24.4 Motor Neuron Disease, Acute Myopathies, Rhabdomyolysis, and CINM (03.O.3–6)
Key Takeaways
- Amyotrophic lateral sclerosis respiratory failure is treated first with noninvasive ventilation; tracheostomy is a goals-of-care decision rather than an automatic next procedure.
- Inflammatory myopathy must be separated from toxic myopathy: statin immune-mediated necrotizing myopathy with anti-HMGCR antibodies continues after the statin is stopped and needs immunosuppression.
- Rhabdomyolysis threatens hyperkalemia, acute kidney injury, and compartment syndrome; treat with isotonic fluids and follow creatine kinase, potassium, and urine output.
- Critical illness neuromyopathy is flaccid quadriplegia after sepsis, corticosteroids, and neuromuscular blockade, presenting as wean failure; it is a diagnosis of exclusion supported by EMG.
- Guillain-Barré syndrome, myasthenia, critical illness neuromyopathy, and spinal shock can all cause flaccid weakness; sensory level, extraocular fatigability, CSF protein, and timing in the ICU separate them.
Four problems that all look like a floppy ICU patient
Blueprint topics 03.O.3–6 sit together because the neuroICU is asked, almost daily, why a patient cannot wean. The answers are not interchangeable. Motor neuron disease is a progressive degenerative diagnosis with an advance-care conversation at its center. Acute myopathies are muscle-limited, often CK-rich, and split into immune versus toxic. Rhabdomyolysis is a medical emergency of potassium, kidney, and compartments. Critical illness neuromyopathy (CINM) is a diagnosis of exclusion after sepsis and ICU treatments. Mixing them produces either futile thymectomy talk or missed compartment syndrome.
Motor neuron disease and the ventilator
Amyotrophic lateral sclerosis (ALS) combines upper and lower motor neuron signs: brisk reflexes or a Babinski sign in a wasted, fasciculating limb is the classic mixed picture. Bulbar ALS presents with dysarthria, dysphagia, and poor cough. The ICU appearance is hypercapnic respiratory failure, aspiration pneumonia, or inability to wean after an unrelated intubation.
Respiratory support is stepwise and preference-sensitive:
- Measure FVC, sniff nasal inspiratory pressure (SNIP) or NIF, and nocturnal oximetry or capnography. Symptoms of orthopnea, morning headache, and REM-related hypoventilation often precede daytime hypercapnia.
- Noninvasive ventilation (NIV), usually nocturnal bilevel positive airway pressure, is first-line when the patient wants respiratory support. It prolongs survival and improves symptoms in ALS with respiratory insufficiency.
- Secretion management (mechanical insufflation–exsufflation, cough assist, suctioning, and sometimes a feeding tube) determines whether NIV can succeed.
- Tracheostomy ventilation can extend life in patients who choose it. It is not an automatic escalation. The conversation covers communication, 24-hour care, and what the patient considers an acceptable life. Do not perform a midnight tracheostomy in a newly diagnosed patient who has never discussed goals.
- Diaphragm pacing is not standard emergency care. Riluzole and edaravone are disease-modifying outpatient drugs, not ICU rescue.
The examination trap is labeling every wasted, areflexic, ventilator-dependent patient as ALS. ALS does not explode over 48 hours after septic shock; CINM does. ALS usually has mixed upper and lower signs and a history of months of twitching and falls. New ALS can present to the ICU, but it still needs a thoughtful diagnosis, not a reflex tracheostomy.
Acute myopathies: inflammatory versus toxic
Inflammatory myopathies (dermatomyositis, overlap/anti-synthetase disease, immune-mediated necrotizing myopathy) produce subacute proximal weakness, often with a CK in the thousands, and extra-muscular clues (rash, interstitial lung disease, arthritis). ICU issues are respiratory muscle weakness, aspiration, and myocarditis in selected antibodies (for example anti-MDA5 or anti-SRP). Treatment is immunotherapy after infection is addressed: corticosteroids, IVIG, rituximab, or other agents depending on the serotype.
Toxic myopathies start with a drug or alcohol history:
| Toxin / syndrome | Timing | CK and antibodies | What to do |
|---|---|---|---|
| Statin-associated immune-mediated necrotizing myopathy | Continues or worsens after the statin is stopped | CK often 2,000–20,000 IU/L; anti-HMGCR (or anti-SRP in non-statin IMNM) | Stop the statin; this is not a wait-it-out toxic myopathy—immunosuppression (steroids, IVIG, rituximab) is usually required |
| Ordinary statin myalgia / self-limited necrotizing injury | Improves after stopping the drug | Mild-moderate CK, antibody-negative | Stop statin, fluids if CK is high, do not rechallenge blindly |
| Alcohol-related necrotizing myopathy | Binge or withdrawal | Very high CK, rhabdomyolysis | Fluids, electrolyte repletion, watch compartments |
| Colchicine, chloroquine, amiodarone | Chronic | Vacuolar myopathy; CK variable | Stop the drug |
| ICU thick-filament myopathy | After high-dose steroids and neuromuscular blockade | CK normal or moderately high | Supportive; overlaps CINM |
Do not restart a statin in anti-HMGCR disease. Do not treat ordinary alcohol rhabdomyolysis with rituximab. The serology and the time course after toxin removal make the split.
Rhabdomyolysis
Rhabdomyolysis is skeletal muscle necrosis releasing myoglobin, potassium, phosphate, and organic acids. Triggers in the neuroICU include prolonged seizure, immobilization, compartment syndrome, neuroleptic malignant syndrome, malignant hyperthermia, cocaine or synthetic cannabinoids, trauma, and the toxic myopathies above.
| Problem | Why it kills | Management |
|---|---|---|
| Hyperkalemia | Ventricular arrhythmia, especially while still seizing or ischemic | Calcium if ECG changes, insulin-glucose, beta-agonist, bicarbonate in selected acidosis, urgent dialysis if oliguric |
| Acute kidney injury | Myoglobin precipitates in tubules; dipstick reads blood with few red cells | Isotonic crystalloid to maintain urine output; avoid NSAIDs; dialysis for usual indications |
| Hypocalcemia / hyperphosphatemia | Released phosphate binds calcium | Do not chase mild hypocalcemia aggressively during the oliguric phase; it rebounds during recovery |
| Compartment syndrome | Swollen muscle raises intra-compartment pressure | Pain out of proportion, tense compartments, rising CK despite fluids; surgical fasciotomy, not more mannitol as a substitute |
| CK tracing | Confirms the diagnosis and trajectory | CK often >5 times the upper limit of normal and frequently in the tens of thousands; treat the complications, not a single CK number |
Urine that dips positive for blood without red cells on microscopy is a classic myoglobin clue. Alkalinization is optional and secondary to volume. Never use succinylcholine if malignant hyperthermia or denervation is in play.
Critical illness neuromyopathy
ICU-acquired weakness after days of critical illness is usually critical illness polyneuropathy (CIP), critical illness myopathy (CIM), or both—together CINM. Typical story: septic shock, multi-organ failure, high-dose corticosteroids, and days of neuromuscular blockade. As the lungs improve, the patient is flaccid, areflexic or hyporeflexic, and cannot wean. Facial and extraocular muscles are usually spared. Sensation is reduced in CIP and relatively spared in pure CIM. Dysautonomia like GBS is not the dominant picture. CSF is normal.
CINM is a diagnosis of exclusion. Before you accept it, rule out residual neuromuscular blockade (train-of-four), occult cervical cord injury, ongoing sedative accumulation, GBS that was the reason for admission, myasthenic crisis, hypophosphatemia, severe hypokalemia, and untreated status epilepticus.
Electrodiagnosis, when feasible:
- CIM: low compound muscle action potential (CMAP) amplitudes, prolonged CMAP duration, relatively preserved sensory nerve action potentials (SNAPs), myopathic recruitment. Direct muscle stimulation shows inexcitable muscle.
- CIP: axonal sensorimotor pattern with low SNAPs and CMAPs, relatively preserved conduction velocities (not GBS demyelination).
- Biopsy, rarely needed, may show myosin thick-filament loss.
There is no IVIG indication for CINM. Treatment is supportive: stop unnecessary steroids and paralytics, treat sepsis, glycemic control, early mobilization, and time. Recovery is weeks to months; CIP recovers more slowly than CIM. Face-sparing flaccid quadriplegia after a septic week is CINM until a better diagnosis is proven—not a reason to start a GBS steroid-free IVIG course without examining the timeline.
Distinguishing GBS, MG, CINM, and spinal shock
| Feature | GBS | Myasthenic crisis | CINM | Spinal shock |
|---|---|---|---|---|
| Timing | Days after infection, community onset | Known MG or subacute fatigable illness; crisis over hours–days | After days of ICU sepsis, steroids, neuromuscular blockade | Immediate after spinal cord injury |
| Pattern | Ascending, relatively symmetric | Fatigable; ocular and bulbar prominent | Flaccid quadriplegia, face usually spared, proximal plus respiratory | Sensory and motor level; arms spared in thoracic lesions |
| Reflexes | Absent | Normal or reduced | Reduced | Absent below the lesion |
| Sensory | Distal loss common | No primary sensory loss | CIP yes, CIM no | Sensory level, often a truncal band |
| Autonomic | Labile BP, arrhythmias, ileus | Usually not GBS-like storms | Not the GBS picture | Neurogenic shock: hypotension with bradycardia, priapism |
| CSF | High protein, few cells (may be delayed) | Normal | Normal | Normal |
| EMG / extra | Demyelinating or axonal neuropathy | Decrement, jitter; normal nerve if not wasted | Axonal CIP, inexcitable CIM, prolonged CMAP | Normal nerve conduction acutely if the lesion is cord |
| Rescue | IVIG or PLEX; no steroids | IVIG or PLEX; steroids later | Supportive; no IVIG | Immobilize, MAP support (often ≥85 mm Hg for 7 days in acute traumatic SCI practice), not NASCIS-dose steroids as routine |
Spinal shock is the temporary loss of all cord function below an acute lesion. It is not a peripheral neuropathy. A sensory level, a history of trauma or aortic surgery, priapism, and bradycardic hypotension send you to spine imaging, not to IVIG.
Examination traps
- Tracheostomy on ALS hospital day 0 without a goals conversation.
- Restarting a statin in anti-HMGCR necrotizing myopathy.
- Treating CINM with IVIG because the patient is areflexic.
- Calling spinal shock GBS because both are flaccid and areflexic.
- Ignoring a tense calf in a patient whose CK will not fall.
- Using succinylcholine in rhabdomyolysis, denervation, or suspected malignant hyperthermia.
A 62-year-old man survives a week of septic shock on a norepinephrine infusion, hydrocortisone, and intermittent cisatracurium. He is now afebrile with improving lungs but has flaccid, areflexic limbs, a weak diaphragm, spared extraocular movements, and normal CSF. EMG shows low CMAP amplitudes with prolonged CMAP duration and relatively preserved SNAPs. What is the most likely diagnosis?
After a prolonged convulsive seizure, a patient's CK is 42,000 IU/L, potassium is 6.4 mmol/L with peaked T waves, and the right thigh is tense and worsening despite fluids. Which plan addresses the life-threatening complications?
Which finding best separates acute spinal shock from Guillain-Barré syndrome in a flaccid, areflexic patient?
A 71-year-old man with a year of progressive mixed upper and lower motor neuron signs develops nocturnal hypercapnia and orthopnea. He is alert, can communicate, and has not discussed long-term ventilation. Which respiratory plan is most appropriate?