Postmortem analysis of pallidotomy in Parkinson?s disease

Abstract

Sirs: We describe neuropathological features, including an immunohistochemical study, of pallidotomy in a patient with idiopathic Parkinson’s disease (PD). A 67-year-old hypertensive man presented at age 52 years with resting tremor affecting the right hand. Over years, the tremor worsened and became prominent, affecting his daily activities. The diagnosis of PD was made a few years after the onset and he responded remarkably well to levodopa, with significant reduction of tremor. His PD continued to progress and he started to develop motor complications four years later, including severe motor fluctuations, peak dose dyskinesias and unpredictable freezing to the point that he was unable to rise from a chair and crawled from place to place. Despite multiple trials of different dopaminergic therapy, his condition became medically intractable. He developed persistent left sided dyskinesia occurring throughout the day. Fifteen years after symptom onset, the patient underwent a right posteroventral pallidotomy because of intractable dyskinesia and severe motor fluctuations. Intraoperative localization of the globus pallidus interna (GPi) was via direct visualization on T2 coronal MRI, with the plane perpendicular to the AC-PC line. Microelectrode recording was then performed to accurately identify the targeted nucleus. After the sensorimotor area of the GPi was identified and the internal capsule and optic tract localized by microelectrode recording, the lesion probe was placed for radiofrequency ablation by increasing the temperature to 60°–90°C for 60 seconds. The patient tolerated the procedure well and experienced immediate relief of left sided dyskinesia as well as improvement in tone and mobility. There were no surgical complications. Three weeks following surgery, the patient collapsed at home and died suddenly. Autopsy (Patient #1) confirmed the cause of death as myocardial ischemia secondary to severe coronary atherosclerosis. A neuropathological study was carried out on patient #1 as well as a 50-year-old man with the autopsy proven diagnosis of PD who had died from acute myocardial infarction (Patient #2), and a 62-year-old man with no neurological disease who died from acute hypoxia (Patient #3). Formalin-fixed paraffin-embedded tissue blocks, including globus pallidus (both interna and externa), putamen and internal capsule, were cut at 5μm thickness, and stained with hematoxylin and eosin. Consecutive serial sections were used for immunohistochemical studies. Immunostaining was performed with the Labelled Polymer (goat anti-rabbit or antimouse immunoglobulins conjugated to peroxidase labeled-dextran polymer, EnVision+TM, DAKO, Carpinteria, CA, USA) method using 3–3’ diaminobenzidine tetrahydrochloride (DAB) as chromogen. Reagents used in the study were polyclonal antibodies against bovine glial fibrillary acidic protein (GFAP, dilution 1:300), monoclonal antibody against CD68 (clone KP1, dilution 1:50), polyclonal antibodies against CD3 (dilution 1:75), and monoclonal antibody against CD20 (clone L26, dilution 1:75) (DAKO, Carpinteria, CA, USA). Specimens for CD68, CD3, and CD20 immunostaining were subjected to microwave boiling in a 0.015M sodium citrate buffer solution (pH 6.0) for 12 minutes as an antigen retrieval procedure before blocking with normal goat serum. Sections were counterstained with hematoxylin. The mean number of CD68-positive microglial cells per 0.25 mm2 was evaluated independently by two of the authors (RB and HM) in the lateral half of globus pallidus externa, putamen and internal capsule, using a X20 objective lens and grid (0.25 mm2) and a microscope (Olympus BX-40, Tokyo, Japan). At least seven areas were randomly chosen for cell counting in each anatomical structure. Coronal sections of the cerebral hemispheres showed the presence of a thin, slit-like and predominantly hemorrhagic lesion in the superior aspect of the right caudate nucleus and extending 3 mm into the anterior limb of the right internal capsule, representing a needle track. The track did not pass through the right putamen or globus pallidus externa (GPe). Inspection of the right globus pallidus revealed a 6-mm focal necrotic and gelatinous area medially, consistent with a necrotic ablative lesion (Fig. 1A). In the brainstem, prominent and symmetrical depigmentation of the substantia nigra and locus coeruleus were observed. Microscopic sections confirmed the diagnostic features of idiopathic PD. There was a well-demarcated area of coagulative necrosis occupying almost the entire right GPi with abundant macrophages and microglial proliferation at its edge. LETTER TO THE EDITORS