Bilateral Subthalamic Deep Brain Stimulation in Parkinson Disease Patients With Severe Tremor

BACKGROUND Previous studies have shown that subthalamic nucleus (STN) deep brain stimulation (DBS) improves tremor in Parkinson disease (PD). However, the patients included in those studies were unselected for tremor severity. OBJECTIVE We specifically assessed the effect of STN DBS on tremor in selected PD patients with severe tremor. METHODS Seventy-two PD patients who had received bilateral STN DBS were included. The effects of STN DBS on the off-medication tremor, the on-medication tremor, and the off-medication action tremor in patients selected as the worst one-third in each category at baseline were evaluated after a mean duration of > 2 years. RESULTS In patients with severe off-medication tremor, off-medication tremor score improved from 12.28 ± 2.80 at baseline to 1.93 ± 2.85 at the last follow-up (P < .001). The off-medication tremor in the off-stimulation state at the last follow-up was less severe than the preoperative off-medication tremor. In patients with severe on-medication tremor, on-medication tremor score improved from 6.17 ± 2.45 to 1.35 ± 2.58 (P < .001). In patients with severe off-medication action tremor, off-medication action tremor score improved from 5.08 ± 1.35 to 1.24 ± 1.42 (P < .001). CONCLUSION STN DBS is effective for severe off- and on-medication tremor and off-medication action tremor in PD. Our findings suggest that STN DBS reduces PD tremor through, at least in part, its effect on the tremor-generating mechanism independent of dopaminergic transmission and that long-term electrical stimulation of STN might induce a structural or neurochemical change leading to the improvement of tremor.

Chronic ingestion of dietary fat is a prerequisite for inhibition of feeding by enterostatin

Enterostatin (Ent), the activation pentapeptide from procolipase, inhibits the intake of dietary fat. The selectivity of the response to fat suggests that the rat must recognize a permissive signal related to dietary fat for the Ent biological response. To investigate the nature of this signal, we studied the effects of Ent in rats that were adapted to either a high-fat (HF) or high-carbohydrate/low-fat (HC) diet and then naively exposed to either HF or HC diets. Ent (1 nmol) was injected into the lateral ventricle of overnight-fasted rats, and food intake was measured. Rats adapted to HF diet and tested with HC diet responded to Ent, but rats adapted to HC diet and tested with HF did not respond to Ent. The groups were maintained on their new test diets for up to 21 days and tested again for their response to Ent at 3, 7, 14, and 21 days. Ent response did not appear in HC-adapted rats switched to HF diet before 21 days. Conversely, the HF-adapted rats, which responded to Ent when tested with HC diet for the first time, did not respond at any subsequent testing time. The data suggest that chronic ingestion of dietary fat is required for Ent action and that chronic consumption of fat initiates a postingestion metabolic, endocrine, or neurochemical change that is required for the biological response to Ent.

Selective Decreases in MAO-B Activity in Post-Mortem Brains from Schizophrenic Patients with Type II Syndrome

The activities of the A and B forms of the enzyme monoamine oxidase (MAO, E.C. 1.4.3.4) have been assessed with the substrates 5-hydroxytryptamine and benzylamine respectively in seven areas of the brains of 39 patients with schizophrenia and 44 control subjects. Whereas previous studies have found the enzyme unchanged in brain in schizophrenia, in this study there was a modest but significant decrease in the activity of MAO-B in frontal and temporal cortices and in amygdala. This decrease could not be accounted for by neuroleptic medication, age, sex or post-mortem variables. In a series of 22 patients who had been assessed in life, the reduction in MAO-B activity was found to be associated specifically with the presence of negative symptoms (flattening of affect and paucity of speech). The findings are therefore consistent with other evidence for structural and neurochemical change in the temporal lobe that have been associated with the type II (defect state) syndrome of schizophrenia. The change in enzyme activity is unlikely to be related to a change in monoamine metabolism but may reflect a disturbance in glial function. The change in MAO-B activity in brain in this study is confined to particular areas of brain and a subgroup of patients; it is thought to be entirely unrelated to earlier reports of reductions of enzyme activity in platelets, which are probably attributable to prolonged neuroleptic medication.

Feeding increases dopamine metabolism in the rat brain

Feeding induced by food deprivation is accompanied by an increased production of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the brains of rats. This neurochemical change occurs in the nucleus accumbens, the posterior hypothalamus, and the amygdala but not in other dopaminergic nerve terminal fields such as the corpus striatum. These results indicate that the release of dopamine from particular groups of central neurons is increased during feeding and suggest that anatomically distinct subgroups of central dopaminergic neurons serve different roles in the regulation of food intake.