Block 5 - Neurology

Question 1

What 4 things should you be thinking with any neurological presenting complaint?

Answer 1

Neurological Complaint: Any neurological presenting complaint think STROKE, BLEED, INFECTION or TUMOUR

Question 2

What are 9 differential diagnosis for a child who presents with fever and neurological symptoms?

Answer 2

Question 3

What is the Meningitis Classic Triad?

Answer 3

Meningitis Classic Triad: Headache + Photophobia + Neck Stiffness

Question 4

How does Bacterial Meningitis present clinically?

• Incubation?
• 6 Symptoms?
• 9 Signs?
• How does neonatal meningitis present?
• Which illness can it be confused with?

Answer 4

Bacterial Meningitis Classic Triad: Fever + Headache + Nick Stiffness

• Incubation: Normally 3-7 days or 2-10 days with meningococcal disease.
• Other Symptoms:
  
  1. Rash (meningococcal)
  2. Nausea & vomiting
  3. Photophobia
  4. Drowsiness, lethargy, irritability,
  5. Poor feeding, loss of appetite
  6. confusion and decreased conscious state.
• ‘Signs:
  
  1. Fever
  2. Meningism (classic features of meningitis)
  3. Kernig’s sign
  4. Brudzinski sign
  5. High pitched cry or irritability
  6. Opisthotonos (spasm of muscles causing backward arching of the head, neck and spine)
  7. Non-blanching petechial/purpuric rash
  8. Decreased GCS or coma, seizures, shock
  9. Bulging fontanelles.
• Neonatal Meningitis: Often nonspecific and without the classic triad of meningitis. Early onset presents with lethargy, vomiting, irritability, poor appetite, dyspnea and abnormal breathing patterns whilst late onset presents with fontanelle bulging, high-pitched crying and seizures.
• NB: Children may often present much like a viral gastroenteritis with fever, irritability and vomiting with no clear distinguishing features.

Question 5

How does Viral Meningitis present clinically?

• Incubation?
• 3 Constitutional Symptoms?
• 3 Meningeal Features?
• Cerebral dysfunction signs?

Answer 5

Viral Meningitis Features:

• Incubation: Normally 2-14 days but depends on virus
• Constitutional: Fever (not inevitable), malaise and/or myalgia
• Meningeal Features: Headache, photophobia and/or neck stiffness
• Cerebral Dysfunction: Altered consciousness, confusion, drowsiness, personality changes and/or seizures, Focal neurological deficit

Question 6

Indicate the cerebrospinal fluid (CSF) profiles in different types of meningitis

Answer 6

Question 7

Indicate the cerebrospinal fluid (CSF) profiles in different types of meningitis

Answer 7

Question 8

What happens to CSF protein levels in Bacterial meningitis and why?

Answer 8

CSF Protein:

Spinal fluid normally contains very little protein since serum proteins are large molecules that do not cross the blood-brain barrier. Bacterial meningitis leads to a more permeable blood brain barrier (due to increased inflammation) allowing protein to leak into the subarachnoid space from the blood, resulting in markedly increased CSF protein levels.

Question 9

What happens to CSF glucose levels in bacterial meningitis and why?

What is the normal CSF glucose level?

Answer 9

CSF Glucose:

Decrease in glucose levels during a CNS infection is caused due to glycolysis by both white cells and the pathogen, and impaired CSF glucose transport through the blood-brain barrier (inflammation of the meninges leads to decreased glucose receptor expression).

CSF glucose is usually 2/3 of serum and bacterial meningitis CSF glucose is usually 1/3 of serum.

Question 10

What are 10 investigations for meningitis and their reasoning?

• What are the indications for LP?
• What will CRP tell us in a patient with a CSF gram stain that did not grow anything?
• What is DIC caused by?
• When should a cranial CT scan be considered before LP? (5)

Answer 10

Investigations for Meningitis:

1. Lumbar Puncture (LP) at L3/L4 → To evaluate CSF in suspected meningitis, subarachnoid hemorrhage, carcinomatosis, multiple sclerosis and syndromes such as Guillain-Barré and can be used to measure CSF pressure.
2. CSF Cell Count, Glucose, Protein, PCR, Gram Stain Culture → Following lumbar puncture, to evaluate CSF. Note that results of culture may be influenced by previous antimicrobial therapy.
3. Blood Culture → To detect pathogens and determine sensitivity. Note that results of blood cultures may be influenced by previous antimicrobial therapy.
4. Blood Glucose → Comparison with CSF glucose.
5. FBC → To determine WCC and predominance of lymphocytes or polymorphonuclear cells.
6. CRP → To evaluate degree of inflammation and monitor management. For instance, in patients where the CSF gram stain is negative and the differential diagnosis is between bacterial and viral meningitis, a normal serum CRP concentration excludes bacterial meningitis with approximately 99% certainty.
7. Electrolytes, Calcium, Glucose and Magnesium → Patients with severe bacterial meningitis often have metabolic abnormalities, especially acidosis, hypokalaemia, hypoglycaemia, and hypocalcemia.
8. Coagulation Profile → Coagulopathy is common in severe meningitis infections. Disseminated intravascular coagulation (DIC) is caused by acquired deficiencies of protein C, protein S, and antithrombin III, increases in plasminogen activator inhibitor and thrombin-activatable fibrinolysis inhibitor and reduced activation of protein C on endothelial cells.
9. Cranial CT Scan → Cranial CT scan should be considered before lumbar puncture in the presence of 1. focal neurological deficit, 2. new-onset seizures, 3. papilloedema (optic disc swelling), 4. altered mental state, or 5. immunocompromised state to exclude a brain abscess or generalised cerebral oedema. Cranial imaging may be used to identify underlying conditions and meningitis-associated complications. Brain infarction, cerebral oedema, and hydrocephalus are common findings especially in pneumococcal meningitis.
10. Throat Swab → For PCR meningococcus.

Question 11

What are the layers pierced when performing an LP?

Answer 11

Question 12

Answer 12

Question 13

What are 7 risk factors for meningitis?

Answer 13

Risk Factors (Susceptible Host):

1. Immunocompromised host
2. Bacteremia/Viremia
3. Endocarditis
4. Asplenia
5. Site- specific infections
6. Cranial injury
7. Surgery.

Question 14

What are the 3 types of meningitis and examples of each?

Answer 14

Types of Meningitis:

Bacterial: Bacterial infection

Aseptic: Viral, TB, fungal or parasitic infection

Sterile: Malignancy (lymphoma), drugs or autoimmune (SLE)

Question 15

What is the Pathophysiology of Meningitis?

• 3 steps?
• Where do most pathogens that cause meningitis colonise first?
• What are 4 ways pathogens can gain access to the CNS?

Answer 15

Pathophysiology of Meningitis:

1. Local colonisation (adherence) or infection of pathogen (skin, nasopharynx, respiratory tract, GIT or GUT). Most pathogens that cause meningitis colonise the nasopharynx or the upper airways.
2. Pathogen invades the submucosa at these sites by overcoming host defences.
3. Pathogens gain access to CNS causing infection and inflammation of meninges (meningitis)
   
   1. Bloodstream invasion and hematogenous dissemination
   2. Contiguous spread of infections in nose, eyes, and ears such as with sinusitis and otitis media
   3. Retrograde transport along or inside peripheral or cranial nerves such as with HSV and VZV
   4. Direct infection (due to trauma or head surgery)

Question 16

What are some routes of entry for CNS infection?

Answer 16

Question 17

List the common organisms (viral, bacterial, fungal and parasitic) that cause meningitis.

• 9 bacterial?
• 8 viral?
• 2 parasitic?
• 1 fungal?

Answer 17

Question 18

List the common organisms (viral, bacterial, fungal and parasitic) that cause meningitis in Newborns? = 5

Answer 18

Pathogens by Demographics: NEWBORNS

1. Group B Streptococcus (most common)
2. Gram-negative bacilli (e.g. Escherichia coli)
3. Listeria monocytogenes
4. Haemophilus influenzae
5. Enterobacter cloacae

Question 19

List the common organisms (viral, bacterial, fungal and parasitic) that cause meningitis in Infants (1-5 months)? = 4

Answer 19

Pathogens by Demographics: Infants (1-24 Months)

1. Streptococcus pneumoniae and Neisseria meningitidis (most common)
2. Listeria monocytogenes
3. Haemophilus influenzae
4. Group B Streptococcus

Question 20

List the common organisms (viral, bacterial, fungal and parasitic) that cause meningitis in Children & Teens? = 6

Answer 20

Pathogens by Demographics: CHILDREN & TEENS

1. Neisseria meningitidis (most common)
2. Streptococcus pneumoniae
3. Listeria monocytogenes
4. Haemophilus influenzae
5. Enteroviruses (e.g. Coxsackievirus and echovirus)
6. Herpes simplex virus (HSV-2)

Question 21

List the common organisms (viral, bacterial, fungal and parasitic) that cause meningitis in Adults (18-60 Years)? = 6

Answer 21

Pathogens by Demographics: ADULTS (18-60 Years)

1. Streptococcus pneumoniae (most common)
2. Neisseria meningitidis
3. Listeria monocytogenes
4. Haemophilus influenzae
5. Enteroviruses (e.g. Coxsackievirus and echovirus)
6. Herpes simplex virus (HSV-2)

Question 22

List the common organisms (viral, bacterial, fungal and parasitic) that cause meningitis in

• Elderly (>60 Years)
• Immunocompromised Patients
• Pregnant Women
• Hospitalised Patients

Answer 22

Question 23

What are the Key Principles in Managing Meningitis?

Answer 23

Key Principles in Managing Meningitis:

• Clinical differentiation of bacterial meningitis from other diagnoses (such as aseptic meningitis, encephalitis or subarachnoid haemorrhage) can be difficult.
• Lumbar puncture to obtain CSF for culture is key to diagnosis and directed therapy for bacterial meningitis.
• Neuroimaging (typically CT scan) may be required for patients with possible raised ICP; it can also be
• important for differential diagnoses.
• Ideally, obtain microbiological samples (e.g. CSF, blood) before starting empirical antibiotic therapy.
• Early empirical broad antibiotic therapy is appropriate when clinical suspicion of bacterial meningitis is high, ideally within 60 minutes of presentation to hospital. Do not withhold treatment if there is a significant delay in performing investigations.
• Once pathogen identified, treat using specific narrow antibiotic therapy with sensitivities.
• Follow Department of Health notifiable disease process if applicable.
• Treat household contacts (clearance antibiotics).
• Treat healthcare workers if exposed to respiratory secretions e.g. intubation or CPR without mask.

Question 24

Outline the current treatment guidelines for meningitis in children

Answer 24

Question 25

What are the 3 brain capillary layers?

Answer 25

Brain Capillary Layers:

1. Endothelium of the capillary wall
2. Relatively thick basal lamina surrounding the external face of each capillary
3. Bulbous “feet” of the astrocytes clinging to the capillaries

Question 26

What is the Blood Brain Barrier?

• Definition?
• What forms the BBB?
• Importance?
• Structure? In which areas is the BBB absent?

Answer 26

Blood Brain Barrier

Definition: A highly selective semipermeable border that separates circulating blood from the brain and ECF in the CNS which functions to maintain a constant environment in the CNS

Formation: Formed by continuous tight junctions between endothelial cells (least permeable capillaries in the body), which prevent water-soluble ions and molecules from passing from the blood into the brain through the paracellular route. These capillaries are non-leaky and have reduced transcytosis.

Importance: Contributes to stabilisation and protection of the neuronal microenvironment by facilitating the entry of needed substances, removing waste metabolites, and excluding toxic or disruptive substances. Protection from endogenous and exogenous toxins in the blood.

Structure: BBB is not completely uniform and is absent in some areas causing the capillaries to be quite permeable to bloodborne molecules. The BBB is absent at the vomiting centre of the brainstem which monitor for poisons in the blood, and at the hypothalamus which samples the chemical composition of the blood to regulate water balance, body temperature and other metabolic activities.

Question 27

How is the movement of substances across the BBB regulated?

• Which substances can cross via simple diffusion?
• Which substances can cross via facilitated diffusion?
• Which carrier mechanisms are present?
• Can potassium enter the brain?
• What is the BBB ineffective against stopping?

Answer 27

Movement of Substances across the BBB

• Small hydrophobic molecules (O2, CO2, ethanol) can diffuse through endothelial cell membrane
• Nutrients such as glucose, essential amino acids, and some electrolytes move passively by facilitated diffusion through the endothelial cell membranes
• Entry of small molecules into the brain is restricted by carrier mechanisms (glucose, GLUT -1 transporter, amino acids, L-1 transporter) within endothelial cells
• Bloodborne metabolic wastes, proteins, certain toxins, and most drugs are denied entry.
• Small nonessential amino acids and potassium ions are prevented from entering the brain and are also actively pumped from the brain across the capillary endothelium.
• The barrier is ineffective against fats, fatty acids, oxygen, carbon dioxide, and other fat -soluble molecules that diffuse easily through all plasma membranes. This explains why bloodborne alcohol, nicotine, and anesthetics can affect the brain.

Question 28

How can drugs be delivered to the CNS?

• What effect does lipid solubility have on transport rate across the BBB?
• Do B-lactams penetrate the BBB well? In which scenario can they cross more easily?

Answer 28

Delivery of Drugs to the CNS:

• The BBB makes the brain inaccessible to many drugs whose lipid solubility is insufficient to allow penetration (must be lipid-soluble to pass)
• While lipid solubility can increase transport rate across the BBB, it can also lower the amount of the drug presented to the BBB given that lipid solubility favours uptake by the peripheral tissues which in turn lowers the concentration of the drug in blood
• B-lactams penetrate the intact BBB poorly
• Inflammation can disrupt the integrity of the BBB, allowing normally impermeant substances to enter
  
  • For example, penicillin can be given intravenously (rather than intrathecally) to treat bacterial meningitis due to inflammation-induced permeable capillaries

Question 29

Discuss the decision-making implications regarding further investigations, e.g. lumbar puncture, CT scan, when physical examination findings for meningitis are equivocal

• Is meningitis an emergency?
• Should you investigate or treat for suspected meningitis first?
• Abs before LP?
• CT before LP?

Answer 29

Meningitis Decision-Making:

Emergency: Meningitis is a medical emergency and treatment should not be delayed for more than 1-2 hours while diagnostic tests are taking place.

Investigations: Do not withhold treatment if there is a significant delay in performing investigations.

Lumbar Puncture Delay: If lumbar puncture (for CSF gram stain and culture) will add significant delay do not hesitate to begin empiric antibiotic treatment first. Blood cultures taken before antibiotic therapy can provide pathogen information.

CT Scan: Not necessary if no lumbar puncture contraindications. If some contraindications are present or if the diagnosis is in doubt, consider a CT scan prior to lumbar puncture but do not delay treatment to do so.

Question 30

Perform an examination focusing on the relevant clinical features in suspected acute meningitis

Answer 30

Question 31

What are fontanelle? How many? Where are they? When do they close?

Answer 31

Fontanelle = growth areas of the skull that are present since before birth up until certain ages in young children.

• The anterior fontanelle known as bregma closes between 4-26 months. It is a diamond-shaped space located between the paired frontal and parietal bones of the fetal/neonatal skull (also described as the junction of the coronal and sagittal sutures).
• The posterior fontanelle known as lambda closes much earlier than the anterior, at only 1-2 months after birth. It is located where the two parietal bones meet the occipital bone (also described as the junction of the sagittal and lambdoid sutures).
• The sphenoidal fontanelle (also known as the anterolateral fontanelle) closes between 2-3 months and is called pterion. It is located at the junction of the sphenoid, parietal, temporal, and frontal bones.
• The final fontanelle, which closes at 12-18 months, takes its name from the area in which it is situated, the mastoid fontanelle, otherwise known as the asterion fontanelle. It is located at the junction of the temporal, occipital, and parietal bones.

Question 32

What are the meninges?

• 4 functions?

Answer 32

Meninges: Three connective tissue membranes that lie just external to the CNS (brain and spinal cord).

1. Cover and protect the CNS
2. Protect blood vessels and enclose venous sinuses
3. Contain cerebrospinal fluid (CSF)
4. Form partitions in the skull

Question 33

What is the Dura Mater?

• What type of tissue is it?
• 2 layers?
• Which 2 features does it contain?

Answer 33

Dura Mater (External): The external, strong, dense and impermeable meninx that envelopes the CNS

• Two-layered sheet of fibrous connective tissue
  
  1. Periosteal Layer: Attaches to the inner surface of the skull (no dural periosteal layer surrounding the spinal cord)
  2. Meningeal Layer: The true external covering of the brain and continues caudally in the vertebral canal as the spinal dura mater
• Dural Venous Sinuses: Venous channels located intracranially between the two layers of dura mater (not fused in these places), which collects venous blood from the brain and directs it into the internal jugular veins of the neck
• Dural Septa: In several places, the meningeal dura mater extends inward to form flat partitions that subdivide the cranial cavity, which limit excessive movement of the brain within the cranium

Question 34

What is the subdural space?

• Where is it located?
• What does it contain?
• Function?

Answer 34

Subdural Space: A narrow serous cavity between the dura and arachnoid mater, which contains a watery fluid, allowing the membranes to glide freely. It provides venous drainage of the brain, also draining the spent CSF via bulk flow through the arachnoid villi.

Question 35

What is the Arachnoid mater?

• What is the subarachnoid space? What is it filled with?
• What are Arachnoid Villi?

Answer 35

Arachnoid Mater:

• The fine, elastic and transparent middle meninx
• It forms a loose brain covering, never dipping into the sulci at the cerebral surface
• Subarachnoid Space: A wide space beneath the arachnoid mater that contains spiderweb-like extensions that span the space and secure the arachnoid mater to the underlying pia mater. Filled with CSF and contains the largest blood vessels serving the brain (blood vessel poorly protected)
• Arachnoid Villi: Knoblike projections of the arachnoid mater protrude superiorly through the dura mater and into the superior sagittal sinus to absorb CSF into the venous blood of the sinus

Question 36

What is the pia mater?

Answer 36

Pia Mater (Internal):

• The internal and delicate meninx that clings tightly to the brain
• Richly invested with tiny blood vessels, where small arteries entering the brain tissue carry ragged sheaths of pia mater inward with them for short distances

Question 37

What are 4 functions of CSF?

Answer 37

CSF Functions:

1. Forms a liquid cushion that gives buoyancy to CNS structures (by floating the jellylike brain, the CSF effectively reduces brain weight by 97% and prevents the brain from crushing under its own weight)
2. Protects the brain and spinal cord from blows and other trauma
3. Nourishes the brain
4. Carries chemical signals (i.e. hormones) from one part of the brain to another

Question 38

What volume of CSF does a normal adult have? How often is it replaced? Total daily volume formed?

Answer 38

CSF Volume: In adults, the total CSF volume of about 150 ml is replaced every 8 hours or so. About 500 ml of CSF is formed daily.

Question 39

What is the composition of CSF?

Answer 39

CSF Composition:

Watery composition similar to blood plasma, but contains less protein, Ca2+ and K+ and more Na+, Cl- and H+ than plasma. Contains glucose, oxygen, vitamins, and ions.

Question 40

How and where is CSF produced?

Answer 40

CSF Production:

• Formed by choroid plexuses that hang from the roof of each ventricle
• Each choroid plexus consists of a knot of porous thin-walled capillaries enclosed first by pia mater and surrounded by a single layer of ependymal cells joined by tight junctions and bearing long cilia
• Choroid plexuses also help cleanse the CSF by removing waste products and unnecessary solutes
• Regulation:
  
  • Fluid leaking from porous capillaries is processed by the ependymal cells to form the CSF in the ventricles.
  • Ependymal cells modify the filtrate by actively transporting only certain ions across their membranes into the CSF pool.

Question 41

What are the brain ventricles?

• How many?
• Location?

Answer 41

Ventricles:

• A set of four interconnected cavities in the brain, where CSF is produced.
• The two largest are the lateral ventricles in the cerebrum.
• The third ventricle is in the diencephalon of the forebrain between the right and left thalamus.
• The fourth ventricle is located at the back of the pons and upper half of the medulla oblongata of the hindbrain.

Question 42

Describe the circulation of the CSF?

Answer 42

CSF Circulation:

Moves freely through the ventricles, where the long cilia of the ependymal cells lining the ventricles help keep the fluid in constant motion.

1. The choroid plexus of each ventricle produces CSF
2. CSF flows through the ventricles and into the subarachnoid space via the median and lateral apertures of the fourth ventricle
3. CSF flows through the subarachnoid space and bathes the outer surfaces of the brain and spinal cord
4. CSF then returns to the blood as it is absorbed into the dural venous sinuses via the arachnoid villi

Question 43

What is a headache?

What are primary headaches? What are the 4 types of primary headache?

• Migraine triggers?
• 4 other headaches?

Answer 43

Headaches: Diffuse pain in various parts of the head, with the pain not confined to the area of distribution of a nerve.

Primary Headaches: Headache in the absence of any structural defects in the CNS (nor organic disease as cause).

1. Tension-Type: Cause unclear. Can be brought on by emotional distress, stress or fatigue. Most common type of headache.
2. Migraine (With/Without Aura): Unknown root cause. Triggers include dehydration, certain foods, insufficient food, hormones, environmental such as sudden changes in weather, oversleeping or too little sleep, physical factors such eye, dental problems, over-exertion or strenuous exercise and certain medications.
3. Cluster
4. Other: Cough headaches, post-coital headaches, headaches following physical exertion and headaches associated with fluctuating hormone levels (start of the OCP, menstruation, perimenopause)

Question 44

What is a Migraine Aura? Pathophysiology? What percentage of migraine patients will have an aura?

Answer 44

Migraine Aura:

• Neuronal hyperexcitability due to spreading cortical depression (a wave of neuronal depolarisation and increased blood flow followed by depressed activity and decreased blood flow spreading slowly anteriorly across the cerebral cortex from the occipital region).
• Aura seen in 20 -30% of migraine patients and associated with expanding scotoma (area of visual blurriness) and spreading paresthesias (tingling/prickling sensation) from hand, arm to face.

Question 45

What is the pathophysiology of pain in migraine?

Answer 45

Migraine - Pathophysiology of Pain:

• Activation of trigeminovascular system (large intracranial vessels and dura innervated by the first division of the trigeminal nerve).
• Release of calcitonin generelated peptide (CGRP), substance P and other vasoactive peptides including 5-HT by activated trigeminovascular neurons causes painful meningeal inflammation and vasodilation.

Question 46

What causes stimuli insensitivity in migraine?

Answer 46

Migraine - Stimuli Insensitivity:

Peripheral and central sensitisation of trigeminal neurons and brainstem pain pathways makes otherwise innocuous sensory stimuli (such as CSF pulsation and head movement) painful, and light and sound perceived as uncomfortable. Central sensitisation associated with facial allodynia whilst peripheral sensitisation associated with cranial blood vessels, intravascular pulsations and inappropriate dural nociceptor activation (occurs with stress such as bending over or exercise).

Question 47

What are cluster headaches?

• What reflex in the brain is activated? What can cause this? (5)
• Clinical features?
• What is an associated sign of cluster headaches?

Answer 47

Cluster headaches

• The commonest trigeminal autonomic cephalgia.
• Headaches that occur upon activation of trigeminal-autonomic reflex pathway in the brainstem.
• The trigeminal nerve is the chief sensory nerve of the face. When activated, the trigeminal nerve leads to eye pain and also stimulates the parasympathetic autonomic system, which causes eye tearing and redness, nasal congestion and discharge.
• Horner’s syndrome is an associated sign.
• The trigeminal nerve can become activated following:
  
  1. Herpes zoster virus (shingles) infection
  2. Compression or irritation of the nerve fibres
  3. Snusitis
  4. Toothache
  5. Nerve injury

Question 48

What are the simplified diagnostic criteria for migraine?

Answer 48

POUND: Pulsatile, One-day duration, Unilateral, Nausea, Disabling

Question 49

What is a Tension headache?

• Epidemiology?
• Duration?
• Frequency?
• Does exertion exacerbate the pain?
• Is Nausea and vomiting usually present?
• Therapy - Acute? Chronic?
• Triggers?
• Character of the pain?
• Other symptoms?
• Course of an attack?
• Prophylaxis?

Answer 49

Question 50

What is a Migraine headache?

• Epidemiology?
• Duration?
• Frequency?
• Age of onset?
• Therapy?
• Triggers?
• Character of the pain?
• Other symptoms?
• Course of an attack?
• Prophylaxis?

Answer 50

Question 51

What is a Cluster headache?

• Epidemiology?
• Duration?
• Frequency?
• Timing of onset?
• Therapy?
• Triggers?
• Character of the pain?
• Other symptoms?
• Course of an attack?

Answer 51

Question 52

Compare migraine, tension, & cluster headache in terms of:

• Location?
• Character?
• Course?
• Additional Symptoms?
• Age of onset?
• Exacerbating factors?
• Which have a high risk of medication-overuse headache?
• Which types will/won’t present with autonomic symptoms?

Answer 52

Question 53

For Cluster, Tension and Migraine headaches explain the:

• Localisation?
• Duration?
• Description?

Answer 53

Question 54

For Trigeminal Neuralgia, Meningitis and Encephalitis headaches explain the:

• Localisation?
• Duration?
• Description?

Answer 54

Question 55

For Intracerebral Hemorrhage, Subarachnoid Hemorrhage and Epidural/Subdural Hemorrhage headaches explain the:

• Localisation?
• Duration?
• Description?

Answer 55

Question 56

For Cerebral Venous Thrombosis, Temporal Arteritis and Stroke headaches explain the:

• Localisation?
• Duration?
• Description?

Answer 56

Question 57

For Tumour, Traumatic Brain Injury, Glaucoma and Medication Overuse headaches explain the:

• Localisation?
• Duration?
• Description?

Answer 57

Question 58

List and discuss the pain-sensitive structures in the head.

• Where are pain receptors in the head located?
• Which nerves are responsible for mediating most head pain?
• What are the 5 intracranial pain sensitive structures?
• What are the 6 extracranial pain sensitive structures?

Answer 58

General Description of Pain Sensitive Structure in Head:

• Pain receptors are located at the base of the brain in arteries and veins and throughout meninges, extracranial vessels, scalp, neck and facial muscles, paranasal sinuses, eyes and teeth.
• Curiously, brain substance is almost devoid of pain receptors.
• Head pain is mostly mediated by CN V and IX and upper cervical sensory roots.

Question 59

CNS Tumours:

• What tissue do most CNS tumour arise from?
• What percentage of CNS tumours are primary and metastatic?
• Most common primary CNS tumours in children vs. adults?
• What are the characteristics of metastatic CNS tumours?
• Where do metastatic CNS tumours usually derive from?

Answer 59

CNS Tumours: Most arise from glial cells (glioma) rather than neuronal cells. The most common group of primary brain tumors, include astrocytomas, oligodendrogliomas, and ependymomas.

Primary (50%): Usually supratentorial in adults and infratentorial in children. Most common tumours in adults are glioblastoma, meningioma, and schwannoma. Most common tumours in children are pilocytic astrocytoma, ependymoma, and medulloblastoma. Primary malignant CNS tumours are locally destructive, but rarely metastasize.

Metastatic (50%): Multiple, well-circumscribed lesions at the gray-white junction, commonly from lung, breast, kidney and melanoma (“Brain Mets KiLl”)

Question 60

What are 10 examples of Primary CNS Tumours?

• What is the Most Common Benign CNS tumour in Children?
• What is the Most Common Benign CNS tumour in Adults?
• What is the Most Common Malignant CNS tumour in Children?
• What is the Most Common Malignant CNS tumour in Adults?

Answer 60

Primary CNS Tumours

1. Fibrillary Astrocytoma
2. Pilocytic Astrocytoma (Most Common Benign Children)
3. Glioblastoma Multiform (Most Common Malignant Adults)
4. Oligodendroglioma
5. Ependymoma
6. Schwannoma
7. Meningioma (Most Common Benign Adults)
8. Medulloblastoma (Most Common Malignant Children)
9. Hemangioblastoma
10. Craniopharyngioma

Question 61

What is a Fibrillary Astrocytoma?

• Where do they often occur?
• How do patients often present?
• 4 Characteristics?
• What is GFAP?
• Which mutation are they associated with?

Answer 61

Primary CNS Tumours - Fibrillary Astrocytoma

• Malignant diffusely infiltrating tumour of astrocytes.
• Often occur in the cerebral hemispheres, pons and spinal cord.
• Patient often presents with epilepsy.
• Characterised by:
  
  1. Microcysts
  2. Atypical cells with high N:C ratio
  3. Nuclear hyperchromasia
  4. No mitoses.
• Tumour cells are GFAP positive (signature cytoskeleton filament of astrocytes).
  
  • Glial fibrillary acidic protein (GFAP) is an important diagnostic marker for astrocytomas; it is almost always positive in glioblastoma multiforme!
• Associated with isocitrate dehydrogenase-1 mutation.
• Anaplastic astrocytoma have all the features of fibrillary astrocytoma plus mitoses and higher pace of growth.

Question 62

What is a Pilocytic Astrocytoma?

• Which age group are they more common in?
• Where do they usually arise?
• What does imaging look like?
• What does biopsy show?
• Characteristics?
• Associated with which mutation?

Answer 62

Primary CNS Tumours - Pilocytic Astrocytoma

• Most Common Benign Children
• Benign circumscribed tumor of astrocytes.
• Most common CNS tumor in children, usually arises in the cerebellum.
• Imaging reveals a cystic lesion with a mural nodule.
• Biopsy shows Rosenthal fibers (thick eosinophilic processes of astrocytes) and eosinophilic granular bodies.
• No necrosis and mitoses rare.
• Tumour cells are GFAP positive.
• Associated with BRAF mutation.

Question 63

What is a Glioblastoma Multiform?

• Which age group are they more common in?
• Where do they usually arise?
• What does imaging look like?
• Characteristics?
• Prognosis?
• Associated with which mutation?

Answer 63

Primary CNS Tumours - Glioblastoma Multiform

• Malignant, high-grade tumour of astrocytes.
• Most common primary malignant CNS tumor in adults.
• Usually arises in the cerebral hemisphere, characteristically crosses the corpus callosum (‘butterfly’ lesion).
• Characterised by regions of necrosis surrounded by tumour cells (pseudopalisading) and endothelial cell proliferation. Cystic areas, hemorrhage and well demarcated but deceptively infiltrative.
• Tumour cells are GFAP positive.
• Poor prognosis.
• Endpoint of neoplastic progression from astrocytoma.
• Associated with histone mutations.

Question 64

What is a Oligodendroglioma?

• Where do they usually occur?
• Characteristics?
• What does imaging look like?
• Clinical presentation?
• Biopsy appearance?

Answer 64

Primary CNS Tumours - Oligodendroglioma

• Malignant tumour of oligodendrocytes.
• Often occurs in cerebral hemispheres, rarely brainstem or spinal cord.
• Hemorrhaging and calcification common.
• Imaging reveals a calcified tumor in the white matter, usually involving the frontal lobe.
• May present with seizures, and often long history of epilepsy.
• ‘Fried-egg’ appearance of cells on biopsy.

Question 65

What is an Ependymoma?

• Which age group?
• Where do they common arise from?
• Clinical presentation?
• Characteristic biopsy finding?

Answer 65

Primary CNS Tumours - Ependymoma

• Malignant tumor of ependymal cells.
• Usually seen in children.
• Most commonly arises in the 4th ventricle.
• May present with hydrocephalus.
• Perivascular pseudorosettes are a characteristic finding on biopsy.

Question 66

What is a Schwannoma?

• Which age group?
• What do they involve?
• Tumour marker?
• In which condition are bilateral tumours seen?

Answer 66

Primary CNS Tumours - Schwannoma

• Benign tumor of Schwann cells.
• Involves cranial or spinal nerves within the cranium, most frequently involves cranial nerve VIII at the cerebellopontine angle (presents as loss of hearing and tinnitus).
• Tumor cells are S-100 positive.
• Bilateral tumours are seen in neurofibromatosis type 2.

Question 67

What is a Meningioma?

• Which age group?
• Clinical presentation?
• Location?
• Imaging features?
• Biopsy features?

Answer 67

Primary CNS Tumours - Meningioma

• Benign tumor of arachnoid cells in leptomeninges.
• Most common benign CNS tumor in adults.
• More commonly seen in women, rare in children.
• May present as seizures.
• Tumour compresses, but does not invade, the cortex.
• Imaging reveals a round mass attached to the dura.
• Histology shows a whorled pattern, psommoma bodies may be present.

Question 68

What is a Medulloblastoma?

• Which age group?
• Histology?
• Prognosis?
• What is ‘drop metastasis’?

Answer 68

Primary CNS Tumours - Medulloblastoma

• Malignant embryonal tumor derived from the granular cells of the cerebellum (neuroectoderm)
• Usually arises in children.
• Histology reveals small, round blue cells. Homer-Wright rosettes may be present.
• Poor prognosis as tumor grows rapidly and spreads via CSF.
• Metastasis to the cauda equina is termed ‘drop metastasis.’

Question 69

What is a Hemangioblastoma?

• Where does it start?
• Characteristics?
• Associated with which syndrome?

Answer 69

Primary CNS Tumours - Medulloblastoma

• A rare, slow growing brain tumour.
• It starts in the cells lining the blood vessels in the brain and sometimes in the spinal cord.
• Characterised as cyst with tumour nodule in wall.
• Associated with von Hippel-Lindau syndrome (autosomal dominant) which is the formation of tumours and fluid-filled sacs (cysts) in many different parts of the body and includes retinal angioma, renal cell carcinoma, phaeochromocytoma and pancreatic, renal and epididymal cysts.

Question 70

What is a Hemangioblastoma?

• Where does it arise?
• Clinical presentation?
• Imaging features?

Answer 70

Primary CNS Tumours - Craniopharyngioma

• Tumour that arises from epithelial remnants of Rathke’s pouch.
• Presents as a supratentorial mass in a child or young adult, may compress the optic chiasm leading to bitemporal hemianopsia.
• Calcifications are commonly seen on imaging (derived from “tooth-like” tissue). Benign, but tends to recur after resection.

Question 71

What are 6 complications of CNS tumours?

6 Types of herniation?

Answer 71

Complications of CNS Tumours:

Peritumoural Oedema: Swelling of surrounding tissue due to vascular compression and increased vascular permeability (transudate), worsens raised ICP effects and is very steroid responsive.

Herniation: Transtentorial, parahippocampal, uncal, subfalcine, tonsillar or superior cerebellar.

Other: Severe disability including seizures, poor memory or speech problems, physical dysfunction and death depending on neurological impact

Question 72

Explain the Pathophysiology of a Non-Penetrating Head Injury.

Answer 72

CNS TRAUMA - Non-Penetrating Head Injury Pathophysiology:

• Acceleration/deceleration forces → Linear or rotational movement → Movement of brain which lags behind skull → Shearing, strain, and compression effects within the skull (diffuse injury).
• Can also result in coup injury (cerebral contusion on the side of an impact) or contrecoup (additional cerebral contusion on the opposite side of impact).
• Contact damage at or just deep to point of impact.
• Common causes dues to falls, motor vehicle accidents, contact sport and gunshot wounds.

Penetrating Head Injury Pathophysiology: Penetration of skull and brain by external object e.g. bullet

Question 73

What are the clinical features of CNS trauma?

Answer 73

CNS TRAUMA - Clinical Features:

1. Headache
2. Amnesia
3. Confusion, disorientation
4. Impaired consciousness
5. Dizziness
6. Nausea and vomiting
7. Impaired speech, impaired coordination, changes in mood and behaviour, focal neurological deficits, seizures and sensory disturbances.

Clinical findings vary depending on the location, severity, and type of injury. In addition to the initial presentation, further symptoms may develop as lesions progress.

Question 74

What are the two types of complications of CNS trauma? Examples of each.

Answer 74

CNS TRAUMA - Complications:

Primary Damage: Scalp laceration, skull fracture (considerable force), cerebral contusions (superficial bruising of brain), cerebral lacerations, intracranial hemorrhage (tearing of bridging veins in dural sinuses) and diffuse axonal injury (shearing stress within brain).

Secondary Damage: Ischaemia, hypoxia, cerebral swelling and raised ICP, infection and neurological deterioration in severe cases.

Question 75

What is an Intracerebral Hemorrhage?

• Pathophysiology?
• Clinical Features?
• Complications?

Answer 75

Question 76

What is an Epidural Hemorrhage?

• Pathophysiology?
• Clinical Features?
• Complications?

Answer 76

Question 77

What is a Subdural Hemorrhage?

• Pathophysiology?
• Clinical Features?
• Complications?

Answer 77

Question 78

What is a Subarachnoid Hemorrhage?

• Pathophysiology?
• Clinical Features?
• Complications?

Answer 78

Question 79

What is a CNS Infarction?

• Ischaemic Stroke Pathophysiology?
• Haemorrhagic Stroke Pathophysiology?
• Clinical Features?
• Complications?

Answer 79

CNS Infarction: Thrombosis, embolism, vasospasm, arteritis and trauma!

Ischaemic Stroke Pathophysiology: Commonly due to large artery atherosclerosis (secondary to hypertension) and occlusion, thrombi, embolisms (cardiac AF emboli, infectious emboli or atheroemboli) or small vessel occlusion. Most important risk factors include arterial hypertension and increasing age.

Haemorrhagic Stroke Pathophysiology: Due to intracerebral hemorrhage or subarachnoid hemorrhage. Both forms of bleeding can be traumatic or nontraumatic (spontaneous).

Clinical Features: Sudden onset of focal neurologic deficits and nonspecific symptoms (impaired consciousness, nausea, vomiting, headache, and less commonly, seizures). May be TIA where symptoms last less than 24 hours. Signs of SAH or ICH if haemorrhagic stroke. Clinical features dependent on vessels affected.

Complications: Elevated ICP and brain herniation, seizures, persistent neurologic deficits and memory impairment. Complications related to SAH and ICH hemorrhage if haemorrhagic stroke.

Question 80

Obtain a relevant history from a patient with a headache and subsequently construct a differential diagnosis of the headache in that patient.

What are some questions you should ask a patient with a headache?

Answer 80

Question 81

What are red flags in the evaluation of acute headaches in adults?

Answer 81

Headache red flags (SNOOP15)

1. Systemic symptoms (e.g., fever, signs of meningitis, myalgia, malaise)
2. Neoplasm in history
3. Neurological deficits/dysfunction (e.g., altered mental status, seizures)
4. Onset of headache is sudden or abrupt
5. Older age at onset (> 50 years)
6. Pattern changes of headache or recent onset
7. Positional headache
8. Precipitated by sneezing, coughing, or exercise
9. Papilledema and other signs of increased ICP
10. Progressive headache and atypical features
11. Pregnancy or postpartum period
12. Pain of the eye with autonomic features and visual deficits
13. Posttraumatic onset
14. Pathology of the immune system (especially due to HIV)
15. Painkiller overuse or new drug at onset of headache

Question 82

Obtain a relevant examination from a patient with a headache and subsequently construct a differential diagnosis of the headache in that patient.

• What is involved in the examination of a patient presenting with a headache?
• What signs/symptoms are you looking out for?

Answer 82

Specific Examination Findings and Differentials:

• Blood pressure measurement to rule out hypertension and/or a hypertensive crisis.
• Focal neurological deficits are typically present in stroke, intracranial hemorrhage, meningoencephalitis, intracranial space-occupying lesions, and/or cerebral venous sinus thrombosis.
• Fever usually indicates an infectious cause of headache.
• Tenderness of pericranial muscles may indicate a tension-type headache.
• The superficial temporal artery is tender and palpably thickened in the case of temporal arteritis.
• Trigger points along the course of the trigeminal nerve may be present in the case of trigeminal neuralgia.
• Painful jaw movement may indicate temporal arteritis or disorders of the temporomandibular joint.
• Examination of the teeth and oral cavity may reveal dental or maxillary disease.
• Eyeball tenderness and/or painful ocular movement may indicate raised intra-ocular pressure.
• Restricted cervical spine mobility may be present in the case of cervicogenic headache.
• Tenderness over the sinuses is present in the case of sinusitis.

Question 83

Discuss the investigation of headache due to cerebral aneurysms or tumours.

• What is the first line investigation for sudden acute headache?
• How does a Subarachnoid Hemorrhage appear on a CT?
• How does a Extra/Epidural Hemorrhage appear on a CT?
• How does a Subdural Hemorrhage appear on a CT?
• How does a Cerebral Metastasis appear on a CT?
• What are 2 other investigations to consider? What are we trying to rule out?

Answer 83

Headache Investigations: Diagnostic tests are usually not indicated in most cases (especially primary headaches). They are used primarily to evaluate secondary headaches and severe, acute headaches, which may be life- threatening (e.g. subarachnoid hemorrhage and trauma)! Clinical presentation often determines investigations.

1) CT Head Scan: Urgent CT is first line investigation for sudden acute headache presentation to determine if it is due to bleeding or mass effect (within 12 hours)

• CT Scan Interpretation: Blood is white and oedema is black/grey. Always look for midline shift (raised ICP) effect.
• Subarachnoid Hemorrhage: Blood diffused throughout sulci
• Extra/Epidural Hemorrhage: Blood is convex (lens) shape like a lemon.
• Subdural Hemorrhage: Blood is concave shape like a banana
• Cerebral Metastasis: Can be solitary or multiple and hyperdense or hypodense on CT

2) Lumbar Puncture: In suspected SAH with normal CT or MRI brain, also helps to rule out meningitis (SAH presents with xanthochromia)

3) Angiography: To diagnose aneurysms and vascular disease

Question 84

What are 9 other investiagtions/imaging to ocnsider in a patient with a headache?

Answer 84

Headache Ixs - Additional Imaging and Tests:

1. Cranial MRI: To diagnose parenchymal lesions
2. Neck Ultrasound: To diagnose arterial dissection
3. Cervical Spine X-Ray: To rule out degenerative cervical spine pathology
4. X-Ray of the Paranasal Sinuses: To rule out sinusitis
5. FBC and ESR: To identify infections or inflammatory conditions
6. Fundoscopy: To identify papilledema (possibly due to raised intracranial pressure)
7. Thyroid Function Tests: To rule out hypothyroidism
8. Tonometry: To identify increased intra-ocular pressure
9. EEG: To identify changes in cortical activity

Question 85

What is the treatment for a tension-type headache?

• Acute?
• Prophylaxis?

Answer 85

Tension-Type Headache

Acute Treatment:

• Simple Analgesics: NSAIDs, paracetamol and aspirin (caffeine 65mg added to above confers an additional benefit)

Prophylactic Treatment:

• Avoid situation that elicit the headache
• Tricyclic Antidepressants: Amitriptyline (note anticholinergic side effects)

Question 86

What is the treatment for a Migraine?

• Acute? (4)
• Prophylaxis? (6)

Answer 86

Migraine

Acute Treatment

1. Simple Analgesics: NSAIDs, paracetamol and aspirin
2. Triptans
3. Ergot Alkaloids
4. Antiemetics

Prophylactic Treatment

1. Pizotifen
2. Antihypertensives
3. Antidepressants (TCAs)
4. Anticonvulsants
5. Herbal/Vitamin Remedies: Feverfew, riboflavin (Vit B12) or Coenzyme Q10
6. Lifestyle changes (sleep, exercise, diet)

Question 87

What is the treatment for a Cluster Headache?

• Acute? (4)
• Prophylaxis? (1)

Answer 87

Cluster Headache

Acute Treatment

1. 100% O2 inhalation for up to 15min
2. Sumatriptan (subcutaneous or nasal spray)
3. Lignocaine
4. Corticosteroids (short course of high dose)

Prophylactic Treatment

1. Verapamil

Question 88

What is the Mechanism of Action of NSAIDs in the treatment of headaches?

Answer 88

NSAIDs (Aspirin/Ibuprofen):

• Block COX-1 and COX-2 enzymes which lowers the levels of circulating prostaglandins and thromboxanes thus reducing prostaglandin-mediated inflammation and pain.
• Has analgesic, antipyretic, anti-inflammatory and antiplatelet actions by preventing synthesis of prostaglandins by non-competitively and non-selectively inhibiting both COX-1 and COX-2 (preventing prostaglandin synthesis inhibits inflammatory mediators which inhibits pain (from odeama and chemoreceptors).

Question 89

What is the Mechanism of Action of Acetaminophen (Paracetamol) in the treatment of headaches?

Answer 89

Acetaminophen (Paracetamol):

• Generally considered to be a weak inhibitor of the synthesis of prostaglandins in the CNS.
• Does not appear to inhibit the function of COX enzymes outside the CNS.

Question 90

What is the Mechanism of Action of Triptans (Sumatriptan) in the treatment of headaches?

Answer 90

Triptans (Sumatriptan):

• 5-HT1 agonists (1b and 1d) to promote cerebral vasoconstriction (may also reduce trigeminal nerve activation) to counteract vasodilation that often accompanies migraines.
• Examples include Sumatriptan (nasal spray or oral tablet), Naratriptan (most tolerated) and Rizatriptan (wafers).

Question 91

What is the Mechanism of Action of Triptans (Sumatriptan) in the treatment of headaches?

Answer 91

Ergot Alkaloids (Ergotamine):

5-HT1 agonists (1b and 1d) to promote cerebral vasoconstriction (may also reduce trigeminal nerve activation) to counteract vasodilation that often accompanies migraines. Not used much, causes a lot of abdominal pain and nausea compared to triptans.

Question 92

What is the Mechanism of Action of Antiemetics (D2 Antagonists) in the treatment of headaches?

Answer 92

Antiemetics (D2 Antagonists):

• Block D2 receptors in the chemoreceptor trigger zone (CTZ) which prevents stimulation of the vomiting centre in the medulla.
• Examples include metoclopramide, prochlorperazine and chlorpromazine.
• Use for nausea and vomiting associated with migraine.
• Prokinetic as well, which increases GIT motility which increases drug absorption.

Question 93

What is the Mechanism of Action of Pizotifen in the treatment of headaches?

Answer 93

Pizotifen:

• 5-HT2 receptor antagonist and weak antihistaminergic effect (sedation).
• Mechanism of action in migraine prevention unknown but seems to work.

Question 94

What is the Mechanism of Action of Tricyclic Antidepressants (Imipramine/Amitriptyline) in the treatment of headaches?

Answer 94

Tricyclic Antidepressants (Imipramine/Amitriptyline):

• Act by inhibiting noradrenaline and serotonin reuptake in CNS.
• Noradrenaline is involved in the descending modulation of pain, so preventing re-uptake promotes a pain damping effect.
• Highly effective in relieving neuropathic pain in some but not all patients.
• Their action is independent of their antidepressant effects.
• SSRIs are not effective.

Question 95

What is the Mechanism of Action of Antihypertensives (β-Blocker) in the treatment of headaches?

Answer 95

Antihypertensives (β-Blocker):

• B-blockers competitively block beta receptors in heart and peripheral vasculature.
• B2 receptors in the periphery (including brain) normally vasodilate, so non-selective B-blockers such as propranolol cause peripheral vasoconstriction.

Question 96

What is the Mechanism of Action of Anticonvulsants (Valproate) in the treatment of headaches?

Answer 96

Anticonvulsants (Valproate):

• Prevents repetitive neuronal discharge by blocking voltage- and use-dependent sodium channels.
• Thought to stop the brainstem wave of depolarisation from initiating migraine.

Question 97

What is the Mechanism of Action of Lignocaine in the treatment of headaches?

Answer 97

Lignocaine

• Block Na+ channels by binding to specific receptors on inner portion of channel, preventing depolarisation and propagation of action potentials.

Question 98

Discuss the psychosocial issues associated with pain and how these influence pain management.

What are 8 Psychosocial Issues Associated with Pain?

Answer 98

Psychosocial Issues Associated with Pain:

1. Negative emotional associations
2. Previous experience of painful or stressful event
3. Individual differences in perception and appraisal of painful or stressful events
4. Poor strategies for coping with pain and stress
5. Poor availability and quality of social support networks and personal relationships
6. Poor mobility and activity levels
7. Negative social comparisons with other patients at different stages of recovery
8. Negative environmental factors

Question 99

Discuss the psychosocial issues associated with pain and how these influence pain management.

What is the significance of psychosocial issues in pain management? (15)

Answer 99

Psychosocial Issues and Pain Management:

1. Psychosocial issues catalyse transition of acute pain into chronic and disabling pain
2. Vigilance may increase pain intensity
3. Distraction may decrease its pain intensity
4. Interpretations and beliefs may increase pain and disability
5. Catastrophising may increase pain
6. Negative thoughts and beliefs may increase pain and disability
7. Expectations may influence pain and disability
8. Cognitive sets may reduce flexibility in dealing with pain and disability
9. Fear may increase avoidance behaviour and disability
10. Anxiety and depression may increase pain disability
11. Distress, in general, fuels negative cognitions and pain disability
12. Positive emotions might decrease pain
13. Avoidance behaviour may increase disability
14. Unlimited activity (overactivity) may provoke pain
15. Pain behaviours communicate pain

Question 100

Describe the role of the nigrostriatal pathway in regulating the extrapyramidal motor system, and how this is involved in parkinsonism.

• What is the Nigrostriatal Pathway?
• Where does it start/finish?
• Function?

Answer 100

Nigrostriatal Pathway: A dopaminergic pathway that connects the substantia nigra with the striatum (caudate nucleus and putamen) to initiate and modulate voluntary movement.

Start of Pathway: Substantia nigra (dopaminergic neurons)

End of Pathway: Striatum (D1 and D2 receptors)

Function: Regulates extrapyramidal motor loops and maintains normal motor output by influencing direct and indirect pathways of movement. The pathway has a modulatory effect on the basal ganglia, with dopamine facilitating the motor loop by exciting the direct pathway and inhibiting the indirect pathway.

Question 101

What are the Direct and Indirect Basal Ganglia Pathways?

• Pathways?
• What do they inhibit/activate?
• Receptors?

Answer 101

Direct Pathway (Excitatory)

• Motor Cortex → Striatum → GPi + SNr → Thalamus → Motor Cortex
• Disinhibits motor thalamus
• Activates thalamus-cortex
• Activates motor cortex
• Facilitates purposeful movements
• D1 excitatory receptors at striatum (Dopamine from SN increases the activity of the direct pathway)

Indirect Pathway (Inhibitory)

• Cortex → Striatum → GPe → STN → GPi + SNr → Thalamus → Motor cortex
• Inhibits motor thalamus
• Inhibits thalamus-cortex
• Inhibits motor cortex
• Inhibits unwanted movements
• D2 inhibitory receptors at striatum (Dopamine from SN decreases the activity of the indirect pathway)

NB: Striatum (Caudate Nucleus and Putamen), Globus Pallidus Interna (GPi), Globus Pallidus Externa (GPe), Substantia Nigra Pars Compacta (SNc), Substantia Nigra Pars Reticulata (SNr), Subthalamic Nuclei (STN)

Question 102

What is Parkinsonism?

• Causes?
• Pathophysiology?
• Effect on Nigrostriatal Pathway?

Answer 102

Parkinsonism: A syndrome (collection of symptoms) found in Parkinson’s disease characterised by lesions in the basal ganglia, predominately in the substantia nigra. Caused by neurodegenerative Parkinson’s disease, but can also be caused by drugs such as antipsychotics, toxins, metabolic disorders and other neurological conditions).

• Pathophysiology:
  
  1. Lesions in the basal ganglia
  2. Loss of dopamine neurons in the substantia nigra
  3. Loss of dopamine terminals in the striatum (nigrostriatal pathway)
  4. Results in dysregulated motor loops and abnormal motor output
  5. Manifests as tremors, rigidity and bradykinesia
• Effect on Nigrostriatal Pathway:
  
  • Loss of dopamine means modulatory effect on the basal ganglia is lost
  • The action of dopamine exciting the direct path and inhibiting the indirect path is lost
  • Results in an imbalance towards overactivity of the indirect pathway and underactivity of the direct pathway
  • Motor programs are excessively inhibited and so there is difficulty in initiating movements

Question 103

What is Neurodegeneration?

• Complex Interplay of which causes/factors?
• Common Features?
• Common Pattern?

Answer 103

Neurodegeneration: Selective progressive and irreversible loss of specific vulnerable neuronal populations

• Complex Interplay: Age, endogenous factors, extrinsic factors and neurogenetic predisposition
• Common Features: Pathological protein aggregation in surviving neurons and formation of extracellular deposits, resulting in neuronal loss, increasing disability and death.
• Common Pattern: Long prodromal period (protein accumulation) followed by cascade of symptoms (2 -20 years). Some familial diseases usually have early onset, other sporadic diseases usually have late onset.

Question 104

What are the Degenerative Diseases of CNS?

• 4 Subcortical Diseases (Movement Disorders)?
• 5 Cortical Diseases (Dementia)?

Answer 104

Degenerative Diseases of CNS:

Subcortical Disease (Movement Disorders)

1. Parkinson’s Disease
2. Huntington’s Disease
3. Motor Neuron Disease
4. Progressive Supranuclear Palsy

Cortical Disease (Dementia)

1. Alzheimer’s Disease
2. Lewy Body Dementia
3. Pick’s Disease
4. Vascular Dementia
5. Prion Proteinopathies

Question 105

What is Parkinson’s Disease (PD)?

• Definition?
• Aetiology?
• Pathophysiology?
• Pathology?
• What are Lewy Bodies?

Answer 105

Parkinson’s Disease (PD):

• Definition: Progressive dopaminergic neuron degeneration in the substantia nigra.
• Aetiology:
  
  • Idiopathic disease
  • Genetic in 10-15% of cases
  • Historically, rare cases were related to MPTP exposure (a contaminant in illicit drugs)
• Pathophysiology: Ubiquitin-dependent proteasomal proteolysis system failure → Accumulation of toxic protein products (α-synuclein) in basal ganglia → Cell dysfunction (some neurons protected by Lewy bodies) → Cell death
• Pathology: Histology reveals loss of pigmented neurons in the substantia nigra and round and eosinophilic inclusions of a-synuclein (Lewy bodies) in affected neurons
• Diagnosis: Clinical diagnosis! A positive response to PD medications is a strong indication of a correct diagnosis. Parkinsonism AND Absence of absolute exclusion criteria AND 2+ Supportive Criteria AND/OR Red Flags

NB: Lewy Bodies are an (protective) accumulation of α-synuclein and ubiquitin

Question 106

What are the Clinical Manifestations of Parkinson’s Disease?

• Cardinal (TRAP)?
• Prodromal?
• Initial?
• Advanced?

Answer 106

Clinical Manifestations of Parkinson’s Disease: Usually manifests at approximately 60 years of age.

• Cardinal (TRAP): Tremor, rigidity, akinesia and postural instability
• Prodromal: Anosmia (loss of smell) and REM sleep behaviour disorder
• Initial: Bradykinesia (slow movement) or akinesia, resting tremor (asymmetrical pill-rolling tremor), rigidity (cogwheel rigidity in extremities), impaired gait (shuffling, slow, stooped, reduced arm movement, freezing and hesitancy), festinating gait (quickening and shortening of normal stride, leaning forward) and impaired balance (falls).
• Advanced: Motor freezing (inability to start movement), postural instability, microphonia (quiet voice), micrographia (small writing), hypomimia (reduced facial expression), cognitive impairment and dementia, depression, hallucinations/delirium, dysautonomia (constipation, urinary problems, dysphagia, pain and drooling) and glabellar tap reflex (tap glabella and patient blinks consistently)

Question 107

What are Parkinson-Plus Syndromes (Atypical Parkinsonism)?

• Definition?
• Aetiology?
• Pathophysiology?
• Clinical Manifestations?
• 4 Types?

Answer 107

Parkinson-Plus Syndromes (Atypical Parkinsonism)

• Definition: A group of neurodegenerative diseases that present with parkinsonism and a variety of additional features. Parkinson-plus syndromes should be considered if parkinsonism does not respond to levodopa treatment, if dementia progresses rapidly, or if gait instability occurs early in the course of the disease.
• Aetiology: Depends on particular syndrome
• Pathophysiology: Damage to the dopaminergic nigrostriatal projection by other conditions
• Clinical Manifestations: Generally poor response to levodopa, dementia, oculomotor dysfunction, and early onset of autononomic dysfunction and gait instability are common. Particular syndromes show further characteristic symptoms. The progression is usually faster and the prognosis is usually worse than in PD.

Types:

1. Progressive Supranuclear Palsy: Neuronal loss and gliosis particularly of the basal ganglia, midline thalamic nuclei and the brainstem. Vertical gaze palsy + Frontal lobe disturbances.
2. Multiple System Atrophy: Secondary neuronal degeneration as a result of Lewy body deposition in glial cells (and subsequent glial and myelin dysfunction), particularly in the putamen, the pons and the cerebellum. Lewy bodies + Autonomic dysfunction with urogenital problems.
3. Corticobasal Degeneration: Asymmetric frontoparietal atrophy and gliosis. Asymmetric motor symptoms + Alien limb phenomenon.
4. Dementia with Lewy Bodies: Cerebral atrophy due to cortical deposition of Lewy bodies. Lewy bodies + Visual hallucinations.

Question 108

What is Parkinsonism (Secondary Parkinsonism)?

• Definition?
• Aetiology?
• Pathophysiology?
• Clinical manifestations?

Answer 108

Parkinsonism (Secondary Parkinsonism):

Definition: A syndrome featuring bradykinesia and either resting tremor or rigidity (or both). Secondary parkinsonism is parkinsonism due to specific cause such as medication, intoxication, and head trauma. Idiopathic parkinsonism is classified as Parkinson’s disease.

Aetiology: Medication (antipsychotics, some antiemetics, some calcium channel blockers, valproate and lithium), metabolic disorders (Wilson’s disease), toxins (manganese, carbon monoxide, carbon disulfide), cerebrovascular disease (vascular parkinsonism), normal pressure hydrocephalus and CNS infections (HSV, HIV, treponema pallidum, toxoplasma gondii, Creutzfeldt-Jakob disease and prion accumulation)

Pathophysiology: Damage to the dopaminergic nigrostriatal projection by other conditions

Clinical Manifestations: Bradykinesia plus either resting tremor or rigidity (or both)

Question 109

What is Huntington’s Disease (HD)?

• Definition?
• Aetiology?
• Pathophysiology?

Answer 109

Huntington’s Disease (HD):

Definition: Degeneration of GABAergic neurons in the striatum, particularly the caudate nucleus of the basal ganglia

Aetiology: Autosomal dominant disease marked by increased number of CAG repeats in the huntingtin gene on chromosome 4, most likely due to DNA polymerase malfunction (normally 10-35 repeats, HD >36 repeats)

Pathophysiology: Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia → Dysfunction of subcortical motor circuits → Indirect pathway (hyperkinetic/choreatic movements) is commonly affected earlier than the direct pathway (hypokinetic movements). Direct pathway dominates leading to excess movement.

Question 110

What are the Clinical Manifestations of Huntington’s Disease (HD)?

• Initial?
• Advanced?
• NB?

Answer 110

Clinical Manifestations of Huntington’s Disease: Symptom onset depends on individual extent of genetic abnormalities but usually occurs around 40 years of age

• Initial: Chorea (involuntary, irregular, nonrepetitive, arrhythmic movements of the limbs, neck, head, and/or face), oculomotor disorders (reduced velocity in optokinetic nystagmus, hypometric saccades), hyperreflexia, sensory deficits and autonomic symptoms (hyperhidrosis, urinary incontinence).
• Advanced: Hypokinetic motor symptoms (dystonia, rigidity, bradykinesia), akinetic mutism (inability to move or speak), motor impersistence (inability to sustain simple voluntary acts such as tongue protrusion), dysarthria and dysphagia, dementia, depression, apathy, anxiety, aggression and psychosis and cachexia (due to dysphagia and high energy consumption). Suicide is a common cause of death.
• NB: Chorea characterises the early stages of the disease while hypokinetic/akinetic symptoms may dominate later on! Dementia, depression, and behavioural disorders are common in advanced stages!

Question 111

What is Motor Neuron Disease?

• Definition?
• Aetiology?
• Pathophysiology?
• Clinical Manifestations?
• 4 Types?

Answer 111

Motor Neuron Disease (MND)

• Definition: Degenerative disorder of upper and lower motor neurons of the corticospinal tract.
• Aetiology: Unknown. Most cases are sporadic, arising in middle age adults (average age of onset 65 years).
• Pathophysiology: Degeneration of upper motor neuron in motor cortex and/or degeneration of lower motor neuron in spinal cord.
• Clinical Manifestations: Progressive muscle wasting and paralysis. LMN degeneration results in flaccid paralysis with muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes and negative Babinski sign. UMN degeneration results in spastic paralysis with hyperreflexia, increased muscle tone, positive Babinski sign. Death is common within 5 years from respiratory failure and aspiration bronchopneumonia.
• Types:
  
  1. Amyotrophic Lateral Sclerosis (ALS): UMN + Somatic LMN
  2. Progressive Bulbular Palsy: UMN + Brainstem LMN only
  3. Progressive Muscular Atrophy: LMN only
  4. Primary Lateral Sclerosis: UMN only

Question 112

What is Alzheimer’s Disease (AD)?

• Definition?
• Aetiology?
• Pathophysiology?

Answer 112

Alzheimer’s Disease (AD):

Definition: Degenerative disease of cortex and most common cause of dementia.

Aetiology: Most cases (95%) are sporadic and seen in the elderly. Risk increases with age (doubles every 5 years after the age of 60). Genetic factors (amyloid precursor protein, Presenilin -1, Presenilin-2 and Apolipoprotein-E). Risk factors include age, family history of dementia, low socioeconomic and/or educational status, Down syndrome, diabetes, obesity, dyslipidemia, lack of physical activity (independent risk factor!), hypertension, peripheral atherosclerosis and cerebrovascular disease, traumatic brain injuries and environmental factors (e.g. second-hand smoke).

Pathophysiology: Extracellular senile plaques composed of Aβ protein + Intracellular neurofibrillary tangle composed of hyperphosphorylated tau protein + Damage to the hippocampus and parahippocampal cortex and progressive diffuse cortical atrophy + Degeneration of cholinergic neurons in the nucleus basalis of Meynert.

Question 113

What are the Clinical Manifestations of Alzheimer’s Disease (AD)?

• Common Cognitive?
• Less Common Cognitive?
• Non-Cognitive?

Answer 113

Clinical Manifestations of AD: Patients with mild to moderate Alzheimer disease are often able to maintain a social facade and preserve certain skills (dressing, hygiene routines)

• Common Cognitive: Short term memory (insidious onset and slow progress), language impairment, temporal and spatial orientation impairment. Not oriented to person, place time and events. Focal neurologic deficits are not seen in early disease.
• Less Common Cognitive: Apraxia, alexia, agnosia, acalculia, primary progressive aphasia and impairment of executive functions and judgment
• Non-Cognitive: Apathy, aggression, agitation or irritability, depression and mood disorders, anxiety and mutism, hallucinations, hyposmia, insomnia, urinary incontinence, myoclonus and seizures

Question 114

What is Pick’s Disease (Frontotemporal Dementia)?

• Definition?
• Aetiology?
• Pathophysiology?
• Clinical Manifestations?

Answer 114

Pick’s Disease (Frontotemporal Dementia):

Definition: Degenerative disease of the frontal and temporal cortex, spares the parietal and occipital lobes

Aetiology: Pathological intracellular inclusion bodies (Pick bodies) that are caused by mutations in tau or progranulin proteins. Also associated with ubiquitin inclusion bodies hypothesized to be caused by dysfunction of the ubiquitin proteasome system. Familial predisposition (autosomal dominant) occurs in 10-25% of cases.

Pathophysiology: Round aggregates of tau protein (Pick bodies) in neurons of the cortex (no AB plaques)

Clinical Manifestations: Behavioral and language symptoms arise early, eventually progresses to dementia. Frontal lobe symptoms such as rapid deterioration in personality and social behaviour. I nitial symptoms are typically not memory-related.

Question 115

What is Vascular Dementia?

• Definition?
• Aetiology?
• Pathophysiology?
• Clinical Manifestations?

Answer 115

Vascular Dementia:

Definition: Gradual cognitive decline caused by small or large vessel disease

Aetiology: Cerebral ischaemia due to age, traumatic brain injury, history of stroke or cardiovascular disease

Pathophysiology: Multifocal infarction and injury due to hypertension, atherosclerosis, or vasculitis

Clinical Manifestations: Cognitive impairment and other symptoms dependent on affected cerebral area

Question 116

What is Multiple Sclerosis?

• Definition?
• Aetiology?
• Pathophysiology
• Clinical Manifestations?

Answer 116

Multiple Sclerosis:

• Definition: A chronic, degenerative disease of the CNS that is caused by an immune-mediated inflammatory process. This process results in the demyelination of white matter in the brain and spinal cord.
• Aetiology: Genetic predisposition and environmental factors such as UV radiation, insufficient vitamin D consumption, cigarette smoking, EBV or HHV 6
• Pathophysiology: Inflammation, demyelination, and axonal degeneration. Activation of autoreactive T- lymphocytes → inflammatory processes → focal demyelination with partial preservation of axons (acute plaques) → loss of axons and atrophy of oligodendrocytes (chronic plaques) → gliosis → inadequate remyelination. Most common sites of demyelination include periventricular areas, brainstem, cerebellum and spinal cord.
• Clinical Manifestations: Optic neuritis (often the earliest sign) with impaired vision and colour blindness and internuclear ophthalmoplegia as a result of a lesion in the medial longitudinal fasciculus. Spinal cord demyelination signs such as pyramidal tract impairment, dorsal column impairment, absent abdominal reflex and electric sensation down neck upon flexion. Cerebellar involvement with dyskinesia, ataxia, speech, hypotonia, intention tremor, nystagmus and gait (DASHING), cranial nerve palsies (IX, X and XI usually spared), autonomic dysfunction and change in mental state.

Question 117

Identify the CNS structures and describe the pathways involved in motor control.

• Basal ganglia?
• Thalamus?
• Hypothalamus?
• Epithalamus?
• Limbic System?

Answer 117

Basal Ganglia: A group of subcortical nuclei, which are situated at the base of the forebrain, and are involved in control of motor behaviour (including planning and execution of movement). Help to start, modulate and stop cortical motor activity. Facilitates wanted movement and inhibits unwanted movements (exert effects contralaterally) Also play a role in cognition, emotion and filtering out inappropriate responses. Disorders here results in too little or too much movement.

Thalamus: Gateway to the cortex, composed of several groups of nuclei. Relay centre for all sensory information (except olfaction) travelling to the cortex, as well as information from the basal ganglia and cerebellum going to the cortex.

Hypothalamus: Controls endocrine and autonomic systems for regulation of general homeostasis and plays a role in emotional behaviours and memory.

Epithalamus: Contains pineal gland that secretes melatonin which is important for circadian rhythms.

Limbic System: Consists of the cingulate gyrus, dentate gyrus, parahippocampal gyrus, hippocampus and amygdala. Functions to establishes emotional states, links the conscious functions with the unconscious autonomic functions and facilitates memory storage and retrieval.

Question 118

Identify the CNS structures and describe the pathways involved in motor control.

• Cerebellum?
• Superior Cerebellar Peduncle?
• Middle Cerebellar Peduncle?
• Inferior Cerebellar Peduncle?

Answer 118

Cerebellum: Receives information from the sensory systems, the spinal cord, and other parts of the brain to regulate and fine-tune motor activity. It does not initiate movement but contributes to p lanning, programming and monitoring of voluntary movement, particularly learned skillful movement, postural adjustments and coordination of eye and head movements. Maintains posture and balance, maintains muscle tone and coordinates smooth movements by influencing timing and force of contractions of voluntary muscles. Disorders here result in uncoordinated movement, slurred speech, poor posture and unstable gait.

• Superior Cerebellar Peduncle: Joins the cerebellum to the midbrain underneath the occipital lobes
• Middle Cerebellar Peduncle: The largest peduncle which connects the two sides of the cerebellum to the pons
• Inferior Cerebellar Peduncle: Joins the cerebellum to the medulla

Question 119

What is the Brainstem? Function?

• Midbrain?
  
  • Superior Colliculi?
  • Superior Colliculi?
  • Red Nucleus?
  • Cerebral Peduncles?
• Pons?
• Medulla?

Answer 119

Brainstem (As A Whole): Contains ascending and descending tracts, cranial nerves, nuclei, and fibres connecting the brainstem with the cerebellum. The Reticular Formation integrates information from all areas of CNS and coordinates many systems.

• Midbrain (Brainstem): Responsible for functions in motor movement, particularly movements of the eye, and in auditory and visual processing.
  
  • Superior Colliculi: Visual reflex centre (receives input from retina and visual cortex)
  • Inferior Colliculi: Auditory reflex centre
  • Red Nucleus: Receives input from frontal cortex
  • Divided into an anterior (tegmentum) and posterior (tectum) area by the cerebral aqueduct
  • Cerebral Peduncles: Connect the midbrain to the cerebrum (one on each side of brain)
• Pons (Brainstem): Involved in the control of breathing, communication between different parts of the brain and sensations such as hearing, taste, and balance.
• Medulla (Brainstem): Responsible for autonomic (involuntary) functions such as breathing, heart rate and blood pressure, the coordination of movement, regulation of mood and relay of nerve signals between the brain and spinal cord.

Question 120

What is the Frontal Lobe? Function?

• Primary Motor Cortex/Precentral Gyrus (Area 4)?
• Pre-Motor Cortex (Area 6)?
• Frontal Eye Fields/Middle Frontal Gyrus?
• Broca’s Area?
• Prefrontal Cortex?
• Blood Supply?

Answer 120

Frontal Lobe: Voluntary motor function and executive functions such as planning, decision -making, problem-solving, motivation, foresight, planning, memory, mood, emotion, social judgment and aggression.

• Primary Motor Cortex/Precentral Gyrus (Area 4): Major source of descending motor fibres, where motor commands leave the cortex on their way to innervate cranial and spinal nerves
• Pre-Motor Cortex (Area 6): Association motor areas that receives processed information from primary motor cortex
• Frontal Eye Fields/Middle Frontal Gyrus: Coordinates eye movements
• Broca’s Area: Posterior part of inferior frontal gyrus for expressive speech
• Prefrontal Cortex: Receives input from all regions of cerebral cortex, limbic system and specific brainstem nuclei and projects to many brain regions for regulation of emotional and cognitive processes

Blood Supply: Anterior Cerebral Artery and Middle Cerebral Artery

Question 121

What is the Parietal Lobe? Function?

• Primary Somatosensory Cortex/Postcentral Gyrus (Areas 3, 1, 2)?
• Somatosensory Association Area?
• Blood Supply?

Answer 121

Parietal Lobe: Sensation and perception functions and integrates sensory input, primarily with the visual system

• Primary Somatosensory Cortex/Postcentral Gyrus (Areas 3, 1, 2): Destination of afferents from sensory receptors, primary site for input somesthetic information to synapse
• Somatosensory Association Area: Immediately adjacent to postcentral gyrus, for the interpretation of the significance of sensory data

Blood Supply: Anterior Cerebral Artery and Middle Cerebral Artery (Lateral Aspect of Lobe)

Question 122

What is the Occipital Lobe? Function?

• Primary Visual Cortex (Area 17)?
• Visual Association Area?
• Blood Supply?

Answer 122

Occipital Lobe: Principle visual centre of the brain

• Primary Visual Cortex (Area 17): Cortex on either side of the calcarine sulcus, medial aspect
• Visual Association Area: Cortical areas surrounding primary visual cortex (areas 18 and19) for meaning and interpretation to what we see

Blood Supply: Posterior Cerebral Artery

Question 123

What is the Temporal Lobe? Functions?

• Primary Auditory Cortex (Area 41)?
• Association Auditory Cortex (Area 42)?
• Primary Olfactory Cortex?
• Wernicke’s Area?
• Blood Supply?

Answer 123

Temporal Lobe: Hearing, smell, learning, memory and some aspects of vision and emotion

• Primary Auditory Cortex (Area 41): Superior surface of superior temporal lobe (transverse temporal gyri or Heschel gyri), primary representation of auditory information from cochlea
• Association Auditory Cortex (Area 42): Interpretation and meaning of sounds
• Primary Olfactory Cortex: Inferior and medial surfaces of temporal lobe
• Wernicke’s Area: Posterior part of superior temporal gyrus for receptive speech
• Blood Supply: Middle Cerebral Artery (Lateral Aspect of Lobe) and Posterior Cerebral Artery

Question 124

Identify the CNS structures and describe the pathways involved in motor control.

• Insula?
• Internal Capsule?
• Spinal Cord?

Answer 124

Insula: A portion of the cerebral cortex folded deep within the lateral fissure, it is connected to the limbic system and associated with emotion (reception of taste and visceral sensations)

Internal Capsule: Carries connections up from the thalamus to the cortex and down from the cortex to the thalamus, brain stem and spinal cord. Entire input and output connections of the cortex are condensed here. Supplied by middle cerebral artery and lenticulostriate branches. Damage results in contralateral paralysis, somatosensory loss and usually visual loss.

Spinal Cord: A long, thin, tubular bundle of nervous tissue and support cells that extends from the medulla oblongata in the brainstem through the vertebral column, in which nerves carry incoming and outgoing

Question 125

What is decussation?

Answer 125

Decussation

1 : the action of crossing (as of nerve fibers) especially in the form of an X. 2 : a crossed tract of nerve fibers passing between centers on opposite sides of the nervous system.

Question 126

What are the motor and sensory spinal pathways?

Answer 126

Question 127

Answer 127

Question 128

What are the 14 Signs and Symptoms of Parkinson’s Disease: Hypokinetic-hypertonic extrapyramidal features?

Answer 128

Signs and Symptoms of Parkinson’s Disease: Hypokinetic-hypertonic extrapyramidal features

1. Resting Tremor
2. Bradykinesia
3. Festinating Gait
4. Motor Freezing
5. Hypomimia/Masked Facies
6. Microphonia
7. Micrographia
8. Rigidity
9. Postural Instability (Late Feature)
10. Cognitive Impairment and Dementia (Sub-Cortical)
11. Dysautonomia
12. Anosmia (Prodromal Feature)
13. REM Sleep Behaviour Disorder (Prodromal Feature)
14. Dyskinesis (Long-Term L- Dopa)

Question 129

Answer 129

Question 130

Answer 130

Question 131

Describe the phases and course of Parkinson’s Disease.

Answer 131

Question 132

Summarise the intellectual changes that occur in the later stages of Parkinson’s disease and other neuropsychiatric illnesses (5).

Answer 132

Intellectual and Psychiatric Changes in Neurodegenerative Disease:

1. Cognitive impairment and dementia
2. Depression and anxiety
3. Hallucination and delirium
4. Personality changes such as apathy and withdrawal
5. Inability to do routine tasks such as swallowing, speech and breathing

Question 133

What are the Principles of Management of Parkinson’s Disease?

Answer 133

Parkinson’s disease - Principles of Management:

• To date there is no cure for PD. Treatment is aimed at relieving symptoms and should generally begin once patients develop significant functional (physical/social) disability.
• With all anti-Parkinson drugs, start at a low dose and increase gradually over days or weeks. This reduces the risk of adverse effects and improves concordance with therapy. A clear response can take 2 to 3 weeks.
• All Anti-Parkinson drugs can cause nausea, but tolerance to this adverse effect usually develops rapidly.
• Taking doses with food can help.
• Avoid metoclopramide, prochlorperazine and other centrally acting dopamine -blocking antiemetics, because
• they often make parkinsonism worse.
• Titrate agents to find correct agent and dose for individual patients. Try to use the lowest doses sufficient to
• control the disease, and observe for evidence of under-treatment and side effects.

Question 134

What are the drugs used in Parkinson’s Disease? (8) Examples?

Answer 134

Pharmacological Management of Parkinson’s Disease:

1. Dopamine Precursors - eg. Levodopa (Sinemet, Madopar and Kinson)
2. Inhibitors of Dopamine/Levodopa Metabolism - eg. Carbidopa, Selegiline and Rasagiline, Entacapone and Tolcapone
3. Dopamine Receptors Agonists (Ergotamine Derivatives) - eg. Bromocriptine, Cabergoline
4. Dopamine Receptors Agonists (Non-Ergot Derivatives) - eg. Pramipexole (Sifrol), Rotigotine
5. Antimuscarinic Agents - eg. Benztropine (Benztrop, Cogentin), Biperiden (Akineton) and Benzhexol (Artene)
6. Amantadine (Symmetrel)
7. Apomorphine Infusion
8. Duodopa L-Dopa

Question 135

What is the Mechanism of Action of Dopamine Precursors in Parkinson’s Disease?

• What is Levodopa? What is it given with? Why?
• Examples?
• L-dopa side effects?

Answer 135

Dopamine Precursors: Improves bradykinesia, rigidity and, less consistently, tremor.

• Levodopa (Most Effective): Metabolic precursor of dopamine which is enzymatically converted to dopamine in the neurons of the substantia nigra. Given with a peripheral dopa decarboxylase inhibitor (carbidopa or benserazide) to decrease peripheral metabolism of levodopa to dopamine (which does not cross the blood–brain barrier).
  
  • Examples: Sinemet, Madopar and Kinson
• L-Dopa Side Effects:
  
  1. Anorexia
  2. Nausea, vomiting
  3. Orthostatic hypotension
  4. Dyskinesia
  5. Episodes of sudden unpredictable loss of mobility (‘off’ effect)
  6. Agitation, insomnia, sudden sleep onset, drowsiness, depression, hallucination and confusion (especially in the elderly)
  7. Impulse control disorders
  8. Dopamine dysregulation syndrome

Question 136

What is the Mechanism of Action of Inhibitors of Dopamine/Levodopa Metabolism in Parkinson’s Disease?

• What is Carbidopa? What is it given with? Why?
• What is the MOA of Selegiline and Rasagiline?
• What is the MOA of Entacapone and Tolcapone?

Answer 136

Inhibitors of Dopamine/Levodopa Metabolism:

Carbidopa: A dopa decarboxylase inhibitor that diminishes the metabolism of levodopa in the GI tract and peripheral tissues thus increasing the availability of levodopa to the CNS. This allows a reduction in levodopa dosage, with subsequent decrease in peripheral dopamine adverse effects (nausea, vomiting, hypotension).

Selegiline and Rasagiline: Selective monoamine oxidase B (MAO-B) inhibitors, which irreversibly inhibits MAO-B, preventing the metabolism of dopamine, thus increasing dopamine levels in the brain. Can be used in combination with levodopa. Mild effect on the symptoms of Parkinson disease.

Entacapone and Tolcapone: Inhibits catechol-O-methyltransferase (COMT), mainly in peripheral tissues, which increases the amount of levodopa available to the brain and prolongs the clinical response to levodopa, enhanced by the actions of carbidopa.

Question 137

What is the Mechanism of Action of Dopamine Receptors Agonists (Ergotamine Derivatives) in Parkinson’s Disease?

• What disorders can these cause?
• 2 examples? Which is no longer used & Why?

Answer 137

Dopamine Receptors Agonists (Ergotamine Derivatives): Improves bradykinesia and rigidity, but are less effective than levodopa. Adding a dopamine agonist to levodopa improves motor fluctuations and allows levodopa dose to be reduced. Can cause impulse control disorders.

Bromocriptine: Dopamine D2 receptor agonist.

Cabergoline: Dopamine D2 receptor agonist (not used as it increases the risk of cardiac valve damage).

Question 138

What is the Mechanism of Action of Dopamine Receptors Agonists (Non-Ergot Derivatives) in Parkinson’s Disease?

• 2 examples? Which receptors do they work on? Why would patients take these?

Answer 138

Dopamine Receptors Agonists (Non-Ergot Derivatives):

Pramipexole (Sifrol): Dopamine D3 receptor agonist. Can be used for a patient who strongly prefers once-daily dosing.

Rotigotine: Dopamine D3 receptor agonist. Transdermal patches, useful for those who cannot swallow.

Question 139

What is the Mechanism of Action of Antimuscarinic Agents in Parkinson’s Disease?

• How often are they used? Why?
• Side effects?
• Examples?

Answer 139

Antimuscarinic Agents:

• Mode of Action: Block muscarinic actions of acetylcholine to reduce relative excess of cholinergic activity that accompanies dopamine deficiency in Parkinson’s disease.
  
  • Used infrequently because of the incidence of adverse effects and relatively poor efficacy.
• Side effects: dry mouth, blurred vision, pupil dilation, light headedness on standing, constipation, urinary retention and confusion. Modest effect on tremor, but little effect on rigidity and bradykinesia. Useful when tremor is the main symptom and response to levodopa is inadequate.
• Examples: Benztropine (Benztrop, Cogentin), Biperiden (Akineton) and Benzhexol (Artene)

Question 140

What is the Mechanism of Action of Amantadine (Symmetrel) in Parkinson’s Disease?

• What kind of antagonist does it act as? In which pathway?
• When is it useful?

Answer 140

Amantadine (Symmetrel):

• Mode of Action: Increases dopamine release and blocks cholinergic receptors. Acts as a N-methyl- D-aspartate (NMDA) antagonist in the glutamatergic pathway from Subthalamic Nucleus to Globus Pallidus.
  
  • Has antiviral activity against some strains of influenza A (prevents release of viral RNA into host cell).
  • Useful when tremor is the main symptom and response to levodopa is inadequate.

Question 141

What is the Mechanism of Action of Apomorphine Infusion in Parkinson’s Disease?

• When is it used?

Answer 141

Apomorphine Infusion:

• Mode of Action: Subcutaneous dopamine agonist infusion, for people severely disabled by motor fluctuations refractory to conventional treatment

Question 142

What is the Mechanism of Action of Duodopa L-Dopa in Parkinson’s Disease?

• Why is it used?

Answer 142

Duodopa L-Dopa:

Mode of Action: L-Dopa in an intestinal gel form delivered by percutaneous duodenal tube to avoid gastric emptying effects, for advanced motor complications.

Question 143

Describe the non-pharmacological management of Parkinson’s Disease? (10)

Answer 143

Other Management of Parkinson’s Disease:

1. Education: Understanding of disease and disease progression, self-awareness of symptoms, awareness of drug side effects and triggers to seek medication changes.
2. Exercise: Helps to improve coordination, balance, mobility and agility as well as mental health.
3. Social Support: Assists with activities of daily living i.e. cooking, cleaning and driving and includes community assistance, support and carers respite.
4. Physiotherapy: Help patients maintain their maximum level of mobility, activity and independence. Provide balance, strength and mobility exercises, and appropriate walking aids.
5. Speech Therapy: Assists with voice projection (Lee Silverman Voice Technique) and help with dysarthria and dysphagia.
6. Occupational Therapy: Help patients continue daily tasks as disease progresses. Provide home modification to improve function and therapy/aids to overcome limitations or difficulties.
7. Psychology: Assist with mental health, anxiety, depression and other psychiatric manifestations.
8. Dietician: Assists with healthy diet and impacts of diet on medications and symptom control.
9. Deep Brain Stimulation: A neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses through implanted electrodes, to specific targets in the brain (subthalamic nucleus and globus pallidum interna) for the treatment of movement disorders. May benefit selected patients with inadequately controlled motor fluctuations and/or dyskinesia despite optimised drug therapy, or those with drug-refractory tremor.
10. Non-Motor Symptom Management: Symptoms such as autonomic dysfunction (orthostatic hypotension, constipation, neurogenic bladder disturbances, sexual dysfunction), sleep disorders, depression, anxiety, cognitive decline (and eventually dementia), sensory complaints and pain are associated with Parkinson’s disease and may require treatment.

Question 144

Evaluate the response to drug treatment of a patient with Parkinson’s disease.

• When do motor complications usually begin?

Answer 144

Evaluate Response of Drug Treatment:

• Symptoms can be controlled with dopaminergic therapy for about 5 years (honeymoon period)
• Levodopa relieves symptoms in most patients with Parkinson’s disease
• After about 5 years of long-term use of levodopa, motor complications begin.
• All anti-Parkinson drugs can cause nausea and other side effects, but tolerance to adverse effects usually develops rapidly

Question 145

Relate the effects of long term treatment with levodopa-containing preparations.

Discuss the motor complications of PD.

Answer 145

Effects of Long-Term L-Dopa Treatment: Most patients with Parkinson disease on levodopa therapy eventually develop motor complications (~10% per year of L-Dopa use)

1. Different patterns of motor fluctuations such as predictable and unpredictable ‘wearing off’ of effect, intermittent dose failures, unpredictable “on-off” fluctuations, delayed or poor effect of individual doses
2. Drug-induced dyskinesia (generally a twisting or writhing motion) or dystonia

NB: In the past, L-Dopa therapy was delayed until symptoms were to some extent disabling, to delay onset of motor complications. Now this thought is to be incorrect, but levodopa-phobia persists on the internet.

Question 146

Of the patients with PD, who are at risk of motor complications? (4)

Answer 146

Those At Risk of Motor Complications:

1. Younger age of Parkinson’s onset
2. Those who have more severe disease
3. Those on a higher levodopa dosage
4. Those who have had the disease longer

Question 147

What are some strategies to manage the motor complications of PD?

Answer 147

Strategies to Manage Motor Complications:

1. Combine levodopa with a dopamine agonist or dopamine/levodopa metabolism inhibitors
2. Decrease the levodopa dose or use a modified-release levodopa
3. Give smaller, more frequent doses of levodopa (reducing dose reduces symptoms)
4. Adjust dietary protein (high-protein meals may interfere with levodopa absorption)
5. Adherence to regular dosing times as variations from the patient’s usual schedule can lead to deterioration in function

Question 148

Benzodiazepines are a group of drugs used to treat anxiety and insomnia. Anxiety is clinically defined as a psycho-physical state characterised by emotional tension, worry and physical changes, e.g., increased blood pressure. Insomnia is any disruption of physiological healthy sleep patterns. Different benzodiazepines vary greatly in duration of action and can be roughly divided into short-, medium- and long-acting compounds. Benzodiazepines may be used in the treatment of epilepsy.

What is the mechanism of action of benzodiazepines?

Answer 148

= c. they facilitate the action of GABA
Other groups of drugs with anti-anxiety effects are antidepressants, some antiepileptics (e.g., gabapentin), buspirone (a 5-hydroxytryptamine - 5-HT1A - receptor agonist), some antipsychotic agents (e.g., olanzapine) and some Beta-blockers (e.g., propranolol).

Question 149

Anti-Epileptic Drugs that act primarily on GABA? (2)

Answer 149

Question 150

What is Diazepam/Lorazepam?

Answer 150

Question 151

Diazepam is a long-acting benzodiazepine. It is converted to active metabolite N-desmethyldiazepam (nordazepam), which has a half-life of about 60 h. Eventually, all benzodiazepines are metabolised and excreted as glucuronide conjugates in the urine.

What is/are the main indication/s of diazepam?

Answer 151

= e. anxiety and to achieve muscle relaxation

As well as acting as a sedative to reduce anxiety (it is a sedative hypnotic), diazepam is also used in the treatment of life-threatening seizure in epilepsy. It can be given intravenously or, in children, rectally to control acute seizures. The anticonvulsant action of benzodiazepines is subject to tolerance. Another important indication of diazepam is the treatment of alcohol-withdrawal syndrome.

By contrast, midazolam is a short-acting benzodiazepine, with a half-life < 12 hours. It is available by many administration routes, the most common in clinical practice are oral, intravenous and intramuscular. Midazolam has several clinical indications, and may be used as an intravenous anaesthetic, and for procedural sedation.

Question 152

Benzodiazepines have a wide margin of safety (high therapeutic index – TI). They share the general adverse effects of CNS depressants, e.g., drowsiness, with consequent impairment of job performance and driving skills. Beside acute toxicity, benzodiazepines present three potential dangers linked to a neurocognitive origin.

Please list the three potential dangers of benzodiazepines, especially in prolonged treatments.

Answer 152

Tolerance, dependence and abuse are three dangers of benzodiazepine usage.

Question 153

Antiepileptic (also known as anticonvulsant) drugs are used to treat epilepsy, a group of neurological disorders characterised by periodic seizures. Not all seizures involve convulsions. Antiepileptic drugs aim to inhibit the abnormal neuronal discharge, rather than to correct the underlying cause. There are several mechanisms of action of antiepileptic drugs.

Please list three main mechanisms of action of antiepileptic drugs.

Question 154

a. absence seizures
b. tonic seizures
c. atonic seizures
d. tonic-clonic seizures
e. clonic and myoclonic seizures

Answer 154

= a. absence seizures
The main side effects of phenytoin include ataxia, vertigo, gum hypertrophy (hyperplasia), hirsutism, megaloblastic anaemia, fetal malformation (Fetal hydantoin syndrome) and hypersensitivity reactions, some of which are potentially fatal (e.g., Stevens-Johnson syndrome).

The daily dose needed for each person may vary greatly, and for each individual needs monitoring and adjustment. At low doses phenytoin is eliminated by first order kinetics (fixed % drug in fixed period of time), but at higher concentrations it is eliminated by zero-order kinetics (fixed amountof drug per unit time - due to saturation of pathways).

Question 155

a. trigeminal neuralgia
b. absence seizures
c. Lennox-Gastaut syndrome
d. status epilepticus
e. migraine

Answer 155

= a. trigeminal neuralgia

Common side-effects of carbamazepine include drowsiness, dizziness, ataxia, hyponatremia, hepatotoxicity and bone marrow depression, with other severe forms of hypersensitivity reactions, especially in people of Asian origin.

Question 156

a. patients over 50 years
b. patients with co-morbidities
c. obese patients
d. patients under 18 years
e. patients who could become pregnant

Answer 156

= e. patients who could become pregnant
Due to its teratogenicity (neual tube defects), valproate is contraindicated in women of childbearing age/pregnancy, because it could produce fetal neural tube defects, e.g., spina bifida.

Common side effects of valproate include hepatotoxicity, bone marrow depression and ataxia.

Valproate inhibits cytochrome p450

Question 157

List some Inducers and Inhibitors of the Cytochrome p-450 enzyme system?

Answer 157

Question 158

a. temporal lobe epilepsy
b. absence seizures
c. status epilepticus
d. partial and generalised tonic-clonic seizures
e. Lennox-Gastaut syndrome

Answer 158

= d. partial and generalised tonic-clonic seizures
Common side effects include headaches, inflammation of the nose and throat, sleepiness, vomiting and irritability. Brivaracetam is similar to levetiracetam.

Question 159

As CNS depressants, antiepileptic drugs have shared and distinctive side effects.

What is/are the most common shared side effect/s of antiepileptic drugs generally?

Answer 159

= a. drowsiness and sedation
Beside shared side effects, commonly sedation, somnolence and nausea, some antiepileptic drugs present distinctive side effects, e.g., withdrawal syndrome (benzodiazepines), depression (phenobarbital), mood changes with occasional psychosis (lacosamide, perampanel, vigabatrin), weight loss (zonisamide), aplastic anaemia and liver damage (felbamate). Classic antiepileptic drugs should be avoided during pregnancy and breastfeeding, for the risk of teratogenesis. Newer antiepileptics lack medical data and trials during pregnancy, so the choice of the treatment depends on the type of seizure and which substance enables optimal control of seizures. The current approach is to optimize seizure control prior to conception, avoid combination therapies, administer the lowest possible efficient dose and monitor plasma concentrations regularly.

Question 160

Define: Seizure?

Answer 160

• Seizure: The clinical manifestation of an abnormal and excessive excitation and synchronisation of a population of cortical neurons. An abnormal, unregulated electrical activity of cortical neurons that results in transient changes in behaviour and/or EEG findings.

Question 161

Define: Epilepsy (Unprovoked)?

Answer 161

**Epilepsy (Unprovoked): **
A tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults. A chronic neurologic disorder characterised by any of the following:
- Two or more unprovoked seizures separated by more than 24 hours
- One unprovoked seizure with an underlying predisposition to seizures (recurrence risk over the next 10
years that is similar to the recurrence risk after two unprovoked seizures)
- Diagnosis of an epilepsy syndrome

Question 162

Define: Status Epilepticus?
SUDEP?

Answer 162

Status Epilepticus: A state of continuous seizure lasting ≥ 5 min, or ≥ 2 repetitive, separate seizures with consciousness not fully regained in the interictal period

Question 163

Define: Acute Symptomatic Seizure (Provoked)?
- 3 types/causes?

Answer 163

Question 164

Classification of Seizures?
- 7 partial?
- 5 generalised?

Answer 164

Partial (Focal) Seizure
1. Simple
2. Complex
3. Secondary Generalised
4. Temporal Lobe (70% of Focal Epilepsy)
5. Frontal Lobe
6. Parietal Lobe (5% of Focal Epilepsy)
7. Occipital Lobe (Rare)

Generalised Seizure
1. Tonic-Clonic (“Grand Mal”)
2. Clonic
3. Myoclonic
4. Atonic (“Drop Attacks”)
5. Absence (“Petit Mal”)

Question 165

Define: Reflex Epilepsy?

Answer 165

Question 166

Define: Drug-resistant epilepsy & Resolved epilepsy?

Answer 166

Question 167

How are seizures generally categorised?

Answer 167

Classification of seizures according to the ILAE 2017 classification
Seizures are classified according to localization of abnormal neuronal activity and then further subcategorized based on symptoms and sometimes level of awareness.

Question 168

Classification of Epilepsy - Levels 1-3?

Answer 168

Question 169

What is a Simple Partial (Focal) Seizure?

Answer 169

** Partial (Focal) Seizure:** Caused by electrical discharge restricted to a limited part of the cortex of one cerebral hemisphere, further sub-divided according to whether or not there is loss of awareness.

Question 170

What is a Complex Partial (Focal) Seizure?

Answer 170

Complex Partial (Focal) Seizure
* Local onset, then spreads
* Impaired conciousness
* Clinical manifestations vary with site of origin and degree of spread - Presence and nature of aura, automatisms, other motor activity
* Temporal lobe epilepsy most common

Question 171

What is Secondary Generalised Partial (Focal) Seizure?

Answer 171

Question 172

What are the different types of Partial (Focal) Seizures by lobe?
- Temporal?
- Frontal?
- Parietal?
- Occipital?

Answer 172

Question 173

What is a generalised seizure?

Answer 173

Generalised Seizure: There is simultaneous involvement of both hemispheres, always associated with loss of consciousness or awareness.

Question 174

Generalised Seizures:
- What is a Tonic-Clonic seizure?
- What is a Clonic seizure?
- What is a Tonic seizure?

Answer 174

Question 175

Generalised Seizures:
- What is a Myoclonic seizure?
- What is an Atonic seizure?
- What is an Absence seizure?

Answer 175

Question 176

Define: Epileptogenesis?

Answer 176

Epileptogenesis: Sequence of events that converts a normal neuronal network into a hyperexcitable network

Question 177

What are a number of seizure triggers?

Answer 177

Precipitant/Trigger: Increases likelihood of seizure for person with epilepsy
1. Stress
2. Excessive physical exertion
3. Sleep deprivation
4. Flashing lights
5. Loud music

Question 178

Biochemical Mechanisms of Seizures (Epileptogenesis)?
- 3 stages?

Answer 178

Question 179

Aetiology of Epilepsy:
- Genetic?
- Cryptogenic?
- Provocative Factor?

Answer 179

Question 180

List some causes of acute symptomatic seizures?

Answer 180

Question 181

**Common Causes of Epilepsy
**- Genetic?
- Structural?
- Metabolic?
- Immune?
- Infectious?

Answer 181

Question 182

Which causes of epilepsy are more common in neonates and infants (<6months)?

Answer 182

Question 183

Which causes of epilepsy are more common in:
- Older infants and children (6months - 10yrs)?
- Adolescents (10-18yrs)?
- Adults (18-60yrs)?
- Older adults (>60yrs)?

Answer 183

Question 184

Pathogenesis of epilepsy?

Answer 184

Question 185

Pathogenesis and Clinical Findings of Status Epilepticus?

Answer 185

Question 186

Generalised Seizures:
- Pathogenesis?
- Clinical Findings?
- Complications?

Question 187

Simple Febrile Seizures:
- Pathogenesis?
- Clinical Findings?

Answer 187

Question 188

Generalised Seizures:
- Definitions?
- Summary of Pathogenesis?

Question 189

Absence (Petit mal) Seizures:
- Clinical Features?
- Pathogenesis?

Answer 189

Question 190

Focal Seizures in Adults:
- Clinical Features?
- Pathogenesis?

Answer 190

Question 191

Epilepsy & Seizures - Generally what are they?
- Pathology & Causes?
- Signs & Symptoms?
- Diagnosis?
- Treatment?

Answer 191

Question 192

Absence Seizures:
- Pathology & Causes?
- Complications?
- Signs & Symptoms?
- Diagnosis?
- Treatment?

Answer 192

Question 193

Febrile Seizures:
- Pathology & Causes?
- Types?
- Risk Factors?
- Signs & Symptoms?
- Diagnosis?
- Treatment?

Answer 193

Question 194

Myoclonic Seizures:
- Pathology & Causes?
- Complications?
- Signs & Symptoms?
- Diagnosis?
- Treatment?

Answer 194

Question 195

Status Epilepticus:
- Pathology & Causes?
- Types?
- Complications?
- Signs & Symptoms?
- Diagnosis?
- Treatment?

Answer 195

Question 196

Tonic Clonic Seizure:
- Pathology & Causes?
- Signs & Symptoms?
- Diagnosis?
- Treatment?

Answer 196

Question 197

Demonstrate how to elicit an appropriate history from and perform an examination on a patient with a recent seizure.

Answer 197

Question 198

Outline an appropriate management plan for a patient presenting to hospital with a seizure.
- What are 4 investigations you would consider?

Answer 198

Question 199

Outline an appropriate management plan for a patient presenting to hospital with a seizure.
- Emergency measures?
- Status epilepticus?
- Lifestyle modifications?
- Safety advice?

Answer 199

Question 200

Seizure first aid?

Answer 200

Question 201

Checklist after a first seizure?

Answer 201

Question 202

Diagnosis of epilepsy?

Answer 202

Diagnosis: The diagnosis of a seizure is essentially a clinical one based on taking a history from the patient and any witnesses. The majority of patients referred to a first fit clinic have not had a seizure. The commonest error is to misdiagnose a syncopal blackout for a seizure.

Question 203

Discuss what you would do to confirm someone has/hasn’t had a seizure?

Answer 203

Question 204

4 Common Investigations for Epilepsy?

Answer 204

Question 205

Electroencephalogram Findings in Epilepsy?

Answer 205

Question 206

**Describe the Pharmacological Treatment of Epilepsy:
**- Goals?
- Criteria for Choice?
- Principles?
- Precautions?
- General Mechanism?

Answer 206

Question 207

**List 4 Treatment options of Epilepsy other than pharmacological:
**

Answer 207

Question 208

Answer 208

Question 209

What are 5 Classic Anticonvulsants (AEDs)?

Answer 209

Classic Anticonvulsants: Have a narrower therapeutic range, stronger side effects and more drug interactions
1. Valproate
2. Carbamazepine
3. Ethosuximide
4. Phenytoin
5. Benzodiazepines

Question 210

Answer 210

Question 211

Answer 211

Question 212

Answer 212

Question 213

Answer 213

Question 214

AEDs: Benzodiazepines
- Indication? (1)
- Mechanism? (1)
- Side effects? (3)

Answer 214

Question 215

List 7 Newer Anticonvulsants?

Answer 215

**Newer Anticonvulsants: **Have a broader therapeutic range, fewer side effects and fewer drug interactions
1. Lamotrigine
2. Phenobarbital
3. Levetiracetam (Keppra)
4. Gabapentin
5. Vigabatrin
6. Topiramate
7. Tiagabine

Question 216

AEDs: Lamotrigine
- Indications? (3)
- Mechanism? (1)
- Side Effects? (4)

Answer 216

Question 217

AEDs: Phenobarbital
- Indications? (3)
- Mechanism? (1)
- Side Effects? (4)

Answer 217

Question 218

AEDs: Keppra
- Indications? (3)
- Mechanism? (1)
- Side Effects? (4)

Answer 218

Question 219

AEDs: Gabapentin
- Indications? (3)
- Mechanism? (1)
- Side Effects? (4)

Answer 219

Question 220

AEDs: Vigabatrin
- Indications? (1)
- Mechanism? (1)
- Side Effects? (1)

Answer 220

Question 221

AEDs: Topiramate
- Indications? (3)
- Mechanism? (2)
- Side Effects? (4)

Answer 221

Question 222

AEDs: Tiagabine
- Indications? (1)
- Mechanism? (1)
- Side Effects? (5)

Answer 222

Question 223

Describe the excitatory synapse of the brain and which AEDs work where?

Answer 223

Question 224

Describe the inhibitory synapse of the brain and which AEDs work where?

Answer 224

Question 225

Epidemiology of Epilepsy & Seizures?

Answer 225

Question 226

What is the Neuropathology of Idiopathic epilepsy? Where does it mostly occur?

Answer 226

Question 227

4 Infective causes of Epilepsy?
5 Vascular causes of Epilepsy?

Answer 227

Question 228

5 Developmental causes of epilepsy?

Answer 228

Question 229

What is Focal Cortical Dysplasia? MRI Findings? (5)

Answer 229

Question 230

What is MESIAL TEMPORAL SCLEROSIS?

Answer 230

Question 231

5 Top causes of epilepsy in Children?

Answer 231

Question 232

6 Top causes of epilepsy in Adults?

Answer 232

Question 233

6 causes of intractable epilepsy?

Answer 233

Question 234

Describe what happens during the Tonic and Clonic phases of a Generalised Tonic-Clonic seizure?
- What do you see on EEG?

Answer 234

Question 235

Describe Absence Seizures
- When do they often start?
- Pathophysiology?
- Timing/Duration?
- GCS?
- Clinical Features?
- EEG findings?

Question 236

Describe Absence Seizures
- When do they often start?
- Pathophysiology?
- Timing/Duration?
- GCS?
- Clinical Features?
- EEG findings?

Answer 236

Question 237

What are the 2 cellular mechanisms of seizure generation?

Answer 237

Question 238

What are 5 targets for AEDs?

Answer 238

Question 239

What is the major inhibitory transmitter in the CNS? 2 types of receptors?

Answer 239

Question 240

Which AEDs are Inducers/ Inhibitors of the Cytochrome P-450 Enzyme System?

Answer 240

Question 241

Phenytoin (Dilantin)
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 241

Question 242

Carbamazepine (Tegretol)
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 242

Question 243

Phenobarbital (Luminal)
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 243

Question 244

Diazepam (Valium) & Lorazepam (Ativan)
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 244

Question 245

Valproate
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 245

Question 246

Ethosuxamide
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 246

Question 247

Gabapentin
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 247

Question 248

Lamotrigine
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 248

Question 249

Levetiracetam (Keppra)
- MOA?
- T1/2?
- Toxicity?
- Interactions?

Answer 249