Path - Degenerative Flashcards
Parkinsonian Symptoms
TRAP resting Tremor Rigidity Akinesia/Bradykinesia Postural Instability
Who gets Parkinson disease?
Elderly men typically
2% of the population
Viral induce Parkinson
Von Economo
MPTP
1-Methyl-4- phenyl tetrahydropyridine
MAOs break down in dopamine cells to MPP+ which kills mitochondria and kills cells
The Frozen Addicts
Late Stage Parkinson’s
Dementia
Parkinson disease neuronal pathway
Decrease in dopamine made by the substantia nigra for the nigrastriatal pathway
Lewy bodies are associated with what degenerative disease?
Parkinson Disease
Pick’s disease (a-synuclein)
Explain the Dopamine synthesis Pathway
Phenylalanine –> Tyrosine –> L-Dopa -> Dopamine
What neurotransmitter is made at Locus Ceruleus
Dopamine –> NE
What neurotransmitter is made at Adrenal Medulla?
NE –> Epinephrine
What are some other clinical signs of Parkinson besides those in TRAP?
Facial is expressionless (mask)
Decrease swallowing causes drooling
What are some treatments for Parkinson symptoms?
L-Dopa (Levodopa)
Neural transplantation into striatum
Deep brain stimulation for motor symptoms
What are some complications of Levodopa use?
Drug can become ineffective
Can cause Levodopa induce dykinesia (chorea, dystonia or athetosis movements)
Who gets Amyotrophic Lateral Sclerosis?
Most cases are sporadic; Middle ages men (50 y/o)
Familial ALS arises from what enzyme defect?
Zinc-Copper superoxide dismutase (SOD1) mutation leading to free radical injury in neurons. Mutation on gene 21q
Where are the defects in ALS?
Motor nuclei in brainstem (e.g. hypoglossal nuclei (LMN)
Degeneration of the Lateral Cortical Spinal tracts in (UMN); and the anterior horn (LMN)
What are some symptoms of ALS?
Patients will have muscle weakness, paralysis, increased tone, hyporeflexive and hyperreflexive and have a Babinski sign
Fassiculations, atrophy, areflexia in LMN; and
Increased tone, positive Babinski sign, hyperreflexia in UMN
What test can be performed to confirm ALS?
Muscle biopsy for grouped atrophy
Patient presents with weakness in hands and arms but has no sensory impairment. What could be a cause?
ALS; hand paralysis without sensation loss is an early sign of ALS
How does ALS progress?
Increase loss of muscles will lead to inability to speak, and loss of respiratory muscles. Intellectual capacity is preserved. The feeling of being trapped inside your body.
Prognosis for patients with ALS?
Clinical course usually does not extend beyond 10 years
What kind of inheritance is Huntington disease?
Autosomal Dominant that also exhibits anticipation. Future generations tend to exhibit symptoms earlier in life than the previous generation
What are the symptoms of Huntington disease?
Chorea (jerky, hyperkinetic movements, sometimes dystonic movements)
Leads to dimentia and depression
What are the genetics for Huntington disease?
Chromosome 4p16.3 encodes for protein huntingtin. Mutation is a trinucleotide repeat within the coding sequence that expands
Where is the degeneration located at in Huntington disease?
GABAergic neurons in the caudate nucleus of the basal nuclei
Describe Chorea movements.
Brief, semi-directed, irregular movements that are not repetitive or rhythmic, but appear to flow from one muscle to the next.
Jerky, involuntary movement of all parts of the body that is a group of neurological disorders called dyskinesias.
Hyperkinesia
What are patients of Huntington disease more at risk for when hearing about being diagnosed?
Suicide
Describe athetosis
Slow, involuntary twisting or writhing movements of the fingers, hands, toes and feet and in some cases the arms, legs , neck and tongue.
An intention tremor is also known as a _____.
Cerebellar tremor. A dyskinetic disorder characterized as a broad, coarse, and low frequency (below 5 Hz) tremor.
Describe Dystonia.
Sustained muscle contraction causing twisting or abnormal postures
Describe Dystonic Tremors
occur when involuntary muscle contraction causes twisting and repetitive motions and/or abnormal posture or positions.
What are spinocerebellar ataxias?
Loss of neurons and neural tracts in the cerebellum, brainstem, and spinal cord
Friedreich’s ataxia is a spinocerebellar ataxia
What are the important genetics of Friedreich Ataxia?
Autosomal recessive mutation.
A triple repeat expansion (GAA) in chromosome 9 of the Fratxin gene. Fritaxin is essential for mitochondrial iron regulation; the iron buildup creates free radical damage.
The primary site of pathology is spinal cord and peripheral nerves. Sclerosis and degeneration of dorsal root ganglion, spinocerebellar tracts, Lateral corticospinal tracts, and posterior columns.[8] The motor neurons of the spinal cord are spared. In peripheral nerves there is a loss of large myelinated fibres.
Who gets Friedreich ataxia?
Children with kyphoscoliosis
Younger kids 5-20 y/o with peak in teens
What are the symptoms of Friedreich ataxia? (bad version)
i. ) Upper and lower extremity ataxia
ii. ) Systemic abnormalities of the MSK system causing scoliosis and Pes Cavus
iii. ) degeneration of the cerebellum and spinal cord (posterior and lateral funiculi of the spinal cord)
iv. ) clumsy hand and gait disturbance
v. ) loss of stretch reflexes
vi. ) flexor spasms, extensor plantar response due to corticospinal tract involvement
What are the signs and symptoms of Friedreich ataxia?
Ataxia of upper and lower limbs and disturbances in gait
Loss of vibratory and proprioception. Pinprick is intact.
Muscle weakness in lower extremities.
Areflexia
Nystagmus
What is the cause of death of patients with Friedreich ataxia?
Hypertrophic cardiomyopathy
Who is effected from Alzheimer disease?
Older women (women:men 2:1)
1-2% of people under 65 years old
10% over 85
What are the genetics for Alzheimer disease?
Most cases are sporadic but some familial.
Early onset chromosome 1,14,21
Late onset chromosome 19
APP encoded on chromosome 21
Presenilin 1 protein gene chromosome 14
Presenilin 2 protein chromosome 1
ApoE4 chromosome 19
What will the brain appear like on an MRI in a patient with Alzheimer’s?
The sulci will be larger and the gyri will have atrophied
What two accumulations are diagnostic for Alzheimer disease?
Amyloid Beta protein (AB) and Neurofibrillary Tangles
What protein has been disrupted in AB for Alzheimer disease?
Amyloid Precursor Protein (APP) is fragmented in Beta Amyloid fragments
What other characteristic of amyloid is helpful for definitive diagnosis?
Red Congo stain. Clumps of amyloid will stain with Congo Red dye and visualize under a polarized light will appear “apple green” birefringence.
Describe Congophilic angiopathy
Neurons and glial cells will accumulate amyolid plaques around blood vessels and will stain with Conga Red dye
Describe Neurofibrillary tangles.
A familial mutation in chromosome 17 wil cause the abnormal configuration of the microtubule associated protein called Tau. These Tau proteins become phosphorylated and form helical aggregations that disrupt the neuron. When the neuron dies the tau tangles are left behind and congregate in the interstitium.
What genetic disease is associated with Alzheimer dementia?
Down syndrome patients have an increased risk of developing Alzheimer
How does Alzheimer disease progress? What areas of the brain does it start and what cognitive impairments occur?
- Start in the hippocampus with memory loss
- Move to around Broca’s area and diminishes ability to speak
- Move to the frontal lobe decreasing congitive ability
- Moves caudally impairing the ability to regulate emotion
- eventuall leads to complete dissemination and death
Describe the pathology of Alzheimer disease
Neurons die Gliosis occurs Gyri Narrow Sulci Expand Cortical atrophy (that is bilateral and symmetrical)
What is Pick’s disease?
Frontal temporal dementias caused by spherical tau protein aggregates
Behavioral and language disturbances; parkinsonian aspects
Who get’s Pick’s disease?
Mid adult life
How is Frontal temporal dementia pathology different from Alzheimer disease
Usually starts unilaterally and is localized just to the frontal temporal regions.
Alzhheimer is symmetrical and bilateral.
Also Alzheimer usually occurs in the older population while Pick’s occurs in mid-adult life
Pick’s patients tend to suffer more from behavioral and language problems than memory issues and may precede memory impairments
What happens to patients with Pick’s disease?
Dementia
Progress to death in 3-10 yrs
How will Alzheimer disease progress?
Early stage dementia will progress to loss of intelligence
- patients will be mute
- incontinence
- bed ridden
- pneumonia will cause death
What is a characteristic feature of cortical atrophy in Pick’s disease
Knife-blade atrophy that leaves edge of gyri thin
What is the inclusion body in Pick’s disease?
argentophilic globules or Pick bodies. hyperchromatic with silver stain.
Tau protein is a major portion of Pick bodies
