Neuro Week 1 Flashcards
Segmental Demyelination
Loss of myelin along a segment of nerve fiber between 2 nodes of ranvier
Onion Bulbs
proliferation of multiple schwann cells around one axon. Indicates repeated re/de-myelination.
Typically seen in hereditary motor neuropathyies (Charcot-Marie-Tooth) and chronic inflammatory demyelinating neuropathies.
Axonal Degeneration
Typically caused by traumatic/metabolic damage. Both axon AND myelin sheath undergo degeneration.
Denervation atrophy of myocytes within the motor units
Wallerian Degeneration
Axonal degeneration distal to point of axonal damage/cell body damage.
the result of Axonal Reinnervation of myocytes after denervation
Adjacent uninjured axons sprout to innervate the de-nervated myocytes. As a result the myocytes may switch types.
Spinal Muscular Atrophy (SMA)
Group of autosomal RECESSIVE motor neuron diseases beginning in childhood or adolescence. the LEADING inherited cause of infant mortality.
Werdnig-Hoffman Disease
Example of spinal muscular atrophy disease… therefore DUE TO MOTOR NEURON DISEASE**
Presents within first 4 months of life as a degeneration of LMNs and clinically as a “floppy baby” with generalized muscle weakness/hypotonia, muscular wasting and tongue fasciculations.
Gross pathology = atrophic ventral horns/roots
Amyotrophic Lateral Sclerosis
Both UMN and LMN degeneration
Age of onset = 50+
10% inherited (auto dom)
Clinically = UMN lesion symptoms (hyperreflexia, +Babinski) and/or LMN dysfunction
Causes denervation atrophy of affected muscles
Pathology: Gross = ant. horn atrophy
Microscopic = wallerian degeneration
Guillian-Barre syndrome (acute inflamm demyelinating polyradiculoneuropathy)
PERIPHERAL NERVE problem
immune-mediated (likely initiated by illness)
Clinically = ascending paralysis
Path = Chronic inflammation; segmental De-myelination
Charcot-Marie-Tooth Disease
Age of onset = child; early adulthood
PERIPHERAL neuropathy (auto dom inheritance)
Clinically = distal muscle weakness with inverted champagne bottle leg appearance (aka atrophy of calf muscles) and pes cavus (aka pathologically high arch foot), also sensory problems also hammertoes are common
Path = ONION bulb formation with segmental demyelination
Diabetic Neuropathy
Most common form is ascending symmetric polyneuropathy
Pathogenesis = micovascular changes due to non-enzymatic glycosylation of proteins etc. due to hyperglycemia ultimately resulting in a decreased ability to respond to reactive oxygen species
Lead Toxicity
PURE motor neuropathy… includes segmental demyelination
Myasthenia Gravis
immune-mediated loss of ACh receptors on postsynaptic terminal in muscle. (NMJ disorder)
Circulating AChR antibodies are almost always present
Extraocular muscles usually present first clinically
electrophysiology shows decreased motor response with repeated stimulation**
Negri Bodies
inclusion bodies composed of viral particles housed within cytoplasm or nucleus of neuron in RABIES specifically
Lewy Bodies
large spherical inclusions in neuron cytoplasm characteristic in Parkinson’s
Neurofibrillary tangles
accumulation of abnormal neurofilaments in cytoplasm of neurons in pts. with Alzheimers
Gliosis
fibrosis and scar tissue formation during neuro-repair due to proliferation of astrocytes.
Alzheimer Type II astrocytes
found in gray matter in pts. with liver disease or matabolic disorders (urea cycle). Cells have very large nucleus NO association with Alzheimers though…
Role of Ependymal cells
line ventricles in brain and central canal of spinal cord… specialized forms of these cells act as part of choroid plexus and are thus responsible for CSF secretion
Vasogenic Cerebral Edema
Most common form
Increased permeability of small VESSELS (BBB disruption)
Escape of proteins, fluids into EXTRAcellular space (especially in white matter)
Cytotoxic Cerebral Edema
Increased perm of cell MEMBRANES secondarily to cell INJURY
INTRAcellular accumulation of excess fluids (more severe in gray matter)
Hydrocephalic (interstitial) Edema
fluid flows from CSF into brain through ventricular lining in cases of hydrocephalus
Neural response to Ischemia
betw 6-12 hrs… acute shrinkage, angularity, and EOSINOPHILIC appearance in cytoplasm
Central chromatolysis
in response to physical damage…
1) cell body swells
2) Nissl bodies disperse peripherally
3) Nucleus displaces peripherally
4) ^ protein synthesis for axon repair
Main goal of microglia
macrophages of the brain, spinal cord… primary immune defense to CNS
Multiple Sclerosis
De-myelination of CNS ONLY…. due to auto-immunity of self-reactive T-cells to self-myelin antigen… Results in recuitment of leukocytes (Th17)and macrophages (Th1)
MUST find presence of 2 separate lesions!!!
CSF shows increase IgG as well as oligoclonal IgG
Commonly presents with visual problems either with optic nerve or MLF
Neuromyelitis optica
development of optic neuritis and spinal cord de-myelination are similar points in time (MS-like)
acute disseminated encephalomyelitis
rapidly progressing de-myelinating disease developing 1-2 weeks after viral infection. (MS-like)
acute necrotizing hemorrhagic encephalomyelitis
severe CNS de-myelination following upper resp. infection
central pontine myelinolysis
de-myelination of pontine tegmenum
Charcot-Marie-Tooth disease. CMT 1/3 vs CMT 2
CMT 1 & 3 are de-myelinating and x-linked have onion bulbs (CMT1 is peripheral myelin protein 22 overexpression and typically presents in childhood)
CMT 2 is axonopathy NO onion bulbs. Is autosomal also
Amyloid Neuropathy
selective pain and temp sensory loss and autonomic problems
pathogenesis due to amyloid deposits in endoneurial and pervascular areas
Tx = LIVER transplant (because transthyretin is over-produced in the liver of those effected)
Summary: Name 4 primary neuropathies (aka inherited) and 6 secondary (aka acquired)
Inherited:
1) Amyotrophic later sclerosis 2) spinal muscular atrophy (werdnig-hoffman) 3) CMTs 4) Amyloid neuropathy
Acquired
1) Guillain Barre
2) Chronic inflammatory de-myelinating polyneuropathy (CIDP)
3) Metabolic (ie diabetic neuropathy)
4) Infection (leprosy/diptheria)
5) Toxicity
6) Trauma
IMPORTANT difference between primary and secondary neuropathies
primary cannot be treated while secondary can be treated/managed
Leprosy induced neuropathy
***tend to affect extremities with lower temperature (ie nose and ear lobes… nose tip falls off)
- widespread infection of schwann cells and skin
- “tuberculoid” with granulomatous inflammation in endoneurium, epineurium, and skin
Diptheria induced neuropathy
non specific axon and myelin loss
the G+ rods actually produce and exotoxin that prevents protein synthesis
Varicella-Zoster neuropathy
painful dermatomally organized skin rash
neuron loss in gangia somewhat unique
Poilio neuropathy
straight kills motor neurons
Rabies
retrograde transport from site of entry back to CNS to cause damage
Vincristine and Vinblastine (“vinca alkaloids”) neuropathy
common chemo agents!!! prevent axoplasmic transport…
slowly progressing bilaterly symmetric weakness
lead neuropathy
“pure” neuropathy
uremic neuropathy
strongly associated with renal insufficiency to clear the toxin
