CNS CPC Year 2: Raised Intracranial Pressure

CPC CNS CPC Raised Intracranial Pressure

• Class: Year 2
• Course: CNS CPC
• Lecturer: Paul Murray
• Date: November 2024

Case History

• A 74-year-old man presented to the Emergency Department with a new onset seizure.
• Past medical history: lung adenocarcinoma 10 years prior, treated with neoadjuvant chemotherapy and resection.
• Examination: drowsy with rhythmic jerking of the right arm.

Four Presenting Features of Brain Tumour

• Seizure
• Symptoms/signs of raised intracranial pressure (headache, especially early morning, vomiting, coma, papilledema), plus/minus hydrocephalus symptoms.
• Focal neurological deficit
• Behavioural alteration

Brain Imaging

• CT brain followed by MRI brain with contrast.
• Ring-enhancing space-occupying lesion with edema.
• Ring-enhancing refers to a distinct outer ring or border of enhanced brightness/contrast surrounding a darker central area on imaging. Contrast agent highlights the blood vessels and the outer border of the lesion.

Questions

• Cerebral edema categorization: localised (rather than generalised).
• One cause of generalised cerebral edema: hypoxia-ischemia.

Presentation of Secondary Brain Tumour

• Multiple brain lesions (50% solitary).
• History of systemic malignancy.
• Mass lesion (e.g., lung) – check CXR.

Cellular Level Cerebral Edema

• Vasogenic edema: Normal blood-brain barrier disrupted, increased vascular permeability, fluid escapes from intravascular to intercellular compartments (e.g., trauma).
• Cytotoxic edema: Increase in intracellular fluid secondary to cellular injury (e.g., neuronal, glial, endothelial), like hypoxia-ischemia. [Sodium/Potassium pump failure due to insufficient ATP.]

Consequences of Raised Intracranial Pressure and Herniation

• Diagram showing herniation types, structures affected (e.g., brain stem, midline shift, tentorial notch distortion, subfalcine/transtentorial herniation of the cingulate gyrus).

Complications of Brain Herniation

• Vascular stretching and compression due to brain movement within the skull.
  • Anterior cerebral artery (ACA): supplies blood to frontal lobes, vulnerable near the falx cerebri.
  • Posterior cerebral artery (PCA): supplies occipital and temporal lobes, vulnerable near the tentorium cerebelli.
  • Perforating vessels in brainstem: small, deep arteries supply blood to brainstem, damage can lead to devastating bleeding areas (e.g., Duret hemorrhage).

Transtentorial Uncal Herniation

• Uncus (medial temporal lobe) herniates over the tentorium cerebelli.
• Clinical signs: Pupillary changes (ipsilateral dilated pupil), altered level of consciousness (drowsiness to stupor/coma), and Cushing's triad (hypertension, bradycardia, irregular respiration)
• Significant and potentially life-threatening.

Biopsy of the Ring-enhancing Lesion in the Motor Cortex

• Four main diagnostic possibilities:
  • Metastatic carcinoma
  • Primary brain tumour
  • Infection
  • Negative/non-diagnostic biopsy

Biopsy Appearance

• Densely cellular glioma with mitoses, vascular proliferation and necrosis. GFAP positivity.
• No gland formation.
• Diagnosis: Glioblastoma multiforme.
• Other techniques for more accurate diagnostic/prognostic information: available?

Molecular Information Impacts on Diagnosis and Prognosis

• Molecular analysis table showing BRAF gene fusion/mutation, IDH1/2 mutation, 1p/19q co-deletion, MGMT methylation, Histone (H3) mutation, and their respective impacts on diagnosis and prognosis.

Interphase FISH

• FISH probes showing TP73 [1p36], ABL2 [19q25], D19S221 [19p13], EHD2 [19q13] used for visualising chromosomal deletions and co-deletions (1p/19q).

Chromosomal Microarray

• Diagram showing chromosomal microarray results with highlighting of the 1p and 19q co-deletion.

Why Might a Grade I Tumour Cause Death?

• Location: Difficulty accessing and high morbidity associated with surgery, especially deep/brainstem location.

How Are Patients With Brain Tumours Managed?

• Gross total resection
• Radiotherapy
• Chemotherapy
• Combinations of the above
• Palliation
• Seizure control

Fill in the Blanks

• Glioma: primary brain tumour arising from glial cells (astrocytes, oligodendrocytes, ependyma).
• Most common malignant glioma in adults: Glioblastoma.
• Most common benign primary brain tumour: Meningioma (arising from meningothelial cells in meninges).
• Meningioma prognosis: Good.
• Tumour most likely to metastasize to the brain: Melanoma (with lung and breast primaries as frequent metastatic occurrences).

Contrast Agents in Brain Imaging

• Contrast agents highlight the "ring" of a lesion, where blood-brain barrier is disrupted in areas of infection, tumour, inflammation.
• Inner, darker area in usually poorly vascularized and necrotic in severe tumours.

Transtentorial Herniation (detailed)

• Medial temporal lobe (especially the uncus) herniates through the tentorial notch.
• Key clinical triad of "blown" pupil, hemiplegia, and coma.
• Compression of CN III (ipsilateral oculomotor nerve) leads to dilated pupil.
• Compression of cerebral peduncles causes hemiplegia.
• Midbrain reticular formation distortion leads to loss of consciousness; coma possible.

Cushing's Triad

• Clinical syndrome of increased intracranial pressure and impending brain herniation: Hypertension (increased blood pressure for perfusion), Bradycardia (slowed heart rate), Irregular respiration (abnormal breathing patterns due to brainstem compression).