What causes myoclonus in a patient with Chronic Kidney Disease (CKD)?

Myoclonus in CKD Patients: Causes

Myoclonus in CKD patients is primarily caused by uremic toxin accumulation, electrolyte disturbances (particularly hyponatremia, hypocalcemia, and hypomagnesemia), and medication toxicity—with gabapentin and cefepime being the most common drug culprits in patients with renal impairment. 1, 2, 3

Primary Metabolic and Uremic Causes

Electrolyte Abnormalities

• Hyponatremia, hypocalcemia, hypomagnesemia, hyperkalemia, and hypokalemia are major triggers for myoclonus and seizures in CKD patients 1
• These electrolyte disturbances become increasingly common as GFR falls below 10-15 mL/min/1.73 m², when the kidneys lose their ability to maintain homeostasis 4, 5
• Hypocalcemia should always be corrected before addressing other metabolic abnormalities in CKD patients with neurological symptoms 5

Uremic Encephalopathy

• Progressive accumulation of uremic toxins occurs when GFR drops below 10-25 mL/min, leading to neurological manifestations including myoclonus 5, 6
• The kidneys' inability to maintain electrolyte and acid-base balance contributes to neurotoxicity 6

Medication-Induced Myoclonus (Critical to Recognize)

Gabapentin Toxicity

• Gabapentin causes myoclonus in ESRD patients even at doses as low as 9-20 mg/kg, typically within 4 months of treatment onset 2
• The myoclonus is characteristically multifocal, involving all extremities, and is more disabling than in patients with normal renal function 2
• Discontinuation of gabapentin resolves myoclonus within 4-15 days 2
• EEG does not show epileptiform discharges with gabapentin-induced myoclonus 2

Cefepime Neurotoxicity

• Cefepime is a severely underappreciated cause of myoclonus and encephalopathy in ICU patients with CKD 3
• Myoclonus occurred in 73% (11 of 15 patients) with cefepime neurotoxicity, along with impaired consciousness in 87% 3
• Patients with chronic kidney disease are particularly susceptible, with 66.7% of neurotoxic cases having CKD versus 35.3% without neurotoxicity 3
• Neurotoxicity occurs more frequently when cefepime dose is not adjusted for renal function (only 28.6% of neurotoxic patients had appropriate dose adjustment versus 75.3% without neurotoxicity) 3
• However, neurotoxic symptoms can still occur despite appropriate dose modifications 3

Other Medications

• Erythropoietin therapy has been associated with seizures in CKD patients, especially during the first 90 days of therapy or with rapid hemoglobin correction 1
• Dobutamine has been reported to cause myoclonus in ESRD patients receiving continuous infusion 7

Secondary Causes

Hypertensive Encephalopathy

• Poorly controlled hypertension associated with CKD can lead to hypertensive encephalopathy with myoclonus or seizures 1
• This is particularly relevant as sodium retention in CKD contributes to hypertension and occurs before oliguria develops 4

Cerebrovascular Disease

• CKD patients have increased risk of cerebrovascular disease, which can manifest with myoclonus 1

Diagnostic Approach

Laboratory Evaluation

• Comprehensive electrolyte panel: sodium, potassium, calcium, magnesium, and phosphate 1
• BUN and creatinine to assess degree of uremia 1
• Focus on identifying hyponatremia (common with GFR <10 mL/min), hypocalcemia, and hypomagnesemia 5

Medication Review

• Immediately review all medications, particularly gabapentin, cefepime, and other renally-cleared drugs 2, 3
• Verify appropriate dose adjustments for renal function 3

Neuroimaging

• Consider imaging to rule out structural causes such as stroke, which is more common in CKD patients 1

Management Algorithm

Immediate Steps

1. Discontinue offending medications (gabapentin, cefepime) if identified 2, 3
2. Correct electrolyte abnormalities, prioritizing hypocalcemia first 1, 5
3. Control blood pressure if hypertensive encephalopathy is present 1

Specific Interventions

• For gabapentin-induced myoclonus: discontinue immediately; expect resolution in 4-15 days 2
• For cefepime neurotoxicity: discontinue and consider alternative antibiotic; symptoms typically resolve after discontinuation 3
• For erythropoietin-related seizures: discontinue until clinical stability is achieved 1

Preventive Measures

• Regular monitoring of electrolytes, especially in dialysis patients 1
• Appropriate dose adjustment of all renally-cleared medications 3
• Use dialysis solutions containing appropriate levels of potassium, phosphate, and magnesium to prevent electrolyte disorders 1

Critical Pitfalls to Avoid

• Failing to recognize medication-induced myoclonus, particularly from gabapentin and cefepime, which are commonly prescribed in CKD patients 2, 3
• Assuming appropriate dose adjustment prevents neurotoxicity—cefepime neurotoxicity can occur despite proper dosing 3
• Overlooking chronic kidney disease as a risk factor for drug-induced neurotoxicity 3
• Not correcting hypocalcemia before addressing other metabolic abnormalities 5