|Year : 2019 | Volume
| Issue : 3 | Page : 74-79
Secondary hypokalemic periodic paralysis: A study of a case series
Vasantha Kamath, Shreyashi Ganguly, BL Avinash, V Vinodh
Department of Medicine, MVJ Medical College and Research Hospital, Bengaluru, Karnataka, India
|Date of Submission||31-Jul-2018|
|Date of Decision||30-Mar-2019|
|Date of Acceptance||15-Apr-2019|
|Date of Web Publication||15-Jul-2019|
Dr. Shreyashi Ganguly
MVJ Medical College and Research Hospital, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Periodic paralysis is a group of heterogeneous disorders of different etiologies, with episodic, short-lived, and hyporeflexic skeletal muscle weakness, with or without myotonia. There is neither sensory deficit nor loss of consciousness. They can be familial (primary) or acquired (secondary). Secondary periodic paralysis is due to demonstrably known causes. The interictal potassium level is abnormal in these cases. Hypokalemic paralysis is more common than hyperkalemic. Materials and Methods: This is a prospective observational study elucidating the clinical profile of the cases of secondary hypokalaemic periodic paralysis seen in our care over a period of 14 months. Results: In this study, we present nine patients with hypokalemic periodic paralysis, in which four were diagnosed with thyrotoxicosis and five with dengue. They were given potassium correction under judicious cardiac monitoring. Antithyroid drugs and beta-blockers were used in thyrotoxicosis. Dengue patient received adequate fluid and antipyretic cover. All the patients made complete recovery, without any neurological sequelae. Conclusion: Secondary hypokalemic periodic paralysis should always be kept in mind as a differential in the setting of acute, painless, flaccid motor paralysis, especially in young patients with no significant family history or risk factors for stroke or Guillain–Barre Syndrome. A clinician must be aware of causes of secondary periodic paralysis as recognition and diagnosis can completely prevent further attacks of periodic paralysis. Routine estimation of thyroid levels should be the initial line of investigation even if features of thyrotoxicosis are absent. In the presence of acute febrile illness, ordering serology for dengue, after ruling out thyrotoxicosis, is the preferred approach in India.
Keywords: Dengue, hypokalemia, periodic paralysis, thyrotoxicosis
|How to cite this article:|
Kamath V, Ganguly S, Avinash B L, Vinodh V. Secondary hypokalemic periodic paralysis: A study of a case series. APIK J Int Med 2019;7:74-9
|How to cite this URL:|
Kamath V, Ganguly S, Avinash B L, Vinodh V. Secondary hypokalemic periodic paralysis: A study of a case series. APIK J Int Med [serial online] 2019 [cited 2021 May 14];7:74-9. Available from: https://www.ajim.in/text.asp?2019/7/3/74/262737
| Introduction|| |
An increasing number of human neurological diseases have been attributed to dysfunctional ion channels. Channelopathies are a heterogeneous group of disorders that result from the dysfunction of ion channels. The dysfunction is due to defects in ion channels, which may be genetic (primary) or acquired (secondary). The defects can lead to loss of function (most common) or gain of function of the ion channels. Therefore, these groups of disorders show remarkable causal heterogeneity and phenotypic variability.
Based on the site of involvement, they are classified into muscular channelopathies that affect the sarcolemma and neuronal channelopathies that affect the neurolemma.
Muscular channelopathies exhibit a clinical spectrum ranging from myotonia (muscle hyperexcitability) to flaccid paralysis (muscle hypoexcitability).
Periodic paralysis is a group of muscular of different etiologies, characterized by episodic, short-lived, and hyporeflexic skeletal muscle weakness. They may present with or without myotonia. The absence of sensory deficits or loss of consciousness is the norm. Periodic paralysis can be inherited or acquired.
The primary (familial) periodic paralysis is an autosomal dominant disease due to a single gene mutation resulting in abnormalities of calcium, sodium, potassium, and chloride channels on the muscle cell membrane. These defects lead to changes in the serum potassium level at the time of the paralysis.
- Hypokalemic periodic paralysis (calcium channel disorder)
- Hyperkalemic periodic paralysis (sodium channel disorder)
- Andersen–Tawil syndrome (potassium channel subunit disorder).
Compared to hyperkalemic periodic paralysis (estimated prevalence of 1:200,000), familial hypokalemic periodic paralysis is much more common (prevalence: 1 in 100,000). It is also more common in men (3–4:1).
Secondary periodic paralysis
These acquired channelopathies are seen due to demonstrably known causes [Table 1]. In these conditions, the interictal serum potassium levels remain abnormal, unlike in primary causes.
| Case Series Study|| |
Here, we report the cases of nine male patients who had presented with acute flaccid paralysis in the setting of hypokalemia. Subsequently, the patients were found to have secondary hypokalemic periodic paralysis – five diagnosed with dengue infection and four had thyrotoxicosis.
A 35-year-old male patient awoke with bilateral paralysis of his extremities. He presented to the emergency department of the hospital 6 h later. He had no associated difficulty in swallowing or breathing, weakness of facial muscles, sphincter disturbances, pain, sensory symptoms, or alteration in mental state. He had no similar episodes in the past. The patient gave a history of experiencing palpitations for several months, heat intolerance, and loss of weight despite a good appetite. He had no known comorbidities. He denied alcohol or illicit drug use and was not on any medication. There was no similar history in the family members.
At the time of presentation, his blood pressure was 122/84 mmHg. His pulse rate was 101/min, regular, and hyperdynamic. He had a diffuse thyroid swelling. He was oriented and cooperative during examination. His higher mental faculties were normal, and the cranial nerve examination was unremarkable. He demonstrated flaccid symmetrical proximal and distal muscle weakness of the arms and legs (power arm: 2/5 and leg: 2/5). Deep tendon reflexes were depressed bilaterally. Sensation was intact. The rest of the systemic examinations were normal.
Blood tests showed serum K + of 2.1 mEq/L. Creatine phosphokinase (CPK) was elevated to 421 IU/L. The rest of his biochemical parameters were within the normal limits. The thyroid profile showed decreased thyroid-stimulating hormone (TSH) (0.013 mIU/L) and increased free T3 and T4. The electrocardiography (ECG) showed sinus tachycardia with 100 beats/min. The presence of U-wave fused with P-waves [Figure 1]. The results of electromyography and nerve conduction study were normal.
|Figure 1: Electrocardiography of Case 1 (thyrotoxicosis associated periodic paralyss) showing the presence of U-waves (U) continuing on to the P wave and the T wave (T) is inverted|
Click here to view
Cases 2–4 also presented in a similar fashion [Table 2] and [Table 3] and were diagnosed to have thyrotoxic periodic paralysis (TPP).
A 39-year-old male patient presented with complaints of high-grade, continuous fever of 3-day duration, arthralgia, and acute-onset symmetric weakness of the lower limbs that ascended within 3 h to affect the upper limbs. At the time of presentation to the emergency department, the patient had paralysis of all the limbs. There was no history of neck pain, sensory symptoms, bladder and bowel involvement, recent vaccination, diarrheal illness, headache, or vomiting. There was no history of excessive exercise before development of limb weakness or family history of episodic weakness.
On examination, the patient was febrile with an oral temperature of 102.6°F. He was tachycardic (pulse rate: 104 beats/min). There was a generalized erythematous rash all over his trunk. His systemic examination revealed a soft, nontender hepatomegaly of 2–3 cm below the costal margin. Neurologically, he was conscious and oriented. His higher mental functions were normal. His cranial nerve examination was unremarkable. He demonstrated flaccid symmetrical proximal and distal muscle weakness of the arms and legs (power arm: 3/5 and leg: 3/5). Deep tendon reflexes were depressed bilaterally. Sensation was intact. The rest of the systemic examinations were normal.
His initial complete hemogram showed an hemoglobin of 11.4 g/dl, total leukocyte count of 4700/mm3, and platelet count of 72,000/mm3. K+ level was 2.0 mEq/L. CPK was elevated to 553.2 IU/L. He also had elevated transaminases (aspartate aminotransferase and alanine aminotransferase). His dengue serology was positive for NS1Ag antigen. The thyroid profile showed euthyroid state (TSH and free T3 and T4). The ECG showed sinus tachycardia with 104 beats/min, first-degree atrioventricular block, and T-wave inversion. The results of electromyography and nerve conduction study were normal.
Cases 6–9 also presented with acute quadriparesis in the setting of fever [Table 2] and [Table 3]. Their serology confirmed the diagnosis of dengue.
All the patients with hypokalemic paralysis received an intravenous (IV) potassium correction at the rate of 20 mEq/h for the first 6 h. This was done to reduce the possibility of rebound hyperkalemia. Subsequently, they were switched over to oral potassium chloride supplementation of approximately 80 mEq/day dose divided into 3–4 times. Serum potassium levels were measured serially in all the patients till their potassium levels normalized. Average time to achieving was 6 h. Bed rest and oral hydration were encouraged.
The patients diagnosed with thyrotoxicosis were also given tablet propranolol at 10 mg twice a day. Carbimazole was started at 30 mg/day in three divided doses and titrated to achieve euthyroid levels. Oral potassium was supplemented as necessary.
The patients with dengue fever were treated supportively, with fluids, paracetamol, in addition to the oral potassium. None of our patients required platelet transfusion.
The mean serum potassium was 2.12 mEq/L and CPK was 327.2 IU/L. Most of the patients achieved normal potassium levels within 8 h of initiation of treatment (mean duration: 6.8 h). Improvements began after an hour of potassium supplementation in all the patients. The muscle strength first improved on the fingers of the upper extremity, then the arms, and finally, the legs. Paralysis had resolved in all the patients within 14 h of admission. Deep tendon reflexes returned to normal within 36 h (mean: 21.5 h). The mean duration of hospitalization was 4.7 days (range: 3–8 days) which was unremarkable [Table 4].
Patients were counseled about the condition. They were informed regarding the possibility of recurrence. They were prescribed a diet rich in potassium but low in sodium and carbohydrates. Precipitating factors were discussed. They were discharged on appropriate medications along with potassium supplementations. On follow-up, the patients have not had any recurrence.
| Discussion|| |
Hyperthyroidism and thyrotoxicosis are common medical conditions seen in the general population. Common systemic features of hyperthyroidism include palpitations, heat intolerance, and weight loss. Several central and peripheral nervous system manifestations may also occur in the patients. The features are common such as cognitive dysfunction, Graves' ophthalmopathy, tremors, myopathy, and polyneuropathy; uncommon such as seizures and myasthenia gravis; or rare such as chorea, stroke, and periodic paralysis. In many cases, the neurologic manifestations occur in conjunction with the systemic features of the disease, but these may be the presenting symptoms in some patients.
Four of our patients had hypokalemic TPP. Thyrotoxicosis is the most common cause of acquired hypokalemic periodic paralysis. TPP is a rare disorder that has been described in the literature in the setting of hyperthyroidism, predominantly occurring in Asian men (prevalence: 2%). The condition affects young (usually third to fifth decades) almost exclusively (95%). It can result from thyrotoxicosis due to any etiology, including exogenous thyroxine overdose. Graves' disorder is the underlying disease in most cases (as in two of our cases).
In our cases, there was a predominance of marked lower extremity weakness, with proximal muscles being more affected than distal. The upper limbs were the last to get affected. The limbs were hypotonic. Deep tendon reflexes were universally depressed. Sensation and higher mental functions were intact. There was no correlation between the serum potassium levels and the severity of weakness. During recovery, the upper limb fingers were the first to recover and the deep tendon reflexes were the last. Only two of our patients had signs of thyrotoxicosis-exophthalmos, lid lag, and fine tremor; the others did not show any signs on physical examination except sinus tachycardia. All the patients had severe hypokalemia on presentation.
The cause [Figure 2] of hypokalemia TPP rests in the fact that thyroid hormone increases the tissue responsiveness to beta-adrenergic stimulation and insulin, which increases the activity of sodium-potassium ATPase. This drives potassium into cells. This causes paradoxical depolarization of the muscle membrane, and this relative inexcitability of the muscle fibers in this state leads to paralysis.
Dengue infection classically presents as a febrile illness, with headache, body ache, rashes, polyserositis, and bleeding manifestations secondary to thrombocytopenia. It can be an acute self-resolving febrile illness to life-threatening hemorrhagic shock and multi-organ dysfunction leading to death. The disease can also have atypical presentations which are due to endothelial inflammation by immunopathological mechanisms leading to increased vascular permeability and coagulation disorder.
Even though dengue was initially not thought to be a neurotropic virus, the manifestations of dengue are changing over time. Diffuse myalgia is the most common neurological symptom. Other neurological manifestations are being reported more nowadays with increased awareness. These manifestations can be grouped into three categories:
- Related to neurotrophic effect of viruses: Encephalitis, meningitis, myositis, rhabdomyolysis, and myelitis
- Related to systemic complications of dengue infection: Encephalopathy, stroke, hypokalemic paralysis, and papilledema
- Postinfection sequelae: Acute disseminated encephalomyelitis, myelitis, neuromyelitis optica, optic neuritis, Guillain–Barre Syndrome (GBS), Miller Fisher syndrome, phrenic neuropathy, long thoracic neuropathy, oculomotor palsy, maculopathy, and fatigue syndrome.
Dengue-associated hypokalemic paralysis often has a rapidly evolving course. It is a rare manifestation, even in the setting of hypokalemia in dengue (the prevalence of hypokalemia varies from 14% to 28%). This dramatic manifestation is otherwise benign and responds very well to potassium correction.
The cause of paralysis in dengue is still being elucidated. It may not be possible to attribute a single definite pathophysiological basis in a patient [Figure 3]. Hypokalemia may be secondary to redistribution of potassium into the cells, transient renal tubular abnormalities leading to increased urinary potassium wasting, and/or loss of potassium due to vomiting and diarrhea in febrile phase of dengue fever.
The secondary redistribution of potassium into the cell may be due to increased catecholamine levels secondary to infections and secondary insulin resistance. Endogenous granulocyte-macrophage colony-stimulating factor and related cytokines in response to neutropenia may be another putative factor leading to intracellular potassium shift and hypokalemia. Increased renin production may also be responsible for hypokalemia in dengue hemorrhagic fever/dengue shock syndrome due to hypovolemic state.
The identification of hypokalemia as the cause of the paralysis should be promptly identified and aggressively treated as initiation of potassium correction leads to rapid reversal of the quadriparesis. The potassium correction should be undertaken in an intensive care setting, under ECG surveillance and serial potassium estimation.
In case of thyrotoxicosis, care should be taken to avoid rebound hyperkalemia. It can occur in 40%–59% of patients being treated. Because hypokalemia in TPP is related to a transcellular shift in potassium and not an overall body depletion, little potassium is needed to correct the deficit. In this study, only one of our patients had developed rebound hyperkalemia (K+ level: 7.7 mEq/L), which is below the average numbers. This was done by slow correction of the potassium deficit (<10–20 mEq/h and no >90 mEq/day), concurrent use of IV beta-blockers, and serial monitoring of potassium levels throughout the process. The patient with hyperkalemia was treated with calcium polystyrene sulfonate 15 g and calcium gluconate 1000 mg to mitigate the serious risks of cardiac arrhythmias such as sinus arrest, ventricular tachycardia, and ventricular fibrillation.
| Conclusion|| |
Secondary hypokalemic periodic paralysis should always be kept in mind as a differential in the setting of acute, painless, flaccid motor paralysis, especially in young patients with no significant family history or risk factors for stroke or GBS. A clinician must be aware of causes of secondary periodic paralysis as recognition and diagnosis can completely prevent further attacks of periodic paralysis.
Routine estimation of thyroid levels should be the initial line of etiological investigation even if features of thyrotoxicosis are absent. In the presence of acute febrile illness, serology for dengue, after ruling out thyrotoxicosis, is the approach to take in India.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]