Neurological Flashcards
What is the pathophysiological of Alzheimer’s Disease?
- Macroscopic changes include widespread cerebral atrophy involving the cortex and hippocampus
- Microscopic changes include cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by aggergation of hyperphosphorylated tau protein
- Biochemical changes include deficit of acetylcholine
- RF include age, family history (presenilin mutation), caucasian ethnicity, Down’s syndrome
What is the 1st line treatment for Alzheimer’s Disease?
Donepezil, galantamine, rivastigmine
These are all acetylcholinesterase inhibitors
What is the 2nd line treatment for Alzheimer’s Disease and when is it used?
Memantine (NMDA receptor antagonist)
Uses:
- Moderate AD who are intolerant or have a contraindication to acetylcholinesterase inhibitors
- As an add on drug to acetylcholinesterase inhibitors for patients with moderate or severe AD
- Monotherapy in severe AD
What are the contraindications for donepezil?
Patients with bradycardia eg. sick sinus syndrome
How are non-cognitive symptoms managed in AD?
Antipsychotics are only used in patients who are at risk of harm to themselves or others, or when agitation is causing them severe distress
NICE do not recommend antidepressants for mild to moderate depression in patients with dementia
What are the features of Lewy Body Dementia?
- Progressive cognitive impairment
- Typically occurs before parkinsonism
- Cognition may be fluctuating
- Early impairments in attention and executive function rather than just memory loss - Parkinsonism
- Visual hallucinations
How is LBD diagnosed?
Usually clinical
SPECT aka DaTScan is increasingly used - this has a sensitivity of 90% and specificity of 100%
How is LBD managed?
Mild/moderate:
1st line - Donepezil or rivastigmine
2nd line - Galantamine, memantine
Do not give neuroleptics (eg. antipsychotics) as patients may develop irreversible parkinsonism - give lorazepam if agitation
What are the features of vascular dementia?
- Thought to account for 17% of dementia in UK (2nd most common)
- Tends to be step-wise deterioration
- History of strokes/vascular disease
- Subtypes include stroke-related, subcortical (small vessel disease), or mixed (VD + AD)
- Can be inherited as CADASIL
- Focal neurological abnormaliites seen
What is the NINDS-AIREN criteria?
Criteria used for probable vascular dementia:
Presence of cognitive decline that interferes with activities of daily living, not due to secondary effects of the cerebrovascular event
- established using clinical examination and neuropsychological testing
Cerebrovascular disease
- defined by neurological signs and/or brain imaging
A relationship between the above two disorders inferred by:
- the onset of dementia within three months following a recognised stroke
- an abrupt deterioration in cognitive functions
- fluctuating, stepwise progression of cognitive deficits
How is vascular dementia managed?
- No specific pharmacological treatment
- Only give AChE inhibitors/memantine if comorbid AD PDD or LBD
- Treatment tends to be symptomatic with aim to address cardiovascular risk factors
What are the features of frontotemporal lobar degeneration?
- Onset before 65
- Insidious onset
- Relatively preserved memory and visuospaital skills
- Personality change and social conduct problems
What are the three recognised types of FTLD?
- Frontotemporal dementia (Pick’s disease)
- Personality change and impaired social conduct
- Changes include focal gyral atrophy with knife-blade appearance , pick bodies, gliosis, neurofibrillary tangles and senile plaque - Progressive non fluent aphasea (chronic progressive aphasia)
- Non-fluent, agrammatic, short utterance with preserved comprehension - Semantic dementia
- Fluent, progressive aphasia
How is frontotemporal lobar degeneration managed?
- No routine pharmacological treatment recommended
What is the Addenbrookes Cognitive Exam? What would you see in each form of dementia?
A validated tool for detection of dementia - a score of 82 or less strongly suggests dementia and a score of 82-88 suggests MCI
Alzheimers - global deficit
Frontotemporal - deficits in fluency and language
Vascular - no consistent pattern
What is the MMSE?
Mini mental state examination - an assessment tool used to detect dementia. A score of <24 out of 30 suggests dementia
Peripheral neuropathy may be divided into conditions which cause a motor or sensory loss. Give examples of each.
Predominately motor loss:
- Porphyria
- Lead poisoning
- Hereditary sensorimotor neuropathies (Charcot-Marie-Tooth)
- Chronic inflammatory demyelinating polyneuropathy
- Diphthreia
Predominately sensory loss:
- Diabetes
- Uraemia
- Lepropsy
- Alcoholism
- Vitamin B12 deficiency
- Amyloidosos
What can excess vitamin B6 lead to (pyridoxine)?
Peripheral neuropathy
What is the typical sensory change with peripheral neuropathy?
Symmetrical glove and stocking
Which conditions tend to cause painful neuropathies?
Alcohol, nutritional deficiencies
Diabetes
Hereditary sensory and autonomic neuropathy
Arsenic
Cryoglobulinaemia
Lyme disease
Paraneoplastic sensory neuropathy
Vasculitis neuropathies
What is Guillain-Barre syndrome?
Immune mediated demyelination of the peripheral nervous system causing progressive symmetrical ASCENDING weakness of all the limbs
Pathogenesis:
- Usually triggered by campylobacter jejuni
- Cross reaction of antibodies with gangliosides in the PNS
- Anti-GBM 1 antibodies found in 25% of patients
What are the examination findings in GBS?
- Progressive, symmetrical ascending weakness
- Reflexes reduced or absent
- Mild sensory symptoms
- Resp muscle weakness
- CN involvement (diplopia, bilateral facial nerve palsy, oropharyngeal weakness)
- Autonomic (urinary retention, diarrhoea)
- Papilloedema
How is GBS investigated?
Lumbar puncture - high protein, normal WCC
NCS - decreased motor conduction, prolonged motor/F wave latency
How is GBS managed?
IV immunoglobulin (or plasma exchange if IgA deficiency/renal failure) + supportive treatment
What are the features of MS?
Diagnose on the basis of two or more relapses and two or more lesions:
Visual:
- Optic neuritis or atrophy
- Uthoff’s phenomenen (worsening of vision following rise in body temperature)
- Internuclear ophthalmoplegia
Sensory:
- Parasthesia/numbness
- Trigeminal neuralgia
- Lhermitte’s syndrome (parasthesiae in limbs on neck flexion)
Motor:
- Spastic weakness most commonly in legs
Cerebellar:
- Ataxia (usually relapse rather than acute)
- Tremor
Others:
- Urinary incontinence
- Sexual dysfunction
- Intellectual deterioration
How is MS investigated?
Disseminated lesions in time and space
MRI:
- High signal T2 lesions
- Periventricular plaques
- Dawsons fingers in FLAIR images
CSF:
- Oligoclonal bands
- Increased intrathecal synthesis of IgG
Visual evoked potentials
- Delayed but well preserved waveform
How is MS treated?
Acute:
- High dose steroids for 5d
DMD - start if relapssing-remitting or secondary progressive:
1st line - IV natalizumab or ocrelizumab (monoclonal anitbodies)
2nd line - fingolimid, beta-interferon or glatiramer acetate
Spasticity:
1st line - baclofen, gabapentin
2nd line - diazepam, dantrolene, tiazindine
Future - cannabis, botox
Bladder dysfunction:
- USS first, if residual volume for intermittitent self-cath
- If no residual, anticholinergics
Oscillopsia (oscillating visual fields):
- Gabapentin
What are the features of MND?
- Upper and lower motor neurone signs
- Most common patterns are ALS, progressive muscular atrophy and bulbar pulsy
- DOES NOT AFFECT EXTERNAL OCULAR MUSCLES OR CEREBELLAR
- poor prognosis (50% of pts die within 3 years)
How is MND managed?
Riluzole
- prevents stimulation of glutamate receptors in ALS (as MND thought to be due to overactivity of glutamate causing nerve damage)
- prolongs life by 3m
Respiratory care
- BIPAP at night
- prolongs life by 7m
Nutrition
- PEG
What are the features of degenerative cervical myelopathy? How is it diagnosed and managed?
Features:
- RF include smoking, genetics and occupation
- Subtle symptoms incl pain, loos of motor/sensroy/autonomic function
- Positive Hoffman’s sign (gently flick one finger on a patients hand - a positive test results in reflex twitching of the other fingers on the same hand in response)
Diagnosis:
- MRI cervical spine; shows disc degeneration and ligament hypertrophy
Management:
- Urgent NS referral
- Early treatment (<6 months) with decompressive surgery
- PHYSIO SHOULD ONLY BE INITIATED BY SPECIALISTS
If symptoms recur - refer urgently to NS
What are the features of porphyric neuropathy?
- Porphyria is a group of liver disorders in chich prophyrins build up in the body due to overproduction of haem
- Porphyric attacks involve brain fog, anxiety and restlessness followed by severe abdominal pain, peripheral neuropathy and PURPLE URINE
- Motor-predominant axonal neuropathy
- Begins symmetrically in the upper extremities followed by lower extremity involvement
- Can progress rapidly to quadriparesis and resp involvement if untreated
What is subacute combined degeneration of the spinal cord?
- Impariment of dorsal columns, lateral corticospinal tract and spinocerebellar tracts
- Due to B12 deficiency
Dorsal column:
- Symmetrical parasthesia/numbness in the legs
- Impaired proprioception and vibration sense
Lateral corticospinal tract:
- Weakness, hyperreflexia, spasticity
- UMN signs
- Brisk knee, absent ankle
- Extensor plantars
Spinocerebellar tract:
- Sensory ataxia
- Positive Rombergs
What are the features and management of trigeminal neuralgia?
Features:
- Severe unilateral electric-shock type pain
- Evoked by light touch
Management:
- Carbamazepine
- Failure to respond or atypical features> urgent neuro referral
How is epilepsy classified?
Focal:
- aka partial
- aware or not aware
- motor or non-motor
Generalised:
- no awareness
- motor or non-motor
- tonic-clonic/absence
Focal to bilateral:
- starts on one side of brain before spreading to both lobes
- aka secondary generalised seizure
How is epilepsy diagnosed and managed?
Diagnosis:
- Brain imaging/EEG
Treatment is typically started after 2nd seizure UNLESS:
- persistent neurological deficit
- structural abnormality on brain imaging
- EEG shows unequivocal epileptic activity
- patient/carer choice
Generalised tonic-clonic/myoclonic or tonic/atonic:
1st line - sodium valproate in males or lamotrigine/levetiracetam in females
Focal:
1st line - lamotrigine/leveutracetam
2nd line - carbamazepine
Absence:
1st line - ethosuxamide
What are the DVLA rules for epilepsy?
Epilepsy with LOC:
- Inform DVLA
- Can drive if seizure free for 1 year UNLESS epilepsy with recent medication change (6 monhths)
First seizure with LOC:
- Inform DVLA
- Can drive if seizure free for 6 months and low risk of recurrence (normal imaging/EEG)
Seizures whilst asleep:
- Inform DVLA
- May still qualify for licence if >12m since last seizure
Seizures with no impairment in consciousness:
- Inform DVLA
- Can qualify for licence if first seizure must have been over 12m ago
How are acute seizures managed?
Basics:
- Check airway +/- oxygen
- Recovery position
- Give rectal diazepam if prolonged seizure, and repeat after 10-15 minutes if necessary
- Midazolam solution is alternative
What is status epilepticus and how is it managed?
Definition:
- Single seizure lasting >5 minutes or >2 seizures within 5 minutes without the person returning to normal between them
Management:
1. ABC
2. Benzo - IV lorazpem in hospital, PR diazepam or buccal midazolam OOH. Repeat once after 5-10 minutes
3. If ongoing start levetiracetam, phenytoin or sodium valproate
4. If ongoing within 45 minutes, general anaesthesia or phenobarbital
How can a pseudoseizure and an epileptic seizure be differentiated?
Pseudoseizure:
- Normal bloods incl prolactin
- Hip thrusting
- Absence of tongue biting
- Only when people watching
- Family member with epilepsy
- Gradual onset
How does carbamazepine work and what are the side effects?
MOA:
- Binds to sodium channels to increase their refractory period
SE:
- P450 enzyme inducer
- Dizziness/ataxia/drowsiness
- Headache and diplopia
- SJS
- Leucopenia and agranulocytosis
- Hyponatremia secondary to SIADH
How does phenytoin work and what are the side effects?
MOA:
- Binds to sodium channels increasing their refractory period
SE:
- Dizziness/diplopia/nystagmus/ataxia
- P450 enzyme inducer
- Megaloblastic anaemia
- Cushings type sx
- Peripheral neuropathy
- Duputryens
- Lupus
- Rashes
- Teratogenic
MONITOR TROUGH LEVELS PRE DOSE
How does sodium valproate work and what are the side effects?
MOA:
- Increases GABA activity
SE:
- Teratogenic (neural tube defects)
- P450 inhibitor
- Alopecia
- Ataxia/tremor
- Hepatotoxicity and pancreatitis
- Hyponatremia
- Encephlatophy secondary to high ammonia; treat with L-carnitine
- Weight gain
What are the red flag features for headache?
- Compromised immunity
- History of malignancy
- Vomiting
- Worse with fever
- Thunderclap
- New neurological deficit or cognitive fysfunction
- Recent head trauma
- ICP signs
- Symptoms suggestive of GCA or glaucoma
- Substantial change in characteristics