Secondary cervical dystonia in iatrogenic hypoparathyroidism associated with extensive brain calcifications
a Parkinson’s Disease and Movement Disorders Unit, “C. Mondino Institute of Neurology” Foundation, Pavia, Italy
b Department of Neuroradiology “C. Mondino Institute of Neurology” Foundation, Pavia, Italy
c Department of Neurology and Otolaryngology, “
Reprint requests to: Dr Francesca Mancini and
Dr Roberta Zangaglia
Parkinson’s Disease and Movement Disorders Unit
IRCCS “C. Mondino Institute of Neurology” Foundation,
Via Mondino, 2 - 27100 Pavia - Italy
Accepted for publication: May 30, 2006
Cervical dystonia (CD) is usually idiopathic, without a known aetiology. Hypoparathyroidism, both primary and secondary, can be associated with brain calcifications and various clinical neurological features.
Anecdotal evidence suggests that patients affected by hypoparathyroidism show a rapid-onset oral dyskinesia after use of neuroleptic drugs.
We report the case of a 60-year-old woman with CD, iatrogenic hypoparathyroidism and extensive brain calcifications. On the basis of the clinical features and the localization of the brain calcifications we suppose that they may have played a role in the development of this CD.
This case may prove to be, after a review of literature, the first report of CD secondary to iatrogenic hypoparathyroidism in a patient with extensive brain calcifications.
KEY WORDS: brain calcifications, cervical dystonia, hypoparathyroidism.
Cervical dystonia (CD), the most frequent focal dystonia (1), is characterised by sustained and involuntary muscle contraction resulting in twisting and/or other abnormal head and neck postures (2).
Deviations may occur in any single plane or in a combination of directions, giving rise to rotational torticollis, laterocollis, anterocollis and retrocollis. CD is usually idiopathic, without a known aetiology (3,4).
Hypoparathyroidism, both primary and secondary, can be associated with brain calcifications (5) and various clinical features (6,7), such as: parkinsonism, oro-facial dyskinesias, hemidystonia, mental deterioration (8), psychiatric symptoms, seizures, cerebellar syndrome and pyramidal signs, aspecific alterations on EEG, and tetany.
Anecdotal evidence suggests that patients affected by hypoparathyroidism show a rapid-onset oral dyskinesia after use of neuroleptic drugs (9,10).
We describe a patient with CD secondary to iatrogenic hypoparathyroidism associated with extensive brain calcifications and transient iatrogenic oral dyskinesia.
MM had been diagnosed with type II diabetes at the age of 28 years, and at 39 had undergone a thyroidectomy with incidental ablation of the parathyroid glands. One year after the thyroidectomy she started to present repeated episodes of tetany associated with hypocalcaemia (<6 mg/dl); to treat these symptoms, at the age of 60, she began continuous treatment with calcium, 1000 mg/day.
At the age of 45, following episodes of severe depression, she had begun therapy with fluoxetine at conventional doses. At 58, she developed delusions and was treated with haloperidol at low doses (20 mg/day); this soon gave rise to disabling oral dyskinesias, which partially improved after reduction of the haloperidol.
Eight months after haloperidol withdrawal, she presented painful CD (rotational cervical dystonia type with prevalently stable posture). Her family history was negative for movement disorders. Upon hospitalisation, MM presented features typical of idiopathic cervical dystonia: hypertrophy of the left sternocleidomastoid muscle (SCM) and the right trapezius muscle, and efficacy of sensory tricks in controlling the abnormal posture.
The abnormal position of the head was maintained by a fixed muscle contraction, without associated involuntary movements. She presented slight oral dyskinesia, mild plastic hypertonia at the lower limbs, postural instability and a slight but global hypokinesia.
Laboratory tests gave the following results: thyroid stimulating hormone (TSH) 0.005 mUI/L (normal range: 0.32-3.73), free thyroxin (FT4) 14.9 pmol/l (normal range: 10-27), serum calcium 6.87 mg/dl (normal range: 8.8-10.2), serum phosphorus 5.6 pg/ml (normal range: 2.7-47.5), parathormone 14 pg/ml (normal range: 12-55), 24-hour urine calcium 36 mg/dl (normal range: 100-300), urine phosphorus 468 mg/dl (normal range: 400-1000).
Brain MRI showed a reduced signal intensity in T2-weighted pulse sequences in the basal ganglia and in the dentate nucleus of the cerebellum, indicative of calcifications; brain CT revealed diffuse bilateral calcifications located in the basal ganglia, caudate nucleus, globus pallidus, thalamus, white matter of the corona radiata (showing a perivascular distribution), subcortical occipital area, gracile and cuneate nucleus of the medulla oblongata and dentate nucleus of the cerebellum. EMG showed a sustained simultaneous contraction of the left SCM and right trapezium muscle in all the head positions examined.
The tetany test was positive at the second trial of prolonged ischaemia with typical multiplets. The neuropsychological assessment revealed deficits of short- and long-term memory, of abstract/conceptual reasoning and of praxic functions.
In February 2002, the patient underwent a treatment with botulinum toxin type A (BTXA) (Dysport) 100 U injected into the right trapezium and 150 U into the left SMC, without benefit. In September 2002, she was injected with botulinum toxin type B (BTXB) (Myobloc) (11): 5000 U in the right trapezium and 5000 U in the left SMC, again without benefit.
On the basis of the clinical features, this case of CD might be interpreted as an idiopathic form or as a tardive form, secondary to the use of a neuroleptic drug (haloperidol), but brain calcifications, particularly in association with the patient’s medical history, are suggestive of a long-term complication of iatrogenic hypoparathyroidism.
Even though the idiopathic hypothesis is supported (4) by the presence of muscle hypertrophy, the rotatocollis and the efficacy of trick manoeuvres, the abnormal brain imaging, and the fixed posture argue against it.
Conversely, the iatrogenic tardive hypothesis is supported (12) by the association of oral dyskinesia with haloperidol treatment, even though CD began more than 8 months after haloperidol withdrawal, and anecdotal evidence suggests that patients affected by hypoparathyroidism show a rapid-onset oral dyskinesia after use of neuroleptic drugs (13).
This clinical case might, after a thorough review of the literature, emerge as the first report of CD secondary to iatrogenic hypoparathyroidism in a patient with extensive brain calcifications.
Anatomical and physiological interactions between the olivopontocerebellar and basal ganglia-thalamocortical circuits that have been demonstrated in rats and primates provide considerable insight into mechanisms potentially operative in cervical dystonia (14,15).
In addition, literature data suggest that the largest percentage of cases of secondary CD was associated with structural lesions of the brainstem (medulla, pons) and/or cerebellum (12,16-20). The localization of the brain calcifications in this patient suggests that they may have played a role in the development of her cervical dystonia.
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