Background Acute flaccid paralysis is a common neurological emergency with diverse causes and variable outcome. There is a paucity of reports documenting the spectrum of hypokalaemic paralysis in neurological practice.
Objective To report the clinical features, aetiology, and outcome of patients with hypokalaemic paralysis in a tertiary care teaching hospital in India.
Methods Consecutive patients with acute flaccid paralysis with hypokalaemia from 2008 to 2010 were included in the study. Patients with Guillain–Barré syndrome, porphyria, polio and non-polio enterovirus infection and myositis were excluded. Detailed clinical examination, urinalysis, renal function tests, arterial blood gas analysis, thyroid hormones, and electrocardiogram were carried out. Patients received intravenous or oral potassium supplementation and their underlying causes were treated.
Results Thirty patients aged 17–52 years, including three females, were included. Secondary causes of hypokalaemic paralysis were present in 13 patients and included thyrotoxic paralysis in five and renal tubular acidosis (RTA) and Gitelman syndrome in four each. All the patients had quadriparesis and 10 had severe weakness (MRC grade <2). Tendon reflexes were reduced in eight and brisk in four patients. Respiratory paralysis was present in six patients and one needed artificial ventilation. Fifteen patients had severe hypokalaemia (<2 mmol/l), four had acidosis, and six had alkalosis. The secondary group had more severe hypokalaemia and needed longer time to recover.
Conclusion 43.3% of patients with hypokalaemic paralysis had a secondary cause for their condition. Patients with severe hypokalaemia with acidosis or alkalosis should be investigated for secondary causes as their management differ.
- Periodic paralysis
- renal tubular acidosis
- thyrotoxic periodic paralysis
- Gitelman syndrome
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- Periodic paralysis
- renal tubular acidosis
- thyrotoxic periodic paralysis
- Gitelman syndrome
Hypokalaemic paralysis is an important cause of acute flaccid paralysis, but it has a number of underlying aetiologies such as thyrotoxicosis, renal tubular acidosis (RTA), Gitelman syndrome, barium poisoning, and diarrhoea; in some cases no cause can be found.1 The muscle weakness may range between mild weakness to severe paralysis with life threatening cardiac arrhythmia and respiratory paralysis.2 Recognition of the underlying causes is essential for the appropriate management of patients with hypokalaemic paralysis. Familial periodic paralysis has been reported as the most common cause of hypokalaemic paralysis in Caucasians.3 Thyrotoxic hypokalaemic paralysis is common in the Asian (oriental) population.4 The aetiology of hypokalaemic paralysis is likely to depend on ethnicity, vigour of the investigation, and the setting of the medical practice. There is a paucity of reports documenting the spectrum of hypokalaemic paralysis in neurological practice. In this study we report the clinical features, underlying aetiology and outcome of consecutive patients with hypokalaemic paralysis attending a tertiary care teaching hospital in India.
Patients and methods
Consecutive patients with acute flaccid weakness due to hypokalaemia (serum K+<3.5 mmol/l) during the period 2008 to 2010, who did not have sensory signs, areflexia, bladder and bowel involvement, and elevated creatine kinase, were included in the study. Patients with Guillain–Barré syndrome, acute transverse myelitis, polio and non-polio enteroviral infections, and those on diuretic therapy, were also excluded.
A detailed medical history and neurological examination were performed. Any history of similar disease in the family was enquired about, and reports of weakness, thyroid disease, drug intake, diarrhoea, vomiting, hypertension, and kidney disease were recorded. The examination included blood pressure, pulse, anaemia, oedema, and autonomic changes. Facial and bulbar weaknesses were noted. Muscle power was assessed on a scale of 0 to 5 using the Medical Research Council (MRC) scale. Muscle tone and tendon reflexes were noted. Sensation of pinprick, touch and joint positions were recorded.
The investigations included blood counts, haemogram, haematocrit, blood urea nitrogen, serum creatinine, sodium, potassium, bicarbonate, chloride, calcium, inorganic phosphate, albumin, globulin, alkaline phosphatase, creatine kinase, and transaminases. Fasting urinary pH and 24 h urinary calcium, inorganic phosphate, and creatinine were estimated. Patients with hyperchloraemic metabolic acidosis with normal anion gap in the absence of gastrointestinal loss and a fasting urine pH >5.5 were regarded as having RTA. In the absence of significant acidosis, an ammonium chloride loading test (0.1 g/kg) was done. The urinary pH and arterial blood gas analysis was carried out at 1 h intervals for 6 h. When the lowest recorded urinary pH was <5.5, the diagnosis of proximal RTA was considered, but if the urine failed to acidify below 5.5, the diagnosis of distal RTA was considered. The diagnosis of distal RTA was supported by nephrolithiasis on abdominal ultrasonography or radiography. Further investigations to diagnose RTA included serum electrophoresis for myeloma protein and serum ceruloplasmin. In suspected patients, a slit lamp examination was also done. The presence of metabolic alkalosis (serum bicarbonate >29 mmol/l) with hypokalaemia (serum potassium <3 mmol/l), hypomagnesaemia (serum magnesium <0.25 mmol/l), and hypocalciuria (urinary calcium <0.05 mmol/kg/day) were regarded as indicative of Gitelman syndrome. In patients with RTA, tests for rheumatoid factor, antinuclear antibody (ANA), and anti-dsDNA were carried out. T3 (tri-iodothyronine), T4 (thyroxine) and thyroid stimulating hormone (TSH) were estimated in all patients. Cerebrospinal fluid was examined if weakness persisted after correction of the hypokalaemia, in order to exclude Guillain–Barré syndrome and polio and non-polio enterovirus myelitis. Cerebrospinal fluid was analysed for protein and cells.
Mild to moderate hypokalaemia (serum potassium >2 mmol/l) was treated by oral supplementation (25 mEq at 6 h interval); patients with severe hypokalaemia (serum potassium <2 mmol/l)5 or with severe clinical manifestations (extreme weakness, arrhythmia) were treated by intravenous supplementation (40 mEq every 4 h). Patients with thyrotoxicosis were treated with carbimazole (5 mg three times daily) and propranolol (20 mg three times daily), and those with RTA were treated with oral sodium bicarbonate tablets. The patients with idiopathic periodic paralysis who were having recurrent attacks were advised to take acetazolamide (250 mg three times daily) and modify their lifestyle.
The relationship between severity of weakness and underlying aetiology was studied. The categorical variables were correlated using Fisher exact tests and continuous variables by independent t test or Mann–Witney U test using SPSS version 15; a value of p≤0.05 was considered significant.
We studied 30 patients with hypokalaemic paralysis whose median age was 32 (range 17–52) years; three of them were females. All the patients were from North India and none were on diuretic therapy. Two patients had a family history of a similar illness. Eleven patients had a history of recurrent weakness in the past, the frequency of attacks ranging between 1 and 20 per year. Two of these patients were diagnosed with hypokalaemic periodic paralysis and one was on acetazolamide therapy who was later diagnosed as having RTA. A history of myalgia was reported by 10 patients, paraesthesias by two, preceding fever by 10, diarrhoea by three, heavy carbohydrate meal by four, and heavy exertion by two patients. All the patients had quadriparesis; 10 had severe weakness (MRC grade 0–1) and 20 had mild weakness (MRC grade 2–4). Deep tendon reflexes were reduced in eight patients, brisk in four, and normal in 18 patients. Sensations were normal in all the patients. Six patients had respiratory paralysis and one needed artificial ventilation for 2 days.
Serum potassium ranged between 1.0–3.41 mmol/l (median 2.2 mmol/l). Severe hypokalaemia was present in 15 patients, acidosis in four, alkalosis in six, hypocalcaemia in 12, and hypomagnesaemia in four patients. Hyperthyroidism was present in five and hypothyroidism in two patients. Electrocardiographic changes of hypokalaemia were present in seven patients; a U wave in seven (figure 1A) and prolonged PR interval in two. Renal calcinosis was present in three patients with distal RTA (figure 1B). The clinical and biochemical parameters in the patients with hypokalaemic periodic paralysis are shown in table 1. The hypokalaemic paralysis was categorised into primary (idiopathic) in 17 (56.7%) patients and secondary in 13 (43.3%) patients. The secondary hypokalaemic periodic paralysis included RTA in four (13.3%; distal RTA in three, proximal RTA in one), Gitelman syndrome in four (13.3%), and thyrotoxic periodic paralysis in five (16.7%) patients (figure 2). All the patients with Gitelman syndrome had hypomagnesaemia (0.62±0.22 mmol/l), whereas in the non-Gitelman group serum magnesium was within the normal range (1.18+0.13 mmol/l).
All the patients improved following potassium supplementation. The patients with RTA were given sodium bicarbonate (<4 mmol/kg in four divided doses for distal RTA and >4 mmol/kg for proximal RTA), and vitamin D (250 IU three times daily). The patients with thyrotoxicosis were treated by carbamizole and β-blockers. None of the patients died during follow-up (median 15 months, range 1–24 months), but one had a recurrence of an attack.
The patients with secondary hypokalaemic periodic paralysis had more severe hypokalaemia compared to the idiopathic group (1.71±0.47 vs 2.61±0.59 mmol/l; p=0.001). The muscle weakness was also more pronounced in the secondary group compared to the idiopathic group, though the difference was not significant (p=0.19). The muscle power in secondary hypokalaemia group was 1.77±1.58 and in the idiopathic group was 2.47±1.06. The secondary group needed longer time (54.46±24.30 h vs 26.47±16.02 h; p=0.002) to recover compared to the patients with primary hypokalaemic paralysis. Out of six patients with respiratory paralysis, five were in the secondary group and one of them needed artificial ventilation. Details are given table 2.
The 24 h renal excretion of potassium was insignificantly higher in the patients with RTA compared to the patients with thyrotoxicosis (32 vs 21.8 mmol/l; p=0.32) (table 3). ANA, rheumatoid factor, and SSA antigen were positive in two patients with distal RTA.
In our study on hypokalaemic paralysis, 43.3% patients had a secondary cause for their condition, which included RTA, Gitelman syndrome, and thyrotoxicosis. Primary hypokalaemic periodic paralysis occurred in 56.7% of patients. Secondary hypokalaemic paralysis was associated with severe hypokalaemia compared to primary hypokalaemic paralysis. The aetiology of hypokalaemic paralysis varies among different ethnic and geographical areas.6–8 In a study from Taiwan, the majority of cases of patients with hypokalaemic paralysis were due to secondary causes (68%); underlying aetiologies included thyrotoxic paralysis in 40.2%, sporadic in 29.8%, familial in 2.1%, primary aldosteronism in 6.2%, renal tubular alkalosis, Bartter and Gitelman syndrome in 6.2%, diuretic use in 3.1%, and ingestion of toluene blue in 3.1% of patients.4 In Caucasians, familial hypokalaemic paralysis is most common, whereas in the Asian population thyrotoxic periodic paralysis is the commonest.6 7 In our study, RTA and Gitelman syndrome were present in 13.3% and thyrotoxicosis in 16.7% of patients. In a study from South India, secondary hypokalaemic paralysis was present in 93.6% of patients. Hypokalaemic periodic paralysis was due to hyperaldosteronism in 42% of patients, RTA in 42%, thyrotoxicosis in 6.4%, Gitelman syndrome in 3.2%, and sporadic periodic paralysis in 6.4% of patients.9 The difference in the aetiology of hypokalaemic paralysis in the South Indian study and in our study may be due to a difference in the population, and the study setting. Our study was conducted in a tertiary care neurology practice, whereas the South Indian study was undertaken in a tertiary care endocrinology practice. None of our idiopathic hypokalaemic patients had hypertension, therefore serum aldosterone concentrations were not estimated.
In our study, the serum potassium concentrations were significantly lower in patients with secondary hypokalaemic paralysis than in those with primary hypokalaemic paralysis. In another study, however, there was no significant difference in potassium, blood urea nitrogen and creatinine values between patients with primary and secondary hypokalaemic paralysis.4 The presence of hypocalcaemia (<2.2 mmol/l), hyperphosphataemia (1.4 mmol/l), and increased alkaline phosphatase (1.63 μkat/l) values suggest underlying metabolic changes in RTA.
Occurrence of recurrent attacks was similar in both idiopathic and secondary hypokalaemic periodic paralysis. Five patients in the secondary group had respiratory compromise and one who had RTA needed ventilatory support. The patients with secondary hypokalaemic paralysis needed higher doses of potassium and a longer recovery time compared to those with primary hypokalaemic paralysis, which is consistent with earlier reports.10 The patients with secondary hypokalaemic paralysis had a significantly negative total body potassium balance, whereas primary hypokalaemic paralysis was associated with an intracellular shift of potassium; therefore, the patients with primary hypokalaemic paralysis needed smaller amounts of potassium compared to the secondary group.
It can be concluded that, in this study, 43% of patients with hypokalaemic paralysis had a secondary cause for their condition. It is important to diagnose the underlying causes of hypokalaemic paralysis as these require specific therapies.
Hypokalaemic periodic paralysis is a medical emergency and needs urgent management. Two-fifths of patients may have an underlying cause such as renal tubular acidosis, Gitelman syndrome, thyrotoxicosis, or hyperaldosteronism.
Severe hypokalaemia (<2 mmol/l) suggests a secondary cause.
The presence of acidosis and alkalosis in arterial blood gas analysis suggests a renal cause. A thyroid function test should be done in all patients and an aldosterone assay in clinically suspected patients.
Weakness is treated by oral potassium in cases of mild to moderate hypokalaemic paralysis and by intravenous potassium in severe cases. To prevent recurrent attacks, sodium bicarbonate is prescribed for renal tubular acidosis, carbimazole and propranolol for thyrotoxicosis, and acetazolamide for idiopathic hypokalaemic paralysis.
Current research questions
The regional variations in the underlying aetiology of periodic hypokalaemic paralysis should be undertaken.
The molecular basis of the episodic nature of weakness in both primary and secondary hypokalaemic paralysis needs further exploration. This understanding may help in the management of these patients.
We thank Mr Rakesh Kumar Nigam for secretarial help.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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