Metabolic Diseases Affecting the CNS Flashcards
What are Neuronal Storage Diseases?
How do they occur?
Neuronal Storage Diseases are disfunctional enzymes that cannot perform their normal task of breaking down specific proteins, leading to a build up of those proteins in the brain.
- The enzymes themselves are dysfunctional due to inheritance of a set of faulty genes (autosomal recessive)
- Specifically, this results in an accumulation of sphingolipids, mucopolysacharrides in neuronal lysosome
What is neuronal ceroid lipofuscinoses?
What is its symptoms and onset?
Neuronal Ceroid Lipofuscinoses: This is a lack of enzymes that typically modify/degrade proteins in neurons
-The result is a build up of lipofuscin inside of the neurons –> dysfunctional neurons
Onset = Childhood –> adult
Symptoms: Blindness, mental and motor deterioration, seizures
What is Tay-Sachs Disease?
What are its symptoms?
Tay-Sachs Disease results from a deficiency of Hexosaminidase A
This results in an accumulation of ganglioside in all tissues (but nervous system shows the most symptoms)
- Ganglioside = a fatty acid that is normally broken down
Onset: Early infancy
Signs: Developmental delay, paralysis, loss of neurologic function (Eventually the child will die in several years)
What is a quick diagnostic feature of Tay-Sachs?
There is a cherry red spot that appears in the eye
-Everything around the spot is defective:The white stuff that is accumulating around the spot are the gangliosides that are building up.
What are Leukodystrophies?
What are some common symptoms of Leukodystrophies?
Leuko = white (white matter in the brain i.e. Myelin)
These are a bunch of autosomal disorders in the myelin that involve lysosomal and peroxisomal enzymes
Symptoms = motor defects more than anything else, ataxia, hypotonia, spacity
What is Krabbe Disease?
What is the onset like?
What are the symptoms?
Krabbe Disease is a deficiency of galactosylceramidase which results in a build up of galactocerebroside
-Galactocerebroside –> Galactosphingosine in the neuron; this is toxic to oligodendrocytes leading to their death.
The net effect of this is a loss of myelin and oligodendrocytes in the CNS and PNS
Onset: 3-6 months
Symptoms: Rapidly progressive muscle stiffness/weakness (The child is just beginning to stand and then crumbles)
-Begin to see fatty macrophages that build up in the brain called Globoid Cells
What are the first signs of Krabbe disease?
A spastic hand or muscle stiffness is one of the first signs.
What are the two syndromes stemming from B1 (Thiamine) Deficiency?
What does B1 Deficiency usually stem from in the U.S.?
There are two diseases that relate to B1 deficiency -Comes from severe malnutrition (usually from alcoholism in the U.S.)
Two Syndromes:
- Wernicke Encephalopathy: Reversible
- Korsakoff Syndrome: Non-reversible
What is Korsakoff Syndrome?
What are the symptoms?
Is this reversible?
A B1 deficiency –> hemmorhage in the mamillary bodies and the walls of the ventricles however macrophages have come and eaten out big holes/cysts.
-Can also result in thalamic lesions
Symptoms: Memory disturbances (make up memories = Confabulation)
This is irreversible if it becomes prolonged
How do you get a B12 deficiency and what can it lead to?
Hard to get deficiency of B12 because they are stored really well (can’t get it from malnutrition). Usually it happens because of malabsorption.
- Anemia: Can be reversed with B12 administration
- Subacute combined degeneration of spinal cord
- This leads to lower extremity numbness, ataxia, and weakness
- This is reversible until you are parapalegic
- Also has swelling of the myelin layers and vacuolization
What is Subacute Combined Degeneration of Spinal Cord?
Combined because both motor and sensory pathways are involved - the Myelin layers of the spinal cord get swollen and drop out.
What are the two types of abnormal blood sugar?
Hypoglycemia (low blood sugar)
Hyperglycemia (high blood sugar)
What is Carbon Monoxide Poisoning?
What tissues are particularly vulnerable to CO poisoning?
CO can bind to hemoglobin way stronger than oxygen does –> carboxy hemoglobin instead of oxygenated hemoglobin - this does not allow for oxygen distribution
- The CO bound to blood also gives the person a pinkish rosy color
- Particularly vulnerable areas are due to hypoxia: Cortex (layers III and V), hippocampus, purkinje cells -Can sometimes see demyelination of white matter tracts
Methanol toxicity results in degeneration of what?
What are the symptoms?
Also a toxin (like CO poisoning) - People sometimes drink this as a recreational drug
Symptoms: The eye is really at risk: develop blurred vision and possibly blindness
This can also result in degeneration of ganglion cells –> death
Ethanol toxicity affects what part of the brain?
What are the symptoms?
Ethanol mainly affects the cerebellum by causing atrophy there
It can also result in loss of granule cells, perkinje cells, and Bergmann gliosis (Proliferation of astrocytes)
- Symptoms in chronic exposure: Truncal ataxia, Unsteady gait, Nystagmus (eyes jolting back and forth)
What are the two broad categories of metabolic disorders in neurons?
What are the subdisorders within those categories?
Genetic Metabolic Diseases
- Neuronal Storage Disease
- Leukodystrophies (white matter diseases)
Toxic and Acquired Metabolic Diseases
- Vitamin Deficiencies
- Metabolic and Toxic Distrubances
Are Neuronal Storage Diseases and Leukodystrophies autosomal recessive or autosomal dominant diseases?
Autosomal recessive
What are the symptoms of Neuronal Storage Diseases?
Symptoms: Loss of cognitive function and possibly seizures
What causes Wernicke Encephalopathy?
What are the symptoms of this disease?
Is it reversible?
Cause: Vitamin B1 (Thiamine) deficiency from malnutrition (usually alcoholism in the U.S.) or malabsorption of B1
Lack of B1 –>Hemorrhage and necrosis of the Mamillary Bodies, and walls of the 3rd and 4th ventricles
Symptoms: Opthalmoplegia (can’t move your eyes), ataxia, confusion
The hemmoraging is reversible but this can lead to necrosis which is not reversible!
What tissues are most vulnerable to hypoglycemia?
What other tissues are vulnerable?
Most vulnerable tissues: Large pyramidal neurons of the cortex (pseudolaminar necrosis)
Other vulnerable: Hippocampus and Cerebellum
What chronic condition is Hyperglycemia most associated with?
What other disorders are associated with hyperglycemia?
Hyperglycemia is most commonly seen in diabetes mellitus
It is also associated with Ketoacidosis or hyperosmolar coma (the increase of sugar pulls water out of cells)
Symptoms: Dehydration, confusion, stupor, coma
