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Periodic Paralyses Differential Diagnoses

  • Author: Naganand Sripathi, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
 
Updated: Mar 24, 2016
 
 

Diagnostic Considerations

Table 3. Differential Diagnosis of Secondary Periodic Paralyses (Open Table in a new window)

HypokalemicHyperkalemic
Urinary potassium-wasting syndromes
  • Hyperaldosteronism
  • Conn syndrome
  • Bartter syndrome
  • Licorice intoxication
 
AlcoholAddison disease



Chronic renal failure



Hyporeninemic



Hypoaldosteronism



Drugs - Amphotericin B, bariumIleostomy with tight stoma
Renal tubular acidosisPotassium load
GI potassium-wasting syndromes
  • Laxative abuse
  • Severe diarrhea
Potassium-sparing diuretics

Table 4. Differential Diagnosis of Other Entities Causing Acute Generalized Weakness (Open Table in a new window)

DisorderPattern and



Distribution of



Weakness



Transient ischemic attacksFollow CNS distribution (ie, hemiparetic)



May have sensory symptoms and signs



Sleep attacksOccur at onset or termination of sleep



Last only minutes



Myelopathy
  • Traumatic
  • Transverse myelitis
  • Ischemic
Sensory symptoms



Presence of a sensory level



Sphincter involvement



Myasthenia gravis



Lambert-Eaton myasthenic syndrome



Subacute in onset



Associated autonomic symptoms in LEMS



Hyporeflexia in LEMS



Abnormal repetitive nerve stimulation



Presence of distinct antibodies



Peripheral neuropathy of acute onset
  • Acute inflammatory
  • demyelinating poly-radiculoneuropathy
  • Porphyria
Pattern of weakness



Absent stretch reflexes



Toxins
  • Ciguatera
  • Tetrodotoxin
Clinical presentation

 

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Naganand Sripathi, MD Director, Neuromuscular Clinic, Department of Neurology, Henry Ford Hospital

Naganand Sripathi, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, Michigan State Medical Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Additional Contributors

Paul E Barkhaus, MD Professor of Neurology and Physical Medicine and Rehabilitation, Department of Neurology, Medical College of Wisconsin; Section Chief, Neuromuscular and Autonomic Disorders, Department of Neurology, Director, ALS Program, Medical College of Wisconsin

Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

References
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Mutations in periodic paralysis.
Table 1. Primary Periodic Paralysis (modified from Jurkat-Rott and Lehmann-Horn[1] )
DiseaseGeneProteinInheritanceMutation
HyperPPSCN4ANav1.4DominantGain
NormoPP   Gain (ω-pore)
ParamyotoniacongenitaGain
HypoPP Type IIGain (ω-pore)
HypoPP Type ICACNA1SCav1.1DominantGain (ω-pore)
ThyrotoxicPPKCNJ18Kir2.18DominantLoss
Andersen-Tawil syndromeKCNJ2Kir2.1DominantLoss
Table 2. Distinguishing Features Among the Common Forms of Periodic Paralyses
SyndromeAge of OnsetDuration of AttackPrecipitating



Factors



Severity of AttacksAssociated



Features



Hyper-kalemic periodic paralysesFirst decade of lifeFew 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 severePerioral and limb paresthesias



Myotonia frequent



Occasional pseudo-hypertrophy of muscles



Hypo-kalemic periodic paralysesVariable -Childhood to third decade



Majority of cases before 16 years



Few hours to almost a week



Typically no longer than 72 h



Early morning attacks after previous day physical activity



High-carbohydrate meal, Chinese food, alcohol



Cold, change in barometric pressure or humidity



Fever, upper respiratory tract infections



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



Potassium- associated myotoniaFirst decadeNo weaknessCold



Rest after exercise



Attacks of stiffness can be mild to severeMuscle hypertrophy
Para-myotonia congenitaFirst decade2-24 hColdRarely severePseudo-hypertrophy of muscles



Paradoxical myotonia



Fixed weakness rare



Thyrotoxic periodic paralysesThird and fourth decadesFew hours to 7 dSame as hypokalemic PP



Hyper-insulinemia



Same as hypokalemic PPFixed muscle weakness may develop



Hypokalemia during attacks



Table 3. Differential Diagnosis of Secondary Periodic Paralyses
HypokalemicHyperkalemic
Urinary potassium-wasting syndromes
  • Hyperaldosteronism
  • Conn syndrome
  • Bartter syndrome
  • Licorice intoxication
 
AlcoholAddison disease



Chronic renal failure



Hyporeninemic



Hypoaldosteronism



Drugs - Amphotericin B, bariumIleostomy with tight stoma
Renal tubular acidosisPotassium load
GI potassium-wasting syndromes
  • Laxative abuse
  • Severe diarrhea
Potassium-sparing diuretics
Table 4. Differential Diagnosis of Other Entities Causing Acute Generalized Weakness
DisorderPattern and



Distribution of



Weakness



Transient ischemic attacksFollow CNS distribution (ie, hemiparetic)



May have sensory symptoms and signs



Sleep attacksOccur at onset or termination of sleep



Last only minutes



Myelopathy
  • Traumatic
  • Transverse myelitis
  • Ischemic
Sensory symptoms



Presence of a sensory level



Sphincter involvement



Myasthenia gravis



Lambert-Eaton myasthenic syndrome



Subacute in onset



Associated autonomic symptoms in LEMS



Hyporeflexia in LEMS



Abnormal repetitive nerve stimulation



Presence of distinct antibodies



Peripheral neuropathy of acute onset
  • Acute inflammatory
  • demyelinating poly-radiculoneuropathy
  • Porphyria
Pattern of weakness



Absent stretch reflexes



Toxins
  • Ciguatera
  • Tetrodotoxin
Clinical presentation
Table 5. Medical Conditions Associated With Hypokalemia
Urine K/C RatioAcid Base StatusOther Associated FeaturesMedical



Conditions



< 1.5Metabolic acidosis Lower GI loss – Laxative abuse, diarrhea
< 1.5Metabolic alkalosisNormal BPSurreptitious vomiting
>1.5Metabolic acidosis DKA, type 1 or type 2 distal RTA
>1.5Metabolic alkalosisNormal BPDiuretic use, Bartter syndrome, Gitelman syndrome
≥1.5Metabolic alkalosisHypertensionPrimary aldosteronism, Cushing syndrome, renal artery stenosis, congenital adrenal hyperplasia, apparent mineralocorticoid excess, Liddle syndrome
Table 6. Diagnostic Studies of Hypokalemic and Hyperkalemic Periodic Paralyses
 Hypokalemic PPHyperkalemic PP
Serum potassiumMildly depressed; may reach 1-5 mEq/LIncreases from baseline but may not increase beyond normal range
Serum CPKModerately elevated during attacksMildly elevated during attacks
ECGBradycardia



Flat T waves, U waves, ST-segment depression



Tall T waves
Table 7. Electrophysiological Patterns to Exercise Testing
 Para-



myotonia



Congenita



Hyper-



kalemic



Periodic Paralysis



Hypo-



kalemic



Periodic Paralysis



Electrophysiological



pattern



IIVV
Channel mutationsSodium T1313M, R1448CSodium T704MCalcium R528H
Short Exercise Test:   
Post exercise myotonic potentialsYesNoNo
CMAP amplitude



change after First trial



Increase or



decrease



IncreaseNo
CMAP amplitude



change after second



and third trial



Gradual



increase



Gradual



increase



No
Long Exercise Test:   
Immediate change of



CMAP amplitude



DecreaseIncreaseNo
Late change of CMAP amplitudeDecreaseDecreaseDecrease
Modified from Fournier et al, 2004.[12]
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