Neuro Flashcards
(99 cards)
1
Q
MND
A
encompasses a range of neurodegenerative conditions, affecting both the peripheral and central MOTOR nerves
2
Q
what does MND result from
A
TDP-43 protein mis-folding in many cases
it can be an inherited condition
~2% of cases are associated with a mutation in the SOD-1 gene
3
Q
which gender is MND more common in?
A
2x more common in males
4
Q
MND age of onset
A
50-60 years for sporadic cases (90% of cases)
5
Q
familial MND cases…
A
10% of cases
often linked to mutations in genes such as:
- SOD1
- FUS
- C9ORF72
6
Q
describe the overlap between frontotemporal dementia (FTD) and MND
A
notable overlap
- the most common genetic mutation in MND is C9ORF72 - this is also found in 40% of frontotemporal dementia cases
7
Q
upper motor neurone signs that may present in MND
A
- spasticity
- hyperflexia
- upgowing planters (although in MND they actually tend to be downing)
8
Q
lower motor neurone symptoms that may present in MND
A
- fasciculations
- muscle atrophy
9
Q
describe the eye and sphincter muscles in MND
A
these tend to be preserved until the later stages of the disease course
10
Q
describe sensory disturbance in MND
A
sensory disturbances tend to be absent in MND. Their presence should prompt consideration of an alternative diagnosis
11
Q
ALS
A
amyotrophic lateral sclerosis
- upper and lower MN signs
- the most common type
- may have bulbar onset (speech, swallowing and breathing)
12
Q
SMA
A
spinal muscular atrophy
- lower MN signs
- predominantly caused by genetic mutations
13
Q
PLS
A
primary lateral sclerosis
- upper MN signs
14
Q
PMA
A
progressive muscular atrophy
- lower MN signs
15
Q
Bulbar MND
A
upper and lower MN signs
- speech swallowing and breathing (bulbar region)
e.g dysarthria and dysphagia
16
Q
MND investigations
A
aim to rule out reversible causes
- TFTs: thyrotoxicosis syndrome
- protein electrophoresis: paraproteinaemias
- MRI: lesions that mimic MND or cervical spondylopathy
- EMG and nerve conduction
17
Q
MND management
A
primarily supportive (pain relief, muscle relaxants e.g baclofen and botox, anticholinergics for drooling , supportive feeding in bulbar disease
- 1 disease modifying drug = Riluzole (only extends life exp. by 3 months)
- non invasive respiratory ventilation for respiratory failure
18
Q
MND life expectancy
A
less than 5 years from diagnosis with most patients succumbing to the respiratory complications of the disease
19
Q
what is dementia?
A
Dementia is a syndrome that involves chronic impairment of multiple higher cortical functions such as memory, thinking, orientation, comprehension, and language.
- It can be a primary neurodegenerative disorder or secondary to another condition.
20
Q
what is the key to diagnosing dementia?
A
identifying a decline in memory and thinking that impairs activities of daily living.
21
Q
what is the most common cause of dementia?
A
Alzheimer’s disease
22
Q
2nd most common cause of dementia is…
A
vascular dementia
23
Q
what are the main causes of dementia?
A
- alzheimer’s disease
- vascular dementia
- fronto-temporal dementia
- Lewy body dementia
24
Q
what are the key investigations for dementia?
A
Key investigations include neuro-imaging and potential genetic tests.
25
what are the management options for dementia?
Management strategies depend on the underlying cause and usually involve a combination of pharmacological treatments and lifestyle changes
26
describe the nature of dementia symptom course.
chronic and progressive
27
examples of secondary (potentially reversible) dementia
- infections (neurosyphilis, CNS infections, AIDs complications)
- head trauma
- post-ictal state
- toxic effects
28
4A's of Alzheimers
Amnesia (recent memories lost first)
Aphasia (word-finding problems, speech muddled and disjointed)
Agnosia (recognition problems)
Apraxia (inability to carry out skilled tasks despite normal motor function)
29
mild-moderate alzheimers pharm. treatment
cholinsterase inhibitors - 'amines' or donpezil
30
moderate-severe alzheimers pharm. treatment
NMDA inhibitor - memantine
31
what causes vascular dementia?
Caused by impaired blood flow to areas of the brain due to vascular damage i.e. lots of micro-infarcts in someone with cardiovascular disease risk factors - these infarcts may progress over time
32
how can vascular dementia be investigated?
Usually a clinical diagnosis. Neuro-imaging can show evidence of significant small vessel disease
33
treatment for vascular dementia...
managing underlying vascular risk factors
34
what is Lewy body dementia?
In Lewy Body Dementia, abnormal protein deposits called Lewy Bodies cause cognitive decline associated with parkinsonism (rigidity, tremor, bradykinesia). Lewy bodies (alpha synuclein) deposits within cells as inclusions. This is also seen in Parkinson's disease.
35
what psychological symptom is Lewy body dementia associated with?
The dementia is associated with visual hallucinations, classically of small creatures/children/figures (Lilliputian bodies.)
36
If the dementia and movement disorder develop within a year of each other, it is referred to as...
Lewy body dementia
37
If the dementia and movement disorder develop a year apart, it is referred to as...
parkinsons disease
38
parkinsons vs Lewy body dementia
It is thought that in Parkinson's, the inclusions first affect the substantia nigra to cause the movement disorder before ascending to involve the paralimbic and neocortical areas to result in dementia; in Lewy body dementia, it starts at the top and eventually descends to the substantia nigra, hence the difference in the timing of these two closely inter-related conditions.
39
management for Lewy body dementia
Neuroleptics which may be given to manage agitation/hallucination (i.e. dopamine blocking medication) can trigger rigidity and Parkinsonism, whilst dopaminergic agents that may be given to help with the rigidity may worsen the hallucinations, therefore the management can be difficult.
Rivastigmine may be of benefit in these patients.
40
frontotemporal lobe dementia
Fronto-temporal dementia presents with cognitive impairment, personality change, repetitive checking behaviour, disinhibition, in keeping with the frontal area of the brain which is affected. Atrophy of the frontal and temporal lobes is seen.
41
key feature seen in the early stages of frontotemporal lobe dementia is...
constructional apraxia
(memory loss is a later feature)
42
the main variants of frontotemporal lobe dementia...
Behavioural variant (60%), characterised by loss of social skills, personal conduct awareness, disinhibition, and repetitive behaviour.
Semantic dementia (20%), characterised by an inability to remember words for things, calling them 'thingy.'
Progressive non fluent aphasia (20%), where the patient can't verbalise; their speech is laboured and difficult.
43
epidemiology of frontotemporal dementia
Classically presents at a younger age than other forms of dementia, and risk factors include repetitive head injury
44
frontotemporal dementia genetics...
Genetic tests can also be used if an inherited form is suspected (i.e. a strong family history.) These usually present as overlap syndromes e.g. mutations of C9orf which result in overlap with MND, and mutations of MAPT which result in overlap with Parkinson's.
45
what is a specific cause of frontotemporal dementia?
One specific cause of Frontotemporal Dementia is Pick's disease. This is diagnosed on post-mortem where ""Pick's bodies"" (accumulations of TAU protein that stain with silver) are found in the neurons. These are histologically distinct from those TAU protein collections seen in Alzheimer's as they stain differently and are found preferentially in other areas of the brain (preferentially damaging the frontal and temporal lobes).
46
frontotemporal dementia on imaging...
SPECT imaging shows reduced metabolic function in frontal lobe, and MRI shows increased T2 signal in the frontal lobe.
47
diagnosis of dementia requires...
Functional history (which may require a collateral history, risk assessment)
Cognitive assessments
Brain imaging
- blood tests (confusion screen)
48
how can you risk assess in dementia patients?
HOme safety (gas)
Wandering
Self neglect
Abuse
Falls
Eating
49
What is peripheral neuropathy?
Peripheral polyneuropathy involves damage to peripheral nerves, resulting in a combination of sensory, motor, and autonomic symptoms. It affects nerves in a length-dependent manner, often first affecting the longest nerves (distally in the legs and arms).
50
what are the causes of peripheral neuropathy? (predominantly sensory)
- diabetes mellitus
- alcoholism
- chronic renal failure (uraemia)
- vitamin B12 deficiency
- leprosy
- amyloidosis
51
what are the causes of peripheral neuropathy? (predominantly motor)
-Guillain-Barré syndrome (GBS)
-Chronic inflammatory demyelinating polyneuropathy (CIDP)
-Lead poisoning
-Acute intermittent porphyria
-Charcot-Marie-Tooth disease (CMT)
52
what are the causes of peripheral neuropathy? (predominantly autonomic)
-Can occur in isolation or alongside motor/sensory neuropathies.
-Symptoms: Postural hypotension, constipation, urinary retention and gastroparesis.
-Causes: DM, amyloidosis, and various neurodegenerative disorders.
53
sensory peripheral neuropathy symptoms
-Painful sensory polyneuropathy is commonly seen in conditions like diabetes mellitus and alcoholism.
Symptoms include numbness, pins and needles, burning pain, and hyperalgesia (increased pain response).
-Stocking-and-glove distribution: Symptoms typically begin in the feet, and later affect the hands as the disease progresses.
-Difficulty with fine finger movements: Numbness and weakness may impair daily activities, causing patients to drop objects or have trouble buttoning clothes.
54
motor peripheral neuropathy symptoms.
Progressive weakness, usually starting distally (e.g., feet and hands) and spreading proximally.
-Foot drop or clumsy hands may be the first signs.
-Over time, patients may experience tripping, difficulty walking, and progressive weakness.
-Lower motor neuron (LMN) signs: These include muscle wasting, fasciculations, weakness, and areflexia.
55
autonomic peripheral neuropathy symptoms
-Postural hypotension (dizziness when standing).
-Gastroparesis (delayed stomach emptying), leading to bloating and vomiting.
-Bladder dysfunction:
Urinary retention or incontinence.
-Constipation or diarrhea: Particularly nocturnal diarrhea.
56
peripheral neuropathy investigations
- history (onset, progression and pattern of symptoms)
- examination (focal deficits)
- nerve conduction studies and EMG
- bloods (glucose- diabetes, B12/folate - deficiency, U+Es - kidney function (uraemia), TFTs, serum protein - paraproteinaemia, autoimmune markers (ANA, ANCA - for vasculitis)
- imaging and invasive:
MRI
CT
*indicated only if structural causes are suspected e.g. compression from tumours or complex conditions i.e. vasculitis or amyloidosis
57
Management of peripheral neuropathies...
underlying cause
symptomatic
manage any secondary autonomic conditions
58
how is neuropathic pain as a result of peripheral neuropathy managed?
anticonvulsants - gabapentin and pregabalin
tricyclic antidepressants - amitriptyline
SNRI - duloxetine
59
how can motor symptoms from peripheral neuropathy be managed?
physical therapy : improve balance, mobility and prevent contractures
- occupational therapy input to assist with daily living activities
-orthotics (for foot drop or other motor deficits)
60
describe the management of the secondary autonomic conditions caused by peripheral neuropathy.
Postural hypotension: Increase fluid and salt intake, wear compression stockings, and consider medications like fludrocortisone.
Gastroparesis: Small, frequent meals and prokinetic agents.
Bladder issues: Urinary catheterization if needed.
61
what is Parkinson's disease?
Parkinson's disease (PD) is a neurodegenerative disorder that presents with generalised slowing of movements (bradykinesia), resting tremor and rigidity.
62
what is the cause of Parkinson's disease?
- exact cause is unknown
- believed to be the result of lewy bodies (misfolded alpha synuclein) accumulation
- Lewy bodies lead to cell death in the dopaminergic cells of the substantial nigra pars compacta of the basal ganglia > characteristic symptoms
63
parkinsons disease core features
- bradykinesia
- asymmetric resting tremor
-rigidity
(cog wheeling= when the tremor coincides with rigidity)
- gait disturbance : shuffling steps that are small and difficulty with initiating walk and turning whilst walking
64
alongside the core parkinsons disease symptoms, what other symptoms may occur?
- hypomimic facies (reduced facial expression)
- micrographia - this is very small hand writing (secondary to a combination of bradykinesia and rigidity)
65
what are the non motor symptoms of parkinsons disease?
- autonomic dysfunction
- olfactory loss
- constipation
- sleep disorders (e.g. REM sleep disorder)
- psychiatric features such as REM behavioural disorder
- psychiatric features including depression, anxiety and hallucinations
66
what should early presentation of cognitive function impairment raise suspicions for?
Lewy body dementia
67
when does postural instability occur in parkinsons disease?
late in the disease
68
what should early presentation of autonomic dysfunction raise suspicions of?
multisystem atrophy
69
what is the investigation for parkinsons disease?
Parkinson's disease is primarily a clinical diagnosis, supported by positive response to treatment trials.
70
what trial result can almost exclude a diagnosis of idiopathic parkinson's disease?
An absolute failure to respond to 1-1.5g of levodopa daily almost excludes a diagnosis of idiopathic Parkinson's disease.
71
what is the management for parkinsons disease?
levodopa (precursor to dopamine) and is used as a dopamine replacement agent
72
who should levodopa be initiated in?
all parkinsons disease patients with significant functional impairment
73
what should levodopa be paired with?
Typically combined with Carbidopa, which decreases side effects and improves CNS bioavailability), oftern referred to as Co-careldopa
74
does response to levodopa conform parkinsons disease diagnosis alone?
response to levodopa does not confirm the diagnosis (as many primary parkinsonian syndromes may also respond).
75
side effects of levodopa...
- peripheral (postural hypotension and N+V)
- drug induced dyskinesia : writhing and uncoordinated movements of the limbs associated with poorly organised dopaminergic control of motor activity.
76
describe loss of response to levodopa
With time, and as the underlying disease progresses, levodopa may become a less effective and patients may report end-of-dose effects, where motor activity progressively declines as the previous dose wears off, and on-off phenomena, which manifest as seemingly random fluctuations in drug effect.
It typically takes 2-5 years to develop complete loss of response
77
anti-emetic of choice in parkinsons
*Domperidone is the anti-emetic of choice in those with Parkinson’s disease which has anti-dopaminergic activity but does NOT cross the blood brain barrier.
78
dopamine agonists in parkinsons
- dopamine agonists e.g Apomorphine - the most potent dopamine agonist and is often used in late stages of the disease as it works well against motor fluctuations and dyskinesia
79
MAO-B inhibitors in parkinsons
- selegiline and rasagiline
- often used alongside levodopa in later stages of the disease
- Reduce dopamine breakdown peripherally & thus increase central update of levodopa.
* may cause serotonin syndrome
80
what drugs are useful in the wearing off effect of levodopa in the treatment of parkinsosns disease?
COMT inhibitors - e.g. tolcapone and entacapone
* tolcapone is more potent but higher risk of hepatotoxicity
81
other pharmacological managements in parkinsons disease
amantidine (NMDA receptor antagonist) - dyskinesia relief
anticholinergics e.g. procyclidine - mild tremors although rarely used
deep brain stimulation (thalamus)
82
describe parkinsons prognosis
Parkinson's disease is typically slowly progressive, but the rate of progression is variable.
The mortality rate for elderly people aged 70-89 years with Parkinson's disease is 2-5 times higher than for age-matched controls in some studies.
The risk of dementia is about 2-6 times higher in people with Parkinson's disease than in healthy controls
83
what is MS
Multiple sclerosis is a chronic autoimmune disease, primarily involving the central nervous system, which is marked by the degeneration of the insulating covers of nerve cells in the brain and spinal cord, leading to demyelination and eventual axonal loss.
84
pathophysiology of MS
combination of genetic and environmental factors, including potential viral pathogens, are believed to be contributing factors.
Pathologically, CD4-mediated destruction of oligodendroglial cells and a humoral response to myelin binding protein are key features of the disease.
85
MS symptoms
Sensory disturbance, marked by patchy paraesthesia
Optic neuritis, characterised by loss of central vision, loss of red desaturation and painful eye movements
Internuclear ophthalmoplegia, a lesion in the medial longitudinal fasciculus of the brainstem
Subacute cerebellar ataxia
Spastic paraparesis, as seen in transverse myelitis, including Lhermitte's sign.
Bladder and bowel disturbance
86
MS classification
-two main groups:
Relapsing-remitting (which may become secondarily progressive)
Primary progressive.
-Relapsing remitting MS makes up 80% of disease at presentation, compared with primary progressive which is <10%.
-The remaining 10% fall into a difficult to classify intermediate group of progressive-relapsing disease.
87
MS investigations
The diagnosis of multiple sclerosis is based on at least two of:
-Clinical history/examination
-Imaging findings
Typically these are periventricular white matter lesions seen on MRI disseminated in time and space
-Oligoclonal bands in the CSF (reflect various immunoglobulins seen on CSF indicating autoimmune process in the CNS)
-Visual evoked potential can help further characterise the diagnosis in patients presenting with optic neuropathy
88
what subtype of MS does insidious neurological progression suggest?
primary progressive
89
MS acute management
-An acute attack of multiple sclerosis should be treated with glucocorticoids involving local neurology services
-1g of intravenous methylprednisolone every 24 hours for 3 days is a typical regimen
-exclude infections prior to initiating drug (bloods, urine)
-this intervention has no evidence to suggest longterm benefit however appear to reduce the duration and severity of an individual attack
90
relapsing remitting multiple sclerosis: disease modifying therapies (DMTs)
-Injectables such as beta-interferon and glatiramer
Common first line agents in mild-moderate relapsing-remitting disease
-New oral agents such as dimethyl fumarate, teriflunomide and fingolimod
(Second line agents)
-Biologics such as natalizumab and alemtuzumab
Natalizumab is increasingly being used first-line in rapidly evolving severe relapsing–remitting multiple sclerosis, defined as two or more disabling relapses in 1 year
91
MS symptomatic therapies
Physiotherapy
Baclofen and Botox for spasticity
Modafinil and exercise therapy for fatigue
Anticholinergics for bladder dysfunction
SSRIs for depression
Sildenafil for erectile dysfunction
Clonazepam for tremor
92
what is bells palsy?
Bell's palsy is an idiopathic syndrome characterized by unilateral, lower motor neuron facial weakness.
93
features of bells palsy...
- unilateral lower motor neurone facial weakness which classically affects the forehead (onset is acute but not sudden)
- mild-moderate postauricular otalgia (pain behind the ears) which may precede the facial paralysis
- hyperacuisis (sensitive to sound)
- nervus intermedius symptoms (e.g. altered taste and dry eyes/mouth)
94
bells palsy investigations...
The diagnosis of Bell's palsy is primarily clinical, based on the characteristic signs and symptoms.
95
causes of bells palsy...
The aetiology of Bell's palsy remains unknown. Viral infections, particularly reactivation of herpes simplex virus type 1 (HSV-1), have been implicated as a possible cause.
Other viral pathogens, such as Epstein-Barr virus (EBV) and varicella-zoster virus (VZV), have also been suggested as potential triggers.
96
what is the acute management for bells palsy?
- Prompt administration of oral steroids: 50mg of oral prednisolone or prednisone once daily for 10 days, followed by a taper.
- Supportive treatments:
Artificial tears and ocular lubricants to manage dry eyes.
Eye patch/tape to prevent corneal exposure and injury.
97
when might acyclovir be used in the acute management of Bell's palsy?
The use of aciclovir is controversial.
Although the pathophysiology of Bell's palsy has not been definitively linked to active herpes virus infection, empirical treatment with aciclovir may be considered, particularly in cases where the clinical distinction between Bell's palsy and Ramsay-Hunt syndrome is difficult.
98
bells palsy long term management
Pain management with analgesics or anticonvulsants may be necessary in cases of severe otalgia or neuropathic pain.
Physical therapy, including facial exercises and massage, may be recommended to maintain muscle tone and prevent contractures during the recovery phase.
Psychological support and counseling may be beneficial for patients experiencing emotional distress or body image concerns due to facial weakness.
99
bells palsy recovery
70-80% full recovery rate - usually within 3 months (greatest recovery within first 6 weeks)
