Hypokalemic periodic paralysis triggered by exertion and cold exposure in a resource-limited Ethiopian setting: a case report

Abstract

Background

Hypokalemic periodic paralysis is a type of periodic paralysis, a rare but life-threatening condition that can cause sudden onset weakness but can be reversed completely with early diagnosis and treatment. Diagnosis of hypokalemic periodic paralysis can be challenging in resource-limited settings where investigations such as genetic testing, Electromyography (EMG) and biochemical tests are not available. We present a case of hypokalemic periodic paralysis in an adult female diagnosed and treated using trigger pattern recognition, basic investigations, exclusion of differential diagnosis and treatment response.

Case presentation

A case of a 35-year-old Ethiopian female is presented here. The patient presented with a sudden onset of weakness with failure to move her extremities for 1-day duration, preceded by vigorous exercise in her farm land. She had experienced a similar illness a year back in the cold season, for which she was treated and discharged improved. Laboratory results were remarkable for markedly low serum potassium. The patient had improvement after 12 hours of starting potassium replacement. On the second day, the serum potassium was 4 mEq/L, and the patient was discharged from the hospital with no residual neurologic deficit.

Conclusion

Early diagnosis and treatment of hypokalemic periodic paralysis (PP) is lifesaving, as late diagnosis can be fatal. Therefore, periodic paralysis should be considered in the differential diagnosis of patients with weakness even in adult female patients who do not fit the common demographic. Careful evaluation of trigger factors, previous historical clues, patient presentation and response to treatment can aid timely diagnosis and management in resource limited settings.

Introduction

Periodic paralysis is a rare and often overlooked cause of weakness [1]. The commonest cause of periodic paralysis is hypokalemic periodic paralysis, with a prevalence of 1 in 100,000. It is a life-threatening condition, but it can be reversed completely with early diagnosis and treatment [2]. Patients present with recurrent episodes of weakness that vary in amount and severity and often coincide with reduced serum potassium levels, with onset most commonly in the first and second decades of life [3]. Triggering factors include intake of food rich in carbohydrates or salts, alcohol, strong emotion, cold exposure, and rest after intense or unusual physical exercise [4]. Here we present an adult female presentation of hypokalemic periodic paralysis triggered by cold exposure and exertion, diagnosed and managed successfully despite the lack of confirmatory investigations in a resource limited setting.

Case presentation

A 35-year-old Ethiopian female patient presented to the Emergency Department with sudden onset generalized body weakness of 1 day duration. The weakness was more pronounced in her lower extremity, limiting her from going to the bathroom unsupported. According to the patient, the incident occurred three hours after she had engaged in vigorous physical activity on her farmland in the planting season. She also experienced a similar episode a year ago following a cold exposure, treated with potassium supplementation and discharged improved. Otherwise, she did not complain of any pain, myalgia or fatigability associated with her current illness. She didn’t report any thyrotoxic symptoms, breathing or swallowing difficulty. She did not notice a tick bite or antecedent respiratory or gastrointestinal infections. She had no known chronic medical illness or physical dysmorphic features. She did not exhibit sensory, autonomic, respiratory or bulbar involvement. She had no history of any medication intake, no history of diarrhea or vomiting. She had no family history of neuromuscular disorders or intermittent muscle weakness. No history of any known hormonal diseases such as Cushing syndrome or hyperaldosteronism. On pertinent physical examination, she was fully conscious, and her vital signs were stable. Her muscle bulk was symmetric bilaterally, and her tone was hypotonic. Muscle strength in major muscle groups, including knee flexion and extension, was graded as 0; ankle dorsiflexion and plantar extension as 1; elbow flexion and extension as 4; and wrist flexion and extension as 5. She also had generalized hyporeflexia. There were no sensory or coordination abnormalities.

The patient’s course of illness can be summarized as shown on the timeline of presentation (Fig. 1).

Fig. 1.

Timeline of presentation (originally produced by authors)

Diagnostic investigations

As shown in Table 1, the only abnormal finding on the initial investigation summary was hypokalemia of 2.5 meq/L. Thyroid stimulating hormone was normal, renal function test and random blood glucose was within the normal level.

Table 1.

Investigation summary (originally produced by authors)

Investigations		Result	Reference level	Remarks
Complete blood count	White blood cells	9,000 cells/µL	4000–11,000 cells/µL	Normal
	Hemoglobin	13 g/dL	12.0–16.0 g/dL	Normal
	Platelets	250,000/µL	150,000–450,000/µL	Normal
Serum electrolytes	Potassium	2.5 mEq/L	3.5–5 mEq/L	Low (hypokalemia)
	Sodium	140 mEq/L	135–145 mEq/L	Normal
	Chloride	98 mEq/L	96–106 mEq/L	Normal
	Total calcium	9.6 mg/dL	8.5–10.5 mg/dL	Normal
RFTs	Creatinine	1.0 mg/dL	0.5–1.1 mg/dL	Normal
	BUN	16 mg/dL	7–20 mg/dL	Normal
TFTs	TSH	2.5 µIU/mL	0.4–4 µIU/mL	Normal
Random blood sugar		104 mg/dL	70–140 mg/dL	Normal
Electrocardiogram		Sinus rhythm	Normal sinus rhythm	Normal

μL microliter, g gram, dL deciliter, mEq miliequivalent, L liter, mg miligram, dL deciliter, μIU microinternational unit, RFTs Renal function test, TFTs Thyroid function test

Other pertinent diagnostic evaluation including serum magnesium levels, creatinine kinase, acid base status, genetic testing and EMG could not be done due to financial limitation and resource availability issues. The limitation was considered during the process of forming a diagnosis.

The differential diagnoses include Guillain–Barre syndrome, spinal masses and epidural abscess, as well as thyrotoxic periodic paralysis. The absence of sensory level, back pain or bowel and bladder dysfunction makes spinal compressive lesions unlikely. Guillain-Barré Syndrome (GBS) was considered less likely with the absence of antecedent infection, typical presentation of ascending paralysis with preceding sensory symptoms and lack of bulbar and respiratory symptoms. In addition to these, a normal TSH level makes Thyrotoxic periodic paralysis highly unlikely. Other possible causes of potassium depletion such as use of diuretics and Gastrointestinal (GI) loss were excluded based on historical evaluation of the patient.

The patient presentation was most consistent with a diagnosis of hypokalemic periodic paralysis due to the typical patient presentation with lower limb predominant flaccid paralysis, recurrent triggered attack, low serum potassium level and exclusion of other differential diagnosis.

Case management

After the diagnosis of hypokalemic periodic paralysis was made, the patient was started on 40 mEq of intravenous (IV) Potassium Cholride (KCl) in 1 L of normal saline over 8 hours with close monitoring of serum potassium to prevent hyperkalemia. IV potassium replacement was preferred over the usual oral potassium supplementation due to clinically significant hypokalemia (2.5 meq/L), profound muscle weakness and concern for potentially fatal complications such as arrhythmias. During the treatment phase, the patient was put on monitor with close cardiac monitoring and serum potassium level follow up. The next day the serum potassium level was corrected to a level of 4 meq/L, and the weakness significantly improved. Since the serum potassium level normalized the patient was not put on any oral potassium supplementation on discharge but non-pharmacologic intervention to avoid subsequent events was given. The patient was counseled on trigger factors, avoidance strategies and prevention of recurrence and was appointed for follow up.

Discussion

One of the commonest neurologic presentations is weakness, and there can be multiple differentials to a patient presenting with weakness. These range from life-threatening conditions such as stroke and compressive mass lesions to common presentations such as post-ictal paralysis [5]. However, another rare and often overlooked cause of acute flaccid paralysis is periodic paralysis (PP) [6]. Periodic paralysis can be of multiple types with different associated metabolic and electrolyte abnormalities [5]. It can broadly be divided into primary and secondary periodic paralysis. Primary periodic paralysis can be further classified into hypokalemic, normokalemic and hyperkalemic PP. Furthermore, conditions such as thyrotoxicosis and K+ abnormalities acquired from multiple systemic diseases can cause secondary PP [7]. Hypokalemic PP is the most common cause of periodic paralysis [5].

Hypokalemic PP has a rare occurrence with an estimated prevalence of 1 in 100,000 [8]. It has a 3:1 male-to-female ratio and can be either hereditary or acquired [7]. Genetic mutations have been implicated in the pathogenesis of hereditary hypokalemic periodic paralysis. It is an autosomal dominant disorder causing episodic attacks of paralysis with varying severity [9]. It is caused by a mutation coding for ion channels, including calcium and sodium channels. Dihydropyridine-sensitive calcium channel disorder is the most common genetic abnormality in hypokalemic PP and is found in approximately 70% of patients [10]. Thyrotoxicosis is a cause of acquired hypokalemic periodic paralysis and is mostly identified in the Asian and Hispanic population [7].

Patients with hypokalemic PP have recurrent episodes of weakness that vary in amount and severity and often coincide with reduced serum potassium level [11]. In hypokalemic PP attacks begin in late childhood or teenage years/the first and second decades of life. The average duration of an attack is 24 hours, but can generally range from 1 to 72 hours [12]. The episodes follow triggering factors such as the intake of food rich in carbohydrates or salts, alcohol, strong emotion, cold exposure, and rest after intense or unusual physical exercise [13]. Clinical manifestations of hypokalemic PP may also include cardiac arrhythmias and ventilator failure caused by hypokalemia, however these presentations are rare. Most patients live a normal life span [11].

Our patient is an adult female who does not fit into the common patient demographic for hypokalemic PP, however, her history of attack provoked by rest after physical exercise and previous attack during a cold season, another triggering factor, is quite indicative of hypokalemic PP.

Neurologic examination during a paralytic attack demonstrates painless weakness usually affecting proximal more than distal muscles and the legs more than the arms with decreased or normal deep tendon reflexes [12]. The physical finding of our patient is also consistent with this as she presented with flaccid paralysis which is more pronounced on the lower limbs and associated hyporeflexia.

During an acute attack, measurement of serum potassium is required for diagnosis and treatment. Mean plasma concentration of potassium was 2.4 mEq/L [14]. Similarly, our patient's serum potassium level was found 2.5 meq/L at presentation which later after proper treatment increased to 4 meq/L. The correction of serum potassium correlated with resolution of her weakness.

The main challenge of this case was unavailability of confirmatory tests such as genetic, provocative testing, EMG and limited availability of biochemical testing to effectively rule out secondary causes. These investigations are unaffordable and usually not easily accessible. However, our patient’s typical presentation and improvement with treatment of hypokalemia demonstrates that even with limited resources, a diagnosis of Hypokalemic Periodic Paralysis can be made with holistic patient evaluation and limited investigation modalities. It reinforces the importance of assessing trigger patterns, previous historical clues, type of muscular weakness and serum potassium level to reach a diagnosis and commence treatment in resource limited settings and urges clinicians to have a high index of suspicion.

A recommended protocol for the management of hypokalemic PP is oral 30 mEq every 30 minutes until the serum potassium level is corrected [15]. In addition, therapeutic education focused on avoiding triggers is important to prevent recurrence [16]. In our patient, counseling regarding avoidance of prolonged rest after vigorous exertion and cold exposure when possible was done and patient was educated about recognizing initial symptoms to seek medical attention early in case of a recurrent attack.

Conclusion

This patient presented with a sudden onset of extremity weakness with a history of preceding vigorous exercise. Complete neurologic recovery was witnessed after potassium was replenished for the patient. Early diagnosis and treatment of hypokalemic PP is lifesaving, as late diagnosis can be fatal. Therefore, periodic paralysis should be considered in the differential diagnosis of patients with weakness even in adult female patients who are not the common demographic. Diagnosis of Hypokalemic Periodic Paralysis (HPP) in resource limited settings is a challenge due to lack of extensive confirmatory investigation modalities, it is possible by assessing trigger patterns, past history, type of weakness and limited investigation modalities. Appropriately addressing the possible risk factor for hypokalemic periodic PP will prevent recurrence. Therefore, patients should have an in depth counseling regarding trigger factors and avoidance strategies, continuous patient follow-up and prevention of recurrence.

Abbreviations

PP

Periodic paralysis

RFTs

Renal function test

BUN

Blood urea nitrogen

TFTs

Thyroid function test

TSH

Thyroid stimulating hormone

IV

Intravenous

KCL

Potassium chloride

K + 

Potassium

mEq

Milliequivalent

Author contributions

Dr Getasew Masresha Baye: conception, design, data acquisition and interpretation, and drafting of the manuscript. Dr Seblewongel Miheret Fenta: data acquisition and interpretation, drafting and critical revision of the manuscript for important intellectual content. Dr. Alemayehu Mequanint Bezabih: data acquisition and interpretation, drafting and critical revision of the manuscript for important intellectual content. Dr. Ruth Girum Tamir: data acquisition and interpretation, drafting and critical revision of the manuscript for important intellectual content.

Funding

The case report received no specific grant or funding support from external sources. The study was conducted as part of the routine clinical practice and academic activities without financial contributions from pharmaceutical companies or other entities.

Data availability

The datasets and materials used for this case report are available upon reasonable request. Researchers interested in obtaining access to the data and materials used in this study may contact the corresponding author for further information.

Declarations

Ethics approval and consent to participate

Ethical approval was not required for this case report, in accordance with our institutional policy.

Consent for publication

Written informed consent was obtained from patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor in chief of this journal.

Competing interests

The authors declare that they have no competing interests that could potentially influence the objectivity or integrity of this case report. No financial, personal or professional competing interests could be perceived as impacting the interpretation or presentation of the finding.