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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
DisPONnectA Case of Pontine Glioma
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
Patient History
Patient History
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
DisPONnectA Case of Pontine Glioma
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
Physical Examination
• 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
Physical Examination
• 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
Physical Examination
• Genitalia– Grossly female genitalia, no discharge
• Extremities– Full and equal pulses, no edema, no cyanosis, CRT
<2 seconds
Physical Examination
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
Neurologic Examination
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%
Neurologic Examination
++ ++
++++
++ ++
++ ++
Neurologic Examination
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
Neurologic Examination
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
DisPONnectA Case of Pontine Glioma
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
DisPONnectA Case of Pontine Glioma
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
DisPONnectA Case of Pontine Glioma
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
Diagnostics: Rationale
• 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)
Diagnostics: Rationale
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
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
Adjunctive Diagnostics
• Impression:– Brainstem mass lesion with
surrounding vasogenic edema. Consider a glioma.
– No evidence of hydrocephalus or herniation noted at this time.
Patient’s MRI
DisPONnectA Case of Pontine Glioma
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
DisPONnectA Case of Pontine Glioma
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
DisPONnectA Case of Pontine Glioma
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
DisPONnectA Case of Pontine Glioma
Brainstem GliomaComplications, Prognosis, Prevention
Complications
Complications
Complications
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%
DisPONnectA Case of Pontine Glioma
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
Child’s Reaction to Diagnosis and Treatment
• School-Age Children– More likely to be verbal about their illness– Developmental period of vigorous inquiry
Child’s Reaction to Diagnosis and Treatment
• 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”
Child’s Reaction to Diagnosis and Treatment
• 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.”
Talking to the Dying Child
• 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?”
Talking to the Dying Child
• “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.
Bereavement in the Family
• Better adjustement if:– With Viable and ongoing “significant other”– Open and responsive communication with child
during illness– Those with consistend life philosophies
Bereavement in the Family
• Siblings should also be informed– Tailored to developmental ages
• Follow-up counseling should be offered
Bereavement in the Family
DisPONnectA Case of Pontine Glioma
Update on AS
DisPONnectA Case of Pontine Glioma
Thank You.“Life is not measured by the breaths we take,
but the moments that take our breath away.”
Hillary Cooper