Transcript Weekday Morning Report

Weekday
Morning Report
Subspecialty: Neurology
February 26, 2010
Ankur Kalra, MD
HISTORY & PHYSICAL
CASE PRESENTATION
History & Physical
 48 year old African American female
 Left-sided headache; left-sided weakness
 History of chronic daily headaches
 Current headache:
 Insidious in onset
 Different in character from headaches in past
 Associated with double vision; left sided weakness of the
face, arm, and leg
 No history of fever, neck stiffness
History & Physical
 History of residual weakness from previous
cerebrovascular accidents
 Current weakness worse than one at baseline
 Associated with decreased sensations on left side
 No history of bladder or bowel incontinence
 No history of seizures
 No history of loss of consciousness
History & Physical
 Past medical history




Gastroesophageal reflux
Essential hypertension
Migraine headache
Recurrent cerebrovascular accidents in the past (first at age 35
years)
 Medication history
 Antiplatelet: Aspirin; Dipyridamole
 Antihypertensives: Lisinopril; Hydrochlorothiazide; Carvedilol;
Amlodipine; Clonidine
 Lipid lowering: Simvastatin
 Analgesia: Acetaminophen-butalbital-caffeine
History & Physical
 Social history
 No tobacco, alcohol, or recreational drug use
 Family history
 Stroke (father, aunts, grandfather) (40s – 50s)
History & Physical
 Physical examination





T 97 F
HR 80 beats/min
BP 167/95 – 237/109 – 173/77 mm Hg
RR 18 breaths/min
SaO2 100 per cent on room air
 CV: normal first & second heart sounds; no murmurs, rubs, or
gallops
 RS: normal vesicular breathing; no added sounds
 GI: soft; non tender; non distended; bowel sounds present
History & Physical
 Neurologic examination








Awake, alert, and oriented to time, place, and person
No dysarthria
Bilateral cranial nerve VI palsy; other cranial nerves intact
Motor strength 4/5 in left upper, and lower extremities
 5/5 in right upper, and lower extremities
Needle prick sensation decreased on the left side
No pronator drift
No dysmetria
Normal affect
INVESTIGATIONS
CASE PRESENTATION
Investigations
 Hb 11.5 WBC 6.6 Platelet 264
 Na 139 K 3.3 Cl 100 HCO3 27 BUN 14 Cr 0.6
 Glucose 141
 Calcium 9.2
 PT/INR 11.6/1.0
 aPTT 25.8
 Cardiac enzymes negative
Investigations
 Chest X Ray No acute cardiopulmonary disease
 EKG Normal sinus rhythm
 CT Head without contrast
 No acute bleed
 Mild white matter changes: nonspecific
 Largest area of abnormal signal intensity in
subcortical matter of right frontal lobe
 Recommend diffusion weighted MRI
Investigations
 MRI Brain without/with contrast
 No acute ischemic event
 Mild nonspecific white matter changes
 MRA Head & Neck unremarkable
 2 D Echo: moderate concentric LVH; EF 60 – 65%
 CT Angiography Head without/with contrast
 Minimal irregularity and thickening of proximal
basilar artery
 MRV Head normal
DIFFERENTIAL
CASE PRESENTATION
Differential Diagnosis
 Prothrombotic states







Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Resistance to activated protein C
Prothrombin gene 2021A mutation
Antiphospholipid syndrome
Elevated homocysteine levels
Differential Diagnosis
 Inflammatory conditions
 Primary vasculitides
 Takayasu arteritis
 Giant cell arteritis
 Polyarteritis nodosa
 Primary angiitis
 Secondary vasculitides
 Collagen vascular disease
 Bacterial meningitis
 HIV
 Syphilis
 Tuberculosis
 Fungal infection
INVESTIGATIONS
CASE PRESENTATION
Investigations
 HbA1c 6.3
 TSH 3.54
 ESR 32 mm/hour (high)
 CRP 2.20 mg/dL (high)
 Immunology
 ANA negative
 ENA to SSA/SSB negative
 ANCA negative
Investigations
 Coagulation




Protein C 104 % (normal)
Protein S 102 % (normal)
Activated protein C resistance 3.8 (normal)
Lupus anticoagulant screen
 Dilute Russel Viper Venom Time negative
 Hexagonal Phase Phospholipid Neutralization negative
 Β2 glycoprotein I negative
 Prothrombin gene 20210A mutation negative
 Factor II mutation negative
Investigations
 Infectious Disease
 Lyme antibody negative
 HIV negative
 RPR negative
Investigations
 CSF normal protein; no hypoglycorrhachia; no white
cells; 58 red blood cells
 IgG/albumin ratio High
 Lyme antibody nonreactive
 Myelin basic protein normal range
 Oligoclonal bands absent
 VDRL nonreactive
 CSF culture No growth
IS THIS A ZEBRA?
CASE PRESENTATION
Differential Diagnosis
 Metabolic disorders




CADASIL
MELAS
Fabry disease
Menke’s disease
CADASIL
Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts and Leukoencephalopathy
REVIEW
CADASIL
 Reported worldwide
 Prevalence of mutation carriers 1 in 50,000 to 1 in
121,000
 One or more of the following four manifestations:




Ischemic episodes
Cognitive deficits
Migraine with aura
Psychiatric disturbances
CLINICAL FEATURES
CADASIL
CADASIL
 Clinical features
 Ischemic stroke and TIA





Most frequent presentation
85 per cent of symptomatic individuals
Age at onset 19 to 67 years
Median age 51 years (men); 53 years (women)
Classic lacunar syndromes (pure motor, pure sensory,
sensorimotor, dysarthria-clumsy hand)
 Ischemic events are recurrent and disabling
CADASIL
 Clinical features
 Cognitive deficits




Second most common feature
60 per cent of symptomatic individuals
75 per cent of mutation carriers develop dementia
Lacunar lesion volume, global brain atrophy, and age
independent predictors
 Loss of executive function; verbal fluency
CADASIL
 Clinical features
 Migraine with aura






30 per cent of CADASIL cases
Early sign
Usually the first symptom with age of onset before 40
Develop hemiplegic, or basilar migraine; isolated aura
Severity of migraine decreases following first stroke
Difficult to differentiate hemiplegic migraine from an ischemic
event
CADASIL
 Clinical features
 Psychiatric disturbances
 25-30 per cent of patients
 Adjustment disorder, depression, panic attacks, hallucinatory
syndromes
 Key feature: apathy – primary loss of motivation with
diminished speech, motor activity, and emotional expression
CADASIL
 Clinical features
 CADASIL and pregnancy
 40 per cent with neurologic deficits
 Initial presentation in pregnancy
 Complications include TIA, migraine, and preeclampsia-like
symptom complex
NEUROIMAGING
CADASIL
CADASIL
 Neuroimaging
 Magnetic Resonance Imaging (MRI)
 Small circumscribed regions isointense to CSF on T1, and
T2-weighted images
 Less well demarcated T2-hyperintensities of variable size:
variable degree of hypointensity on T1-weighted images
clearly distinct from CSF
 Subcortical white matter, brainstem, subcortical gray matter
CADASIL
 Neuroimaging
 Magnetic Resonance Imaging (MRI)
 Temporal lobe and external capsule hyperintensities
 Subcortical lacunar lesions
 Cerebral microbleeds
 31 to 69 per cent of patients
 Not specific for CADASIL
 2 mm – 5 mm multifocal areas of hemosiderin deposition
 Brain atrophy
DIAGNOSIS
CADASIL
CADASIL
 Diagnosis




Positive family history of stroke and dementia
Typical clinical features
Typical brain MRI
Plus one or both:
 Documentation of NOTCH 3 mutation by genetic analysis
 Documentation of characteristic ultrastructural deposits
within small blood vessels by skin biopsy
CADASIL
 Diagnosis
 Genetic screening
 80 different mutations
 Notch3 transmembrane receptor of (epidermal growth factor)




EGF-like repeat domain
95 per cent missense mutations
Highly stereotyped; involve cysteine residues
85 per cent exons 2 – 6
Skin biopsy if genetic screening negative
CADASIL
 Diagnosis
 Skin biopsy
 EM: Granular osmiophilic material (GOM) within vascular
basal lamina of arteries, arterioles, and precapillaries
 Extracellular domain of Notch3 transmembrane receptor in
vascular media
MANAGEMENT
CADASIL
CADASIL
 Management
 General issues
 General principles of stroke medicine
 Low dose aspirin
 Adequate blood pressure control (increased systolic pressure
associated with brain atrophy and cerebral microbleeds)
 Adequate glycemic control with HbA1c < 7.0
 No role of anticoagulation
CADASIL
 Management
 Symptomatic therapy
 Emotional lability with pathologic crying or laughing –
selective serotonin reuptake inhibitors (SSRI)
 Migraine headache – nonpharmacologic therapy; NSAID;
triptans contraindicated
NOTCH 3 GENE MUTATION
GENETIC ANALYSIS RESULTS NEXT WEEK
THANK YOU
NEXT PRESENTATION: MARCH 16, 2010