Idiopathic hypoparathyroidism with clinical and electrophysiological myotonia– An unusual occurrence
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.241408
Source of Support: None, Conflict of Interest: None
Hypoparathyroidism is the third-most common endocrine disease of calcium metabolism characterized by hypocalcemia and hyperphosphatemia. Hypoparathyroidism can result either from impaired parathyroid hormone (PTH) secretion or its action. The idiopathic variety of hyoparathyroidism is a diagnosis of exclusion. Hypoparathyroidism leads to hypocalcemia which is variably symptomatic. The neurological manifestations are due to neuromuscular irritability and include carpopedal spasm (70%), paraesthesias (54%), seizures (54%), irritability (20%), fasciculations (9%), psychosis (7%), ataxia, myopathy, and pyramidal and extrapyramidal symptoms.
The electrophysiological evaluation of patients with hypocalcemia reveals bursts of spontaneous activity in the form of singlets, doublets, triplets, and multiplets, firing asynchronously at a rate of 4–15 Hz, interspersed with periods of relative silence. Neuromyotonia and the occurrence of long trains of spontaneous potentials lasting over a minute have also been documented.
To date, this case report is the first of its kind to document myotonia on needle electromyography in a patient of hypoparathyroidism with hypocalcemia.
A 33-year old man presented with muscle cramps for 20 years and seizures for the last 5 years. He underwent bilateral cataract surgery 10 years ago. Initial assessment revealed Chvostek's and Trosseau's sign with intrinsic hand and foot muscle weakness, absence of bilateral ankle reflex, and hand grip myotonia.
On investigation, he was found to have hypocalcemia [serum calcium: 6 mg/dL (normal range: 8.6–10.2 mg/dL)], hyperphosphatemia [serum phosphate: 5.6 mg/dL (normal range: 2.8–4.5 mg/dL)], hypoparathyroidism [serum parathyroid hormone [PTH] <0.12 pg/mL (normal range: 15–65pg/mL)] and grossly elevated creatine phosphokinase (CPK) levels [CPK: 3588 IU/L (normal range: 20–200 IU/L)]. He had normal values of serum magnesium, vitamin D, lactate dehydrogenase (LDH), aspartate transaminase (AST), aldolase, and urine calcium: creatinine ratio. All other biochemical parameters including albumin, electrolytes, oral glucose tolerance test, hormonal assays, and cardiac evaluation were found to be normal.
Plain computed tomography (CT) of the brain showed extensive calcifications in the regions of bilateral basal ganglia and thalamus, as well as cerebral and cerebellar white matter. The nerve conduction study (NCS) was normal; constant compound muscle action potential (CMAP) amplitude was obtained despite a short exercise for 5 minutes and a local exposure to cold.
Needle electromyography (EMG) revealed spontaneous activity in the form of doublets, triplets, and multiplets [Figure 1]a, normal motor unit action potential analysis, and recruitment. It also showed myotonic discharges, which were characteristically waxing and waning at varying frequencies of up to 150 Hz with a dive bomber sound, being provoked by voluntary contraction, muscle percussion, and needle insertion [Figure 1]b and c]. The muscle histology was normal and the genetic analysis was negative for myotonic dystrophy.
The patient was offered symptomatic treatment in the form of calcium infusions (10 ampoules of calcium gluconate 10% weight/volume equivalent to 900mg of elemental calcium infused over 24 hours on 2 consecutive days while monitoring the serum Ca 2+ levels and the clinical status), which evoked a good clinical and biochemical response. The same reflected in the needle electromyography (EMG) as disappearance of myotonia but with very occasional presence of multiplets [Figure 2]. He was discharged on oral calcium supplements at a dose of 1 g/day and vitamin D3 at 60,000 IU/day.
Hypocalcemia is usually caused by hypoparathyroidism, vitamin D deficiency, hypomagnesemia, and drugs. It can manifest as myopathy with either symmetrical proximal weakness of the limbs or rarely with distal weakness, as was seen in our patient.
An inverse relationship between the serum levels of calcium and LDH, aldolase, and CPK is well documented in the literature. In the aforementioned case, the inverse relationship between serum calcium and CPK levels alone could be established. This is in accordance with the hypotheses that explain the occurrence of increased levels of CPK in hypocalcaemia. This phenomenon is related to an increased membrane permeability, resulting in muscle enzyme release  and the sustained contraction of muscles in tetany because of the presence of a hyperexcitable muscle membrane.
The usual EMG finding that is seen in patients with hypocalcemia is spontaneous activity in the form of singlets, doublets, or multiplets, caused by an altered sodium conductance leading to membrane depolarization and repetitive nerve firing. In severe hypocalcemia, EMG reveals neuromyotonia (bursts of spontaneous discharges firing rhythmically and continuously at high frequencies of up to 300 Hz with intra-burst waning, resembling a torpedo) with a pinging sound. The marked decrement in the successive amplitude of the discharges in each burst results from an inability of the motor unit to follow rapidly recurring nerve impulses. As tetanic contraction abates with infusion of curare, but not with peripheral nerve block, neuromyotonia seems to occur at the distal most segments of the peripheral nerve twigs.
Apart from these classical findings on needle EMG, Snowdon et al., for the first time, described long trains of spontaneous myotonic potentials in a patient with paranoid psychosis, whose muscle biopsy showed hypocalcemic myopathy. Owing to the unanswered questions pertaining to abnormal renal parameters, urinary sediment, raised erythrocyte sedimentation rate, fluctuating AST levels, raised protein-bound iodine level, and non-availability of post-treatment muscle biopsy findings, the causative association between hypocalcemia and myotonia could not be firmly established.
In contrast, our case report is one of idiopathic hypoparathyroidism –hypocalcemia without any confounding factors, manifesting with myotonia that completely resolved with the correction of the former. Normal muscle biopsy, absence of paramyotonia, negative genetic analysis for myotonic dystrophy, complete resolution of muscle weakness, and EMG signs of myotonia with restoration of serum calcium levels prove beyond doubt the causative association between myotonia and hypocalcemia.
Extracellular calcium is known to neutralize the fixed negative charges residing on amino acids, oligosaccharides, and phospholipids on the extracellular side of cell membranes. This increases the transmembrane potential difference, which is functionally akin to hyperpolarization. Experimental augmentation or dampening of myotonia with decrease or increase in extracellular calcium, respectively, is well documented in rat muscles perfused continuously with aromatic monocarboxylic acids (which inhibit muscle membrane chloride conductance). We believe that the presence of chronic hypocalcemia in our patient contributed to myotonia by producing changes in the electrophysiological characteristics of the muscle membrane.
To date, there is no literature in support of myotonia attributable to hypocalcemia caused by idiopathic hypoparathyroidism. Though the causative association is not well established, we suggest that the electrophysiological change in the muscle membrane was the underlying cause of myotonia in a muscle chronically depleted of extracellular calcium. This hypothesis needs to be supported by further studies on a larger sample size and a longer period.
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[Figure 1], [Figure 2]