Positive ice pack test in a patient with Lambert‐Eaton myasthenic syndrome

The ice pack test is a simple, non-invasive, quick, cost-effective bedside test that helps in the diagnosis of myasthenia gravis with ocular involvement. Here, we report the effect of the ice pack test in a patient with Lambert-Eaton myasthenic syndrome (LEMS). A 72-y-old man presented with a 1-y history of gradually progressive difficulty in climbing stairs and standing from a seated position and of easy fatigability. He needed support to transition from supine to sitting and sitting to standing. He had constipation, dry mouth, and erectile dysfunction for the past 10 mo and drooping of the right upper eyelid for the last 6 mo. He reported no upper limb weakness, diplopia, dysphagia, dysarthria, or dyspnea. On examination, he had prominent right ptosis with fatigability on sustained upgaze. Ocular movements were full with normal pupillary reactions. The remainder of the cranial nerve examination was normal. An ice pack was applied to the right eyelid for 2 min. Repeat measurement within 10 s after removal of the ice pack showed more than 2 mm improvement in the inter-palpebral fissure distance (Figure 1). His strength was Medical Research Council (MRC) grade 4+ in proximal muscles of both upper limbs, 4in proximal lower limbs, and 5 in distal muscles. Neck flexion was 4+ and extension was 4. Muscle stretch reflexes were absent at rest but were elicitable after brief maximal voluntary muscle contraction. The sensory examination was normal. Nerve conduction studies showed low compound muscle action potential (CMAP) amplitudes upon stimulation of the median, ulnar, tibial, and fibular nerves. Repetitive nerve stimulation (RNS) at 3 Hz of the ulnar and median nerves, recorded over the abductor digiti minimi (ADM) and abductor pollicis brevis (APB) muscles, respectively, showed decrements of the CMAP amplitudes of 16% and 12% from first to the fourth stimuli. CMAP amplitude significantly (>100%) improved following 10 s of maximal muscle contraction, confirming the presence of a pre-synaptic neuromuscular (NM) junction disorder (Table 1). Sensory nerve conduction studies of the median, ulnar, sural, and superficial peroneal nerves were normal. His P/Q type antivoltage-gated calcium channel (anti-VGCC) antibodies level were 1184 pmol/L (positive >100). Acetylcholine receptor (AChR) antibodies and anti-muscle-specific kinase (anti-MuSK) antibodies were negative. Comprehensive evaluation, including whole-body positron emission tomography (PET) scan, revealed no evidence of malignancy. Simpson first described the effects of temperature in myasthenia gravis in 1960. Bronestein and Desmedt later showed that local cooling improved myasthenic NM block, whereas warming had an opposite effect. Ricker et al described two patients with LEMS with improvement in amplitude of CMAP and muscle twitch force with local cooling. They found that muscle cooling had a similar effect to guanidine and proposed an enhanced release of acetylcholine (ACh) quanta from the pre-synaptic terminal as the reason for improved NM transmission. Several other mechanisms by which cooling may improve NM transmission include increased open time of sodium channels in the ACh receptor, increased amplitude of ACh-induced depolarizations, increased facilitation secondary to prolonged half-life of Ca++ in the pre-synaptic nerve terminal allowing more ACh to be released, and decreased activity of the the enzyme acetylcholinesterase, resulting in increased availability of ACh. The usefulness of the ice pack test in LEMS and other presynaptic NM junction disorders is not well known. The sensitivity and specificity of the ice pack test were 76.9% and 98.3%, respectively, for a cohort of patients with ocular myasthenia. The frequency of false positives in the ice pack test ranges from 0% to 2.6%. Sources of error include inaccurate measurement of the inter-palpebral fissure distance, delay in measurement, difficulties in taking photos with a ruler, and confirmation bias as investigators are unblinded.