Abstract
Isolated foot dystonia following exercise is a rare manifestation of early PD. It may precede the onset of parkinsonism by years and can be clinically indistinguishable from familial exercise-induced dystonia. The authors present a patient with dystonic claudication where dopamine transporter SPECT using 123I-FP-CIT allowed early diagnosis of PD and enabled effective symptomatic treatment with a dopamine agonist.
Dystonic foot cramps as the presenting symptom of PD were first described in 1898.1 Their restricted appearance only after leg exercise was described later2 and the term dystonic claudication was proposed. Intermittent painful leg cramps on exercise can have a variety of underlying causes. In the absence of other physical signs that might suggest lumbar canal or peripheral vascular disease, the main differential diagnoses are familial paroxysmal exercise-induced dystonia and early PD. Early differentiation between these conditions is important because they differ with respect to prognosis and treatment.
We report a patient with isolated exercise-induced unilateral leg dystonia where SPECT using [123I]-2β-carbomethoxy-3β-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) indicated nigrostriatal dopaminergic degeneration and facilitated the early diagnosis of PD.
123I-FP-CIT is a new SPECT ligand that binds with high specific affinity to presynaptic dopamine transporters. SPECT results obtained with 123I-FP-CIT have been shown to match those found with the ligand 123I-β-CIT in healthy volunteers and in patients with PD.3 Whereas 123I-β-CIT reaches an equilibrium after about 24 hours, the faster kinetics of 123I-FP-CIT allow for scanning within 3 to 6 hours after administration.
Case report.
A 43-year-old man who had been previously well and kept a regular exercise regime noticed recurrent painful cramps in his left foot when exercising in the gymnasium. These consistently occurred after 5 minutes on the treadmill and 15 minutes on the exercise bicycle. On stopping the exercise, the cramps subsided within less than a minute. There was no family history of neurologic disease.
Five months earlier, the patient had presented to an orthopedic surgeon with pain in his left shoulder, which was precipitated by movement. MRI showed mild narrowing of the acromioclavicular distance and mild supraspinatus tendonitis, considered to be in keeping with a clinical diagnosis of rotator cuff tendonitis. Anti-inflammatory drugs and physiotherapy were of some help.
He went back to the orthopedic surgeon when the foot cramps developed. Spinal canal stenosis was suspected but results of MRI of the lumbar spine and EMG were normal.
The patient was referred for a neurologic opinion. On neurologic examination, no abnormalities were found, and the patient was asked to provide a home video depicting his difficulties. This revealed clawing of the toes and dorsiflexion of the left big toe after exercise. MRI of the brain had normal results. SPECT was performed on a GE XCT single detector gamma camera/STAR computer system (GE, Milwaukee, WI) fitted with a high-resolution parallel hole collimator, 3.5 hours after IV injection of 123I-P-CIT (185 MBq). Total striatal binding potential index (BP%) was obtained using the following formula: [(BG − Bk)/Bk] × 100 for each hemisphere (right and left), where basal ganglia uptake (BG) = specific + nonspecific binding, and nonspecific binding = background (Bk) = occipital cortex. SPECT showed bilateral and asymmetric reduction of striatal tracer uptake, thus confirming a presynaptic dopaminergic deficit (figure 1). Total striatal BP% compared to nonspecific uptake in the occipital cortex was 29.06% on the right and 37.88% on the left. This was compared to a group of 10 age-matched healthy controls (mean age 43.8 years; mean striatal BP% bilaterally 70.25, range 49.89 to 97.30) and to 9 age-matched patients with PD (mean age 44.8 years; mean striatal BP% 24.83, range 10.29 to 40.81). Tracer uptake was predominantly reduced in the posterior putamen, with a caudate/putamen ratio of 1.97 on the right and 1.30 on the left, corresponding to the typical pattern of neurodegeneration in PD (mean caudate/putamen ratio in the normal control group: 1.15, range 1.0 to 1.38; PD control group: 1.72, range 1.39 to 2.21; figure 2).
Figure 1. 123I-FP-CIT SPECT: Axial brain images show caudate and putamen of the patient (A) and an age-matched normal control (B). Total striatal binding potential index: A: right 29.06%, left 37.88%; B: right 57.83%, left 62.40%.
Figure 2. Radioactivity ratios for striatal subregions for the patient (filled circles), 9 age-matched patients with PD (gray boxes; mean ± 95% CI), and 10 age-matched normal controls (white boxes; mean ± 95% CI). Sbi = Striatal binding index = ratio of radioactivity counts between each striatal subregion and occipital cortex; PP = posterior putamen; AP = anterior putamen; CN = caudate nucleus; contralateral = hemisphere contralateral to clinically more affected side in PD and right hemisphere in normal controls.
At follow-up 3 months after the scan, very mild stiffness of the left hand as well as slight rest tremor and stiffness of the left leg were detected on neurologic examination. Treatment was started with the dual target of improving dystonia as well as parkinsonism, and a dopamine agonist (pramipexole, at a dosage of 1.4 mg/day) was chosen. This led to an improvement in the patient’s mild parkinsonian signs and symptoms and had a marked effect on his ability to exercise in that the amount of time he could exercise without cramps occurring increased to about 30 minutes.
Discussion.
This atypical presentation highlights the potential usefulness of dopamine transporter SPECT in the early diagnosis of PD. Cramping leg pain following physical exercise usually raises suspicion of arterial occlusive disease with intermittent hypoperfusion of a limb distal to an atherosclerotic stenosis or lumbar spinal canal stenosis with cauda equina compression. Lumbar canal stenosis with foot dystonia has also rarely been described.4 Other, rarer causes include exercise-induced hypocalcemic tetanic spasms in hypoparathyroidism.5 In dopa-responsive dystonia, where parkinsonism may also be present, diurnal fluctuation, a sustained buildup of dystonia as the day goes by, irrespective of the degree of physical exercise, is more characteristic.
The familial conditions paroxysmal kinesigenic dyskinesia (PKD) and paroxysmal nonkinesigenic dyskinesia (PNKD) differ from the pattern observed in our case. In PKD, very brief and frequent attacks are provoked by sudden movements, whereas in PNKD, external factors such as fatigue, alcohol, or caffeine provoke attacks that last from 10 minutes to several hours.
Paroxysmal exercise-induced dyskinesia is a rare familial condition with an autosomal dominant pattern of inheritance in most described families.6 Prolonged exercise is usually required to trigger an attack, and abnormal posturing takes 10 to 15 minutes to resolve.6 Symptomatic treatment options for paroxysmal exercise-induced dystonia are limited at present, although in rare cases, response to acetazolamide,6 carbamazepine, or l-dopa7 has been described.
The first cases of dystonia as the presenting feature of PD were described by Purves Stewart.1 In two out of three cases, foot dystonia was triggered by walking, and dystonia preceded other features of parkinsonism by up to 2 years. There have since been a few further reports of PD presenting with intermittent lower limb dystonia.8 One case2 resembling ours has been reported: in a 42-year-old marathon runner, prolonged running provoked disabling, unilateral foot dystonia, and the patient went on to develop typical parkinsonism a year later. Intervals of months to 13 years have been described between onset of dystonia and the emergence of other signs of parkinsonism.9 Dystonia at onset appears to be more frequent in parkin-positive patients.10
Treatment with l-dopa has been reported to lead to a deterioration of the dystonia in at least some cases,9 whereas dopamine agonists or anticholinergics can abolish it.8 Despite the absence of any treatment that can slow disease progression in PD, early diagnosis is important to instill confidence, avoid further inappropriate medical referrals, and advise on prognosis and subsequent symptomatic therapy.
Our case shows that in a case of intermittent exercise-induced focal cramps, the possibility of an atypical presentation of PD should be kept in mind. In the absence of the cardinal physical signs of PD, detection of dopaminergic neurodegeneration by dopamine transporter SPECT would provide support for dopamine replacement therapy.
- Received May 13, 2002.
- Accepted August 19, 2002.
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