General Data

• DS• 65 year old• Female• Informants: Patient and Husband• Reliability

– Patient 70%– Husband 80%

• Right- handed

Chief Complaint

• “Numbness of the left hand”

History of Present Illness

• Nine months PTA,– “pins and needles” sensation; left hand– one episode of generalized tonic- clonic seizure

• Head tilting to the right• Eyes rolling upward• Stiffening of upper and lower extremities• Tongue biting• Lasting for 1- 2 minutes

– (-) blurring of vision, palpitations, tremors, nausea, vomiting, dizziness, sweating, urinary incontinence

History of Present Illness• Admitted in the hospital for 10 days

– CT scan was done– Discharge summary: Seizure. Two old right

parietal lobe hemorrhagic infarcts. Hypertension. Diabetes Mellitus Type II. Hypercholesterolemia.

– Medications prescribed: • Aspirin 75 mg OD• Dipyridamole 200 mg OD• Perindopril 8 mg OD

– No memory of what happened– Patient was able to go back to work

History of Present Illness

• One hour PTA, – (+) inward movement and numbness of the

left hand– (+) disorientation and confusion– (+) stiffness of truncal extremity– (+) rapid and incoherent speech

History of Present Illness

• At the ER,– Two episodes of generalized tonic- clonic

seizures similar to the one in January• 30 minutes apart

History of Present Illness

• At the ACSU– throbbing headache located on the top of her

head,(6/10)– (+) generalized weakness– (-) memory of what happened

Review of Systems

• Neurologic: (-) history of gait imbalance, frequent headaches

• General: (-) fever, weight loss, easy fatigability• HEENT: (-) tinnitus, colds, epistaxis, otorrhea• Respiratory: (-) difficulty of breathing, coughing• Cardiovascular: (-) chest pains, orthopnea, PND• Gastrointestinal: (-) change in bowel movements,

abdominal pain, melena, hematochezia

Review of Systems

• Genitourinary: (-) dysuria, frequency, incontinence, tea colored urine

• Endocrine: (-) heat or cold intolerance, excess thirst, excess sweat, polydipsia, polyuria

• Musculoskeletal: (-) joint pain and swelling • Dermatologic: (+) dermatoses/ trophic skin

changes

Past Medical History

• Illnesses– Angina 2007 maintained on ISMN (Imdur) 60 mg tab

OD– Hypertension maintained on Bisoprolol 10 mg OD and

Perindopril 8 mg OD– DM Type II 2000 maintained on Insulin glargine

(Lantus) 40 mg SQ OD– Hypercholesterolemia 2000 maintained on Atorvastatin

20 mg/ tab OD• (-) Trauma• (-) History of febrile seizures

Past Medical History

• Surgeries: None• Hospitalization: January 2010• Allergies: No known allergies

Past Medical History

• Ob- gyne– G3P3(3003) – LMP 55 years old– (+) OCP use for 6 months; 1981 (36 yo)– (-) hormone replacement therapy– (+) preeclampsia: third pregnancy– (+) blood transfusion: third pregnancy

Medications

• Compliant with:

1) Aspirin 75 mg OD

2)Dipyridamole 200 mg/ tab OD

Family Medical History

• Diabetes• Hypertension• Breast Cancer• Stroke• Cardiovascular disease

Personal and Social History

• Married with three children • Occupation: nurse• Occasional drinker• Non- smoker

Physical Examination

Physical Examination

• Awake, not in cardiorespiratory distress• Height: 165 cm• Weight: 80 kg• BMI = 34• BP = 160/70• HR = 73• RR = 14• T = 36.5OC

Physical Examination

• HEENT– Anicteric sclerae; pink palpebral conjunctiva– No nasal congestion– Moist buccal mucosa– (-) cervical lymphadenopathy, tonsillopharyngeal congestion,

enlarged thyroid gland– non- distended neck veins, (-) carotid bruit

• Respiratory– Symmetric chest expansion– No retractions– Clear breath sounds

Physical Examination• Cardiovascular

– Adynamic precordium– Apex beat at 5th ICS LMCL– Regular rhythm, normal rate– Distinct S1 at apex and S2 at base– (-) Murmurs

• Abdominal– Flabby, soft abdomen– Normoactive bowel sounds– No tenderness– No organomegaly

Physical Examination

• Extremities– Full and equal pulses (2+)– (-) edema– Good skin turgor

• Skin– Normal hair and scalp, nails– Trophic skin changes/ dermatoses– No pallor or jaundice

Physical Examination• Neuro examination at the ER:

– Awake, confused and disoriented, able to follow some verbal commands; GCS 14

– Intact cranial nerves– Intact sensory– Motor

• Minimal spasticity on the left. • Left arm can lift 30˚.

– Supple neck– (+) Babinski reflex, L

Neurologic Examination• GCS 15 • Mental Status Exam:

– Cooperative towards examiner– Awake, alert with intact attention span– Euthymic with appropriate affect– Non- spontaneous, normoproductive speech– No perceptual disturbances– Goal oriented with normal thought content– Oriented to time, place and person– Intact memory and calculation– Good fund of information– Good insight and judgment– (-) agnosia, apraxia

Neurologic Examination– Cranial Nerves

• I – Not done• II – Pupils 3mm, equally reactive to light; visual fields full to

confrontation• III, IV, VI – Full EOM’s• V – Corneal reflex not done, sensory- intact bilaterally in all

three divisions for sharp, dull, touch stimuli; motor- temporal and masseter strength intact

• VII – No facial weakness and asymmetry• VIII – Gross hearing intact• IX, X – (+) gag reflex• XI- (+) shoulder shrug, head turn, 5/5• XII – tongue at midline

Physical Examination• Neurologic

– Motoro (-) muscle, involuntary movementso 5/5 on all extremities except for left upper extremity (4/5)o Drift on the upper left extremityo DTRs: ++ on bilateral brachioradialis, biceps, triceps, patellar and

ankle; (-) Babinski– Somatic

o 100% touch/pain on all extremities. Temperature sensation intact bilaterally and symmetrically. Position sense intact bilaterally and symmetrically intact except for left upper extremity

– Cerebellaro No dysmetria, dysdiadochokinesia (RAMs, finger to nose, heel

along shin intact bilaterally)– Supple neck, (-) Brudzinski, Kernig's

Initial Impression

• Epileptic seizure

• R/o space- occupying lesion vs. CVD

• Hypertension Stage II

• Diabetes Mellitus Type 2

Differential Diagnoses

Syncope

Rule In Rule OutLoss of consciousness

-LOC and GTC movements <15-30 seconds- Loss of postural tone-Rare tongue biting and headache

Transient Ischemic Attack

Rule In Rule Out-Focal neurologic deficit-altered consciousness -Presence of risk factors

- Generalized seizures

Neoplastic

Rule In Rule Out

-Family history of cancer-Focal neurologic deficit

-Slowly decreasing level of consciousness-No weight loss, nausea, vomiting, irritability

Infection

Rule In Rule Out

Seizures -No fever, nausea, vomiting, irritability-Supple neck, (-) Kernig's and Brudzinski

Stroke

Rule In Rule Out

-Headache, confusion, lapse of consciousness-(+) hypertension, diabetes mellitus-(+) Risk factors of hypertension, diabetes mellitus

Hypoglycemia

Rule In Rule Out- seizure-Confusion-Headache-History of insulin use

- Diaphoresis- Pallor- Dizziness- Blurred or double vision

Subarachnoid Hemorrhage

Rule In Rule Out- focal neurologic deficit- altered level of conciousness/confusional state

-Severe headache at onset, may be with neck stiffness and vomiting-Generalized seizures

Initial Imaging Studies

• Head CT– Wedge shaped I'll defined hypodense focus is

seen in the cortical subcortical region of the right parietal lobe.

– Underlying gyrus and sulci are effaced. – Patchy hypodensities along the periventricular

white matter of both frontal and parietal lobes are also noted.

– The rest of the grey-white matter interface is maintained.

Initial Diagnostics

• CT– Malacic changes

• CBC– Hgb 138– Hct .42– WBC 8.5

• N .72• L .24• M .04

– PC 137

• PT 12.2• INR 0.89• ALT 27.04• BUN 4.48• Creatinine 99.01• Na 137• K 3.9• Lipid Profile (results to follow)

Initial Management

• Phenytoin– Loading dose 1gm– Maintained at 100 mg/cap TID

• Admit to ACSU– Cardiac, CBG monitoring– O2 Support, seizure precautions

• Diazepam 5 mg IV• Ketorolac 30 mg IV then q8 prn for headache• Continue maintenance medications

Day 1 -3 (Nov 7-9)

S O A PNo recurrence of seizureSome difficulty sleeping

GCS 15Stable vitalsClear breath sounds NRRR, distinct S1/S2Soft abdomen

CBG=256 mg/dL

Post-stroke seizureHypertensionDM 2

Dx:MRI, MRA, MRV (Nov 8 )Tx:Citicoline Insulin glulisine

Possible discharge Nov. 11

Imaging Results

• Cranial MRI– Wedge-shaped Right inferior parietal cortical-

subcortical encephalomalacia, gliosis and siderosis, presumably sequelae of a previous water-shed type infarction with hemorrhagic conversion

– Mild microvascular white matter ischemic changes on the left centrum semiovale

– Mild central cerebral volume loss

Imaging Results

• MRA: No aneurysm or any significant stenosis or vascular malformations seen

• MRV: No evident cortical vein or dural sinus thrombosis

Day 4 (Nov 10)

S O A P

Asymptomatic: (-) palpitations, chest pain, dizziness

Atrial Fibrillation in RVR recorded for 3 hours (3:40 am)

Paroxysmal AF Dx: 12L ECGTx: BisoprololCardio referral

Cardio: BP 116 / 77HR 52Sinus bradycardiaGood S1, NRRR (-) carotid bruit

Paroxysmal AF, now back in sinusHypertension, stage 2

Dx: 2D ECHO TFTsTx: Amlodipine, Enoxaparin,Clonidine,ISMN

Neuro:No recurrence of seizures

MRI/MRA/MRVCholesterol 3.75 (3.4 – 5.2)HDL 2.33 (high)LDL 1.39Triglycerides 0.93vLDL 0.42

Post Gliotic SeizureCVD infarct, Right MCA

Tx: Levetiracetam, Sitagliptin

Diagnostics

• ECG: Atrial Fibrillation, RVR• TFT:

– TSH 3.01 uIU/mL– FT3 2 pg/mL– FT4 0.83 ng/dL

• EEG: abnormal EEG due to a focal theta slowing on the right temporo-parietal occipital region with wave epileptiform discharges on the right temporo-occipital region consistent with a focal cerebral dysfunction and a tendency toward localization-related seizures at the right temporo-occipital region

Day 5-7 (Nov 11-13)

S O A P

Neuro/Cardio:AsymptomaticComfortableNo recurrence of AF, seizures

GCS 15Stable vitalsClear breath sounds NRRR, distinct S1/S2Soft abdomen

Post-Gliotic SeizureParoxysmal AFHypertensionDM 2

Tx: d/c Amlodipine, Enoxaparinstart Diltiazem, Dabigatran

Cardio: MGH (11/12); follow up OPD

Neuro: MGH (11/13); follow up OPD

Take Home Medications

Generic Name Brand Name Dose Administration Indication

Dipyridamole Persantine 200 mg / tab BIDAntiplatelet. Thromboxane and Phosphodiesterase inhibitor

ASA 80 mg / tab OD Antiplatelet. COX inhibitorDabigatran Pradaxa 110 mg / tab BID Anticoagulant. Direct thrombin II inhibitor

Perindopril Conversyl 8 mg / tab OD Long-acting ACE inhibitorISMD Imdur 60 mg / tab OD Nitro-vasodilatorBisoprolol Concore 10 mg / tab OD Selective Beta1 Blocker

Insulin Glargine Lantus 42 Units OD, SQ Antidiabetic. Long-acting insulin analogue

Sitagliptin Januvia 50 mgOD,

pre-breakfast Antidiabetic. Secretagogue, DPP-4 inhibitor

Diltiazem Dilzem 30 mg / tab TID Antiarrhythmic. Calcium Channel blockerAtorvastatin Lipitor 20 mg / tab OD Statin. HMG-CoA reductase, LDLCo-Amoxiclav Amoclav 625 mg / tab TID till 11/19 Antibiotic. Penicillin + Beta-lactamase inhibitorCiticoline Zynapse 1 g /tab BID Nootropic. Psychostimulant

Levetiracetam Keppra 500 mg / tab BID AnticonvulsantPhenytoin Dilantin 100 mg / cap TID Anticonvulsant, Antiarrhythmic. Sodium channel blocker.

Case Discussion

Pathophysiology Video

Epileptogenesis

• Transformation of a normal neuronal network into one that is chronically hyperexcitable

• Trauma, stroke, or infection• Injury lowers the seizure threshold in the

affected region

• CVD is the number one cause of epilepsy in the elderly• Oxfordshire Stroke Community Project (OSCP)

– 11.5% of patients with stroke are at risk of developing late-onset post-stroke seizures within 5 years

• Naess and colleagues– 10.5% developed post-stroke seizure over mean follow up

of 5.7 years.• Hart and colleagues

– recurrence after a first seizure after stroke of 40% in 12 months

Early Onset Seizure• occurs w/in first two

weeks• peak 24 hrs after stroke

Late Onset Seizure• occurs after two weeks of

stroke onset• peak 6-12 months after

stroke

• associated with the persistent changes in neuronal excitability and gliotic scarring

• Cortical location – Best-characterized risk

factor for early seizures after ischemic stroke

– Significant risk factor in the SASS study (HR, 2.09; 95% CI, 1.19 to 3.68; P<0. 01)

• Stroke severity – Independently associated

with the development of seizures after ischemic stroke (HR, 10; 95% CI, 1.16 to 3.82; P<0.02)

Seizures and Epilepsy After Ischemic StrokeOsvaldo Camilo and Larry B. Goldstein, 2004

Management

• Antiepileptic Drug Therapy– Goal: completely prevent seizures without

causing untoward side effects

• Treat the underlying conditions– Reverse the problem and prevent its

recurrence

What is the drug of choice for adults with generalized-onset tonic–clonic

seizures?Patient’s Medications Upon Admission

• Phenytoin (Dilantin) 100mg/cap TID

ILAE Treatment Guidelines:

• Effectiveness-outcome evidence– Based on RCT efficacy and

effectiveness evidence, CBZ, LTG, OXC, PB, PHT, TPM, and VPA are possibly efficacious/effective as initial monotherapy for adults with GTC seizures and may be considered for initial therapy in selected situations (level C) (Glauser, et al. 2006)

Glauser, Tracy, Elinor Ben-Menachem, Blaise Bourgeois, and et. al. "ILAE Treatment Guidelines: Evidence-based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes." (Internationl League Against Epilepsy) 27, no. 7 (2006): 1094 -1120.

Were these maintenance medications necessary?

• Maintenance since Jan 2010, post stroke– ASA

80mg/tab OD

– Dipyridamole (Persantine) 200mg/tab BID

• International Stroke Trial (IST, Lancet 1997;349:1569-1581)– Aspirin treated patients had slightly fewer deaths at 14 days,

significantly fewer recurrent ischemic strokes at 14 days and no excess of hemorrhagic strokes

• Dipyridamole for Preventing Stroke and Other Vascular Events in Patients With Vascular Disease: An Update 2008– Compared with control, dipyridamole had no clear effect on

vascular death (RR 0.99, 95% CI, 0.87 to 1.12). – Compared with control, dipyridamole appeared to reduce the

risk of vascular events (RR 0.88, 95% CI, 0.81 to 0.95). – Routine use of dipyridamole alone as first line antiplatelet

treatment is not supported. The combination of dipyridamole plus aspirin is associated with a lower risk of further vascular events than aspirin alone.

What maintenance medications does this patient need?

• Home Medications– Citicoline 1gm/tab BID– ASA 80 gm/tab OD– Levetiracetam 500mg

tab BID– Phenytoin 100mg/cap

TID

Public Health Perspective

The Philippine Scenario

• The statistics are grim– Less than half of hypertensive patients are

aware that they have high blood pressure– Only about 1/4th are taking antihypertensive

medications– Only about 10 percent or less have

adequately controlled high blood pressure.• Filipinos trivialize Hypertension

Castillo, Dr. Rafael. Stroke Prevention Campaigns. Philippine Daily Inquirer, 2007.  

Complications After Stroke Deprive Patients of Years of Optimum Health

• Researchers used data on patients enrolled in the Complication in Acute Stroke Study (COMPASS) (n=1254)

• Average DALYs lost due to a stroke was 3.82• The more complications the patient

experienced, the more DALYs lost – 1 complication – 1.52 more DALYs lost– 2 or more complications – 2.69 more DALYs lost

A U.S. National Institutes of Health and the American Heart Association funded study, July 2010

AWARENESS CAMPAIGNS

I-Stroke Campaign http://www.otsuka.com.ph/istroke/