Periodic Paralysis: A Case Series with a Literature Review

The different forms of periodic paralysis can be primary or secondary, involving recurrent episodes of flaccid paralysis. Primary periodic paralysis can be divided into hypokalemia, normokalemia, and hyperkalemia varieties. Secondary periodic paralyzes are connected with thyrotoxicosis, primary aldosteronism, or potassium (K) abnormalities in conditions like diabetic acidosis and renal tubular acidosis. It may connect genetically through the RYR1 myopathy variant [1].

Inherited periodic paralysis encompasses a range of conditions, most of which are inherited as autosomal dominant traits. However, there are exceptions to this pattern, such as X-linked paralysis, episodic muscle weakness, and mitochondrial and motor neuropathy, which may arise from maternal inheritance or occur sporadically. It is three times more prevalent in males than in females. The paralysis attacks are usually nocturnal and occur after a period of vigorous exercise [2]. In this clinical setting, it is important to exclude diagnostic entities such as hypokalemic or normokalemic periodic paralysis, episodic weakness periodic paralysis, Guillain-Barre syndrome, myasthenia graves, Eaton-Lambert syndrome, multiple sclerosis, transient ischemic attacks, metabolic defects of muscle (impaired carbohydrate or fatty acid utilization), chronic renal failure, and surreptitious diuretic abuse based on the nature of presentation, physical examination, and paraclinical studies [3].

Although weakness is associated with low levels of serum K, in this condition, it can begin at K levels higher than that which would cause paralysis in a normal individual, and it can have some association with hyperthyroidism [4]. The CARE Checklist has been completed by the authors for this case series, and it is attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000541585).

We are conducting a thorough retrospective study on patients who were diagnosed with periodic paralysis from February 1, 2022, to February 15, 2023, at Hazm Mebaireek General Hospital, Hamad Medical Corporation, Doha, Qatar. Our team will analyze electronic medical records, imaging studies, surgical notes, and follow-up data to gather comprehensive information on each case. This study will provide invaluable insights into this condition, ultimately leading to better diagnosis and treatment outcomes.

A 36-year-old male patient with no prior medical history presented to the emergency department with weakness in his upper and lower limbs, which had been ongoing for 1 day. There were no complaints of double vision, difficulty with swallowing, or incontinence, and no history of trauma was reported and also no significant family history. Upon physical examination, the patient was found to be alert and oriented with a power of 2/5 in the lower limbs and 3/5 in the upper limbs. There were slightly decreased reflexes in all limbs but no significant findings otherwise. Initial lab tests showed an increase in white blood cells of 18.1 × 10³/μL, a low K level of 2.5 mEq, a high thyroid-stimulating hormone (TSH) of 6.01 mIU/L, and a low FT4 of 10.4 pmol/L.

Based on these findings, the patient was admitted for investigation and treatment of hypokalemic paralysis. During his admission, he was started on a K infusion of 40 mmol over 4 h and 50 mg of levothyroxine. Further investigations showed a high titer of anti-thyroglobulin Abs of 269 IU/mL. After 2 days of his admission, the patient was diagnosed with hypothyroidism and hypokalemic paralysis and discharged on levothyroxine 50 mg, magnesium hydroxide 75 mg, and potassium chloride 600 mg orally. He was referred for follow-up in the clinic, and genetic testing was not done due to the patient’s financial issues.

A 27-year-old man with no prior medical history presented to the emergency department complaining of muscle weakness, which had lasted for 1 day. He did not exhibit any other symptoms, such as slurred speech, double vision, headache, trauma, palpitations, or excessive sweating. This was his first episode, and there was no significant family history. Physical examination revealed a power of 2/5 in his upper limbs and 3/5 in his lower limbs, accompanied by decreased reflexes throughout his body. No significant abnormalities were discovered in other systems. Initial lab results showed an elevated white blood cell count of 11.3 × 10³/μL, a low K level of 2.1 mEq, high myoglobin levels of 135 ng/mL, a TSH of 0.02 mIU/L, and a low FT4 of 22.6 pmol/L.

The patient was admitted for further investigation and management of periodic paralysis caused by hypokalemia with hyperthyroidism. He was given K replacement therapy. During his stay, tests revealed a high titer of anti-thyroglobulin antibodies at 3,383 IU, and he was started on carbimazole 5 mg BID. After a couple of days from his admission, the patient was discharged and referred to the outpatient department for follow-up, and genetic testing was not done due to the patient’s financial issues.

A 61-year-old male patient with a history of diabetes mellitus and hypertension, on amlodipine/valsartan, metoprolol, and indapamide, presented with a dry cough and fatigue that had persisted for 5 days. He had no fever, palpitations, chest pain, numbness, or difficulty walking. Initial vital signs showed high blood pressure of 173/109, but the rest were normal. Initial examination showed no abnormalities. Lab results showed low K levels of 2.4 mEq with an elevated blood pH of 7.5 and no other significant findings.

The patient was admitted to the ward as a case of hypokalemia with metabolic alkalosis for further investigation and management. He was started on his regular medication along with IV K of 40 mg, and indapamide was discontinued. During the admission, an elevated level of aldosterone was found at 1,160, with a renin of <0.14 and an aldosterone-renin ratio of 183.34. The patient underwent an abdominal CT to assess the adrenals, and a right adrenal lesion consistent with adrenal adenoma was found. The left adrenal was normal. The patient continued on oral K replacement and was started on spironolactone. After 6 days after his admission, the patient was discharged when his K levels and hypertension were corrected. He was diagnosed with Connʼs syndrome and was referred to the outpatient department for further management.

A 37-year-old male patient with a known history of Graveʼs disease and positive TRAB had not taken carbimazole for more than a month. He presented with lower-limb weakness that prevented him from walking or standing. He had no history of headache, fever, decreased or loss of consciousness, bladder/bowel incontinence, or recent infections, and no significant family history. Initial vitals showed a pulse of 108 and a BP of 127/68. Initial examination showed a power of 3/5 in the lower limbs with normal power in the upper limbs. No other significant findings were found. Initial labs showed a low level of K of 2 mEq with normal blood pH, TSH <0.01 mIU/L, and T4 of 76.7 pmol/L, with no other findings.

As a result, the patient was admitted for management and investigations as a case of periodic paralysis with thyrotoxicosis. He was started on an IV K replacement of 40 mg. During the admission, he was started on propranolol 20 mg and carbimazole 20 mg, K was corrected to 4.4 mEq, and the weakness improved. Three days after his admission, he was discharged on propranolol 20 mg and carbimazole 20 mg referred to the outpatient department for follow-up, and genetic testing was not done due to the patient’s financial issues.

A 46-year-old man with a history of autoimmune hypothyroidism and currently on levothyroxine 100 mg presented with sudden symmetrical weakness in both his legs after working in hot weather. He was unable to stand or walk. He had experienced similar symptoms twice before. He had no fever, trauma, back pain, or autonomic involvement. His initial vital signs were normal, and his examination revealed muscle power of 3/5 in all limbs with hypotonia and hyporeflexia. There were no significant findings in the other systems. His initial investigations showed an elevated creatinine level of 114 mmol, a low K level of 2.1 mEq, urinary K of 22 mmol, a TSH of >100 mIU/L, a T4 of 6.6 pmol/L, and a blood pH of 7.1.

The patient was admitted as a case of hypokalemic periodic paralysis due to type 1 RTA and acute kidney injury from heat exhaustion and was started on levothyroxine 100 mg, 40 mg IV K replacement, and IV fluids for management. After 2 days of treatment, the K level was corrected to 4 mEq, and the weakness improved significantly along with the creatinine level. Due to these improvements, the patient was discharged on the third day and referred to the outpatient department for follow-up, and genetic testing was not done due to the patient’s financial issues.

A 27-year-old male patient with no prior medical history presented with progressive weakness in his upper and lower limbs that persisted for 2 days. He did not have a fever, headache, trauma, recent infection, or incontinence. There was no significant family history. His vitals were normal, and he was alert and oriented. However, he had a power of 3/5 in both upper and lower limbs, and his cranial nerves were normal, while other systems showed no abnormalities. Lab investigations revealed low K levels of 2.5 mEq, but no other significant findings were noted.

The patient was admitted to the ICU for monitoring, management, and further investigations as a case of hypokalemic paralysis. He received 20 mg of IV K and MgSO₄, and the next day, his K levels had improved to 5.2 mEq, and his weakness had subsided. Consequently, he was transferred to the medical ward. Further lab tests showed an aldosterone level of 119, TSH of 3.38 mIU/L, and T4 of 16.7 pmol/L. After 2 days, the patient was discharged and referred to the outpatient department for follow-up, and genetic testing was not done due to the patient’s financial issues.

Hypokalemic periodic paralysis is a condition that may either be hereditary or acquired, and it may be associated with thyrotoxicosis. Although this condition is rare, it is a well-documented complication of uncontrolled hyperthyroidism in eastern Asian populations [5]. Hypokalemic periodic paralysis affects males more frequently, even though thyrotoxicosis is more prevalent among females [5]. Autosomal recessive mutations in skeletal muscle L-type calcium or sodium channel genes are the cause of primary hypokalemic periodic paralysis, whereas it is thought to be caused by overactivity of Na-K ATPase, which is stimulated by excessive thyroid hormone [6]. This overactivity results in greater intracellular shifts of K, hypokalemia, and hyperpolarization of skeletal muscle membranes. These episodes may be triggered by large, carbohydrate-laden meals or heavy exercise. In acquired hypokalemic periodic paralysis, paralysis may be evoked by thyrotoxicosis rather than controlled hyperthyroidism [5].

Hypokalemic periodic paralysis is a condition that causes acute intermittent muscle weakness. Although it might be hereditary, it is similar to familial periodic paralysis [7, 8]. This condition is more common in Asian or Hispanic males with thyrotoxicosis, where up to 10% of thyrotoxic patients may experience periodic paralysis. The exact cause of thyrotoxic periodic paralysis is unclear, but there is evidence of a decrease in the activity of the calcium pump [9‒11].

There are several reasons why this condition is associated with a lack of K outside of cells. Its detection can be challenging or even misdiagnosed because normal functioning and K levels can occur between attacks, making diagnosis more difficult [12]. As a result, it is important to maintain a high level of suspicion and rule out other neurological or medical conditions that may show similar symptoms. These conditions have varying degrees of severity that require different management approaches, so it is essential to decide on them as soon as possible. Hyperthyroidism can be subtle or even subclinical and may not always be apparent [13].

All participants in our study presented with mild to severe hypokalemia (2–2.5 mEq) upon initial assessment. Hypokalemia is recognized as the most consistent electrolyte abnormality in hypokalemic periodic paralysis and is a defining characteristic of the syndrome alongside hyperthyroidism. Previous research has shown that hypokalemia is a result of K shifting into cells rather than a depletion of total body K [14‒16]. The patients in our study were administered potassium chloride in a total dose of 20–40 mg, with an average of 33 mg, and were able to recover from hypokalemia within one to 8 h, with an average of 3.5 h, after being admitted to the hospital.

During previous episodes of weakness when the patients did not seek medical attention, the attacks typically lasted for an average of half a day, which is consistent with the duration of attacks reported by others [15]. Our observations showed that the most common electrocardiographic changes were ST segment depression with T wave flattening, sinus tachycardia, and U waves, all of which are typical in hypokalemia and thyrotoxicosis. In addition, sinus arrest and second-degree atrioventricular block have also been noted in patients with periodic paralysis [17], ventricular fibrillation [18], and ventricular tachycardia [19].

The effective management of hyperthyroidism is of paramount importance. The suggested course of action for managing this condition involves the oral administration of 27 mEq of potassium chloride every 2 h for 6 h, followed by administration every 4 h, with close monitoring [6]. Nonselective β-blockers such as propranolol may be useful in preventing paralysis attacks in patients who are receiving antithyroid medications but have not yet attained euthyroid status [20]. It is uncertain whether potassium chloride supplementation can prevent paralysis attacks in such patients. Patients with hyperthyroidism may possess specific genetic variations that can affect the effects of thyroxine on ion channels, rendering them more susceptible to experiencing paralytic episodes if their thyroid function is not closely monitored [5].

During the assessment of a patient, it is crucial to take into account their social and family history in a comprehensive manner. Even if such information is not available, it is essential to keep in mind the possibility of a diagnosis that could have significant implications for the individual’s life. Additionally, the origin of such a diagnosis should be considered, as it may be treatable with straightforward and well-tolerated methods. Failure to identify and treat this condition promptly may lead to severe and even fatal consequences. As a result, early recognition and intervention are critical for effective management and patient safety.

The study was conducted by the principles of the institutional ethical standards and national research committee. The article describes a case series. Therefore, an Institutional Review Board approval was taken from the Medical Research Center at Hamad Medical Corporation Ethical Committee approval under MRC-04-23-927. Written informed consent was obtained from the patients to publish this case series and any accompanying data or images in this manuscript.

The authors have declared that no competing interests exist.

This case series was not funded.

Data collection, literature search, and manuscript preparation (draft and final editing): B.A.H., M.A.H., M.S., O.A.A., Y.A.H., and M.K.K. All authors read and approved the final manuscript.

The data supporting this study’s findings are available in this article, and further inquiries can be directed to the corresponding author.