Case report

A 44 year old man was admitted to the Department of Neurology of the Istituto San Raffaele because he had had 2 years of repeated spells of involuntary movements characterised by dystonic postures starting from his right foot and then involving the ipsilateral leg, arm, and face, without any alteration of consciousness. Spells were characterised by leg hyperextension, arm flexion, and face grimacing. The episodes were sudden, of brief duration (10 to 20 seconds), and triggered by movements such as standing up, starting to run or walking rapidly, particularly after prolonged sitting. The frequency of these spells was initially low (one attack/week) and then gradually increased to 10 episodes/day. Sometimes the patient reported sensations of paraesthesias, a feeling of stiffness or a tense feeling at the beginning of the paroxysms. Some attacks were aborted by stopping movement or slowly warming up.

On admission, general and neurological examinations were normal. Routine laboratory tests were normal except for decreased serum total and ionised calcium concentrations (1.30 mmol/l, normal value 2.10–2.60; 0.69 mmol/l, normal value 1.18–1.30, respectively) and increased serum phosphate concentrations (1.60 mmol/l, normal value 0.8–1.5). Plasma parathyroid hormone (PTH) concentrations were not detectable. Echography of the neck was normal. Brain MRI showed low signal T2 weighted images and hyperintense signal T1 weighted images in bilateral basal ganglia, thalamic and dentate nuclei, and cerebral white matter, suggesting calcium deposits. Repeated EEG examinations, including two 24 hour recordings, failed to show electrical abnormalities even during bursts of involuntary movement. A diagnosis of PKC secondary to IPH was made. A quantitative [¹⁸F]-FDG PET study was performed and the methods and the results are reported below.

Results

At the first [¹⁸F]-FDG PET examination, under conditions of overt hypoparathyroidism, the patient showed a significant bilateral hypometabolism in the ventral striatum—namely, the inferior component of the caudate nucleus and the putamen. This was shown by the SPM procedures (table 1 and fig 1), as well as in comparison with normative values using ROIs (table 2). Indeed, quantitative measurements of glucose consumption in the ventral striatum showed a reduction below 2 SD of normal values before, and a recovery after treatment. The SPM map showed a hypofunction extended to the left striatum.

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Figure 1

Bottom: three dimensional SPM brain rendering with superimposed regions of significant hypometabolism according to a colour scale (p<0.01, Z:2.33). Top: the corresponding coronal slice of the atlas of Tailarach and Tournoux.14

Oral calcitriol (0.25 mg three times daily) and calcium supplementation (1 g/day) therapy was then started. Progressive disappearance of the motor attacks was seen concomitantly with normalisation of serum calcium concentrations, and the patient was able to resume his working activity. One year later, the patient was readmitted to the Department of Neurology of the Istituto San Raffaele for clinical and instrumental re-evaluations. Under conditions of normal serum total and ionised calcium concentrations (2.30 and 1.25 mmol/l, respectively) he was free of any occurrence of episodes of PKC. A brain MRI was superimposable on the previous one (fig 2, A and B). Specifically, calcifications in the dorsal basal ganglia and in the dentate nuclei were still evident, and unmodified in size. On the other hand, ROI measurements of glucose consumption showed values within the normal range in the dorsal basal ganglia and the SPM analysis did not show any difference between patient and controls in this region.

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Figure 2

Superimposable MRI images before (1A) and 1 year after (1B) therapy, showing no changes of calcifications in bilateral basal ganglia, thalamic and dentate nuclei, and cerebral white matter.

Discussion

Paroxysmal dyskinesias are a heterogeneous group of disorders characterised by involuntary movements in bursts with return to normality within variable periods. There are two forms of paroxysmal dyskinesias: prolonged attacks lasting for more than 5 minutes (paroxysmal dystonia) and brief attacks precipitated by movement, lasting less than 5 minutes (PKC). Both can be familial or sporadic, and the second may be primary or secondary. Among the secondary forms of PKC, four patients have been described in association with IPH. All the affected patients previously reported on were young, had the typical picture of hypoparathyroidism (hypocalcaemia, basal ganglia calcifications), and showed remission of dyskinesias after calcium/calcitriol supplementation therapy. The patient of the present report, who developed his symptoms at the age of 42, represents, therefore, the fifth case of PKC associated with IPH described so far, and the first showing onset of the disease in adulthood. Furthermore, the instrumental examinations performed on our patient allowed new insight into the mechanisms underlying the development of PKC in IPH. Different hypotheses have been proposed in the past. One emphasised the role of calcium deposits in the basal ganglia and of their consequent dysfunction. Another considered PKC a sort of “reflex epilepsy”, based on the sporadic finding of EEG abnormalities and on the efficacy of anticonvulsant drugs in reducing the frequency of the episodes. The data of the present study seem to rule out the epileptic nature of the PKC, as the repeated EEG recordings performed, also during clinical attacks, failed to show any abnormalities. Our findings rather suggest that an impaired function of the basal ganglia plays a crucial part in the pathogenesis of PKC associated with IPH. A significant hypometabolism of the ventral putamen and inferior caudate was found with [¹⁸F]-FDG PET. Furthermore, normal metabolism of the basal ganglia, together with disappearance of the clinical symptoms were found after calcium/calcitriol therapy, suggesting that hypocalcaemia, and not calcium deposits (that were still present 1 year after the start of the therapy), are responsible for the altered function of the basal ganglia found with [¹⁸F]-FDG PET. Noteworthy, the calcifications shown by the MRI in the dorsal striatum seem not to affect glucose metabolism as indicated by the ROI quantitative values and SPM analysis (table 2 and fig 3). In addition, the patient never had parkinsonism or related neurological signs. It is possible that calcium deposits are confined to the pericellular space with no effect on neuronal viability.

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Figure 3

Comparable axial slices of the first and second [¹⁸]-FDG PET study showing normal glucose metabolism at the level of the dorsal striatum (see text for comments).

The [¹⁸F]-FDG PET data also suggest that hypocalcaemia leads to PKC by determining neural hypofunction; this is by contrast with what was previously hypothesised by some authors,18who considered PKC the consequence of a neural hyperexcitability due to an increased membrane permeability. Of note is that the reduction of glucose metabolism in the striatum has also been reported in other movement disorders, such as different types of dystonias.19 Furthermore, previous reports by Janavset al 20 suggest an impairment of the indirect pathway of the thalamocorticobasal ganglionic circuitry as the cause of the choreic phenomena. Indeed, the hypofunction of the indirect pathway from the striatum to the internal globus pallidus may lead to inappropriate disinhibition of thalamic projections to the premotor and motor cortex.

In conclusion, our data provide experimental evidence for the possible anatomofunctional correlates underlying PKC associated with IPH, and provide a basis for further studies to fully elucidate the neural networks involved in such a neurological disorder.