Levodopa-responsive hemiparkinsonism after acute mesencephalic injury (vascular or traumatic damage of the SN with ipsilateral nigrostriatal denervation) is an uncommon syndrome that can pose a therapeutic challenge.[1-9] Here, we describe the successful outcome of unilateral globus pallidus internus (Gpi) DBS in a young patient who developed severe unilateral motor complications.
A 27-year-old male presented with sudden-onset headache, diplopia, and left-limb weakness. Examination disclosed an incomplete Weber's syndrome, and neuroradiological studies showed a spontaneous right mesencephalic hemorrhage with no identified vascular anomalies, suggesting the possible rupture of a cavernous angioma. A favorable outcome was obtained within a few weeks, leaving only a slight clumsiness in the left limbs. Two months later, he began with shaking, rigidity, and increased motor difficulty in the left hemibody. These symptoms were slowly progressive, but not properly recognized, until 2 years later, when he was diagnosed with hemiparkinsonism. In the meantime, the patient had developed avascular necrosis of the left hip, which further impaired his gait and confounded the clinical picture. Brain MRI and 123I-ioflupane single-photon emission CT showed abnormalities (Fig. 1A,B). l-dopa treatment at 300 mg/day resulted in a major clinical improvement, but he developed “end-of-dose deterioration” and “peak-dose” dyskinesia in the left hemibody after 1 year. Over the next few years, unilateral motor fluctuations became more severe and complex, and nonmotor fluctuations manifested as a depressive mood disorder during off periods. Several dosage regimens were tried with no satisfactory control. The patient voluntarily suspended all treatments and developed a severe depression that was resolved after reintroduction of l-dopa. At the age of 35 years (5 years with l-dopa treatment), he was referred for DBS surgery. Neurological examination on admission is shown (see Video, Segment 1). UPDRS-III score was 30 in the off state and 8 in the on state (73% improvement). Severe choreodystonic dyskinesia appeared in the left limbs as a peak-dose effect (CAPSIT-PD Dyskinesia Rating Scale = 5/28). A comprehensive neuropsychological study revealed deficits in executive functioning and verbal and visual memory, but no major interference in daily living activities.
Under local anesthesia, a quadripolar DBS electrode (model 3387; Medtronic, Minneapolis, MN) was implanted into the right Gpi after microelectrode recordings. Coordinates in the Cosman-Roberts-Wells frame were x = 20, y = 3, and z = −5 mm. During surgery, high-frequency micro- and macrostimulation induced a dramatic motor improvement (see Video, Segment 2). Under general anesthesia, a rechargeable pulse generator (model 37612; Medtronic) was implanted into the abdominal wall. Postsurgical MRI confirmed the proper placement of the electrode, with no structural complications (Fig. 1C). The patient was discharged from the hospital within 1 week with no adverse events. The pulse generator was programmed at 2 weeks postsurgery, with an optimal setting of monopolar stimulation on contact 2 at 250 Hz, 90 μs, and 3 V. The patient showed a marked improvement in off-hemiparkinsonism and on-dyskinesia and continued under l-dopa treatment. Over the subsequent months, he developed a tolerance phenomenon, requiring gradual increases in amplitude up to 6 V. A rigorous check of all devices detected no failures, and attempts to optimize the programming with other configurations failed. Finally, the patient was instructed to turn off the generator at night and maintained an adequate symptomatic control thereafter, with no further stimulation adjustments. He suppressed l-dopa treatment, with no recurrence of depression or other adverse effects. At 2 years after surgery, the patient shows almost complete abolition of hemiparkinsonism during waking hours (UPDRS-III = 5; see Video, Segment 3), with major functional and quality-of-life benefits.
Our patient exhibited l-dopa-responsive hemiparkinsonism as a consequence of destruction of the right SN and its surrounding structures, with subsequent denervation of ipsilateral dopaminergic pathways. Besides the dorsal (motor) striatum, other projection areas were likely impaired, contributing to the cognitive and mood disorders encountered. However, unlike in Parkinson's disease (PD) patients, the neuronal loss remained localized and nonprogressive, and this distinction makes the case of interest for investigating pathophysiological aspects and response to surgery. The development of unilateral motor complications shortly after the initiation of l-dopa treatment indicates that the extent of nigrostriatal denervation, regardless of its origin, is the key factor. The gradual appearance of complications in the absence of functional nigrostriatal terminals highlights the importance of progressive postsynaptic changes in their pathophysiology.
Whereas functional neurosurgery is often considered for patients with severe Holmes tremor after a midbrain lesion, we found only two reports in patients with associated hemiparkinsonism, who underwent thalamotomy and double thalamic/subthalamic DBS, respectively. In our case, STN-DBS was rejected because of safety concerns about targeting the area adjacent to the bleeding site. Although no previous cases were reported, Gpi-DBS was considered to have a better safety profile for our patient, and markedly improved hemiparkinsonism, dyskinesia, and mood status, permitting medication withdrawal. The nonprogressive nature of the disorder in this syndrome may possibly imply superior long-term outcomes in these patients in comparison to PD patients.