raumenisyndrome

• Gorlin syndrome

• neurofibromatosis types 1 & 2

• multiple endocrine neoplasia type 1

• tuberous sclerosis complex

• von Hippel-Lindau disease

• Turcot syndrome

• Lynch syndrome

Investigations

• O'

, MR1 with contrast,stereotactic biopsy (tissue diagnosis and molecular markers for prognosis),

tumour resection (often performed as initial step rather than biopsy), metastatic workup, tumour

markers (i.e. germ cell tumours)

Treatment

• conservative:serial history, physical, imaging for slow growing/benign lesions

• medical:corticosteroidsto reduce 1CP, cytotoxic cerebral edema; pharmacologic (i.e. pituitary

adenoma)

• surgical: total or partial excision (decompressive, palliative)

• radiotherapy: conventional fractionated XR1, hvpofractionated XRT, SRS (e.g. Gamma Knife*)

• chemotherapy:e.g. alkylating agents (i.e. temozolomide, vincristine, cyclophosphamide, etc.)

• targeted therapy: e.g. trastuzumab for HER2-positive breast cancer and brain metastases, osimertinib

for EGER-mutant lung cancer and brain metastases

New onset communicating

hydrocephalus in a patient with

cancer should raise the suspicion of

leptomeningeal carcinomatosis

r n

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Table 10. Tumour Location: Etiology and Clinical Features

Supratentorial Infratentorial (Posterior Fossa)

Epidemiology

Glioma (all grades) (50%)

Craniopharyngioma (2-5%)

Others: pineal region tumours,choroid

plexus tumours,ganglioglioma.

dysembryoplastic neuroepithelial tumours

(DNET)

High -grade glioma (12-15%.e.g.GSM)

Metastasis (15-30%. includes infratentorial)

Meningioma (15-20%)

Low-grade astrocytoma (8%)

Pituitary adenoma (5-8%)

Oligodendroglioma (5%)

Other: colloid cyst. CNS lymphoma, dermoid/

epidermoid cysts

Medulloblastoma (15-20%)

Cerebellar astrocytoma (15%)

Ependymoma (9%)

Brainstem astrocytoma

Age <15 yr

Incidence:2-5 in 100000 per yr

60% infratentorial

Age ^15 yr

80% supratentorial

Metastasis

Acoustic neuroma (schwannoma) (5-10%)

Hemangioblastoma (2%)

Meningioma

Clinical Features

Shared Features(from devoted ICP) H /A: usually worse in AM and made worse with straining , coughing

N/V

Papilledema

Diplopia - CN VI palsy

Seizure: commonly the First symptom

Progressive neurological deficits (70%)

Frontal lobe:hemiparesis.dysphasia,

personality changes,cognitive changes

Temporal lobe:auditory/olfactory

hallucinations,memory deficits, contralateral Vertigo

superior quadrantanopia

Mental status change: depression, apathy,

confusion. lethargy

"Tumour TIA" (transient ischemic attack)

stroke like symptoms caused by

a) occlusion of vessd by tumour cells

b) hemorrhage

c) V to "steal phenomenon"

- blood isshunted

Irom ischemic regions tonon-ischcmic regions

Endocrine disturbance: pituitary tumouis (see

Endocrinology.E22)

Distinguishing Features Brainstem involvement:CN deficits and long

tractsigns

H /V:compression on vagal nucleus/area

postrema

Diplopia: direct compression CN VI

Nystagmus

Truncal ataxia + titubation:cerebellar vermis

lesions

limb ataxia,dysmotria, intention tremor:

cerebellar hemisphere lesions

Obstructive hydrocephalus more common

than supratentorial lesions

Figure 10. Multiple brain metastases

(see arrows)

Metastatic Tumours

Brain Metastasis

• most common intracranial tumour in adults(~50% of all brain tumours)

• afflict ~25% of patients with any cancer

• hematogenous spread most common

• 80% are hemispheric,often at grey-white matter junction or temporal-parietal-occipital lobe junction

• likely emboli spreading to terminal middle cerebral artery (MCA ) branches

Most Common Cancers that

Metastasize to the CNS

She of Primary Frequency of CNS

metastasis

Lung 44%

Breast 10%

Kidney (RCC)'

Investigations

• identify primary tumour

• full metastatic workup CXR,Cl'

chest/abdomen, abdominal U/S, nuclear medicine scan/RUT,

mammogram)

• CT with contrast > round, well-circumscribed, often ring enhancing, H- I edema, often multiple

• contrast-enhanced MRI more sensitive, especially for posterior fossa

• consider biopsy in unusual cases or if no primary’ tumour identified

n

61 6\

Melanoma 3%

•RCC Mcnul cell mclnorod

Treatment

• medical

phenvtoin (or levetiracetam) for seizure prophylaxis if patient presents with seizure

dexamethasone to reduce edema given with H2 blocker

role of chemotherapy limited because of poor penetration across BBB

targeted therapies are currently being investigated (e.g. HGI-

’R (epidermal growth factor receptor)

inhibitors in patients with HCil'

R-mutant lung cancer and brain metastases)

• radiation

• SRS (highly focused fraction of radiation targeted to tumour): for discrete, deep-seated/

inoperable tumours

Itiple lesions: use WBRT (upwards of 10 lesions); consider SRS if <4-10 lesions

postoperative adjuvant radiotherapy consideration: SRS to surgical cavity following resection

emerging evidence supports avoidance of WBRT and use of focal radiation to spare cognitive

functions (refer to Brown et al., 2016)

1. Heterogenous contrast enhancement

2.Ill-defined borders (inliltrativel

3 Peiitumoural edema

4. Central necrosis

jCompression of ventricles,midline shill y

• mu

+

• surgical Figure 11. High-grade glioma on CT

» single/solitary lesions or dominant lesion with significant mass effect orsymptoms:surgical

resection and radiation in carefully selected patients

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Prognosis

• median survival without treatment once symptomatic is ~1 mo, with optimal treatment 6-9 nio; may

be prolonged survival in some patient subgroups (e.g. HBR2/neu breast cancer, EGl-

'R-mutant lung

cancer)

the disease-specific Graded Prognostic Assessment (DS-GPA) is a useful prognostic index

• depending on primary tumour type, prognosis may depend on a combination of patient age,

Karnofsky score, extent of extracranial metastatic disease, number of intracranial lesions, and

molecular disease subtype

Surgical Resection vs. Watchful Wailing in low- Grade Gliomas

fcin Oncol 2017:28:19421948

Purpose: Thisstudy eie~ ined the effect of up-frort

surgery vs.watchful waiting for treatment of lowgrade gliomas on long term survival.

Methods: Ihe study was designed as a population -

based parallel cohortstudy that compared outcomes

from a hospital lavoaring watchful wailing (n *

6$

patients) and one favouring early resection (n-8?

patients),follow up was between 7 and 18 yr postdagnosis.The two groups were eq.ve ert in terms of

baseline parameters.

Results: Overall,surv.nral wassigmfkantly better

with early surgical resection. Patientsfrom the

centre favouring watchful waiting had a nedan

sur vival of 5.8 yr (95% Cl 4.5-7.21 whereas patients

fiom the centre favounng early resection had a

median survival of 14.4 yr (95% Cl10.4-18.5).The

enhanced survival benefit remained after adjusting

for molecular markers.

Conclusions: Early surgical resection of low grade

gliomas Is associated with significantly Improved

overall survival compared to watchful waiting.

Adult Diffuse Gliomas

• most common primary intra-axial brain tumour, common in 4th-6th decades

Table 11. WHO 2021 Diffuse Gliomas Classification

WHO Grade’ Typical CT/MRI

Findings

Type Altered Molecular Prognosis

Profiles

Oligodendroglioma 2.3 Low grade: areas ol

calcification on CT, t

enhancement

Defining: IDH- mulant Low grade:

-

10 yr

Ollier: TEH!promoler. CIO. High grade: 5 yr

fUBPI, N0TCH1

High grade:enhancement

2, 3, 4 Low grade:mass effect,no Defining:IDH mutant and Low grade:3yr

1pf19q codeleted

Astrocytoma

enhancement

High grade:1.5-2 yr

Other: ATRX , TP53,

C 0KN2A /B

Defining: IDH -wildtype 15 mo

High grade: complex

enhancement

Necrosis (ring

enhancement)

Glioblastoma 4

Olher:TERT promoler.

chromosomes 7/10. EGER

Comparison ota Strategy favouring Early Surgical

Resection vs. a Strategy favouring Watchful

Wailing in Lov*

-6rade Gliomas

JAMA 2012:308(18):188t 18S8

Purpose: to examine’watchful waiting’vs.eaify

surgical resection of low-grade gliomas.

Study: A population-based paralel cohort study

was undertaken between two hospitals Ihateach

favoured different management approaches lor lowgrade gliomas(biopsy and watchful wailing vs.early

surgical resection).

Results: 66 patients were included from the watchful

waiting hospital and 87 patientsfrom Ihe early

reseebon centre. Median follow-up was 7.0 and 7.1

pat each centre,the two groups were equivalent

m feints ol baseline parameters.Overall,survival

wassignificantly bettev wdh eaily surgical resection

Iwatchlul waiting:median survival of 5.9 yr 95% Cl,

4.S-7.3 vs.early resection:median survival was no!

reached due to prolonged lenglh of life,P'

0.01).

Conclusions: Early surgical resection of low-grade

q onasis associated with better overallsuruvtlas

compared to watchful waiting.

'grade based on natural history

Clinical Features

• sites: cerebral hemispheres»cerebellum, brainstem,spinal cord

• symptoms:recent onset of new/worsening H/A, N/V,seizure, ± focal deficits orsymptoms of increased

IGF

Investigations

• CT/MRI with contrast: variable appearance depending on grade

hypodense on CT, hypointense on T1 MRI, hyperintense on T2 MR1

• low-grade:most do not enhance and have calcification on CT

• high-grade: most enhance with CT contrast dye/gadolinium, possibly with central necrosis

(especially if IDH wildtype)

• histology during surgical resection or biopsy

Treatment

• low-grade diffuse gliomas

close follow-up, radiation, chemotherapy, and surgery are all valid options

• dedilferentiation to more malignant grade; typically occurs faster when diagnosed after age 45

surgery: maximal safe resection, not curative, trend towards better outcomes, provides tissue

sample for histologic/molecular characterization

XRT alone or postoperative prolongs survival (retrospective evidence)

chemotherapy: initial therapy in all patients with high-risk low-grade glioma

• high-grade ditTuse gliomas

• goal is to prolong “quality" survival

surgery

gross total resection: maximal safe resection + fractionated radiation with 2 cm margin +

concomitant and adjuvant temozolomide

- except: nearing end-of-life;or extensive brainstem, bilateral, or dominant lobe GBM

involvement

Bevaciiumab Plus Radiolherapy-Temozolomide

for Newly Diagnosed Glioblastoma

NEJM 2014;370:709-722

Purpose: fo evaluate the effect of combined

bevaciiumab andXRI-tenoiolomidem the treatment

of newly diagnosed glioblastoma.

Methods:Patientswith supratentorial GBM were

randomly assigned to receive IV bevaciiumab (ir458|

or placebo plus XII and oral temoiolomIde (n-463)

for 30 wh total in cycles,followed by bevacitumab or

placebo monotherapy.Outcomes were progressionfree survival and overall survival.

Results:the median progression-free survival

was longer mlhe bevacizumebgroup compared

with placebo (10.6 mo vs.6.2 mo.HR 0.64, 05% G

0.55 0.74|. although overallsurvival did not differ

significantly between groups ( HR 0.88. 95% Cl

0.764.02). Baseline health - related quality-of life

and performance status were maintained longei a

the bevaciiumabgroup although there was a higfcefrequency of adverse events.

Conclusions: Ire addition of hevaciiumab to XRTtemorolomide improves progression-tree sunmral but

Ml overall survival ut patientswith glioblastoma.

awake craniotomy for tumours in “eloquent” regions (e.g.speech and language regions or

near motor strip)

stereotactic biopsy if resection not possible, followed by fractionated radiation with 2 cm

margin

ri

c.J

- expectant:based on functional impairment Karnofsky score <70; patient’s/family’s

wishes

• chemotherapy: temozolomide (agent of choice); better response to temozolomide predicted by

MGMT gene methylation

• multicentric gliomas

• WBRT ± chemotherapy

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Primary Central Nervous System Lymphoma

Interim Resultsfrom theCATRON trial [EORTC

study 26053 2 2054) of Treatment with

C oncurrent and Adjuvant tlmoiolomlde for Ip 19q

Nonco- deleted Anaplastic Glioma:a phase 3.

randomised,open-label intergroup study

lancet 2017:390(10103):1645 S3

Purpose fo assessthe use ol radiotherapy vnth

concurrent and adjuvant tenwolomide in adultswith

non-co-deleled anaplastic gliomas.

Methods:Patientswith newly diagnosed non-codeleted anaplastic glioma were randomized to receive

radiotherapy alone or with adjovant temozotamide:

or torecerve radiotherapy with concurrent

temozoiomde ISiug/m2per day. with or without

adjuvant temomlumide.Ihe primary endpoint was

overallsurvival.

Results:Overall survival at 5years was 55-9%

(35% Cl 4) 2-63-81with and 44-1% (363-51 6)

without adjuvant temozolonide. Grade 3-4 adverse

events were seen in 8-12% of 549 patientsassigned

temozolomide.and were mainly haematological and

reversible.

Conclusions: Adjuvant temozoiomide chemotherapy

wosassooaled with isignificant survival bentit

in patients with newly diagnosed non-co-deleted

anaplastic glioma.

•highly aggressive, non-Hodgkin lymphoma confined to the CNS;

-95% are large B-lymphocyte

•brain t spinal cord,leptomeningeal,CSF,and ocular manifestations possible

•intracranial lesions predominantly supratentorial

Clinical Features

•occurs in both immunocompetent and immunocompromised populations(multifocal lesions in 2D40% of immunocompetent patients, and in 30-80% of immunocompromised patients)

•epidemiology:0.47 in 100000 per yr;M:F=1.35:1;age of onset 50-70 (30-40 in immunocompromised

individuals)

•symptoms: focal neurological deficit, cognitive/behavioural symptoms ± increased ICP or seizures or

CN palsies

blurred vision + floaters if ocular involvement

« high association with Epstein-Barr virusin patients with HIV

Investigations

•CT:hyper- or iso-attenuated lesions;significant enhancement with contrast

•MRI with contrast (imaging of choice):intensely enhancing lesions,often localized to periventricular

space

• immunocompetent -> homogenous enhancement ± minimal edema

• immunocompromised > heterogenous or ring enhancement, necrosis, edema ± hemorrhage

• restriction on diffusion imaging due to hypercellularity helpful to distinguish from other brain

tumours

•confirmation by stereotactic biopsy and histopathology

• corticosteroids may prevent histopathological diagnosis > avoid until biopsy complete when

clinically possible

Treatment

•chemotherapy:first

-line treatment; induction therapy using M ATKix regimen (high-dose

methotrexate (HDMTX) + cytarabine + thiotepa + rituximab) preferred

•surgery:generally reserved forstereotactic biopsy; resection discouraged

•radiation: WBRT used in consolidation therapy and for palliation;consider as second-line induction

therapy in HDMTX-lneligiblc patients

significant risk of neurotoxicity when combined with HDMTX

• vl

' A 1

-2

/

Prognosis

•age and performance status are key prognostic factors

•median survival:26 mo across all age groups; <7 mo for patients 270 yrold

3

1. Homogenous contrast enhancement

2. Dural attachment

Meningioma Distinct margins

Figure 12. Meningioma on CT

•most common primary intracranial tumour, arising from arachnoid cap cells

•sometimes calcified,often causes hyperostosis of adjacent bone (detectable on imaging)

•classically see Psammoma bodies(“meningocytic whorls") on histology

•location:70% occur along the parasagittal convexity,falx cerebri,and sphenoid bone;other locations:

tubcrculum sellae,foramen magnum, olfactory groove, and CPA

Clinical Features

•middle aged,slight female predominance (M;P=1:1.8),many expressthe progesterone receptor

(increase in size with pregnancy)

•many are asymptomatic and can he an incidental finding; when symptoms occur focal neurologic

deficitsspecific to location, ± seizures,symptoms of increased ICP

•molecular changes: between 40-80% of meningiomas contain mutations in chromosome 22 (involved

in suppressing tumour growth);some have extra copies of PUG1

:R and EGER;some are associated with

mutations in the h'

1

'

2 gene

WHO Classification of Meningioma

(by histology)

Grade 1:low-risk of recurrence

Grade 2:intermediate risk of recurrence

Grade 3:high-risk of recurrence

Recommendationslor Management oi

Meningiomas

l ancet Oncol 2016;T7(9):e383-391

European Association of Nemo-Oncology assessed

available literature, rated scientific evidence,and

graded recommendation levels.

Key recommendations:

1. Firststandard therapy sgrosstotalsurgical

resection (including imrotred dura).

2.Alternative treatmentsinclude radiosurgery lot

small tumours and fractionated Xtl in large/

previously treated tumours.

3. New treatment conceptscombining surgery and

radiosurgeiy/lractionated XRI to treat complete

tumour volume are being developed.

4. Although pharmacological treatments are still

experimental, antiangiogenic drugs, peptide

receptor radionuclide therapy, and targeted

agents ate candidatesfor future pharmacological

approacheslo treat refractory meningioma ot all

WHO grades.

Investigations

•CT with contrast:homogeneous, densely enhancing, along dural border (“dural tail"),well

circumscribed, usually solitary (10% multiple, likely with loss of NE2 gene/22q 12 deletion)

i MRI with contrast: characterization of mass and provides a belter assessment of the patency of dura )

venoussinuses

•angiography

most are supplied by external carotid feeders (meningeal vessels)

can assess venoussinus involvement, "tumour blush'

commonly seen (prolonged contrast image)

Treatment

•conservative management:asymptomatic and/or non-progressive on CT/MK1serial monitoring for

interval growth changes

•surgery: often curative if complete resection and Indicated when symptomatic and/or documented

growth on serial C1/MR1

t

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•endovascular:embolization for highly vascularized,likely bloody, tumoursto facilitate surgery

•radiation:SRS may be an option for lesions <3cm partially occluding the superiorsagittal sinus;SRS

or XRT for non-resectable, recurrent atypical/malignant meningiomas

Prognosis

•5 yr survival is >85% for Cirade 1, 60-90% for Grade II, and 35-65% for Grade 111

•depends on extent of resection

•Simpson’s classification: degree ofsurgical resection completeness with symptomatic recurrence

Progressive unilateral or asymmetrical

sensorineural hearing loss - vestibular

schwannoma until proven otherwise

Table 12. Simpson Grade of Meningioma Resection

Grade Criteria

I Macroscopically complete removal ol tumour, with excision of its dural attachment and of anyabnormal bone

Macroscopically complete removal ol tumour, with coagulation olits dural attachment

Macroscopically complete removal oltumour without resection or coagulation ol dural attachment or extradural extensions

Partial removal ol tumour

Simple decompression with or without biopsy

II

III

IV

V

Vestibular Schwannoma (Acoustic Neuroma)

•slow-growing (60% show no growth over 1 yr; average rate for growing tumours 1-2 mrn/yr), benign

posterior fossa tumour (8-10% of tumours)

•arises from vestibular nerve of CN Vlll in internal auditory canal, expanding into bony canal and CPA

•if bilateral, diagnostic of NF2

•epidemiology:1.5 in 100000; all age groups affected, peaks at 4th-6th decades

Clinical Features

•early clinical triad:(tumour <2 cm) unilateral progressive hearing loss 98%, tinnitus, and

disequilibrium (compression ofCN Vlll)

•later clinical features

tumour usually >2 cm: otalgia, facial numbness + weakness, changes to taste (due to CN V and

VII compression, respectively)

tumour usually >4 cm: ataxia,H/A, N/V, diplopia, cerebellar signs (due to brainstem

compression;± obstructive hydrocephalus)

Investigations

•MKI with gadolinium or T2 fast imaging employing steady-state acquisition (FIESTA)sequence

(>98% sensitive/specific);CT with contrast 2nd choice

•audiogram, brainstem auditory evoked potentials, caloric tests

Treatment

•expectant:serial imaging (CT/MRI q6 mo) and audiometry if tumour issmall, hearing is still

preserved, high perioperative risk, or elderly patient

•radiation:SRS

•surgery: if lesion >3cm, brainstem compression, edema, hydrocephalus

•curable if complete resection (almost always possible)

•operative complications:CS1

;

leak, meningitis,required shunt;CN V, VU, VIII dysfunction

(proportional to tumour size; only significant CN VIII disability if bilateral)

•implications for testing of family members of NT2 mutation carrier

Figure 13. Vestibular schwannoma

(tumour in CPA)

Pituitary Adenoma

•primarily from anterior pituitary, 3rd-4th decades, M=l-, associated with multiple endocrine neoplasia

type 1 (MEN-1)syndrome

•incidence in autopsy studies approximately 20%

•classification

microadenoma <I cm;macroadenoma >1 cm

endocrine active (functional/secretory) vs. inactive (non-functional)

most common functional: prolactinomas, adrenocorticotropic, GH-producing

• differential diagnosis: parasellar tumours (e.g. craniopharyngioma, tuberculum sellae

meningioma), carotid aneurysm

Clinical Features

•mass effects

•H/A

•bitemporal hemianopia (compression of optic chiasm); hydrocephalus (3rd ventricle compression)

•invasive adenomas:CN III, IV, VI, V2, VI palsy (cavernoussinus compression); proptosis and

chemosis (cavernoussinus occlusion)

Go Look For The Adenoma Please -

GH, LH, FSH.TSH.ACTH, Prolactin

A compressive adenoma in the pituitary

will impair hormone production in this

order (i.e.GH-secreting cells are most

sensitive tocompression)

r >

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• endocrine effects (see Endocrinology, E22)

hyperprolactinemia (prolactinoma):infertility, amenorrhea,galactorrhea, decreased libido

AC i H production:Cushing'

s disease, hyperpigmentation

GH production: acromegaly/gigantism

panhypopituitarism:due to compression of pituitary (hypothyroidism, hypoadrenalism,

hypogonadism)

DI -rare, except in apoplexy

• pituitary apoplexy (sudden expansion of mass due to hemorrhage or necrosis)

• abrupt onset H/A, visual disturbances,ophthalmoplegia,reduced mental status,

panhypopituitarism and Dl

CSF rhinorrhea and seizures (rare)

signs and symptoms of SAH (rare)

Investigations

• formal visual fields, CN testing

• endocrine tests (prolactin level, TSH, 8 AM cortisol, fasting glucose, l

'

SH/LH, insulin-like growth

factor 1 (IGF-I)), electrolytes, urine electrolytes, and osmolarity

• imaging (MK1 with and without contrast)

1.Antodor cerebral artory

2. Internal carotid artery (communicating part)

3. Pituitary gland

4.Oculomotor nerve

5.Trochlear nerve

6. Internal carotid artery (cavernoussegment)

7. Ophthalmic nerve

8.Abducens nerve

9.Cavernoussinus

10.Maxillary nerve

Treatment

• medical

for apoplexy:rapid corticosteroid administration ± surgical decompression

for prolactinoma:dopamine agonists(e.g.bromocriptine)

for Cushing’

s:serotonin antagonist (cyproheptadine), inhibition of cortisol production

(ketoconazole)

for acromegaly:somatostatin analogue (octreotide) ± bromocriptine

endocrine replacement therapy

• surgical

endoscopic endonasal trans-sphenoidal, and less commonly trans-cranial approaches(i.e. for

significant suprasellar extension)

• postoperative concerns:Dl, adrenal insufficiency (Al), CSF leak

Dl and Al: AM cortisol,serum sodium and osmolality, urine output and specific gravity

(treatment - Al:glucocorticoids; Dl:desmopressin/DDAVP"

)

• CSF rhinorrhea: test for p-transferrin

Figure14.Cavernous sinus

Genetic Associations

• sellar masses have known associations with several classic oncogene mutations, including:

MEN1:loss-of-function mutations are common

GNSA1:activating mutationsfound in -40% ofsomatotroph adenomas

AIP:mutations associated with familial pituitary'adenomas

Cerebral Abscess

Definition

• pus in brain substance,surrounded by tissue reaction (capsule formation)

Etiology

• modes of spread: 10-60% of patients have no identifiable cause

• pathogens

• Streptococcus (most common), often anaerobic or microaerophilic

Staphylococcus(penetrating injury)

Gram-negatives, anaerobes( Bacteroides,l

:

usobacterium)

in neonates:Proteus and Citrobacter(exclusively)

immunocompromised:Toxoplasma, Nocardia,Candida albicans, Listeria monocytogenes,

Mycobacterium, and Aspergillus

Sources of Pus/Infection

• four routes of microbial access to CNS

1.hematogenous spread:arterial and retrograde venous

adults: chest is most common source (lung abscess, bronchiectasis, empyema)

• children: congenital cyanotic heart disease with K-lo-L shunt

• immunosuppression (AIDS toxoplasmosis)

2.direct implantation (dural disruption)

trauma

• iatrogenic (e.g.following LP, postoperative)

congenital defect (e.g. dermal sinus)

3.contiguousspread (adjacent infection):from airsinus, naso/oropharynx,surgicalsite (e.g. otitis

media, mastoiditis,sinusitis, osteomyelitis,dental abscess)

4.spread from peripheral nervoussystem (PNS) (e.g.viruses:rabies, herpes zoster)

[]

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•common examples

epidural abscess: in cranial and spinal epidural space, associated with osteomyelitis

treatment: immediate drainage and antibiotics,surgical emergency if cord compression

subdural empyema:bacterial/fungal infection, due to contiguous spread from bone or airsinus,

progresses rapidly

treatment:surgical drainage and antibiotics, 20% mortality

meningitis, encephalitis (see Infectious Diseases.ID17)

cerebral abscess Li

Risk Factors

•lung abnormalities (infection, AVTs;especially Osler-Weber-Rendu syndrome/hereditary

hemorrhagic telangiectasia)

•congenital coronary heart disease: R-to-L shunt bypasses pulmonary filtration of microorganisms

•bacterial endocarditis

•penetrating head trauma

•immunosuppression (e.g. AIDS)

•dental abscess, poor dentition 1. Surrounding edema

2. Central low density (pus)

Clinical Features 3.Ring enhancement

•focal neurological signs and symptoms

• H /A, decreased LOG

•mass effect, increased 1CP and sequelae (cranial enlargement in children)

•hemiparesis and seizures in 50% of cases

•± signs and symptoms of systemic infection (low-grade fever, leukocytosis)

Figure 15. Cerebral abscess on CT

Recommendationsfor Duration ol Antibiotic

Therapy lor Brain Abscesses

Int1Infect Bis 2010;14Supp!4:S79-92

Systematic literature search 111:

9 UEOIINE database

for studies dur. 1191988 2008 to nrethoilologicaly

evaluate antibiotic therapy duration pertaining to

brain abscess.

Key recommendations:

t. Prudent per od of 4 -6 wk of antibiotic theiapy (or

surgically heated abscesses.

2.6-8wkof IVtreatment for abscesses treated

medically only.

3. 6 8 wk of IVtreatment lor multiple abscesses nrtien

laiger ones are healed surgically.

Complications

•with abscess rupture: ventriculitis, meningitis, venous sinus thrombosis

•CS1

:

obstruction

•transtentorial herniation

Investigations

•CT scan often first test in emergency department

.MR1

• imaging of choice

• restriction on diffusion imaging (also seen in lymphoma)

apparent diffusion coefficient (ADC) used to differentiate abscess ( black) from tumour (white)

•WBC/ESR may be normal, blood cultures rarely helpful and LR contraindicated if large mass

•CSF:non-specific (high 1CP, high WBC, high protein, normal carbohydrate), rarely helpful, usually

negative culture

Treatment

•aspiration ± excision and send for Gram stain, acid-fast bacillus (APB), C&S,fungal culture

•excision preferable if location suitable

•antibiotics

empirically: vancomycin + ceftriaxone + metronidazole or chloramphenicol or rifampin (6-8 wk

therapy)

revise antibiotics when C&S known

•anticonvulsants (1-2 yr)

•follow-up is done clinically and with MRI

Prognosis

•-10% mortality with appropriate therapy, permanent deficits in -50% of cases

Table 13. Stages of Cerebral Inflammation/Infection

Stage CT Features MRI Features Microstructural changes

Early cerebritis(1-3d) Low attenuation abnormality

Mass effect

Low 11signal

High 12 signal

Patchy contrast enhancement

Increased lesion demarcation

Neotrophil accumulation

Tissue necrosis and edema

Microglia andaslrocyte activation

Macrophage and lymphocyte infiltration

Microglia and astrocyte activation

Late cerebritis(4-9 d)

Early capsule

formation (10-13 d)

Late capsule

formation (> 14 d)

Ring contrast enhancement, Seller demarcation ol lesion formation ol thin,well-vasculamed wall

particularly in lale capsule

formation

Ring contrast enhancement Microglia and astrocyte activation

Sued(MlWithll,inner media

'

Wa"

,hiCk CaPSU

'

e mU"

iple

'

ayerS

r “i

L J

Microglia and astrocyte activation

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Blood

Table 14. Comparison of Epidemiology and Etiology of Intracranial Bleeds

Types of Etiology

Hematoma/

Hemorrhage

Epidemiology Clinical

Features

CT Features Treatment Prognosis

CT Density and MRI Appearance

of Blood

Epidural

Hematoma

Skull fracture M» f (4:1J.

causing middle associated with

meningeal

bleed

lucid Interval Hyperdense Craniotomy

before loss of lenticular mass

consciousness with sharp

margins, usually

limited by suture

lines

Hyperdense

crescentic mass,

crossing suture

lines

Good with prompt

management; respiratory

arrest can occur from

uncal herniation;89%

recovery at 6 mo

time Cl MRIT1 MRI 12

Acute Hyperdense Grey Slack trauma

(<72 h|

Subacute Isodense White White

ft3*

|k

Chronic Hypo-dense Black Black

tfrrt)

Acute SDH Ruptured

subarachnoid associated with

bridging vessels trauma

Age »50. No lucid

interval,

hemiparesis,

pupillary

changes

Craniotomy if bleed

>1cm thick

40-60% mortality in

patients requiring surgery

M8M1-

-fcorpe Wuihfiglun Dllilge"

MRI 12.-Orto* cookie - Bl.uV WluU Bl.ick

Chronic SDH Age >50.

ElOH users.

Often 8.6% mortality at 6 mo

with drain.18.1% without

Ruptured

subarachnoid

bridging vessels anticoagulated

Hypodense

asymptomatic, crescentic mass,

minor H /A, crossing suture

confusion,signs lines

of increased

Burr hole to drain;

craniotomy if recurs

ICR. lightheadedness

SAH Trauma.

spontaneous

(aneurysms.

idiopathic,

AVM)

Age 55-60.20%

cases under

age 45

Sudden onset

thunderclap

H/A,signs of

increased ICP

Hyperdense blood Honsurgical: NP0.

in cisterns/fissures IV normalsaline

(sensitivily

decreases over

time)

Traumatic;

0.6% mortality with

isolated SAH in the setting

of mild traumatic brain

injury|GCS >13)

|NS), ECG, Foley, BP

120-150, vasospasm

prophylaxis

(nlinodipine):open

vs. endovascular

surgery to repair if

rebleed;

external ventricular

More severe IBI is

typically associated with

additional forms of brain

injury.

drainage or internal

CSf diversion may be Aneurysmal:

needed if secondary 50% mortality at1month

hydrocephalus without treatment.

20- 40% with moderate

to severe disability with

treatment

Hyperdense Medical:decrease BP. Poor: 44% mortality due to

inlra parenchymal control ICP

Surgical:craniotomy

ICH HTN . vascular

abnormality,

tumours.

infections,

coagulopathy

Age >55.

male, drug use

(cocaine.EtOH,

amphetamine)

TIA-likc

symptoms,

signs of

increased ICP

cerebral herniation

collection

Epidural (Extradural) Hematoma

Etiology

• temporal

-parietal skull fracture; 85% are clue to ruptured middle meningeal artery; remainder of

cases are due to bleeding from middle meningeal vein, dural sinus, or bone/diploic veins

Epidemiology

• young adult, M:F=4:1; rare before age 2 or after age 60

• 1-4% of traumatic head in juries

Clinical Features

• classic sequence (seen in <3096): post-traumatic reduced LOC, a lucid interval of several hours, then

obtundation, hemiparesis, ipsilateral pupillary dilation, and coma

• signs and symptoms depend on severity but can include H /A, N /V, amnesia, altered LOCI, aphasia,

seizures, HTN, and respiratory distress

• deterioration can take hours to days

I Compression olvonlricloslMLSI

2. Blood

Figure 16. Extradural hematoma

on CT

r n

Investigations

• CT without contrast: “lenticular-shaped,” usually limited by suture lines but not limited by dural

attachments (not visible on initial CT in 8% of cases)

L J

Poor Prognostic Indicators for Epidural

Hematoma

• Older age

• Low CCS on admission

• Pupillary abnormalities (especially

nonreactive)

• longer delay in obtaining surgery (if

needed)

• Postoperative elevated ICP

Treatment

• admission, close neurological observation with serial CT indicated if all of the following are present

small volume clot (<3() mL), clot thickness <15 mm, minimal midline shift (MLS <5 mm),(iCS

>8, no focal deficit

• otherwise, urgent craniotomy to evacuate clot, follow-up CT

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•patients with initial epidural hematoma >10 mL on CT within 2 h or epidural hematoma enlargement

in temporoparietal region are more likely to develop epidural hematoma enlargement and require

close CT follow-up at 5-6 h post impact

•mannitol preoperative if elevated ICP orsigns of brain herniation

•reverse anticoagulation if on warfarin

Prognosis

•good with prompt management, as the brain is often not damaged

•worse prognosis if bilateral Babinski or decerebration preoperatively

•death is usually due to respiratory arrest from uncal herniation (injury to the midbrain)

Compression of ventricles MLS

Blood

Subdural Hematoma

Table 15. Comparison of Epidemiology and Etiology of Acute and Chronic SDH

Acute SDH Chronic SDH

Time Course 1-2 d after bleeding onset

Rupture of vessels that bridge the subarachnoid space

(c.g. cortical artery,large vein,venous sinus) or cerebral

laceration

>15 d after bleeding onset

May start out as acute SDH

Often due to minor injuiies or no history of injury

Blood within the subdural space evokesan inflammatory

response:

Fibroblast invasion of clot and formation of

neomembranes within days -*

growth of neocapillaries

»fibrinolysis and liquefaction of blood clot|forming

a hygroma)

Course is determined by the balance of rcbleeding from

noomcmbtancs and resorption of fluid

Advanced age,alcoholics,patients with CSF shunts,

anticoagulants,coagulopathies,shaken baby syndrome

Etiology

Old blood

Risk Factors Trauma,acceleration-deceleration injury,anticoagulants.

EtOH. cerebral atrophy,infant head trauma,shaken baby

syndrome

Altered LOC,pupillary irregularity,hemiparesis

Up to 50% of patients can present with coma from the time

of injury

Clinical Features May presentwith minor H/A.confusion,language

difficulties.TIA -like symptoms, symptoms of raised

ICP t seiiures. progressive dementia, gait problem,

light-headcdness

Presents with global rather than focal deficits,such as

disturbance of consciousness:“the great imitator* of

dementia, tumours

CT:hyperdense.concave, crescentic mass,crossing suture CT:hypodense (liquefied clot),crescentic mass

lines

Indications lor craniotomy:if clinically symptomatic,

hematoma >1cm thick. MIS >5 mm. CCS decreased by >2

from time of injury to hospital admission,or ICP persistently Burr hole drainage of liquefied clot indicated if

>20 mmHg (optimal if surgery <4h from onset) symptomatic or thickness >1cm:craniotomy if recurs

Otherwise observe with serial imagingif stable or

improving

Poor overall since Ihe brain parenchyma is often injured Good overall as brain usually undamaged,but may

(mortality range is 50-90%,due largely to underlying brain require repeat drainage

Injury)

Prognostic factors:initial CCS and neurological status,

postoperativeICP

Figure 17. Subdural hematoma on CT

Investigations

Use of Drains vs.No Drains After Burr-Hole

Evacuation For Treatment of Chronic Subdural

Hematoma

CochraoeDB Syst Rev 2016:|S):(DOI1402

Purpose: Tocompate eiternal subdural drams to

no drains after burr-hole evacuation for treatment

of chronicSDH

Methods:Systematic renew withcomprehensive

search strategy databases eitracbog9 RCTs|n*9G8)

Results : SgrTirant reduction m the risk of

recunence with subdural drains (RR 0 45.95%

Cl0.32 C-61). no strong evidenceod increase in

comptcations (RR 0.78.95% Cl 0.77-1.72).mortality

(SR 0.78.95%Cl 0.45-1.33).poovfunctional outcome

(SR 0.68.95% Cl 0.44-1.05).

Conclusions

1. Some evidence that postoperative drainageis

effective in reducing the symptomatic recurrence

of chronic subdural hematoma.

2.Ihe effect of drainage on the occurrence olsurgical

complications,mortality,and xor functional

outcomes isuncertain due tolow quality evidence.

3.No strong evidence olincrease hi complications

when drains aroused.

Seiture prophylnais only ilpost traumatic seiiute

Reverse coagulopathies

Treatment

more than twice

Prognosis

Cerebrovascular Disease

Cerebrovascular disease may be divided into two general categories:

Ischemic Cerebral Infarction (80% of disease)

• includes embolism, thrombosis of intracerebral arteries, vasculitis, hypercoagulability, etc. (see

Neurology.Stroke, N5I )

Intracranial Hemorrhage (20% of disease)

• includes SAH,spontaneous1CH, 1VH

• may occur due to ruptured intracranial aneurysms

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t. Anterior communicating artery. 30%

2. Middle cerebral artery.20%

3. Internal carotid/posterior

communicating artery. 30%

4. Basilar bp. 2%

5. Superior cerebellar artery,3%

6. Vertebrobasilar junction. 2%

7 Posterior inferior cerebellar artery.3%

Hemiuanicctomy inOlder Patients withExtensive

Middle-Cerebral-Artery Stroke

N EJM 2014:370:1091 1100

Purpose lodeletm.ne il early decompressive

hetnicraniectomy reduces mortality among patients

>60 yr.

Methods:112 patients >60 yr (medan age 70 yr)

wdh malignant MUinfarction randomly assigned

10 conservative ICU treatmentis. bemicraniectomy.

Endpoint was survival without severe disability

(modified Rankin scale score 0-4).

Results: Ine proportion of patients who survived

without seiere drsahilily was 3S\ m the

bemicraniectomy group and 18% in the control group

(OR 2.91.95*o a1.06-7.49). Modified Rankin scale

scores inhemicramectomy vs.control group in terms

of percentagesod patients:0 2 (0% vs.0%|, 3 or

moderate dlsabakty (7%is. 3%). 4 or moderate severe

disabil ty {32% is.15%), 5 or severe disahility (28%

us.13%),ard 6 or death|33%n.70%).Infections

were more frequent in the hemicramectomy group

and herniation morefieguent in the control group.

Conclusions: Hemitraniectomy "

(leased survival

withoutseiere disability among patients>60 yr with

a malignant MCA infarction.

3

Types of Aneurysms

4

5

6

Saccular Fusiform Dissecting

^

7

§

Imi

© Jerry Won 2014, after Kristina Neuman 2011

Figure 18. Aneurysms of the Circle of Willis:figure outlines most common aneurysms In the vessels

Subarachnoid Hemorrhage

Definition

• bleeding into subarachnoid space (intracranial vessel between arachnoid and pia)

Etiology

• trauma (most common)

• spontaneous

• ruptured aneurysms (75-80%)

• idiopathic (14-22%)

• AVMs (4-5%)

• coagulopathies (iatrogenic or primary), vasculitides, tumours, cerebral artery dissections(<5%)

Epidemiology

• ~10-28 in lOOOOO population peryr

• peak age 55-60, 20% of cases occur under age 45

Risk Factors

• H1N

• pregnancy/parturition in patients with pre-existing AVMs, eclampsia

• oral contraceptive pill

• substance use disorder (cigarette smoking, cocaine, EtOH)

• conditions associated with high incidence of aneurysms (see Intracranial Aneurysms, XS2-I)

Hunt and Hess Grade (Clinical

Grading Scale for SAH)

Grade Description

Mo 5« or mildH/A and/or mild

meningismus

Grade 1 <- CM palsy

Confuboitflethaigy.mild

hemipareur, oraphaua

GCS<IS but >8.moderate-severe

heniparesis. mild rigidity

Coma (GC$ <9). decerebrate,

moribund appearance

1

2

3

Clinical Features of Spontaneous SAH

• sudden onset (seconds) ofsevere “thunderclap” H /A usually following exertion and described as the

“worst headache of my life" (up to 97% sensitive, 12-25% specific)

• N/V,photophobia

• meningismus (neck pain/stiffness, positive Kernig's and Brudzinski’ssign)

• decreased LOG (due to either raised 1GP, ischemia, or seizure)

• focal deficits:cranial nerve palsies (GN 111, IV ), hemiparesis

• ocular hemorrhage in 20-40% (due to sudden raised IGF compressing central retinal vein)

• reactive HTN

• sentinel bleeds

• represents undiagnosed SAH

• SAH-like symptoms lasting <1 d (“thunderclap H/A")

may have blood on CT or LF

• -30-60% of patients with full blown SAH give history suggestive of sentinel bleed within past 3

wk

• differential diagnosis:sentinel bleed, dissection/thrombosis of aneurysm, venous sinus thrombosis,

benign cerebral vasculitis, benign exertional H/A

4

5

Mortality ot Grade1-2 20uu,increased with grade

r “t

LJ

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Investigations

• non-contrast CT (NCCT) for diagnosis of SAH

• 98% sensitive within 12 h,93% within 24 h; 100% specificity

• may be negative if small bleed or presentation delayed several days

acute hydrocephalus, 1VH, 1CH,infarct or large aneurysm may be visible

• LP (highly sensitive) for diagnosis of SAH if CT negative but high suspicion:

• elevated opening pressure (>I 8 cm Hit))

• bloody initially, xanthochromic supernatant with centrifugation (“yellow") by -

12 h, lasts 2 wk

• RBC count usually >100000/mm 3withoutsignificant drop from first to last tube (in contrast to

traumatic tap)

elevated protein due to blood breakdown products

• four vessel cerebral angiography (“gold standard" for aneurysms)

• demonstrates source of SA H in 80-85% of cases

• angiogram negative SAH: repeat angiogram in 7-14 d, if negative > “perimesencephalic SAH"

• MRA and CT angiography/angiogram (CTA):sensitivity up to 95% for aneurysms,CTA>MRA for

smaller aneurysms and delineating adjacent bony anatomy

World Federation of Neurological

Surgeons (WFNS) Grading of SAH

WfNS Grade CCS Score Aphasia,

Hcmiparesis.

or Hemiplegia

ll1 IS

2 tt-14

3 13-14

4 M2 pr

-

S 36 or -

*kilaclaneurysm

Blood in

basal cisterns

Blood in Blood in

suprasellar cistern interhemisplieric fissure

Nontraumatic Subarachnoid Hemorrhage in

the Setting of NegathreCranial Computed

Tomography Results:External Validation of a

Clinical and Imaging Prediction Rule

A- n imerg Med 2013:61|1|:110

Purpose: lo validate twodfosion rules for the

dagnosisol SAH: (1|A cIvricM prediction rule stales

that patientswith acute severe H/A but without

the dinical variables age >40 yr, neck pain,loss of

consciousness, oionsef ofH'

Awith exertion are at

low-risk for SAH;(2) An rmagirg prediction lule hoses

diagnosis on non-contrast cranial Cl loi patients

vrl

'