A Rare Cause of a Treatable Abnormal Movement, Not to Miss

Parkinsonism is a syndrome composed of tremor at rest, bradykinesia, rigidity, loss of postural reflexes, flexed posture, and freezing.1 There are various acquired etiologies causing parkinsonism, such as dopaminergic blocking agents, cerebrovascular diseases, brain neoplasm, the intoxication of various toxins, brain trauma, and metabolic disturbances. Abnormal calcium metabolism causing hypo- or hypercalcemia can lead to adverse effects of the human nervous system. Although neurological manifestations of hypercalcemia mainly present as an alteration of consciousness or depression, the manifestations of hypocalcemia range from muscle twitching, spasms, tetanic contraction, numbness, altered mental status, encephalopathy, and seizures.2, 3 Movement disorders, such as chorea and parkinsonism, are unusual complications of hypocalcemia. Herein, we report a case of hypocalcemia attributed to post-thyroidectomy hypoparathyroidism that presented with acute parkinsonism and psychomotor retardation. Those symptoms were dramatically improved after correcting hypocalcemia. A 74-year-old Thai woman had been diagnosed with hypertension for 7 years. She had been taking enalapril 5 mg/day and propranolol 10 mg/day. She had had a thyroidectomy 30 years ago due to a large goiter. For 3 days, she was hospitalized because of a severe, disabling right-hand tremor and psychomotor retardation. She had a history of diarrhea and vomiting 4 to 5 times/day without fever for 5 days. Neurological examination demonstrated several parkinsonian features, including a masked face; chin tremor; and resting, postural, and intention tremors at the right upper extremity. Bradykinesia presented in both the upper and lower extremities bilaterally (Video 1, segment 1). She also developed severe psychomotor retardation and attention deficit. Trousseau's and Chvostek's signs were negative. In segment 1 (pretreatment), physical examination revealed signs of parkinsonism, including masked face, chin tremor, resting, postural, and intention tremor approximately 3 to 4 Hz at the right upper extremities. Bradykinesia presented both upper and lower extremities bilaterally. Wide-based gait and decreased arm swing on both sides predominantly on the right were observed. In segment 2 (posttreatment), after 4 days of calcium supplementation, parkinsonian symptoms and psychomotor retardation were markedly improved. In segment 3 (posttreatment), after 8 months of proper calcium supplementations, parkinsonian symptoms have not recurred. Video content can be viewed at https://onlinelibrary.wiley.com/doi/10.1002/mdc3.13540 Routine blood chemistry showed acute kidney injury (blood urea nitrogen of 36.4 mg/dL, creatinine of 2.22 mg/dL, baseline creatinine of 1.2 mg/dL) with severe hypocalcemia (4.4 g/dL; normal range, 8.8–10.2 mg/dL), normal serum albumin (4.3 g/dL), hyperphosphatemia (7.8 mg/dL; normal range, 2.5–4.5 mg/dL), hypomagnesemia (1.0 mg/dL; normal range, 1.6–2.6 mg/dL), a low 25-hydroxyvitamin D level (21.4 ng/mL; normal range, ≥ 30 ng/mL), and a low parathyroid hormone level (8.13 pg/mL; normal range, 15–65 pg/mL). An electrocardiogram showed a prolonged QT interval. Axial T2 fluid-attenuated inversion recovery sequence of the brain magnetic resonance imaging showed a diffuse patchy confluence over the bilateral periventricular white matter without evidence of acute ischemic stroke by diffusion-weighted imaging and apparent diffusion coefficient, and brain computer tomography showed calcification at the bilateral globus pallidus (Fig. 1). Lumbar puncture was performed. The result was normal, including a negative viral meningoencephalitis panel. Hypocalcemia was corrected by intravenous calcium gluconate, and plasma calcium level was monitored closely. After 4 days of treatment, plasma calcium returned to the normal level concomitant with a remarkable improvement of both the parkinsonism and psychomotor speed (Video 1, segment 2). The patient was discharged from the hospital 7 days after admission. Calcium and vitamin D supplements were prescribed without dopaminergic medication. 18F-fluorodopa and 18F-fluorodeoxyglucose positron emission tomography were performed. The results showed no evidence of abnormal presynaptic dopamine deficit and no hypometabolic pattern compatible with neurodegenerative parkinsonian syndromes (Fig. 1). At 8 months after taking calcium and vitamin D, the parkinsonism had vanished and never recurred (Video 1, segment 3). We report a case of acute parkinsonism and psychomotor retardation attributed to hypocalcemia, which was a complication of post-thyroidectomy hypoparathyroidism. Parkinsonism in patients with hypocalcemia is rare. Its frequency increases in chronic hypocalcemia (Video 2). Full video from the 2021 Video Challenge discussion of this case. Video content can be viewed at https://onlinelibrary.wiley.com/doi/10.1002/mdc3.13540 The neurological manifestations of hypocalcemia can occur in the peripheral nervous system (PNS) and central nervous system (CNS). In the PNS, signs and symptoms of neuromuscular hyper-excitability including muscle twitching, tetanic contraction, trismus, and opisthotonos can be observed. The manifestations in CNS include encephalopathy, seizures, and, rarely, movement disorders.3-5 Hypocalcemia can result from hypoparathyroidism, pseudohypoparathyroidism, and post-thyroidectomy hypoparathyroidism.6 Early evidence of the association between parkinsonism and hypocalcemia in patients with hypoparathyroidism was reviewed by McKinney.5 He reviewed cases of hypoparathyroidism and hypocalcemia with symptoms other than tetany between 1950 and 1960, finding that 3 of 90 patients had presented with parkinsonism. He also found calcification of the basal ganglion did not correlate with the presentation of abnormal movements.5 Subsequently, Abe and colleagues reported a summary of published cases of hypocalcemia attributed to hypoparathyroidism presenting with movement disorders.6 They found 31 reported cases in the literature published between 1965 to 1994.6 Of those, 18 cases presented with parkinsonism including their own cases.6 We have summarized the reports of parkinsonism associated with hypocalcemia to date in Table 1.7-11 Mood: improved Parkinsonism: persisted Brain imaging of hypocalcemia frequently showed basal ganglia calcifications, especially in chronic hypoparathyroidism.2 Precipitation of calcium-phosphorus hydroxyapatite crystals in the basal ganglia and cerebellum of patients with hypoparathyroidism has been proposed as the possible pathogenesis for developing movement disorders in patients with hypoparathyroidism.10 However, this hypothesis cannot explain why some patients with hypoparathyroidism develop movement disorders despite the absence of basal ganglia calcification. Our patient had experienced acute parkinsonism and psychomotor retardation attributed to hypocalcemia caused by hypoparathyroidism. Despite its rarity, hypocalcemia could be a treatable cause of acute parkinsonism. Physicians should be aware of this condition, and it should not be missed. Early recognition and prompt treatment provides excellent clinical outcomes. 1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique; Y.P.: 1A, 1B, 1C, 2A J.S.: 1A, 1B T.S.: 1A, 1B W.S.: 1A, 1B P.S.: 1B, 2B The patient gave written informed consent for this case report. Our case report was approved for ethics (protocol number 878/2564) by the Human Research Protection Unit, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. There are no funding sources or conflicts of interest related to this case. The authors have no financial disclosures to report.