Exercise-induced periodic paralysis may be a feature of skeletal muscle channelopathies. This case describes a 50-year-old man who presented with a two-year history of periodic right-sided paralysis, always precipitated by exertion.
A 50-year-old man presented with a two-year history of periodic right-sided paralysis, always precipitated by exertion. Initially, he was diagnosed with hemiplegic migraine and was also admitted to the stroke unit with hemiparetic attacks, but had normal brain imaging each time.
He reported 2-3 episodes per week, most resolved within a few hours of rest, the longest was about 16 hours long. In a typical attack, he felt right sided facial numbness and droopiness. He also felt jelly-like sensation in his legs, mainly on the right side, which progressed to weakness. Before this hemiparesis started, he also felt “a thud” over the back of his head, which can be very uncomfortable and lasted for a few hours. On another occasion, he described this sensation as warm water running all over him. During an attack, he may become dysarthric and may also experience blurring of vision.
There was no bladder or bowel dysfunction. He denied precipitation of these attacks with increased carbohydrate or potassium-rich diet, change in temperature or emotional triggers. Gradually his symptoms evolved to involve both sides of the body but never experienced any impairment in swallowing, breathing or diplopia. There was no family history of a similar disorder; his mother, however, had Parkinson’s disease.
He had a trial of several medications including sodium valproate, pregabalin, propranolol and topiramate on the suspicion of migraine. However, he did not derive any benefit from these treatments. Also, he was treated with intravenous frusemide and magnesium infusions which had some effect. Treatment with acetazolamide did not have any positive or negative effect.
He was investigated with video telemetry to rule out exercise-induced epilepsy. During telemetry, he was exercised on a treadmill for 45 minutes which provoked weakness. His serum potassium was normal during the attack. No EEG abnormality was detected. He also had an assessment of respiratory muscles with spirometry which showed a normal forced vital capacity.
The neurophysiological assessment demonstrated normal sensory and motor conduction studies. Long exercise testing was performed, stimulating the left ulnar nerve at the wrist and recording from left abductor digiti minimi. Readings were taken prior to, at 30s intervals, during and 1-2 minute intervals after the five-minute maximal voluntary contraction of abductor digiti minimi (with occasional 5s breaks to prevent muscle ischaemia).
During exercise, testing there was an initial increment in compound motor action potential (CMAP) of 24% from baseline. However, following exercise, there was a slow but inexorable decline in CMAP amplitude over the next 90 minutes with a decrease in CMAP amplitude of 63.1%. This is considerable outside the published normal values for this test.1
The EMG study of left abductor digiti minimi revealed a single run of fibrillation and occasional motor unit potentials of short duration, though most were normal. Figure 1 illustrates the graph of the exercise test.
The neurophysiology supported the clinical diagnosis of exercise-induced periodic paralysis. Genetic testing did not demonstrate common point mutations in calcium channel gene (CACNA1S) associated with hypokalemic periodic paralysis (hypoPP) and sodium channel gene (SCN4A) associated with hyperkalemic periodic paralysis (hyperPP) and rarely with hypoPP. This does not exclude other emerging mutations in CACNA1S and SCN4A that may cause period paralysis.2,3
Figure 1 Long exercise test
Exercise-induced periodic paralysis may be a feature of skeletal muscle channelopathies. Skeletal muscle channelopathies are a group of disorders, caused by mutations in the genes coding for sodium, potassium, and calcium channels. The presentation is with attacks of muscle weakness of variable duration and severity, triggered by factors such as cold, exercise, high carbohydrate or potassium rich diet. They are phenotypically and genetically heterogeneous disorders and new mutations are emerging. The topic is nicely reviewed by Platt and Griggs.4
Periodic paralysis (PP) has been historically classified as hyperkalaemic or hypokalaemic (hyperPP and hypoPP), depending on the serum potassium levels during an attack. HypoPP is the commonest form of PP.3 Serum potassium level may be normal during an attack in periodic paralysis giving rise to the possibility of an intermediate disease - normokalaemic periodic paralysis. 4 The majority of cases with periodic paralysis begin in the first decade, however, presentation after the age of 20 has been reported.5
In the absence of a genetic mutation, clinical characterisation between hypoPP and hyperPP is difficult for this patient. However, a useful clinical feature to distinguish between hypoPP and hyperPP is the absence of myotonia in hypoPP, which favours hypoPP in our patient.
Exercise testing (McManis test) may be used as a reliable method to diagnose periodic paralysis. In one study of patients with hypokaleamic and hyperkalaemic periodic paralysis, amplitude decrements of > 40% from maximum CMAP during-or-after exercise showed a sensitivity of 100%.6
Neurophysiological examination during an attack may reveal a partially depolarised and inexcitable muscle cell membrane.
Management includes avoiding precipitating factors. acetazolamide and dichlorphenamide can be used as preventive therapy for periodic paralysis.7 Although muscle weakness is periodic and reversible, fixed muscular weakness may develop after a certain time.
Dr Muhammad K Rafiq is a Consultant Neurologist and Honorary Senior Lecturer, Norfolk and Norwich University Hospital NHS Foundation Trust
Conflict of interest: none declared
2.Lehmann-Horn F, Orth M, Kuhn M, Jurkat-Rott KA novel N440K sodium channel mutation causes myotonia with exercise-induced weakness- exclusion of CLCN1 exon deletion/duplication by MLPA. Acta Myologica; 30(2): 133-7