Hemiparkinsonism-Hemiatrophy Syndrome

The syndrome of hemiparkinsonism-hemiatrophy is an uncommon form of secondary Parkinsonism that presents with unilateral body Parkinsonism plus variable atrophy on the same side. Diagnosis of this syndrome needs a complete past medical history taking, as well as assessment of the familial history, clinical examination and complete paraclinical tests. The response to medical therapy has been variable in various researches. This case showed a good response to the addition of a dopamine agonist to

with tremor for around eight years. The tremor began insidiously and progressed gradually to involve his right hand, particularly at rest. The patient had dif¿culty with his handwriting or with holding a cup while drinking, and general tasks that required manual dexterity. Also he felt that his balance was not quite as good as what it used to be. He has also noticed a mild twisting motion in his right hand and foot.
The patient had no history of head trauma, surgery, drug therapy, smoking, and other possible causes for movement disorders as well as relevant positive family history. He was born via natural labor without complications, but no documents exist to indicate a safe labor. On examination, the patient had a rather regular tremor of approximately 4 to 6 cycles per second (Hz) with his right hand prominently at rest and mild dystonia in the right upper and lower limbs, particularly during working or walking. During speaking, he exhibited mild dysarthria and hypotonia. Otherwise, he had 4/5+ right hemiparesia plus mild and brief right hemiatrophia. Deep tendon reÀexes were generally brisk. He had a mild bradykinesia without prominent rigidity. No autonomic problems such as orthostatic hypotension or urinary incontinence were detected. Except for mild right hemifacial atrophy, other cranial nerves were normal. His mental and cognition status, and other gener-al and neurological exams were normal apart from a mild depression. His Uni¿ed Parkinson's Disease Rating Scale (UPDRS) scale in ¿rst visit before treatment with levodopa or other antiparkinson drugs was 43 (in the ¿rst 3 steps of the UPDRS).
Brain CT-scan showed the asymmetry between the cerebral hemispheres and ventricular asymmetry. Mild atrophy on the left hemisphere plus left lateral ventricle enlargement without other prominent lesions were also noted in the brain MRI (Figures 1 and 2).
Laboratory tests, which included FBS, hemoglobin and hematocrit, serum cholesterol, triglycerides, BUN, Cr, serum Cu, and ceruloplasmin, were all normal. Protein C and S, ANA, anti-ds-DNA, anti-phospholipids, and anticardiolipin antibodies were normal as well. Cerebrospinal Àuid analysis was normal. Genetic tests for familial Parkinson (PARK1 and PARK2) were negative. No ¿ndings for motor neuron disease, neuropathies or other muscle or peripheral nervous system disorders were seen with the EMG-NC test. H/M amplitude ratio in the right extremities was also normal. We began the patient's treatment with Rasagiline ® 5 mg per 12 hours and biperidine 2 mg/8 hr because of the hand tremor, however, no improvement was noted. After three months, levodopa-carbidopa 50 mg 3 times daily was started and gradually increased to 250 mg 3 times daily over a period of three months. In contrast to previous reports, favorable results from levodopa-carbidopa alone were not seen and after ¿ve months, a dopa-agonist agent was added to the patient's treatment program after which a remarkable response was seen. Currently, the patient is on 250 mg/8 hr levodopa-carbidopa and Sifrole ® 0.18 mg/8 hr plus biperidine 2 mg/8 hr.
Thus far, we have not observed any motor Àuctuation or other complications during treatment. Dystonia and Parkinsonism symptoms and signs have been suppressed and cur-Archives of Iranian Medicine, Volume 14, Number 2, March 2011 153 rently the patient is stable and it seems that progression of his disorders has stopped. However, there are no changes in hemiathrophia. After one year of treatment his UPDRS score from the ¿rst three steps has reached 32.

Discussion
Hemiparkinsonism-hemiatropy (HPHA) syndrome is a rare form of secondary Parkinsonism that usually begins in the third or fourth decade of life; it is characterized by unilateral body atrophy and ipsilateral Parkinsonian ¿ndings with slow progression. 1 Hemiatrophy may be unnoticed. 2 Interestingly, one patient showed no hemiatrophy, however, an enlarged lateral ventricle was a sign of brain atrophy. 3 Patients may present initially with dystonia that is often action induced and may involve only one leg or arm. There is no right or left sided prominence. Patients often have scapular winging, raised shoulder, brisk reÀexes, and extensor plantars. Scoliosis is common. 2 Occasionally some patients with HPHA syndrome may have problems in his fetal or perinatal periods as asphyxia or early development especially in walking. 3 It has been reported that lesions of the postcentral gyrus, which occur before the age of three are associated with a relative smallness of the contralateral parts of the body. 4 Accordingly, it has been suggested that the occurrence of Parkinsonism in HPHA patients is related to additional subcortical lesions. 5 Similarly, Giladi et al. have presented neuroradiological evidence of contralateral brain hemiatrophy in 64% of their patients. Since an association between perinatal asphyxia, brain hemiatrophy, and delayed-onset hemidystonia has been shown, therefore HPHA could represent an example of a movement disorder with delayed onset as a consequence of neonatal brain injury. 3 CT-scan and MRI in one study showed contralateral brain asymmetry in 64% of investigated patients, 3 but Bushman et al. found no evidence of cerebral hemiatrophy. 6 Giladi et al. have reported 11 cases of HPHA in which 6 patients presented with body and contralateral cerebral hemispheric hemiatrophy as seen on brain imaging, 4 with solely body hemiatrophy and one with only brain hemiatrophy. MRI ¿ndings were asymmetric lateral ventricles, volume loss, thalamic, or arachnoid cysts. Unilateral changes included calvarial thickening, expansion of the ethmoid, frontal sinuses, or mastoid cavities, and elevation of the petrous ridge and greater wing of the sphenoid bone. 2 Studies that utilized 18F-Àuorodeoxyglocose and positron emission tomography (PET) have shown focal hypometabolism in the basal ganglia and the medial frontal cortex of the contralateral side. 7 In contrast to presynaptic involvement in parkinsonism's disease (PD), PET scaning have provided evidence of presynaptic and postsynaptic nigrostriatal dopaminergic dysfunction in patients with HPHA syndrome. 8,9 One patient with HPHA syndrome was found with a mutation in the Parkin gene on chromosome 6. 1 Negative signs and symptoms that are rare or not seen at all include axial signs such  as swallowing or speech dif¿culty or symmetric freezing. 2 Responses to the drug therapy with levodopa vary among studies. In case reports from Giladi et al., three patients showed good response to levodopa (33%), four had moderate response (44%) and two patients (22%) had a poor response. 3 Bushman et al. have presented the HPHA syndrome as a dopa-responsive condition. 6 Wijmann et al. reported good response to levodopa in 18 (60%), moderate in 6 (20%), and poor in 6 cases (20%). 2 Jenkins et al. reported a case of HPHA syndrome that showed dramatic improvement with subthalamic nucleus stimulator (STN) implantation. 10 However, the effects of dopamine agonists in treatment of HPHA syndrome are not clear due to the low numbers of cases and lack of published results with these agents. We have used these agents based upon their therapeutic effects in idiopathic Parkinson's disease. As a result of the good response of our patient, therefore we recommend this combination therapy in levodopa-resistant cases of HPHA syndrome. Up to the knowledge of authors, only few cases of this disease have been reported worldwide, and its real pathophysiology is not clearly known.