Neurology: Neuromuscular Weakness Flashcards
What is motor neurone disease (MND)?
Condition in which there is progressive degeneration of both upper and lower motor neurones. Ultimately fatal when motor neurones stop functioning. Exact cause is unclear although there are some known risk factors. No effect on sensory neurones.
There are multiple types of motor neurone disease; state some examples, and how each presents, highlighting the most common and second most common
- Most common (50%): amyotrophic lateral sclerosis (typically LMN signs in arms & UMN signs in legs)
- Second most common: progressive bulbar palsy (affects muscles of chewing, swallowing, talking)
- Others:
- Primary lateral sclerosis: UMN signs only
- Progressive muscular atrophy: LMN signs only, affects distal muscles before proximal, best prognosis
*NOTE: some pts may present with combination of patterns
State some risk factors for MND
- Family history
- >40yrs (rarely presents in people <40yrs)
- Smoking
- Heavy metal exposure (e.g. lead)
- Certain pesticides
Describe typical presentation of MND, including:
- Age & gender of pt
- Symptoms
- Signs
Typically a late middle aged man (e.g. 60yrs) with gradual onset of progressive symptoms:
- Weakness (often first noticed in upper limbs)
- Increased fatigue when exercising
- Clumsiness/dropping things/tripping over
- Slurred speech
- Dysphagia (may say they cough or choke on liquids/foods)
- Dyspnoea or orthopnoea (due to increased diaphragmatic weakness)
Signs:
- Fasciculations
- Absence of sensory signs/symptoms
- Mixture of UMN & LMN signs
- Wasting of muscles (common in small hand muscles)
What investigations are done to diagnose MND?
Diagnosis is clinical but investigations can be done to exclude other pathology e.g.:
- Nerve conduction studies: show normal motor conduction
- Electromyography: reduced number of action potentials with increased amplitude
- MRI: exclude cervical cord compression & myelopathy
Discuss the management of MND
MDT management centred around slowing progression of disease and supporting pt and family to allow them the best possible quality of life (no treatments to halt or reverse progresion).
- Medications:
- Riluzole (glutamate inhibitor): extend survival by ~3/12
- Edaravone: not currently used in UK, used in USA
- Other supportive care:
- NIV
- Antidepressants if required
- Nutritional support
- Mobility aids
- Palliative care involvement
Discuss the prognosis of MND
- Median survival is 3-5yrs (although can be highly variable)
- Most pts die due to respiratory failure or pneumonia
What type of dementia is MND associated with?
FTD
What is myasthenia gravis?
Autoimmune condition which causes muscle weakness that gets progressively worse with activity and improves with rest (i.e. fatigable muscle weakness)
Explain the pathophysiology of myasthenia gravis
-
85% cases due to immune system producing acetylcholine receptor antibodies
- Bind to post synaptic receptors at neuromuscular junction and block acetylcholine from binding
- Antibodies also activate complement system causing damage to cells at post synaptic membrane- increasing degradation of AChR
- Antibodies also promote aggregation & internalisation of ACh- further increasing degradation of AChRs
-
15% caused due to immune system producing MuSK and LRP4 antibodies
- Both MuSK and LRP4 are important proteins involved in production & organisation of AChRs
- Hence, destruction of these proteins leads to decreased number of AChRs
State some risk factors for myasthenia gravis
- Thymoma (20-40% of pt with thymoma develop MG)
- Family history of autoimmune conditions
Discuss typical age of presentation of myasthenia gravis in men & in women
- Men: >60yrs
- Women: <40yrs
*Generally more common in women
State symptoms of myasthenia gravis
Symptoms can vary from mild to severe/life-threatening. Symptoms most affect proximal muscles & small muscles of head & neck; they are worse with activity and improve with rest (hence are often worse in the evening):
- Ptosis
- Diplopia (due to extraocular muscle weakness)
- Fatigue in jaw when chewing
- Difficulty swallowing
- Slurred speech
- Weakness in facial movements
- Progressive weakness with repetitive movements
State what you might find on examination of pt with myasthenia gravis
-
Fatigability in muscles:
- Prolonged upward gazing will exacerbate diplopia
- Repeated blinking exacerbate ptosis
- Repeated abduction of 1 arm 20 times will cause unilateral weakness in ipsilateral arm when comparing both sides
- Thymectomy scar
What investigations are done for myasthenia gravis/how is it diagnosed?
-
Antibody testing:
- Acetylcholine receptor (ACh-R antibodies)
- Muscle-specific kinase (MuSK antibodies)
- Low density lipoprotein receptor-related antibodies (LRP4)
- CT or MRI of thymus gland (look for thymoma)
- Edrophonium test (if doubt about diagnosis)
- Spirometry: FVC reduced
What is the edrophonium test (also called Tensilon test)?
What result supports diagnosis of myasthenia gravis?
- Give IV dose of edrophonium chloride (or neostigmine)
- Edrophonium blocks cholinesterase inhibitor enzymes
- Increases ACh at neuromuscular junction
- Briefly & temporarily relieves weakness
Discuss the management of myasthenia gravis
- Reversible acetylcholinesterase inhibitors (pyridogstigmine, neostigmine)
- Immunosuppressants
- Prednisolone
- Azathioprine
- Thymectomy (can improve symptoms even if don’t have thymoma)
- Monoclonal antibodies:
- Rituximab: targets B cells (CD20) to reduce production of antibodies
**NOTE: there is research as to whether eculizumab, monoclonal antibody that targets complement protein C5, could prevent complement activation & destruction of cells in post-synaptic neuromuscular junction. Not currently offered by NHS or recommended by NICE.
For a myasthenic crisis, discuss:
- What it is
- Potential triggers
- Presentation
- Management
- Myasthenic crisis is a life-threatening condition that is defined as worsening of myasthenic weakness requiring intubation or non-invasive ventilation
- Potential triggers: infection, illness, childbirth/pregnancy, stress (e.g. from surgery or trauma), lack of sleep…
- Presentation:
- Dyspnoea (can ask to count to 20 in one breath and can’t)
- Weak cough
- Difficulty swallowing
- Slurred speech
- Treatment is with immunomodulatory therapies e.g.
- IV immunoglobulins
- Plasma exchange
Explain the pathophysiology of GBS
Due to “molecular mimicry”
- B cells produce antibodies against antigens on pathogen causing the infection
- The antibodies also match/target protein on nerve cells
- Antibodies can target myelin sheath or the nerve axon
Describe typical presentation of GBS (include symptoms & signs)
- Pain (~65% have at the start- particularly in the back & legs)
- Symmetrical ascending weakness (starts at feet & moves up)
- Hyporeflexia/areflexia
- Peripheral paraesthesia (glove & stocking distribution)
- Bulbar dysfunction
- Dysphagia
- Dysarthria
- Cranial nerve involvement:
- Facial weakness
- Extra-ocular muscle weakness (15%. May lead to diplopia)
- Respiratory muscle weakness (20-30%)
- Dysautonomia
- Tachycardia
- Hypertension
- Postural hypotension
- Urinary retention
- Ileus
Outline the typical clinical course/progression of GBS
*I.e. when do symptoms start, when do symptoms peak, how long last for etc…
Explain the pathophysiology of Lambert-Eaton myasthenic syndrome
- Can occur in association with SCLC or as part of general autoimmune state
- If it occurs in association with SCLC, the tumour membrane expresses voltage-gated calcium channels. (If not in association with SCLC it is unclear why develop these antibodies)
- Immune system produces antibodies against these voltage-gated calcium channels
- Antibodies produced also target and damage the pre-synaptic voltage-gated calcium channels at the neuromuscular junction
- Causes reduction in number of pre-synaptic voltage gated calcium channels
- These channels are responsible for assisting the release of acetylcholine into synapse
- Hence, less acetylcholine is released into synapse
Describe typical presentation of Charcot-Marie-Tooth Disease (symptoms & signs)
Not all features will apply to all patients; most commonly causes motor loss. Classical features include:
- Pes cavus
- Distal muscle wasting (resulting in stork leg deformity)
- Weakness in lower legs (particularly ankle dorsiflexion- may have foot drop)
- Weakness in hands
- Hyporeflexia
- Hypotonia
- Peripheral sensory loss
- Hx of sprained ankles
- Hammer toes
*Think about it, it affects peripheral motor and sensory so motor signs will be LMN
State some causes of peripheral neuropathy- try to categorise as you would in an OSCE
*mnemonic ABCDE can help think of some
Examples using ABCDE mnemonic
- Alcohol
- B12 deficiency
- Cancer & CKD
- Diabetes
- Drugs (e.g. isoniazid, amiodarone, cisplatin)
- Every vasculitis
Predominately motor loss
- Guillain-Barre syndrome
- porphyria
- lead poisoning
- hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
- chronic inflammatory demyelinating polyneuropathy (CIDP)
- diphtheria
Predominately sensory loss
- diabetes
- uraemia
- leprosy
- alcoholism
- vitamin B12 deficiency
- amyloidosis
For Duchenne’s muscular dystrophy, discuss:
- Defect/mutation
- Inheritance pattern
- Presentation
- Management
- Defective dystrophin gene on X-chromosome (dystrophin is a protein that helps hold muscles together at a cellular level)
- X-linked recessive (therefore daughters have 50% chance being carrier and sons have 50% of being affected)
- Presentation:
- History of motor developmental delay, frequent falls
- 3-5yrs with weakness in muscles around pelvis
- Calf psuedohypertrophy
- Gower’s sign
- Walking on toes with legs apart and belly pointed out
- Sway back/lordosis
- Weakness progresses so all muscles affected- usually in wheelchair by their teens
- More likely to have ADHD, ASD, learning disorders e.g. dyslexia, OCD
