Makindo Medical Notes

Related Subjects: |Neurological History taking |Motor Neuron Disease (MND-ALS) |Miller-Fisher syndrome |Guillain Barre Syndrome |Multifocal Motor Neuropathy with Conduction block |Multiple Sclerosis (MS) Demyelination |Transverse myelitis |Acute Disseminated Encephalomyelitis |Progressive Multifocal Leukoencephalopathy (PML) |Inclusion Body Myositis |Cervical spondylosis |Anterior Spinal Cord syndrome |Central Spinal Cord syndrome |Brown-Sequard Spinal Cord syndrome |Spinal Cord Compression |Spinal Cord Haematoma |Spinal Cord Infarction

🧠 Multiple Sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS) that causes demyelination and progressive neurological disability.

📊 Epidemiology

• 👥 Affects ~100,000 people in the UK.
• 🚶‍♀️ Most common cause of serious physical disability in working-age adults.
• ⚖️ Prevalence: ~1 in 500, women affected twice as often as men.
• ☀️ More common at higher latitudes (possible vitamin D link).

🔬 Pathology

• Well-defined demyelinating plaques in brain and spinal cord.
• Infiltration with CD8+ T-cells, B-cells, plasma cells, complement.
• Myelin destroyed but axons initially preserved → impaired saltatory conduction ⚡.
• Common sites: periventricular white matter, optic nerves, cervical cord, brainstem, cerebellar peduncles.

🩺 Clinical Presentation

• Requires ≥2 distinct CNS episodes separated in time ⏳ and space 🌍.
• Clinically Isolated Syndrome (CIS): Single demyelinating event (may progress to MS).
• Optic Neuritis 👁️: Monocular vision loss, pain on eye movement. 25% of patients, 50% risk of MS.
• Fatigue 💤: Severe and disabling.
• Transverse Myelitis: Spastic weakness, sensory level, bladder dysfunction, Lhermitte’s sign ⚡.
• Cerebellar: Ataxia, nystagmus, diplopia, wide-based gait.
• Brainstem: INO, dysarthria, facial numbness.
• Sensory: Paraesthesia, trigeminal neuralgia.
• Uhthoff’s Phenomenon 🔥: Worsening in heat (e.g., hot bath).
• Cognitive/psychiatric: Memory loss, mood change, advanced dementia.

🧠 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. :contentReference[oaicite:0]{index=0}
• 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. :contentReference[oaicite:1]{index=1}
• 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. :contentReference[oaicite:2]{index=2}

🧬 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. :contentReference[oaicite:3]{index=3}
• 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. :contentReference[oaicite:6]{index=6}
• 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.

🌀 Forms of MS

• Relapsing-Remitting (RRMS): 85%. Attacks with recovery between episodes.
• Primary Progressive (PPMS): 10–20%. Steady progression from onset.
• Secondary Progressive (SPMS): RRMS evolves into steady decline.
• Fulminant MS: Rare (<10%), rapid disability.

📏 Diagnostic Criteria

• Dissemination in time (DIT) + space (DIS) required (McDonald criteria).
• MRI with gadolinium highlights active plaques ✨.

🧪 Investigations

• Bloods: FBC, ESR/CRP, LFTs, U&E, Ca, glucose, TFT, B12, HIV.
• CSF: Oligoclonal bands (IgG).
• Visual Evoked Potentials: Abnormal in 95% 📉.
• MRI: FLAIR/T2 lesions, T1 “black holes” for axonal loss.
• MRI brain ± spinal cord is the key investigation:
  • Looks for demyelinating plaques typical of MS: periventricular, juxtacortical, infratentorial and spinal cord lesions.
  • 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.
• 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}

💊 Management

• 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. :contentReference[oaicite:17]{index=17}
• Disease-Modifying Therapy (DMTs):
  • 🧬 Interferon beta (relapsing MS, ↓ relapse by ~⅓).
  • 💉 Glatiramer acetate.
  • ⚠️ Mitoxantrone (cardiotoxic risk).
  • 🔒 Natalizumab (aggressive MS, risk of PML).

⚖️ Symptom Management

• Fatigue: Amantadine, exercise, yoga.
• Spasticity: Baclofen, tizanidine, botulinum toxin.
• Oscillopsia 👀: Gabapentin, memantine.
• Bladder Dysfunction 🚻: Tolterodine, self-catheterisation.
• Emotional lability 😊😢: Amitriptyline.
• Nocturnal enuresis 🌙: Desmopressin spray.

📉 Prognosis

• Better: Onset <40, female, optic neuritis/sensory onset, complete recovery early.
• Worse: Male, truncal ataxia, tremor, pyramidal signs, progressive course.

📚 References

• NICE Guidance on MS Treatment

Cases — Multiple Sclerosis (MS)

• Case 1 — Optic Neuritis 👁️: A 27-year-old woman presents with subacute painful loss of vision in her right eye, worsened by eye movements. Exam: reduced visual acuity, central scotoma, relative afferent pupillary defect. Diagnosis: Optic neuritis as the first presentation of MS. Management: High-dose IV methylprednisolone; MRI brain/spine for demyelinating lesions; neurology follow-up for DMT (disease-modifying therapy).
• Case 2 — Transverse Myelitis 🦵: A 32-year-old man develops sudden bilateral leg weakness, sensory loss up to the umbilicus, and urinary urgency. Exam: spastic paraparesis, brisk reflexes, sensory level at T10. MRI spine shows demyelinating plaques. Diagnosis: Relapse of MS presenting as transverse myelitis. Management: IV steroids for relapse; physiotherapy; bladder management; long-term DMT (e.g., interferon, ocrelizumab).
• Case 3 — Brainstem Involvement 🎯: A 29-year-old woman complains of double vision and vertigo. Exam: internuclear ophthalmoplegia (failure of left eye adduction with right eye nystagmus). MRI: periventricular white matter lesions. Diagnosis: MS relapse with brainstem involvement. Management: IV steroids; DMT initiation; supportive neurorehab.
• Case 4 — Progressive MS ⏳: A 45-year-old man with past relapsing MS now has insidiously worsening gait stiffness and difficulty with bladder control over 2 years, without clear relapses. Exam: spastic paraparesis, broad-based gait. Diagnosis: Secondary progressive MS. Management: Symptomatic — baclofen/tizanidine for spasticity, bladder medications, neurorehab; consider newer progressive MS therapies (e.g., siponimod, ocrelizumab).

Teaching Commentary 🧠

MS is a chronic, immune-mediated demyelinating disorder of the CNS, typically affecting young adults (20–40 years), more common in women. Key subtypes: - Relapsing–remitting (RRMS): most common initial course. - Secondary progressive: develops after years of RRMS. - Primary progressive: gradual progression from onset. Clinical signs are disseminated in time and space: optic neuritis, transverse myelitis, brainstem/INOs, sensory and motor relapses. Dx: MRI (disseminated white matter lesions), CSF oligoclonal bands. Mx: acute relapses (IV methylprednisolone), long-term disease-modifying therapies (interferons, ocrelizumab, natalizumab, fingolimod), and symptomatic treatment. Red flags: progressive, asymmetric, or peripheral signs suggest MS mimics (NMO, sarcoid, vasculitis).