Multiple Sclerosis Flashcards
MS - Mx
Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses. There is no cure.
MS - ACUTE RELAPSE Mx
High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse. It should be noted that steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)
MS - Disease modifying drugs
BETA-INTERFERON has been shown to reduce the relapse rate by up to 30%. Certain criteria have to be met before it is used:
- relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
- secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
- reduces number of relapses and MRI changes, however doesn’t reduce overall disability
Other drugs used in the management of multiple sclerosis include:
- glatiramer acetate: immunomodulating drug - acts as an ‘immune decoy’
- natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier
- fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph nodes. An oral formulation is available
MS - Mx of Fatigue
Mx of Fatigue in MS:
- once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of amantadine
- other options include mindfulness training and CBT
MS - Mx of Spasticity
Mx of Spasticity in MS
- Baclofen and Gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine
physiotherapy is important
- Cannabis and Botox are undergoing evalulation
MS - Mx of Bladder Dysfunction
Bladder dysfunction:
- May take the form of urgency, incontinence, overflow etc
- Guidelines stress the importance of getting an ultrasound first to assess bladder emptying
- IF significant residual volume → intermittent self-catheterisation
- IF no significant residual volume → anticholinergics may improve urinary frequency (NB anticholinergics may worsen symptoms in some patients
MS -Oscillopsia
Oscillopsia= When visual fields apper to oscillate!
Mx = Gabapentin 1st line
Multiple Sclerosis - MRI Ix : Example Question
A 65-year-old male presents to the neurology outpatient department with a history of recurrent bouts of unsteadiness and vomiting over the last 10 years, with partial resolution. He has also had episodes of visual problems, which he describes as the sudden loss of vision in the right eye, with an almost complete recovery of vision over the course of the next few weeks. He has a history of type 2 diabetes and is hypertensive and is generally non-compliant with his treatment. He is also a smoker with a 50 pack year history.
His medication includes glimepiride 2mg daily and metformin 500mg TDS. He also takes telmisartan 40mg daily.
On examination, he has nystagmus in the right eye with the fast component towards the right. His gait is ataxic and he has evidence of spasticity in both lower limbs with exaggerated reflexes and bilateral ankle clonus. Fundoscopic examination revealed a pale optic disc.
MRI brain shows diffuse lesions in multiple sites. The report queried demyelinating plaques vs multiple infarcts.
Which of the following would be the most appropriate next investigation?
> MRI spinal cord CSF examination for oligoclonal bands MR angiography of the verterbrobasilar system Titres of anti-Hu antibodies Visual evoked potentials
The diagnosis, in this case, is that of multiple sclerosis and the question aims to assess the candidate’s ability to plan further investigations if the MRI of the brain is inconclusive.
An MRI of the brain is a sensitive imaging modality for the detection of plaques in patients with MS, but it lacks specificity. Over the age of 50, small ischaemic lesions may be difficult to distinguish from demyelination. The presence of spinal cord lesions, however, is quite specific for inflammatory disorders such as MS rather than ischaemic lesions. Thus cord imaging is useful when there is diagnostic difficulty.
Multiple Sclerosis - Diagnosis with MRI
An MRI of the brain is a sensitive imaging modality for the detection of plaques in patients with MS, but it lacks specificity. Over the age of 50, small ischaemic lesions may be difficult to distinguish from demyelination. The presence of spinal cord lesions, however, is quite specific for inflammatory disorders such as MS rather than ischaemic lesions. Thus cord imaging is useful when there is diagnostic difficulty.
MS and Oligoclonal Bands
Oligoclonal bands are found in the CSF in >90% of cases of MS but are not specific for MS. They are also found in Lyme disease Systemic lupus erythematosus Neurosarcoidosis Subacute sclerosing panencephalitis Subarachnoid hemorrhage Syphilis Primary central nervous system lymphoma Sjögren's syndrome Guillain-Barre syndrome Meningeal carcinomatosis Neuromyelitis optica
MS - Ix
Diagnosis requires demonstration of lesions disseminated in time and space
MRI
high signal T2 lesions
periventricular plaques
Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
CSF oligoclonal bands (and not in serum) increased intrathecal synthesis of IgG
Visual evoked potentials
delayed, but well preserved waveform
MS DIAGNOSIS
Diagnosis requires demonstration of lesions disseminated in time and space
MS - Mx of acute relapse: Example Question
A 35-year-old female presents to the Emergency Department with three days of increasing weakness in the left arm and reduced visual acuity in the left eye. She was diagnosed with relapsing-remitting multiple sclerosis two years earlier. She takes fingolimod as maintenance therapy and denies any compliance issues.
On examination, she has weakness in wrist extension and finger abduction in the left hand and visual acuity in the left eye was measured at 6/24 with an associated reduction in colour saturation. Her blood tests were unremarkable and in particular, her white cell count was normal. Her MRI scan does show two new enhancing lesions in the right pericallosal region.
How should this be managed acutely?
Commence high dose oral prednisone and wean over a month Commence intravenous dexamethasone Commence natalizumab infusion > Commence high dose methylprednisolone for 3-5 days Biopsy the enhancing lesions
Given that this patient has relapsed on maintenance therapy, and that she has multi-focal signs affecting vision and motor function, she should be admitted to hospital and commenced on high-dose intravenous methylprednisolone.
Acute relapses can be treated with either high dose oral prednisolone or intravenous therapy. The choice depends on multiple factors including the severity of symptoms, the requirement for hospital admission for monitoring, and co-morbidities such as diabetes and depression.
After this patient has recovered from this acute relapse a review of her maintenance therapy should occur, and this may be escalated through her neurologist based on a number of criteria.
Multiple Sclerosis and Disease Modifying Therapies -Example Question
A 43-year-old female presents with a second episode of loss of sensation in her left anterior thigh and right foot. This is her second episode within the past four months. She had recently reported an episode of left anterior shin numbness 1 year ago when an MRI with gadolinium demonstrated ‘spots in her spinal cord’ and she was diagnosed with transverse myelitis. Her past medical history also includes ulcerative colitis, diagnosed aged 27 years old and primary sclerosing cholangitis. Her serum tests are as follows:
Hb 125 g/l
Platelets 274 * 109/l
WBC 7.5 * 109/l
Na+ 139 mmol/l K+ 4.4 mmol/l Urea 4.7 mmol/l Creatinine 78 µmol/l Bilirubin 49 µmol/l ALP 305 u/l ALT 180 u/l
You commence five days of high dose oral methylprednisolone. What is the most appropriate next management?
Interferon beta > Glatiramer acetate Fingolimod Natalizumab Mitoxantrone
The patient presents with a clear history of recurrent relapses of relapsing-remitting multiple sclerosis (RRMS), isolated in time and location. In addition, NICE recommends that any patient experiencing more than two debilitating episodes of RRMS be considered for disease modifying therapies.
A number of 1st line disease modifying therapies are available and the choice is made on a patient-by-patient basis. Interferon beta 1a, beta 1b, glatiramer acetate, diethyl fumarate and teriflunomide are all valid choices. However, deranged liver function is contraindicated in the use of interferons, as in this case, where the patient has a cholestatic pattern of liver dysfunction secondary to primary sclerosing cholangitis. Glatiramer acetate is not contraindicated in liver dysfunction and hence the only suitable choice.
Fingolimod is a sphingosine 1 phosphate receptor modulator affecting lymphocyte migration that has been proven to reduce the number of relapses and slow the rate of number of new MRI lesions. However, it was also associated with increased incidence of varicella zoster, tumour formation and progressive multifocal leucoencephalopathy (PML), another demyelinating central nervous system condition. As a result, fingolimod is reserved for patients who fail 1st line therapies. Similarly, while natalizumab is effective in modifying multiple sclerosis progression, it is also associated with PML and not considered a 1st line treatment. Mitoxantrone is a chemotherapy agent that inhibits DNA synthesis and repair, associated with significant cardiotoxicity, reserved only for RRMS patients who have failed other therapies with rapidly progressive disease.
MS - Second Line Pharmacological Mx
Observational studies have reported that escalation from a first-line therapy to a second-line drug reduces relapse rate at one year.
Evidence suggests that alemtuzumab, natalizumab and fingolimod outperformed other disease-modifying therapies at preventing relapse at 2 years. In addition, natalizumab also reduced 2-year disability progression rates.
Natalizumab is strongly associated with progressive multifocal leukoencephalopathy, an infection of the central nervous system with the John Cunningham virus (JCV). Therefore, JCV antibody status is an essential part of assessing an individual for treatment with natalizumab. Patient’s who are seropositive for JCV are not treated with natalizumab or switched to another drug.
Example Question:
A 42-year-old woman attends neurology clinic for review of her treatment strategy for multiple sclerosis. The patient had first developed symptoms of multiple sclerosis five years previously. Her first episode had involved sensory loss and motor weakness affecting her left leg. An MRI brain scan conducted at this time had demonstrated multiple lesions suggestive of multiple sclerosis. At this point in time, the patient had decided against receiving disease modifying therapy.
One year after her first episode, the patient suffered an episode of optic neuritis. A repeat MRI scan had demonstrated a progression of the previously observed radiographic lesions. Subsequently, the patient had been initiated on treatment with interferon beta. This treatment was continued for two years during which time the patient suffered no further relapses of multiple sclerosis. However, the patient found the unwanted effects of interferon beta to be progressively harder to tolerate and she eventually decided against continuing with this treatment. A subsequent trial of glatiramer acetate was quickly halted due to the patient experiencing severe symptoms of flushing.
Following the cessation of disease-modifying therapy, the patient had experienced multiple further relapses, including one episode where she had required hospitalisation due to cranial nerve involvement. Further assessment during this period found that the patient met the local criteria for aggressive or highly active multiple sclerosis. Accordingly, later line therapies were discussed with the patient who was keen to proceed.
Aside from her history of multiple sclerosis the patient suffered from no other significant medical problems and took no regular medications. The patient was a science teacher that had been unable to work for the past year due to her multiple relapses.
The later line therapy recommended for the patient is natalizumab. What is the essential investigation that must be completed prior to initiation of treatment with natalizumab?
Transthoracic echocardiogram > JCV antibody status Pulmonary function tests Thyroid function tests CMV antibody status
The patient has highly active multiple sclerosis causing significant morbidity. While she had obtained benefit from the standard initial therapies interferon beta and glatiramer acetate, these treatments were ultimately not tolerated. In this situation, consideration of escalation to second-line disease-modifying therapy is appropriate.
