Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results.

The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.

Transplantation of embryonic porcine mesencephalic tissue in patients with PD.

OBJECTIVE: To assess the safety and the effect on standardized clinical rating measures of transplanted embryonic porcine ventral mesencephalic (VM) tissue in advanced PD. METHODS: Twelve patients with idiopathic PD underwent unilateral implantation of embryonic porcine VM tissue; six received cyclosporine immunosuppression and six received tissue treated with a monoclonal antibody directed against major histocompatibility complex class I. Patients were followed for 12 months and assessed by clinical examination, MRI, and 18F-levodopa PET. Porcine endogenous retrovirus testing was conducted by PCR-based method on peripheral blood mononuclear cells. RESULTS: Cell implantation occurred without serious adverse events in all patients. Cultures were negative for bacterial and unknown viral contamination. No porcine endogenous retrovirus DNA sequences were found. MRI demonstrated cannula tracts within the putamen and caudate, with minimal or no edema and no mass effect at the transplant sites. In the medication-off state, total Unified Parkinson's Disease Rating Scale scores improved 19% (p = 0.01). Three patients improved over 30%. There were two patients with improved gait. 18F-levodopa PET failed to show changes on the transplanted side. CONCLUSIONS: Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical PD rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue.

Myasthenia gravis mimicking stroke in elderly patients.

Myasthenia gravis is the most common disease of neuromuscular transmission; however, it may be difficult to diagnose in the elderly patient with comorbid illnesses and vague symptoms. We report two cases of myasthenia gravis in elderly women, in whom the initial diagnosis of ischemic stroke by neurologists was inaccurate; radiographic evidence of stroke was considered confirmatory. In light of the high prevalence of silent cerebrovascular disease in elderly patients, incidental neuroimaging findings may mislead clinicians. Current aggressive therapies, including thrombolysis, can cause significant morbidity in patients whose condition is misdiagnosed as stroke. Although myasthenia gravis most commonly occurs in younger people, 13 to 20% of all patients with this disease are in the seventh decade of life or beyond. When faced with new-onset weakness in an elderly patient, particularly of cranial musculature, clinicians should consider myasthenia gravis as a diagnostic possibility.

Hypertensive putaminal hemorrhage presenting with hemichorea.

A progressive motor deficit primarily manifested by hemichorea developed in a 42-year-old hypertensive man. CT scan demonstrated contralateral putaminal hemorrhage. The patient's course was benign. Previous cases of acute hemichorea familiar to use and documented by CT scans have involved nonhemorrhagic lesions of either the putamen or caudate.

Stroke due to vasculitis.

Vasculitis should be suspected as a cause of stroke in younger patients or older patients with an elevated erythrocyte sedimentation rate, especially in the presence of systemic disease and mononeuritis multiplex. Corticosteroids and cyclophosphamide show promise of producing remission.