Neuro II (b) Flashcards
Autoimmune demyelinating disorder
Multiple Sclerosis
Epi of Multiple Sclerosis
Most common demyelinating disorder
F>M
Patho of Multiple Sclerosis:
* ————– -> Increased risk for MS
* Polymorphisms in the genes encoding receptors for ———-
* Increased Th17 and Th1 CD4+ cells
* Contribution from CD8+ T cells and B cells
- HLA-DR2 Variants–> Increased risk for MS
- Polymorphisms in the genes encoding receptors for IL-1 & IL-7
- Increased Th17 and Th1 CD4+ cells
- Contribution from CD8+ T cells and B cells
Macroscopic Features:
Characteristic lesions (“plaques”): Multiple, well circumscribed, slightly depressed, glassy-appearing, gray-tan, irregular shaped
features of?
Multiple Sclerosis
Multiple sclerosis
Macroscopic Features:
Characteristic lesions (“———-”): Multiple, well circumscribed, slightly depressed, ———– -appearing, gray-tan, irregular shaped
Macroscopic Features:
Characteristic lesions (“plaques”): Multiple, well circumscribed, slightly depressed, glassy-appearing, gray-tan, irregular shaped
location of “Plaques” in Multiple sclerosis
- Paraventricular regions (most common)
- Optic nerves and chiasm
- Brain stem
- Cerebellum
- Spinal cord
Microscopically in Multiple Sclerosis Active plaques are identified, which type of Active plaque is this?
———–: Sharp margins, macrophage infiltrates
Type I
Microscopically in Multiple Sclerosis Active plaques are identified, which type of Active plaque is this?
———-: Sharp margins, macrophages + complement deposition
Type II
Microscopically in Multiple Sclerosis Active plaques are identified, which type of Active plaque is this?
———-: Less well-defined borders, oligodendrocyte apoptosis
Type III
Microscopically in Multiple Sclerosis Active plaques are identified, which type of Active plaque is this?
———–: Non-apoptotic oligodendrocyte loss
Type IV
CM of Multiple Sclerosis
1) Mild changes in Cognitive function (thinking and learning)
2) Gradual, neurologic Deficits (Abnormal reflexes, inability to speak)
Inherited dysmyelinating diseases
Leukodystrophies
cause of Leukodystrophies
Abnormal myelin synthesis or turnover
(Dysmyelinating disease)
Macroscopic Features:
* Diffuse gray and translucent colour of the white matter
* Decrease in the volume of the white matter –> Brain atrophy, Ventricular enlargement, Secondary changes in the gray matter
Microscopic Findings:
* Myelin loss
* Lipid stuffed macrophages
features of?
Leukodystrophies
Clinical presentation of Leukodystrophies
- Affected children –> Normal at birth, but developmental abnormalities manifested during infancy and childhood
- Deterioration in motor skills
- Spasticity
- Hypotonia
- Ataxia
Examples of Leukodystrophies
1) Alexander disease
2) Canavan disease
3) Krabbe disease
etc
CM of Acute Disseminated Encephalo-Myelitis
- Development of symptoms, 1-2 weeks after an antecedent infection
Non-localising Symptoms:
* Headache
* Lethargy
* Coma
Macroscopic features:
* Swollen and softened Pons and Medulla
Microscopic features:
* perivascular cellular infiltrate, composed of Macropahges and mononuclear cells
* Myelin loss associated w/ a perivascular macrophage infiltrate (Heidenhain stain)
features of?
Acute Disseminated Encephalo-Myelitis
Epi of Acute Haemorrhagic Leukoencephalitis
- More devastating related disorder
- Affects children and young adults
More devastating compared to acute disseminated encephalomyelitis
Macroscopic features:
* Multiple scatterd petechial haemorrhages
Microscopic features:
* Multiple foci of inflammatory demyelination,
with diffuse oedema in the adjacent white matter
* Perivascular neutrophil infiltrates in cerebral white matter
features of?
Acute Haemorrhagic Leukoencephalitis
——– :Inflammatory demyelinating disease; Ab-mediated autoimmune disorder
Neuro-myelitis Optica (NMO)
Loc of Neuro-Myelitis Optica
optic nerves and spinal cord
Microscopic features:
* Spinal Cord lesion with extensive destruction of the parenchyma
* Perivascular infiltrates of eosinophils and neutrophils
features of?
Neuro-Myelitis Optica (NMO)
Cause of Central Pontine Myelinolysis
- Alcoholism
- Severe electrolyte or osmolar imbalance
CM of Central Pontine Myelinolysis
Rapidly evolving quadriplegia
(paralysis of the 4 limbs)
Central Pontine Myelinolysis is characterised by the development of ———-, induced by changes in osmotic pressure –> loss of ——- in the ——- of the ——–
Central Pontine Myelinolysis is characterised by the development of Oedema, induced by changes in osmotic pressure –> loss of Mylein in the center of the pons
cause of Thiamine Deficiency (vitamine B1)
- Chronic alcoholism
- Gastric disorders (Carcinoma, Chronic Gastritis)
Thiamine Deficiency –> ———
Wernicke Encephalopathy
CM of Wernicke Encephalopathy
- Abrupt onset of confusion
- Abnormalities in eye movement
- Ataxia
CM of Thiamine Deficiency
1) Systemic effects (beri-beri)
2) Abrupt onset of confusion, Abnormalities in eye movement, Ataxia - Wernicke Encepahlopathy
3) Irreversible memory disturbance (Korsakoff syndrome)
Macroscopic Features:
* Foci of haemorrhage and necrosis, in the mamillary bodies and para-ventricular (3rd & 4th ventricles)
Microscopic Findings:
* Early lesions: Dilated capillaries with prominent endothelial cells Haemorrhages
* Late lesions: Cystic spaces with haemosiderin-laden macrophages
* Lesions in the medial dorsal nucleus of thalamus –> Association with Korsakoff syndrome
features of?
Wernick Encephalopathy Thaimine Deficiency
Microscopic features of Acute/Chronic Wernike’s Encephalopathy
cause of Hepatic Encephalopathy
Elevated levels of urea together with inflammation and hyponatriaemia
patho of Hepatic Encephalopathy:
———- metabolism within ———- through glutamine synthetase
Ammonia metabolism within astrocytes through glutamine synthetase
Microscopic Findings:
* Astrocytes (Alzheimer type II cells) with swollen, pale nuclei in the cortex and basal ganglia
featurse of?
Hepatic Encephalopathy
Toxic Disorder caused by Lead?
Diffuse Encephalopathy
Toxicity from Aresnic causes?
Encephalopathy and peripheral Neuropathy (SensoryMotor Axonopathy)
Mercury Toxicity –> ——
Tremors, emotional changes, insomnia, muscle
atrophy, disturbances in sensations, changes in nerve responses, cognitive dysfunction
Organophosphates (in pesticides) Toxicity —> ——–
Memory, cognitive, mental,
emotional, motor and sensory deficits
Methanol Toxicity –> ——-
Blindness
**
Carbon Monoxide Toxicity –> ——-
Hypoxic injury to the Globus pallidus
Ethanol Toxicity –> ——
Chronic alcoholism –> Atrophy in the anterior
cerebellar vermis –> Truncal ataxia, unsteady gait
and nystagmu
Ionising radiation toxicity –> ——
Headaches, nausea,
vomiting and papilloedema
Microscopic features:
* Large areas of coagulative necrosis,
* oedema and
* thick-walled vessels with intramural fibrin-like material
* Haemosiderin accumulation
* Extensive vascular hyalinisation
* Neurofibrillary tangles
features of?
Toxicity due Ionising radiation
Most common cause of dementia in the elderly population
Alzehimer disease
Epi of Alzheimer disease?
3% –> 65-74 years old; 19% -> 75-84
years old; 47% –>84 years old
* Elderly
Increased risk for AD in Patients with ?
Down Syndrome
CM of Alzheimer disease
- Insidious onset of impaired higher intellectual
function - Altered mood and behaviour
- Disorientation, memory loss, aphasia (later in the disease)
- Disabled, mute and immobile patient
(after 5-10 years)
Pathogenesis of Alzheimer Disease:
* Progressive accumulation of ———— in the brain
* —– leads to hyper-phosphorylation of —– –> Redistribution of tau from axons into dendrites and cell bodies –> Formation of ———–
- Progressive accumulation of beta Amyloid (Αβ) in the brain
-
Αβ leads to hyper-phosphorylation of Tau –> Redistribution of tau from axons into dendrites and
cell bodies –> Formation of tangles
Macroscopic Features:
* Variable degree of cortical atrophy –> Widening of the cerebral sulci and thinning of the gyri
* Hydrocephalus ex vacuo
* Neuritic and Diffuse Plaques (extra-cellular lesion)
* Neurofibrillary tangles (intra-cellular lesion)
features of?
Alzheimer Disease
Microscopically in AD there are plaque formation extracellualry, Diffuse and Neuritic plaques.
which one is this?
* Focal, sphaerical, collections of tortuous(dystrophic plaques) around a central Αβ-amyloid core
* loc. Hippocampus, amygdala and neocortex
Neuritic Plaque
Microscopically in AD there are plaque formation extracellualry, Diffuse and Neuritic plaques.
which one is this?
* Αβ-deposits lacking the surrounding neuritic reaction
* Localisation: Cerebral cortex, basal ganglia, cerebellar
cortex
Diffuse Plaques
Alzeheimer Disease
Microscopic Findings:
——————-:
* Paired helical filaments –> Basophilic fibrillary
structures in the cytoplasm of the neurons
* Abnormally hyper-phosphorylated tau protein –> Major component of paired helical filaments
* Localisation: Entorhinal cortex, hippocampus, amygdala, basal forebrain
Neuro-Fibrillary Tangles (NFTs)
CM of Fronto-Temporal Lobar Degeneration
1) Behavioural changes (cases that frontal lobes
more affected)
2) Language problems (cases that temporal lobes
more affected)
3) Memory disturbances (later in the course of the
disease)
Subtype of Fronto-Temporal Degeneration-tau ?
Pick disease
(characteristic smooth, globular, pale basophilic inclusions, [Pick bodies])
Pick disease (FTLD-tau) is characterised by the presence of?
characteristic smooth, globular, pale basophilic inclusions, [Pick bodies])
Macroscopic features:
* “Knife-like” thinning of the gyri
Microscopic features:
* Pick bodies
features of?
Pick disease
———-: Movement disorder in the absence of a toxic exposure or other underlying known aetiology (dopamine antagonists or toxins)
Parkinson Disease
cause of Parkinson disease
Damage to the dopaminergic neurons
Macroscopic Features:
* Pallor of the substantia nigra and locus coeruleus
Microscopic Findings:
* Loss of the pigmented Neurons and gliosis in the above regions
* Presence of Lewy Bodies in the remaining neurons
* Lewy Bodies:
- Intra-cytoplasmic, eosinophilic, round inclusions with a dense core and a peripheral pale halo
- Composed of α-Synuclein, Neurofilaments and Ubiquitin
- Lewy Neurites: Dystrophic neurites containing abnormally aggregated α-Synuclein
features of?
Parkinson Disease
CF of Parkinson Disease
- Tremor
- Rigidity
- Bradykinesia
- Instability
Tx for Parkinson Disease
L-DOPA
Autosomal dominant movement disorder
Caused by CAG trinucleotide expansion ?
Huntington Disease
CM of Huntington Disease
- Choreiform (dance-like) movement disorder –> Increased and involuntary jerky movements of all body parts
- Twisting movements of the extremities
- Forgetfulness
- Affective disorders
- Severe dementia (possible)
Macroscopic Features:
* Small brain
* Prominent atrophy of the Caudate Nucleus, and less severe the Putamen
* Atrophy of the Globus Pallidus, secondarily
* Dilatation of the lateral and third ventricles
Microscopic Findings:
* Severe loss of neurons from Striatum
* Fibrillary gliosis
* Intra-nuclear inclusions (aggregates of ubiquition)
features of?
Huntington Disease
cause of Freidreich Ataxia
AR disorder, GAA trinucleotide repeat expansion in the gene encoding Frataxin
CM of Friedreich Ataxia
cause of Amyotrophic Lateral Sclerosis
Loss of motor neurons in the:
* Spinal cord and Brain stem (lower motor neurons)
* Motor cortex (upper motor neurons –> Betz cells)
Amyotrophic Lateral Sclerosis is caused by mutations in the genes —– and FUS
TDP-43
CM of Amyotrophic Lateral Sclerosis based on loss of lower motor neurons
- Denervation of muscles
- Muscular atrophy
- Weakness
- Fasciculations
CM of Amyotrophic Lateral Sclerosis based on Loss of Upper motor Neurons
- Paresis
- Hyper-reflexia
- Spasticity
Macroscopic Features:
* Thin and gray anterior roots of the spinal cord
* Mildly atrophic pre-central gyrus (severe cases)
Microscopic Findings:
* Lwey body-like inclusions
* Degeneration of the lateral cortico-spinal tracts
* Reactive gliosis
* Loss of anterior root myelinated fibers
* Cytoplasmic inclusions (TDP-43 [+]), with exception the SOD-1 cases
* Hyaline inclusions
* Bunina bodies
features of?
Amyotrophic Lateral Sclerosis
progression and prognosis of Amyotrophic Lateral Sclerosis :
Involvement of the respiratory muscles –> Recurrent bouts of pulmonary infections -> ——
Death
