nervous system 4 1) hiv and the nervous system 2) tumours of the nervous system prof john simpson
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Nervous System 41) HIV and the nervous system
2) Tumours of the nervous system
Prof John Simpson
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NS infection in immunosuppressed
• infections common and often fatal in immunosuppressed, esp.
– atypical mycobacteria – CMV– papovaviruses – Candida albicans – Aspergillus fumigatus – Cryptococcus neoformans – Toxoplasma gondii – Entamoeba histolytica
• diagnosis often difficult before death• multiple infections common, particularly in HIV
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HIV and nervous system
• NS commonly involved in both AIDS and pre-AIDS stages
• route of infection uncertain– ? carried across blood brain barrier in
macrophage-type cells (“Trojan horse” theory)– ? actual direct infection of nerve cells and
other glial cells
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HIV and the nervous system
• NS presentations common in HIV/AIDS • at death at least 80% of AIDS patients have CNS
pathology resulting from - 1. multiple opportunistic infections (e.g. toxoplasma, fungi) 2. viral infections (e.g. CMV, papovavirus) 3. primary cerebral lymphoma4. cerebral HIV infection (subacute encephalitis causing
cerebral atrophy with progressive dementia) • sometimes preAIDS• diagnosis by blood serology or PCR on CSF
• also peripheral neuropathy (incl. after antiretroviral therapy)
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NS tumours
• gliomas
• nerve cell tumours
• germ cell tumours
• lymphomas
• meningionas
• metastases
• tumours of nerves
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NS tumours
• quite common - intracranial ~ 10 - 20 per 100,000 intraspinal ~ 1 - 2 per 100,000
• around two thirds primary and one third metastatic
• in adults, two thirds in cerebral hemispheres
• in children, where CNS tumours = 20% all tumours, two thirds in posterior fossa
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Pie chart of CNS tumour frequency in adults
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Pie chart of CNS tumour frequency in children
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NS tumours are “different”
• benign/malignant distinction often blurred– mostly because even benign tumours can expand
enormously in soft brain, so having major effects– so tumour site may be more important than behaviour
for prognosis• soft brain tissue makes tumours (espec glial
ones) difficult to remove• pattern of spread differs tumours elsewhere
– rarely metastasise outside the NS– other than direct spread, only path for spread is
subarachnoid space, so seeding along brain and cord can occur in tumours getting into CSF
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Brain tumours
• most important primary brain tumours are gliomas
• can arise from any glial cell– astrocytomas, oligodendrogliomas and
ependymomas
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Astrocytomas
• various types, each usually with its own histology, age range and clinical effect, e.g.– fibrillary astrocytoma– pilocytic astrocytoma – glioblastoma
• only important differences to remember– glioblastomas are malignant, others usually more benign– likely behaviour of more benign ones can be predicted by
“grading”, if biopsy representative – genetic analysis of tumour also correlates with likely behaviour
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Astrocytomas
• around 80% of adult primaries
• usually found in hemispheres, but can occur anywhere in brain or cord
• age range 40s – 60s
• most common presenting signs/symptoms– seizures, headaches and focal neurological
signs depending on tumour site
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Appearance of astrocytomas
• more benign ones– poorly defined, infiltration expanding/distorting and distort brain
(edge between tumour and normal can be difficult see even histologically)
– range in size few cms to lesions filling a hemisphere– usually homogenous, but may be cystic
• more malignant ones – glioblastoma (essentially = anaplastic astrocytomas)– often well-demarcated (speed of growth)– variable cut surface with areas of necrosis, haemorrhage and
cystic degeneration– often surrounding oedema, because of abnormal vessels – can
be seen on imaging
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Well-differentiated astrocytoma
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Well-differentiated astrocyoma
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NMR of glioma
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Glioblastoma multiforme
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Gliomatosis cerebri
• unusual condition
• multiple regions, occasionally whole brain, infiltrated by neoplastic astrocytes
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Astrocytomas – clinical effects
• depend partly on location and growth rate• tendency to increase with time• if “more benign”, symptoms/signs may not
change or only slowly over years, but eventual faster deterioration as dedifferentiation occurs– mean survival around 5 yrs
• prognosis for glioblastoma poor – <10% of patients alive after 2 yrs
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Pilocytic astrocytoma ( a more benign type) – cystic tumour with
nodule
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Oligodendrogliomas
• ~ 10% all gliomas• most common in 30s-40s• often prolonged history before diagnosis
– neurological problems, often with fits
• mostly affect cerebral hemispheres, particularly white matter
• usually better prognosis than astrocytomas• with treatment, average survival of 5 to 10 years
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Ependymomas
• most often arise beside ventricles or central canal of cord
• in children and adolescents, usually near the fourth ventricle
• in adults, usually in spinal cord, especially in neurofibromatosis
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Ependymomas
• often block 4th ventricle, causing hydrocephalus
• poor prognosis and CSF dissemination because of site
• average survival of about 4 years after treatment – better for supratentorial and spinal sites, since
often resectable
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Ependymoma in roof of 4th ventricle
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Ependymoma in 4th ventricle
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Nerve cell tumours
• ganglion cell tumours– gangliocytomas or gangliogliomas (mixed with
glial cells– usually slow growing, but glial component can
become anaplastic
• neuroblastomas– highly aggressive tumours of cerebral
hemispheres in children
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Medulloblastoma
• neuroectodermal origin
• usually undifferentiated, but sometimes neuronal and/or glial markers
• 20% of brain tumours in children
• always cerebellum
• highly malignant, but very radiosensitive
• with treatment 5 year survival can be up to 75%
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Medulloblastoma on CT
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Medulloblastoma in cerebellum
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NS lymphoma
• primary NS lymphoma (PCNSL) ~ 2% of extranodal lymphomas
• 1% of intracranial tumours overall
• commonest NS neoplasm in immunosuppressed
• in non-immunosuppressed incidence increasing, especially in old people
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Primary NS lymphoma
• often multiple tumour sites in brain
• nodal, marrow or extranodal involvement outside NS rare and late
• (NHL arising elsewhere rarely involves NS– can produce malignant cells in CSF and
round nerve roots and occasionally infiltrate superficial cortex or cord)
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Primary NS lymphoma
• mostly B-cell tumours
• in immunosuppressed, tumours contain EBV genomes in transformed B cells
• always aggressive disease– poor response to chemotherapy, cf. peripheral
lymphomas
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Primary NS lymphoma
• lesions frequently multiple, involving cortex, white matter and central nuclei
• periventricular spread common.
• relatively well defined compared to gliomas, but less so than metastases
• almost always high-grade lymphomas
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Germ cell tumours
• (can be same types as in testis/ovary)
• occur in midline, most commonly in the pineal (strong male predominance) and suprasellar regions
• rare in most countries, though up to 10% brain tumours in Japan
• 90% occur in first two decades
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Meningiomas
• predominantly benign adult tumours
• slow growing
• usually attached to dura
• arise from stromal cells
• may be found on any external brain surface or in ventricles
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Meningioma – and histology showing psammoma bodies
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Meningiomas
• usually rounded masses with well-defined base• compress brain, but easily separated from it • rarely involve overlying bone• usually encapsulated and often lobulated
– other pattern is en plaque variant - tumour spreads in sheets along dura, commonly with overlying reactive new bone
• usually firm, even gritty and may be heavily calcified (“psammoma bodies”)
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Meningiomas
• behaviour can be predicted by grading
• most are ”benign”
• different histological patterns of NO significance – e.g. syncitial, fibroblastic, psammomatous
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Meningiomas
• only a few infiltrate brain - broad pushing edges or as single cells
• brain invasion means increased risk of recurrence, but does not alter histological grade and so clinical behaviour
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Meningiomas
• usually slow-growing and solitary
• present either with vague symptoms or focal findings due to pressure on underlying brain
• commoner in women, espec. in cord– often express progesterone receptors– rapid growth reported in pregnancy
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Metastases
• mostly carcinomas• around 25% brain tumours
– most commonly lung, breast, melanoma of skin, kidney and GIT
– some tumours (e.g. prostate) almost never do, though can affect nearby bone and dura.
• meninges are also frequent site for metastases • present clinically as SOLs
– occasionally as first sign of cancer
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Pontine metastases from CA lung
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Tumours of nerves
• Schwann cell tumours (= Schwannomas = neurilemmomas)
• neurofibromas
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Schwann cell tumours
• well-circumscribed, encapsulated masses• attached to nerve, but can be separated from it • in cranium only common site is in
cerebellopontine angle attached to the vestibular branch of the eighth nerve – “acoustic neuromas”– present with tinnitus and deafness
• elsewhere schwannomas most common in association with large nerve trunks
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Schwannoma
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Neurofibromas – 2 types
• common form in skin or peripheral nerve– sporadically or in neurofibromatosis – sometimes hyperpigmentation over skin lesions– may be large and pedunculated– malignant transformation rare
• rare one is plexiform neurofibroma– diffusely permeating tumours– probably only in neurofibromatosis – difficult to remove– significant potential for malignant transformation
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Spinal cord tumours
• more or less any tumour affecting brain can also arise in cord
• similar mass effects from lesions in bones or discs
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Fetal NS infections
• rubella (deafness, blindness, microcephaly)
• CMV (microcephaly)
• toxoplasma (microcephaly)
• syphilis (tertiary forms include GPI, tabes dorsalis and meningovascular syphilis)
• (HIV)
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Mets