Neurodegenerative Disease Flashcards
Motor neuron disease is also referred to as …
amyotrophic lateral sclerosis
What is Motor Neurone disease ?
it is a progressive condition characterised by the regeneration of upper and lower motor neurons
What are some speculated causes of motor neuron disease?
unknown
no evidence of toxins
genetic - small number cases
speculated chronic virus
minerals/chronic calcium ion deficiency
What are the macroscopic features of motor neuron disease?
thinning of anterior roots spinal cord
What are the microscopic features of motor neuron disease?
loss of neurons in the motor cortex
loss of neurons in cranial nerve nuclei and in anterior horns
What are the clinical features of motor neuron disease?
asymmetric weakness and wasting of extremities 75%
(motor neuron cut off from muscle leads to muscle wasting)
dysphagia and dysarthria (difficulty speaking because muscles are too weak) (25%)
frontal dementia 3-5%
List features that are not indicative of motor neuron disease
- sensory signs
- bladder involvement
- ocular muscle weakness
What clinical investigations can be used for motor neurone disease (MND) diagnosis ?
electromyography - denervation and fibrillation
Nerve conduction studies
MRI- to exclude compression on the nerve (e.g. tumour)
thyroid and calcium studies to exclude metabolic mimic
Damage to the upper motor neuron is indicative of a lesion in what part of the CNS?
lesion would be above the spinal cord
[UMN starts in the motor cortex]
What are lower motor neuron signs of MND?
Hypotonia (loss of strength)
hyporeflexia
fasciculations (dying movements observed in the early days of the disease)- twitching
What are upper motor neuron signs of MND?
Weakness
Hypertonia (increase in strength)
Hyperreflexia
How is a definitive diagnosis of MND arrived at?
Presence of:
LMN signs >/= 2 limbs
UMN signs >/= 1region
progression of disease
Absence of:
sensory signs
neurogenic sphincter disturbance (i.e. no bladder involvment)
CNS/PNS disease
exclusion of MND like syndromes
What is the primary symptom management for MND?
Feeding
ventilation
physiotherapy
What is the only approved medication for MND? Give the MOA and the dose administered
Riluzole (100mg oral dose)
anti-glutamate properties- reduces release of glutamate, prevents excitotoxicity of the neurones and thus prevents their deterioration
What are the dental considerations for MND?
oral hygiene may be impaired
drooling and dysphagia may occur
botox in salivary glands to reduce saliva production
airway protection may be impared
What is the cause of parkinsons disease?
this is the loss of pigmented cells (dopaminergic neurons) in the substantia nigra. The remaining cells often have atypical eosinophilic inclusions in the cytoplasms called lewy bodies
The substantia nigra is part of the _____________ which is concerned with ____________
Basal ganglia
concerned with reward and movement
(indirect and direct pathways of movement)
What is the presentation of parkinsons disease ?
coarse tremor - beings unilaterally then spreads to al 4 limbs
pill-rolling at rest then disappears with sleep (thumbs rolll up and down the plantar surface of the palm)
rigidity
flexed posture
bradykinesia
parkinsonian handwriting- micrographia (smaller hand writing)
shuffling gait
mask-like epxression
sialorrhea (disturbance of swallowing)
depression in 50%
dementia in 80% by 20 years after diagnosis
voice quiteness- no power in voice
disturbances in voluntary movements
How is parkinsons disease diagnosed?
difficult to diagnose - 25% incorrectly diagnosed in life
Diagnostic use of L-Dopa
Functional imaging
How is parkinsons disease managed ?
treatment with dopamine agonists
dopamine replacements
What are some dental considerations for PD patients?
anxiety can increase their tremor, may affect tongue and lips
raise patients carefully in chair- some anti-PD medications can cause hypotension
take great caution with sharp or rotating instruments
Anti-PD medications can cause: dry mouth, red saliva, taste disturbances
Why is the use of 2% lidocaine 1 in 80 000 epinephrine contraindicated for PD patients taking levodopa and dopamine decarboxylase inhibitor or COMT inhibitor
[COMT- metabolism of catecholamines- adrenaline, noradrenaline and dopamine]
these drugs essentially inhibit enzymes that metabolise catecholamines such as adrenaline
This means that adrenaline is not metabolised which can lead to systemic toxicity; it can cause tachycardia, arrhythmias and hypertension (increased blood levels of adrenaline)
What other drugs are contraindicated for prescription to PD patients?
erythromycin (macrolide)
pethidine (opioid)
In parkinsons disease, sensitivity of receptors to replacement dopamine decreases. True or false
True
What is multiple sclerosis (MS)?
common demyelinating disease characterised by focal disturbance of function and a relapsing and remitting course
risk > females compared to males (unlike MND and PD)
Briefly describe the pathophysiology of MS
peri- venous plaques present in white matter (axons) of brain and spinal chord
the plaques appear grey in colour
1mm to several cm in size
How do new lesions of MS present?
show myelin destruction with relative axon sparing
[full length of the axon not destroyed]
How do old lesions of MS present?
relatively acellular with bare axons and axonal loss
more extensive axonal loss
What are the causes of multiple sclerosis?
disordered autoimmmune response
genetic predisposition
environmental exposure (virus)
age of individual at exposure
What are the vague early symptoms of MS?
anergia (lack of energy)
depression
headache
What are the precise early symptoms of MS?
sensory disturbance (40%)
acute optic neuritis (17%)
limb weakness
Diplopia ( CNIII, IV or VI) - 11%
Vertigo
ataxia (group of disorders that affects speech, coordination and balance)
sphincter disturbance
What are the clinical courses of MS (stages of the disease)
Relapsing and remitting (70% pass through this stage)
Secondary progressive
Primary progressive
Benign
What does the relapse and remitting stage of MS entail?
episodes of acute worsening of neurological function with partial or complete recovery
this phase may exist for many years
Unknown cause of relapses
What is the secondary progressive stage of MS?
after/following for the period of relapses and remissions, the attacks are followed by an incomplete recovery
there is a cumulative loss of function
often present 6-10 years after initial symptoms
What is the primary progressive stage of MS?
this stage is common in late onset of the disease (at >45 years old; MS usual onset = 20-40 years old)
there is insidious progression- slow/steadily worsening progression
What is the benign phase of MS?
here there is low disability 10 years after onset of disease
What clinical investigations are required to diagnose MS?
Neurophysiology
CSF- mild pleocytosis, elevated total protein and gammaglobulin
MRI
What is required for a diagnosis of MS?
2 or more episodes of symptoms attributable to demyelination at least 30 days apart at different sites of the CNS
exclusion of alternative pathology is required
How is symptomatic MS managed?
Spasticity- anti-spasmodics e.g. baclofen, dantrolene, botox; physio; splinting; IT baclofen
Urinary- anti-cholinergics, intermittent self-cathetherisaton
bowel- laxative
pain
depression
Tremor- beta blocker
How is MS managed in the acute relapse phase?
methylprednisolone 3g IV over 3 days
(autoimmune disorder; immune suppression with steroid)
What medication is administered to “modify history” in MS patients ?
natalizumab (monoclonal Ab)
beta interferon and glatiramer acetate
autoimmune disorder
What are some dental considerations for MS patients?
oral hygiene may be poor
do not put patients with severe MS supine- may worsen breathing symptoms
avoid nitrous oxide (theorertically causes demyelination)
abnormal perioral sensation or facial pain
steroid use (immunosuppressant; risk of infections)
What are some dental considerations for MS patients?
oral hygiene may be poor
do not put patients with severe MS supine- may worsen breathing symptoms
avoid nitrous oxide (theorertically causes demyelination)
abnormal perioral sensation or facial pain
steroid use (immunosuppressant; risk of infections)
State the meaning of chorea
involuntary, irregular, jerking movements affecting limb and axial muscle groups (trunk muscles?)
involuntary, uncoordinated movements
What is the inheritance pattern of huntingtons disease?
autosomal dominant disease
50% chance of getting the disease
How is huntingtons disease characterised ?
progressive localised neural cell death
characterised by chorea and dementia
What is the function of the striatum in the basal ganglia?
[secretion of GABA; GABAergic neurons]
they essentially keep things calm and prevent overactivation
What is the genetic defect identified in huntingtons disease?
increased length of CAG repeats in “huntingtin” gene on chromosome 4 (p16.3)
Huntingtons disease becomes more severe with each succeeding generation. True or false
True
Outline the pathology of huntingtons disease
there is neuronal loss in the striatum- this means that there are less neuronal projections from the striatum to other parts of the basal ganglia
there is loss of deep frontal and parietal cortex cells lost
Therefore there is a deficiency of GABA and ACh; this leads to unopposed dopamine activity (dopaminergic neurons unaffected hence the jerky uncoordinated movements
[look and indirect and direct pathways for reminder]
What are the stages of presentation for huntingtons disease?
chorea- initial symptoms; progress so that feeding and walking is impossible
Demential- subcortical damage
Behavioural disturbances- personality changes, psychosis, affective disorder
Hypotonicity (decreased muscle tone)
What clinical investigations can aid a huntingtons disease diagnosis?
genetic testing
MRI to confirm
The treatments for huntingtons disease are mainly supporting. Outline some treatments administered to patients with HD
Risperidone, haloperidol, tetrabanzine may reduce movements
SSRI (Antidepressant)fo affective disorders
Parkinsonism is a side effect of SSRIs
What kinds of drugs can cause parkinsonism?
drugs that block the action of dopamine (e.g. dopamine antagonists)
essentially mimic parkinsons disease but there is no damage to substantia nigra
What are the dental considerations for huntingtons disease?
communication
physical control of head (uncontrolled, uncoordinated movements)
consider GA or sedation
oral hygiene may be impaired due to lack of dexterity
orofacial trauma due to chorea
What is dementia?
progressive deterioration of intellect, behaviour and personality as a consequence of diffuse disease of the cerebral hemispheres, maximally affecting cortex and hippocampus.
The rate of progression of dementia is dependent on …
the underlying cause of dementtia
Give examples of causes of dementia
Infection:
Encephalitis (can take weeks for rapid progression to occur)
Creutzfeldt-Jakobs disease (can take months for rapid progression to occur)
Syphillis
HIV
Structural disorders
Normal pressure hydrocephalus (months to years for rapid progression)
Degenetative:
Alzheimers (can take months or years for rapid progression of disease)
Chronic inflammatory:
MS
vasculitis
Metabolic:
liver & thyroid disease
Nutritional:
wernickes encephalopathy
B12 deficiency)
Dementia plus syndromes:
lewy bodies
PD
huntingtons
Other:
Trauma
neoplasia
Cerebrovascular (20%)
What is the most common cause of dementia?
alzheimers disease
What are the biological features of alzheimers disease?
amyloid plaques
neurofibrillary tangles (caused by tau proteins)
unknown cause
There is a possible causal link of oral infection and alzheimers disease. True or false
True
[read paper linked in the text and make flash cards]
What are the presentations of alzheimers disease?
Introspective- unsure of self
difficulty coping with ordinary routine
loss of insight, behavioural changes, loss of inhibition
long term care
mutism, incontinence, death
What clinical investigations are required for a dementia diagnosis?
CT/MRI to rule out reversible pathology
biopsy (tumour)
genetics (huntingtons)
CSF immunology (inflamatory disease and infection)
serum antibodies (HIV, syphillis)
nutritional state
metabolic status
identifying the potential cause of the dementia
What are the dental considerations for dementia?
good communication
oral hygiene may be impaired
forgotten appointments
lost dentures
behavioural problems- including biting
carry out treatment with carers present
avoid long and complicated procedures
