Paroxysmal dyskinesias (PDs) and some motor manifestations of epileptic seizures have been difficult to differentiate clinically. Whether the two disorders are clinically distinct or share common pathophysiologic mechanisms remains undetermined. The classification of PD has been revised according to its precipitating factors as kinesigenic, nonkinesigenic, exertional, or hypnogenic (1). Most sporadic and all familial cases of PD are idiopathic. Symptomatic PD accounts for only a minority of sporadic cases, such as multiple sclerosis, hypoxic encephalopathy, and hypoparathyroidism (2). We report a case of pseudohypoparathyroidism (PHT) with kinesigenic PD and secondary generalization of tonic–clonic seizures.
A 25-year-old male soldier was admitted to our hospital after losing consciousness twice within a month. In one episode, he remembered running and accelerating down a slope but could not recall what happened later. According to the witness's statement, he was running very fast, then suddenly fell down with trismus and generalized tonic–clonic movements for 3 min. A postictal confusional state was noted. A similar episode occurred when he was doing strenuous horizontal bar exercises. After several successive up-and-down exercises, he lost consciousness and was found with generalized tonic–clonic movements. Records show he had a history of paroxysmal movement disorder since junior high school. The movement disorder always occurred in 100-m running tests. At 70–80 m, he had to decelerate and stop when he felt his arms tightly flex and twist. The duration of each episode was ∼1 min. Episodes never occurred at rest or during moderately paced activities. No history of other neurologic disease was known.
A general physical examination noted a short stature (158 cm), alopecia, round face, and a stocky figure. The general examination was otherwise unremarkable. A neurologic examination showed mild cognitive impairment (20 for Mini-mental Status Exam). Trousseau and Chvostek signs were positive.
Laboratory examinations revealed a normal chemistry profile with the exception of a calcium total of 4.9 mg/dl; phosphorus, 5.2 mg/dl, and Mg, 1.6 mg/dl. Complete blood count and thyroid function studies were normal. Serum parathyroid hormone level was 164.2 pg/ml. These are consistent with a diagnosis of PHT. Sphenoid electroencephalography (EEG) was normal, except for some focal slow waves (5–6 Hz) over the bilateral frontotemporal regions. Magnetic resonance imaging of the head revealed marked, symmetric calcifications on the bilateral putamen and dentate nucleus. No family history of similar paroxysmal dyskinesia was found.
During admission, we set up a portable EEG and video recording for the patient and stressed that he run as fast as possible. At 70 m, he felt marked tightness in his arms, and his fists clenched tightly and twisted. He experienced no pain and stopped immediately. The choreoathetoid movement gradually resolved after 1 min. The EEG recording showed paroxysmal generalized sharp-and-slow waves at 4–5 Hz, especially in the frontal areas during the attack (Fig. 1).
The patient was treated with supplemental calcium and vitamin D with near normalization of his serum calcium in 2–3 months. The paroxysmal movement disorder gradually resolved after calcium replacement and elevation of the serum calcium levels. Cognitive performance improved (25 for Mini-mental Status Exam). By the third month, no further events of PD were reported. The EEG was normal.
Hypoparathyroidism with hypocalcemia and basal ganglion calcification has been described as a secondary cause of kinesigenic PD (3). Hypocalcemia in the absence of renal disease, in association with elevated parathyroid hormone levels, as well as Albright osteodystrophy, are diagnostic of PHT, as in this case. Rare case reports concern PHT and kinesigenic PD. The PD manifested by this patient is precipitated by very strenuous exercise. The choreoathetoid movement and the absence of pain suggest dyskinesia, rather than carpopedal spasm. The following loss of consciousness, trismus, and generalized tonic–clonic convulsion would be most consistent with an epileptic seizure. To our knowledge, it is the first case report of PD leading to secondary generalization of a tonic–clonic seizure.
It has been argued that PD may represent one expression of epileptic seizures (1,2). Our case showed episodes of kinesigenic PD with secondary generalization of tonic–clonic seizures. In the presence of extremely intensive kinesigenic stimuli; that is, a strong sensory (proprioceptive) input to the subcortical thalamic relay and then to the basal ganglia; subcortical-cortical spreading develops (4). Thus in the presence of hypocalcemia, the subcortical-cortical spread may be enhanced owing to increased excitability and lead to the development of secondary generalization of tonic–clonic seizure. However, it is not known in whom with PHT will kinesigenic PD and generalization develop.
Recently it was suggested that dopaminergic hypersensitivity in the striatum, known to be a cause of PD, is a secondary phenomenon of γ-aminobutyric acid (GABA)ergic disinhibition (5). The decrease in extracellular calcium lessens the probability of vesicle release and posttetanic potentiation of GABAergic inhibitory postsynaptic currents in central neurons (6). Therefore it may be postulated that GABA may act as an important modulator with hypocalcemia in the pathogenesis of PD and even generalization, because GABAergic dysfunction may alter GABA inhibitory postsynaptic potentials in thalamic relay neurons and may result in rebound bursts of action potential in thalamocortical circuits.
We suggest that people with symptomatic PD, such as PHT, avoid rigorous exercise as much as possible. If a kinesigenic PD is followed by a secondary generalization of tonic–clonic seizure, the existence of PHT should be investigated, because this is a potentially treatable disorder.