of  becoming unaware dementia is one of of the near time and place Late 1 stage/  having difficulty total recognizing relatives and Sever dependence and friends e inactivity. Memory Deme disturbances are  having an increasing need for ntia serious and the assisted self-care physical signs and  having difficulty walking symptoms become more obvious.  experiencing behavior changes that may escalate and include aggression.  DIAGNOSIS OF DEMENTIA No single test can determine dementia. Diagnosis is based on: ◦ Clinical including neurological examination ◦ Mental status examination ◦ Other laboratory tests to rule out other causes Not all confusion and memory loss indicate dementia, so it’s important to rule out other conditions, such as drug interactions and thyroid problems. Mini-Mental State Examination (MMSE) The MMSE is a questionnaire for measuring cognitive impairment. The MMSE uses a 30-point scale and includes questions that test memory, language use and comprehension, and motor skills, among other things. A score of 24 or higher indicates normal cognitive function. While scores 23 and below indicate that you have some degree of cognitive impairment.  WHEN TO REFER? A patient suspected to have dementia should be referred to a specialist in the presence of the following features: Rapidly progressive cognitive dysfunction Worsening impairment in activities of daily living Presence of focal neurological deficits such as paralysis of one half of the body Headache and vomiting Fever  Involuntary weight loss and loss of appetite Incontinence of bowel or bladder Self-injury or injury to a caregiver Recent history of head trauma Associated seizures  DIFFERENTIAL DIAGNOSIS There are some conditions that may mimic dementia. These include: a.Delirium b.Depression c.Metabolic/ Endocrine Conditions d.Drugs  PHARMACOLOGICAL INTERVENTION Pharmacological treatment is largely guided by the type of dementia that is diagnosed. There is no curative therapy for dementia, and hence, the focus is on the treatment of symptoms and associated comorbidities, including psychiatric concerns. Some drugs that may be useful, predominantly for Alzheimer's disease, may be useful in other forms of dementia also, including: Cholinesterase Inhibitors These medications prevent the breakdown of acetylcholine in the brain, which helps in transmitting signals between neurons in the brain. These drugs include: Donepezil (5 mg, 10 mg, 23 mg), Rivastigmine (transdermal patch 4,6 mg/24 hours or 9.6 mg/ 24 hours), Galantamine (8 mg, 16 mg, 24 mg)  Although these drugs may provide some benefit in memory, attention, and other symptoms, they mainly slow down the progression of dementia for a period of time. Some of the side effects include nausea, vomiting, diarrhea, fatigue, insomnia Memantine Memantine mainly helps to balance a substance called glutamate in the brain. It is used predominantly for moderate to severe Alzheimer's disease. Side effects may include giddiness, headache, constipation, fatigue, and somnolence. Occasionally, the above two drugs may be combined.  NON- PHARMACOLOGICAL INTERVENTION Environmental modification Alterations must be made in the environment of the patient with dementia to make it safe and comfortable for the patient. There should be adequate lighting, handrails in the washroom, nightlight while sleeping etc. to ensure that the patient does not trip and fall. Noise and clutter should be reduced. Memory training External memory aids such as reminder notes or alarms on the patient’s phone may be used. Patients with dementia should be encouraged to participate in activities that demand mental activity such doing the crossword, playing sudoku to keep their mental abilities sharpened. Adequate sensory cueing Vision and hearing issues among persons with dementia must be corrected with the help of spectacles or hearing aids so that they are able to better interact with their family and friends. Simplification of tasks Complex tasks may be simplified or broken down into several simpler individual tasks to avoid confusing the patient with dementia. Dementia support groups Patients with dementia must be encouraged to maintain their social network and possibly, become part of a dementia support group for moral support and social interactions. Other therapies Other therapies which may provide relaxation among these patients include music therapy, aroma therapy, light exercises, art therapy.  PSYCHOSOCIAL INTERVENTION S Cognitive behavioral therapy Psychotherapy and psycho-educational interventions Behavioural management therapy Prognosis Patients with dementia have shorter lifespans than those without dementia. Women tend to live longer than men. Several features are associated with shortened survival: feeding issues, malnutrition, swallowing difficulties, admission to hospital and advanced stages of dementia. Additionally, the presence of comorbid diabetes, heart failure, cancer, and infections further worsen prognosis.  ALZHEIMER’S DISEASE Alzheimer’s is a degenerative disease that is caused by complex brain changes following cell damage. It leads to dementia symptoms that gradually worsen over time. The most common early symptom of Alzheimer’s is trouble remembering new information because the disease typically impacts the part of the brain associated with learning first. Risk Factors Advancing age, illiteracy, addiction, hypertension, diabetes, poor socioeconomic status, trauma, familial or genetic factors, nutritional factors, and stroke.  Sign and Symptoms The initial and most common presenting symptom is episodic short-term memory loss with relative sparing of long-term memory and can be elicited in most patients even when not the presenting symptom. Short-term memory impairment is followed by impairment in problem-solving, judgment, executive functioning, lack of motivation and disorganization, leading to problems with multitasking and abstract thinking.  This is followed by language disorder and impairment of visuospatial skills. Neuropsychiatric symptoms like apathy, social withdrawal, disinhibition, agitation, psychosis, and wandering are also common in the mid to late stages. Difficulty performing learned motor tasks (dyspraxia), olfactory dysfunction, sleep disturbances, extrapyramidal motor signs like dystonia, akathisia, and Parkinsonian symptoms occur late in the disease. This is followed by primitive reflexes, incontinence, and total dependence on caregivers.  Pathophysiology of AD Amyloid beta normally plays an essential role in neural growth and repair, but It’s misfolded, resulting in Plaque. Called Amyloid Plague It is characterized by amyloid plaques in the cerebral cortex and in the walls of meningeal and cerebral blood vessels. In general, all pathologic changes are most prominent in the hippocampus, entorhinal cortex, association cortex, and basal forebrain. This accounts for the early symptoms of memory loss and disturbance of higher cortical functions, with preservation of primary sensory and motor function until later in the course. Treatment- cholinesterase inhibitors Connections of hypothalamus Nervous and endocrine systems work together Hypothalamus receive many nervous signals e.g., pain, emotion, olfactory. Also, hypothalamus receive substances (e.g., nutrients, electrolytes, H2O & hormones) from blood. Those substances blood excite or inhibit various portions of the hypothalamus. Then, hypothalamus contribute to endocrine system via regulation of pituitary gland secretion. Endocrine cells (Blood Neurohorm Neurohormone- vessel) one- ADH, hypophysiotropic oxytocin hormones Hypothalamus secrete neurohormones, including antidiuretic hormone, oxytocin, and hypophysiotropic hormones, which control the secretion of anterior pituitary hormones.,  Arousal, Sleep-wake cycle  The reticular activating system is excited by a wide variety of stimuli.  It is most compact in the midbrain and can be damaged by central midbrain lesions, resulting in failure of arousal or coma.  Less severe dysfunction causes confusional states in which consciousness is clouded and the patient is sleepy, inattentive, and disoriented.  Alertness is reduced, and the patient appears drowsy or falls asleep easily without frequent stimulation Damage to hypothalamus and weight gain Damage to the hypothalamus disrupts the carefully coordinated balance between energy intake and expenditure, often leading to increased calorie intake and/or decreased calorie burning, and thereby to rapid weight gain. This weight gain can be Hypothalamic-Pituitary Adrenal Axis It involves hypothalamus, pituitary and adrenal gland Infection/micro-organism stimulates the secretion of Interleukin and other cytokines from macrophages Cytokines travel to the hypothalamus to stimulate the release of corticotropin-releasing Hormone (CRH) Then, via endocrine circuit connection with the pituitary gland to release adrenocorticotropic hormone. This stimulates Cortisol secretion in the Adrenal gland. Corticol in the bloodstream serves negative feedback on the macrophages and inhibits further cytokine release. Distruption of this system causes Hypothalamic-Pituitary Gonadal Axis/ Vagal Inflammatory reflex HPG axis responsible for regulating reproductive activity and release of hormones. Similarly, the Vagus nerve from the brain innervates internal organs, including reproductive organs. These organs have a high concentration of phagocytic and macrophage-like cells. Sensory fibers of the vagus can detect cytokines ( IL-1 and TNF-alpha) released by infection sites of these organs. The info is transmitted to the brainstem, which stimulates the centre that controls the parasympathetic NS. The efferent parasympathetic postganglionic fibres ( including Vagus) release acetylcholine, which binds to nicotinic receptors on the macrophages in the organs. Binding of Acetylcholine to the macrophages inhibits the secretion of proinflammatory cytokines ( IL-1 and TNF-alpha). That’s The vagus nerve helps to reduce inflammation in the reproductive organs. Damage to the vagus nerve/ and brainstem can cause severe or exaggeration of inflammatory responses of the reproduction organs. Thus, infertility. Thank You Thanks for listening QUESTIONS? 6 9 69