Neurological Disease & Haematology Flashcards
Definition of Primary headache?
Definition of Secondary headache?
Approach to patient with a headache?
Red flags for Headache? (SNOOP10)
What are the life threatening conditions you need to consider with a patient presenting with a headache?
Describe the classification of headache. What are the 4 types of primary headache?
Tension Type Headache:
- Epidemiology
- Duration
- Frequency
- Therapy
- Course of an attack
- Character of pain
- Prophylaxis
Migraine:
- Epidemiology
- Duration
- Frequency
- Age of onset
- Therapy
- Course of an attack
- Character of pain
- Triggers
- Additional symptoms
- Prophylaxis
Cluster Headache:
- Epidemiology
- Duration
- Frequency
- Age of onset
- Therapy
- Course of an attack
- Character of pain
- Triggers
- Additional symptoms
- Prophylaxis
Secondary headaches
List 7 types of primary headache?
Differentials for headache:
- 4 Bleeding?
- 7 Vascular?
- 1 Autoimmune?
- 4 Toxins?
Differentials for headache:
- 4 Bleeding?
- 7 Vascular?
- 1 Autoimmune?
- 4 Toxins?
Migraine
- Epidemiology?
- Aetiology/Potential Triggers?
Describe the pathophysiology of Migraine?
What is the clinical course of Migraine - 4 stages and clinical features of each?
Migraine is characterized by recurrent attacks and may occur with aura (∼ 25% of cases) or without aura (∼ 75% of cases). A typical migraine attack passes through four stages, and the aura (if present) typically occurs before the headache.
Diagnostic criteria for Migraine with/without aura?
Describe the treatment of migraine:
- All patients?
- Mild/Moderate?
- Moderate/Severe?
Which 2 drugs can cause adverse effects when combine with triptans or ergotamine?
What adverse effect can occur if a triptan is used in combination with ergotamine?
What is the non-pharmacological and pharmacological prophylaxis for migraine?
Nonpharmacological treatment that can help migraine includes:
- cold packs over the forehead or back of the skull (targeting the supraorbital and greater occipital nerves)
- hot packs over the neck and shoulders (targeting the innervation of the scalp)
- neck stretches and self-mobilisation
- rest in a quiet dark room.
What is Status Migrainosus?
What are the warning features of a new onset headache and their possible diagnoses?
Discuss the options for Acute treatment for migraine with nonopioid analgesics and antiemetics.
Discuss the therapeutic guideline recommendations for Acute treatment for migraine with a triptan.
Discuss the therapeutic guideline recommendations for Migraine prophylaxis.
Discuss the therapeutic guideline recommendations for management of tension-type headaches.
Discuss the therapeutic guideline recommendations for management of headaches associated with exerciese or physical activity.
Discuss the therapeutic guideline recommendations for the acute treatment of cluster headaches.
What is Trigeminal neuralgia and what is the best treatment for it?
Trigeminal neuralgia is recurrent, unilateral, shock-like pain in one or more divisions of the trigeminal nerve. t can be due to demyelination or neurovascular compression. Request imaging to exclude a structural cause, especially in the presence of sensory loss, which suggests trigeminal neuropathy. Request specific views of the trigeminal nerve and ganglion.
Drugs are first-line therapy for trigeminal neuralgia. There is stronger evidence for carbamazepine, but oxcarbazepine may be better tolerated.
Define:
- Stroke
- Ischaemic stroke
- Transient ischaemic attack
- Haemorrhagic stoke
- Intracerebral haemorrhage
- Subarachnoid haemorrhage
- Intraventricular haemorrhage
What is the the most important nonmodifiable risk factor and the most important modifiable risk factor for stroke?
For both ischemic and hemorrhagic strokes, age is the most important nonmodifiable risk factor and arterial hypertension is the most important modifiable risk factor.
Describe the workup/management for suspected stroke?
What percentage of strokes are ischaemic/haemorrhagic - intracerebral? SAH?
Which arteries form the circle of Willis?
What are 5 clinical features of an MCA stroke?
MCA Stroke
A middle cerebral artery infarct (left-sided in this case) typically leads to the following clinical features:
– Contralateral hemiparesis
– Contralateral hemisensory loss
– Contralateral central (upper motor neuron) facial nerve palsy (The patient can raise both eyebrows because the forehead receives bilateral facial nerve innervation.)
– Aphasia, if the dominant hemisphere is affected
What are 7 clinical features of an ACA stroke?
ACA Stroke
An anterior cerebral artery infarct (left-sided in this case) typically leads to the following clinical features:
– Contralateral lower extremity weakness
– Contralateral lower extremity sensory loss
– Urinary incontinence
What are the clinical features of a PCA Stroke?
- 4 General Findings?
- 4 Types of midbrain syndromes?
- 5 Features of thalamic injury?
PCA Stroke
A posterior cerebral artery infarct (left-sided in this case) typically leads to the following clinical features:
– Contralateral sensory loss (due to lateral thalamic involvement)
– Contralateral homonymous hemianopsia with macular sparing (because the macula receives collateral vascular supply from the middle cerebral artery)
What is the Motor homunculus?
The motor homunculus is a map of the primary motor cortex (located in the precentral gyrus of the frontal lobes) that illustrates which areas of the brain process the motor output to which part of the body. The distorted representation of the body and the size of the correspondingly labeled cortical areas illustrate the proportional amount of motor output sent to the individual parts of the body. Accordingly, since areas like the tongue, face, and hands receive most motor innervation, these areas are represented as disproportionately large compared to other areas, like the trunk and lower limbs.
What is the Sensory homunculus?
The sensory homunculus is a map of the primary somatosensory cortex (located in the postcentral gyrus of the parietal lobes) that illustrates which areas of the brain process the sensory input from which part of the body. The distorted representation of the body and the size of the correspondingly labeled cortical areas illustrate the proportional amount of sensory input received from the individual parts of the body. Accordingly, since the sensory nerves arriving from, e.g., the face and hands, terminate over larger areas of the brain than, e.g., those of the arms and legs, these parts of the body are represented as disproportionately large.
What are 6 factors that are associated with an increased risk of subsequent stroke following a TIA?
Factors associated with an increased risk of subsequent stroke include:
1. Age older than 60 years
2. Raised blood pressure (more than 140/90 mmHg)
3. Motor or speech symptoms
4. Symptoms that last longer than 1 hour
5. Diabetes.
4. At greatest risk are patients with established infarction on brain imaging, atrial fibrillation or a high-grade symptomatic carotid stenosis.
What are the clinical features of a basilar artery stroke?
What is Multiple Sclerosis? Epidemiology?
Multiple sclerosis (MS) is a chronic degenerative disease of the CNS characterized by demyelination and axonal degeneration in the brain and spinal cord, which are caused by an immune-mediated inflammatory process.
Discuss the aetiology of MS?
- Which allele increases the risk?
- Which allele is protective?
- 4 Environmental risk factors?
Define each of the following in the context of MS:
- Exacerbation?
- Remission?
- Pseudorelapse?
- Radiologically isolated syndrome?
- Diffuse cerebral sclerosis (Schilder disease)?
What are the 3 Clinical phenotypes of MS, their characteristics and their frequency?
Relapsing-remitting (RR) MS (∼ 90 % of patients): either full recovery between exacerbations (left column) or increasing residual disability with each exacerbation (right column).
Secondary progressive (SP) MS: > 50 % of patients initially presenting with relapsing-remitting MS later develop a pattern of continuous progression (left column), which may also include further exacerbations (right column).
Primary progressive(PP) MS (∼ 10 % of patients): continuous worsening of symptoms from disease onset (left column), but may include phases of no progression or even mild clinical improvement (less pronounced than in relapsing-remitting MS; right column). Exacerbations may also occur (not depicted).
What is the pathophysiology of MS?
Clinical Features of MS:
- 2 Constitutional symptoms?
- Often the earliest manifestation?
- Which type of visual disturbance?
- Features associated with demyelination of pyrimidal tract?
- Lhermitte sign?
- Uhthoff phenomenon?
How is MS diagnosed?
- Diagnosis of MS depends on a combination of clinical findings (e.g., optic neuritis, Lhermitte sign, sensory abnormalities, cerebellar signs), imaging, and laboratory results.
- The McDonald Criteria for both DIT and DIS must both be met to confirm a diagnosis of MS:
- Dissemination in time (DIT): the appearance of new CNS lesions over time that can be confirmed clinically, with imaging, or with CSF analysis
- Dissemination in space (DIS): the presence of lesions in different regions of the CNS that can be confirmed clinically or in MRI
Which imaging modality is gold standard for MS? What will you see on imaging?
MRI is the imaging study of choice for the diagnosis and monitoring of MS.
Typical findings on MRI
1. Multiple sclerotic plaques (most commonly found in the periventricular white matter) with finger-like radial extensions (Dawson fingers) related to demyelination and reactive gliosis
2. Contrast-enhancement of active lesions; usually resolves after 2–8 weeks
Other than imaging which investigation is often performed to confirm the diagnosis of MS? What are the results?
Give 5 differentials for Multiple Sclerosis (Autoimmune diseases associated with inflammatory demyelination)?
Differentials for MS:
1. Neuromyelitis optica spectrum disorders
2. Acute disseminated encephalomyelitis
3. Transverse myelitis
4. Neurosyphilis
5. HIV encephalopathy
What are the general principles of treatment of MS?
- Acute exacerbations?
- Long term management?
The emphasis in treating MS is on:
- introducing immunotherapy early, to slow or minimise disability
- using corticosteroids for acute inflammatory clinical events (relapses)
- easing symptoms caused by neurological damage (eg pain).
Discuss the supportive care and symptom management for MS?
- 4 General measures?
- Meds for urinary/bowel dysfunction?
- 1 Med for spasticity?
- Meds for tremors?
- Meds for neuropathic pain?
What is Parkinson’s Disease?
Parkinson disease (PD) is a neurodegenerative condition that involves the progressive depletion of dopaminergic neurons in the basal ganglia, particularly the substantia nigra.
What is the epidemiology of Parkinson’s Disease?
- Prevalence?
- Age of Onset?
- 4 Risk Factors?
What is the aetiology of Parkinson’s Disease?
- List 4 Genetic factors that contribute to PD?
PD = Idiopathic
List 6 causes of Secondary Parkinsonism?
Pathophysiolgy of Parkinson’s Disease?
Pathology/Morphology of PD?
What is the pathology of Parkinson’s Disease?
Lewy bodies and Lewy neurites
Microscopy of the substantia nigra of a patient with Parkinson disease (staining with antibodies against alpha-synuclein, counterstaining with Mayer hematoxylin)
Both Lewy bodies (spherical intracytoplasmic aggregates of alpha-synuclein) and the strand-like Lewy neurites (neurites containing alpha-synuclein aggregates; white arrows) are visible.
4 Clinical Features of Parkinson’s Disease in the Pre-clinical Stage?
List 8 Motor Signs of Parkinson’s Disease in the Clinical Stage?
- TRAP?
List 7 Non-Motor signs of Parkinson’s Disease in the Clinical Stage?
In terms of the diagnosis of Parkinson’s Disease, which symptoms are required?
- 4 features that support the diagnosis of PD?
- 5 Atypical features that don’t support a PD diagnosis?
- Atypical disease trajectory?
- Atypical distriibution of symptoms?
What are the general principles in the management of Parkinson’s Disease?
- List 5 supportive care measures to consider in the management of a patient with PD?
What are 6 pharmacological treatments for Parkinson’s Disease?
What is the most effective treatment for motor symptoms in PD?
What is its mechanism of action?
Levodopa is the most effective treatment for motor symptoms in PD but is associated with time- and dosage-dependent increase of dyskinesia.
**Dopamine precursors (e.g., L-DOPA/levodopa) **are converted by DOPA decarboxylase at the presynaptic neuron resulting in direct dopaminergic effects (especially in D2 receptors).
DOPA-Decarboxylase (DDC) inhibitors (e.g., carbidopa) decrease the peripheral conversion of L-DOPA to dopamine, which results in reduced peripheral side-effects of L-DOPA. These drugs cannot cross the blood-brain barrier and therefore do not reduce dopamine production in the brain nor do they have central side-effects.
Pathogenesis of PD?
Antiparkinson Drugs: Dopamine Agonists
- 2 Types?
- Examples?
- Mode of action?
- Indication?
- Adverse effects?
Dopamine agonists (e.g., ropinirole, bromocriptine) bind to the dopamine receptor, mimicking the action of dopamine.
Overstimulation of D2 receptors by levodopa or dopamine agonists may induce psychosis and hallucinations, especially in older patients with concurrent dementia or other psychiatric disorders.
Antiparkinson Drugs: COMT Agonists
- Examples?
- Mode of action?
- Indication?
- Adverse effects?
COMT inhibitors (e.g., entacapone, tolcapone) inhibits central (tolcapone) or peripheral (entacapone) catechol-O-methyl transferase (COMT) resulting in the reduced metabolization of dopamine, increase in dopamine effects, a decreased demand for L-DOPA, and a longer therapeutic effect with each dose.
Antiparkinson Drugs: NMDA antagonists
- Examples?
- Mode of action?
- Indication?
- Adverse effects?
**NMDA antagonists **(e.g., amantadine) act as antagonists at the glutamate N-methyl-D-aspartate (NMDA) receptor, which results in a dopaminergic effect.
Antiparkinson Drugs: MAO-B inhibitors
- Examples?
- Mode of action?
- Indication?
- Adverse effects?
**MAO-B inhibitors **
(e.g., selegiline) reduce the metabolism of central dopamine by inhibiting the monoamine oxidase B enzyme, which normally breaks down dopamine (and catecholamines) in the brain. This results in a prolonged dopamine effect and reduced demand for L-DOPA.
Antiparkinson Drugs: Anticholinergics
- Examples?
- Mode of action?
- Indication?
- Adverse effects?
Anticholinergic drugs
(e.g., benztropine) inhibit excitatory cholinergic neurons, resulting in a proportionately lower concatenation of acetylcholine to dopamine.
List the 4 Parkinson’s Plus Syndromes?
Progressive Supranuclear Palsy:
- Definition?
- Epidemiology?
- 4 Clinical Features?
- MRI Sign?
- Macroscopic pathology?
- Microscopic pathology?
- Prognosis?
Corticobasal Degeneration:
- Epidemiology?
- 3 Clinical Features?
- MRI Signs?
- Macroscopic pathology?
- Microscopic pathology?
- Prognosis?
Multiple System Atropy
- What is it?
- Pathogenesis?
Multiple System Atropy
- Definition?
- Epidemiology?
- Aetiology?
- Clinical Features?
- Diagnostics?
- Pathology?
- Differential Diagnoses?
Guillain-barré Syndrome
- What is it?
- Pathogenesis?
- Morphology?
Guillain-Barré syndrome (GBS) is an acute postinfectious polyneuropathy characterized by symmetric and ascending flaccid paralysis.
Guillain-barré Syndrome
- Incidence?
- Prevalence by Sex?
- Aetiology - Top 3 associated pathogens?
Guillain-barré Syndrome
- Pathophysiology?
- Clinical Features?
What are 5 Subtypes/Variants of guillain-barré syndrome?
- Acute inflammatory demyelinating polyneuropathy (AIDP)
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Miller-Fisher syndrome
- Multifocal motor neuropathy (MMN)
- Acute motor axonal neuropathy (AMAN)
6 Diagnostics for Guillain-Barré syndrome?
Tests to confirm the diagnosis include a cerebrospinal fluid examination—typically, the protein concentration is raised and the cellular response is absent or minimal. Early in the illness the only finding in nerve conduction studies may be the absence of F-waves, but later in the illness nerve conduction slows. Magnetic resonance imaging can exclude other causes and may show enhancement of nerve roots.
What is the treatment for Guillain-Barré syndrome?
What is the prognosis of Guillain-Barré syndrome?
What are Prion Diseases?
List 4 in Humans?
Describe the pathogenesis of Prion Diseases?
What is Creutzfeldt-Jakob Disease (CJD)?
- Epidemiology?
Creutzfeldt-Jakob Disease (CJD)
- Aetiology?
-
Creutzfeldt-Jakob Disease (CJD)
- 5 Diagnostics?
- Treatment?
What is Kuru?
- Definition?
- Aetiology?
- Pathophysiology?
- Clinical Features?
- Treatment?
What is Gerstmann-Sträussler-Scheinker syndrome?
- Definition?
- Pathophysiology?
- Clinical Features?
- Treatment?
What is Alzheimer disease? Epidemiology?
Aetiology of Alzheimer’s Disease
- What are 4 Genetic Factors associated with AD?
- List some other risk factors?
- Amyloid precursor protein (APP) gene
- Presenilin-1
- Presenilin-2
- Apo ε
Describe the pathophysiology of Alzheimer disease?
**Amyloid-β plaque formation in Alzheimer disease
**
The fundamental abnormality in AD is the accumulation of two proteins (Aβ and tau) in specific brain regions, likely as a result of excessive production and defective removal. The two pathologic hallmarks of AD, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Plaques are deposits of aggregated Aβ peptides in the neuropil, while tangles are aggregates of the microtubule binding protein tau, which develop intracel- lularly and then persist extracellularly after neuronal death.
The transmembranous amyloid precursor protein (APP) can be processed via two different pathways:
1. Nonamyloidogenic pathway (predominates under physiological conditions): APP is cleaved by α-secretase into sAPPα and C83. C83 is then further cleaved into the nontoxic fragments p3 and AICD by γ-secretase.
2. Amyloidogenic pathway (increases under pathological conditions): APP is cleaved into sAPPβ and C99 by β-secretase. C99 is then further cleaved into Aβ42 and AICD by γ-secretase. Aβ peptides aggregate and form insoluble extracellular plaques, which are associated with Alzheimer disease.
What are the clinical features of AD - Cognitive vs. Non-cognitive?
Clinical Features of AD
The progression of AD is slow but relentless, with a symptomatic course often running more than 10 years. Initial symptoms are forgetfulness and other memory disturbances; with progression, other symptoms emerge, including language deficits, loss of mathematical skills, and loss of learned motor skills. In the final stages, affected individuals may become incontinent, mute, and unable to walk; intercurrent disease, often pneumonia, is usually the terminal event. Current clinical trials are focused on treat- ing subjects in early, preclinical stages of the illness, using strategies that include clearing Aβ from the brain through immunologic approaches, disrupting the generation of Aβ with pharmacologic agents that target secretases, as well as approaches aimed at preventing alterations in tau.
What is the Diagnostic criteria for Alzheimer disease?
What will you see on a brain MRI of someone with Alzheimer disease?
There is bilateral cerebral atrophy, with prominent sulci (green overlay).
Multiple small hyperintense foci in the white matter (examples outlined) are enlarged perivascular spaces (Virchow-Robin spaces).
Pathology of Alzheimer Disease:
- Macroscopic?
- Microscopic?
What are 3 types of Antidementia medications?
- Indications?
- Mode of Action?
- Adverse effects?
- Acetylcholinesterase inhibitors (AChEIs) = Inhibits acetylcholinesterase and thus the breakdown of endogenous acetylcholine, which prolongs the action of the neurotransmitter in the neural junction.
- NMDA receptor antagonist: memantine
- Aβ monoclonal antibody: aducanumab
List 6 toxic and metabolic causes of seizures and give examples for each?
Toxic and metabolic causes of seizures refer to conditions where the seizure activity is triggered or influenced by substances or imbalances in the body.
List 7 groups of medications that have the potential to cause seizures?
Describe 9 brain diseases that may cause seizures.
What are 3 potential consequences of status epilepticus?
What is the treatment for status epilepticus?
What are bleeding disorders and how are the categorised?
What is primary haemostasis?
What are the 2 components of it?
Primary haemostasis = processes involved in the formation of a platelet plug (white thrombus) following endothelial injury.
What is Secondary haemostasis? What are the 3 pathways involved and the factors involved in each of them?
Secondary haemostasis: processes that lead to stabilization of the platelet plug (white thrombus) by creating a fibrin network.
- Coagulation cascade: a sequence of events triggered by the activation of the intrinsic or extrinsic pathway of coagulation that results in the formation of a stable thrombus
- Coagulation factors: Substances that interact with each other to promote blood coagulation
- Activated factors are designated with an “a” (e.g., activated factor VII = factor VIIa).
- Extrinsic pathway of coagulation, Intrinsic pathway & Common pathway of coagulation
Describe the processes involved in the Inhibition of hemostasis. (6)
In order to prevent hypercoagulability as well as excessive bleeding, activation of the coagulation cascade and the processes that inhibit it occur simultaneously in the circulatory system (procoagulant-anticoagulant balance).
List Disorders of primary hemostasis.
- 3 Inherited Platelet dysfunction disorders?
- 4 Acquired Platelet dysfunction disorders?
- 3 Drugs?
- 3 Disorders affecting the vessel wall?
List Disorders of secondary hemostasis (disorders of the coagulation cascade).
- 3 Intrinsic pathway?
- 1 Extrinsic pathway?
- 6 Both pathways?
Hyperfibrinolysis
- Definition?
- 5 Aetiologies?
- Pathophysiology?
- Treatment?
Hypofibrinogenemia
- Definition?
- 2 Aetiologies?
- Pathophysiology?
- Symptoms and findings?
- Treatment?
What are the Clinical features of bleeding disorders?
- Primary vs. Secondary?
- DIC?
Superficial, petechial bleeding indicates defects of primary hemostasis, whereas large, palpable ecchymoses and deep tissue bleeding suggest defects of secondary hemostasis!
What is Hemophilia? 3 Types?
Haemophilia
- Epidemiology?
- Aetiology?
What are the clinical features of haemophilia?
Haemophilia
- Diagnosis? (5)
- Treatment? (3)
What is Von Willebrand’s Disease?
Von Willebrand disease
- Epidemiology?
- Aetiology/Variants?
- Most common congenital bleeding disorder.
- Prevalence: estimated to affect approx. 1% of the US population.
Von Willebrand disease
Clinical features?
Von Willebrand disease
- Diagnostics?
- Treatment - Inherited vWd?
- Treatment - Acquired vWd?
What are Bleeding assessment tools (BATs)? What do they assess?
List 7 medications other than anticoagulants and antiplatelet medications which can cause bleeding disorders?
List 7 Diagnostic tests you would consider for bleeding disorders?
What is the platelet count, platelet function test, INR and PTT test results in:
- Disorders of primary haemostasis?
- Disorders of secondary haemostasis?
What is the Ristocetin cofactor assay test?
What is the Rumpel-Leede test?
- In which 5 diseases is it positive in?
Describe the parameters of the full blood picture.
- Medicare Benefits Schedule Item Number 65070 - Full blood examination?
??
Blood Transfusions - Contraindications
- What are the 2 contraindications to platelet transfusion?
Contraindications to platelet transfusion include thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia
Blood Transfusions - Complications
- 11 Acute?
- 7 Delayed?
- Infection
- Immunologic reactions
- Volume overload
- Hyperkalemia
- Iron overload
What values are indicative of critical physiologic derangement and Critical Bleeding Massive Transfusion?
- Temperature?
- pH?
- ionised calcium?
- platelet count?
- PT?
- INR?
- APTT?
- fibrinogen level?
Massive transfusions occur due to severe bleeding related to trauma, a ruptured aortic aneurysm, surgery and obstetrics complications.
What are the Suggested criteria for activation of a Massive Transfusion Protocol (MTP)?
Outline the steps in the Massive transfusion protocol (MTP)?
Indications for Transfusion of Plasma Products?
Indications for Transfusion of Platelets in Adults?
Describe an algorithm for Red blood cell (RBC) transfusion decisions in adults?
