Ebook Essentials for the canadian medical licensing exam - Review and prep for MCCQE part I: Phần 2

(BQ) Part 2 book Essentials for the Canadian medical licensing exam - Review and prep for MCCQE part I presents the following contents: Hematology, neurology, obstetrics and gynecology, oncology, ophthalmology, orthopedics and rheumatology, psychiatry, pulmonary medicine, urology.

Clearance ofabnormal RBCs

• Abnormalities of RBC shape (hereditary spherocytosis/elliptocytosis)

• Hemoglobinopathies (thalassemias)

• Nutritional anemiasInfection • Acute (infectious mononucleosis, hepatitis, SBE)

• Chronic (TB, AIDS, malaria, brucellosis, syphilis)

• Bacterial septicemia

• Splenic abscessAutoimmune • RA (Felty syndrome)

• SLE

• Collagen vascular diseases

• Drug reactionsExtramedullary

hematopoiesis

• Myelofibrosis

• Marrow toxicity (chemotherapeutic agents, radiotherapy)

• Marrow infiltration (solid tumors, leukemia, storage diseases)Altered splenic circulation • Cirrhosis

• Portal vein obstruction

• Splenic vein obstruction

• CHFSplenic infiltration • Storage diseases (Niemann-Pick, Gaucher, nonlipoid)

• Treat underlying disease

• Avoid splenectomy when possible toavoid risk of OPSI

• If necessary administer vaccines versus Strep

pneumo, HiB, N meningitidis, and annual

influenza vaccine and prophylactic Abx Tx

C L I N I C A L B O X

Dx of Splenomegaly on Exam

Castell method: If the spleen is normal, percussion in the lowest intercostal space (eighth to ninth) in theleft anterior axillary line of the supine patient elicits a resonant note throughout the respiratory cycle Ifpercussion on full inspiration produces a dull note (Castell sign), this is suggestive of splenic enlargement

BLEEDING TENDENCY/BRUISING

RATIONALE

Bleeding that is spontaneous or excessive/delayed in relation to the inciting trauma must

be examined for underlying pathology

APPLIED SCIENTIFIC CAUSES

See Figure 11.2

CAUSAL CONDITIONS

The clinical history should consider likely etiologies:

1 Personal history of bleeding diathesis

2 Family history of bleeding diathesis

3 Medication use

Figure 11.2 Coagulation cascade.

C 2 L E O B o x

Reporting Child Abuse

Children with extensive bruises

may represent child abuse and

there may be a requirement for

reporting

C L I N I C A L B O X

Medications that Affect Coagulability

1 Affect platelet function: FANTAStic Queen

2 Affect coagulation pathway: Abx that affect gut flora and induce Vit K deficiency

Table 11.2 Causal Conditions of Bruising and Bleeding

Coagulation Disorders Purpuric Disorders (1◦Hemostasis) (2◦Hemostasis) Platelet Plug Formation

• Immune (ITP,SLE, quinidine)

• ↑ Sequestration • Inherited (von

Wille-brand, BernardSoulier, Glanzmann

• Acquired (uremia,ASA, NSAIDs,antiplatelet agents)

• Congenital (collagendisease, heredi-tary hemorrhagictelangiectasia)

• Acquired culitis, steroids)

(vas-• Inherited (factorVIII, IX deficiency)

• Acquired (liverdisease, Vit Kdeficiency, antico-agulants, inhibitors)

• Fibrinolysis (DIC,inhibitors)

C 2 L E O B o xPrenatal Dx and Counseling

• Counseling on prenatal Dx of sickle cell disease and thalassemia should be nondirective and notrestricted to those willing to have an abortion

• Reproductive decisions must not be forced by the results of tests

• Because the only pragmatic options for mothers are abortion or no children, it is vital that women not bepressured into prenatal Dx

• PTT—intrinsic pathway factors (VII, IX, XI, XII), monitor heparin Rx

• PT-INR —extrinsic pathway factor (VII), monitor warfarin Rx

• IT —measures fibrinogen deficiency or↓ prothrombin activation

C 2 L E O B o xBlood Transfusion Refusal

In patients who are bleeding but refuse blood transfusion, it must be determined whether the decision can

be justified within the context of a relatively stable set of values If a coherent and consistent justificationdoes not exist, identify a substitute decision maker

C L I N I C A L B O X

PTT 1:1 Dilution

If PTT corrects with 1:1 dilution=

absolute deficiency in factor level

If PTT remains high= factor

• Thrombophilia refers to the congenital deficiency of a normal protein such that there is

an↑ risk of thrombotic events

CAUSAL CONDITIONS

Table 11.3 Causal Condition for Hypercoagulable State

Inherited Thrombophilia

(<50-yr old) • Antithrombin deficiency• Protein C, S deficiency

• Factor V Leiden (APC resistance)

• Prothrombin 20210 mutation

• HyperhomocysteinemiaAcquired

disorders /riskfactors

Cellular elements(hypercoagulability)

• Inherited defects: APC resistance (factor V Leiden), prothrombin 20210 mutation, factor VIII level

• Acquired defects/risk factors: antiphospholipid Ab (lupus anticoagulant, anticardiolipin Ab)

• Discontinue heparin —cannot

replace with LMWH

(cross-reactivity), warfarin (skin

necrosis), ASA, or IVC filter

• Instead, switch to either

direct thrombin inhibitors or

heparinoid anticoagulation

Figure 11.4 Approach to hypercoagulability states.

C L I N I C A L B O X

Diagnostic Testing

1 1◦Tests

• Compression U/S: gold standard in veins above the calf

• Pulmonary angiography: gold standard for PR

• Spiral CT: becoming more commonly used in suspected CT but cannot be used in patients withcompromised renal function

2 2◦Tests

• Contrast venography: if U/S not feasible/informative but difficult for patient

• MRI: accurate as venography but expensive, used for patients with pregnancy, poor renal function, orcontrast agent allergy

• V/Q scan: routinely used in suspected PE

APPLIED SCIENTIFIC CONCEPTS

Table 11.4 Megaloblastic Anemia—Caused by Vitamin B 12

• Absorption depends on secretion of intrinsic factor

by gastric parietal cells; if Vit B12compound taken

up in terminal ileum

• Impaired parietal cell function (gastrectomy, cious anemia —autoimmune destruction of parietalcell mass

perni-• Disease of distal ileum (Crohn ileitis, tapeworm,lymphoma)

CAUSAL CONDITIONS

Table 11.5 Causal Conditions of Anemia

Microcytic (<80 fL) Normocytic (80–100 fL) Macrocytic (>100 fL)

Figure 11.5 Approach to anemia.

Figure 11.5 (Continued ).

C L I N I C A L B O X

Drugs that can induce megaloblastic anemia (depress/affect metabolism of Vit B12or folate): PAM ASA MOM

• Pyrimidine analogs (5-FU, zidovudine)

• Anticonvulsants (phenytoin, phenobarbital, primidone)

• 6-Mercaptopurine and other purine analogs (acyclovir)

Confirm Baseline Levels of B 12

Do not administer folic acid without confirming Vit B12levels; normalized folate will resolve the anemiaand mask Vit B12deficiency, allowing hemopathy to progress

POLYCYTHEMIA VERA/ELEVATED HEMOGLOBIN

RATIONALE

• Elevated hemoglobin levels (>185 g/L [men], >165 g/L [women]) can be attributed to:

• PCV, a myeloproliferative disorder with clonal expansion of erythroid, myelocytic,and megakaryocytic lineages

• Erythrocytosis, 2◦to underlying systemic processes

APPLIED SCIENTIFIC CONCEPTS

• Hemoglobin and hematocrit measure the ratio of RBC mass to plasma volume; therefore,

they are sensitive to changes in either one

• Determination of polycythemia must be based on direct assessment of RBC mass and plasma volume ‘‘True’’ polycythemia involves an absolute ↑ of RBC mass, whereas

‘‘relative’’ polycythemia (Gaisb ¨ock) is a↓ in volume

• Erythropoiesis begins with a pluripotent hematopoietic stem cell and follows a hierarchicprocess of lineage commitment and differentiation

CAUSAL CONDITIONS

Table 11.6 Causal Conditions of PCV

True Polycythemia Appropriate ↑ EPO

(2◦Erythrocytosis) Inappropriate ↑ EPO Relative Polycythemia

• Hypoxemia (living at highaltitude, COPD, congeni-tal cardiac anomalies)

• Hemoglobinopathies (with

an↑ affinity for O2)

• PCV

• Renal pathology (renal artery stenosis)

• Malignancy (renal cell, lular, ovarian, uterine tumors)

hepatocel-• Cerebral hemangioma

• ↑ Carboxyhemoglobin (chronic ing, exposure to carbon monoxide)

smok-• ↓ Plasma volume(burns, diarrhea)

• Jewish men (slight predominance)

• Headache (2◦to↓ cerebral circulation)

• Abdominal discomfort

• Tired (↑ risk of TIA)

• ↓ Exercise tolerance and ↑ Epistaxis

• Blurred vision and ↑ Blood viscosity

• Itchy (pruritus 2◦to histamine release)

• Gouty arthritis and GI bleeding

• BIG Spleens (splenomegaly)

1 ↑ Platelets (>400,000/μL)

2 ↑ WBC (>12,000/μL)

3 ↑ Leukocyte alkalinephosphatase

• The location of the enlarged node is helpful in localizing the site of foreign antigeninvasion; generalized lymphadenopathy suggests systemic involvement.

ADVANCED SCIENTIFIC CONCEPTS

• Lymphatic system consists of lymph nodes and vessels as well as the thymus, spleen,and Peyer patches in the gut

For a simplified schematic of immune system, see Figure 15.10

Figure 11.7 Anatomy of a normal lymph node (Image from Rubin E, Farber JL Pathology , 3rd ed Philadelphia: Lippincott Williams & Wilkins;

• Immune system malignancies (leukemia, lymphoma) and Inflammatory conditions (collage diseases,

vas-culitides, amyloidosis, sarcoidosis)

• Neoplasms (all other tumors)

• Drainage of local infection or Disseminated infection

Table 11.7 Causal Conditions of Lymphadenopathy

Endo • Thyroid pathology (inflammation, hyperthyroidism)

• Adrenal insufficiencyInfectious • Viral (EBV, CMV, hepatitis, HIV)

• Bacterial (pyogenic bacteria, syphilis, TB)

• Fungal (histoplasmosis)

• Parasitic (toxoplasmosis)Immune/inflammation • Collagen diseases (RA, SLE, Kawasaki, Sj¨ogren)

• Serum sickness

• Drug reactions (phenytoin, allopurinol)

• Sarcoidosis

• AmyloidosisHematologic

malignancy

• Leukemia (AML/CML, ALL/CLL)

• Lymphoma (non– Hodgkin)

• Hemoglobinopathies (Waldenstr¨om, multiple myeloma)Other malignancy • Breast/lung carcinoma

• Kaposi sarcoma

• Head/neck CAStorage diseases • Gaucher, Niemann-Pick

immuno-APPLIED SCIENTIFIC CONCEPTS

• Thermoregulation is centrally regulated in the preoptic area of the hypothalamus, whichstimulates various heat-retention and dissipation responses to maintain a thermal setpoint

• Pyrogenic cytokines released by mononuclear phagocytes have the capacity to raisethis set point

• RES includes the spleen, lymph nodes, liver, marrow, and lung in its tissue componentand macrophages and monocytes in its cellular component

• Spleen has two components:

• White pulp produces lymphocytes

• Red pulp filters blood and contains phagocytes that ingest/phagocytose circulatingmicroorganisms and eliminates senescent RBCs

CMI defects: predispose to

infec-tion with intracellular pathogens

asplenia predispose to

infec-tion with encapsulated bacteria:

Strep pneumo, H influenza,

N meningitidis

CAUSAL CONDITIONS

ASC Box

Complement and Immune Dysfunction

Normally involved in inducing inflammation, leukocytosis; protective against viruses, improves bacterialopsonization, produces bacterial cell wall/membrane lysis

Inherited complement deficiencies:predispose to frequent and recurrent infections with encapsulatedbacteria

Acquired complement deficiencies: can develop with rheumatologic disorders (SLE)

Table 11.8 Causal Conditions of Fever in the Immunocompromised Host

B Inherited CMI defect

C Natural killer cell deficiency

• Phagocytes

A Phagocytosis (1◦/acquired)

B NeutropeniaCirculating

function

• Hyposplenism/functional asplenia (hemoglobinopathy [sickle cell disease], congenital)

• Therapeutic splenectomy (splenic injury/trauma, malignancy, thrombocytopenia, hemolytic anemia)Extrahematologic • Anatomic barriers are abnormal

Table 11.9 Classical Findings in Neutropenic Patients

and Their Associated Pathogens

Physical Exam

Oral mucositis Viridans streptococci, HSV, Candida spp

Black eschar Aspergillus, mucorNecrotizing skin lesions P aeruginosa, aspergillus

Subcutaneous nodules (nontender) Nocardia, cryptococcusSkin papules (nontender) Candida

RLQ abdominal tenderness (+/−

pan, distention, bloody diarrhea)

Typhlitis (neutropenic enterocolitis) 2◦to

pseudomonas, E coli, Clostridium spp.

Perineal tenderness Gram-negative bacilli, anaerobesInflammation/pain at IV, catheter

Diffuse interstitial infiltrate P jirovecii, viral pathogen

titers indicates infection with

specific pathogens and level of

function of the humoral immune

system

FEVER OF UNKNOWN ORIGIN

See also Chapter 18

DEFINITION

• Documented 3 or more wk without Dx after 1 wk of investigation

• Fever is a feature of not only most infectious conditions but also a feature of noninfectiousprocesses

APPLIED SCIENTIFIC CONCEPTS

• Fever: body temperature (≥38.3◦C)

• Hyperpyrexia: excessive fever (>41.5◦C) caused by↑ in body’s thermal set point thermia:↑ in body temperature beyond the body’s thermal set point

Hyper-• Exogenous pyrogens: substances (notably microbial cell wall components, LPS) thatinduce the formation of endogenous pyrogens from host cells (primarily macro-phages)

• Pyrogenic cytokines: cytokines (primarily IL-6) that act on the preoptic hypothalamus to

↑ body temperature by releasing PGE2

• Antipyretics inhibit synthesis of PGE2

• Corticosteroids inhibit phospholipase A2

• ASA, NSAIDs inhibit cyclooxygenase

C L I N I C A L B O X

Avoid Pharmacological Dx

Using response to medication as a means to establish Dx is discouraged:

• Illness may temporarily respond to corticosteroids, but eventually worsens due to induced pression

immunosup-• Abx use is often unspecific and impedes Dx of many infectious processes

CAUSAL CONDITIONS

Figure 11.10 Approach to FUO.

Table 11.10 Causal Conditions by Etiology for FUO

Infection • Upper/lower respiratory tract infection

• Abdominal abscess (hepatic, splenic, intestinal, renal)

• SBE, TB, bacteremia, travel/HIV-associated infections

• Osteomyelitis

• Meningitis, cerebritisInflammatory/

• 1◦Tumors in colon, pancreas; hepatoma, renal cell CA

• MetastasesMiscellaneous • DVT, PE

• Neutropenia (ANC <1,500/μL): Defects in neutrophils (PMNLs) may be due to

1◦ or underlying pathology, or 2◦ to medication use, and lead to compromisedimmunity

• Neutrophilia (ANC>7,700/μL]: Common etiologies include infection (leading to ↑production, release), and benign reactive neutrophilia, 2◦to epinephrine release, commonwith vigorous exercise and stress (↑ demargination)

• Spinal cord compression

• Hypertension (intracranial, pulmonary, portal)

• Obstruction (intestinal, ureteric)

• Pericardial tamponade

• Skin nodules

APPLIED SCIENTIFIC CONCEPTS

• Neutrophils are derived from a common progenitor that also gives rise to erythrocytes,megakaryocytes, eosinophils, basophils, and monocytes

• Proliferation of the common progenitor is stimulated by IL-3 and GM-CSF

• Later differentiation is regulated by granulocyte colony-stimulating factor

• Production of granulocytes involves movement from marrow to blood to tissue.

• The peripheral neutrophil count reflects equilibrium between several ments

compart-• WBC count and differential measures only neutrophils in the circulating pool duringtheir brief 3- to 6-h period of transit from the bone marrow to tissue

• PMN granules contain toxic substances

• Neutrophils migrate to sites of infection or inflammation via paracellular and transcellularroutes through endothelial cell layers

neu-trophils tend to be mature

and not clonally derived

(contrast with leukemia)

• Most frequently associated

with septicemia and severe

bacterial infections,

includ-ing shigellosis,

salmonel-losis, meningococcemia

• If 12% of all cells are

imma-ture, then it is known as

left shift and indicates

a rapid release of cells

from bone marrow

• May see↑ in band forms

and in metamyelocytes/

myelocytes, which usually

do not circulate

• Higher degree of left shift is

associated with more

imma-ture neutrophil precursors

and suggests serious

bacte-rial infection, trauma, burns,

surgery, acute hemolysis,

or hemorrhage

CAUSAL CONDITIONS

Table 11.11 Causal Conditions for WBC Abnormalities

Neutropenia (ANC <1,500/μL, isolated— no other cell lines)

↑ Destruction • Autoimmune disorders (SLE, Felty, Wegener granulomatosis)

• Splenic/lung trapping

• Drugs (sulfa-containing Abx,α-methyldopa)

↓ Production • Marrow invasion (aplastic anemia, tumor, myelofibrosis)

• Infection (TB, infectious mononucleosis, viral hepatitis, AIDS)

• Drugs (alkylating agents, antimetabolites, anti-inflammatory agents,antipsychotics)

• Nutritional deficiency (Vit B12, folate —especially in alcoholics)

• Idiopathic, cyclic neutropeniaTransient neutropenia

↑ Production • Hypersensitivity states

• Myeloproliferative diseases (myelocytic leukemia, PCV)

• Bacterial, fungal, occasionally viral infections

• Collagen vascular diseases

↓ Margination • Drugs (epinephrine, glucocorticoids, NSAIDs)

• Stress, vigorous exerciseMiscellaneous • Metastatic CA

• Metabolic disorders (ketoacidosis, eclampsia, acute poisoning/renalfailure)

• Acute hemorrhage/hemolysis

• Lithium

APPROACH

See Figure 11.11

Dr Hernish Jayant Acharya, Dr Scott Edward Jarvis,

and Dr Ted Roberts

GAIT DISTURBANCES AND ATAXIA

DEFINITIONGait:the manner of walking

Ataxia:impaired ability to coordinate muscular movements resulting in unsteadiness

Abrupt onsetExtreme slownessUnusual or uneconomic postureExaggerated effort

Sudden buckling of the knees(Adapted from Snijders A, van de Warrenburg B, Giladi N, et al Neurological gait disorders in elderly

people: Clinical approach and classification Lancet Neurol 2007;6(1):63 –74.)

310

Table 12.1 Approach to Gait Disturbance

Clinical fx Investigations Management Impaired balance

1 Cerebellar

A Midline lesion

(tumor, hemorrhage, MS,drugs, tox)

Ataxia, nystagmus,disequilibrium, widebased, reeling,↑ stride tostride variability,abnormal postural sway

MRI, tox screen, EtOHlevel

If mass lesion, consultneurosurgery

If drug/tox related, refer

to emergency

B Hereditary Wide based, unsteady

gait, uncoordinated limbsand speech, FHx

Genetic testing availablefor some, vitamin B12,TSH

Refer to neurology,genetic counseling

i Catalytic/inborn errors

MRI, TSH, B12, Cr, LFTs Refer to neurology

B Proprioceptive Patient may compensate

by watching feet, positiveRomberg, impairmentworse in dark

MRI, TSH, B12, Cr, LFTs Refer to neurology, PT/OT

C Visual Poor visual acuity, poor

peripheral vision

Snellen chart Corrective visual aid

Refer to ophthalmology

Impaired locomotion

1 Weakness See Hemiplegia/Hemisensory loss topic

2 Hypokinetic See Movement D/Os topic

3 Higher level dysfunction (frontal

lobes, basal ganglia,thalamus, midbrain,tumor, dementia,hydrocephalus)

Abnormal cognitivetesting, abnormalcorrective response toperturbation, bizarre gait,worse in unfamiliarenvironment

MRI, cognitive testing Refer to neurology, OT

4 Antalgia (MSK D/O,

arthropathies,deformities)

Hx of MSK disease,improves with analgesia,normal neurologic exam

As per clinical situation As per clinical situation

HEADACHE

DEFINITION

Headache (h/a) can be 2◦to severe disease requiring emergent management

C 2 L E O B o xPhysician Legal Responsibility

Physicians are legally bound to perform complete clinical assessment on all patients presenting with h/a

APPLIED SCIENTIFIC CONCEPTS

Brain parenchyma is not pain sensitive

Figure 12.2 Neurovascular/serotonin

theory of migraine pathophysiology

Figure 12.3 Cranial pain sensitive

structures

CAUSAL CONDITIONS

Figure 12.4 Approach to h/a.

Clinical Signs Suggestive of ↑ ICP

‘‘Put on your thinking cap, COG CAP’’

Cushing triad (bradycardia, HTN, widened pulse pressure) Ocular palsies

GI: N/V Consciousness, altered LOC A.M h/a, worse in recumbency Papilledema

C L I N I C A L B O X

Hypercoagulable W/U

CBC, INR, PTTFibrinogenProtein C, protein SActivated protein C resistance (factor V Leiden)Antiphospholipid antibodies

Anticardiolipin antibodies

Lupus anticoagulantHyperhomocysteinemiaProthrombin G20210A mutationAntithrombin III deficiencyPregnancy test

Malignancy w/u

Table 12.2 Red Flag H/A Should be Evaluated in a Hospital Setting

Vascular

SAH Sudden onset, preceded by Valsalva, meningismus CT: acute blood in subarachnoid space Refer to neurosurgery

LP: xanthochromiaTemporal arteritis >50 yr, monocular blurred vision, tenderness over

TA, proximal muscle tenderness

↑ ESR TA biopsy, high-dose

corticosteroidsVenous thrombosis Diffuse h/a, Hx clot, hypercoagulable state, low

flow state

Abnormal hypercoagulable w/u (seeclinical box Hypercoagulabe w/u),MRV: thrombosis

Nonvascular

↑ CSF pressure See clinical box Hypercoagulable w/u CT: slit-like ventricles, obliteration of

fourth ventricle

Refer to neurosurgeryIntracranial infection

• Meningitis Febrile, sepsis, meningismus, rash,↓ LOC Bacterial:↑↑ protein, ↓ gluc., ↑↑ WBCs Immediate broad-spectrum

Viral:↑ protein, gluc normal, ↑ WBCs IV antibiotics, do not wait

CT: ring-enhancing lesion Refer to neurosurgery and ID

Table 12.3 Fx of Benign Primary H/A

<8 d/mo (Symptomatic) >12 d/mo (Prophylactic)

Migraine N/V, photo/phonophobia, aura (e.g., scintillating

scotoma), worse with activity

Triptans, DHE Propranolol, TCAs, AEDs

Tension type Later in the day, no associated symptoms/signs NSAIDs, acetaminophen TCAs, AEDs

Dull, aching, band-like h/a associated with stressCluster ♂ > ♀, severe stabbing, periorbital pain with

ipsilateral autonomic signs (tearing, miosis, hydrosis,conjunctival injection), seasonal recurrence of multipleepisodes with intermittent remission

O2, triptans, DHE Steroids (short term), verapamil,

Drug holiday, d/c offending agent if possible

HEMIPLEGIA/HEMISENSORY LOSS

DEFINITIONHemiplegia:loss of power on the left or right side of the body

Hemisensory loss:loss of sensation on the left or right side of the body

APPLIED SCIENTIFIC CONCEPTS

Figure 12.5 Circle of Willis and major arteries of the CNS Shown is the Circle of Willis, where the anterior (internal carotid)

circulation meets the posterior (vertebrobasilar) circulation Important clues for localizing lesions in the CNS vasculature

include weakness (leg> arm = face)—contralateral ACA; weakness (face = arm > leg) ± aphasia—contralateral MCA(aphasia if the lesion is on the dominant side); transient monocular blindness (amaurosis fugax) —ipsilateral ICA (with

emboli to the ophthalmic artery); and dysarthria, diplopia, vertigo, N/V —vertebrobasilar circulation

Figure 12.6 Effect of CO2in CNS

vasculature CO2is a potent

vasodilator Therefore, decreasing

CO2, by hyperventilation or↑ tidal

volume, will cause vasoconstriction,

leading to↓ blood flow and a ↓ ICP

Therefore, in the management of

acute ICH, for example, it is

important to keep pCO2from 30 to

35 Remember:↓ CO2→ ↓ blood

flow→ ↓ ICP Note: When

monitoring ICP, one may also

measure the MAP and then calculate

the CPP using the formula CPP=

MAP – ICP

Figure 12.7 Cardiac sources of

thromboembolism DCM; PFO allows

right-sided thrombus through

congenital heart defect Note:

Implication of PFO in stroke etiology

requires two additional fx to be

present: (a) DVT and (b) RA pressure

> LA pressure (e.g., RV hypertrophy)

to allow right to left flow of clot

through the PFO PFO is present in

DX

Onset of clinical symptoms in ischemic and hemorrhagic strokes:

• Ischemic stroke: develops over minutes to hours

• Thrombotic stroke: maximal at onset

• Lacunar stroke: stuttering progression± periods of improvement/deterioration common

• ICH: develops over minutes to hours

• SAH: abrupt, severe ‘‘thunderclap’’ h/a, other symptoms within hours

• TIA: onset and resolution of symptoms within 1 h (was previously defined as a neurologicdeficit<24-h duration)

RFs for hemorrhagic stroke

• Cardiac sources of thromboembolism: see Figure 12.8

• Atherosclerosis∗(intracerebral [ICA] and extracerebral [ECA])

• Obstructive sleep apnea (independent RF; mechanisms unclear†)

• Hypercoagulable states: see clinical box Hypercoagulable w/u

• Hypoperfusion: cardiac arrest, acute MI, tamponade, PE

• Sickle cell disease

∗

Mechanisms = (a) perfusion failure (e.g., carotid stenosis [ECA]), (b) plaque rupture (local thrombosis [ICA] +/− distal arterioarterial thromboembolism [ICA and ECA]), and (c) occlusion of small artery origins (ICA)

Table 12.4 Common Causes of Hemiplegia/Hemisensory Loss and Differentiating Factors

Duration of

Stroke (hemorrhagic) Immediate

See clinical box Clinical Signs Suggestive of ↑ ICP

Hours to permanent Confused/

disoriented with ICH Possible ↓ LOC with SAH

Sudden, severe h/a.

‘‘Worst ever’’ with SAH

Diplopia, field cuts common, depending

paresis)

Postseizure (typically clonic, GTC)

Common Diplopia can occur Uncommon,

transient Inflammatory (MS) Can be abrupt, but

typically over days

Deficit may be permanent or resolve completely

↓ LOC, h/a, vision  (common) and aphasia can all occur in MS, but will not be due to the same lesion causing hemiplegia/hemisensory loss

Viral encephalitis Over days Depends on latency

to Rx, can be permanent

Confusion → delirium → lethargy

→ coma

Common Photophobia,

nystagmus, diplopia (2 o ocular palsy)

2 o ↓ LOC

Trauma, acute SDH Abrupt, or following

lucid interval (SDH)

Can be permanent Initially alert, then

rapid ↓ LOC with acute SDH

Severe Common—diplopia Common

Mass lesion (tumor,

Gradual ↓ LOC with Chron SDH

Common, may become severe

Depends on lesion location

Common

Conversion D/O is a common cause of hemiplegia/hemisensory loss, but is considered a Dx of exclusion Suggestive of conversion D/O:

• Pattern of weakness cannot be explained by a single lesion

• Give-way weakness and discontinuous power during strength testing

• Sensory s do not correspond to dermatomes

Syncope does not cause hemiplegia or hemisensory loss, and can generally be differentiated from seizures by considering the criteria in Table 12.16

INVESTIGATIONS

Standard w/u for stroke/TIA patients

• CBC, Lytes, Cr, BUN, gluc., INR, PTT

• LFTs, CK (before starting statin Rx)

• Fasting lipid profile, fasting gluc

• Tox screen if suspected in SAH

• ESR, CRP if inflammatory process suspected

• EKG

• Noncontrast CT head

If clinically suspicious of hemorrhage, and CT head is negative for acute bleed, do LPfor xanthochromia (xanthochromia present in all SAH≥2 wk postbleed)

Imaging studies in stroke/TIA patients:

• Noncontrast CT—always done Differentiates hemorrhagic stroke from ischemic stroke

(blood is white on CT) Faster as an initial screen in patients with acute symptoms, lesssusceptible to motion artifact, and cheaper than MRI Used to determine whether tPA isgiven

• CT angiography—gold standard for imaging atherosclerosis and dissection in carotid,

vertebral, and basilar arteries Highly effective for identifying site of intracranial vascularlesions Requires injection of dye (potentially nephrotoxic)

• MRI—superior to CT for detecting aneurysms, AVMs, other structural lesions Much

more sensitive than CT for acute ischemics (within the first few hours of stroke) andsuperior for imaging the posterior fossa MRI–DWI can detect early ischemics within

10 min of an event PWI is employed to demonstrate penumbral tissue at risk GRE–MRIhas the highest sensitivity for detecting early hemorrhagics

• MR angiography—useful in identifying extracranial arterial dissections Less tion on intracranial vascular lesions than CT angiography, but does not require injection

• TEE—typically performed after TTE is invasive but has a much higher yield in detecting

atrial thrombi, atheromatous aortic disease, valvular disease, and PFO

• Carotid Doppler ultrasound —rapid, noninvasive, dye-free initial assessment of carotid

artery stenosis High sensitivity and specificity for carotid stenosis ≥50% Does notaccurately assess stenosis<50% nor is it useful for assessing vertebral circulation Usefulfor screening stroke/TIA patient for carotid stenosis—guides and accelerates clinicaldecision to use angiography

C L I N I C A L B O X

PEx Findings Useful in

Predicting the Etiology

of Stroke

Retinal hemorrhages —HTN and

diabetic retinopathy

Purpura, ecchymoses —platelet

D/O, coagulation D/O, vascular

Osler nodes, Janeway lesions,

Roth spots, splinter

hemor-rhages, petechiae —endocarditis

DVT findings (in combination

with PFO) —thromboembolism STROKEPREVENTION

• Surgical management (carotid endarterectomy) if:

• Symptomatic (i.e., patient has had stroke/TIA)

• ≥70% carotid stenosis (determined by angiography or noninvasive imaging)

• Performed within 2 wk of stroke/TIA

• Acceptable surgical risk

• Medical management

• Primary prevention

• Lifestyle modifications (smoking cessation, regular exercise, weight loss, diet ifications, EtOH consumption one to two drinks per day)

mod-• BP: maintain BP≤140/90, ≤130/80 for diabetics (first line = ACEI/ARB, diuretics)

• Lipids: LDL≤4 mmol/L, TC/HDL ≤5 if no RFs; LDL ≤2 mmol/L, TC/HDL ≤4 ifmultiple RFs Initiate statin at low dose (e.g., simvastatin 20 mg qHS) and titrate up

as needed If needed, add on additional agent —ezetimibe, fibrate, niacin

• DM: maintain tight glycemic control; targets= fasting BG <7, HbA1 C≤7.0%

• Afib: target INR 2.5, range 2.0 to 3.0

• 2◦Prevention (i.e., following a TIA)

• All of the above

• Aggrenox (dipyridamole 200 mg+ ASA 25 mg) b.i.d may be superior to ASA—can

be used instead of ASA, but not in addition to ASA

• Lipids: target LDL <2.0, TC/HDL ≤4

Medical and Surgical Management of Acute ICH

• Ensure airway patency, intubate for GCS<8, adequate oxygenation

• Treat HTN only if severe and persistently elevated Goals: sBP≤220 mm Hg and dBP

≤120 mm Hg† Use labetolol 10 mg IV q5-10 min and enalapril 2.5 mg For refractoryHTN, consider nitroprusside, hydralazine, clonidine Do not drop BP more than 25%from baseline in the first 24 h

• Correct coagulation abnormality (FFP, vitamin K‡)

• If GCS<9, consider ICP monitor (with ventricular catheter)

• If↑ ICP (on monitor, and look for midline shift, herniation, mass effect) Rx include:

• Intubate and hyperventilate with target Paco230 to 35 mm Hg (see Figure 12.6)

• Drain CSF through ventricular catheter

• Furosemide and either mannitol or hypertonic saline

• Elevate head of bed 30 to 45 degrees (reverse Trendelenberg)

• Craniotomy/evacuation of hematoma to reduce risk of brain herniation (from cerebellarlesion>3 cm, hemorrhage 2◦structural lesion, lobar hemorrhage in young patients)

Medical Management of Acute Ischemia/TIA

• Ensure airway patency, all patients on O2

• IV fluids only if hypotense, avoid D5 W

• tPA if no contraindications and time from onset<3 h [Notes: (a) if tPA to be given, risk

of ICH makes BP control critical—keep sBP≤185 and (b) no additional anticoagulantswithin 24 h of tPA administration]

• Treat HTN only if severe and persistently elevated, as for ICH (above)

• Treat arrhythmias appropriately (or consult)

• Treat Lyte abnormalities

• Avoid hyperthermia (acetaminophen 650 mg PO/PR q4 h, cooling fan)

• ASA 160 mg loading dose, then 81 mg q.d (hold for 24 h post-tPA)

• Admit to stroke unit

POSTSTROKEREHAB

• Passive movement of paralyzed limbs should begin within 2 d of the event, regardless ofpain, to avoid contractures and potential CRPS

• Intense PT results in better recovery

• SLP for dysphagia early in recovery to assess risk of aspiration

• Brain tissue remodeling and reorganization continues for months poststroke—mosthemiplegics recover some ability to walk by 6 mo

HOARSENESS/DYSPHONIA/SPEECH AND LANGUAGE ABNORMALITIES

DEFINITIONLanguage D/O:impaired comprehension, form, content, or function of language

Speech D/O:correct word choice and syntax, impaired articulation

Hoarseness: in quality of voice

C L I N I C A L B O X

Conservative Management for Speech D/Os

Voice rest, fluids, humidity, antireflux, smoking cessation

If conservative measures fail>2 wk, refer for laryngoscopy to R/O neoplasm (RF: smoker/drinker/Asiandescent)

Table 12.5 Language D/Os

Classification Common Etiologies Management Language D/Os

Developmental Learning disability, ADHD Refer to pediatrics, SLPDegenerative Mucopolysaccharidosis, aphasia Refer to neurology, SLPNeglect/abuse/head trauma SW, refer to pediatrics/

neurology, SLP

Speech D/Os

A Articulation D/O

1 Nasal/badly articulated/slurred

• Dysarthria± dysphagia CVA, tumour, CP Refer to emergency/neurology

• Hearing impairment Cerumen impaction Disimpaction, SLP

Sensorineural loss Refer to audiology

• Soft palate paralysis MG, MS, cleft lip/palate Refer to neurology/ENT

• Bulbar/psuedobulbar palsy ALS Refer to neurology

2 Speech apparatus lesions/hoarseness

• Inflammation Infection, allergy, voice abuse,

smoking, EtOH, GERD

Treat as per cause, see clinicalbox Conservative Managementfor Speech D/Os

If persists>2 wk, refer to ENT

• Neoplasms Laryngeal benign/malignant

neoplasms

Refer to ENT for laryngoscopy

i Recurrent nerve palsy Para/thyroidectomy, tumor Refer to ENT

ii Hyperfunction Muscle tension, spasmodic

dysphonia

Refer to neurology/ENT

3 Silent/non-speaking Catatonia, depression, brainstem Refer to psychiatry/neurology/

pediatrics

APPLIED SCIENTIFIC CONCEPTS

Figure 12.9 Schematic of language

and speech dysfunction

DELIRIUM: ALTERED MENTAL STATUS

DEFINITIONDelirium:Medical emergency characterized by acute, fluctuating disturbance of conscious-ness with reduced ability to focus, sustain, or shift attention

Affects 10% to 15% of elderly at presentation to hospital and up to 30% as inpatients.Dementia is a major RF for delirium (acute  in behavior in demented patient mayrepresent delirium)

Table 12.6 Etiology, Investigations, and Management of Delirium

Systemic

Deficiency

HypoxemiaGlobal ischemia Sao2, ABG Supplement O2, consult neurologySevere anemia CBC Varies with cause, transfusionEndocrine deficiency

Drugs/Tox EtOH level, other drug levels

formal drug review

ABCs, stop absorbption, antidote,supportive care, consult ICU, d/canticholinergic medicationsOrgan failure

Uremia Urea, Cr Consider dialysis, consult nephrologyHepatic failure ALT, AST, ALP, albumin,

coagulation studies

Consult gastroenterologyCHF CXR, ECHO Consult internal medicineHypercarbia ABG Supplemental O2, hyperventilate, correct

acid– base abnormalitySepsis SWU ABCs, antibiotics, antifungals, antiviralsLytes Lytes, Ca2 +, Mg2 +, PO4 Determine underlying cause, correct Lytes

Local CNS

Infectious SWU, LP ER, consult neurologyVascular event CT head ER, consult neurology/neurosurgeryPostictal CT head, EEG Consult neurology

Neoplasm CT/MRI Consult neurosurgery

APPLIED SCIENTIFIC CONCEPTS

Figure 12.10 Acetylcholine in the

pathophysiology of delirium

DEMENTIA: ALTERED MENTAL STATUS

DEFINITIONDementia: reversible or irreversible impairment of higher intellectual functions in theabsence of impairment in arousal

APPROACH

Establish cognitive decline (patient and collateral Hx)

• Cognitive Hx (serial MMSE, memory, perception, language, visuospatial function,judgement)

• Functional Hx (basic and instrumental ADLs, family involvement)R/O reversible causes (10% to 15%)

• Frontal lobe dementia

• Potentially reversible —toxic/medication

• EtOH/drugs (tox screen)

• Heavy metals

• Mass lesions/neoplasms (CT/MRI)

• CNS neoplasms

• Chron subdural hematoma

• Normal pressure hydrocephalus

• B12/thiamine deficiency (B12level)

• Lyte disturbance (Lytes)

• Depression

MANAGEMENT

• Patient education/counseling appropriate to cognitive function/level of disability

• Elicit patient/family wishes, community support, functional status of patient

• Consider interdisciplinary approach (OT, psychology, etc.)

• Consider consulting neurology for medical management

COMA: ALTERED MENTAL STATUS

DEFINITIONComa:state of pathological, unarousable unconsciousness

CAUSALCONDITIONS

Table 12.7 Localizing Brain Involvement in Altered Mental State

Imaging: CT/MRI Investigations: Sao2, ABG, CBCD, Lytes, Ca2+,

Mg2 +, vitamin B12, urea, ALT, AST, albumin,

SWU, urinalysis (+ketones, C&S), TSH, CT head

PEx: response to painful stimuli andtone, brainstem reflexes

Symmetric, normal Asymmetric, abnormal Deficiencies Excesses Bilateral

hemispheric

hemorrhage,infarction, mass,neoplasm, abscess,trauma

Brainstem

Hemorrhage, infarction,mass (herniation), trauma

Hypoxemia, hypocarbia,Lyte deficiency,hypoglycemia,hypothermia, vitamin

B12/thiamine myxedema

Uremic/hepaticencephalitis, metabolicacidosis, DKA/HONK,↑Lytes, hyperthermia,thyroid storm, drug/tox

• Consider narcotic antagonist

• Consider selective benzodiazepine antagonist

APPLIED SCIENTIFIC CONCEPTS

Extrapyramidal clinical symptomatology results from basal ganglia dysfunction

Figure 12.11 Basal ganglia

circuitry Parkinson disease:↓

dopamine from the SNc through D1

and D2 to the striatum switches the

balance of activity in the direct and

indirect pathways, leaving the

indirect pathway↑ and the direct ↓

CAUSAL CONDITIONS

Figure 12.12 Characterization of the movement by clinical examination.

C L I N I C A L B O X

Possible Tests in Abnormal Movements

CBC, Lytes, Cr, BUN, LFTsPeripheral smear —neuroacanthocytosisTSH —hypo- or hyperthyroidismGluc

EEGWilson tests —serum ceruloplasmin (↓),serum, urine copper (↑), slit lamp forKayser-Fleischer rings If positive, test family

Table 12.8 Differential Dx of Hyperkinetic Movement D/Os

Phenomenology Clinical/Labor Findings Management

Hyperkinetic

Tic

A Primary

1 Tourette syndrome Childhood onset, multifocal tics,>1yr Refer to pediatric neurology

2 Huntington disease Onset in third decade, insidious onset of chorea/cognitive

Creutzfeldt-Jacob Rapidly progressive psychiatric/behavioral symptoms Referral to neurology for LP, imaging, EEG

Sydenham chorea 1–6 wk post GAS pharyngitis Referral to pediatrics for w/u of rheumatic fever

Drugs Methylphenidate, pemoline, amphetamines, cocaine Remove offending drug

Stereotypies With autism or mental retardation, failure to

achieve/regression of developmental milestones

Refer to pediatrics/pediatric neurology

Essential tremor FHx, inability to take soup with a spoon, better with EtOH If severe, trial of propranolol, R/O Wilson disease

Myoclonus Can occur alone or in combination with other neurologic

disease

Refer to neurology for assessment (many etiologies,symptomatic control can require polypharmacy)

Table 12.9 Differential Dx of Hypokinetic Movement D/Os

Phenomenology Clinical/Lab Findings Management Hypokinetic

Parkinson disease Tremor, rigidity, bradykinesia

Table 12.10 Differential Dx of Tremors

Phenomenology Clinical/Lab Findings Management Tremor

Resting (Parkinsondisease, Wilsondisease)

Rest tremor, rigidity, bradykinesia,postural instability

Trial of L-Dopa or dopamine agonistRefer if Dx unclear

See clinical box Possible Tests in Abnormal MovementsEssential tremor FHx, inability to take soup with a spoon,

better with EtOH

If severe, trial of propranolol, R/OWilson disease

Intention/kinetic(cerebellar disease)

Ataxia, nystagmus, dysdiadochokinesis Refer to neurology for imaging and Rx

MS Multiple neurologic deficits

disseminated in time and space

Refer to neurology for imaging and RxMidbrain stroke Acute onset, vascular RFs Refer to neurology for imaging and RxTrauma Hx of trauma, external signs ATLS, rehab

Enhanced physiologic Worse with anxiety, fever, fatigue,

caffeine, EtOH withdrawal, FHx

Table 12.11 Localize the Lesion

Distribution of Symptoms Associated Fx Common Etiologies Investigations

Cerebral cortex Unilateral arm/face± leg

(follows homunculus)

Hemiplegia, apraxia, aphasia, neglect,impaired, two- point discrimination,agraphesthesia

Stroke, demyelination, tumor CT/MRI

Brainstem Arm/body/leg and

Back pain, bowel/bladder dysfunction Cord infarction, tumor, MS,

syringomyelia, B12deficiency

MRI, EMG/NCS,

B12levelPeripheral nerve

Stocking/glove Sensory± motor DM, uremia, vasculitis, B12

deficiency, HIV, Lymedisease, EtOH,paraneoplastic, amyloid

HbA1c, B12level,HIV viral load,CD4 count, TSH

Figure 12.13 Patterns of sensory loss.

C L I N I C A L B O X

Management of Mononeuropathy (e.g., Carpal Tunnel Syndrome)

Hx and PEx suggestive of mononeuropathyR/O EtOH, DM, TSH abnormalities, mass effect, vasculitis (ESR, CRP), sarcoidosis (SPEP),uremic neuropathy (Cr, urea), lupus (RF, ANA)

R/O subacute ascending neuropathy with areflexia (GBS)Determine functional limitations

Conservative Rx: task modification, wrist splints (carpal tunnel syndrome)

If conservative measures fail: EMG/NCS

If severe/axonal loss: surgical release

NEUROPATHIC PAIN AND COMPLEX REGIONAL PAIN SYNDROME

DEFINITIONNeuropathic pain: Pain resulting from dysfunction/disruption of either the central orperipheral nervous system

Description: burning, sharp,

stab-bing, shooting, electrical shock

Allodynia: painful response to a

stimulus which is not normally

painful (e.g., light touch, cool air)

Hyperalgesia:↑ pain in response

to a stimulus which is normally

nominally painful (e.g., pin prick)

Table 12.12 Differentiating Diabetic Neuropathic Pain

from Diabetic Vascular Pain

Neuropathic Pain Vascular Pain Location Distal (feet, ankles) Calves

Perception Sharp, burning, tingling Deep pain