Neurology Flashcards
Define Parkinson’s Disease
A chronic progressive neurodegenerative disorder of the dopaminergic neurones of the substantia nigra characterised by cardinal symptoms of bradykinesia, resting tremor, rigidity and postural instability.
Explain the risk factors of Parkinson’s Disease
Increasing age
Family history of young-onset Parkinson’s
Genetics
MPTP exposure
Chronic exposure to metals causes Parkinsonism syndrome
Male sex
Head trauma
Toxin exposure
Explain the aetiology of Parkinson’s disease
Sporadic/Idiopathic Parkinson’s Disease:
Most common
Unknown aetiology
Genetic predisposition with subsequent environment factors/exposures
May be related to environmental toxins and oxidative stress
Secondary Parkinson’s Disease:
Neuroleptic therapy (e.g. for schizophrenia)
Vascular insults (e.g. in the basal ganglia)
MPTP toxin from illicit drug contamination
Post-encephalitis e.g. influenza
Repeated head injury (i.e. boxing)
Familial Forms: genes implicated are LEEK2, PARK 2 (Parkin), PARK 7, PINK 1, SNCA (α-synuclein)
Summarise the epidemiology of Parkinson’s Disease
One of most common neurodegenerative disorders
Prevalence is 1% worldwide
Mean age of onset is 65 years old
More common in men
Young onset Parkinson’s Disease = in 21-40 year olds
What are the presenting symptoms of Parkinson’s Disease?
Insidious, often asymmetrical onset
Resting tremor mainly in hands Stiffness and slowness of movements Difficulty initiating movements Freezing of gait Postural instability - Frequent falls, imbalance Smaller hand writing (Micrographia) Mental slowness/slowness of thought (Bradyphrenia) Fatigue Constipation Dementia in mid to late-stage disease
What are the signs on physical examination of Parkinson’s Disease?
Pill rolling tremor at rest (4-6Hz): decreased on action, usually asymmetrical
Rigidity: ‘lead pipe rigidity’ of muscle tone: enhanced by distraction. Cogwheel rigidity
Gait: shuffling, stooped, small-stepped, reduced arm swing, difficulty initiating walk
Postural Instability: Falls easily with little pressure from the back or the front
Psychiatric: Depression & Cognitive issues and Dementia
Expressionless hypomimic face
Soft monotonous voice (Hypophonia)
Tendency to drool
Mild-impairment of up-gaze
Impaired olfaction
What are the appropriate investigations in Parkinson’s Disease?
Mainly a clinical diagnosis
Dopaminergic agent trial if questioning diagnosis (LEVODOPA TRIAL) - will notice improvement in symptoms
MRI brain if atypical features present - exclude other causes eg hydrocephalus
Dopamine transporter imaging to distinguish from Vascular Parkinson’s
Olfactory and Genetic testing to confirm diagnosis
Bloods: Serum caeruloplasmin: rule out Wilson’s disease as a cause of Parkinson’s disease (would be low if this was the case)
24hr urine copper test - elevated if Wilson’s disease if the cause
What is the management of Parkinson’s Disease?
Medical: symptomatic therapy by dopamine replacement i.e. levodopa, dopamine receptor agonist, COMT inhibitors, anti-cholinergic, MAO-B inhibitors.
Domperidone is used to treat nausea & vomiting
Surgical: Deep Brain Stimulation (only moderate-severe)
Other: physio, SALT, OT to improve QOL, encourage physical activity
What are the possible complications of Parkinson’s Disease?
Levodopa-induced dyskinesias - need to lower medication doses or increase dosing intervals Motor fluctuations Autonomic Dysfunction (postural hypotension, constipation, urinary retention) Death (usually due to pneumonia or PE) Dementia Psychosis Depression Anxiety
What is the prognosis of Parkinson’s Disease?
There are no curative or disease-modifying treatments
Progressive but variable in rate, with many patients having a normal life span
Optimal treatment can delay impact of disability by 5-10 years
Factors to predict more rapid rate of progression are:
Older age at symptom onset
Rigidity/hypokinesia as presenting symptoms (versus rest tremor)
Associated comorbidities
Decreased response to dopaminergic medications.
Define Huntington’s Disease
An slowly progressive, autosomal dominant, neurodegenerative disorder characterised by chorea, cognitive decline, loss of coordination and personality change. It is a trinucleotide repeat disorder and typically appears in mid-adult life.
Explain the aetiology/risk factors of Huntington’s Disease
Huntingtin gene codes for a protein called huntingtin
Huntington’s disease is caused by an expanded CAG repeat at the N-terminus of the gene that codes for the huntingtin protein.
Huntington’s shows anticipation - earlier age of onset with each successive generation
Risk factors:
Expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
Family history
Other genetic factors
Summarise the epidemiology of Huntington’s
Prevalence is 4-8 per 100,000.
Duration of disease - 20 years from time of diagnosis to death.
Affects men and women equally
Onset usually 35-45 years old
What are the presenting symptoms of Huntington’s?
INSIDIOUS onset in middle-age of progressive fidgeting and clumsiness
Involuntary, jerky, dyskinetic movements often accompanied by grunting and dysarthria (twitching/restlessness)
Lability (rapid, often exaggerated changes in mood: irritability/temper outbursts)
Dysphoria (a state of unease or generalised dissatisfaction with life)
Mental inflexibility (may make unusual purchases, snap decisions, gambling)
Anxiety
Dementia
Loss of coordination - dropping things, stumbling, motor vehicle accidents
IN LATER STAGES: rigid, akinetic & bed-bound
What are the signs on physical examination of Huntington’s?
Chorea: random movement of fingers & toes, odd facial expressions, occasional peculiar postures of hand, trunk or limbs are typical of early disease
Dysarthria
Deficit in fine motor coordination - slow irregular tempo when asked to tap finger
Slow voluntary saccades and supranuclear gaze restriction (slowed rapid eye movements)
Motor impersistence - cannot protrude tongue fully or close eyes tightly for 10 seconds
Parkinsonism and Dystonia (uncontrollable muscle contraction)
MMSE shows cognitive and emotional deficits
What are the appropriate investigations for Huntington’s?
The diagnosis is usually CLINICAL so requires no tests
CAG repeat testing - more than 40 repeats on one of the alleles is a positive result, 36 to 39 repeats means they may or may not develop symptoms
MRI or CT scan - evident caudate or striatal atrophy
Define cluster headache
A neurological disorder characterised by recurrent, severe headaches on one side of the head typically around the eye, tending to recur over a period of several weeks.
Unilateral headache attacks lasting 15 minutes to 3 hours, associated with parasympathetic hyperactivity and sympathetic hypoactivity.
Pain is often localised to the unilateral orbital, supra-orbital, and/or temporal areas and can occur from once every other day to 8 times per day.
Explain the aetiology/risk factors of cluster headaches
Aetiology is unknown
Associated factors: Head trauma Heavy cigarette smoking Heavy alcohol intake Sleep apnoea - treatment of apnoea improves headache control
Risk factors: Male sex Family history Head Trauma Cigarette smoking Heavy drinking
Summarise the epidemiology of cluster headaches
Affects predominantly men
1 in 500 people
Age of onset between 20 and 40 years old
What are the presenting symptoms of cluster headaches?
Repeated attacks of unilateral pain around the eye which peaks within minutes and lasts 15 minutes to 3 hours
Autonomic symptoms: ipsilateral lacrimation, rhinorrhoea, partial Horner’s syndrome, nasal congestion, eye lid swelling, facial swelling, flushing
Nausea and vomiting
Photophobia and phonophobia
Migranous aura
Agitation - unable to stay still during an attack, pacing, banging head on wall
Suicidal thoughts
Headaches lasting 6-12 weeks at the same time each year every 1-2 years
Often occur at night 1-2 hours after falling asleep
What are the two types of cluster headache?
- Episodic: occurring in periods lasting 7 days-1 year, separated by pain-free periods lasting a month or longer. Cluster periods usually last between 2 weeks-3 months.
- Chronic: occurring for 1 year without remissions or with short-lived remissions of less than a month. Chronic cluster headaches can arise de novo or arise from episodic cluster headaches.
What are the signs on physical examination of cluster headache?
Evidence of autonomic symptoms ie eye lid or facial swelling
What are appropriate investigations for cluster headaches?
CLINICAL DIAGNOSIS - investigations are to rule out other causes.
Brain CT or MRI - normal if primary cluster headache. Allows elimination of secondary causes.
ESR - normal in cluster headache. Used to eliminate giant cell arteritis in patients over 50 y/o.
Pituitary function tests (TFTs, LH, FSH, cortisol, prolactin etc in bloods) - normal in primary cluster headache. Allows exclusion of pituitary adenoma as secondary cause.
ECG - exclude conduction abnormality before starting CCB
Define migraine
Migraine is a chronic, genetically determined, episodic, neurological disorder that usually presents in early-to-mid life. It is characterised by nausea, photophobia, and disability, along with headache and often has a preceding aura.
Explain the aetiology/risk factors of migraine?
Brain hyperexcitability to various stimuli
Neuronal depolarisation is believed to be the precipitating event in migraine aura
Risk factors: Family history of migraines High caffeine intake Exposure to change in barometric pressure (altitude and weather changes) Female Obesity Habitual snoring Stress Overuse of headache medication Lack of sleep OCP Allergies or asthma Hypertension Hypothyroidism Diet (alcohol, cheese, chocolate)
Summarise the epidemiology of migraines
High prevalence - 14% of individuals
More likely in females (3:1 F:M)
Prevalence rises in early adult years then decreases in late 40s-50s
More common in white patients
Highest amongst low income patients
Highest in Americas and Europe, lowest in Asia
What are the presenting symptoms of migraine?
Prolonged headache - 4-72 hours, may be throbbing
Nausea/vomiting
Decreased ability to function
Sensitivity to light
Headache made worse by activity - distinguish between migraine and tension headache (tension not worsened by exertion)
Sensitivity to noise
Aura: Visual disturbances (Flashing lights, Spots, Blurring, Zigzag lines, Blind Spots), Other sensory symptoms (tingling or numbness in limbs)
What are the signs on physical examination of migraine?
Nil signs of note
What are the appropriate investigations for migraine?
Mainly a clinical diagnosis from the history
Investigations to rule out other causes:
ESR - if raised, suggests temporal arteritis
Lumbar puncture - if abnormal could be SAH, meningitis or low or high cerebrospinal fluid pressure
CSF culture - if CNS infection
CT head/MRI brain - may show space-occupying lesion, ischaemic lesions, SAH
What is the management of migraine?
Acute with persistent symptoms: paracetamol, codeine, anti-emetics, triptans (5-HT agonists) eg sumatriptan, high flow oxygen, IV corticosteroid (NSAIDs)
Prophylaxis (if > 2 months): β-blockers, Amitriptyline, Topiramate, Sodium Valproate (tricyclic antidepressants, anticonvulsants)
Menstrual migraines can be controlled with the oral contraceptive pill
Advice: Encourage Regular meals and Sleep Caffeine Restriction Measures to Reduce Stress Symptom Diary Avoid triggers Rest in quiet, dark room during episodes
What are the possible complications of migraines?
Disruption of daily activities
Can progress into analgesia-overuse headaches in people who use analgesia regularly
Status migrainosus - migraine occurring for more than 72 hours
Migranous infarction - occurs when an aura lasts more than 1 hour
Migraine-triggered seizures
Depression
Chronic migraine - 15 or more days per month for more than three months with no medication overuse
Persistent aura without infarction
What is the prognosis of migraine?
Patients do well with treatment
The frequency of migraines decreases with age
Usually chronic
Define transient ischaemic attack
Sudden onset of neurological signs and symptoms caused by focal brain, spinal cord or retinal ischaemia (temporary occlusion of part of cerebral circulation) without acute infarction which resolves completely within 24 hours.
Summarise the aetiology of TIA
Most common cause = carotid artery stenosis
Cardioembolic events:
Carotid atherosclerosis
Emboli can arise from the heart: AF, atrial myxoma, mitral valve disease
Small vessel occlusion: microatheromas, fibrinoid necrosis
Others: occlusion due to hypercoagubility, dissection, vasculitis, vasospasm
What are the risk factors for TIA?
HYPERTENSION AF Coronary Artery Disease Diabetes Increasing age Male Obesity Hypercholesterolaemia Family history Valvular disease Smoking Alcohol
Summarise the epidemiology of TIA
2000 people per year in England have first TIA
Prevalence increases with age
More common in men
Less common in white patients
What are the presenting symptoms of TIA?
Clinical features depend on the part of the brain affected:
Carotid Territory:
Unilateral
Affect the MOTOR AREA
Weakness of arm, leg or one side of the face
Dysarthria
Broca’s dysphasia
Amaurosis fugax (painless fleeting loss of vision caused by retinal ischaemia)
Vertebrobasilar Territory: Homonymous hemianopia (if ophthalmic cortex is involved) Bilateral visual impairment Hemiparesis Hemisensory symptoms Diplopia Vertigo Vomiting Dysarthria Dysphagia Ataxia
What are the signs on physical examination of TIA?
Neurological examination may be NORMAL because the TIA may have resolved
Check pulse for irregularly irregular rhythm (AF)
Carotid bruit (carotid atherosclerosis)
Elevated BP (rises acutely after a cerebral ischaemic effect by increasing cerebral blood flow)
What are the appropriate investigations for TIA?
Bloods:
Glucose - hypoglycaemia can cause similar symptoms
FBC
ECG - check for AF
MRI brain - may show infarct
Carotid doppler ultrasound if expecting carotid stenosis
MR/CT angiography to further investigate carotid stenoses
Echo - check for valvular disease
