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Flashcards in Multiple sclerosis Deck (65):



What is multiple sclerosis?

MS is a chronic autoimmune T-cell mediated inflammatory disorder of the CNS. Multiple plaques of demyelination occur throughout the brain and spinal cord, occurring sporadically over years (dissemination in space and time which is crucial for diagnosis).




What gender does MS more commonly occur in?







What is the mean age of onset of the disease?



Approximatley 30 years (range 20-40)




What immune cell is impliated in the development of MS?



T-cell mediated autoimmune disease




What parts of the nervous system does MS affect?


  • Brain
  • Optic nerve
  • Spinal Cord




What neuronal structures are affected by MS?


  • Myelin sheaths
  • Oligodendrocytes




What are the cardinal pathological features of of MS?



Plaques of demyelination (2-10mm)




Where do plaques most commonly occur in MS?

Can occur anywhere in CNS, but most commonly:

  • Optic nerves
  • Periventricular region
  • Corpus callosum
  • Brainstem and cerebellar connections
  • Cervical cord (corticospinal and posterior columns)




What does the focal acute inflammation cause in terms of nerve conduction?



Conduction block




What are the pathologial outcomes that can occur from acute demyelinating episodes?



Recovery and remyelination, or permanent axonal destruction




What is the pathological basis for the progression of MS as a disesase?



Progressive axonal damage




What proportion of individuals with relapsing remitting MS develop secondary progressive MS?







What are the different types of progression of MS?


  • Relapsing remitting MS
  • Secondary Progressive MS
  • Primary Progressive MS




What is relapsing remitting MS?


Symptoms occur in attacks (relapses) with a characteristic time course: onset over days and typically recovery, either partial or complete, over weeks. Patients may accumulate disability over time if relapses do not recover fully.




How often do relapses occur on average in relapsing remitting MS?



On average patients have one relapse per year but occasionally many years may separate relapses (benign MS – 10% of patients).




What is secondary progressive MS?


Late stage of MS consists of gradually worsening disability progressing slowly over years. 80% of those with RRMS progress to this stage by 35 years. Relapses may sometimes occur in this progressive phase (relapsing–progressive MS).




What is primary progressive MS?


Characterized by gradually worsening disability without relapses or remissions. Typically presents later and is associated with fewer inflammatory changes on MRI.





What proportion of those with MS have primary progressive MS?







How do those with MS most commonly present?

Wide variety of possible symptoms may occur depending on the anatomical site of lesions. Common ones include:

  • Optic neuritis
  • Brainstem demyelination
  • Spinal cord lesions




What are features of MS affecting the brainstem?

  • Diplopia
  • Vertigo with nystagmus
  • Facial numbness/weakness
  • Dysarthria
  • Dysphagia
  • Pyramidal signs
  • Bilateral internuclear opthalmoplegia - Pathognomonic of MS




What is internuclear opthalmoplegia?

Characterised by

  1. Impaired adduction of the eye on the abnormal side
  2. Horizontal jerk nystagmus in the opposite eye upon lateral gaze away from the side of the lesion




What is the mechanism behind internuclear opthalmoplegia?


INO is caused by a lesion in the medial longitudinal fasciculus (MLF). The MLF connects the abducens nerve (CNVI) nuclei to the oculomotor nerve (CNIII) nuclei and facilitates conjugate eye movements during lateral gaze by coordinating adduction with abduction.




What are features of spinal cord lesions in MS?


  • Paraparesis - developing over days/weeks
  • Limb numbness/weakness + tingling
  • Lhermitte's sign positive
  • Tight band sensation around chest - thoracic lesion




What is optic neuritis?


A demyelinating inflammation of the optic nerve. It is also known as optic papillitis (when the head of the optic nerve is involved) and retrobulbar neuritis (when the posterior part of the nerve is involved)




What are causes of optic neuritis?


  • Idiopathic
  • MS
  • SLE
  • Sarcoidosis
  • Sjogren's syndrome
  • Behcets disease
  • Syphillis
  • Vitamin deficiency
  • Diabetes




What are signs of optic neuritis?


  • Altered visual acuity - may range from 6/6 to PL
  • RAPD 
  • Lack of red reflex/retina obsured - large haemorrhage
  • Red desaturation 
  • Central scotoma
  • Swollen optic disc - if inflamamtion anterior





What are the symptoms of optic neuritis?

Usually a woman, aged 20-40

  • Disturbance of vision of one eye - scotoma, floaters
  • Pain that worsens on eye movement




What are common symptoms seen in MS?

  • Visual changes
  • Sensory symptoms
  • Clumsy limbs
  • Ataxia/Unsteadiness
  • Urinary incontince - urgency/frequency
  • Constipation
  • Pain
  • Fatigue
  • Spasticity
  • Depression
  • Sexual dysfunction
  • Temperature sensitivity




What sensory features are often seen in individuals with MS?


  • Dysaesthesia
  • Pins and needles
  • Trigeminal neuralgia
  • Reduction/Loss in proprioception in feet
  • Feeling of water trickling down skin
  • Uthoff's Phenomenon




What eye signs might you see in MS?


  • Blurred vision - optic neuropathy
  • Diplopia
  • Hemianopia
  • Optic neuritis - disc swelling
  • Internuclear Opthalmoplegia
  • RAPD
  • Optic disc swelling
  • Argyll-Robertson pupil





Why do individuals with MS become clumsy and ataxic?



Due to cerebellar lesions and loss of proprioception




Why do individuals with MS develop urinary urgency/frequency?



Hyper-reflexia of the bladder




What is Uthoff's Phenomenon?



 Signs/symptoms worse on hot day or after exercise e.g. after a hot bath




What is the cause of Uthoff's Phenomenon?



Heat slows conduction in nerve fibres, causing worsening of symptoms




What are argyle robertson pupils?

Characterised by:

  • Miosis (small pupils)
  • Absence of the pupillary light response
  • Brisk accommodation reaction
  • Bilateral involvement.




What is the mechanism behind Argyll-Robertson pupils?


Caused by a pretectal lesion in the dorsal midbrain affecting the fibres of light reflex, which spare the fibres of the accommodation pathway that innervate the Edinger–Westphal nuclei




What are motor features of MS?


  • Spasticity
  • Features of Myelitis




What sexual/GU features can occur in MS?


  • Erectile dysfunction
  • Anorgasmia
  • Urine retention/incontinence




What are GI features of MS?


  • Dysphagia
  • Constipation




What features might suggest non-MS causes of some of the neurological features seen in MS?


  • Hyperthermia
  • Nausea/vomiting
  • Positional vertigo
  • Seizures
  • Aphasia
  • MEningism
  • Bilateral optic neuritis
  • CSF leucocytosis




What are features of late stage MS?

  • Spastic tetraparesis
  • Ataxia
  • Optic atrophy
  • Nystagmus
  • Brainstem signs (e.g. bilateral INO)
  • Pseudobulbar palsy
  • Urinary incontinence
  • Cognitive impairment, often with frontal lobe features




What criteria are used to diagnose MS?


The Mcdonald Criteria




What investigations would you perform if you suspected MS?


  • MRI
  • LP 
  • Visual evoked potentials




What might you see on MRI in someone with 


  • Demyelinating Plaques - in 85% of clinical presentations
    • Multiple plaques are usually present in MS 





If someone with MS was experiencing fatigue, what other causes of fatigue would you want to exclude?


  • Anaemia
  • Lack of sleep/apnoea/poor sleep hygeine
  • Hypothyroid
  • Medication
  • Depression




What is Devic's Disease?


Neuromyelitis optica

Considered a subtype of MS, presents with features of optic neuritis and Acute transverse myelitis




What do plaques signify in terms of disease activity in these areas?



There is active disease in areas where plaques are present




What would you be looking for on LP in someone with features of MS?


Oligoclonal bands of IgG on electrophoresis




What is rule of thumb with the presence of Oligoclonal bands in CSF and diagnosis of MS?



Present in CSF, but not in Serum




What is visual evoked potential testing?


Detect lesions in visual pathway - The patient has EEG probes on the skull the measure brain response to visual stimuli. They are then given a visual stimulus, and the time between the visual stimulus and the brain response (on EEG) is measured. If the response is delayed this is evidence of some sort of optic nerve lesion.




What other conditions can mimic MS lesions on MRI?


  • Sarcoidosis
  • SLE
  • Bechet's syndrome




What non-pharmacological apsects would you consider when managing someone with MS?

Discuss the following

  • Education
  • Living arrangements
  • Job
  • General future plans
  • Lifestyle advice - exercise, smoking, avoid stress
  • MDT input - physio, OT, psychiatry etc.




If someone had an acute relapse of MS, how would you manage them?



IV/PO Methyprenisolone - 3-5 days (shortens relapse)




What dose of methyprednisolone would you give someone having an acute relapse of MS?



0.5-1g/24 hrs




What disease modifying medications would you use in an attempt to reduce relapse rate in RRMS?


  • Dimethyl Fumarate
  • Fingolimod
  • Teriflunomide
  • Cladribine
  • Natalizumab
  • Alemtuzumab

B-interferon and Glatiramer Acetate now no longer recommended by NICE in England and Wales




How would you manage symptoms of spasticity in someone with MS?



  • 1st line - Baclofen, Gabapentin
  • 2nd line - Tizanidine, dantrolene
  • 3rd line - benzodiazepines





How would you manage tremor symptoms in someone with MS?



Botulinum toxin




How would you manage symtpoms of urinary incontinence in someone with MS?


  • Antimuscarinic medications - tolterodine, oxybutinin
  • Teach self-Catheterisation




How would you manage symptoms of fatigue in someone with MS?


  • Amantadine
  • CBT
  • Exercise




How would you manage symptoms of constipation in someone with MS?







How would you manage symptoms of dysaesthesia/pain in someone with MS?



  • Amytriptilline
  • Gabapentin
  • Pregabalin




How would you manage speech/swallowing difficulties in someone with MS?



SALT input




When should you commence treatment for urinary symptoms seen in MS?



Once residual bladder volume > 100ml




Which individuals would be involved in an MDT managing someone with MS?


  • MS nurse
  • Physiotherapist
  • Occupational therapist
  • Speech and language therapist
  • Dietician
  • Rehab sepcialist
  • Continence advisor
  • Psychology/Psychiatry
  • Care workers




How do individuals with MS most commonly die?


  • Bronchopneumonia
  • Renal failure