Makindo Medical Notes

🧠 What is a Clinically Isolated Syndrome?

• Clinically isolated syndrome (CIS) is a first clinical episode of neurological symptoms caused by inflammatory demyelination in the CNS, lasting at least 24 hours, in a person with no prior history of demyelinating attacks.
• The presentation is “MS-like” (optic neuritis, brainstem event, partial myelitis, hemispheric syndrome) but by definition you cannot yet say the person has multiple sclerosis, because dissemination in time (and sometimes space) has not been demonstrated.
• CIS is therefore best thought of as a high-risk state for MS rather than a diagnosis in its own right – some people will never have another event, others will convert to clinically definite MS over the following years.
• In the UK NICE documents, CIS is explicitly described as a first episode of symptoms suggestive of inflammatory demyelination, often representing the onset of MS.

🧬 Pathophysiology & Relationship to MS

• Pathologically, CIS reflects the same processes as relapsing–remitting MS: immune-mediated attack on CNS myelin and oligodendrocytes, with focal inflammatory plaques causing conduction block along affected tracts.
• Whether someone remains “CIS only” or evolves into MS is influenced by:
  • Baseline burden and distribution of silent MRI lesions,
  • Presence of CSF oligoclonal bands, and
  • Genetic and environmental factors (e.g. HLA-DRB1*1501, smoking, vitamin D).
• Conceptually, CIS sits on a spectrum with:
  • Radiologically isolated syndrome (RIS) – MRI lesions typical of MS but no clinical event yet,
  • Clinically definite MS – once dissemination in space and time has been demonstrated using McDonald criteria.

🩺 Typical Clinical Presentations

CIS is a single attack with an MS-compatible syndrome. Common presentations include:

• Optic neuritis
  • Subacute unilateral visual loss over days, pain on eye movement, reduced colour vision, central scotoma.
  • Relative afferent pupillary defect; disc may be normal (retrobulbar) or swollen.
• Partial myelitis
  • Sensory level, limb weakness, Lhermitte’s symptom, sphincter disturbance.
  • Spinal MRI shows a short segment lesion (typically <3 vertebral segments) rather than the long lesions seen in NMOSD.
• Brainstem / cerebellar syndrome
  • Diplopia, internuclear ophthalmoplegia, trigeminal sensory loss, ataxia, vertigo.
• Cerebral hemispheric syndrome
  • Focal weakness, numbness, aphasia, visual field defects – often with MRI white matter lesions in a vascular-nonterritorial pattern.

Red flags (e.g. fever, headache, encephalopathy, longitudinally extensive myelitis, prominent systemic features) should prompt consideration of alternative diagnoses such as AQP4-NMOSD, MOGAD, vasculitis, infections or metabolic/toxic causes.

🧪 Investigations – How Do We Work Up CIS?

• MRI brain ± spinal cord is the key investigation:
  • Looks for demyelinating plaques typical of MS: periventricular, juxtacortical, infratentorial and spinal cord lesions. :contentReference[oaicite:7]{index=7}
  • Gadolinium enhances active lesions, helping show dissemination in time if both enhancing and non-enhancing lesions are present at baseline.
• CSF examination
  • Detection of oligoclonal IgG bands unique to CSF supports a diagnosis of MS and improves risk stratification after CIS. :contentReference[oaicite:8]{index=8}
• Blood tests to exclude mimics: B12, folate, copper, HIV, syphilis, autoimmune screen, AQP4-IgG, MOG-IgG where phenotypically indicated.
• Evoked potentials are less central now but can demonstrate subclinical lesions (e.g. VEP abnormalities in asymptomatic eye) and support dissemination in space. :contentReference[oaicite:9]{index=9}

📋 McDonald Criteria – When Does CIS Become MS?

• The 2017 revision of the McDonald criteria allows earlier diagnosis of MS in someone with CIS if you can show:
  • Dissemination in space (DIS) – MRI lesions in at least 2 of 4 typical CNS regions (periventricular, juxtacortical/cortical, infratentorial, spinal cord), and
  • Dissemination in time (DIT) – either new lesions on follow-up MRI, simultaneous enhancing and non-enhancing lesions at baseline, or the presence of CSF oligoclonal bands. :contentReference[oaicite:10]{index=10}
• If a patient with CIS already meets DIS + DIT at first evaluation, they are diagnosed with MS rather than “pure” CIS, even if they have had only one clinical event.
• If they do not meet McDonald criteria, they remain CIS and require clinical and MRI surveillance to detect a second event or new lesions over time.

📊 Risk of Conversion from CIS to MS

• Depending on cohort and follow-up, around 30–80% of people with CIS eventually develop clinically definite MS.
• High-risk features for conversion include:
  • Multiple T2 hyperintense lesions typical of MS on the baseline MRI, particularly if periventricular or infratentorial,
  • Presence of CSF oligoclonal bands,
  • Younger age at onset, male sex, and certain lesion patterns (e.g. spinal cord + brain lesions).
• Low-risk CIS:
  • Normal brain MRI or very few non-specific lesions,
  • Negative CSF oligoclonal bands.
• Markov models suggest a variable time course, but many conversions occur within the first 2–5 years after CIS, which underpins the push for early risk stratification and follow-up.

🇬🇧 UK Clinical Context & NICE

• The NICE MS guideline (NG220) and associated committee discussions explicitly address CIS as a first inflammatory demyelinating event and emphasise careful assessment, monitoring, and patient information.
• Key practical steps in UK practice:
  • Refer suspected CIS to a neurologist with an interest in MS for MRI and risk stratification.
  • Offer clear information on the meaning of CIS, uncertainty around prognosis, and what to look for if another relapse occurs.
  • Arrange follow-up, often including repeat MRI (e.g. at 6–12 months) in higher-risk cases.
• NHS England DMT algorithms are written for confirmed relapsing MS, but many centres consider early DMT in high-risk CIS on a case-by-case basis, guided by MRI, CSF and patient preference.

💊 Treatment – Acute Episode

(Always follow local neurology guidance – this is a broad overview.)

• High-dose corticosteroids are commonly used to speed recovery from the first demyelinating attack:
  • Typical regimen: IV methylprednisolone (e.g. 1 g daily for 3–5 days) ± oral taper, or high-dose oral equivalent.
  • Steroids improve the speed of recovery but do not clearly change long-term disability; they are mainly about function in the weeks–months post-attack.
• Concurrently:
  • Address symptom control (pain, spasticity, mood),
  • Consider occupational and physiotherapy input early,
  • Provide advice about driving (DVLA guidance usually requires patients to report if the event may affect safe driving) and work adjustments.

🛡️ Should We Start Disease-Modifying Therapy (DMT) in CIS?

• Randomised trials show that early use of interferon beta or other DMTs in high-risk CIS can delay conversion to clinically definite MS and reduce MRI activity.
• However, because not all CIS patients develop MS, and DMTs carry side-effects and monitoring burdens, treatment decisions are nuanced:
  • Most UK centres reserve DMT for:
    • CIS with high-risk MRI/CSF features, and/or
    • Cases where the neurologist feels McDonald criteria for MS are effectively met or nearly met.
• In practice, this is a shared decision in an MS specialist clinic, balancing:
  • Risk of future relapses and disability,
  • Patient values and risk tolerance,
  • Local commissioning and NHS England DMT criteria.

🔍 CIS vs Radiologically Isolated Syndrome vs “MS Mimics”

• CIS – clinical event + MRI/CSF supportive of demyelination, but criteria for MS not yet fulfilled.
• Radiologically isolated syndrome (RIS) – incidental MRI lesions typical of MS without any clinical event; management is usually surveillance ± research/clinical trial enrolment.
• Key mimics to exclude at first presentation:
  • Stroke/TIA (vascular lesions are territorial and respect arterial boundaries),
  • Compressive myelopathy, subacute combined degeneration, infections (HIV, syphilis, Lyme),
  • NMOSD and MOGAD, vasculitis, sarcoidosis, leukodystrophies.

✅ Take-Home Points for Clinicians

• CIS = first demyelinating attack in the CNS with MS-like features; many but not all will go on to MS.
• Risk of conversion is driven by MRI lesion burden/pattern and CSF oligoclonal bands – a “clean” MRI and negative OCBs are reassuring, whereas multiple typical lesions and positive OCBs are high-risk.
• The McDonald criteria allow some patients with CIS to be diagnosed with MS at first presentation if DIS + DIT are demonstrated by MRI and/or CSF.
• In the UK, CIS should trigger neurology referral, MRI, CSF where appropriate, structured follow-up and patient education; high-risk cases may be offered early DMT within MS services.
• From an acute physician’s perspective: treat the event (steroids, rehab, symptom control), exclude mimics, and ensure robust hand-over to an MS specialist clinic for long-term decisions.