disponnect a case of pontine glioma the medical city | department of pediatrics asmph interns –...

DisPONnectA Case of Pontine Glioma

The Medical City | Department of PediatricsASMPH Interns – Group 2

Outline• Patient Information and Data• Approach to Diagnosis• Course in the Wards• Diagnostics• Therapeutics• Prognosis and Complications• Biopsychosocial Aspect: Palliative

Care


Patient History

Identifying InformationPatient Name: SAAge: 8 years oldNationality: FilipinoReligion: Roman CatholicHandedness: RightAdmitted: November 15, 2013Information: EC and RA, patient’s

parentsGood Reliability

Chief Complaint

Inarticulation(Nabubulol at Nagba-babytalk)

Patient History

Review of Systems

Past Medical History• Past Illnesses

– No previous history of cancer, stroke, seizures, eye correction, pneumonia, PTB, cardiac disease, hypertension, diabetes, asthma, kidney or thyroid disease

• Hospitalizations– Previously admitted for Dengue Fever in 2012

• Surgeries– No previous surgical procedures

• Trauma– No history of trauma

• Allergies– No allergies to food or medications

• Medication– No current medication use

• Patient is of Filipino descent from Maybunga, Pasig City

• Bronchial Asthma in the maternal aunt

• No family history of cancer, stroke, seizures, diabetes, hypertension, heart disease, allergies

• Household Members:– Patient– Patient’s Siblings– Patient’s Parents– Patient’s maternal Aunt

Family History

History of Birth and Infancy

Birth History• Born full term via normal

spontaneous delivery to a 37-year old G3P3 (3003)

• Birth Weight: 3.08kg• Good Activity, Good Cry• Attended by: OB-GYN• No perinatal or neonatal

complications

Nutritional History• Not breastfed

– Due to low maternal milk production

• Formula Milk: NAN HA, Gain, Lactum

• Weaned at 6mo of age• Current Diet: meats,

vegetables and fruits• Preferences: sour foods

(e.g. sinigang isda)

24-Hour Food Recall

Regular Days Days Immediately Prior to Illness

Breakfast 1c rice, 1 egg, 1pc hotdog Beginning 6 days prior to illness, patient was only able to consume fluids as solids would cause her to

choke (e.g. ½c clear broth)Lunch 1c rice, ½c chicken adobo

Snack 1 cheese sandwich

Dinner 1c rice, 1 pork chop

Immunization History

Vaccine Complete Incomplete None Unknown

BCG X

DPT/Polio (1-2-3 booster 1-2) X

Hemophilus influenza B (HIB) (1-2-3 booster) X

Hepatitis B (1-2-3) X

MMR (1-2) X

Measles (1) X

Varicella (1) X

Pneumococcal (1-2-3 booster) X

Influenza X

Rotavirus (1-2) X

Hepatitis A (1-2) X

Typhoid X

History of Childhood

Developmental History• Gross Motor

– Able to do backward heel to toe walk

• Fine Motor– Able to draw a complete person– Can write fairly well

• Language– Can add and subtract– Can distinguish between left and

right

• Personal/Social– Can dress self completely

Personal and Social History• Grade 3 Student

– Above average performance (6th honor)

• Favorite Subject: Science and English

• Hobbies: Spend time with friends, singing and dancing

• Has shown interest in the opposite sex, but has no crushes

Environmental History• Residence: 1-story cement structure

– Maybunga, Pasig City• Electricity: Meralco• Water: Manila Water Company, Inc.• Near to major roads, but not near any factory• No exposure to tobacco, toxins or environmental

hazards• Waste: Daily, not segregated

Stakeholder Analysis

Stakeholder Role Stand on the Issue

Intensity of Stand Degree of Influence

Insight

Mother Primary Caregiver Ally HighMother and Father

both regularly check up on the health

status of the patient

HighDecision making

regarding patient’s health concerns is largely decided by

the parents and the maternal aunt

MidMother and Father are worried about , but not fully aware

of the possible severity of the

patient’s condition

Father Primary Breadwinner

Ally

Brothers and Sisters Secondary Breadwinners,Social Support

Ally ModerateHigh Father regularly

checks up on the health status of the

patient

HighDecision making

regarding patient’s health concerns is largely decided by

the parents

MidSiblings are worried about, but not fully

aware of the possible severity of

the patient’s condition

Maternal Aunt Secondary Caregiver, Decision-Maker

Ally High

The aunt was one of the companions of the patient when

she was brought in at the ER

High

At the ER, the mother would often let the aunt decide on what to do with

the patient

Mid

Aunt is worried about, but not fully

aware of the possible severity of

the patient’s condition


Physical Examination

Physical ExaminationAnthropometricsWeight: 34.5kg

Z-score (0,2)

Height: 138cm Z-score (0,2)

BMI: 18.11kg/m2 Vital SignsBP: 118/76mmHgHR: 82bpmRR: 20cpmTemperature: 36.5CPain: 0/10

General SurveyAwake, AlertNot in CardioRespiratory

DistressGCS 15

• Eyes:– Anicteric sclerae, pink palpebral conjunctivae, no

cataracts or discharge• Skin: – Fair color, no rashes, good skin turgor, hair evenly

distributed, nails with no clubbing• Ears:– No visible mass or lesion, no discharge, no auricular

tenderness, patent canal, intact tympanic membrane with cone of light


• Nose– No deformities, no nasal discharge, no nasal

congestion• Throat– Lips moist and pink, no cleft lip or palate, no

tonsillopharyngeal congestion• Neck– Flat neck veins, no cervical lymphadenopathy


• Chest/Lungs– Symmetric chest expansion, no retractions, clear

breath sounds, no rales, no wheezes• Cardiovascular– Adynamic precordium, normal rate, regular rhythm,

good S1/S2, no murmurs, heaves or thrills• Abdomen– Flat, no previous surgical scars, normoactive bowel

sounds, no masses palpated, no organomegaly, no tenderness


• Genitalia– Grossly female genitalia, no discharge

• Extremities– Full and equal pulses, no edema, no cyanosis, CRT

<2 seconds


Cranial NervesI Intact SmellII Visual acuity: intact

Confrontation fields: no visual field cuts

Fundoscopy: (+) RO ReflexDisc: Sharp margins, yellowish, round, cup to disc ratio < 0.5Vessels: AV ratio 2:3. No indentations. No arterial light reflex.Macula: 2.5 disc distance temporal to disc. No vessels noted around the macula.

II and III Pupils equally reactive to light and accomodation

III, IV, and VI Intact EOM movement along all cardinal positions of gaze

Neurologic Examination

Cranial NervesV Touch/ pin-prick intact along V1, V2, and V3

Intact Masseter and Temporalis toneVII Forehead Crease: No asymmetry

Palpebral fissures, lid closure: No asymmetryShallow nasolabial fold, right

VIII Intact gross hearing

IX and X Midline uvula, (-) gag reflex

XI Shrugs shoulder, can turn head from side to side against resistance

XII No tongue deviation


Extremity Strength Sensation

Right Upper Extremity

5/5 100%

Left Upper Extremity

4/5 100%

Right Lower Extremity

5/5 100%

Left Lower Extremity

4/5 100%


++ ++

++++

++ ++

++ ++


No Flaccidity or RigidityNo Atrophy or Hypertrophy

• Cerebellar– Dragging gait on the left– Dysdiadochokinesia: Left– Dysmetria: Left

• Babinski: Bilateral• Meningeal signs– Negative Kernig’s and Brudzinski’s sign– No neck rigidity


SUBJECTIVE• 8-year old female• No history of neurologic

disease• 3 week history of right-

sided facial weakness• 6 day history of drooling,

dysphagia and slurred speech

• Left-sided weakness• Unstable gait

OBJECTIVE• Stable VS, GCS 15• Shallow nasolabial fold, right• Dysarthria• Absent gag reflex• Left-sided motor weakness

(4/5)• (+) Dysdiadochokinesia,

dysmetria, left • (+) Dragging gait• (+) Babinski, bilateral

Salient Features


Approach to Diagnosis

Neurologic Diagnosis

What is the Lesion?

Stroke in the Young

• Abnormal shunting of blood expansion of vessels and a space-occupying effect or rupture of a vein and intracerebral bleeding

•May remain asymptomatic throughout life but can rupture and bleed any time

•History of ipsilateral seizures and migraine-like headaches

• Ruptured AV malformation: severe headache, vomiting, nuchal rigidity, progressive hemiparesis, and seizure

What is the Lesion?

Arteriovenous Malformation

Aneurysm•Usually asymptomatic

• Located at the carotid bifurcation or on the anterior and posterior cerebral arteries rather than the circle of Willis.

• Results from a congenital weakness of the vessel

• Ruptured aneurysms: intense headache, nuchal rigidity, coma, intracerebral hemorrhage and progressive hemiparesis

What is the Lesion?

• Acute infection of the central nervous system (CNS)

•May present acutely, subacutely and chronically (>1week)

•Often preceded by fever, respiratory or gastrointestinal symptoms, followed by nonspecific signs of CNS infection such as increasing lethargy and irritability

• Systemic infection + meningeal symptoms, seizures and altered mental status

What is the Lesion?

Meningitis

•Most common in children 4 -8 years old

• Causes: emboli, meningitis, chronic otitis media and mastoiditis, sinusitis, soft tissue infection of the face or scalp, orbital cellulitis, dental infections, penetrating head injuries, immunodeficiency states, and infection of ventriculoperitoneal shunts

• 80% of abscesses are found in the frontal, parietal and temporal lobes

• Clinical presentation: low grade fever, headache and lethargy vomiting, severe headache, seizures, papilledema, focal neurologic signs (hemiparesis), coma• Cerebellar abscess: nystagmus, ipsilateral ataxia and

dysmetria, vomiting, and headache

What is the Lesion?

Brain Lesion

•2nd most frequent malignancy in childhood •Higher incidence in children >7 years •Progressive Symptoms•Brainstem tumor effects: motor weakness, cranial

nerve deficits, cerebellar deficits, and/or signs of increased intracranial pressure

•Uncommon• Primary neoplasia: ALL, lymphoma, neuroblastoma,

rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and clear cell sarcoma of the kidney

What is the Lesion?

Primary CNS Lesion

Metastatic Lesion

Is There a Lesion?• Yes!

Baby Talk and Slurring of Speech Dysarthria• Dysarthria: disorders in articulating speech sounds

– Vs. Dysphonia– Vs. Dysprosody– Vs. Dysphasia

• Motor paralysis of organs of articulation

Dysarthria: http://trialx.com/curetalk/wp-content/blogs.dir/7/files/2011/05/diseases/Dysarthria-1.jpg

Dysarthria

Cause of Dysarthria

• Drooling + Dysphagia– Swallowing Problem

• Absent Gag Reflex

CRANIAL NERVE IX and X Palsy

Dysarthria

• Possible Location of Lesion:– Left Corticobulbar Tract– Above the Facial Nucleus

(located at the Pons)

Central Facial Nerve Palsy, Right

• Corticospinal Tract– Cerebral Cortex– Mesencephalon– Pons– Medulla– Spinal Cord

• Contralateral lesion above decussation

Left-Sided Weakness

• Unsteady gait• Dysmetria, Left• Dysdiadochokinesia, Left

• Possible Locations:– Cerebrum– Cerebellum– Midbrain– Pons– Midbrain

http://www.asn.org/neurographics/3/2/1/2.shtml

Cerebellar Signs

• CN involvement– Above Nucleus: Contralateral– At Nucleus and Below:

Ipsilateral Manifestations • Corticospinal Tract

– Contralateral weakness

Cranial Nerves and the Brainstem

• Cranial Nerve Nuclei– Abducens nerve (CN VI)– Trigeminal nerve (CN V)– Cochlear and the lateral and

superior vestibular (CN VIII)– The superior and inferior

salivatory nuclei and the lacrimal nucleus (cranial nerves VII and IX)

• Fiber Tracts – Corticospinal, corticobulbar, and

corticopontine, spinocerebellar, spinothalamic, lateral tectospinal, rubrospinal, and corticopontocerebellar tracts

Pontine Lesions

Brainstem Lesion, Possibly Pontine

Localization


Course in the Wards: Diagnostic

• Patient was admitted in her 3rd week of illness• S/O > Weakness of the left upper extremity (4/5), slurring of speech,

drooling and shallow nasolabial fold, right• A> Vascular Insults probably right MCA, space-occupying lesions vs. Stroke

in the Young• P> Referral to Pediatric Neurology; Neurovital signs to be monitored every

4 hours with strict aspiration precaution

Diagnostics Laboratories: CBC with PC, serum electrolytes (Na,

K, Cl, iCa), creatinine, ESR, PT and aPTTImaging: Cranial MRI plain and with IV contrast

Course in the Wards: Diagnostic


Patient’s Diagnostics

DIAGNOSTIC RATIONALE FOR USE IN OUR PATIENT

Laboratory

Complete Blood Count

To check for infection, or provide clues for possible causes of stroke in the young (polycythemia, thrombocytosis or thrombocytopenia)

Estimated Sedimentation Rate

To check for signs of inflammation

Serum Electrolytes To rule out electrolyte imbalances which can present with weakness or mimic stroke in the young

Creatinine To establish baseline before undergoing cranial MRI with contrast

Imaging

Cranial MRI To evaluate cranial anatomy and identify signs of infection, swelling or mass lesions

Diagnostics: Rationale

• Erythrocyte Sedimentation Rate – Rate at which RBC sediment in a period of 1 hour– Non-specific test used to detect conditions associated with acute and

chronic inflammation (infection, cancers, autoimmune diseases)– A young stroke patient will often have signs of inflammation in the

blood

Adams et al., 2003; European Stroke Initiative Executive Committee and the EUSI writing committee, 2003


• Coagulation Tests (PT, aPTT)– Measure how quickly the blood clots– Abnormal results may either point to excessive bleeding or excessive

clotting which present as risk factors to stroke (ischemic or hemorrhagic)


Adams et al., 2003; European Stroke Initiative Executive Committee and the EUSI writing committee, 2003

Diagnostics: CBCNovember 15, 2013

Result Reference RangeHemoglobin 134g/L 115-155

Hematocrit 0.41 0.35-0.45

Red Blood Cell 5.06 x 10^12/L 4.00-5.20

White Blood Cell 11.30 x 10^9/L 4.50-10.00

Mean Corpuscular Hgb 26pg 25-33

Mean Corpuscular Hgb Conc. 0.32 0.31-0.37

Mean Cell Volume 83fl 77-95

RDW 12.5 11.5-16.0

Thrombocyte (Platelet) 238 x 10^9/L 140-440

Differential Count

Neutrophil 0.82 0.56-0.66

Lymphocyte 0.14 0.22-0.40

Monocyte 0.04 0.04-0.06

Eosinophil 0.00 0.01-0.04

Basophil 0.00 0.00-0.01

Erythrocyte Morphology Normocytic, Normochromic

Diagnostics: Clotting Factors, ESR | November 15, 2013

Result Reference RangeProthrombin Time

Control 13.0 seconds

Patient 12.2 seconds 12.0-14.0

Percent (%) Activity 1.15 0.70-1.30

INR 0.92

Activated Partial Thromboplastin Time

Control 30.8 seconds

Patient 27.5 seconds 28.0-37.0

Result Reference RangeESR 10mm/hr 6-20

Diagnostics: Blood ChemistryNovember 15, 2013

Result Reference RangeCreatinine (Blood) 0.80mg/dL 0.41-0.58

Ionized Calcium 4.72mg/dL 4.48-5.26

Sodium 135.00mmol/L 136.00-145.00

Potassium 3.00mmol/L 3.50-5.10

Chloride 105.00mmol/L 98.00-107.00

Biopsy is seldom performed outside specialized biomedical research protocols for DIPG, unless the

diagnosis of this tumor is in doubt. Biopsy may be indicated for

brain stem tumors that are focal or atypical, especially when

the tumor is progressive or when surgical excision may be possible.

Childhood Brain Tumor Foundation April 2010

If imaging findings are typical, biopsy is not usually

necessary to confirm the diagnosis and should only be performed in the context of a

formal clinical trial Diffuse Pontine Glioma, UpToDate

Nov 2013

Literature: Biopsy on Brain Glioma

Literature: Biopsy on Brain Glioma

Biopsy in children with MR findings of a diffuse intrinsic tumor is controversial and is

not recommended unless there is suspicion of another diagnosis, such as infection, demyelination, vascular malformation,

multiple sclerosis, or metastatic tumors.

Nelson’s Textbook of Pediatrics 19th Ed.

Stereotactic biopsy done for clarifying a diagnostic imaging

in brainstem tumors is important in obtaining a

definitive diagnosis with a low rate of complications.

Perez, et al. “Stereotactic biopsy for brainstem tumors in pediatric patients”,

Jan 2010

• MRI is the neuroimaging standard for primary brain tumors– Both diagnostic and prognostic– Help distinguishes between diffusely infiltrating and focal nodular

tumors

Ropper and Brown. 2005. Adam and Victor’s Principles of Neurology. 8th ed. New York: McGraw-Hill

Literature: Radiologic Imaging

• Diffuse Type– More common– Mass effect with hypointense signal

on T1 and heterogenously increased signal on T2

– Asymmetric enlargement of the pons

Ropper and Brown. 2005. Adam and Victor’s Principles of Neurology. 8th ed. New York: McGraw-Hill

Literature: Magnetic Resonance Imaging

• Tumors in the pituitary/suprasellar region, optic path, and infratentorium – Better delineation with MRI than with CT

• Tumors of the midline and the pituitary/suprasellar/optic chiasmal region – Evaluation for neuroendocrine dysfunction

• Tumors affecting the optic path– Formal ophthalmologic examination: oculomotor function, visual

acuity, fields of vision

Kumar et. al. Nelson’s Textbook of Pediatrics, 19th Ed. New York: McGraw-Hill

Adjunctive Diagnostics


• Suprasellar and pineal regions– Preferential sites for germ cell tumors– Serum and CSF B-HCG and AFP

• Tumors that spread to the leptomeninges– Medulloblastoma/PNET, ependymoma, and germ

cell tumors– Lumbar puncture and cytologic analysis of the CSF

Kumar et. al. Nelson’s Textbook of Pediatrics, 19th Ed. New York: McGraw-Hill


• Impression:– Brainstem mass lesion with

surrounding vasogenic edema. Consider a glioma.

– No evidence of hydrocephalus or herniation noted at this time.

Patient’s MRI


Brainstem GliomaEpidemiology, Etiology, Classification and

Pathogenesis

• Brainstem Gliomas– 10-20% of all CNS tumors in children– More common in children than adults

• Diffuse Intrinsic Pontine Glioma (DIPG)– Leading cause of brain tumor–related death in

children– 15% of all childhood brain tumors– 58-75% of all brainstem tumors

Khatua, et al. 2011. Diffuse intrinsic pontine glioma – current status and future strategies. Child Nervous System Journal. 27: 1391-97. Springer-Verlag.

Jallo, G. 2005. Brainstem gliomas. Child Nervous System Journal. 22: 1-2. November 2005.

Epidemiology

Khatua, et al. 2011. Diffuse intrinsic pontine glioma – current status and future strategies. Child Nervous System Journal. 27: 1391-97. Springer-Verlag.

Jallo, G. 2005. Brainstem gliomas. Child Nervous System Journal. 22: 1-2. November 2005.

Epidemiology

• Mean age at diagnosis is at 7 to 9 years• Males and females equally affected• USA: 200-300 children per year with this

diagnosis of which 60-75% are DIPG• Incidence is greater in whites (18.52 per

100,000 person-years) than in blacks• Philippines and India – low incidence

countries

Brainstem Anatomy

• Localization• Diffuse

– Diffuse Intrinsic

Pontine

• Non-Diffuse– Focal (e.g. Tectal)– Cervicomedullary– Dorsal Exophytic

Classification

WHO GRADING SYSTEM FOR ASTROCYTOMA

Grade Name Histologic Features

I Pilocytic Astrocytoma

No pleiomorphic cells, low proliferative potential

II Low-Grade Astrocytoma

Low cellularity, minimal atypia

III Anaplastic Astrocytoma

Anaplasia, Mitotic activity

IV GBM Microvascular proliferation

• Pontine tegmentum• Cranial nerves V, VI, VII VIII

Pons

• 80% of gliomas• Acute onset, high-grade• Rapid deterioration in 1-2 months• TRIAD:

– Multiple cranial nerve deficits (CN VI, CN VII most common)

– Long tract signs– Ataxia

• Late stage: invasion of adjacent levels of brainstem and cerebellar peduncles

Diffuse Intrinsic Pontine Gliomas

Midbrain

• 5% of Gliomas• Can be located anywhere in brainstem• Most common: tectum of midbrain• Well-defined margins• Indolent course

Tectal gliomas: OBSTRUCTIVE hydrocephalus

Focal Gliomas

• 10-15% of gliomas

• Arise from subependymal glial tissue in floor of 4th ventricle

• Over 90%: Pilocytic Astrocytomas

• Grow along path of least resistance (4th ventricle)

• Long history of nonspecific headache and vomiting

• Long tract signs usually not present

Dorsal Exophytic Gliomas

Cervicomedullary Lesions

• CN IX, X, XI, XII

Medulla

• 5-10% of brainstem gliomas

• Arise from the lower medulla or the upper cervical spinal cord

• Slow-growing, low-grade

• Medulla: dysphagia, sleep apnea, dysarthria, recurrent URTI

• Cervical cord: chronic neck pain, spasticity, weakness

• Hydrocephalus: unusual in cervicomedullary gliomas.

Cervicomedullary Gliomas

• Platelet-derived growth factor (PDGF) and its receptor (PDGFR): major driving forces of tumorigenesis

• Gain Poly (ADP-ribose) polymerase (PARP-1)

• Epidermal growth factor receptor (EGFR)– Expression indicates high grade tumor

• p53 mutations

Molecular Genetics of Brainstem Gliomas

• Varied symptoms depending on the location of the lesion

• Usually present with a short duration of symptoms (<3 months)

• Common: abnormal or limited eye movements, diplopia, asymmetric smile, clumsiness, difficulty walking, loss of balance, weakness

Clinical Presentation

• Classical Triad1. Multiple cranial neuropathies (77%)2. Long tract signs (53%)3. Cerebellar signs (87%)

• Cranial nerve palsies, long tract signs (e.g. hemiparesis) and ataxia– Over 50% of patients

• Hydrocephalus with elevated ICP – Less than 10% of patients

• Intratumoral hemorrhage– 6% of patients

Donaldson, et al. 2008. Advances toward an understanding of brainstem gliomas. Journal of Clinical Oncology. 24 (8): 1266-72. American Society of Clinical Oncology.

Clinical Presentation


Course in the Wards: Therapeutics

• Subjective/Objective– Afebrile and with stable vital signs – Awake and comfortable with no symptoms of headache,

vomiting, dizziness – Still presented with a shallow nasolabial fold, right and left-

sided extremity weakness (4/5) with no deterioration• Assessment

– Supratentorial Mass, r/o Malignancy• Plan

– Monitored every 4 hours and maintained on strict aspiration precautions

Hospital Day 01

• Subjective/ Objective– Afebrile with stable vital signs – Awake and comfortable– Previously mentioned symptoms of right shallow nasolabial fold and

extremity weakness were noted to have progressed, from a 4/5 to 1/5; intact extraocular muscles, (-) gag reflex

– MRI results revealed brainstem mass lesion, possibly glioma• Assessment

– t/c Brainstem Glioma• Plan

– Referral to Oncology service– IVF D5NL (based on maintenance)– Dexamethasone 40mg/IV every eight hours– Additional monitoring through pulse oximetry– Stand-by intubation was ordered and a request for a family conference

was initiated

Hospital Day 02: AM

• Subjective/Objective– Patient had throbbing frontal headache, spontaneously

resolving, with 2 episodes of vomiting, non-bilious, non-projectile

– Patient was noted to have 94% oxygen saturation at room air• Assessment

– t/c Brainstem Glioma• Plan

– Oxygen support via nasal cannula at 2lpm– Mannitol 20% (50ml) was started every 8 hours and monitoring

was changed to every 2 hours – Neurosurgery was called upon for further evaluation but was

eventually deferred

Hospital Day 02: PM

• Subjective/Objective– Improvement in the severity of the headache, no

recurrence of vomiting– Afebrile with stable vital signs – No progression of neurologic symptoms

• Assessment– Diffuse Pontine Glioma

• Plan – Family Conference

Hospital Day 03

• Attendees: Attending Physician, Pediatric Oncologist, Pediatric Resident, Patient’s Parents, Sister and two Aunts

• Diagnosis and prognosis were disclosed to the family members and pertinent points discussed included the different options for the patient including surgery, radiation, chemotherapy and palliative care.

• After discussion, patient’s family arrived at a consensus and opted to give the patient a good quality of life and asked for a referral to palliative care and subsequent home care.

Family Conference

• Subjective/Objective– Patient more comfortable – Able to tolerate feedings of soft, pureed foods with no

difficulty in breathing – Still with left-sided extremity weakness, without progression

• Assessment– Pontine Glioma

• Plan– Further discussion and action with palliative care– Patient was deemed fit for discharge

Hospital Day 04


Therapeutic Options

Surgical Resection

CONCLUSION:Surgery is advocated for patients with well delineated, posteriorly, posterolaterally and ventrolaterally located tumors having slow progression and relative preservation of motor power

FINDINGS:• 43 patients with a defined clinico-radiological diagnosis of DIPG

treated with radiotherapy + Temozolomide (75mg/m2), after which up to 12 courses of 21 days of adjuvant Temozolomide (75-100mg/m2) were given 4x weekly

Chemotherapy

FINDINGS:• Overall survival: 56% • Median survival: 9.5months• 2 year survivors: 5 (median age of 13.6years at diagnosis)• No survival benefit of the addition of dose dense temozolomide, to

standard radiotherapy in children with classical DIPG. • Further exploration: Prolonged survival in adolescents

Chemotherapy

FINDINGS: • Time to tumor progression and survival times are longer than

those previously reported in other DPG series• Arguments for therapeutic benefits:

– Stable disease– Partial responses in DPG on MR imaging – Enhanced delivery of chemotherapy afforded by osmotic

BBBD supports the further examination of this treatment modality for patients with DPG.

Chemotherapy

FINDINGS:• VAE can be used as a novel virus-gene therapy strategy

for glioma since it significantly inhabits GSC activity– Expression of exogenous Endo-Angio fusion gene can inhibit

HBMEC proliferation.

Immunology

FINDINGS:• Amplification of the D-type cyclins and CDK4/6• Loss of Ink4a-ARF leading to aberrant cell proliferation• Targeting: cyclin-CDK-Retinoblastoma pathway in a genetically

engineered PDGF-B-driven brainstem glioma mouse model

Immunology

FINDINGS:• 7-day treatment course with PD significantly prolonged survival

by 12% in the PDGF-B; Ink4a-ARF deficient BSG model. • Furthermore, a single dose of 10 Gy radiation therapy followed

by 7 days of treatment with PD increased the survival by 19% in comparison to RT alone.

Immunology

• External Radiation Therapy – Uses a machine outside the body to send radiation toward the cancer

• Internal Radiation Therapy – Uses a radioactive substance sealed in needles, seeds, wires, or

catheters that are placed directly into or near the cancer

Radiation Therapy

• Conformal Radiation Therapy – Creates a 3D picture of the

tumor and customizes radiation beams to fit the tumor, allowing precise and high dose radiation to reach its target

Methods of Radiation

• Hyperfractionated Radiation Therapy – Total dose of radiation is divided into small doses

and given more than once in a day.

Methods of Radiation

CONCLUSION: We conclude that r beta IF plus hyperfractionated therapy can be tolerated by children with newly diagnosed brain stem gliomas, although there is occasional dose-limiting hepatic, blood, and central nervous system toxicity. This therapy did not result in a higher rate of disease control.

Other Treatment Options

CONCLUSION:

The major conclusion from this trial is that the hyperfractionated method of Rx 2 did not improve event-free survival (p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional fractionation regimen of Rx 1, and that both treatments are associated with a poor disease-free and survival outcome.

Other Treatment Options

CONCLUSION:

IFN-beta gene therapy following tumor cell lysate-pulsed dendritic cells immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.

Future Management


Brainstem GliomaComplications, Prognosis, Prevention

Complications

• Survival period is shorter in children who presented with cranial nerve palsies (more likely to have malignant tumors)

• Children with histologically malignant tumors had poorer outcomes– Best Survival Time: presence of Rosenthal fibers and

calcification– Poor Survival Time: presence of mitoses

• Decreased survival associated with two CT-Scan features:– Hypodense tumor prior to contrast– Tumor involving the entire brainstem

Prognosis

Albright et al. Prognostic factors in pediatric brainstem gliomas. Journal of Neurosurgery. 1986. 65 (5): 751-755

• Median Survival Duration: 9-12 months even with treatment

Prognosis

Time Survival Rate

1 Year 37%

2 Year 20%

3 Year 13%


Brainstem GliomaBiopsychosocial Impact: Palliative Care

• Single parents or two parent families functioning at a single parent family

• Preexisting chronic health or mental health problems• Economic problems: rural or urban poor: overextended middle-

class families (debts): Job loss and minimal or no health insurance

• Seperation, divorce• Chronic Unresolved Conflicts• Language difference: immigrant, foreign national, significantly

different subculture• Families away from their cultural support network because of

the child’s need for medical treatment

Factors that Place Families at High-Risk

• Family’s Reaction to Diagnosis– Shock, disbelief, guilt, anger, and fear– As the diagnosis is accepted, anger and guilt

become significant emotions

Initial Diagnostic Period: A Time of Crisis

• Family’s Reaction to Diagnosis– An important task is to decide about telling the

child about his or her diagnosis

Initial Diagnostic Period: A Time of Crisis

• School-Age Children– Immediate concerns revolve around

hospitalizaton, separation from parents, and fear of medical procedures

– Constant reassurance is needed– Behavioral interventions may be necessary to gain

cooperation

Child’s Reaction to Diagnosis and Treatment

• School-Age Children– May have delayed or immediate reactions• Psychosomatic complaints• Nightmares• Labile emotions• Regressions• Stoic, adult-like acceptance


• School-Age Children– More likely to be verbal about their illness– Developmental period of vigorous inquiry


• School-Age Children– A special physician-child education session may be

necessary• Can enhance compliance with procedures and

treatment

– Major activity outside the home is school, may help towards having some “normalcy”


• Normalcy is emphasized• “Burden of Normalcy” is created – The family has to reorganize itself but seem

“normal”

Treatment and Adaptation Period

• Two modes of Communicaton– Protective Approach– Open Approach

Talking to the Dying Child

• “Understanding, acceptance, and convetance of permission to discuss any aspect of the illness decreases feelings of isolation and alienation from parents and other meaningful adults and gives the child the sense that his or her illness is not too terrible to discuss.”


• Common questions– “Am I going to die”

• If yes, then

– “When?”– “What will death be like?”– “What will happen to me after I die?”– “Will the “bad things” I have done or thought case me to

be punished?”– “Will my parents be all right?”– “When can I be with my family again”– “Will it hurt when I die?”


• “Helping a child on his way” and “Ending a child’s suffering”– Open discussion does not yet warranted to

chidren• Active euthanasia: Implies unwarranted

assumption of infallibility on the part of the physician

• Children should not be allowed to die in agony

End of Life Challenges: On Active and Passive Euthanasia

• “... More intense grief reactions of somatic types, greater deression, anger and guilt with accompanying feelings of despair”

Bereavement in the Family

• Parents suffer from both the loss of the child and the loss of what the child represented to them.


• Better adjustement if:– With Viable and ongoing “significant other”– Open and responsive communication with child

during illness– Those with consistend life philosophies


• Siblings should also be informed– Tailored to developmental ages

• Follow-up counseling should be offered



Update on AS


Thank You.“Life is not measured by the breaths we take,

but the moments that take our breath away.”

Hillary Cooper

disponnect a case of pontine glioma the medical city | department of pediatrics asmph interns –...

Documents

history of birth

admission slide

information patient

history of trauma allergies

family history of cancer

previous history of

infancy birth history

past medical history