Multiple sclerosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The main goals of treatment are prevention of disability and improvement of quality of life. Treatment is generally divided into three main categories: management of acute worsening/relapses; disease-modifying therapy; and symptomatic management. Disease-modifying treatment should be managed by a neurologist.

Non-pharmacological interventions, such as cognitive training and psychological interventions, may offer some benefit to patients with MS, particularly regarding quality of life outcomes.[46][47] Results should be interpreted cautiously; further studies, with improved design, are required to assess the effectiveness of non-pharmacological interventions.[48][49] [ ]

Acute management of relapses

The first step in management of acute worsening and/or relapse is to be certain that there is no concomitant illness or infection. Patients with MS commonly experience worsening of their condition during urinary tract infections (which may be asymptomatic), sinusitis, viral infection, cellulitis and other skin infections, or fevers from any cause. Underlying infections should be appropriately treated.[50][51]

If the relapse affects function (e.g., decreased or double vision, difficulty walking, or difficulty using a hand due to coordination or weakness problems), treatment with high-dose methylprednisolone and oral taper can be offered if not contraindicated by infection or poorly controlled diabetes or hypertension.[52][53] Whether this treatment has any long-term effect on disability is unknown, but symptomatic improvement is often observed. Intravenous administration is the standard route; however, if this is not possible, high-dose oral administration may be considered and is non-inferior to intravenous administration.[54] Various oral regimens exist; a specialist should be consulted when selecting an oral regimen.

In cases of neuromyelitis optica spectrum disorders (NMOSD), high-dose intravenous corticosteroid treatment is first-line treatment. A longer oral taper may be required to prevent relapse, especially for patients who are seropositive for myelin oligodendrocyte glycoprotein auto-antibodies. For more information, see our topic on Transverse myelitis.

Patients with severe acute relapse or rapidly progressing disability may benefit from plasma exchange or plasma exchange plus intravenous corticosteroids.[55]

Disease-modifying therapy - clinically isolated syndrome (CIS)

There is evidence supporting reduced risk of progression to clinically definite MS with immunomodulatory treatment of CIS.[56]

Disease-modifying therapies for patients with a first clinical episode and magnetic resonance imaging (MRI) features consistent with MS include glatiramer, interferon beta-1b, interferon beta-1a, teriflunomide, dimethyl fumarate, and diroximel fumarate. [ ] [ ] In the US, fingolimod and siponimod may also be used.

Disease-modifying therapy - relapsing-remitting MS (RRMS)

Disease-modifying therapy should be considered for all patients with relapsing-remitting MS (RRMS).[15][57] However, some patients may have a benign course, or be in an age group (generally, >55 years) where the benefits of disease-modifying therapy may be less clear.

Interferon beta preparations, glatiramer, dimethyl fumarate, diroximel fumarate, and teriflunomide are generally considered to be first-line agents.[58][59][60][61][62] [ ] [ ] [Evidence B] In some countries, fingolimod and siponimod may also be used as first-line agents. However, fingolimod, siponimod, natalizumab, ocrelizumab, cladribine, and alemtuzumab are more commonly reserved for patients who have more aggressive disease and/or have not tolerated or responded to previous disease-modifying agents.[58][59][63][64][65][66][67]

In patients with RRMS, further investigation is required to determine whether long-term outcomes are more favourable when treatment is initiated with: moderately effective, safer medications, with escalation as needed; or with higher efficacy disease-modifying therapies from the outset.[68][69][70]

Interferon beta and glatiramer

Interferon beta preparations and glatiramer are believed to interfere with the formation of new demyelinating plaques in the central nervous system. Systematic reviews and meta-analyses indicate that they reduce relapse rates by approximately 30%.[71][72] One network meta-analysis concluded that interferon beta and glatiramer both reduce relapse rates and delay progression, with comparable effectiveness, although there was a high risk of bias across studies.[73] Long-term observational data (median 21 years from randomised controlled trial enrolment) suggest that early treatment with interferon beta-1b is associated with prolonged survival in initially treatment-naive patients with RRMS.[74]

Interferon beta preparations are metabolised in the liver and require periodic monitoring of full blood count and hepatic function. Glatiramer does not have the flu-like side effects of the interferons, but may take 6-9 months for clinical effect.[75][76] Tolerability and adherence to interferon beta preparations and glatiramer do not appear to differ markedly.[77]

Local injection-site reactions and a wide spectrum of generalised cutaneous adverse events are frequently reported with these disease-modifying therapies, particularly the subcutaneous formulations.[78] However, most are mild and do not require cessation of therapy.

Glatiramer is available as different subcutaneous formulations that can be given either once daily or three times weekly.[79] Peginterferon beta-1a is also available as a subcutaneous formulation and is given every 2 weeks.[80][81]

Dimethyl fumarate

An oral disease-modifying therapy that reduces annual relapse rates by around 40% to 50% when compared with placebo.[82][83]

Monitoring of blood counts is required during dimethyl fumarate therapy. Possible adverse effects include full-body flushing, gastrointestinal (GI) events, and headache. [ ] Full-body flushing may continue throughout treatment, although it can be controlled with the use of aspirin. GI-related adverse effects are usually transient, lasting for approximately 8 weeks following initiation of dimethyl fumarate; they are reduced by taking the medication with food, particularly foods containing some type of fat or oil. Over-the-counter treatments for heartburn and indigestion can be used to help to alleviate GI adverse effects.

Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients receiving dimethyl fumarate; persistent lymphopenia appears to be a risk factor.[84] Monitoring of lymphocyte counts every 6 months while on therapy is advised.

Clinically significant cases of liver injury in patients treated with dimethyl fumarate have been reported.[85] The onset ranged from a few days to several months after initiation of treatment. Liver function tests should be obtained at baseline and considered at 6- to 12-month intervals.

Diroximel fumarate

Diroximel fumarate, an orally administered agent, is similar to dimethyl fumarate with comparable efficacy. Both drugs have the same active metabolite (monomethyl fumarate).[86]

In one open-label phase 3 study, diroximel fumarate was associated with lower rates of GI adverse events than dimethyl fumarate.[87] Risk of clinically significant cases of liver injury should be considered in patients on diroximel fumarate; liver function tests should be monitored during treatment.

Teriflunomide

Teriflunomide is a selective oral immunosuppressant with anti-inflammatory properties. It has been shown to reduce annual relapse rates by around 31% when compared with placebo.[88] [ ]

Monitoring of blood work is required during therapy, specifically liver function (every month for 6 months) and baseline tuberculosis testing. Patients taking teriflunomide may experience GI events such as nausea and diarrhoea, and elevated blood pressure, as well as hair thinning/loss, in the initial 8 months of treatment.

Teriflunomide is a potential teratogen; pregnancy should be excluded before starting treatment, and contraception must be used during treatment. A drug elimination procedure must be undertaken before trying to conceive.

Fingolimod

An oral sphingosine 1-phosphate (S1P)-receptor modulator whose mechanism of action involves preventing egress of lymphocytes from lymph nodes.[89] Fingolimod has been shown to significantly reduce annual relapse rates compared with placebo, to improve other MRI outcomes, to improve quality of life, and to have an acceptable safety profile.[90] [ ]

Fingolimod is a non-selective S1P agonist and is associated with potential off-target adverse effects, including persistent bradycardia, bronchoconstriction, and macular oedema. The UK Medicines and Healthcare products Regulatory Agency (MHRA) stipulates a number of contraindications relating to fingolimod use in patients with pre-existing cardiac disorders.[91]

Patients require an ECG and ophthalmological examination, preferably including optical coherence tomography, prior to initiating fingolimod. ECG is repeated 6 hours after the initial dose of fingolimod. Exact protocols regarding first dose-monitoring vary, but must involve heart rate monitoring for bradycardia. The initial dose should be administered in a setting with resources available to manage symptomatic bradycardia.

Patients require periodic full blood count and hepatic function monitoring. Repeat optical coherence tomography occurs 3-4 months after initiation of the medication. Patients should be monitored for the development of severe headaches, which may be due to vasospasm, and pulmonary issues such as shortness of breath and reduction in vital capacity.[89][92] Severe worsening of MS has been reported after stopping fingolimod; the disease can become much worse than before the medication was started or while it was being taken. Although this is rare, it can result in permanent disability. Patients should be monitored closely for evidence of exacerbation of their condition after stopping treatment.[93]

The potential exists for fatal reactivation of herpes virus infections in patients receiving fingolimod.[89][92] PML has been reported in patients taking fingolimod. A baseline MRI, as well as routine MRIs during treatment, should be performed.[3]

Cases of basal cell carcinoma have been reported in patients taking fingolimod, and the drug is contraindicated in patients with basal cell carcinoma.

Siponimod

An S1P receptor modulator for oral use with a similar mechanism of action to fingolimod. Siponimod is approved by the US Food and Drug Administration (FDA) for the treatment of adults with relapsing forms of MS, including RRMS (and clinically isolated syndrome and active secondary progressive disease). One randomised extension of a phase 2 study reported that disease activity was low in patients with RRMS during 24 months of siponimod treatment.[94]

Potential adverse effects of siponimod therapy include increased risk of infection, macular oedema, lymphopenia, and transient decreases in heart rate. Siponimod selectively modulates S1P receptor type 1 and type 5, so may be associated with a reduced risk of adverse effects induced by S1P3 receptor activation.[95]

Cladribine

Works by gradually depleting T and B lymphocytes. One placebo-controlled phase 3 trial reported significantly reduced relapse rates at 2 years in patients with RRMS who were randomised to treatment with oral cladribine.[96]

Adverse effects include lymphopenia and increased risk of infection (specific concern for herpes infections). Cladribine may increase the risk of malignancy and of fetal harm; it must not be used by patients with current malignancy, or by women and men of reproductive age who do not plan to use effective contraception.

Oral cladribine is approved by the FDA in the US for the treatment of relapsing forms of MS in adults, including RRMS. It is licensed by the European Medicines Agency (EMA) for the treatment of adult patients with highly active relapsing MS.

Natalizumab

A monoclonal antibody given by intravenous infusion every 4 weeks. It reduces annual relapse rates by over 60% in patients with RRMS or secondary progressive MS.[97]

Natalizumab is associated with an increased risk of PML. Factors associated with this increased risk are believed to include John Cunningham virus (JCV) antibody positivity, particularly with higher titres of the antibody, length of time on natalizumab, and prior exposure to chemotherapy or immunosuppressive agents (not including corticosteroids).[98][99] Expert panel recommendations regarding the stratification and ongoing monitoring of natalizumab-associated PML risk have been published.[100] There is evidence that the incidence of PML among MS patients taking natalizumab has decreased since the introduction of JCV testing and risk-stratification recommendations.[101] A baseline MRI should be performed, as well as routine MRI during treatment.[3]

Ocrelizumab

A humanised anti-CD20 monoclonal antibody approved by the FDA and the EMA for the treatment of relapsing forms of MS.[102][103] Network meta-analyses indicate that ocrelizumab is at least as effective as other currently approved disease-modifying therapies for relapsing MS, with a similar safety profile.[104][105]

Ocrelizumab can cause infusion-related reactions, which can be severe, and increase risk of infection. It may also increase the risk for malignancies, particularly breast cancer.

Rituximab

A chimeric anti‐human CD20 monoclonal antibody used off-label for the management of MS in some countries.[106] There is evidence for the efficacy and safety of rituximab in patients with RRMS.[107][108]

Alemtuzumab

A monoclonal antibody directed against the CD52 antigen, alemtuzumab is approved for use in adult patients with RRMS.[109][110][111] It is given by intravenous infusion for two treatment courses separated by 12 months. One Cochrane review found that, compared with interferon beta-1a, alemtuzumab reduced the proportion of patients with RRMS who experienced relapse, disease progression, change of expanded disability status scale score, and development of new T2 lesions on MRI over 24-36 months.[112] [ ]

Rare, serious adverse effects, some fatal, reported within 3 days of alemtuzumab infusion include myocardial ischaemia, myocardial infarction, cerebral haemorrhage, cervicocephalic arterial dissection, pulmonary alveolar haemorrhage, and thrombocytopenia.[113] Immune-mediated conditions can occur many months after treatment. A risk of serious and life-threatening infusion reactions, infections, and an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders, have also been reported.[112] [ ] Serious cases of stroke and tears in the lining of arteries in the head and neck (cervicocephalic arterial dissection) have been reported in patients soon after alemtuzumab treatment (usually within 1 day). These can result in permanent disability and even death.[114] Healthcare professionals should consider stopping alemtuzumab in patients who develop signs of any of these conditions.

Alemtuzumab should be given in a hospital with ready access to intensive care facilities and specialists who can manage serious adverse reactions. Vital signs should be monitored before and during each infusion, liver function tests should be performed before and during treatment, and patients should be monitored for signs of pathological immune activation. Patients should be informed of the signs and symptoms of these conditions at each infusion, and advised to seek immediate medical attention if they experience symptoms.[115]

Because of its safety profile, alemtuzumab is approved by the FDA for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. In Europe, the use of alemtuzumab is restricted to patients with RRMS that is highly active despite adequate treatment with at least one disease-modifying therapy or if the disease is worsening rapidly, with a minimum of two disabling relapses in 1 year and brain imaging showing new damage. Alemtuzumab must not be used in patients with certain heart, circulation, or bleeding disorders.[115]

Pregnancy and the postpartum period: disease-modifying therapy

It is important to discuss family planning and pregnancy with women and girls of childbearing age, starting at or soon after diagnosis of MS.[116] MS does not affect fertility, and contraception should be used when pregnancy is not wanted.

There is uncertainty regarding the potential harms to neonates from the use of disease-modifying drugs pre-conception and during pregnancy. For all drugs, the risk of potential harm to the neonate must be weighed against the risk of relapse in individual patients.[57] Guidelines from the Association of British Neurologists outline considerations with specific medications and circumstances.[116]

Prospective data indicate that among pregnant women with MS (who were only allowed short courses of glucocorticoids for treatment of MS during pregnancy), risk for relapse is lower during pregnancy than at baseline.[117] However, approximately 1 in 4 women had a relapse in the first 3 months post partum.[117] It has been postulated that breastfeeding during the postnatal period may reduce relapse in patients with MS, but this requires further investigation.[118]

Recommendations regarding specific agents

The EMA recommends that, because of the risk of major congenital malformations, fingolimod must not be used in pregnant women or in women of childbearing age who are not using effective contraception. If a woman becomes pregnant while using fingolimod, the medicine must be stopped and the pregnancy should be closely monitored.[119]

Cladribine may increase the risk of fetal harm, so it must not be used by women of childbearing age who are not using effective contraception.

Teriflunomide is a potential teratogen. A drug elimination procedure must be undertaken before trying to conceive.

Disease-modifying therapy - progressive MS

Patients with rapid disease progression or who have a mixture of progression and relapses may be treated with many of the same medications used for RRMS.

Secondary progressive MS

The following medications are FDA-approved for relapsing forms of MS, including active secondary progressive disease: siponimod, cladribine, interferon beta-1a, interferon beta-1b, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, diroximel fumarate, and alemtuzumab. Siponimod is the only therapy with demonstrated efficacy in a large randomised controlled trial of patients with secondary progressive MS.[120]

Siponimod reduced the risk of disability progression compared with placebo (statistically significant lower percentage of patients with confirmed progression of disability in 3 months in the siponimod group) in a large double-blind, randomised controlled trial of patients with secondary progressive MS.[120]

Intravenous methylprednisolone (FDA-approved for the treatment of acute exacerbations of MS) administered using a pulse-dose protocol has been used regularly with some benefit in patients with secondary progressive MS. However, there is no consensus on optimal dosing. It may be considered in patients who do not have other treatment options, but the benefit must be weighed against potential adverse effects.

Cladribine reduced relapses and MRI lesion activity in a 96-week phase 2 randomised study of patients with active relapsing MS for whom interferon was not effective.[121] However, patients with secondary progressive MS made up only a small percentage of the trial population.

Interferon beta preparations do not appear to prevent the development of permanent physical disability in secondary progressive disease.[122][123]

Natalizumab did not reduce disability progression on the primary composite endpoint of a phase 3, randomised, double-blind, placebo-controlled trial of patients with secondary progressive MS.[124] However, it did reduce upper limb worsening.[124]

Mitoxantrone has been shown to reduce annualised relapse rate by about one half in both RRMS and secondary progressive MS patients. However, it may be poorly tolerated due to GI and fatigue-related side effects. Mitoxantrone has the potential for serious adverse effects including cardiotoxicity (requiring regular monitoring of left ventricular ejection fraction) and acute myelogenous leukaemia, and so it is rarely used.[125][126] Close monitoring of liver function and blood count should be undertaken in patients receiving mitoxantrone; neither mitoxantrone nor other systemic immunosuppressants should be used in patients who have frequent urinary tract infections or concomitant illness.[127]

Primary progressive MS

Ocrelizumab, approved by the FDA for the treatment of primary progressive MS, was associated with lower rates of clinical and MRI progression than placebo in a phase 3 trial of patients with primary progressive MS.[103] However, ocrelizumab has not been studied in patients older than age 55 years or in those with severe disability (expanded disability status scale >6.5). Thus, in Europe it is approved in early-stage primary progressive MS only.[128]

Other medications that have been used include cyclophosphamide, methotrexate, and azathioprine, but there is no consensus regarding their benefits in primary progressive MS.[129] These medications may be used in locations where ocrelizumab is not available.

Symptomatic management - fatigue

Non-pharmacological management

Practitioners should obtain full blood count with differential, thyroid-stimulating hormone, vitamin B12, and vitamin D levels, as well as a brief sleep history, before assuming that the patient has MS-related fatigue.
Some patients with MS who report fatigue simply are not getting enough sleep or have poor sleep habits and sleep hygiene, or excessive caffeine intake. Other patients have disturbed sleep due to depression, restless legs, spasticity, pain, or bladder frequency, and these conditions should be treated appropriately. Caffeine and alcohol use can have effects on the bladder and cause disruption. Some patients have concomitant sleep disorders, such as sleep apnoea.
Most patients with MS benefit from regular exercise programmes, which promote restful sleep and reduce fatigue.[130][131] [ ] [ ] Progressive resistance training is a rehabilitation tool that may help to reduce fatigue.[132]
Some patients with fatigue may benefit from mind-body therapies, such as yoga and relaxation, or from cognitive behavioural therapy. Although the evidence supporting the use of these therapies in patients with MS is limited, they are relatively safe and can be used in conjunction with pharmacological management.[133][134][135]

Pharmacological management

If the patient continues to report fatigue following non-pharmacological approaches, amantadine can be trialled. Side effects include livedo reticularis and occasional disturbances of thought processes.
An alternative medication are modafinil or armodafinil.[136][137]
Although methylphenidate and amfetamine and/or dextroamphetamine have not been shown to be effective in trials, some patients respond favourably to them in practice.

Symptomatic management - gait impairment

Non-pharmacological management

Various physiotherapy regimens improve gait and balance in patients with MS, particularly those with mild to moderate levels of disability.[138][139][140] Progressive resistance training may help to improve balance.[132]

One systematic review found that virtual reality training is at least as effective as conventional training in improving balance and gait in people with MS.[141]

Pharmacological management

Fampridine can be used to improve gait endurance, and may increase gait speed.[142][143] Clinical trials and post-marketing surveillance indicate a dose-related increased risk of seizures with fampridine.[143] Doses should be administered 12 hours apart. Patients must have normal creatinine levels and no history of seizures before starting fampridine.[144] Healthcare providers should monitor for seizures in patients taking fampridine, and provide adequate patient education.

Symptomatic management - sensory symptoms

Patients with MS often report paraesthesias and other unpleasant sensations. These do not have to be treated with medications, but can be if they are bothersome to the patient or interfere with functioning.[145]

Exacerbations or relapses that involve solely sensory symptoms, such as paraesthesias, do not require intravenous corticosteroids and may be treated with low doses of anticonvulsants such as gabapentin or the newer carbamazepine derivatives.[146]

Various types of pain can occur in patients with MS: trigeminal neuralgia, painful dysaesthesias, painful tonic spasms and other spasticity-related pain, and musculoskeletal pain. Central or neuropathic pain can be treated with anticonvulsant and antidepressant medication.[147]

Symptomatic management - spasticity

Patients with MS often experience increased muscle tone, particularly in their legs. This can be very unpleasant and painful, disturbing sleep with leg cramps in the calves, and affecting ambulation.

The first line of management is gentle stretching exercises, which are best provided by a knowledgeable physiotherapist.

Treatment of constipation and bladder dysfunction can also be helpful.

Baclofen can be used to treat spasticity. Side effects include fatigue, clouding of mental functioning, and unmasking of underlying muscle weakness, resulting in patients reporting increased weakness. Intrathecal pumps that deliver either a constant or a variable rate of baclofen are options for:

wheelchair- or bed-bound patients, in whom spasticity limits their ability to sit in a chair or perform personal hygiene, and,
select ambulatory patients, who are affected by the side effects of high-dose oral antispasticity medications.

Tizanidine is helpful for spasticity, but is more sedating than baclofen.[148] It may therefore be useful at bedtime. Tizanidine may affect liver function and lower blood pressure. It should not be used with ciprofloxacin, which potentiates its action.[149]

Clonazepam or gabapentin can be very helpful for bedtime spasms and restless legs.

Localised botulinum toxin injections have been demonstrated to be effective in the management of spasticity associated with MS; maximum benefit is generally obtained with concomitant physiotherapy. The treatment of spasticity with localised botulinum toxin injections must balance potential symptom benefit with possible decrease in functional strength.[150][151][152]

Cannabinoids may be effective for treating symptoms of spasticity in MS.[153][154][155][156] The College of Family Physicians of Canada recommends that clinicians may consider medical cannabinoids for refractory spasticity in MS, and specifies delta-9-tetrahydrocannabinol/cannabidiol oromucosal spray (also known as nabiximols) as the medical cannabinoid of choice.[157] The National Institute of Health and Care Excellence in England recommends a trial of delta-9-tetrahydrocannabinol/cannabidiol oromucosal spray to treat moderate to severe spasticity in adults with MS in whom other pharmacological treatments for spasticity are not effective.[158]

Symptomatic management - urinary dysfunction

There is currently no agreed consensus on the management of urinary dysfunction ('neurogenic bladder') in patients with MS, and this topic remains controversial.[159] Furthermore, the progressive nature of MS can make the management of symptoms such as urinary dysfunction difficult and complex.

Optimisation of bladder management may require consultation with a urologist, neurourologist, or urogynaecologist for testing and management, but some simple measures can be very helpful.

Patients with MS should limit intake of caffeine and 'vitamin waters', as these are significant sources of bladder irritation leading to frequency.

Bladder function can be improved by management of constipation and simple timed voiding.

Some MS patients with urinary dysfunction may benefit from mind-body therapies, such as yoga and relaxation.[160] They are relatively safe, albeit with limited supporting evidence, and can be used in conjunction with pharmacological management.[133][134]

Asymptomatic bladder infections are a major problem in MS, particularly if patients have urinary retention, and preventative measures, such as increasing fluid intake and prophylactic antibiotics, may be needed. Although there are little supporting data in the medical literature, some patients have found that consuming cranberry capsules has reduced their incidence of urinary tract infections substantially.

Oxybutynin and other agents such as solifenacin, darifenacin, tolterodine, fesoterodine, and trospium can be used to reduce urinary frequency, but patients should be assessed for post-void residual volume before prescribing these agents.

Botulinum toxin injections have been effectively used to treat detrusor muscle over-reactivity and decrease patients’ urinary frequency, urgency, and incontinence.[150][161][162] Intermittent self-catheterisation is often required after this treatment.

Symptomatic management - tremor

Patients with MS may exhibit tremors of many types. It is important to distinguish true tremors from clonus (either ankle or knee), which would be managed as spasticity; paroxysmal symptoms, which would respond best to anti-seizure medications; or tremulousness from a variety of causes such as anxiety or hyperthyroidism.

The most disabling and difficult tremor to manage in MS is cerebellar tremor, which may involve the head, trunk, and extremities, as well as the voice. In severe cases, tremor alone prevents ambulation and often inhibits performance of activities of daily living such as dressing, toileting, and eating.

The most common pharmacological interventions are propranolol, primidone, and clonazepam. Care must be taken with each of these therapies because of potential adverse effects. Propranolol can produce hypotension and depression. Primidone can be very sedating, and is therefore often initiated with single dose given at night, which can be increased to a 3-times-daily dosing regimen, depending on the clinical response. Clonazepam is also sedating and may be habit-forming. It is usually initiated at a low dose, which can be titrated to higher doses depending on the clinical response.[163][164]

Peripheral venous cannulation animated demonstration

How to insert a peripheral venous cannula into the dorsum of the hand.

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