CNS + Eyes Flashcards
What is medulloblastoma?
Medulloblastoma is a malignant brain tumor that occurs predominantly in children and exclusively in the cerebellum.
What markers are nearly always expressed in medulloblastoma?
Neuronal and glial markers are nearly always expressed in medulloblastoma.
What is the prognosis for untreated patients with medulloblastoma?
The prognosis for untreated patients is dismal; however, medulloblastoma is exquisitely radiosensitive.
What are primitive neuroectodermal tumors (PNETs), and how are they related to medulloblastoma?
Tumors of similar histologic type and a poor degree of differentiation found elsewhere in the nervous system are called primitive neuroectodermal tumors (PNETs), which are related to medulloblastoma.
Describe the morphology of medulloblastoma.
Medulloblastomas are extremely cellular, with sheets of anaplastic (“small blue”) cells. Individual tumor cells are small, with little cytoplasm and hyperchromatic nuclei.
Focal neuronal differentiation may be seen in the form of the Homer Wright or neuroblastic rosette.
What are some clinical features associated with medulloblastoma?
Tumors with MYC amplifications are associated with poor outcomes, while those linked with mutations in genes of the WNT signaling pathway have a more favorable course.
Many tumors also have mutations that activate the sonic hedgehog (shh) pathway, which plays a critical role in tumorigenesis.
T167 What is cerebral edema?
Cerebral edema is the accumulation of excess fluid within the brain parenchyma, resulting in widened gyri, narrowing of sulci, and compression of ventricles. It can be focal or diffuse.
What are the two types of cerebral edema that often occur together, particularly after injury?
The two types of cerebral edema are vasogenic edema and cytotoxic edema.
Describe vasogenic edema
Vasogenic edema occurs when the integrity of the normal blood-brain barrier (BBB) is disrupted, allowing fluid to shift from the vascular compartment into the extracellular spaces of the brain.
It can be either generalized or localized and is often associated with focal lesions such as primary metastatic tumors or abscesses.
Describe cytotoxic edema
Cytotoxic edema involves an increase in the intracellular fluid, secondary to neuronal and glial cell membrane injury, such as that following a generalized hypoxic-ischemic insult or exposure to certain toxins.
What is interstitial edema?
Interstitial edema results from increased intracerebral influx of cerebrospinal fluid (CSF) through the ependymal lining, leading to fluid accumulation in the periventricular white matter. It is typically a complication of hydrocephalus.
How does the brain appear macroscopically in generalized cerebral edema?
In generalized edema, the gyri are flattened, the sulci are narrowed, and the ventricular cavities are compressed, giving the brain a softer appearance that seems to “overfill” the cranial vault.
What is intracranial pressure (ICP)?
Intracranial pressure is the pressure exerted inside the skull, which can increase due to various factors and may result in or from brain injury.
What are some causes of increased intracranial pressure?
Some causes of increased intracranial pressure include:
a. Rise in pressure of the cerebrospinal fluid (CSF), such as in increased CSF volume or meningitis.
b. Tumors.
c. Hydrocephalus.
d. The added mass of epidural, subdural, and intracranial hematomas.
e. Cerebral edema, which can develop around large contusions, from diffuse vascular injury, or as a result of hypoxic-ischemic encephalopathy (HIE).
How can increases in intracranial pressure damage the brain?
Increases in intracranial pressure can damage the brain by:
Decreasing perfusion, which can lead to the collapse of brain capillaries and result in global ischemia.
Displacing tissue across dural barriers inside the skull or through openings in the skull, known as herniation.
What is herniation?
Herniation is the displacement of brain tissue between the dural barriers or out of the skull, occurring when the volume inside the skull increases beyond the limit permitted by compression of veins and displacement of cerebrospinal fluid (CSF) due to increased intracranial pressure.
What are the main types of herniation?
Subfalcine, Transtentorial (uncinate) herniation, Tonsillar herniation, Retrograde transtentorial herniation., Herniation out of the skull, not through the foramen magnum.
Subfalcine (cingulate) herniation
Unilateral or asymmetric expansion of a cerebral hemisphere displaces the cingulate gyrus under the edge of the falx, potentially compressing branches of the anterior cerebral artery.
Transtentorial (uncinate) herniation
The medial aspect of the temporal lobe is compressed against the free margin of the tentorium,
leading to compression of the third cranial nerve (resulting in pupillary dilation and impairment of ocular movements), compression of the posterior cerebral artery (resulting in ischemic injury to the primary visual cortex), and potentially ipsilateral hemiparesis if the contralateral cerebral peduncle is compressed against the tentorium.
Tonsillar herniation
Displacement of the cerebellar tonsils through the foramen magnum, causing compression of vital respiratory and cardiac centers in the medulla and presenting a life-threatening situation.
What is hydrocephalus?
Hydrocephalus is the accumulation of excessive cerebrospinal fluid (CSF) within the ventricles of the brain.
What are the main reasons for hydrocephalus?
Impaired CSF flow.
Impaired CSF resorption.
Rarely, overproduction of CSF (e.g., tumor of the choroid plexus).
What are the two types of hydrocephalus?
- Non-communicating hydrocephalus: Caused by CSF flow obstruction, resulting in enlargement of a portion of the ventricles while the remainder doesn’t. Mainly due to obstruction of the foramen of Monro or compression of the cerebral aqueduct.
- Communicating hydrocephalus: Caused by impaired CSF reabsorption in the absence of CSF flow obstruction between the ventricles and the subarachnoid space, leading to enlargement of the entire ventricular system.
What is the difference in presentation between hydrocephalus developing in infancy and that developing after cranial suture closure?
Hydrocephalus developing in infancy before the closure of cranial sutures is associated with enlargement of the head. In contrast, hydrocephalus developing after fusion of the sutures is associated with expansion of the ventricles and increased intracranial pressure, without a change in head circumference.
What is hydrocephalus ex vacuo?
Hydrocephalus ex vacuo is the dilation of the ventricular system with a compensatory increase in CSF volume secondary to a loss of brain parenchyma, such as after infarcts or with degenerative diseases.
T168 What are neural tube defects (NTDs)?
Neural tube defects are malformations of the spinal cord and brain caused by the failure of closure of the neural tube during embryonic development.
What is the most common cause of NTDs, and how can it be prevented?
Folate deficiency during the initial weeks of gestation increases the risk of NTDs. Supplementation with folate has been shown to reduce the risk of NTDs.
What are the main types of spina bifida, and how do they differ?
- Spina bifida occulta: Vertebral arches are absent, but there is no protrusion of the spinal cord or meninges.
- Meningocele: A meningeal sac protrudes through the bone defect in the lumbosacral area.
- Meningomyelocele: The sac contains malformed spinal cord tissue. In severe cases, neural tissue lies on the dorsal surface of the fetus.
What are the malformations associated with the anterior end of the neural tube?
- Anencephaly: The brain protrudes through a defect in the cranial vault and is gradually destroyed, leaving a small, disorganized mass of neural tissue.
- Encephalocele: Brain tissue protrudes through a defect in the skull, usually in the occipital area. Large occipital encephaloceles can be incompatible with life.
- Craniorachischisis: Defective closure of the hindbrain-cervical junction.
How can NTDs be detected early?
Screening for elevated α-fetoprotein levels has increased the early detection of neural tube defects.
What are forebrain malformations characterized by?
Forebrain malformations are characterized by abnormalities in the development of neurons and glial cells, resulting in structural anomalies in the brain.
Các dị tật ở não trước được đặc trưng bởi những bất thường trong sự phát triển của các tế bào thần kinh và tế bào đệm, dẫn đến các bất thường về cấu trúc trong não.
What are the main types of forebrain malformations?
- Megalencephaly (abnormally large brain volume) or microencephaly (abnormally small brain volume).
- Lissencephaly (agyria) or pachygyria: Absent or reduced gyration of the brain, leading to a smooth-surfaced cortex with abnormal thickening.
- Polymicrogyria: Increased number of irregularly formed gyri, resulting in a bumpy or cobblestone-like brain surface.
- Holoprosencephaly: Disruption of the normal midline division of the forebrain, ranging from mild forms with absence of olfactory bulbs to severe forms with a single undivided brain hemisphere.
- Focally disordered cortex (dysplastic cortex) and neuronal heterotopias: Abnormalities in cortical organization, with neurons stranded beneath the cortex in nodules or bands.
What are some causes of forebrain malformations?
Mutations in genes that control neuronal migration are implicated in forebrain malformations. Other factors such as fetal alcohol syndrome and viral infections (e.g., HIV-1 acquired in utero) can also contribute to these malformations.
What are posterior fossa anomalies characterized by?
Posterior fossa anomalies result in abnormalities of the cerebellum.
Describe the Chiari type II malformation
là một rối loạn cấu trúc nghiêm trọng, trong đó hành não và tiểu não bị đẩy xuống qua lỗ lớn (foramen magnum) vào ống sống. Thường liên quan đến tật nứt đốt sống (spina bifida).
The Chiari type II malformation is characterized by abnormalities of the posterior fossa, including a large foramen magnum, low insertion of the tentorium, and a shallow posterior fossa.
This results in crowding and displacement of the cerebellum and brainstem into the cervical canal. Additionally, the cerebellum may prolapse upward through the tentorial opening.
What is the Chiari type I malformation?
The Chiari type I malformation involves low-lying cerebellar tonsils that extend through the foramen magnum.
What is Dandy-Walker malformation?
Dandy-Walker malformation is a spectrum of posterior fossa abnormality characterized by complete or partial agenesis of the cerebellar vermis, with preservation of the cerebellar hemispheres.
This condition is associated with obstruction of cerebrospinal fluid (CSF) flow out of the fourth ventricle, leading to dilation of the ventricle and the formation of a large posterior fossa cyst.
What are the major types of injury that occur in the perinatal period?
The major types of injury that occur in the perinatal period are hemorrhages and infarcts.
What is cerebral palsy?
Cerebral palsy is a term for nonprogressive neurologic motor deficits characterized by spasticity, dystonia, ataxia or athetosis, and paresis attributable to injury occurring during the prenatal and perinatal periods.
What is a common risk factor for intraparenchymal hemorrhage in premature infants?
In premature infants, there is an increased risk of intraparenchymal hemorrhage within the germinal matrix, most often adjacent to the anterior horn of the lateral ventricle.
What is periventricular leukomalacia?
Periventricular leukomalacia refers to infarcts that may occur in the supratentorial periventricular white matter, especially in premature babies. The residua of these infarcts are chalky yellow plaques consisting of discrete regions of white matter necrosis and mineralization.
T169 What are the two main classifications of meningitis based on the appearance of cerebrospinal fluid?
Meningitis can be classified as purulent (bacterial) or serous (viral) based on the appearance of cerebrospinal fluid.
What are the common signs of infectious meningitis?
Common signs of infectious meningitis include headache, neck stiffness, fever, photophobia, nausea and vomiting, mental confusion, somnolence, Brudzinski sign, and Kernig sign.
What are the most common bacteria causing acute bacterial meningitis?
The most common bacteria causing acute bacterial meningitis include Group B streptococcus, E. coli, and Listeria monocytogenes affecting neonates;
Neisseria meningitidis affecting children and young adults; and Streptococcus pneumoniae affecting adults and the elderly.
What are the common signs of aseptic (viral) meningitis?
Common signs of aseptic (viral) meningitis include fever, photophobia, and meningeal irritation.
What is the typical cell type seen in cerebrospinal fluid analysis for bacterial meningitis?
Neutrophils are typically seen in cerebrospinal fluid analysis for bacterial meningitis.
What are the main causes of chronic meningitis?
Chronic meningitis is mainly caused by mycobacteria (e.g., M. tuberculosis) and spirochetes (e.g., Treponema pallidum).
What are the signs of tuberculous meningitis?
Signs of tuberculous meningitis include headache, malaise, mental confusion, and vomiting.
What are the typical findings in cerebrospinal fluid analysis for tuberculous meningitis?
In cerebrospinal fluid analysis for tuberculous meningitis, there is a moderate increase in protein level and mononuclear cells, while glucose level is reduced or normal.
Trong phân tích dịch não tủy cho viêm màng não do lao, có sự gia tăng vừa phải mức protein và các tế bào đơn nhân, trong khi mức glucose giảm hoặc bình thường.
What is a characteristic lesion associated with tuberculous meningitis?
A characteristic lesion associated with tuberculous meningitis is a tuberculoma, which is a circumscribed intraparenchymal mass.
What are the neurological manifestations of paretic neurosyphilis?
Paretic neurosyphilis manifests as progressive loss of mental and physical functions with mood alterations, terminating in severe dementia.
What is tabes dorsalis?
Tabes dorsalis is a form of neurosyphilis resulting from damage to the sensory nerves in the dorsal roots, leading to impaired joint position sense, ataxia, loss of pain sensation, and other sensory disturbances.
What are the complications of meningitis?
Complications of meningitis include:
Hydrocephalus resulting from obstruction of CSF due to scarring of meninges
Neurologic defects due to destruction of underlying brain tissue
Epilepsy due to focal damage of the brain or scarring of meninges
Abscess formation in the brain or subdural spaces (especially in children)
Spinal or cranial nerve compression or constriction, as seen in tabes dorsalis.
What is viral encephalitis?
Viral encephalitis is a parenchymal infection of the brain almost always associated with meningeal inflammation, known as meningoencephalitis.
It is primarily caused by viruses and can involve either diffuse inflammation throughout the brain or localized inflammation to specific areas.
Characteristic histologic features include perivascular and parenchymal mononuclear cell infiltrates, microglial nodules, and neuronophagia.The nervous system is highly susceptible to viruses such as rabies and polio.
Additionally, the CNS can be damaged by immune mechanisms following systemic viral infections, and intrauterine viral infections may lead to congenital malformations like those seen in rubella.
Arboviruses morphology, characteristics
Herpes simplex virus morphology, characteristics
Cytomegalovirus morphology, characteristics
Polio and rabies morphology, characteristics
Hiv virus
Jc virus
What are the characteristics of fungal encephalitis?
Fungal infections in the brain typically result in parenchymal granulomas or abscesses, often accompanied by meningitis.
What are the distinctive patterns of fungal infections in the brain?
- Candida albicans: It produces multiple microabscesses, with or without granuloma formation.
- Mucormycosis: Usually affects the nasal cavity or sinuses of diabetic patients with ketoacidosis. It may spread to the brain through vascular invasion or direct extension through the cribriform plate.
- Aspergillus fumigatus: Causes widespread septic hemorrhagic infarctions due to its predilection for blood vessel wall invasion and subsequent thrombosis.
- Cryptococcus neoformans: Can lead to meningitis and meningoencephalitis, particularly in immunocompromised individuals. The CSF may show few cells but elevated protein, with mucoid encapsulated yeasts visible on India ink preparations.
Extension into the brain follows vessels in the Virchow-Robin spaces, resulting in a “soap bubble”–like appearance.Other fungi such as Histoplasma capsulatum,
Coccidioides immitis, and Blastomyces dermatitidis may also infect the CNS, especially in immunosuppressed individuals, particularly in endemic areas
What is cerebral toxoplasmosis, and what are its clinical manifestations?
Cerebral toxoplasmosis is a cerebral infection caused by the protozoan Toxoplasma gondii, often occurring in immunosuppressed adults or newborns infected in utero. In adults, symptoms are subacute and may be both focal and diffuse. Lesions typically exhibit edema, resulting in ring-enhancing lesions
What are the clinical features of cerebral toxoplasmosis in newborns infected in utero?
In newborns, cerebral toxoplasmosis manifests as the triad of chorioretinitis, hydrocephalus, and intracranial calcifications. The severity of CNS abnormalities is highest when the infection occurs early in gestation, potentially leading to obstruction of the aqueduct of Sylvius and hydrocephalus.
Describe the morphological features of cerebral toxoplasmosis in immunosuppressed adults
In immunosuppressed adults, cerebral toxoplasmosis presents with abscesses, often multiple and commonly involving the cerebral cortex and deep gray nuclei
Acute lesions show central necrosis with variable petechiae, surrounded by acute and chronic inflammation, macrophage infiltration, and vascular proliferation.
Ở người lớn bị suy giảm miễn dịch, bệnh toxoplasmosis não biểu hiện dưới dạng các áp xe, thường là nhiều và thường liên quan đến vỏ não và các nhân xám sâu. Các tổn thương cấp tính cho thấy hoại tử trung tâm với các nốt xuất huyết nhỏ khác nhau, bao quanh bởi viêm cấp tính và mãn tính, thâm nhiễm đại thực bào và tăng sinh mạch máu.
- Bệnh toxoplasmosis não ở người lớn bị suy giảm miễn dịch thường xuất hiện dưới dạng áp xe, thường là nhiều, liên quan đến vỏ não và các nhân xám sâu.
- Tổn thương cấp tính: Hoại tử trung tâm, nốt xuất huyết nhỏ, viêm cấp tính và mãn tính, thâm nhiễm đại thực bào và tăng sinh mạch máu.
What is cysticercosis, and how does it manifest within the brain?
Cysticercosis is the result of an end-stage infection by the tapeworm Taenia solium. Larval organisms, if ingested, encyst within the brain and subarachnoid space.
Manifestations typically include mass lesions and seizures. The cyst contains a smooth lining, and the body wall and hooklets from mouth parts are often identifiable.
Explain the clinical syndromes associated with amebiasis.
Amebiasis can manifest with different clinical syndromes depending on the causative pathogen. Naegleria spp. cause rapidly fatal necrotizing encephalitis associated with swimming in warm nonflowing fresh water.
Acanthamoeba can lead to chronic granulomatous meningoencephalitis.
T171 What are transmissible spongiform encephalopathies (TSEs), and what causes them?
TSEs are neurodegenerative diseases caused by the accumulation of abnormal prion proteins resulting from misfolding of normal prion proteins (PrPc).
This abnormal folding, converting PrPc into PrPSc, leads to neuronal degeneration and loss. PrPSc is resistant to proteases and forms insoluble aggregates.
How do prion diseases propagate and spread within the body?
Prion diseases are unique in that they are self-propagating and transmissible. Once abnormal PrPSc is generated endogenously or introduced into the body, it converts normal PrPc into abnormal forms. This propagation process perpetuates the disease within the body.
What are the main categories of human prion diseases, and how do they differ?
Human prion diseases can be categorized into sporadic, familial, and environmentally acquired forms. Sporadic cases, like sporadic Creutzfeldt-Jakob disease (sCJD), arise spontaneously due to spontaneous conformational changes in PrPc.
Familial cases (fCJD) result from mutations in the PRNP gene, accelerating the rate of conformational change.
Environmentally acquired cases, such as iatrogenic transmission or ingestion of contaminated meat (e.g., BSE), result from exposure to infectious PrPSc.
Describe the pathological features of prion diseases in the brain
Pathologically, prion diseases exhibit intracytoplasmic vacuoles in neurons and glial cells.
As the disease progresses, vacuolization becomes more pronounced, and the cortical neuropil develops a spongy appearance, leading to the term “spongiform encephalopathy.”
What is Creutzfeldt-Jakob disease (CJD), and how does it typically occur?
CJD is the most common spongiform encephalopathy, often occurring sporadically but rarely associated with exposure to prion-infected human tissue, such as through human growth hormone or corneal transplant.
What are the clinical features of Creutzfeldt-Jakob disease (CJD)?
CJD manifests as a rapidly progressive dementing illness, characterized by a short duration from the onset of subtle changes in memory and behavior to death in less than a year.
Symptoms include rapidly progressive dementia, ataxia (cerebellar involvement), and startle myoclonus. EEG may show spike-wave complexes.
Describe the pathological features of Creutzfeldt-Jakob disease (CJD) in the brain.
Pathologically, CJD is characterized by spongiform transformation of the cerebral cortex and deep gray matter structures (such as the caudate and putamen).
There is typically little macroscopic evidence of brain atrophy, and no inflammatory infiltrate is present. The presence of proteinase K–resistant PrPsc in tissue confirms the diagnosis.
Thông thường, không có bằng chứng đại thể rõ ràng về sự teo não, và không có sự thâm nhập viêm hiện diện. Sự có mặt của PrPsc kháng proteinase K trong mô xác nhận chẩn đoán.
What is Variant Creutzfeldt-Jakob Disease (vCJD), and how does it differ from classic CJD?
vCJD is a form of the disease associated with exposure to bovine spongiform encephalopathy (“mad cow disease”).
It affects young adults and often presents with behavioral disorders in early stages.
The neurologic syndrome progresses more slowly compared to other forms of CJD.
Pathologically, it shares a similar appearance with other types of CJD, but vCJD also exhibits abundant cortical amyloid plaques surrounded by spongiform change.
What distinguishes Familial Fatal Insomnia from other prion diseases?
Familial Fatal Insomnia is an inherited form of prion disease characterized by severe insomnia and an exaggerated startle response.
T172 What is neurodegeneration, and what are its main characteristics?
Neurodegeneration is the progressive, slow, and irreversible loss of neurons within the gray matter, often due to the accumulation of proteins that damage neurons. This process is characterized by the loss of memory, language, and planning abilities, with normal consciousness.
What are the two main groups of clinical manifestations associated with neurodegenerative diseases?
The two main groups are dementias, which affect the cerebral cortex and result in loss of memory, language, and planning abilities, and movement disorders, which affect the basal ganglia and brain stem.
What is Alzheimer’s disease, and what are its key features?
Alzheimer’s disease is a degenerative disease of the cerebral cortex and is the most common cause of dementia in the elderly, accounting for 75% of cases.
It primarily affects the elderly, with risk increasing with age.
Genetic factors such as the epsilon 4 allele of apolipoprotein E and mutations in presenilin 1 and 2 proteins are associated with increased risk.
In Alzheimer’s disease, the amyloid precursor protein (APP) is broken down into unprocessable products, leading to the accumulation of beta-amyloid (Aβ) plaques in the brain.
These plaques disrupt neurotransmission, elicit inflammatory responses, and lead to hyperphosphorylation of tau protein, resulting in the formation of neurofibrillary tangles and neuronal dysfunction.
What are the clinical manifestations of Alzheimer’s disease as it progresses?
Alzheimer’s disease typically manifests with slow-onset memory loss, starting with short-term memory loss and progressing to long-term memory loss, along with progressive disorientation.
It also leads to impairment of higher intellectual functions such as judgment, abstract thinking, problem-solving, language, and visual-spatial function, often accompanied by mood and behavioral changes.
In later stages, patients may experience severe cortical dysfunction, leading to progressive disorientation, memory loss, and aphasia. Ultimately, patients become profoundly disabled, mute, and immobile.
What is the macroscopic appearance of the brain in Alzheimer’s disease during autopsy?
During autopsy, the brain in Alzheimer’s disease shows diffused cerebral atrophy, characterized by widening of the cerebral sulci and narrowing of gyri.
There is compensatory ventricular enlargement, known as hydrocephalus ex vacuo, which occurs due to atrophy of cerebral matter rather than increased cerebrospinal fluid (CSF).
Describe the histologic appearance of Alzheimer’s disease, focusing on key features such as neuritic plaques and neurofibrillary tangles
In Alzheimer’s disease, neuritic plaques are spherical masses primarily composed of amyloid fibrils and interwoven neuronal processes.
They can be found in various brain regions, including the hippocampus, amygdala, neocortex, basal ganglia, and cerebellar cortex.
Neurofibrillary tangles are basophilic fibrillary structures found in the cytoplasm of neurons.
They consist of abnormally hyperphosphorylated tau protein and are commonly observed in cortical neurons, especially in the entorhinal cortex, hippocampus, amygdala, basal forebrain, and raphe nuclei.
What are the clinical features of Frontotemporal Lobar Degeneration (FTLD)?
FTLD is characterized by progressive deterioration of language and changes in personality.
Unlike Alzheimer’s disease, in FTLD, behavior and language disorders often precede memory impairment.
These changes stem from the degeneration and atrophy of the frontal and temporal lobes, leading to a clinical syndrome commonly referred to as frontotemporal dementia.
Describe the morphology associated with Frontotemporal Lobar Degeneration
FTLD-tau: Chứa protein tau, có cấu hình khác với các đám rối tau trong bệnh Alzheimer.
FTLD-TDP43: Chứa protein TDP-43, liên quan đến suy giảm nhận thức thùy trán.
The morphology of FTLD involves atrophy of the brain, primarily affecting the frontal and temporal lobes.
Different subgroups of FTLD are characterized by neuronal inclusions found in the affected regions.
In some cases, these inclusions contain the protein tau (FTLD-tau), which can have a configuration different from the tau-containing tangles observed in Alzheimer’s disease.
Another major form of FTLD involves aggregates containing the DNA/RNA-binding protein TDP-43 (FTLD-TDP43), which is associated with predominantly frontal lobe cognitive impairment.
What are the main clinical features of Lewy body dementia (LBD)?
Patients with Lewy body dementia typically present with fluctuating attention and cognition, visual hallucinations, and motor parkinsonian manifestations such as bradykinesia, rigidity, and tremor.
Unlike Parkinson’s disease, where dementia typically appears in later stages, dementia manifests early in the course of LBD, often within the first year of diagnosis.
Describe the histological findings associated with Lewy body dementia.
The prominent histological correlate of Lewy body dementia is the presence of Lewy bodies in neurons within the cortex and brainstem.
Lewy bodies are abnormal collections of alpha-synuclein protein within the cytoplasm of neurons.
Additionally, staining for α-synuclein reveals the presence of abnormal neurites containing aggregated protein, known as Lewy neurites.
T173 What is Parkinson’s disease (PD) characterized by?
Parkinson’s disease is a neurodegenerative disorder characterized by the primary loss of dopaminergic neurons in the substantia nigra pars compacta. This results in dysfunction of the nigrostriatal pathway, which utilizes dopamine to regulate voluntary movement initiation.
What are the etiological factors associated with Parkinson’s disease?
The majority of Parkinson’s disease cases are sporadic with an unknown etiology, although aging is a significant risk factor. However, about 5-10% of patients have a monogenic form of PD, either autosomal dominant or recessive.
Mutations in genes such as α-synuclein (SNCA) and Parkin (PARK2) are associated with autosomal dominant and recessive forms, respectively.
Additionally, individuals with Gaucher disease (GD) or carrying GBA1 mutations have an increased risk of developing PD. Environmental factors like exposure to toxins or certain drugs can also induce Parkinson’s disease, such as MPTP, which selectively harms dopaminergic neurons.
Describe the pathomechanism of Parkinson’s disease
Parkinson’s disease primarily affects the dopamine-producing neurons of the substantia nigra (SN). The accumulation of α-synuclein protein aggregates is a key pathology in PD, leading to cellular toxicity.
This accumulation impairs the functioning of cellular organelles such as mitochondria, lysosomes, and endoplasmic reticulum, and disrupts microtubular transport.
Dopamine depletion in the striatum due to the degeneration of dopaminergic nigrostriatal pathway correlates with the clinical symptoms of rigidity, bradykinesia, and tremor at rest observed in PD.
Morphology of Parkinson’s Disease
- Gross findings often include pallor of the substantia nigra and locus ceruleus due to the loss of pigmented, catecholaminergic neurons.
- Lewy bodies, large aggregates of α-synuclein protein, are found in neuron bodies. They appear as round eosinophilic cytoplasmic inclusions with a dense core surrounded by a pale halo. Lewy neurites, fibrils made of insoluble polymers of α-synuclein, are deposited in neuronal processes and glial cells.
- With disease progression, Lewy bodies and neurites appear in the cerebral cortex. Initially, subtle Lewy bodies and neurites are found in brain regions outside the substantia nigra, starting from the medulla and pons before involving the substantia nigra.
Clinical Features of Parkinson’s Disease
Progresses over 10 to 15 years, leading to severe motor slowing and near immobility.
Clinical features can be remembered by the acronym “TRAP”:Tremor: Pill-rolling tremor at rest that disappears with movement.
Rigidity: Cogwheel rigidity in the extremities.
Akinesia/Bradykinesia: Slowing of voluntary movement.
Postural Instability and Shuffling Gait.
Death often results from intercurrent infections or trauma due to frequent falls caused by postural instability.
Dementia typically appears in the late stages of the disease.
Causes of Parkinsonism
Lewy body dementia (LBD) occurs when dementia arises within 1 year of the onset of motor symptoms.
Idiopathic Parkinson’s disease (paralysis agitans) is the most common cause.
Other causes include ischemia of the basal ganglia, head trauma (e.g., boxers), and Shy-Drager syndrome, which presents with idiopathic parkinsonism associated with hypotension and other autonomic symptoms.
What is Amyotrophic Lateral Sclerosis (ALS)?
ALS is a fatal degenerative disorder of upper and lower motor neurons characterized by progressive muscle weakness, atrophy, and eventual paralysis.
Who does ALS primarily affect?
ALS affects men more than women, typically occurring in individuals over 50 years old.
What are the typical initial symptoms of ALS?
ALS usually begins with subtle asymmetric distal extremity weakness.
What is the usual cause of death in ALS patients?
The usual cause of death in ALS patients is respiratory failure due to involvement of the respiratory muscles.
What is the pathogenesis of ALS?
The pathogenesis of ALS involves degeneration and loss of motor neurons in the anterior horns of the spinal cord, affecting both upper and lower motor neurons.
What are some genetic factors associated with ALS?
Mutations in genes such as SOD-1, TDP-43, FUS, and C9ORF72 have been associated with ALS, either in familial cases or sporadic cases.
What are some common clinical features of ALS?
Common clinical features of ALS include muscle weakness, atrophy, fasciculations, spasticity, hyperactive tendon reflexes, and eventually respiratory paralysis.
What is the typical prognosis for ALS patients?
ALS is relentlessly progressive, and the majority of patients die within 2-3 years from the onset of symptoms, usually from respiratory paralysis.
What are some morphological changes seen in ALS?
Morphological changes in ALS include thinning and gray discoloration of anterior roots of the spinal cord, loss of anterior horn cells, and neurogenic atrophy of skeletal muscles.
What is Huntington’s disease (HD)?
Huntington’s disease is a fatal autosomal dominant neurodegenerative movement disorder characterized by degeneration of the striatum (caudate and putamen), involuntary jerky movements, and behavioral changes.
What is the pathogenesis of Huntington’s disease?
Huntington’s disease is caused by CAG trinucleotide repeat expansions in a gene located on chromosome 4 that encodes the protein huntingtin. Larger numbers of repeats result in earlier-onset disease. Expanded huntingtin protein forms aggregates (inclusions) in the nuclei and dendrites of affected neurons, leading to neurodegeneration.
What are some morphological changes seen in Huntington’s disease?
Teo: Nhân đuôi và nhân bèo sẫm bị teo.
Giãn não thất: Sừng trước của não thất bên bị giãn.
Bao thể trong nhân: Chứa các tập hợp protein huntingtin ubiquitin hóa.
Morphological changes in Huntington’s disease include atrophy of the caudate nucleus and putamen, dilatation of the anterior horns of the lateral ventricles, and intranuclear inclusions containing aggregates of ubiquitinated huntingtin protein.
What are the clinical presentations of Huntington’s disease?
Huntington’s disease presents with chorea (abnormal involuntary movements), early cognitive symptoms such as forgetfulness, later progressing to severe dementia, and behavioral changes including depression. The disease is progressive, with death typically occurring after a course of about 15 years.
T174 What are cerebrovascular diseases, and what is their significance?
Cerebrovascular diseases are brain disorders caused by pathologic processes involving blood vessels. They are a major cause of death in the developed world.
What are the two main mechanisms by which cerebrovascular diseases cause damage to the brain?
Cerebrovascular diseases primarily cause damage to the brain through ischemia (85% of cases) or hemorrhage (15% of cases).
Ischemia results from thrombotic or embolic occlusion of vessels, while hemorrhage occurs due to vascular rupture.
What is the clinical term used for symptoms arising from cerebrovascular problems?
“Stroke” is the clinical term used for symptoms that arise from cerebrovascular problems, particularly when symptoms begin acutely.
What are the three main types of cerebrovascular pathologies?
The three main types of cerebrovascular pathologies are thrombotic occlusion of vessels, embolic occlusion of vessels, and vascular rupture.
These pathologies can lead to ischemic injury, infarction, or hemorrhage in the brain, depending on the mechanism involved.
Ba loại bệnh lý mạch máu não chính:Tắc mạch do huyết khốiTắc mạch do thuyên tắcVỡ mạch máuHậu quả:Tổn thương thiếu máu cục bộNhồi máuXuất huyết trong não
What is ischemic encephalopathy, and what is its underlying cause?
Ischemic encephalopathy is a condition characterized by widespread ischemic or hypoxic injury to the brain due to inadequate blood supply.
It occurs when the brain tissue does not receive sufficient glucose and oxygen from the blood, leading to functional hypoxia or ischemia.
What are the clinical outcomes associated with global cerebral ischemia?
Thiếu máu não toàn cầu: Kết quả lâm sàng phụ thuộc vào mức độ và thời gian tổn thương.
Tình huống nhẹ: Lú lẫn tạm thời, hồi phục hoàn toàn
.Tình huống trung bình: Nhồi máu ở vùng ranh giới (watershed areas).
The clinical outcomes of global cerebral ischemia vary depending on the severity and duration of the insult. In mild situations, patients may experience a transient confusional state with usually full recovery.
In moderate situations, infarcts may occur in regions fed by the very end of the circulation, known as watershed areas.
What factors contribute to ischemia in the brain?
Ischemia in the brain can result from various factors, including low perfusion (such as due to atherosclerosis), acute decreases in blood flow (e.g., cardiogenic shock), chronic hypoxia (e.g., anemia), or repeated episodes of hypoglycemia.
What are the main reasons for global cerebral ischemia?
The main reasons for global cerebral ischemia include severe systemic hypotension (systolic pressures of less than 50 mmHg) due to conditions such as cardiac arrest, shock, and severe hypotension.
Nguyên nhân chính của thiếu máu não toàn cầu:Hạ huyết áp hệ thống nghiêm trọng (huyết áp tâm thu dưới 50 mmHg).
Do ngừng tim, sốc, và hạ huyết áp nghiêm trọng.
