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Periodic paralysis
Periodic paralysis is defined by episodic, short-lived skeletal muscle weakness, which can be classified into primary (hereditary) and secondary (due to identifiable causes) types. The document details the pathophysiology, epidemiology, classification, and clinical approach to diagnosing and treating various forms of periodic paralysis, noting that serum potassium levels play a crucial role in diagnosis and management. Treatment options vary by type but are aimed at preventing attacks and addressing underlying causes.
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Periodic paralysis
- 1. PERIODIC PARALYSIS Dr AbdullahAnsari PG-2 (Medicine) AMU ALIGARH
- 2. Introduction… A group ofdisorders of different etiologies with • episodic, short-lived, and hypo-reflexic skeletal muscle weakness • with or without myotonia • without sensory deficit • without loss of consciousness
- 3. Pathophysiology • The physiologicbasis of flaccid weakness is inexcitability of the muscle membrane • Defects in the ion channels that allows ions to leak in or out of the muscle cell altering its polarization • Alteration potassium level is not the principal defect, the altered potassium metabolism is a result of the PP
- 4. Epidemiology • The frequenciesof hyperkalemic PP, paramyotonia congenita, and potassium-aggravated myotonias are not known • Hypokalemic PP has a prevalence of 1 per 100,000 • Thyrotoxic PP more common in males (85%) of Asian descent with a frequency of 2%
- 5. Primary or familialperiodic paralysis • Hereditary • A single gene mutation • Ca++, Na+or K+ chloride channels abnormalities on muscle membrane • “Channelopathies” or “Membranopathies”
- 6. Secondary periodic paralysis •A demonstrably known causes • Serum potassium abnormal even in inter-ictal phase
- 7. Conventional classification ofperiodic paralysis Primary or familial periodic paralysis: 1. Hypokalemic periodic paralysis 2. Hyperkalemic periodic paralysis 3. Normokalemic periodic paralysis All have autosomal dominant inheritance.
- 8. Secondary periodic paralysis: 1.Hypokalemic periodic paralysis. a. Thyrotoxicosis b. Thiazide or loop-diuretic induced c. Potassium losing nephropathy d. Drug-induced: gentamicin, carbenicillin, amphotericin-B, alcohol e. Primary or secondary hyperaldosteronism f. GI potassium loss
- 9. 2. Hyperkalemic periodicparalysis a. Chronic kidney disease b. High dose of ACE-i c. K+ supplements with K+sparing diuretics and/or ACE-i d. Andersen Tawil syndrome e. Paramyotonia congenita 3. Potassium-aggravated myotonia
- 10. Classification of primaryperiodic paralysis based on ion-channel abnormalities Disease Gene Protein Inheritance Mutuation Hyperkalemic PP SCN4A Nav1.4 Dominant Gain Normokalemic PP ,, ,, ,, Paramyotonia congenita ,, ,, ,, Hypokalemic PP Type II ,, ,, ,, Hypokalemic PP Type I CALCL 1A3 Cav1.1 ,, ,, Thyrotoxic PP KCNJ18 Kir2.6 ,, Loss Andersen-Tawil syndrome KCNJ2 Kir2.1 ,, ,,
- 11. Clinical approach toa case of periodic paralysis • Detailed history • Clinical examination • Simple laboratory investigations • ECG and EMG • Muscle biopsy
- 12. History of muscleweakness • Episodic short-lived paralysis of one, two, or all four limbs • Without loss of consciousness or sphincter dysfunction • Weakness may start proximally and spread distally • Paralysis may last for hours to several days • Frequency daily to yearly
- 13. • Strength normalin between attacks • Fixed weakness may develop later in some forms • In rare cases, respiratory muscles and cranial musculature may be involved • Fatal if not recognized and treated promptly
- 14. Age of onset •Early childhood : hyperkalemic PP and paramyotonia congenita • Soon after puberty but earlier than 25-30 yr : hypokalemic PP • after 25 yr : secondary periodic paralysis
- 15. Family history • Usuallya strong family history in primary PP • 33% cases are sporadic
- 16. Timing • Periodic paralysisoccurs typically on waking from sleep or on rest after exercise • It never occurs in the midst of vigorous exercise • This differentiates it from myasthenia gravis
- 17. Intensity • Attacks –mild or severe • During mild attacks, feeling of tiredness and fatigue of muscles that usually disappears in an hour • In severe attacks, complete immobility of affected limbs
- 18. History of administrationof certain drugs • Diuretics, ACE-i, ARBs, gentamicin, carbenicillin, etc • History of gastroenteritis, oliguria or anuria, severe PPH, or septic abortion be asked
- 19. Clinical examination • Mostpatients present during the inter-ictal period • No positive physical finding in the primary PP
- 20. During paralytic attacks •Muscles are flaccid • Tendon jerks are absent • Babinski’s sign is negative • There is no cloudiness of sensorium • No sensory deficit is present • Myotonia can be elicited in few cases of paramyotonia congenita with hyperkalemic periodic paralysis • Myotonia may be marked in eyelids in the hyperkalemic type
- 21. • In secondaryPP, features of causative disorders like thyrotoxicosis, CKD, diabetic nephropathy, acute glomerulonephritis, or ATN may be present • In thyrotoxic PP, the initial attack may occur before, during, or soon after diagnosis of thyrotoxicosis
- 22. Syndrome Age ofonset Duration of attack Precipitating factors Severity of attacks Associations Hyper-kalemic periodic paralyses First decade of life Few minutes to less than 2 h (mostly less than 1 h) Low carbohydrate intake (fasting) Cold Rest following exercise Alcohol Infection Emotional stress Trauma Menstrual period Rarely severe Perioral and limb paresthesias Myotonia frequent Occasional pseudo- hypertrophy of muscles Hypo-kalemic periodic paralyses Childhood to third decade Majority of cases before 16 years Few hours to almost a week Typically no longer than 72 hr Early morning attacks after previous day physical activity High-carbohydrate meal, alcohol Cold, change in barometric pressure or humidity Fever, URTI Lack of sleep, fatigue Menstrual cycle Severe Complete paralysis Occasional myotonic lid lag Myotonia between attacks rare Unilateral, partial, monomelic Fixed muscle weakness late in disease
- 23. Syndrome Age ofonset Duration of attack Precipitating factors Severity of attacks Associations Potassium- associated myotonia First decade No weakness Cold Rest after exercise Attacks of stiffness can be mild to severe Muscle hypertrophy Para-myotonia congenita First decade 2-24 hr Cold Rarely severe Pseudo- hypertrophy of muscles Paradoxical myotonia Fixed weakness rare Thyrotoxic periodic paralyses Third and fourth decades Few hours to 7 days Same as hypokalemic PP Hyper-insulinemia Same as hypokalemic PP Fixed muscle weakness may develop Hypokalemia during attacks
- 24. Andersen-Tawil syndrome • Autosomaldominant • Onset in early childhood • Triad of dysmorphic features, periodic paralysis, and cardiac arrhythmias • Patients may have short stature, hypertelorism, low-set ears, micrognathia, fifth finger clinodactyly, and scoliosis • Episodic weakness lasting a few to several hours • Not associated with myotonia • Prolonged QT interval and ventricular arrhythmias are the most common cardiac manifestations
- 25. Differential Diagnosis ofSecondary Periodic Paralysis Hypokalemic • Urinary potassium wasting • Hyperaldosteronism • Bartter syndrome • Alcohol • Drugs - Amphotericin B, barium • Renal tubular acidosis • GI potassium-wasting Hyperkalemic • Addison disease • Chronic renal failure • Hyporeninemic • Hypoaldosteronism • Ileostomy with tight stoma • Potassium load • Potassium-sparing diuretics
- 26. Differential Diagnosis ofOther Entities Causing Acute Generalized Weakness • Transient Ischemic Attacks • Sleep attacks • Myelopathy • Myasthenia gravis • Acute inflammatory demyelinating polyneuropathy • Porphyria • Toxins
- 27.
- 28. Serum K+ • Themost important investigation • Serum K+ in between attacks • Secondary PP : abnormal • Primary PP : usually normal • During attack, serum K+ may be high, low, or in upper or lower range of normal • Random testing for serum K+ may show periodic fluctuation in normokalaemic PP
- 29. “Abnormal serum potassiumlevel in absence of any other obvious cause in a patient with history of episodic short lived paralysis of skeletal muscle is almost diagnostic of periodic paralysis”
- 30. Cont…. • Urinalysis, bloodsugar, blood urea, serum creatinine, T3, T4 and TSH to exclude diabetic nephropathy, chronic or acute renal failure, and thyrotoxicosis • Phosphorus and magnesium may be low in secondary hypokalaemic periodic paralysis
- 31. CPK and serummyoglobin • Serum CPK is high in primary PP during or just after attack • Serum myoglobin may be high
- 32. ECG • ECG tocorelate the serum potassium levels • In Andersen Tawil syndrome, ECG and Holter reveal prolonged QT interval and ventricular arrhythmias
- 33. EMG • During attacks,EMG shows electrical silence • In between attacks, there may be fibrillation and complex repetitive discharges, increased by cold and decreased by exercise (in hypokalaemic PP)
- 34. Nerve conduction studies •Compound muscle action potential amplitude declines during attacks • Sensory nerve conduction study usually normal
- 35. Provocative Testing General precautions •physician presence during testing • performance in an intensive care setting • avoidance in potassium disturbances, diabetes mellitus, or renal or cardiac dysfunction • close monitoring of ECG • capability for rapid electrolyte and glucose correction
- 36. Hypokalemic periodic paralysis •Oral glucose loading test • Intravenous glucose challenge • Intra-arterial epinephrine test Hyperkalemic periodic paralyses • Oral Potassium chloride test
- 37. Muscle Biopsy • Themost characteristic abnormality is the presence of vacuoles in the muscle fibers • More marked in hypokalemic PP • Signs of myopathy include muscle fiber size variability, split fibers, and internal nuclei • Muscle fiber atrophy in clinically affected muscles • Tubular aggregates in some hypoPP, subsarcolemmal in location • Muscle fiber necrosis rare
- 38.
- 39. Hypokalemic Periodic Paralysis •Acute paralysis : Oral KCl (0.2–0.4 mmol/kg) every 30 min • Muscle strength and ECG should be monitored • IV therapy rarely required (e.g., when swallowing problems or vomiting is present) • Avoid potassium in dextrose solution • Mannitol is the preferred vehicle for IV potassium
- 40. • The long-termgoal is to avoid attacks, may reduce late-onset, fixed weakness • For prophylaxis, dichlorphenamide 50-100 mg BD or Acetazolamide 125–1000 mg/d in divided doses • If attacks persist, oral KCl should be added • Triamterene 25–100 mg/d or spironolactone 25–100 mg/d are 2nd line drugs
- 41. Thyrotoxic periodic paralysis •In acute attacks, potassium restore muscle strength and prevent complications • Caution advised as the total amount of potassium in the body is not decreased and potassium levels may overshoot ("rebound hyperkalemia") • Slow infusions of potassium therefore recommended
- 42. • Symptoms typicallyrespond to propranolol • Treatment of thyrotoxicosis usually leads to resolution of the paralytic attacks • Dichlorphenamide 50-100 mg BD or propranolol in doses of 20-40 mg BD control recurrent attacks
- 43. Hyperkalemic periodic paralyses •Attacks mild and rarely require treatment • In severe attacks, therapeutic measures that reduce hyperkalemia are utilized • Continuous ECG monitoring during the treatment • Thiazide diuretics and carbonic anhydrase inhibitors for prophylaxis
- 44. Paramyotonia congenita • Weaknessuncommon, treatment aimed at reducing myotonia • Thiazide diuretics (chlorothiazide 250–1000 mg/d) and mexiletine (slowly increase dose from 450 mg/d) Andersen-Tawil syndrome • Acetazolamide may decrease attack frequency and severity • Implantation of a cardiac defibrillator has rarely been performed
- 45. Diet • Hypokalemic periodicparalyses: Low-carbohydrate and low-sodium diet may decrease frequency of attacks • Hyperkalemic periodic paralyses: Glucose-containing candy or carbohydrate diet with low potassium may improve the weakness
- 46. Prognosis Hyperkalemic periodic paralysesand paramyotonia congenital • When not associated with weakness, usually do not interfere with ability to work • Myotonia may require treatment • Life expectancy not known to be affected Hypokalemic periodic paralyses • Untreated patients may experience fixed proximal weakness, which may interfere with activities • Several deaths reported, related to aspiration pneumonia or inability to clear secretions
- 47. Summary • PP characterizedby episodic short-lived paralysis of skeletal muscles • Idiopathic (primary or familial PP) or due to identifiable causes (secondary PP) • Serum potassium level abnormal during attacks • Both these groups are eminently treatable • Specific treatment for underlying disorders in secondary PP must be instituted
- 48.