Numerous studies confirm the safety and efficacy of DBS. Various targets have been used for suppressing specific symptoms. The subthalamic nucleus (STN) is the preferred surgical target for DBS in Parkinson's disease [4,12,15-20].

Data on complications of the intervention are inconsistent and cannot be compared. Adverse events associated with STN stimulation are quite common with a high incidence of mental changes though these are typically transient in nature [21-30].

Only limited data are available on the long-term clinical course of patients after DBS surgery [31-34]. Because of this lack of data, it has not been possible so far to definitively answer questions regarding an age limit for DBS, a possible loss of effectiveness over time, or potential neuroprotective effects of DBS [35-37]. The study presented here aimed at determining whether STN DBS is as effective in elderly patients as it is in younger ones and whether there are any differences in the long-term outcome of treatment between older and younger patients.

The patients were divided into two groups for analyzing effects of age on outcome: Group I included 37 patients aged up to 65 and group II included 36 patients aged 65 or above. The cut off was chosen because 65 year limit is also known for therapy decisions e.g. in neurooncological diseases, due to increased comorbidity in elderly patients [38]. The age range of the total study population operated on was 44 to 76 years (mean 64.1 ± 7.2 years). There was no significant difference in the age distribution between the two participating centers. For evaluation the patients were summarized.

The patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), the Activity of Daily Living scale (ADL, Schwab and England), and the Hoehn & Yahr scale. In addition, changes in medication as well as complications and adverse events associated with surgery were recorded. Complications were defined as all events that considerably prolonged a patient's hospital stay or required treatment because they impaired quality of life. Adverse events were defined as stimulation-dependent problems responding to changes in stimulation parameters.

UPDRS data at 24-month follow-up were available from 42 of 51 patients in center A and from 16 of 22 patients in center B. Stimulation parameters, Hoehn & Yahr scores, ADL scores, and data on complications and adverse events were available from all 73 patients.

The Hoehn & Yahr scores showed a significant improvement for the "medication off" and "stimulation on" state (mean total score: 3.9 preoperatively versus 2.8* postoperatively, 2.6 at 6-month follow-up, and 2.7 at 24-month follow-up, *p < 0.05, significant difference in scores before and after stimulator implantation). The difference was significant for the study population as a whole and for the two age groups (p < 0.05). The differences between two age groups were not significant (Fig. ​(Fig.22).

The patients' quality of life also improved significantly. The ADL scores improved homogeneously in both groups (Fig. ​(Fig.3).3). L-Dopa equivalent medication could be reduced by a mean of 45% during the first 12 months after electrode implantation (p < 0.01). The dose reduction was significant for the total study population (n = 73) and for the two age groups after 6 and 12 months (p < 0.01) (Fig. ​(Fig.44).

Stimulation parameters were constant during the first twelve months after electrode implantation. For tremordominant Parkinson's disease higher frequencies were used to suppress tremor symptoms. (Table ​(Table33)

While successful suppression of cardinal motor symptoms is well established, only little data is available on the limitations of DBS. Although DBS is supposed to be as effective in elderly patients as in younger ones, systematic studies on the complication rate, the effectiveness and therefore the risk-benefit ratio of DBS in elderly patients are still lacking.

The two age groups investigated here were comparable with regard to their baseline clinical status prior to DBS. Both groups showed comparable improvement of the motor subscale of the UPDRS (part III) and this improvement was seen throughout the follow-up period of 24 months.

As DBS has become a routine therapeutic option, many centers now strive to develop a quality standard by establishing uniform techniques of target localization and electrode implantation. So far, no direct correlation has been established between the generous use of imaging techniques with microelectrode recording and a patient's outcome. Nevertheless, state-of-the-art imaging techniques for target definition (MRI, image fusion) are more and more replacing the older methods such as ventriculography [4,54-61]. The long-term results achieved by the two participating centers did not differ although they used different techniques for defining and locating the targets of electrode implantation (center A ventriculography and stereotactic CT, center B stereotactic CT an image fusion with contrast enhanced MPRAGE), suggesting that the technique of target localization has no significant effect on the results of DBS in our study population. Improvement of motoric symptoms confirmed the efficacy of the procedure in both groups. The rate of improvement corresponds to the results of larger multicenter trials [62-64]. The medication doses could be reduced to the same extent in both age groups. The dose reductions were in the range reported in the literature [65-68].

A uniform definition of complications does not exist. This is why complication rates reported in the literature vary widely. Many studies did not report both mechanical complications and psychic abnormalities associated with STN stimulation. Those studies that report mechanical complications provide only incomplete data on neurologic and psychic changes. Even the multicenter studies published so far present a very heterogeneous picture [28,69-77]. Only the incidences of intracerebral bleeding as the most severe complication and of infection as the most common complication are reported by all investigators.

In the present study, we defined complications as all events that prolonged a patient's hospital stay or/and caused significant morbidity. The incidence of dementia during the 2-year follow-up does not differ between the two age groups and is the same as for the natural history of Parkinson's disease. Mental alterations were frequent after bilateral STN stimulation in both age groups (Tab. ​(Tab.2).2). These complaints were independent of stimulation. There were retrospectively more related to withdrawal of medication and operative stress. Further prospective evaluation was started to systematically analyze these symptoms. Reports in the literature again present a fairly heterogeneous picture. Major differences existed between both age groups with regard to the complications that occurred: Infections were significantly more frequent in the older age group than in the younger patients (p < 0.05). A total of 7 patients died during the 2-year follow-up period. In 6 patients deaths were unrelated to surgery (2 pneumonia, 1 suspected pulmonary embolism, 3 patients with cardiac failure, all deaths >6 months postoperatively). One suicide was determined to be related to surgery. This particular patient suffered from a young onset tremordominant Parkinson's disease and has had no significant history of psychiatric disorders. After surgery he developed transient manic-depressive state, which were stimulation dependend, i.e. especially stimulation of the lower two contacts led to a worsening of manic symptoms. Although motoric improvement was significant under stimulation, psychic deteriorations limited the outcome of the patient. With maximum stimulation of 1.5 V, 90 μs and 130 Hz, tremor was only partially influenced, however without psychic symptoms. These symptoms led also to a worsening of his however previously disturbed social interactions of the patient. He got finally divorced and he committed suicide 15 months after surgery. Not counting the suicide, significantly more elderly patients died (p < 0.05) compared with the younger age group. This is not surprising if one takes into account natural life expectancy. However, as shown by the results presented here, the effectiveness of DBS is independent of patient age. This is a supporting argument against an age limit for DBS. Nevertheless, DBS should be contemplated as a therapeutic option already in younger patients and in patients with earlier stages of Parkinson's disease, for example, at the time when complications of long-term levodopa therapy first manifest themselves. With such an approach, patients can benefit from STN stimulation for a much longer period of time.