Author: Fionn Bellis, Rasheed Kaja Mohammad / Editor: Yasmin Sultan / Reviewer: Rasheed Kaja Mohammad, Mohamed Elwakil / Code: NeuC7, NeuP7, NeuP8, SLO1 / Published: 25/04/2023

Previously-well patients may present to the emergency department (ED) with a wide range of neurological symptoms that may be attributable to multiple sclerosis (MS) but may also indicate other aetiologies.

Patients with an established diagnosis of MS may present to the ED with acute complications for which treatment needs to be instituted promptly in order to minimise complications [1,2].


MS is an idiopathic, inflammatory demyelinating disorder of the brain and spinal cord [Image shown: Demyelination with cell loss].

It is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences.

It is the major cause of non-traumatic disability in young adults.

Patterns of MS


a) Clinically Isolated Syndrome (CIS)

CIS is the first episode caused by inflammation and demyelination in CNS. This episode must last for at least 24 hours. People who develop CIS may or may not go on to develop MS.

When CIS is accompanied by brain MRI lesions characteristic of MS, the person has higher likelihood of a second episode of neurological symptoms and diagnosis of relapsing remitting MS.

b) Relapsing Remitting MS (RRMS)

The most common disease course, characterised by clearly defined attacks (also called relapses/ exacerbations) followed by periods of partial or complete recovery (remissions).

During remissions all symptoms may disappear or some symptoms may continue and become permanent but there is no apparent progression of disease.

85% of MS patients are initially diagnosed with RRMS.

c) Secondary Progressive MS (SPMS)

Most patients with an initial relapsing remitting course have an eventual transition to secondary progressive course of neurological worsening and accumulation of disability over time.

d) Primary Progressive MS (PPMS)

PPMS is characterized by worsening neurological function from onset of symptoms, without relapse or remissions. 15 % of MS patients are diagnosed with PPMS.



The MRI displays a person with MS. The MRI shows the sclerotic plaques associated with the condition.

What is MS?

MS is a multicentric, multiphasic inflammatory disorder of the central nervous system (CNS) in which focal lymphocytic infiltration leads to damage to myelin and axons. The inflammation is initially transient with a degree of remyelination but over time there is chronic neurodegeneration. The end stage is the formation of sclerotic plaques [3].

What is the underlying disease process?

The disease process starts with the migration of reactive T-lymphocytes across the blood brain barrier. The exact nature of the target auto-antigen is not clear but is most likely to be a myelin protein.

Learning Bite

MS is an acquired inflammatory neurodegenerative disorder.

Clinical presentations in MS include11:

  • loss or reduction of vision in 1 eye with painful eye movements
  • double vision
  • ascending sensory disturbance and/or weakness
  • problems with balance, unsteadiness or clumsiness
  • altered sensation travelling down the back and sometimes into the limbs when bending the neck forwards (Lhermitte’s symptom).

People with MS present with symptoms or signs as described above, and:

  • are often aged under 50 and
  • may have a history of previous neurological symptoms and
  • have symptoms that have evolved over more than 24 hours and
  • have symptoms that may persist over several days or weeks and then improve.

MS should not routinely be suspected if a person’s main symptoms are fatigue, depression or dizziness unless they have a history or evidence of focal neurological symptoms or signs.

The underlying pathophysiology accounts for some of the characteristic symptoms of MS:

  • Partially demyelinated fibres conduct slowly, explaining symptoms relating to physiological fatigue
  • Partially demyelinated fibres can also discharge spontaneously giving rise to unpleasant distortions of sensation
  • Increased mechanical sensitivity of neurones can give rise to symptoms induced by movement such as flashes of light on eye movement and an electric shock sensation felt in the spine or legs on neck flexion (Lhermittes symptom)
  • Conduction can fail with an increase in temperature, accounting for temporary exacerbations of symptoms on exercise or after a hot bath (Uhthoff symptom)

MS lesions characteristically involve the optic nerve and peri-ventricular white matter of the cerebellum, brain stem, basal ganglia and spinal cord. The peripheral nervous system is rarely involved.

Learning Bite

MS is characterised by episodes of multiple neurological dysfunction, e.g. vision and sensory disturbances, limb weakness, gait problems and bladder and bowel symptoms followed by incomplete recovery.


MS is the most common debilitating illness affecting young adults.

Incidence: The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries.

Sex: The male to female ratio is 1:2.

Age: The typical age range of presentation is 20-50 years. Occurrence of MS is very rare under 15 or over 60 years.

Geography: There is a marked geographical and race distribution of MS, with the condition occurring twice as commonly in Caucasians than in any other race.

The incidence is highest in Canada and Scotland.

Overall MS is five times more prevalent in temperate climates than in the tropics, but this increased risk is only associated with childhood years spent in temperate climates [4].

The trigger for the autoimmune process in MS is not clear but is certainly multifactorial with combined genetic, environmental and/or infectious triggers:


Genetically, there is a well-established association of the incidence of MS with certain MHC-II alleles.

There is a familial rate of 20% with up to 30% concordance in monozygotic twins but only 5% in dizygotic twins; strongly favouring the existence of a secondary environmental trigger [5].


Geographically, the incidence of MS rises with increasing distance from the equator suggesting the lack of sunlight and possibly Vitamin D as potential triggers.

Recently, mechanisms linking the major genetic and environmental risk factors have been identified.


Various infectious triggers have also been implicated including human herpes virus 6, EpsteinBarr virus (EBV)and chlamydia

Learning Bite

The aetiology of MS includes a complex interaction of environmental factors in genetically susceptible individuals. It occurs most commonly in middle-aged people, females and people who have spent their pre-adult life in northern latitudes.

MS is suspected when a young person presents several times with neurological symptoms that suggest different areas of pathology, often with resolution of prior symptoms.

Lower extremities are typically affected more than upper extremities.

Patients may describe sensations of:

  • Heaviness
  • Weakness
  • Stiffness

Physical examination will demonstrate:

  • Decreased strength
  • Increased tone
  • Babinskis reflex (Image)
  • Impairment of:
    • Vibration sense
    • Proprioception
    • Pain detection
    • Temperature detection

Cerebral MS, though uncommon (affecting less than 5% of patients), can cause disabling loss of intellect and seizures.

The image displays Babinski’s reflex. Babinski negative is a normal reaction. A positive Babinski test is a common finding in patients with MS.

Optic neuritis, inflammation or demyelination of the optic nerve, is the initial presentation of 15% of patients with MS.

Approximately 50% of all patients who present with optic neuritis have MS. Isolated episodes of optic neuritis, however, even if they are recurrent, are not diagnostic of MS [6].

Eye involvement in MS:

  1. Optic Neuritis (ON) is the Inflammation of optic nerve at any point and is a frequent presenting symptom manifesting as:
    • variable degree of visual loss affecting mainly central vision and sometimes decreased colour vision.
    • Relative Afferent Pupillary Defect (RAPD), causing Marcus Gunn Pupil.
    • Fundoscopy may be normal or rarely shows papillitis.
    • Central or cecocentral scotoma on visual field mapping.
    • visual loss is often preceded by retrobulbar or extraocular muscle pain that may be reproduced by periorbital palpation.
    • 90% of patients regain normal vision, typically over a period of 2 to 6 months.
  2. Bilateral, simultaneous ON is rare in MS and may suggest other diagnosis.
  3. Oculomotor pathway involvement (may be in association with brainstem or vestibulo-ocular lesions):
    • Cranial nerve VI, III and IV may be involved.
    • Nystagmus is common in MS
    • Acquired pendular nystagmus of eyes in primary position is characteristic of MS.
    • Oscillopsia: Subjective oscillation of objects in the field of vision due to nystagmus (often bilateral) is a frequent symptom in MS.

There are three phenomena associated with optic neuritis:

Light flashes

Phosphenes, or flashes of light, are usually precipitated by eye movements.

Uhthoff phenomenon

Uhthoff phenomenon or deterioration of vision is induced by exercise, a hot meal or a hot bath.

Pulfrich effect

The Pulfrich effect occurs when latencies between the eyes are unequal, resulting in a sense of disorientation in moving traffic.

Other presentations associated with MS include:

Transverse myelitis

Rarely, patients may present with a complete, or incomplete, loss of motor function below a certain segment of the spinal cord i.e. an acute transverse myelitis.

This motor deficit is often accompanied by sensory, autonomic, reflex, and sphincter disturbances.

The differential diagnosis includes mechanical compression of the spinal cord and cauda equina syndrome secondary to tumour or prolapsed disc [7]. Urgent MRI imaging is essential to identify which patients may benefit from emergency surgical decompression.

Neuromyelitis optica

This a rare disorder characterised by Optic neuritis and Acute myelitis that is often misdiagnosed as MS. It is diagnosed based on specific guidelines by neurologists.

It is an antibody-meditated disease involving demyelination of the optic nerve and spinal cord which responds to immunosuppressive treatments. It has a high mortality rate if not diagnosed and treated appropriately.

Learning Bite

A patient presenting with an episode of isolated optic neuritis, should be confirmed by an ophthalmologist, and referred to a consultant neurologist for further assessment10.

Acute disseminated encephalitis

Acute disseminated encephalitis is pathophysiologically and radiographically identical to MS.

It is characterised by acute onset of motor, sensory, cerebellar, and cranial nerve dysfunction with encephalopathy, progressing to coma and eventual death in 30% of such cases.

The nature of the investigations undertaken depends on whether the patient is one in whom MS is a new diagnostic possibility or a patient where the diagnosis is already known.

In a patient suspected with MS in the ED, before specialist referral

The priority is to rule out other differentials by the following recommended initial tests10:

1. Full blood count Significant anaemia
2. Inflammatory markers (ESR, CRP) Alternative infectious or inflammatory process
3. Liver function tests Baseline function before treatment
4. Renal function tests Renal function needed for further contrast neuroimaging
5. Calcium Hypocalcaemia – MS like sensory symptoms

Hypercalcemia in sarcoidosis

6. Glucose Diabetic peripheral neuropathy, hypoglycaemia
7. Thyroid function tests Hypothyroidism – MS like sensory symptoms
8. Vitamin B12 Deficiency related neurologic deficit
9. HIV serology HIV can mimic MS due to transverse myelitis

HIV may be associated with neurosyphilis

Further investigations for patients in whom a diagnosis of MS is possible

CT scanning of the brain may be indicated if the differential diagnosis suggests an acute intracerebral pathology.

MRI for the exclusion of a surgically decompressible spinal cord lesion in patients with symptoms consistent with acute transverse myelitis.

CSF analysis may be indicated if the diagnosis is uncertain and the presentation raises suspicion of CNS infection. CSF protein and gamma globulin concentrations are elevated in many MS patients although some patients with MS will have normal or atypical CSF findings.

Serum electrolytes to determine abnormalities associated with neurological or muscular defects – potassium, calcium, phosphate; coagulation screen if lumbar puncture is considered.

Further evaluation may be carried by the specialist/ neurologist based on individual presentation and may include syphilis serology, autoimmune screening etc

Learning Bite

There is no single diagnostic test for MS in patients who present with signs consistent with MS, and in whom the diagnosis has not been made previously, urgent discussion with a Neurologist and MRI scanning is required.

Investigations for patients in whom a diagnosis of MS is established already

In patients with known MS who present with a further decline in their neurological function, investigations are required to identify reversible causes. Routine investigations will include:

  • Full blood count with differential to look for infection
  • Urinalysis to exclude urinary tract infection (UTI) (see Management page)

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Investigations in the ED will largely be focussed on management of acute complications of MS such as fever and urinary tract infection and the exclusion of serious reversible alternative diagnoses, especially spinal cord compression

Patients with MS may present with symptom changes due to:

  • Another illness (eg. infection)
  • Further relapse
  • Change of disease of status

To manage patients with MS, a Coordinated multidisciplinary approach is recommended and should consist of:

  • Consultant neurologists
  • MS nurses
  • Physiotherapists and occupational therapists
  • Speech and language therapists, psychologists, dietitians, social care and continence specialists
  • GPs

single point of contact should be designated to coordinate care & help access services for MS patients and they should be informed when MS patients present with symptom changes.

It is recommended that an agreed care planto manage significant symptom changes in MS patients should be in place.

The goals of medical management of MS are to:

  • Delay onset of further symptoms
  • Slow disease progression
  • Relieve symptoms of the presenting features
  • Reduce complications associated with an acute exacerbation

Relieving symptoms and reducing complications are the focus of management of MS in the ED.

Management of initial presentations

Disseminating acute encephalitis

The focus is to stabilise acute life-threatening conditions, initiate supportive care and seizure precautions and monitor for increasing intracranial pressure (ICP).

Other presentations

Acute MS episodes are thought to be secondary to an episode of demyelination. Therefore, treatments that modify the inflammatory process and immune system are used in an attempt to minimise this demyelination.

Any individual who experiences an acute episode (including optic neuritis) sufficient to cause distressing symptoms or a limitation of activity should be offered a course of high-dose corticosteroids [9].

Relapse (Attack/ exacerbation)

A clinical episode with patient reported symptoms and objective findings typical of MS reflecting a focal or multifocal demyelination in the CNS, developing acutely or subacutely, with a duration of atleast 24 hours, with or without recovery and in the absence of fever or infections. When it is the first episode it is Clinically Isolated Syndrome.

Treating acute relapse of MS

  1. Under guidance of professionals with expertise in treating MS, since not all relapses need steroids.
  2. Oral methylprednisolone 0.5 g daily for 5 days should be offered to patients with relapse.
  3. Intravenous methylprednisolone 1 g daily for 3-5 days is an alternative if:
    • oral steroids have failed or not tolerated.
    • Patients requiring admission for a severe relapse or monitoring of medical or psychological conditions such as diabetes or depression.
  4. Steroids should not be prescribed at lower doses than methylprednisolone 0.5 g daily for 5 days to treat an acute relapse of MS.
  5. Patients with MS should not be a supply with steroids to self-administer at home for future relapses.
  6. High-dose steroid prescription should be done after explaining possible temporary effects on mental health (such as depression, confusion and agitation) and worsening of blood glucose control in people with diabetes.

Other treatment options might be considered by specialists which may include diet modification, beta interferon, glatiramer acetate, azathioprine, mitoxantrone, IV IG, plasma exchange, intermittent pulsed methylprednisolone etc.

Management of the complications of MS

Fever: Fever must be reduced to minimise the increased weakness caused by even a small elevation of core temperature. Aim to normalise body temperature with surface cooling and antipyretics.

Infection: Aggressively seek and treat any cause of infection. Urinary tract infections and pyelonephritis must be excluded in any acute exacerbation of MS. A microscopy culture and sensitivities (MC&S) must be sent and antibiotics started if screening dipstick testing suggests a urinary tract infection (UTI).

Urinary retention: Especially in patients with symptoms of UTI, a post-voiding residual volume determination should be made with sterile catheterisation if indicated. Patients may need to be referred for advice on intermittent sterile catheterisation to avoid a long-term indwelling catheter.

Respiratory function: Respiratory infections must be managed aggressively. Endotracheal intubation may be complicated by a higher risk of aspiration.

Autonomic lability: MS patients are at higher risk of hypotension at induction of anaesthesia. Spontaneous ventilation may be disrupted.

Seizures: Seizures should be treated according to the usual algorithms.

Issues faced by MS patients Recommendations
Risk factor modification
Exercise May provide long term benefits and has no harmful effects on MS.
Vaccination Live vaccinations are contraindicated in those treated with disease modifying agents.

Flu vaccine should be given in accordance with national guidance and individualised approach.

In relapsing remitting MS, there is a risk of relapse after flu vaccine.

Coronavirus (COVID-19) vaccination should be given as soon as practical for all patients with MS.

Stress Anxiety, depression and difficulty in sleeping must be actively addressed.
Pregnancy Relapse rates may reduce during pregnancy and may increase in the first 3 to 6 months postpartum.Pregnancy does not increase disease progression.
smoking It may increase progression of disability and should be discouraged.
Symptom management
Spasticity Constipation, infection, pressure ulcers etc. may aggravate spasticity.Self-adjusted drug treatment under guidance with agents like baclofen, gabapentin, tizanidine etc.

Benzodiazepines may be used as 3rd line agents.

Mobility, Ataxia & tremor Supervised exercise programme and moderate resistance training. Vestibular rehabilitation should be considered if balance problems are identified.
Oscillopsia Gabapentin and memantine are recommended but specialist is needed review if no improvement
Emotional lability Amitriptyline
Fatigue May be exacerbated by heat, over – exertion and stress. Mindfulness training and Cognitive Behavioural therapy are beneficial.

Aerobics, balance and yoga training.

Amantadine may be offered.

Vitamin B 12 should not be used to treat fatigue in MS.

Memory & cognitive impairment Neuropsychological rehabilitation
Ataxia & tremor, Fatigue, mobility, pain, spasticity Supervised self-management programme
Vitamin D Should not be offered solely for the purpose of treating MS.
Omega fatty acids (3 & 6) There is no evidence of effect on MS relapse or progression
Chronic pain Established chronic pain guidelines and pain specialist referral.
Disease modifying therapy, symptom control & rehabilitation Comprehensive yearly review and additional review as per individual needs.
Advance care planning & power of attorney A shared plan based on discussion with patient family and multidisciplinary professionals including palliative care and end of life care when appropriate.

Other therapies

Advocates of medical marijuana believe that MS symptoms, especially spasticity, can be improved with the use of cannabis.

However, in randomized trials, cannabinoids have failed to provide consistent improvement in MS-related outcomes [15,16].

New treatments for MS

  • Fingolimod (Gilenya) was the first FDA-approved oral DMT. In The TRANSFORMS trial the annualized relapse rate was significantly reduced in fingolimod groups compared with the interferon beta-1a group.
  • Dimethyl fumarate another oral treatment, In the CONFIRM and DEFINE trials, an oral formulation of dimethyl fumarate(BG-12) significantly reduced relapse rates and the development of new brain lesions on MRI in patients with active MS.
  • Ponesimod was approved by the FDA in March 2021 for the treatment of adults with relapsing forms of MS.

Most patients with the relapsing and remitting form of MS progress to a stage where relapses become much less frequent, but they continue to accumulate disabling symptoms. This new phase of the disease is termed ‘secondary progressive multiple sclerosis’.

No treatment for MS is curative. The average life expectancy is reduced by 5 to 10 years, with only 40% of patients reaching the age of 70.

The ability to walk is an important aspect of independence and is retained by 90% of MS patients 10 years after diagnosis and 75% at 15 years.

Two-thirds of MS patients die of the complications of their disease, especially pulmonary complications.

Suicide is significantly more common. For those whose disease progresses rapidly over a few years, the suicide risk is seven times greater than the population as a whole.

Generally, sensory and cranial nerve symptoms predict a less unfavourable outcome than those caused by motor nerves or cerebellar dysfunction.

A minority of patients have a very mild form of the disease with little or no disability. Their neurological disability may barely affect their daily activities, and the disease does not shorten their life span.

Acute fulminant MS:

A rare aggressive, rapidly deteriorating form of MS has been described that leads to death or severe residual disability within days.

Learning Bite

MS is associated with a 5- to 10-year reduction in life expectancy with death occurring as a result of respiratory and renal complications or suicide in two-thirds of patients.

The emergency physician should be aware of the following pitfalls:

  • Assuming that symptoms of transverse myelitis are due to MS
  • Failing to exclude a surgically treatable compressive lesion in the first instance
  • Making the diagnosis of MS in the ED: there are a number of differentials, and formal diagnosis requires neurological expertise. The patient should be assessed urgently by a neurologist
  • New-onset MS is an unlikely diagnosis in those younger than 16 years or older than 50 years
  • Failing to ensure that MS patients with an acute relapse are referred/admitted for appropriate therapy
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