Diagnosis of familial hypokalemic periodic paralysis: role of the potassium exercise test.

Familial hypokalemic periodic paralysis (FHOPP) is a rare, dominantly inherited disease, the diagnosis of which may require the induction of paralysis. We studied whether the increase in plasma potassium concentration during exercise can be used in the diagnosis of FHOPP. Potassium concentration increased 0.3 +/- 0.1 mEq/l in patients with FHOPP and 0.6 +/- 0.1 mEq/l in healthy controls (p < 0.001) during a 10-minute bicycle exercise test, and 0.3 +/- 0.1 mEq/l in patients with FHOPP and 0.8 +/- 0.2 mEq/l in healthy controls (p < 0.001) during a 30-minute bicycle exercise test. We conclude that the potassium exercise test may be useful in the diagnosis of FHOPP.     

The muscle fiber conduction velocity and power spectra in familial hypokalemic periodic paralysis

Surface EMG has been used to determine the average muscle fiber conduction velocity (MFCV) and power spectra of the m. biceps of 10 patients and 15 asymptomatic offspring of a large kinship with familial hypokalemic periodic paralysis (HOPP). The MFCV of the patients was 3.37 +/- 0.35 m/sec (mean +/- SD, n = 9), the median frequency (Fmed) of the power spectra was 55.0 +/- 5.8 Hz (mean +/- SD, n = 9), both values are significantly (P0.001, Student's t-test) lower than the control values: MFCV = 4.55 +/- 0.33 m/sec; Fmed = 88.6 +/- 15.5 Hz (mean +/- SD). In 6 of the 15 asymptomatic relatives, the surface EMG results were also abnormal. It is concluded that the MFCV is reduced in familial HOPP. This results in a predominantly low-frequency content of the power spectra, thereby providing a new model for studying the relationship between the MFCV and the frequency spectrum of surface EMG. Asymptomatic relatives that have inherited the disease probably can be detected with this method.     

Intravenous treatment of hypokalemic periodic paralysis

Acute attacks of weakness in patients with hypokalemic periodic paralysis can usually be treated with oral potassium preparations. Occasional patients, however, require intravenous (IV) potassium administration. We studied a patient with hypokalemic periodic paralysis to determine the effect of using 5% glucose as a diluent for potassium administration during acute attacks of weakness. Administration of IV potassium chloride in 5% glucose (50 mEq/L) was associated with a worsening of strength and no rise in potassium level. Intravenous potassium in 5% mannitol was associated with a rise in potassium and improvement in strength. This study confirms the hazard of using glucose-containing solutions for correction of hypokalemia.     

Treatment of hypokalemic periodic paralysis with topiramate

Hypokalemic periodic paralysis (hypoPP), the most common form of periodic paralysis, is a disorder characterized by attacks of transient muscle weakness associated with a drop in serum potassium level.The mainstay of treatment is potassium supplementation and drugs that inhibit the enzyme carbonic anhydrase. In this report we describe 11-year-old twins with hypoPP who were treated with topiramate, an anti-epileptic drug known to have carbonic anhydrase inhibitory properties. The patients experienced a decrease in the severity of their attacks upon initiation of treatment. Topiramate may warrant further investigation as a treatment option in hypoPP.     

Idiopathic hypokalemic periodic paralysis presenting peculiar insulin secretion

A 24-year-old male was admitted to our hospital because of the paralytic attack. He was well until he went to bed the day before, and he found his limbs unmovable in the morning. The initial attack occurred at age 11 and subsequently he had two episodes of the reversible generalized weakness which always appeared in the morning and continued for about one day at age 14 and 21, respectively. The provocative factors were uncertain. There was no family history of paralytic attacks nor thyroid diseases. On the neurologic examination he presented flaccid tetraparesis without the facial and respiratory involvements. The laboratory studies showed that the serum potassium was 2.4 mEq/l and the thyroid function was normal. The oral and intravenous potassium chloride was given and within two days the serum potassium turned back to the normal level, and he has recovered completely from the paralysis. An oral 75g glucose load was performed. The serum immunoreactive insulin (IRI) was elevated from the basal level to 289 microU/l, showing the prominent peak response at 30 min after the load, and both the serum potassium and the grasping power decreased significantly, although the blood glucose fluctuated within the normal level. After the prophylactic treatment with acetazolamide 2,000 mg daily for 7 days, this markedly elevated initial insulin response has disappeared and moreover the weakness of grip was milder, however, the serum potassium decreased notedly. This case revealed that in the idiopathic hypokalemic periodic paralysis the attack was possibly induced by the extraordinarily secreted insulin which was supported by the acetazolamide treatment.     

低钾型周期性麻痹的临床及病理研究

目的 总结低血钾型周期性麻痹(hypoPP)的临床表现及其肌肉组织病理学改变的特点。方法 回顾分析42例hypoPP患者的主要临床表现及辅助检查，并对其中的3例行肌肉组织病理学检查。结果 总体来看，血钾越低患者临床症状及其他辅助检查变化也就越重、治疗效果越差，但患者的肌无力和腱反射的变化与血钾的变化并不完全平行，肌力下降也可不对称，2例患者出现呼吸肌麻痹，其中1例还同时伴有脑神经支配肌肉的受损，11例患者出现主观感觉障碍，54．5％(18／33例)的患者肌酸磷酸激酶(CPK)增高。患者骨骼肌病理学检查中可见空泡样肌纤维及管状集合物。结论 血清钾水平与肌无力症状不完全平行；主观感觉异常、CPK增高、恢复时间较长与肌肉组织的病理改变有关；不典型低钾型周期性麻痹应与吉兰—巴雷综合征、多发性肌炎等进行鉴别，必要时应进行骨骼肌病理学检查。     

Dysfunction of sensory nerves during attacks of hypokalemic periodic paralysis.

Reversible electrophysiologic abnormalities of sensory nerve function were found by chance in three patients with hypokalemic periodic paralysis, a disorder previously considered to affect the function of muscle membranes only. A formal, prospective study was therefore conducted. Serial nerve conduction studies were done in ten additional patients. Amplitude of sensory action potentials was significantly smaller during paralytic attacks, but did not differ from controls after normalization of serum potassium concentration. These apparently novel findings might be explained by previous electrodiagnostic studies either not involving the testing of sensory nerves at all, or not being repeated after recovery from an attack. Involvement of sensory nerves in hypokalemic periodic paralysis is suggested to arise through dorsal root ganglia having an incomplete blood-nerve barrier and sensory neurons being particularly vulnerable to derangements affecting nerve cell metabolism. Neuronal inexcitability is postulated to occur consequent upon possible inactivation of the sodium-potassium pump by the low concentration of extracellular potassium. In patients with acute areflexic limb weakness, the diagnosis of hypokalemic periodic paralysis should not be excluded by abnormal results of sensory nerve conduction studies.     

Acetazolamide treatment of hypokalemic periodic paralysis. Probable mechanism of action.

Following administration of glucose and insulin to three patients with hypokalemic periodic paralysis, serum K+ fell 1.9 mM. After administration of acetazolamide, 250 mg four times daily, serum K+ fell 0.9 mM, a substantial difference. In normal persons glucose and insulin lowered serum K+ 0.5 mM, and this was not changed substantially by acetazolamide. The metabolic acidosis induced by the drug appears to be responsible for the change in decrement of serum K+ and for the amelioration of symptoms in the patients. The findings agree with earlier reports that metabolic acidosis lowers the rate of entry of K+ into muscle, thus opposing the heightened or pathological entry of K+ into muscle cells during attacks of the disease.     

Treatment of “permanent” muscle weakness in familial hypokalemic periodic paralysis

Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichloro-phenamide, a more potent carbonic anhydrase inhibitor. Dichloro-phenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third. Muscle groups graded 4/5 (MRC scale) returned to normal; very weak (0–3/5) atrophic muscles, improved to a minor degree. In one patient with acetazolamide-resistant paralytic attacks, dichlorophenamide also diminished the frequency and severity of the acute attacks. Dichlorophenamide had, in the present study, less effect than acetazolamide in reducing serum HCO and elevating Cl^?. Its effectiveness may be related to the degree of sensitivity of certain HOPP patients to alterations of Cl^? and/or HCO serum levels or to a different action of the drug unrelated to carbonic anhydrase inhibition or acidosis. Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide.     

Gender differences in penetrance and phenotype in hypokalemic periodic paralysis

Introduction: Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant skeletal muscle ion channelopathy. Sex hormones are natural ion channel regulators. Different sex hormones have different effects on ion channels. A comparison of the penetrance and phenotype between males and females with HypoPP mutations should aid in proving that sex hormones play different roles in HypoPP and also provide the basis for the development of therapies against HypoPP. Methods: We identified all mutation carriers in 4 HypoPP families using PCR sequencing techniques. All patients underwent clinical investigation. Results: There were 8 men and 7 women mutation carriers in the 4 families. Male carriers had 100% penetrance, but female penetrance was only 28.57%. The highest attack frequency was 50–150 times/year for the men, whereas it was 30–50 times/year for the women. The attacks disappeared during pregnancy. Conclusions: The penetrance and attack frequency were lower in women than in men with HypoPP mutations. Muscle Nerve, 2013     

Interictal conduction slowing in muscle fibers in hypokalemic periodic paralysis

Conduction velocity in muscle fibers of the short head of biceps brachii was reduced between attacks in all the affected members of a family suffering from hypokalemic periodic paralysis. This finding represents a further evidence of a primary alteration of sarcolemmal function in this disease. Interictal conduction slowing in muscle fibers is consistent with the prevailing pathophysiologic hypothesis, which considers an increased membrane permeability to sodium ions as the fundamental defect underlying all forms of familial periodic paralysis.     

Case of Bartter syndrome presenting with hypokalemic periodic paralysis

Hypokalemic periodic paralysis can occur secondarily to excessive potassium loss. Thyrotoxicosis, diuretic ingestions, hyperaldosteronism, barium poisoning, Gitelman syndrome, and Bartter syndrome are among the disorders causing secondary hypokalemic periodic paralysis. Clinical presentation of Bartter syndrome with hypokalemic periodic paralysis is rare. A 12-year-old boy was admitted to our hospital because of transient paralysis. He had been suffering from transient weakness attacks for 2 years and had had a total of 10 attacks, lasting 1 to 3 days. He had growth retardation, polyuria, and polydipsia. Laboratory examinations revealed hypokalemic alkalosis, normomagnesemia, hypercalciuria, and hyperaldosteronism. The clinical and laboratory findings were in accordance with Bartter syndrome. He has been followed up for 6 months and has suffered no further paralytic attacks under indomethacin therapy. This case highlights the importance of blood pH measurement in patients with hypokalemic periodic paralysis; it might prevent misdiagnosis and mismanagement in such diseases.