# Clinical Cases: Neuromuscular Disorders

## Case 1: Guillain-Barre Syndrome (AIDP)

### Patient Demographics
- **Age:** 45 years
- **Sex:** Male
- **Occupation:** Construction supervisor

### Chief Complaint
"My legs feel weak and tingly, and it's getting worse."

### History of Present Illness
The patient developed tingling and numbness in his feet 5 days ago. Over the following days, he noticed progressive weakness in his legs, starting distally and moving proximally. He now has difficulty climbing stairs and getting up from a chair. Since yesterday, he has noticed weakness in his hands as well. He reports back pain. Two weeks ago, he had a diarrheal illness lasting 4-5 days with crampy abdominal pain (suspected Campylobacter). He denies shortness of breath or difficulty swallowing at this time, but his wife noticed his voice sounds different. No bladder or bowel dysfunction.

### Neurological Examination Findings

**Mental Status:**
- Alert, oriented, anxious about progressive weakness

**Cranial Nerves:**
- **Facial weakness bilateral** (cannot fully close eyes, weak smile)
- Mild dysarthria
- Gag reflex: Mildly diminished
- Extraocular movements: Intact
- No ophthalmoplegia

**Motor Examination:**
- **Ascending pattern of weakness:**
  - Ankle dorsiflexion: 2/5 bilateral
  - Knee flexion/extension: 3/5 bilateral
  - Hip flexion: 4/5 bilateral
  - Shoulder abduction: 4+/5 bilateral
  - Grip strength: 4/5 bilateral
  - Fine finger movements: Intact
- Hypotonic throughout

**Sensory Examination:**
- Decreased vibration sense distally (ankles)
- Mild stocking-pattern sensory loss to pinprick
- Preserved proprioception

**Reflexes:**
- **Areflexia:** 0 throughout (all four extremities)
- Plantar responses absent/mute

**Coordination:**
- Limited by weakness

**Gait:**
- Unable to walk without assistance
- Foot drop bilateral

**Respiratory Assessment:**
- Negative inspiratory force (NIF): -35 cm H2O (critical if < -20 to -30)
- Forced vital capacity (FVC): 2.8 L (65% predicted) - needs monitoring

### Brighton Criteria for GBS
- Bilateral flaccid weakness (YES)
- Decreased or absent deep tendon reflexes (YES)
- Monophasic course with nadir 12 hours to 28 days (YES - ongoing)
- No alternative diagnosis

### Neuro Workup
- **Lumbar Puncture:**
  - Opening pressure: 14 cm H2O (normal)
  - **Albuminocytologic dissociation:** Protein 185 mg/dL (elevated), WBC 3 (normal)
  - Glucose: Normal
- **Electrodiagnostic Studies (NCS/EMG):**
  - Prolonged distal latencies (demyelination)
  - Conduction block in multiple nerves
  - Prolonged F-wave latencies
  - Reduced CMAP amplitudes
  - Findings consistent with **AIDP (acute inflammatory demyelinating polyneuropathy)**
- **Labs:**
  - Campylobacter serology: IgM positive
  - Anti-GM1 antibodies: Positive (associated with axonal variant)
  - HIV, Lyme: Negative
- **Pulmonary Function:** Serial FVC monitoring q4-6 hours

### Diagnosis
**Guillain-Barre Syndrome (GBS)** - AIDP variant, post-infectious (Campylobacter jejuni)

### Management

**Acute Immunotherapy (within 2-4 weeks of onset):**
1. **IVIG 0.4 g/kg/day for 5 days** (2 g/kg total) - PREFERRED in this setting
   - OR **Plasmapheresis:** 5 exchanges over 1-2 weeks
2. Both equally effective; IVIG more convenient
3. **Steroids NOT effective in GBS** (unlike CIDP)

**Respiratory Monitoring (critical):**
1. Serial FVC and NIF every 4-6 hours
2. **"20-30-40 rule" for intubation:**
   - FVC <20 mL/kg
   - NIF < -30 cm H2O
   - FVC decline >30% from baseline
3. ICU admission recommended for this patient

**Supportive Care:**
1. DVT prophylaxis (SC heparin + SCDs)
2. Pain management (gabapentin, opioids for severe pain)
3. Autonomic monitoring (BP, HR fluctuations - can have dysautonomia)
4. Physical therapy (prevent contractures)
5. Nutrition support
6. Psychological support

**Complications to Monitor:**
1. Respiratory failure (25-30% need ventilator)
2. Dysautonomia (arrhythmias, BP lability)
3. DVT/PE
4. Hospital-acquired infections
5. SIADH

**Prognosis:**
1. Most patients recover fully (70-80%)
2. Recovery over weeks to months
3. 5-10% mortality (respiratory failure, dysautonomia)
4. 20% have persistent disability

### Clinical Image
![GBS Nerve Conduction Study](case_01_image.jpg)

**Image Description:** Nerve conduction study demonstrating prolonged distal motor latency and temporal dispersion of the compound muscle action potential, consistent with demyelinating neuropathy in Guillain-Barre syndrome.

**Attribution:** Image from Wikipedia Commons, public domain. Source: https://commons.wikimedia.org/wiki/File:Nerve_conduction_study.png

---

## Case 2: Myasthenia Gravis

### Patient Demographics
- **Age:** 32 years
- **Sex:** Female
- **Occupation:** Nurse

### Chief Complaint
"My eyelids droop and I see double, especially at the end of the day."

### History of Present Illness
The patient first noticed drooping of her right eyelid 3 months ago. It was intermittent, worse in the evening and after reading. Over time, both eyelids became affected, and she developed double vision. She has also noticed that her voice becomes weak and nasal after talking for extended periods, and she has difficulty swallowing pills. Recently, she has noticed weakness in her arms when brushing her hair and difficulty climbing stairs. Symptoms improve after rest or sleep. She was recently diagnosed with hypothyroidism. No respiratory symptoms at this time.

### Neurological Examination Findings

**Mental Status:**
- Alert, oriented, normal cognition

**Cranial Nerves:**
- **CN II:** Visual acuity normal
- **CN III, IV, VI:**
  - **Bilateral ptosis** - right worse than left
  - Ptosis worsens with sustained upgaze (fatigable ptosis)
  - **Curtain sign positive:** Manually elevating drooping lid worsens ptosis on other side
  - Ophthalmoparesis: Variable weakness, not conforming to single nerve
  - **Diplopia** on lateral gaze
  - **Cogan's lid twitch:** Brief lid overshoot after looking down then up
- **CN VII:** Bilateral facial weakness, "snarling" smile
- **CN IX, X:** Nasal voice after sustained counting, mild dysphagia
- **CN XII:** Tongue normal

**Motor Examination:**
- Proximal weakness:
  - Deltoids: 4/5 initially, 3/5 after repetitive abduction (fatigable)
  - Hip flexors: 4/5
- Distal strength: 5/5
- **No muscle atrophy**
- Normal tone

**Sensory Examination:**
- Intact throughout

**Reflexes:**
- 2+ symmetric
- Plantar responses flexor

**Coordination:**
- Normal

**Respiratory Assessment:**
- FVC: 3.2 L (88% predicted) - within normal limits
- No dyspnea

### Myasthenia vs Other Causes of Ptosis/Diplopia

| Feature | Myasthenia Gravis | CN III Palsy | Horner Syndrome |
|---------|------------------|--------------|-----------------|
| Ptosis | Bilateral, fatigable | Unilateral, severe | Mild (2mm) |
| Diplopia | Variable pattern | Fixed pattern | No |
| Pupil | Normal | Dilated (if complete) | Miosis |
| Fatigability | YES | No | No |
| Ice test | Positive | Negative | Negative |

### Neuro Workup
- **Ice Pack Test:** Ptosis improves after 2 minutes of ice application (positive - suggests MG)
- **Serology:**
  - **Acetylcholine receptor (AChR) antibodies: POSITIVE** (diagnostic, 85% sensitivity)
  - If negative: Test anti-MuSK antibodies, anti-LRP4 antibodies
- **Electrodiagnostic Studies:**
  - **Repetitive nerve stimulation (3 Hz):** >10% decremental response in facial and proximal muscles
  - **Single-fiber EMG:** Increased jitter (most sensitive test)
- **CT Chest:**
  - **Thymoma identified** (10-15% of MG patients have thymoma; 50% of thymoma patients develop MG)
- **Pulmonary Function:** FVC and NIF baseline
- **Thyroid Function:** TSH elevated, T4 low (hypothyroidism - autoimmune association)

### Diagnosis
**Myasthenia Gravis** - AChR antibody positive, with thymoma
- MGFA Class IIb: Mild generalized (predominantly limb/axial weakness)

### Management

**Symptomatic Treatment:**
1. **Pyridostigmine (Mestinon) 60 mg TID** - acetylcholinesterase inhibitor
   - Start low, titrate to effect
   - Side effects: Cholinergic (diarrhea, cramping, salivation)
   - Do not use as monotherapy in moderate-severe disease

**Immunosuppressive Therapy:**
1. **Prednisone 20 mg daily, titrate up to 60-80 mg/day, then slow taper**
   - Most effective immunotherapy
   - Can cause initial worsening (start low, monitor closely)
2. **Steroid-sparing agents:**
   - Azathioprine (first-line adjunct)
   - Mycophenolate mofetil
3. For refractory disease: Rituximab, eculizumab (especially MuSK-MG)

**Thymectomy:**
1. **STRONGLY indicated** - patient has thymoma
2. Even without thymoma, thymectomy improves outcomes in AChR+ MG
3. Perform after optimization of symptoms

**Crisis Prevention:**
1. **Avoid myasthenia-exacerbating medications:**
   - Aminoglycosides, fluoroquinolones
   - Beta-blockers
   - Magnesium
   - Botulinum toxin
   - Certain anticonvulsants
2. Monitor for myasthenic crisis (respiratory failure)
3. Stress-dose steroids for surgery

**Myasthenic Crisis Management (if occurs):**
1. ICU admission, intubation if FVC <15 mL/kg or NIF < -20
2. **IVIG 2 g/kg over 5 days** OR **Plasmapheresis (5 exchanges)**
3. Identify trigger (infection, medication, surgery)
4. Hold pyridostigmine during intubation (can cause secretions)

### Clinical Image
![Myasthenia Gravis CT Chest](case_02_image.jpg)

**Image Description:** CT chest demonstrating an anterior mediastinal mass (thymoma) in a patient with myasthenia gravis.

**Attribution:** Image from Radiopaedia.org, Case courtesy of Dr. David Cuete. Licensed under CC BY-NC-SA 3.0. Source: https://radiopaedia.org/cases/thymoma-7

---

## Case 3: Amyotrophic Lateral Sclerosis (ALS)

### Patient Demographics
- **Age:** 58 years
- **Sex:** Male
- **Occupation:** Attorney

### Chief Complaint
"I'm tripping over my right foot and my arm keeps twitching."

### History of Present Illness
The patient first noticed weakness in his right foot 6 months ago, causing him to trip. He has since developed weakness in his right hand, making it difficult to write and button his shirt. He has noticed involuntary twitching (fasciculations) in his arm and leg muscles. Over the past 2 months, his speech has become slurred. He has lost 15 lbs unintentionally. He denies sensory symptoms, bladder dysfunction, or double vision. No family history of similar illness. He has no pain. He is frightened because his symptoms continue to progress.

### Neurological Examination Findings

**Mental Status:**
- Alert, oriented, appropriately concerned
- Cognition: Intact (frontotemporal dysfunction possible in ALS)
- Pseudobulbar affect: Occasional inappropriate crying

**Cranial Nerves:**
- Tongue: **Atrophy with fasciculations** (LMN sign)
- Speech: Dysarthria (mixed spastic and flaccid)
- Jaw jerk: **Brisk** (UMN sign)
- Gag reflex: Present
- No extraocular movement abnormalities (typically spared in ALS)

**Motor Examination:**
- **Mixed UMN and LMN signs in same regions:**
- Right upper extremity:
  - Weakness: Hand intrinsics 3/5, finger extensors 4/5
  - **Atrophy:** First dorsal interosseous, thenar eminence
  - **Fasciculations:** Visible in biceps and forearm
- Left upper extremity: 5/5 but fasciculations present
- Right lower extremity:
  - Foot dorsiflexion 3/5, hip flexion 4/5
  - Foot drop present
  - Atrophy of anterior tibial compartment
- Left lower extremity: 4+/5 distally
- **Spasticity:** Increased tone in all extremities (UMN)

**Sensory Examination:**
- **Normal** throughout (key feature - rules out most mimics)

**Reflexes:**
- **Hyperreflexia throughout** (3+ upper, 3+ lower) - UMN sign
- **Bilateral Babinski positive** - UMN sign
- **Hoffman sign positive** bilaterally
- Despite atrophy, reflexes are brisk (pathognomonic combination)

**Coordination:**
- Limited by weakness, no ataxia

**Gait:**
- Spastic gait with right foot drop
- Uses AFO (ankle-foot orthosis)

### El Escorial Criteria Assessment
**Revised El Escorial Criteria for ALS:**
- Evidence of LMN degeneration (atrophy, fasciculations, weakness): Present in bulbar, cervical, and lumbar regions
- Evidence of UMN degeneration (hyperreflexia, spasticity, Babinski): Present in same regions
- Progressive spread of symptoms
- Absence of sensory, sphincter, visual, autonomic involvement, parkinsonian features
- **Classification: Clinically Probable ALS** (UMN + LMN signs in ≥2 regions)

### Neuro Workup
- **Electrodiagnostic Studies (EMG/NCS):**
  - Active denervation (fibrillations, positive sharp waves) in 3 body regions
  - Chronic denervation (large polyphasic MUPs)
  - Fasciculation potentials
  - Motor NCS: Normal or low CMAP amplitudes
  - **Sensory NCS: Normal** (critical for diagnosis)
- **MRI Brain and Spine:**
  - Rules out structural lesion (cervical myelopathy, syrinx)
  - May show corticospinal tract hyperintensity
- **Labs (to exclude mimics):**
  - B12, TSH, PTH: Normal
  - HIV, Lyme: Negative
  - Serum protein electrophoresis: Normal
  - Creatine kinase: Mildly elevated (from denervation)
  - Heavy metals: Negative
- **Genetic testing:** Consider SOD1 mutation if family history (10% familial ALS)
- **Pulmonary Function:** FVC 72% predicted

### Diagnosis
**Amyotrophic Lateral Sclerosis (ALS)** - sporadic, limb-onset with bulbar involvement

### Management

**Disease-Modifying Therapy:**
1. **Riluzole 50 mg BID** - glutamate release inhibitor
   - Modest survival benefit (2-3 months)
   - Monitor LFTs
2. **Edaravone (Radicava)** - antioxidant, IV infusion
   - May slow functional decline in early ALS
3. **Tofersen** - if SOD1 mutation positive (antisense oligonucleotide)
4. **AMX0035 (Relyvrio)** - newer approval, mitochondrial/ER stress modulator

**Symptomatic Management:**
1. Spasticity: Baclofen, tizanidine
2. Sialorrhea (drooling): Glycopyrrolate, atropine drops, botulinum toxin to salivary glands
3. Pseudobulbar affect: Dextromethorphan/quinidine (Nuedexta)
4. Depression/anxiety: SSRIs
5. Pain: Often from immobility, contractures - PT, NSAIDs, gabapentin
6. Sleep: Non-invasive ventilation improves sleep

**Nutritional Support:**
1. Swallowing evaluation
2. Modified diet consistency
3. PEG tube when oral intake insufficient (ideally before FVC <50%)
4. Maintain weight (weight loss = poorer prognosis)

**Respiratory Management:**
1. Serial FVC monitoring (every 3 months)
2. **Non-invasive ventilation (BiPAP)** when FVC <50% or symptomatic
   - Improves survival by 7-10 months
   - Improves quality of life and sleep
3. Cough assist device
4. Discuss invasive ventilation preferences early

**Multidisciplinary ALS Clinic:**
1. Neurology, pulmonology, nutrition, PT, OT, speech therapy, social work, palliative care
2. Equipment: AFO for foot drop, wheelchair, communication devices
3. Home modifications

**Advance Care Planning:**
1. Goals of care discussion early
2. Document preferences for intubation, tracheostomy
3. Palliative care and hospice referral
4. Average survival 2-5 years from diagnosis

### Clinical Image
![ALS Tongue Fasciculations](case_03_image.jpg)

**Image Description:** Clinical photograph showing tongue atrophy and fasciculations in a patient with amyotrophic lateral sclerosis, demonstrating lower motor neuron involvement of the bulbar region.

**Attribution:** Image from Wikipedia Commons, public domain. Source: https://commons.wikimedia.org/wiki/File:Amyotrophic_lateral_sclerosis.jpg