# Clinical Cases: Multiple Sclerosis and Demyelinating Diseases

## Case 1: Relapsing-Remitting Multiple Sclerosis

### Patient Demographics
- **Age:** 28 years
- **Sex:** Female
- **Occupation:** Marketing coordinator

### Chief Complaint
"I can't see out of my right eye and my legs feel numb."

### History of Present Illness
The patient developed pain behind her right eye 5 days ago that worsened with eye movement. Over the following 2-3 days, she noticed progressive vision loss in that eye, now describing it as "looking through frosted glass." She also reports that her legs have felt "pins and needles" and heavy for the past week, making it difficult to climb stairs. On further questioning, she recalls an episode 2 years ago when she had numbness and tingling from her feet up to her waist that resolved spontaneously over several weeks. She also mentions that hot showers seem to make her vision worse (Uhthoff phenomenon). No recent infections, vaccinations, or travel.

### Neurological Examination Findings

**Mental Status:**
- Alert, oriented, appropriate
- Mildly anxious about symptoms

**Cranial Nerves:**
- **CN II (Right):**
  - Visual acuity: 20/200 (reduced from baseline 20/20)
  - Color vision: Unable to identify red (dyschromatopsia)
  - Relative afferent pupillary defect (RAPD) present - Marcus Gunn pupil
  - Visual field: Central scotoma
  - Fundoscopy: Optic disc mildly swollen (papillitis) vs normal (retrobulbar neuritis)
- **CN II (Left):** Visual acuity 20/20, normal
- **Extraocular movements:** Pain with right eye movement, otherwise intact

**Motor Examination:**
- Upper extremities: 5/5 bilateral
- Lower extremities: 4+/5 hip flexion bilaterally, 4+/5 knee flexion
- Increased tone in both legs (mild spasticity)

**Sensory Examination:**
- Decreased sensation to pinprick and light touch below T10 level bilaterally
- Vibration sense reduced at ankles
- Lhermitte sign positive - electric shock sensation down spine with neck flexion

**Reflexes:**
- Upper extremities: 2+ symmetric
- Lower extremities: 3+ bilateral (hyperreflexia)
- Bilateral Babinski signs positive

**Coordination:**
- Finger-to-nose: Normal
- Heel-to-shin: Mildly impaired (sensory ataxia)

**Gait:**
- Mildly spastic, circumduction of legs

### McDonald Criteria Assessment
**2017 McDonald Criteria for MS:**
1. **Dissemination in Space (DIS):** Lesions in ≥2 of 4 CNS areas:
   - Periventricular (YES - see MRI)
   - Cortical/juxtacortical (YES)
   - Infratentorial (YES)
   - Spinal cord (YES - clinical myelopathy)
2. **Dissemination in Time (DIT):** Can demonstrate by:
   - New T2 or enhancing lesion on follow-up MRI, OR
   - Simultaneous presence of enhancing and non-enhancing lesions, OR
   - History of prior relapse (YES - episode 2 years ago)

### Neuro Workup
- **MRI Brain with and without contrast:**
  - Multiple periventricular T2/FLAIR hyperintense lesions, ovoid, perpendicular to ventricles ("Dawson's fingers")
  - Several lesions enhance with gadolinium (active/acute)
  - Several non-enhancing lesions (chronic)
  - Right optic nerve enhancement (optic neuritis)
- **MRI Spine with contrast:**
  - T2 hyperintense lesion at T8 level, partial spinal cord involvement
  - Enhancement present
- **Lumbar Puncture:**
  - Opening pressure: 14 cm H2O (normal)
  - WBC: 8 (mildly elevated lymphocytes)
  - Protein: 55 (mildly elevated)
  - Glucose: 65 (normal)
  - **Oligoclonal bands: Present in CSF, absent in serum** (95% MS)
  - IgG index: Elevated (0.85; normal <0.7)
- **Visual Evoked Potentials:** Prolonged P100 latency in right eye
- **Labs:** B12, TSH, NMO-IgG (aquaporin-4), MOG antibody - all negative

### Diagnosis
**Relapsing-Remitting Multiple Sclerosis (RRMS)** with acute relapse
- Current attack: Optic neuritis + myelitis
- Prior attack: Transverse myelitis (2 years ago)
- McDonald criteria fulfilled (DIS + DIT)

### Management

**Acute Relapse Treatment:**
1. **IV methylprednisolone 1 g daily for 3-5 days**
   - Shortens duration of relapse
   - Does not affect long-term outcomes
2. Oral prednisone taper optional
3. If no response: Plasmapheresis (PLEX) for severe relapses

**Disease-Modifying Therapy (DMT):**
1. **Initiate DMT** - proven to reduce relapse rate and slow disability accumulation
2. **First-line options:**
   - High-efficacy: Ocrelizumab (anti-CD20), natalizumab (anti-VLA-4), ofatumumab
   - Moderate efficacy: Dimethyl fumarate, fingolimod, teriflunomide
   - Injectable: Interferon beta, glatiramer acetate (less commonly used now)
3. **Choice for this patient:** Ocrelizumab or natalizumab (high disease activity - optic neuritis + myelitis)
4. **Pre-DMT workup:** JC virus antibody, hepatitis B/C, TB, varicella immunity, CBC, LFTs

**Symptomatic Management:**
1. Fatigue: Amantadine, modafinil, or amphetamine-based stimulants
2. Spasticity: Baclofen, tizanidine, physical therapy
3. Bladder dysfunction: Anticholinergics, intermittent catheterization
4. Depression: SSRIs
5. Neuropathic pain: Gabapentin, pregabalin

**Rehabilitation:**
1. Physical therapy for gait and balance
2. Occupational therapy for energy conservation

**Counseling:**
1. Vitamin D supplementation (maintain levels >30-40 ng/mL)
2. Smoking cessation (smoking worsens MS)
3. Regular exercise
4. Reproductive planning - discuss DMT safety in pregnancy

### Clinical Image
![MS Brain MRI](case_01_image.jpg)

**Image Description:** Axial FLAIR MRI showing multiple periventricular white matter lesions perpendicular to the lateral ventricles (Dawson's fingers), characteristic of multiple sclerosis.

**Attribution:** Image from Radiopaedia.org, Case courtesy of Dr. Frank Gaillard. Licensed under CC BY-NC-SA 3.0. Source: https://radiopaedia.org/cases/multiple-sclerosis-15

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## Case 2: Neuromyelitis Optica Spectrum Disorder (NMOSD)

### Patient Demographics
- **Age:** 35 years
- **Sex:** Female
- **Occupation:** Social worker
- **Ethnicity:** African American

### Chief Complaint
"I went blind in both eyes and can't move my legs."

### History of Present Illness
The patient presented 10 days ago with severe bilateral vision loss and weakness in both legs that progressed to complete paralysis over 48 hours. She had intractable nausea, vomiting, and hiccups for 2 weeks before the current symptoms (area postrema syndrome). She also developed urinary retention requiring catheterization. Three years ago, she had an episode of bilateral leg weakness and numbness that was diagnosed as "transverse myelitis" and treated with steroids with partial recovery. She has a history of systemic lupus erythematosus (SLE). No similar symptoms in family.

### Neurological Examination Findings

**Mental Status:**
- Alert, oriented, distressed

**Cranial Nerves:**
- **CN II (bilateral):**
  - Visual acuity: Light perception only in both eyes (severe bilateral visual loss)
  - RAPD: Difficult to assess with bilateral involvement
  - Color vision: Unable to test
  - Fundoscopy: Bilateral disc edema
- Extraocular movements: Intact
- Intractable hiccups during examination

**Motor Examination:**
- Upper extremities: 5/5 bilateral
- Lower extremities: 0/5 bilateral (complete paraplegia)
- Hypotonic legs (acute stage)

**Sensory Examination:**
- Complete loss of all sensory modalities below T4 level
- Sensory level at T4

**Reflexes:**
- Upper extremities: 2+
- Lower extremities: Absent (spinal shock)
- Babinski: Mute initially (may become positive after spinal shock resolves)

**Other:**
- Urinary retention - Foley in place

### NMOSD vs MS: Key Differentiating Features

| Feature | This Patient (NMOSD) | Typical MS |
|---------|----------------------|------------|
| Optic neuritis | Bilateral, severe | Unilateral, moderate |
| Myelitis | Longitudinally extensive (≥3 segments) | Short segment (<2 segments) |
| Recovery | Poor | Usually good |
| MRI brain | Normal or atypical lesions | Typical periventricular lesions |
| Ethnicity | More common in non-white populations | More common in white populations |
| Associated autoimmunity | Common (SLE, Sjogren's) | Uncommon |

### Neuro Workup
- **MRI Spine:**
  - **Longitudinally extensive transverse myelitis (LETM):** T2 hyperintensity extending from C2-T6 (>3 vertebral segments)
  - Central cord predominance
  - Enhancement present
- **MRI Brain:**
  - Area postrema lesion (dorsal medulla)
  - No typical MS lesions (no periventricular Dawson's fingers)
- **MRI Orbits:**
  - Bilateral optic nerve enhancement and edema, extending to optic chiasm
- **Serum:**
  - **Aquaporin-4 (AQP4) antibody (NMO-IgG): POSITIVE** - diagnostic
  - MOG antibody: Negative
- **LP:**
  - WBC: 85 (neutrophilic pleocytosis - more than MS)
  - Protein: 110 (elevated)
  - Oligoclonal bands: Absent (unlike MS)
- **Labs:** ANA positive, anti-dsDNA positive (known SLE)

### Diagnosis
**Neuromyelitis Optica Spectrum Disorder (NMOSD)** - AQP4-IgG seropositive
- IPND 2015 criteria met:
  - Core clinical characteristic (optic neuritis + myelitis + area postrema syndrome)
  - AQP4-IgG positive

### Management

**Acute Attack Treatment:**
1. **High-dose IV methylprednisolone 1 g daily for 5 days** - initiated immediately
2. **Plasmapheresis (PLEX)** - given severity and poor response to steroids after 3 days
   - 5-7 exchanges
3. Consider IVIG if PLEX unavailable

**Long-term Immunosuppressive Therapy:**
1. **Essential** - untreated NMOSD has high relapse rate and accumulating disability
2. **First-line approved therapies:**
   - Eculizumab (complement C5 inhibitor)
   - Inebilizumab (anti-CD19)
   - Satralizumab (anti-IL-6 receptor)
3. **Off-label options:**
   - Rituximab (anti-CD20)
   - Azathioprine
   - Mycophenolate mofetil
4. **Avoid MS drugs** - interferon beta and fingolimod may worsen NMOSD

**Symptomatic Management:**
1. Intractable hiccups: Baclofen, gabapentin, chlorpromazine
2. Neurogenic bladder: Intermittent catheterization, anticholinergics
3. Neuropathic pain: Gabapentin, pregabalin
4. Spasticity: Baclofen, tizanidine

**Rehabilitation:**
1. Intensive inpatient rehabilitation
2. PT for mobility, OT for ADLs
3. Low vision services for visual impairment

**Prognosis:**
- More severe attacks and worse recovery than MS
- 50% require walking aid within 5-10 years
- Mortality higher than MS if untreated

### Clinical Image
![NMOSD Longitudinal Myelitis](case_02_image.jpg)

**Image Description:** Sagittal T2-weighted MRI of the cervical and thoracic spine showing longitudinally extensive transverse myelitis (LETM) spanning more than 3 vertebral segments, characteristic of neuromyelitis optica spectrum disorder.

**Attribution:** Image from Radiopaedia.org, Case courtesy of Dr. Yuranga Weerakkody. Licensed under CC BY-NC-SA 3.0. Source: https://radiopaedia.org/cases/neuromyelitis-optica-1

---

## Case 3: Acute Disseminated Encephalomyelitis (ADEM)

### Patient Demographics
- **Age:** 8 years
- **Sex:** Male
- **Occupation:** 3rd grade student

### Chief Complaint
Mother: "He had a cold last week, now he's confused and can't walk."

### History of Present Illness
The patient had a viral upper respiratory infection 2 weeks ago with fever, cough, and runny nose, which resolved. Four days ago, he developed headache and low-grade fever. His mother noticed he became increasingly confused - not recognizing family members and speaking incoherently. He became progressively weaker and ataxic, unable to walk by day 3. He has been more drowsy than usual. No prior neurological history. Immunizations are up to date (no recent vaccines). No travel or tick exposure.

### Neurological Examination Findings

**Mental Status:**
- Drowsy, arousable to voice
- Oriented to name only
- Confused, inattentive
- Encephalopathy present (required for ADEM diagnosis)

**Cranial Nerves:**
- Pupils equal, reactive
- Bilateral CN VI palsy (abducens - sign of increased ICP)
- Fundoscopy: Mild bilateral papilledema
- Facial weakness (bilateral, suggesting brainstem involvement)

**Motor Examination:**
- Upper extremities: 4/5 bilateral
- Lower extremities: 3/5 bilateral
- Hypotonic

**Sensory Examination:**
- Decreased sensation to pinprick below T6

**Reflexes:**
- Upper extremities: 3+ bilateral
- Lower extremities: 3+ bilateral
- Bilateral Babinski positive

**Coordination:**
- Finger-to-nose: Dysmetria bilaterally
- Unable to assess gait (cannot stand)

### ADEM vs First Attack of MS

| Feature | This Patient (ADEM) | MS First Attack |
|---------|---------------------|-----------------|
| Age | Children/young adults | Adults 20-40 |
| Encephalopathy | Required | Rare |
| Polyfocal symptoms | Common | Usually monofocal |
| Preceding infection | Typical | Uncommon |
| MRI lesions | Bilateral, poorly-defined, gray matter | Periventricular, well-defined, white matter |
| Course | Monophasic (usually) | Relapsing |
| Prognosis | Usually full recovery | Variable |

### Neuro Workup
- **MRI Brain:**
  - Bilateral, asymmetric, large, poorly-demarcated T2 hyperintensities
  - Involvement of subcortical white matter, deep gray matter (thalami, basal ganglia)
  - Some lesions enhance with gadolinium
  - No periventricular Dawson's fingers pattern
- **MRI Spine:**
  - Long segment thoracic cord T2 hyperintensity
- **LP:**
  - Opening pressure: 28 cm H2O (elevated)
  - WBC: 120 (lymphocytic pleocytosis)
  - Protein: 85 (elevated)
  - Glucose: Normal
  - Oligoclonal bands: Absent (present in only 10% of ADEM)
  - MOG antibody (serum): Positive
  - AQP4 antibody: Negative
- **EEG:** Diffuse slowing consistent with encephalopathy, no seizures
- **Labs:** Respiratory viral panel positive for rhinovirus

### Diagnosis
**Acute Disseminated Encephalomyelitis (ADEM)** - MOG antibody-associated
- Post-infectious (following viral URI)
- Meets diagnostic criteria: Encephalopathy + multifocal CNS demyelination + supportive MRI

### Management

**Acute Treatment:**
1. **IV methylprednisolone 30 mg/kg/day (max 1 g) for 5 days**
   - High-dose steroids are first-line
2. If no improvement: **IVIG 2 g/kg divided over 2-5 days**
3. If still refractory: **Plasmapheresis**

**Supportive Care:**
1. ICU monitoring given encephalopathy and signs of increased ICP
2. Seizure precautions (ADEM can present with seizures)
3. Fever management
4. DVT prophylaxis (mechanical)
5. Physical therapy early mobilization

**Monitoring for MS:**
1. ADEM is usually monophasic, but some children develop MS
2. Follow-up MRI at 3-6 months
3. If new lesions or clinical relapse: Consider MS diagnosis
4. MOG-positive ADEM may have relapses (MOGAD)

**Prognosis:**
1. Generally good - 70-90% full recovery
2. Recovery over weeks to months
3. Cognitive deficits may persist in some
4. MOG-positive cases may relapse (need close follow-up)

**Long-term Management (if MOG antibody positive):**
1. No consensus on maintenance therapy after first ADEM
2. If relapse occurs: Consider IVIG, steroids, rituximab, mycophenolate
3. Regular neuro-ophthalmology follow-up (optic neuritis common in MOGAD)

### Clinical Image
![ADEM MRI Brain](case_03_image.jpg)

**Image Description:** Axial T2-weighted MRI of the brain showing bilateral, asymmetric, large white matter and deep gray matter lesions characteristic of acute disseminated encephalomyelitis (ADEM).

**Attribution:** Image from Radiopaedia.org, Case courtesy of Dr. Bruno Di Muzio. Licensed under CC BY-NC-SA 3.0. Source: https://radiopaedia.org/cases/acute-disseminated-encephalomyelitis-adem-6