Neuropathology 2 Flashcards
what are the problems of
- Sampling error
- Accessibility of tissue
- Often tissue only available late in disease process (i.e. post- mortem)
• Amyotrophic lateral sclerosis (ALS)
brisk reflexes AND fasciculations!
most commonest type of MND
begins with cramps and weakness on one side followed by progression to the same area on the other side
patients often die due to the disease progressing to the respiration centres
genetic mutation in the super oxide dismutase
• primary lateral sclerosis
affects Upper MNs predominantly
• spinal muscular atrophy
affects lower motor neurons predominantly
UMN cell bodies are
in brain or brainstem and do not project outside the CNS
LMN cell bodies are in
brainstem or spinal cord and project outside the CNS to muscle
common characterisation of ALS
- focal weakness and clumsiness which spreads
- painful fasciculation and cramping
- dysarthria, dysphagia or respiratory issues
- upper and lower motor neurone signs
EMG would revel evidence of denervation and re-innervation in two extremities or body segments, arm and trunk or leg and head etc.
which nuclei are effects by ALS
brainstem nuclei hypoglossal nuclei
dementia key points to remember
- is a syndrome not a disease
- pathology post mortem is ultimately the only definitive diagnostic test
- no single reliable biomarker
- treatments work better the longer they are used
what are the different types of dementia
- Alzheimer’s Disease 65%
- Dementia with Lewy Bodies 20%
- Vascular Dementia 10%
- Frontotemporal dementias 5%
Alzheimer’s disease pathology
- Reducedbrainweight
- Cortical atrophy (reduced thickness)
- Enlarged ventricles
- Cell loss evident in medial temporal lobes and hippocampi
Microscopic Pathological features of Alzheimers dementia
Neurofibrillary Tangles (NFTs) - these are not unique to AD
- predominantly composed of tau
- normal tau stabilises axons
- In AD tau is hyperphosphorylated in tangles and forms paired helical filaments in cytoplasm
amyloid plaques
- Extracellular insoluable proteinaceous deposits
* Largely composed of Amyloid β peptides (Aβ peptides)
diffuse plaque
often found in older people with no dementia
neuritic plaque
surrounded bu thick distorted neuronal processes
strongly associated with cognitive decline
parkinsons pathology
repetitive pill rolling movements
persistent tremors
shuffling gait, taking small steps
• PD is characterised by:
• neuronal loss in the substantia nigra
• degeneration of the nigrostriatal tract
• profound loss of dopamine in the Basal nuclei (less than 20%
of normal)
Lewy
bodies
Surviving nigral neurons contain these,
They can be stained with antibodies to alpha- synuclein
Prion diseases in spongiform encephalopathies
Caused by a misfolded cell surface protein – causes cells and proteins to clump together resulting in cell death
Most common human form is CJD (Creutzfeldt-Jakob disease)
Varient CJD communicable by ingestion of meat infected with ‘mad cow disease’
Symptoms of CJD
Rapidly developing dementia – key trigger for investigation (MRI, Biopsy) •Difficulty walking – needing a cane or frame
•Muscle stiffness and fatigue
•Speech problems
In later the stages patients can suffer from
•Hallucinations •Confusion
CNS inflammation – Multiple Sclerosis
• Immune cells are stimulated to phagocytose the Myelin normally found insulating the axons of
nerve cells
• Where axon insulation is removed, the signal transmission along the fibre slows, and within a
pathway can become delayed
• Proprioceptive and other feedback systems do not then synchronise well with motor output
• Muscles fatigue and patients find it difficult to control movement properly
Peripheral Neuropathy causes
- Diabetes Mellitus
- Idiopathic (cause unknown)
- Toxic – alcohol, drugs
- Vitamin Deficiency (B12)
- Post-infectious (Guillain-Barre syndrome)
- Paraneoplastic (T-cell autoimmune response)
- Leprosy
- Amyloid, other inflammation (e.g. vasculitis)
Charcot- Marie-Tooth
Inherited Peripheral Neuropathy
Loss of distal motor and sensation with associated muscle wasting and weakness
‘peripheral myelin P22’ gene
Sural nerve biopsy
loss sensation, 30% pain
• Slow twitch (I) fibers innervated by
alpha 2 motor neurons, smaller of the two α motor neurons
• Fast twitch (II) fibers innervated by
alpha 1 motor neurons, larger of the two α motor neurons
have higher excitation threshold and faster conduction velocity
Motor Unit Recruitment
- Motor neurons recruited in order of size: Size Principle
- Smallest alpha motor neurons, α2, which belong to slow twitch recruited first
- Largest alpha motor neurons, α1, which belong to fast twitch recruited last
Muscle Fibre Staining Properties
- Slow twitch (type I) have myosin isoforms with low ATPase activity.
- Fast twitch (type II) have myosin isoforms with high ATPase activity that promotes rapid breakdown of ATP for energy of high-speed muscle shortening.
ST distribution
• Most individuals possess between 45 and 55% ST
Muscle biopsy
- Usually done under LA
- Usually deltoid, quadriceps or tibialis anterior (often muscle & nerve) • Way of dealing with biopsy depends on what you’re looking for.
- Usually have done CPK and EMG first
