Comparison of elderly and young patient populations treated with deep brain stimulation for Parkinson's disease: long-term outcomes with up to 7 years of follow-up.

OBJECTIVE: Deep brain stimulation (DBS) is the procedure of choice for Parkinson's disease (PD). It has been used in PD patients younger than 70 years because of better perceived intra- and postoperative outcomes than in patients 70 years or older. However, previous studies with limited follow-up have demonstrated benefits associated with the treatment of elderly patients. This study aims to evaluate the long-term outcomes in elderly PD patients treated with DBS in comparison with a younger population. METHODS: PD patients treated with DBS at the authors' institution from 2008 to 2014 were divided into 2 groups: 1) elderly patients, defined as having an age at surgery ≥ 70 years, and 2) young patients, defined as those < 70 years at surgery. Functional and medical treatment outcomes were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS III), levodopa-equivalent daily dose (LEDD), number of daily doses, and number of anti-PD medications. Study outcomes were compared using univariate analyses, 1-sample paired t-tests, and 2-sample t-tests. RESULTS: A total of 151 patients were studied, of whom 24.5% were ≥ 70 years. The most common preoperative Hoehn and Yahr stages for both groups were 2 and 3. On average, elderly patients had more comorbidities at the time of surgery than their younger counterparts (1 vs 0, p = 0.0001) as well as a higher average LEDD (891 mg vs 665 mg, p = 0.008). Both groups experienced significant decreases in LEDD following surgery (elderly 331.38 mg, p = 0.0001; and young 108.6 mg, p = 0.0439), with a more significant decrease seen in elderly patients (young 108.6 mg vs elderly 331.38 mg, p = 0.0153). Elderly patients also experienced more significant reductions in daily doses (young 0.65 vs elderly 3.567, p = 0.0344). Both groups experienced significant improvements in motor function determined by reductions in UPDRS III scores (elderly 16.29 vs young 12.85, p < 0.0001); however, reductions in motor score between groups were not significant. Improvement in motor function was present for a mean follow-up of 3.383 years postsurgery for the young group and 3.51 years for the elderly group. The average follow-up was 40.6 months in the young group and 42.2 months in the elderly group. CONCLUSIONS: This study found long-term improvements in motor function and medication requirements in both elderly and young PD patients treated with DBS. These outcomes suggest that DBS can be successfully used in PD patients ≥ 70 years. Further studies will expand on these findings.

Cognitive and neuropsychiatric effects of subthalamotomy for Parkinson's disease.

Since the advent of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD), subsequent cognitive and neuropsychiatric effects of this procedure have become well-chronicled. Yet, thermolitic lesion of the subthalamic nucleus (STN) is still a valid option when DBS cannot be applied, and little has been published regarding its impact on cognition and mood. We examined the cognitive and neuropsychiatric functions of 10 consecutive patients with advanced PD undergoing simultaneous bilateral subthalamotomies. With 24 months of follow-up, the patients, three of whom were on anticholinergics prior to surgery, showed no deterioration in cognitive assessments including verbal fluency. Hypoactive behaviors (depression and apathy) showed lasting improvement, while hyperactive behaviors (euphoria and disinhibition) transiently increased after surgery. Improvement in hypoactive behaviors correlated with improvement in hypokinetic movements, and enhanced hyperactive behaviors followed the course of post-operative hyperkinetic movements. Such correlations may support the role of the STN in modulating limbic connections between the basal ganglia and frontal cortex. The results of this proof-of-concept pilot study suggest the need for larger, long-term, randomized controlled studies to assess motor, neuropsychiatric, behavioral and radiologic correlations after subthalamotomies.

Palliative care in amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis, Parkinson's disease, atypical parkinsonian syndromes, and multiple sclerosis are progressive neurologic disorders that cumulatively afflict a large number of people. Effective end-of-life palliative care depends upon an understanding of the clinical aspects of each of these disorders. OBJECTIVES: The authors review the unique and overlapping aspects of each of these disorders with an emphasis upon the clinical management of symptoms. DESIGN: The authors review current management and the supporting literature. CONCLUSIONS: Clinicians have many effective therapeutic options to choose from when managing the symptoms produced by these disorders.

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates.

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.