Chapter Notes: Central Nervous System

Table of Contents
1. Cerebral Herniation
2. Developmental Abnormalities of the Brain
3. Neural Tube Defects
4. Cerebral Hemorrhage
5. Cerebral Ischemia
6. Intracranial Aneurysms
7. CNS Infections
8. Demyelinating Disorders
9. Degenerative Disorders
10. Tumors
11. Peripheral Nerve Sheath Tumours
View more

Cerebral Herniation

The cranial cavity is divided into sections by folds of the dura. The two brain hemispheres are separated by the falx, while the tentorium separates the front and back sections. Herniation means brain tissue moves into a space it usually does not occupy. The most common type is transtentorial herniation, where brain tissue shifts from the supratentorial to the infratentorial areas through the tentorial opening. There are three main types of herniation: transtentorial, transfalcine (subfalcine), and tonsillar (foraminal).

Transtentorial Herniation

Transtentorial herniation is the most common type, occurring when brain tissue shifts from the supratentorial to the infratentorial compartments through the tentorial opening. There are two main types:

• Temporal (uncal) herniations. In this type, the anterior medial temporal gyrus (the uncus) pushes into the tentorial opening near the midbrain. This displacement compresses the third cranial nerve, leading to symptoms such as mydriasis (dilated pupils) and ophthalmoplegia (eye muscle paralysis), with the pupil turning down and out on the same side.
• Central transtentorial herniation. This involves a downward shift of the thalamic medial structures through the tentorial opening, compressing the upper midbrain. Signs of this type include miotic (constricted) pupils and drowsiness.

Transfalcine Herniations

Transfalcine herniations occur when the medial part of the cerebral hemisphere, specifically the cingulate gyrus, herniates under the falx. This can potentially compress the anterior cerebral artery.

Tonsillar Herniation

Tonsillar herniation occurs when masses in the cerebellum push the cerebellar tonsils into the foramen magnum. This can lead to compression of the medulla and respiratory centers, resulting in life-threatening conditions.

Concept
Tonsillar herniation may also occur if a lumbar puncture is performed on a patient with increased intracranial pressure. Therefore, it is crucial to check for papilledema before conducting a lumbar puncture.

Developmental Abnormalities of the Brain

• Dandy
• Dilated 4th ventricle
• Walker
• Water on the brain (hydrocephalus)
• Syndrome
• Small or absent vermis
• Triad of tuberous sclerosis: Seizures + mental retardation + congenital white spots or macules (leukoderma).

Syringomyelia

• The most common place for a syrinx is the cervical region, leading to loss of pain and temperature sensations in both arms.
• The diagnosis of syringomyelia is best made with an MRI of the cervical spine.

Neural Tube Defects

• Neural tube defects are linked to higher levels of α-fetoprotein (AFP) in the mother's blood.
• Adequate maternal folate levels before pregnancy can help reduce the risk of these defects.
• AFP is a protein made by the yolk sac and the fetal liver; raised levels can also indicate conditions like yolk sac tumours of the testes and liver cancer.
• Note that low AFP levels are associated with Down syndrome.

Types of Developmental Abnormalities

• Arnold-Chiari malformation. This includes herniation of the cerebellum and fourth ventricle into the foramen magnum, flattening of the skull base, and spina bifida with meningomyelocele. Newborns may develop hydrocephalus shortly after birth due to blockage of the cerebral aqueduct.
• Dandy-Walker malformation. This condition involves severe hypoplasia or absence of the cerebellar vermis, cystic distention of the roof of the fourth ventricle, hydrocephalus, and possibly agenesis of the corpus callosum.
• Tuberous sclerosis. Characterised by firm, white nodules called tubers in the cortex and subependymal areas that may protrude into the ventricles, resembling 'candle drippings'. Facial angiofibromas (adenoma sebaceum) may also occur.
• von Hippel-Lindau disease. Involves multiple benign and malignant tumours such as hemangioblastomas of the retina, cerebellum, and medulla oblongata, as well as kidney and liver angiomas, and renal cell carcinomas.
• Sturge-Weber syndrome. A non-inherited condition that features angiomas in the brain, leptomeninges, and the same side of the face, commonly known as port-wine stains (nevus flammeus).

Syringomyelia Symptoms

• Bilateral loss of pain and temperature sensations in both arms is typically due to syringomyelia, a chronic condition resulting from a cavity (syrinx) forming in the spinal cord's central grey matter.
• This area is where pain fibres cross to join the opposite spinothalamic tract, leading to a loss of pain and temperature sense while touch and pressure senses remain intact.
• Other signs of syringomyelia include wasting of the small muscles in the hands (claw hand) and thoracic scoliosis.
• The cause of syringomyelia is unknown, but one type is linked to a Chiari malformation that blocks the foramen magnum.

Neural Tube Defects

Neural tube defects happen when the neural tube doesn't close properly. These defects can occur anywhere along the neural tube and are classified into two main types: cranial defects and caudal defects.

Cranial Defects

• Cranial defects occur when the cranial end of the neural tube fails to develop correctly, leading to a condition called anencephaly.
• Anencephaly is characterized by the absence of the forebrain, which is replaced by a disorganized mass of glial tissue and blood vessels known as cerebrovascular tissue.
• Ultrasound scans of affected individuals will typically reveal an abnormal head shape with the absence of a skull.

Caudal Defects

• Caudal defects include conditions such as spina bifida, which can manifest as spina bifida occulta. This occurs when the vertebral arches at the back do not close properly.
• Spina bifida occulta is a mild form of the condition where the meninges and spinal cord are present and intact.
• In more severe cases, if the meninges bulge out, the condition is referred to as meningocele.
• If both the meninges and the spinal cord protrude, the condition is known as meningomyelocele.

Neural tube defects are associated with factors such as maternal obesity and low levels of folate during pregnancy. Research has shown that taking folate supplements can significantly reduce the risk of these defects occurring during pregnancy.

Cerebral Hemorrhage

There are four types of cerebral hemorrhage: epidural, subarachnoid, subdural, and intraparenchymal.

Epidural hemorrhage

• Occurs in the space between the dura and the skull.
• Caused by severe trauma, often leading to a skull fracture.
• Results from the rupture of a meningeal artery, which supplies the dura.
• Bleeding is rapid because it comes from an artery, causing quick symptoms.
• Patients may appear normal for a few hours, known as a lucid interval.
• Can increase intracranial pressure, potentially leading to tentorial herniation and death.

Subarachnoid hemorrhage

• Less common than other types of hemorrhagic strokes, such as hypertensive intracerebral hemorrhage.
• Often caused by the rupture of a berry aneurysm, which is a congenital defect.
• These aneurysms are usually found at artery bifurcations.
• Rupture leads to significant bleeding in the subarachnoid space.
• Symptoms include severe headaches, often described as the worst headache ever.
• Other symptoms may be vomiting, neck pain, and stiffness due to irritation.
• In some cases, this can be fatal.

Subdural Hemorrhage

• Occurs in the space beneath the inner dura mater and the outer arachnoid layer.

Cerebral Ischemia

• Cerebral ischemia refers to a decrease in blood flow to the brain, which can be either general (global) or specific (localized).
• Global ischemia occurs when there is a widespread reduction in blood flow to the brain. This can happen during situations such as shock, cardiac arrest, or hypoxic episodes, such as near-drowning incidents or carbon monoxide poisoning. In this context, it is important to understand hypoxia, which refers to a lack of oxygen reaching the tissues.

Gross Changes from Global Hypoxia

• Watershed infarcts typically occur at the boundary between areas of the brain supplied by the anterior cerebral artery and the middle cerebral artery.
• Laminar necrosis is associated with the short, penetrating blood vessels that originate from the pial arteries.

Microscopic Changes from Global Hypoxia

• The earliest microscopic changes in the brain due to global hypoxia occur within the first 24 hours and include the formation of red neurons, which indicate acute neuronal injury. This is characterized by increased eosinophilic staining in the neuronal cytoplasm, followed by pyknosis (nuclear shrinkage) and karyorrhexis (nuclear fragmentation).
• Subacute changesoccur between 24 hours and 2 weeks after the insult, depending on individual factors. These changes include:
  • Tissue necrosis
  • Vascular proliferation
  • Reactive gliosis (proliferation of glial cells in response to injury)

Intracranial Aneurysms

• Charcot-Bouchard Aneurysms:These aneurysms develop when the wall of a cerebral artery weakens due to lipohyalinosis, a condition caused by the buildup of fats and a clear substance due to high blood pressure. This can result in:
  • Hypertensive bleeding, especially in areas supplied by the lenticulostriate arteries, which branch from the middle cerebral artery.
  • Small lacunar bleeds or larger ones that can damage the corpus striatum, including the putamen and internal capsule.
  • Common occurrences in the cerebellum and pons, leading to severe health issues, particularly with major bleeding.
• Berry Aneurysms:These are small, sac-like bulges caused by congenital weaknesses in blood vessel walls, commonly found in the Circle of Willis. They are typically located:
  • At the junction of the anterior communicating artery and the anterior cerebral artery.
  • At the junction of the middle cerebral artery and the posterior communicating artery.
• Atherosclerotic Aneurysms:These are spindle-shaped aneurysms usually found in major cerebral vessels. They:
  • Rarely rupture but may become obstructed by blood clots.
• Mycotic (Septic) Aneurysms: These aneurysms result from infected blood clots, most commonly associated with subacute bacterial endocarditis.
• Epidural Hemorrhage: The artery involved is typically the middle meningeal artery, a branch of the maxillary artery, often affected by fractures in the temporal region.
• Subarachnoid Bleeding: Excluding trauma, berry aneurysms are the leading cause.
• Subdural Hemorrhage: This usually results from the rupture of bridging veins.
• Vulnerable Cells: Purkinje cells in the cerebellum and pyramidal neurons in Sommer's sector of the hippocampus are particularly susceptible to damage from reduced blood flow.

CNS Infections

Progressive Multifocal Leukoencephalopathy (PML) is characterized by the presence of cloudy nuclei in oligodendrocytes in areas where myelin has been damaged due to viral infection.

Dorsalis

• Degeneration of the dorsal column
• Orthopaedic pain associated with Charcot joints
• Decreased deep tendon reflexes
• Shooting pain sensations
• Argyll-Robertson pupils, which react to accommodation but not to light
• Locomotor ataxia, or difficulty in coordinating movements
• Impaired proprioception, or awareness of body position

Syphilis

• Meningoencephalitis caused by HIV is characterized by the presence of microglial nodules in the brain. These nodules are composed of mononuclear cells, microglia, and scattered multinucleated giant cells.
• Cytomegalovirus (CMV) Infection. CMV infection in the central nervous system is marked by the presence of enlarged cells (cytomegaly) with intranuclear and cytoplasmic inclusions.
• Progressive Multifocal Leukoencephalopathy (PML). PML is caused by the JC polyomavirus infecting oligodendrocytes in the central nervous system. It leads to symptoms such as dementia, ataxia, and vision and speech difficulties. PML often occurs as a late complication in individuals with weakened immune systems, particularly those with AIDS.
• Prion Diseases. Prion diseases, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), fatal familial insomnia, and kuru, are characterized by spongiform changes in the grey matter without inflammation. These changes resemble "cluster of grapes" vacuolation. Prion diseases are linked to abnormal forms of prion protein (PrP), where the normal α-helix form (PrPc) is altered to an abnormal β-pleated sheet form (PrPsc). Mutations in the PRNP gene can lead to increased PrPsc formation, contributing to familial forms of CJD, GSS, and fatal familial insomnia.
• Rabies Virus Infection. The rabies virus, a single-stranded RNA rhabdovirus, causes distinct inclusions known as Negri bodies in neurons. Rabies is transmitted through the bite of an infected animal, usually a dog, and reaches the brain via peripheral nerves. Symptoms result from the destruction of brainstem neurons and include irritability, difficulty swallowing, throat spasms (leading to hydrophobia), seizures, and delirium. Rabies is nearly always fatal.
• Herpes Simplex Virus Infection. The herpes simplex virus induces Cowdry type A intranuclear inclusions in infected neurons and glial cells.
• Neurosyphilis. Neurosyphilis is the third stage of syphilis and includes syphilitic meningitis, paretic neurosyphilis, and tabes dorsalis. Syphilitic meningitis is characterized by lymphocyte and plasma cell infiltrates around blood vessels, leading to endarteritis and fibrosis of the meninges. Tabes dorsalis results from degeneration of the spinal cord's posterior columns, leading to loss of joint position sensation, ataxia, and loss of pain sensation, which can result in joint damage (e.g., Charcot joints) and Argyll-Robertson pupils.

CSF Findings in CNS Infections

• Normal values:Bacterial MeningitisTuberculous MeningitisViral MeningitisPressure. 50-180 mm water RaisedGross appearance. Clear and colourless TurbidClear (may clot)Protein. 20-50 mg/dL HighVery HighSlightly highGlucose. 40-70 mg/dL Very lowLowChloride. 116-122 µg/dL CellsNeutrophilsPleocytosisLymphocytosis

Meningitis

Meningitis, which is the inflammation of the arachnoid and cerebrospinal fluid (CSF), can be classified into three types: acute pyogenic, aseptic, and chronic meningitis. Each type has different causes and CSF findings.

Acute Pyogenic Meningitis

• Usually caused by bacteria.
• CSF appears cloudy (not bloody, as blood suggests a subarachnoid hemorrhage).
• Increased pressure, neutrophils, protein, and decreased glucose levels are observed.

Chronic Meningitis

• For example, meningitis caused by Mycobacterium tuberculosis.
• CSF appears clear, with only a slight increase in leukocytes (either mononuclear or mixed).
• Significant increase in protein, raised pressure, and normal or moderately decreased levels of glucose are noted.

Brain Abscesses and Subdural Empyemas

Brain abscesses and subdural empyemas are infections that impact the area surrounding the meninges rather than the meninges themselves. These conditions lead to:

• Increased CSF pressure, with a more significant increase in abscess cases due to the mass effect.
• Elevated levels of inflammatory cells, including lymphocytes and polymorphonuclear cells.
• Increased protein levels in the cerebrospinal fluid.
• Normal glucose levels in the CSF.
• Clear CSF appearance.

Encephalitis
Encephalitis, which also does not involve a direct infection of the meninges, results in:

• Clear CSF.
• Increased pressure in the CSF.
• Elevated protein levels.
• Normal glucose levels.
• Potentially increased lymphocytes, depending on the type of encephalitis.

However, the composition of CSF can vary based on the specific type of encephalitis involved.

Meningitis
Meningitis is primarily caused by organisms that originate from the nasopharynx. Viral meningitis is often transmitted through the:

• fecal-oral route.

Meningitis leads to:

• Increased CSF protein levels in viral, bacterial, and fungal meningitis cases.
• Decreased CSF glucose levels, particularly in bacterial and fungal meningitis cases.

Demyelinating Disorders

Multiple Sclerosis

• Primary CNS demyelination refers to the damage of myelin sheaths while the axons remain relatively unharmed.
• This type of demyelination is primarily seen in conditions like multiple sclerosis, perivenous encephalomyelopathies, and progressive multifocal leukoencephalopathy (PML).
• Multiple sclerosis (MS) is an illness of unknown origin that causes dispersed areas of primary demyelination throughout the central nervous system (CNS), especially in the white matter near the angles of the lateral ventricles.
• MS predominantly affects young adults between the ages of 20 and 40 years, with symptoms including:
• Visual disturbances
• Tremors
• Paresthesias (abnormal skin sensations)
• Lack of coordination
• The disease usually presents in a remitting-relapsing pattern.
• Initial signs may include weakness in the lower limbs and visual problems accompanied by retrobulbar pain.
• In addition to the Charcot triad, a characteristic sign of MS is internuclear ophthalmoplegia (INO), or MLF syndrome, resulting from demyelination of the medial longitudinal fasciculus.
• This condition leads to:
• Medial rectus palsy during lateral gaze
• Monocular nystagmus in the outward-moving eye, along with convergence
• Cerebrospinal fluid (CSF) analysis in MS patients typically shows:
• Elevated T lymphocytes
• Increased protein levels
• Normal glucose concentrations
• Protein electrophoresis of the CSF often reveals oligoclonal bands, which are specific spikes, although this finding is not exclusive to MS.

Neuromyelitis Optica (Devic Disease)

• This disorder is characterized by the simultaneous occurrence of bilateral optic neuritis and demyelination of the spinal cord.

Degenerative Disorders

Degenerative diseases of the CNS are conditions that affect the gray matter, characterized by the gradual loss of neurons in specific brain regions.

Alzheimer's Disease (AD)

• Alzheimer's disease (AD) is the most common cause of dementia in older adults, followed by vascular multi-infarct dementia and diffuse Lewy body disease.
• AD usually begins slowly with memory problems and progressively leads to dementia.
• Histologically, AD is marked by the presence of numerous neurofibrillary tangles and senile plaques containing amyloid protein.
• Although tangles and plaques can be found in other conditions (such as neurofibrillary tangles in Down syndrome), they are more abundant in AD.
• Silver stains are used to visualize these tangles and plaques, while Congo red detects amyloid in plaques and blood vessel walls.
• AD also exhibits a high number of Hirano bodies, and granulovacuolar degeneration affects more than 10% of the neurons in the hippocampus.
• Grossly, brain atrophy (narrowed gyri and widened sulci) is primarily observed in the frontal and superior temporal lobes.
• Age is the main risk factor for AD, and the gene for beta-amyloid (A-beta) is located on chromosome 21.
• Individuals with trisomy 21 (Down syndrome) have a significantly increased risk of developing AD at an earlier age.

Parkinson's Disease (PD)

• Idiopathic Parkinson's disease (PD) is the most prevalent cause of parkinsonism.
• In PD, Lewy bodies (eosinophilic intracytoplasmic inclusions) are found in the surviving neurons of the substantia nigra.
• No mutations in the gene encoding alpha-synuclein have been identified in Shy-Drager syndrome.
• Huntington's disease (HD) impacts the extrapyramidal system, leading to the atrophy of the caudate nuclei and putamen.
• The exact cause of AD remains unclear, but it is evident that multiple pathways contribute to the disease.
• AD is associated with abnormalities in four specific genes.
• The cleavage of the beta-amyloid precursor protein (beta-APP) by alpha-secretase prevents the formation of beta-A.
• However, cleavage by beta-secretase (BACE-1) or gamma-secretase produces fragments that aggregate into harmful amyloid fibrils.
• While beta-amyloid deposition is crucial, it is not sufficient for the development of AD.
• Early-onset familial Alzheimer's is linked to mutations in presenilins, with the presenilin 1 (PS1) gene located on chromosome 14 and the presenilin 2 (PS2) gene on chromosome 1.

Lewy Body Disorders

• Lewy bodies are intracytoplasmic eosinophilic inclusions composed of fine filaments, densely packed in the center but looser at the edges.
• These filaments include neurofilament antigens, parkin, and ubiquitin, but the primary component is alpha-synuclein.
• The presence of Lewy bodies can be observed in various disorders (Lewy body disorders) depending on their location.
• In classic Parkinson's disease, Lewy bodies are found in the nigrostriatal system, leading to extrapyramidal movement disorders.
• In Lewy body dementia, they are located in the cerebral cortex, causing dementia and ranking as the third most common cause of dementia.
• In Shy-Drager syndrome, Lewy bodies are present in sympathetic neurons in the spinal cord, causing autonomic dysfunction, including orthostatic hypotension, impotence, abnormal sweat and salivary gland secretion, and pupillary issues.

Huntington's Disease (HD)

• Huntington's disease is characterized by choreiform movements and progressive dementia, usually appearing after the age of 30.
• It is an autosomal dominant disorder caused by an abnormal gene (with CAG repeats) on chromosome 4.
• There is degeneration of GABA neurons in the striatum, leading to decreased function (less inhibition) and increased movement.

Huntington's Disease and Other Genetic Conditions

• Huntington's Disease is linked to CAG repeats in the DNA. This means that there is a repeated sequence of three nucleotides, cytosine (C), adenine (A), and guanine (G), in the genetic material. This repeat can cause the disease because it leads to the production of an abnormal protein that damages brain cells.
• Other Conditions such as fragile X syndrome, myotonic dystrophy, and spinal and bulbar muscular atrophy are caused by different mechanisms involving long sequences of three nucleotides that repeat. These conditions are not caused by CAG repeats but by other types of nucleotide repeats in the DNA.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig's disease, is a serious condition that impacts the motor neurons in the body. These motor neurons are crucial for controlling muscle movements and are mainly located in three areas:

• Anterior Horn Cells: These are found in the spinal cord and are responsible for sending signals to the muscles to initiate movement.
• Motor Nuclei of the Brainstem: These neurons control muscles involved in essential functions such as breathing, swallowing, and speech.
• Upper Motor Neurons of the Cerebral Cortex: These neurons send signals from the brain to the spinal cord, helping to coordinate voluntary movements.

Symptoms and Progression of ALS
Early Symptoms
The initial signs of ALS can include:

• Weakness:. general feeling of weakness in the muscles, making it difficult to perform everyday tasks.
• Cramping: Muscles may cramp more frequently, causing discomfort.

Disease Characteristics
ALS shows features of both lower motor neuron (LMN) and upper motor neuron (UMN) diseases:

• Lower Motor Neuron (LMN) Symptoms:
  Weakness: Progressive muscle weakness.
  Fasciculations: Involuntary muscle twitches.
• Upper Motor Neuron (UMN) Symptoms:
  Spasticity: Increased muscle stiffness.
  Hyperreflexia: Exaggerated reflexes.

Advanced Stages
As ALS progresses, the symptoms worsen and may include:

• Muscle Atrophy: Muscles begin to shrink due to lack of use and nerve signals.
• Fasciculations: Muscle twitches become more prominent.

Reflex Changes
Reflexes may become hyperactive in both the upper and lower limbs. A positive extensor plantar reflex, also known as the Babinski reflex, may occur due to the loss of upper motor neurons.

Disease Progression and Complications
ALS is a rapidly progressing disease. As it advances, complications related to breathing and respiratory function can arise, which may ultimately lead to death.

Tumors 

CNS tumors can be classified into various types, including gliomas, neuronal tumors, poorly differentiated neoplasms, meningiomas, and metastatic tumors.

1. Gliomas

a. Astrocytoma

• Astrocytoma is the most prevalent primary brain tumor in adults and ranges from low-grade to high-grade tumors, with glioblastoma multiforme being the most aggressive form.
• Grade I astrocytomas are the least aggressive and can be challenging to differentiate from reactive astrocytosis.
• Grade II astrocytomas exhibit some microscopic variation.
• Grade III astrocytomas, known as anaplastic astrocytomas, show significant cell variation and increased cell division.
• Grade IV astrocytomas, or glioblastoma multiforme, are highly aggressive tumors characterized by abnormal blood vessel growth and areas of cell death, often crossing the brain's midline (referred to as the "butterfly tumor").

Low-grade astrocytomas can progress to higher-grade tumors, such as secondary glioblastoma multiforme, due to genetic alterations like issues with the p16/CDKN2A gene or increased levels of PDGF-A and its receptor. However, not all low-grade astrocytomas progress to glioblastomas.

b. Oligodendroglioma

• Oligodendrogliomas primarily affect the cerebrum (hemispheres) in adults and typically grow slowly, but they have a tendency to recur.
• Some oligodendrogliomas can exhibit rapid and aggressive growth and may contain a malignant astrocytoma component.
• Histologically, oligodendrogliomas are characterized by sheets of cells with clear halos, often referred to as the "fried-egg" appearance, and varying degrees of calcification visible on X-rays.
• Cytogenetic changes, such as deletions on 19q or 1p, are crucial for treatment decisions, as only oligodendrogliomas with these deletions respond to chemotherapy.

c. Ependymoma

• Ependymomas typically develop adjacent to the ependyma-lined ventricular system, including the central canal of the spinal cord.
• Spinal cord ependymomas are commonly associated with neurofibromatosis type 2.

2. Neuronal Tumors

• The most prevalent CNS tumor featuring mature-looking neurons (ganglion cells) is ganglioglioma, which is usually located in the temporal lobe and often includes binucleated ganglion cells.

3. Poorly Differentiated Neoplasms

• The most common poorly differentiated neoplasm is medulloblastoma, along with atypical teratoid/rhabdoid tumors.

a. Medulloblastoma

• Medulloblastoma is a type of primitive neuroectodermal tumor (PNET) that can be found within or outside the CNS.
• Symptoms may include weakness in the hands and forearms, slight stiffness in the legs, and heightened reflexes without sensory changes, which can mimic conditions like amyotrophic lateral sclerosis (ALS).
• Treatments for ALS, such as riluzole (an NMDA antagonist) and baclofen, may be used in these cases.

4. Meningioma

• Meningiomas are tumors attached to the dura mater, arising from the arachnoid villi of the brain or spinal cord.
• These tumors typically develop in middle or later life, although some cases occur in individuals aged 20 to 40.
• Meningiomas commonly arise along the venous sinuses, such as the parasagittal region, sphenoid wings, and olfactory groove.

Note:

• Both oligodendroglioma and craniopharyngioma often exhibit calcification.
• Oligodendroglioma is usually located in the frontal lobe, while craniopharyngioma occurs around the third ventricle with suprasellar calcification.

Common Intracranial Tumours

• Breast
• Skin (melanoma)
• Kidney
• GIT

Meningiomas: Cytogenetic Abnormalities

• Deletion of region 12 on chromosome 22 is a common cytogenetic abnormality in meningiomas.
• However, there are other significant abnormalities associated with meningiomas as well.

Medulloblastomas: Genetic Abnormalities

• Duplication of the long arm of chromosome 17 is the most common genetic abnormality seen in medulloblastomas.

CNS Tumours and Age

Astrocytomas occur predominantly in:

• the cerebral hemispheres in adults and the elderly,
• the cerebellum and pons in children,
• the spinal cord in young adults.

Pilocytic Astrocytoma:

• The pilocytic astrocytoma, also known as juvenile pilocytic astrocytoma, is the most common brain tumour in children.
• It is characterised by its location in the cerebellum and is associated with a better prognosis.
• Meningiomas peak in incidence during the fourth and fifth decades of life.
• Glioblastoma multiforme, a highly malignant tumour, primarily occurs in adults.
• Oligodendrogliomas also involve the cerebrum in adults.
• Ependymomas are most frequently found in the fourth ventricle of the brain.
• Choroid Plexus Papilloma. This variant of ependymoma is most commonly found in the lateral ventricles of young boys.
• Medulloblastoma :
• Medulloblastomas arise exclusively in the cerebellum, with the highest incidence towards the end of the first decade of life.
• In children, medulloblastomas are typically located in the midline of the cerebellum, while in adults, they are found in more lateral locations.

Peripheral Nerve Sheath Tumours

Schwannomas

Peripheral nerve sheath tumours, including Schwannomas and acoustic neuromas, are important because they impact nerve function. These tumours are usually non-cancerous and often present as highly cellular spindle cell growths, sometimes containing elements that resemble bone, cartilage, and muscle.

Schwannomas, also known as neurilemomas, are typically benign, single, encapsulated tumours found in nerve sheaths. They can occur on peripheral nerves, spinal nerves, or cranial nerves.

Acoustic neuromas are a specific type of Schwannoma, commonly located at the cerebellopontine angle or within the internal acoustic meatus. When these tumours are small, they can cause symptoms by pressing on cranial nerves CN VIII (the vestibulocochlear nerve) and CN VII (the facial nerve).

• Symptoms related to CN VIII may include:
• Unilateral tinnitus (ringing in one ear)
• Unilateral hearing loss
• Vertigo (dizziness)

If the facial nerve (CN VII) is affected, symptoms may include:

• Facial weakness
• Loss of corneal reflex

Histologically, an acoustic neuroma is characterized by:

• Cellular areas known as Antoni A areas
• Loose, edematous areas known as Antoni B areas

Verocay bodies, which are clusters of palisaded nuclei, may be observed in the more cellular regions of the tumour.

Familial Tumour Syndromes

1. Tuberous Sclerosis

• A genetic disorder passed down in families (autosomal dominant) known as tuberous sclerosis is characterised by the presence of angiofibromas, seizures, and intellectual disability.
• Individuals with this condition develop hamartomas in the central nervous system, referred to as "tubers," which are made up of disorganised neurons and glial cells.
• Tuberous sclerosis is associated with various tumours, including subepedymal giant cell tumours, rhabdomyomas of the heart, and angiomyolipomas of the kidney.
• Mutations at specific locations, such as the TSC1 locus (hamartin) and the TSC2 locus (tuberin), are linked to this condition. These mutations inhibit mTOR, a crucial regulator of cell growth.

Note:

• mTOR activity problems are associated with various hamartoma syndromes, including tuberous sclerosis, von Hippel-Lindau syndrome, Peutz-Jegher's syndrome, and PTEN-related hamartoma syndromes.

2. von Hippel-Lindau Disease

• von Hippel-Lindau disease is a rare genetic disorder passed down in families (autosomal dominant) that leads to the development of multiple benign and malignant growths.
• Affected individuals may experience hemangioblastomas in the retina and brain (specifically in the cerebellum and medulla oblongata), angiomas in the kidney and liver, and renal cell carcinomas, which are found in 25 to 50% of cases and are typically multiple and bilateral.

3. Neurofibromatosis Type 1

• Neurofibromatosis type 1 (NF-1) is a genetic disorder passed down in families (autosomal dominant) characterised by the presence of café-au-lait skin macules, axillary freckling, and multiple neurofibromas.
• Individuals with NF-1 also develop plexiform neurofibromas and Lisch nodules (pigmented iris hamartomas), with 95% of patients experiencing these features after the age of six.
• There is an increased risk of developing meningiomas or pheochromocytomas, as well as the potential for malignant transformation of a neurofibroma into a neurofibrosarcoma.
• The gene associated with NF-1 is located on chromosome 17 and encodes neurofibromin, which plays a role in regulating the p21 oncoprotein.

4. Neurofibromatosis Type 2

• Neurofibromatosis type 2 (NF-2) is a genetic disorder passed down in families (autosomal dominant) where individuals develop a variety of tumours, primarily bilateral VIII nerve schwannomas and multiple meningiomas.
• Some patients may also experience gliomas, typically ependymomas of the spinal cord.
• Non-neoplastic lesions associated with NF-2 include schwannosis (nodular ingrowth of Schwann cells into the spinal cord), meningioangiomatosis (proliferation of meningeal cells and blood vessels into the brain), and glial hamartia (nodular collections of glial cells in abnormal locations).
• The NF2 gene, located on chromosome 22, encodes for merlin, a protein involved in tumour suppression.

Acoustic Neuroma

• Acoustic neuroma, also known as vestibular schwannoma, is a type of tumour that arises from Schwann cells covering the vestibulocochlear nerve (CN VIII).