FACULTY OF MEDICINE AND HEALTH SCIENCES

UNIVERSITI SAINS ISLAM MALAYSIA (USIM)

BREAKTHROUGH
SEIZURES
1) Patient’s data
Name: Mrs. Siti Hajar Mahmod
Age: 30-year-old
Gender: lady.
Race: Malay.
Status: Single, unmarried.
Registration no: 022337-05
Date of admission and clerking: 14th September 2009
Source of information: Patient and her sister who live with her.

a) Presenting complaint/illness
Mrs. SHM, presented to emergency department with fits two times a
day prior to admission.

b) History of presenting complaint/illness

She was a known case of breast cancer stage II
since August 2008, diagnosed by excision biopsy of the left periaerolar breast
lump, which was taken during wide local excision on 2 nd September 2009.
Axillary clearance was done on 21st October 2009. Both surgeries were being
performed in Temerloh Hospital
There were no sign and symptoms of distant metastasize at that
particular time.
She was referred to oncology department in Hospital Kuala Lumpur
(HKL) and later completed six cycles of chemotherapy for breast cancer in
HKL, from December 2008 till April 2009; followed by 5 cycles radiotherapy
of breast and lymph nodes in HKL, from May 2009 till June 2009. She
claimed having tiredness, nausea and rashes after each cycle of them, which
lasted for about 4-5 days. She also experienced hair loss.
She was prescribed hormonal treatment, tamoxifen, by doctors in the
surgical department of HKL, during the whole duration, but has stopped
taking it since her first attack of seizures due to doctors’ recommendation. The
first attack of seizure was on July 2009. It was similar to this recent one. She
was being warded in HKL and extensive investigation has been performed to
her, including CT scan of brain. The doctor there diagnosed her for having

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 secondary metastatic brain lesion and was being prescribed with phenytoin
330mg once daily. She later underwent palliative radiotherapy in HKL, on 15th
July 2009. She was a right-handed person.
The recent attack was on 14th September 2009 at 1 am and 5am in the
morning, which last for about 10 minutes and 20 minutes, respectively. Both
occurred during her sleep and resolved spontaneously. She denied any
prodromic event or aura before them. During the attack, she was unconscious
and her sister cited that she was having stiffness of the body, which later
followed by generalized jerking of the body. They were also associated with
up rolling of eyeball, urinary incontinence and drooling of saliva. After the
attack, she experienced post-ictal drowsiness, headache and lethargy, and
vomiting, however, they were no bitten tongue, fever, sore throat, neck
stiffness and feacal incontinence.
The vomiting was projectile, voluminous, and the vomitus was clear
watery fluid. However, there was no haematemesis. It was associated with
nausea and loss of appetite without significant loss of weight.
She also experienced early morning headache, however, there were no
symptoms of focal neurological deficit such as, hemiparesis, dysphasia,
dyslexia, dysgraphia, and dyspraxia.
She also experienced backbones’ pain. However, it was not associated
with any other breast lumps, breathlessness, jaundice and abdominal pain.
She went to Jengka Hospital, due to logistic problem, and was referred
to Temerloh Hospital.

c) Past medical history

No history of childhood seizure, hypertension, diabetes mellitus,

asthma and malignancy.

Multiple history of admission to wards due to:

1) Wide local excision of breast lump in Temerloh Hospital on 2nd September
2008.
2) Stage II Axillary clearance on 21st October 2009.

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 3) Completed chemotherapy for breast cancer in HKL, from December 2008
till April 2009. Admission once in every 3 weeks depending on her health
status.
4) Completed Radiotherapy for breast cancer in HKL, from May 2009 till
June 2009.
5) Admission on July 2009 in HKL due to fits.
6) Palliative radiotherapy for metastatic lesion of the brain in HKL, on 15 th
July 2009

d) Past surgical history

1) Wide local excision of breast lump in Temerloh Hospital on 2 nd September

2008.
2) Stage II Axillary clearance in Temerloh Hospital on 21st October 2009.

No surgical complication for both surgeries.

3) Family history
She is fourth out of ten siblings. She has an elder sister who does not
have history of breast cancer and any other malignancy. No other first-degree
relatives suffering from the same condition and no history of hypertension,
diabetes mellitus, asthma, malignancy and sudden death run in family.

4) Social history
Unmarried. Now, she was unemployed due to health problems.
Previously worked as a teacher and claimed having a stable financial status.
Live with her family in terrace house with western type of toilet. No history of
smoking and consuming alcohol. She rarely performed physical exercise at
home.

5) Drug/medication history
Currently on Phenytoin 330mg OD for her generalized seizures. She
claimed compliance to it.

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 No known drugs allergies, however has seafood allergies. The reaction
includes having rashes all over the body.

6) Menstrual history

Last menstrual period was on 8th September 2009. She has duration of
amenorrhea from April 2009 till August 2009; otherwise her menstrual cycles
were regular about 6 to 7 days per cycle, consuming 2 to 3 pads per day. She
has her first menarche at the age of 12 years old.

6) Dietary history

She claimed having a balanced diet but apparently liked to consumed high-
fats and cholesterol meals. Her previous weight was 60kg, however was
unsure about her most recent weight

Physical Examination
a) General Examination
She was alert and conscious, lying on the bed. Glasgow coma scale
was 15/15. She looked weak, lethargic and mild pallor. She was alopecia.
Pulse was 86 rates per minute, normal volume and regular rhythm. Blood
pressure was 119/67 mmHg, temperature was 37 degree Celsius, O2
saturation was 99.8% on room. Her body mass index (BMI) was
24.5kg/m2.
Hands was cold, no sweating, no clubbing, no stigmata of liver disease,
no peripheral cynosis, capillary refill was less than 2 seconds, no flapping
tremor.
Pallor was present, however no jaundice. No central cynosis, hydration
was poor and oral hygiene was good.
Jugular venous pressure was not raised. Lymphadenopathy and pedal
oedema was absent.

b) Systemic Examination
Central Nervous System:

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 Patient was well oriented with time, place and person. Higher mental
function, both long and short terms memories, were preserved.
There were no cerebellar signs, such as nystagmus, past-pointing, arm
drifting, rebound, intention tremor, and dysdiadochokinesia. Test for gait and
Romberg test cannot be performed due to patient’s condition.
All cranial nerves are grossly intact. Proper examination for some cranial
nerves cannot be done, as patient cannot be seated up.
- Olfactory nerve (I) was intact.
- Facial nerve (II)- both visual field and acuity cannot be examined.
Fundoscopy showed no papilloedema.
- Oculomotor (III), Trochlear (IV) and abducent (VI) nerves were intact. –
Both pupils are reactive to lights.
- Trigeminal nerve (V) was intact.
- Facial nerve (VII) was intact.
- Acoustic nerve (VIII) was intact.
- Glossopharyngeal nerve (IX) and vagus (X) were intact.
- Acessory nerve (XI) was intact.
- Hypoglossal nerve (XII) was intact.

Peripheral Nervous System:

Upper limb:

Right Left
Tone: Normal Normal
Power: Shoulder 5/5 5/5
Elbow 5/5 5/5
Wrist 5/5 5/5
Fingers 5/5 5/5
Reflexes: Brachioradialis Normal Normal
Biceps Normal Normal
Triceps Normal Normal
Coordination No past-pointing, No past-pointing,
dysdiadochokinesia, and dysdiadochokinesia, and

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 rebound. rebound.
Sensation: Pain Intact Intact
Vibration Intact Intact
Proprioception Intact Intact
Light touch Intact Intact

Lower Limb:

Right Left
Tone: Normal Normal
Power: Hip 5/5 5/5
Knee 5/5 5/5
Ankle 5/5 5/5
Tarsal 5/5 5/5
Reflexes: Knee Normal Normal
Ankle Normal Normal
Plantar Normal Normal
Babinski Negative Negative
Coordination Heel-shin test and foot- Heel-shin test and foot-
tapping test were normal, tapping test were normal,
no incoordination. no incoordination.
Sensation: Pain Intact Intact
Vibration Intact Intact
Proprioception Intact Intact
Light touch Intact Intact
Gait Cannot be performed Cannot be performed

Breast:
Inspection: Both breast were symmetrical and equal in size. No skin changes
were noted. Right breast was normal. There was a scar, measuring 4cm at left
periaerolar region of breast, at 7o’clock position, measuring 4cm. No obvious
lumps even when raising hands upwards and when performing the pectoral

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 contraction manouvre. Nipples were symmetry and at the same level. No
nipple retraction or discharge.

Palpation: No palpable lumps on both breasts.

Abdomen: Soft, non-tender, no organomegaly.

Respiratory system: Lungs were clear and equal air entry on both sides.
Cardiovascular system: Dual rhythm, no murmur.
Musculoskeletal system: No spine bone tenderness. No skin nodules.

CASE SUMMARY

This 30-year old unmarried lady with fits which was not preceded by aura.
During the attack, she was unconscious with stiffness of the body, which later
followed by generalized jerking. After it, she experienced post-ictal drowsiness,
headache, lethargy and vomiting. She was a known case of breast cancer stage II, has
done wide local excision, axillary clearance, chemotherapy and radiotherapy.
Examination revealed intact higher function and no cerebellar signs. Both cranial and
peripheral nerves were intact.

My provisional diagnosis is recurrent seizures secondary to metastatic breast

carcinoma.

Differential diagnosis:

- Recurrent seizures secondary to primary carcinoma in the brain.

- Recurrent seizures secondary to hypoglycemic attack.

5) Investigation
Baseline investigation:
- Full blood count
 To check hemoglobin level, red blood cell, white blood cell and platlet level
as metastasize to bone can lead to pancytopenia.

Hb level 12.1 (N= 11.5-16g/dL)

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RBC 4.02 (N=3.9-5.6 X 1012L)
Platlet 206 (N= 150-400 X 109/L)
WBC 4.5 (N= 4-11 X 109/L)
- Neutrophils 2.5 (N= 2-7.5 X 109/L)
- Lymphocytes 1.4 (N= 1.5-4.5 X 109/L)
- Monocytes 0.6 (N= 0.2-0.8 X 109/L)
- Eosinophils 0.0 (N= 0.04-0.4 X 109/L)
- Basophils 0.0 (N= 0-0.1 X 109/L)

Impression: RBC, platlet and WBC were normal but all are at the lower
interval. Possibly, due to side effect of recent palliative radiotherapy leads to
pancytopenia.
- Blood urea serum electrolyte
 To assess the dehydration status, as it can be complicated by acute renal
failure.
 To assess the electrolytes level, as vomiting can lead to electrolytes loss.
Urea 2.2 (N= 2.5-6.7 mmol/L)
Sodium 139 (N= 135-145mmol/L)
Potassium 3.7 (N=3.5-5mmol/L)
Chloride 107 (N= 100-108mmol/L)
Creatinine 56 (N=70-150umol/L)

Impression: A low in creatinine level may indicate progressive weakness and

degeneration of smooth muscles.
- Arterial blood gas (ABG)
As prolonged vomiting can lead to metabolic alkalosis.
PO2 294.9 (N= 75-100mmHg)
PCO2 40.1 (N= 35-45mmHg)
pH 7.35 (N= 7.35-7.45)

Impression: This ABG was taken when the patient experienced status
epilepticus in the wards. Vital signs were being monitored and her oxygen was

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 maintained by nasal prong. This explained the high concentration of oxygen.
However, the pH was normal.

To confirm the diagnosis:

- Random blood glucose, to check whether hypoglycemia is the precipitating
factor for the seizure.

Glucose (Random)= 7.0mmol/L (N=6.5-10mmol/L)

Impression: Normal level. The attack

- Blood calcium level, to check for metastasized to bone.

Calcium 2.3 (N= 2.12-2.65mmol/L)

Magnesium 0.9 (N=1.25-2.5 mEq/L)
Inorganic Phosphate 1.2?

- Chest x-ray, to check whether there is metastasized to lungs.

 Shows no suggestive metastatic lesion in lungs.

- Plain and contrast enhanced cranial CT

 Shows multiple rim enhancing lesion involving both cerebral, cerebellar,
brainstem and 4th ventricle. Lesions ranging from 0.5 cm to 2.0 cm in diameter.
No hyperdence lesion suggesting heamorrhage. No mass. No midline shift and no
hydrocephalus. Grey and white matter differentiation is preserved.

Impression: Metastatic lesion forms sharply demarcated lesion and often is

multiple. This is more suggestive of metastatic lesion in correlation with patient’s
history and physical examination.

*** I would like to suggest:

Urine Full Examination Microscopic Examination and Mid stream urine
culture and sensitivity to rule out the cause of seizures.

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 Liver Function test and ultrasound liver to check for distant metastasize to
liver.
Plain x-ray of skull and spine for metastatic tumor spread.
Magnetic Resonance imaging of the brain, to visualized the anatomy of the
normal and abnormal brain in millimeter detail

6) Management

1) Tablet phenytoin 330mg OD

2) Tablet Dexamathasone 4mg TD
3) Tablet sodium valproate 4 mg TD
4) Tablet carbamazepin, 200mg BD
5) Palliative radiotherapy at HKL
6) Fitting and Glasgow Coma Scale chart
7) Electroencephalography should be performed after a first fits.
6) Plan for CT scan bone at Hospital Kuala Lumpur.
7) To refer oncology department at Hospital Kuala Lumpur.
8) To refer neurosurgical team in HKL.

Management of status epilepticus includes:

1) Supportive measures:
- Put patient at the left lateral position.
- Maintain the airway- insert oral airway, intubate if necessary.
- Check the vital signs and Glasgow Coma Scale.
- Suction (if necessary)
2) Slow IV bolus phase – lorazepam 4mg
3) IV infusion phase of diazepam– 100mg in 500mL of 5% dextrose. – if the
seizure still continue.

7) Discussion
All breast lumps need to undergo triple assessment to rule out
malignancy, which includes 1) history and clinical examination 2) Ultrasound and
mammography 3) Cytology and biopsy.

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 In this patient, the breast lump was at the left periaerolar region at 7
o’clock position, measuring about 5cm X 3cm which was painless, normal in
temperature, mobile, smooth surface, well-defined margin, and hard in consistency.
There was no nipple discharge and no overlying skin changes.
There was nodal involvement at the left axillary region that was
painless, measuring 2cm X 2cm, smooth surface, well-defined margin, firm in
consistency and mobile. However, at this stage there was no known symptom of
distant metastases.
Later she went to do full needle aspiration cytology of her left breast
and the results showed smears with high cellularity made up of some loose
aggregates of atypical ductal cells showing moderate variation in nuclear size
associated with similar atypical nuclei devoid of cytoplasm. The nuclear chromatin
morphology was compromised by poorly fixed smear and that time they do not
biopsied the nodes. Urgent biopsy or excision of lump was needed at that time for
histological diagnosis. Breast conserving surgery was performed in Temerloh
Hospital, as the mass was still unsure to be malignancy in origin.
The results came out to be intraductal carcinoma with grade II, which
shows moderately pleomorphic ductal cells arraged at glands, clusters and sheets;
with positive estrogen and progesterone receptor but negative CERB-2 receptor.
Histopathology of the lymph nodes revealed 7 out of 20 nodes involved by tumor.
The breast cancer was being staged as T 2N1M0, which is stage II. The
prognosis of the cancer is highly depends on the tumor size and nodal involvement.
Nottingham Prognostic Index (NPI) and survival can predict the prognosis.
NPI= (0.2 X size in cm) + lymph node stage (1=no nodes, 2= 1-3 nodes, 3= 4 and
above lymph nodes) + histological grades (score1=grade I, 2 for grade II, 3 for grade
III)
= (0.2 X 5cm) +2 + 2
= 5, moderate II with 75% 10-year survival.
The management for this patients, include, previous wide local
excision and stage II axillary clearance followed by chemotherapy and radiotherapy.
Breast conserving therapy, which will be removing the tumor plus at least 1cm of at
least normal tissue, was found to be as effective as total mastectomy except that it has
higher rates of local recurrence, which can be overcome with radiotherapy.
Apparently in this patient, as the lump was located at periaerolar region, the nipple

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was spared and the superior border of the rim was compromised. Total Mastectomy
remains the best choice for big tumors and central tumors beneath or involving the
nipple.
At this time, there was no sign of distant metastases; but slowly, later in
time patient can develop symptom and sign of distant metastases. This is quite
common in breast cancer cases due to micro invasion that occurred even before the
removal of breast.
In a patient, having an adulthood seizure, extensive investigation needs to be
done to rule out the cause. If epilepsy develops in adult life, the chance of finding an
unsuspected tumour is around 3%. Brain tumors can be either primary or secondary.
Investigation was performed to rule out secondary metastasize to brain.
Generally, histological and radiographical distinction between benign and malignant
lesions may be subtler in the central nervous system than in other organs.
The vast majority of malignant bone tumors are metastases; where two-thirds
arise from carcinoma of breast and prostate. Most of them are osteolytic and will lead
to hypercalcemia and punched-out lesion. Pathological fracture can also occur in this
case.
In the management of this patient, she was initially given phenytoin, which is
effective in almost all types of seizure. As it has lots of adverse effect, it was slowly
changed to valproic acid that is most effective in myoclonic seizures and later to
carbamazepine, which is the first line of drug for tonic-clonic seizure. And several
times in wards, patient having acute attack of seizures, and patient need to be
managed accordingly. Attention needs to be given on biting the side of the tongue and
slow recovery of the normal mental function.
For management of metastatic brain tumors, surgery can be indicated
to reduce the symptoms of alleviated intracranial pressure; otherwise steroids can be
given to reduce the cerebral oedema.

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