MN Disease and MS Flashcards
MND
- Kills within 2 yrs
- Cause unknown and no cure
- Sensation is preserved
- Few groups of MNs spared: sphincter control and extraocular muscles
MND: treatment
- Only current licensed treatment is riluzole
- NMDA antagonist (glutamate)
- Extends life by only 3 months
MND: Symptoms
- Characterised by upper and/or lower motoneuronal loss
- (-) muscle weakness, cramps, flaccid paralysis
- (+) hyperreflexia, spastic paralysis
MND: Diagnosis
- Possible/probably MND is diagnosed
- Confirmation only viable post-mortem
- Rule of other diseases
- Motoneuronal degeneration determined by: clinical tests and electrophysiological studies
Types of MND
- 95% is sporadic (unknown cause)
- 5% is genetic/familial
Sporadic (Typical) MND
- Middle-late onset
- Slight preference for males to fremales
- UMN +/- LMN loss
- Muscle weakness, cramps, wasting, paralysis
- Death ~2yrs due to respiratory-related issues
Genetic Example: MND
Spinal Muscular Atrophy
- Progressive loss of LMNs
- Types: infantile and juvenile
- Characterised by LMN symptoms (weakness, wasting, loss of reflexes and fasciculations)
- Recessive mutation in survival motor neuron gene (SM1)
Hypothesis on the causes on MND
- genetic
- excititoxicity
- oxidative stress
MND: Excitotoxicity
- Loss of glial glutamate transporters
- Excessive glutamate
-> act on NMDA receptors
BUT: - only some reports of decreased glutamate transporters and increased glutamate in CSF of MND patients
- Most work done invitro
- NMDA antagonist (riluzole) only extends life by 90 days
MND: Oxidative stress
- SOD-1 scavenges free-radicals
-> mutation in SOD-1, increased free-radicals
BUT: - SOD-1 mutations kill other cells too -> not specific to motoneuronal death as seen in MND
Other Hypotheses
- Smoking
- Immune disorder
- Mitochondrial abnormalities
MND research at Adelaide Uni
- Young MNs don’t equal old MNs
- > difference in target-dependency
- Inflammaging and glial environment
- > old MNs in an inflamed environment unlike young MNs
- > could glia of OLD injured cells be diff?
- Care should be taken when extrapolating from young and genetic models of research to clinical settings of old and non-genetic patients
MS
- Autoimmune demylinating disorder
- Elapsing episodes of immunologically mediated demyelination and the lesions are separated in time and space
- Diagnosis usually 20-40yrs
- 1M:2F
Types MS
- Relapsing remitting pattern (85%0
- Progressive pattern (15%)
Relapsing Remitting MS
RRMS
- Acute episodes of neurological symptoms lasting for days, weeks or months, before completely for partially resolving
- The intervals between attacks can be varied but one average occur every 1-2 yrs
SRRMS
- occur in ppl with RRMS
- symptoms worsen over time, with or without the occurrence of relapses and remissions
- 60% of people who start with RRMS, develop secondary RRMS after 15 yrs
Progressive MS
Primary Progressive MS
- Affects around 10% of people with MS from the onset
- They experience no relapses or remissions, with slowly worsening symptoms
Progressive Relapsing MS
- rare form in about 5% of the people from the outset
- characterised by a steadily worsening disease state from the beginning, with acute relapses but no remissions, with or without recovery
MS Course
- MS starts as a mainly inflammatory disease with bouts of new disease attacks and remissions
- Overtime it then develops into a chronic progressive disease
- The no of relapses in the first and second year tend to correlate with progression of the disease over many years
Pathogenesis MS
- T cell mediated inflammatory disease
- T cells enter the CNS when they are activated in the peripheral circulation
- When they encounter their antigen in the CNS they get reactivated
- These reactivated T cells then activate macrophages and microglia
- These cells either alone or in conjunction with antibodies damage the myelin sheaths and the oligodendrocytes
5 Major Health Problems of MS
- Motor control: muscular spasms and problems with weakness, coordination, balance and functioning of the arms and legs, tendency to drag one foot
- Fatigue: including heat sensitivity
- Other neurological problems: including vertigo, pins and needles, neuralgia and visual disturbances
- Continence problems: including bladder incontinence and constipation
- Neuropsychological symptoms: including memory loss, depression and cognitive (thought-related difficulties)
Clinical Symptoms MS
Early common clinical symptoms:
- limb weakness
- blurring of vision
- incoordination
- abnormal sensation
- optic neuritis
Diagnosis MS
MRI: diagnosis and monitoring - detecting brain lesions (plaques)
CSF: elevated IgG levels, increased IgG synthesis rate and oligoclonal bands
- However, oligoclonal bands and elevated CSF IgG are MS- specific
MS Macroscopic
- Plaques in brain and SC
- Most cases have at least 12 plaques
- Active lesions: salmon pink and granular
- Old lesions: demarcated, grey pink and firm, may contain cavitations
- General correlation between location of lesions and clinical symptoms
- Can occur anywhere in white matter, at a junction between the cerebral grey and white matter and within the cortical grey matter and deep grey nuclei
MS Microscopic
- Active lesions = hypercellular
- Inactive lesions = hypocellular
