Deep brain stimulation for Parkinson disease in Australia: current scientific and clinical status.

There is currently no cure for Parkinson disease (PD). Disease management is directed primarily at motor symptom relief, but the impact of non-motor symptoms associated with PD should not be underestimated. Medical and surgical treatment options aim to increase functional independence and quality of life. Deep brain stimulation (DBS) has proven to be a safe, effective and cost-efficient surgical treatment option. In 2009, the Australian referral guidelines, developed to provide a synopsis of DBS therapy for PD, were introduced, and since then novel findings have been reported regarding the timing of intervention, target selection and symptom management. Our aim is to provide an update of DBS for PD in Australia. Intervention at earlier stages of the disease can potentially improve quality of life over a longer period with greater possibilities for meaningful social and professional contributions. For less responsive motor symptoms (e.g. freezing of gait, postural instability), the pedunculopontine nucleus has emerged as a promising new surgical target. Traditional PD treatment is focused on improvement of motor symptoms, but the disorder is also characterised by non-motor symptoms, often undiagnosed or undisclosed, that have the potential to impact quality of life to a greater extent than motor symptoms. It is essential to identify and routinely monitor for non-motor symptoms as they can emerge at all stages of the disease or can result from treatment. Many of these current advances require long-term monitoring of treatment outcomes to improve future clinical practice, refine patient selection and ensure best patient outcomes.

Theoretical & experimental analysis of the Non Markov Parameter to detect low frequency synchronisation in time series analysis.

A theoretical investigation into the behaviour of the Non-Markov Parameter is performed from a signal processing perspective in contrast to previous methodologies based on stochastic processes theory. The results indicate that the NMP can be regarded as an informational metric which is indicative of the degree of low frequency synchronisation in a complex system. These results have deep implications for physiological analysis of biological systems where the presence of sychronisation is often a marker of pathological functioning. The NMP measure is then applied to in vivo micro-electrode recordings from the subthalamic nucleus.

Fate of amnion-derived stem cells transplanted to the fetal rat brain: migration, survival and differentiation.

We have recently characterized a stem cell population isolated from the rodent amniotic membrane termed amnion-derived stem cells (ADSCs). In vitro ADSCs differentiate into cell types representing all three embryonic layers, including neural cells. In this study we evaluated the neuroectodermal potential of ADSCs in vivo after in utero transplantation into the developing rat brain. A clonal line of green fluorescent protein-expressing ADSCs were infused into the telencephalic ventricles of the developing embryonic day 15.5 rat brain. At E17.5 donor cells existed primarily as spheres in the ventricles with subsets fused to the ventricular walls, suggesting a mode of entry into the brain parenchyma. By E21.5 green fluorescent protein (GFP) ADSCs migrated to a number of brain regions. Examination at postnatal time points revealed that donor ADSCs expressed vimentin and nestin. Subsets of transplanted ADSCs attained neuronal morphologies, although there was no immunohistochemical evidence of neural or glial differentiation. Some donor cells migrated around blood vessels and differentiated into putative endothelial cells. Donor ADSCs transplanted in utero were present in recipients into adulthood with no evidence of immunological rejection or tumour formation. Long-term survival may suggest utility in the treatment of disorders where differentiation to a neural cell type is not required for clinical benefit.

Effects of subthalamic deep brain stimulation on noun/verb generation and selection from competing alternatives in Parkinson's disease.

BACKGROUND AND AIMS: Impaired generation of verbs relative to nouns has been reported in Parkinson's disease (PD) and has been associated with the frontal pathophysiology of PD. The aim of the present study was to measure noun/verb generation abilities in PD and to determine whether noun/verb generation is affected by stimulation of the subthalamic nucleus (STN). PATIENTS AND METHODS: 8 participants who had been diagnosed with PD and had received surgery for deep brain stimulation (DBS) of the STN as well as 15 control participants completed a noun/verb generation task with four probe-response conditions-namely, noun-noun, verb-noun, noun-verb and verb-verb conditions. Patients with PD were assessed while receiving STN stimulation and without stimulation. RESULTS: During the off stimulation condition, patients with PD presented with a selective deficit in verb generation compared with control participants. However, when receiving STN stimulation, patients with PD produced significantly more errors than controls during the noun-noun and verb-verb conditions, supporting evidence from previous studies that STN stimulation modulates a frontotemporal network associated with word generation. Finally, errors during verb generation were significantly correlated with item selection constraint (ie, the degree to which a response competes with other response alternatives) in the on stimulation condition, but not the off stimulation condition. CONCLUSION: Our results suggest that STN stimulation affects the ability to select from many competing lexical alternatives during verb generation.

Long-term cryopreserved amniocytes retain proliferative capacity and differentiate to ectodermal and mesodermal derivatives in vitro.

Putative stem cells have recently been isolated from several extra-embryonic tissues, including Wharton's Jelly and umbilical cord blood. Relevant studies have focused on primary cultures established from freshly isolated tissues. In this report, we examine the plasticity of 472 cells, a cryopreserved human amniocyte cell line originally isolated in 1974. Under conditions conducive for proliferation, the amniocytes displayed fibroblast-like morphologies and expressed Oct4 and Rex1, genes associated with pluripotency. Perhaps indicative of inherent plasticity, 472 cells simultaneously expressed ectodermal beta-III-tubulin and mesodermal fibronectin. When cultured under conditions that promote neural differentiation, the cells adopted neuronal morphologies and expressed neuronal genes, including Gap-43, NF-M, tau, and synaptophysin. Exposure to culture conditions that encourage osteogenic differentiation resulted in increased expression of alkaline phosphatase (ALP) and the deposition of mineralized matrix, established markers of bone cell differentiation. In sum, this population of human amniocytes appears to be multipotent, capable of in vitro differentiation to ectodermal and mesodermal cell types. Retention of this plasticity through decades of cryopreservation suggests that amniocytes might be candidates for future cell-based therapies.

Rapid subthalamic nucleus deep brain stimulation lead placement utilising CT/MRI fusion, microelectrode recording and test stimulation.

Subthalamic nucleus (STN) deep brain stimulation (DBS) has become an established treatment strategy for patients with medically refractory Parkinson's disease (PD). There are however numerous strategies employed for STN lead placement. Variations include method of STN localisation, use of microelectrode recording, number of microelectrode recording passes and time taken for the procedure. We describe a relatively simple and rapid technique of STN lead placement utilising CT/ MRI image fusion, microelectrode recording and test stimulation. The first 58 consecutive patients undergoing STN DBS were assessed pre- and post-operatively. UPDRS scores, medication use and any surgical complication were assessed. Bilateral STN DBS was an efficacious treatment option for medically refractory PD. We have described a technique which can be performed with effect and low morbidity, and in a time which is well tolerated by patients.

Self-rated quality of life measures: effect of change to a low-fat, high-fiber, fruit and vegetable enriched diet.

The Polyp Prevention Trial (PPT) was a multicenter, randomized clinical trial to determine the effect of a low-fat (20% of energy from fat), high-fiber (18 g/1,000 kcal/day), high-fruit/vegetable (3.5 servings/1,000 kcal/day) eatingplan on the recurrence of large bowel adenomatous polyps. The PPT provided an opportunity to examine the impact of dietary changes on quality of life. At baseline and annuallyfor 4 years, participants in the Quality of Life Substudy of PPT completed a Quality of Life Factors (QF) Questionnaire, a modified Block-National Cancer Institute Food Frequency Questionnaire, and a Health and Lifestyle Questionnaire. The 51-item QF Questionnaire assessed changes in nine domains: taste, convenience, cost, self-care, social, health assessment, health belief health action, and life satisfaction. The analysis compared annual changes in domain scores for intervention (n = 194) and control (n = 200) participants. At Year 1, 363 (92%) completed a questionnaire, and 325 (82%) participants completed a Year 4 questionnaire. There were no statistically significant differences between treatment groups in the change from baseline to Year 1 for the convenience, cost, taste, health assessment, and life satisfaction domains. At Year 1, intervention participants rated the self-care (p < .001), health belief (p = .021), and health action (p < .001) domains significantly higher and the social domain significantly lower (p <.001) than control participants. These changes were consistent through Years 2, 3, and 4. This study

Avoidance responding following amphetamine-induced dopamine depletion.

The effect of an amphetamine-induced depletion of striatal dopamine on active and passive avoidance responding of rats was examined. Sixteen animals received two sets of 4 injections each of 15 mg/kg d-amphetamine, administered at 2 hr intervals with each set delivered one week apart. One week after the last injection, animals were given 50 consecutive active avoidance trials in a shuttle box. Animals treated with amphetamine exhibited a 50%, depletion of striatal dopamine and showed a slower learning curve, as evidenced by significantly fewer avoidances and a slower escape latency during trials 21-30. Both groups demonstrated a 90% avoidance rate by trials 41-50. A separate group of rats was treated as above and trained for several weeks on the active avoidance procedure. Haloperidol (0.01-0.10 mg/kg intraperitoneally) dose-dependently decreased avoidance number and increased avoidance and escape latency in both groups, an effect that was exaggerated in those animals previously treated with amphetamine. Finally, these animals were tested in the same apparatus using a passive avoidance procedure. The amphetamine treatment produced a significantly higher mean number of avoidances in this procedure compared to saline-treated animals during trials 1-20. These results suggest that the impairment in conditioned avoidance following amphetamine treatment is due to a motoric, rather than a cognitive deficit.

Treatment of an intracranial germinoma spinal metastasis.

A 20-year-old male with a solitary intradural extramedullary spinal metastasis from a pineal germinoma presented with progressive spinal cord compression. This was initially treated with radiotherapy and the patient showed rapid clinical improvement with complete resolution of his neurological symptoms and signs. Subsequent systemic chemotherapy resulted in complete radiological resolution of the lesion. This case is presented to demonstrate radiotherapy and chemotherapy as a treatment option for germinoma 'drop' metastasis causing spinal cord compression, along with a review of the literature.

Outcomes following treatment of metastatic spine tumors.

Fifty seven consecutive patients with metastatic spine tumors were assessed for their suitability for operative treatment or radiotherapy and/or chemotherapy using a modified version of the Nihon University scoring system. Using this scoring system 29 patients underwent surgery and 28 received radiotherapy/chemotherapy. The outcomes were assessed to determine if a modified scoring had any effect on patient survival. No statistical difference was found between the two groups, though a trend was noted--the group receiving surgery had a mean survival of 30 weeks compared to a mean survival of 16 weeks found in the non-surgical group.

Effect of dietary ribonucleic acid on bacterial translocationand survival following blood transfusion and thermal injury.

Ribonucleic acid (RNA) has been shown to have a key role in the maintenance of normal cellular function and host resistance to infection. The effect of experimental diets containing RNA on microbial translocation, killing of translocated bacteria and the survival rate of the host was studied in a burn animal model which included immunosuppression. Balb/c mice were fed for 10 days with an RNA supplemented diet (AIN/76A). Control groups were fed with two commercial diets: AIN-76A or Purina chow 5001 (chow). After 10 days of feeding, all animals received an allogenic transfusion. On day 15 the animals were gavaged with 10(10)(14)C radiolabeled or unlabeled Escherichia coli, and given a 20% total body surface area (TBSA) burn injury. Animals gavaged with unlabeled bacteria were observed for survival (n = 60) and animals gavaged with labeled bacteria were sacrificed 4 h post-burn (n = 30) and the mesenteric lymph nodes, liver and spleen were harvested. Slightly less translocation was observed in the liver and spleen of animals fed on RNA diet. Bacterial counts were measured and the percentages of translocated organisms that survived in the tissues were calculated and showed no statistical differences between the three groups. Survival was 45% in RNA group versus 55% in the non-supplemented AIN-76A and 50% in the chow group. It is concluded that a diet enriched in RNA slightly affects bacterial translocation but does not affect survival after severe injury.

The validity of classification for the clinical presentation of intracranial dural arteriovenous fistulas.

A number of classification schemes for intracranial dural arteriovenous fistulas (AVFs) have been published that claim to predict which lesions will present in a benign or aggressive fashion based on radiological anatomy. We have tested the validity of two proposed classification schemes for the first time in a large single-institution study. A series of 102 intracranial dural AVFs in 98 patients assessed at a single institution was analyzed. All patients were classified according to two grading scales: the more descriptive schema of Cognard, et al. (Cognard) and that recently proposed by Borden, et al. (Borden). According to the Borden classification, 55 patients were Type I, 18 Type II, and 29 Type III. Using the Cognard classification, 40 patients were Type I, 15 Type IIA, eight Type IIB, 10 Type IIA+B, 13 Type III, 12 Type IV, and four Type V. Intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit was considered an aggressive presenting clinical feature. A total of 16 (16%) of 102 intracranial dural AVFs presented with hemorrhage. Eleven of these hemorrhages (69%) occurred in either anterior cranial fossa or tentorial lesions. When analyzed according to the Borden classification, none (0%) of 55 Type I intracranial dural AVFs, two (11%) of 18 Type II, and 14 (48%) of 29 Type III intracranial dural AVFs presented with hemorrhage (p < 0.0001). After exclusion of visual or cranial nerve deficits that were clearly related to cavernous sinus intracranial dural AVFs, nonhemorrhagic neurological deficits were a feature of presentation in one (2%) of 55 Type I, five (28%) of 18 Type II, and nine (31%) of 29 Type III patients (p < 0.0001). When combined, an aggressive clinical presentation (ICH or nonhemorrhagic neurological deficit) was seen most commonly in intracranial dural AVFs located in the tentorium (11 (79%) of 14) and the anterior cranial fossa (three (75%) of four), but this simply reflected the number of higher grade lesions in these locations. Aggressive clinical presentation strongly correlated with Borden types: one (2%) of 55 Type I, seven (39%) of 18 Type II, and 23 (79%) of 29 Type III patients (p < 0.0001). A similar correlation with aggressive presentation was seen with the Cognard classification: none (0%) of 40 Type I, one (7%) of 15 Type IIA, three (38%) of eight Type IIB, four (40%) of 10 Type IIA+B, nine (69%) of 13 Type III, 10 (83%) of 12 Type IV, and four (100%) of four Type V (p < 0.0001). No location is immune from harboring lesions capable of an aggressive presentation. Location itself only raises the index of suspicion for dangerous venous anatomy in some intracranial dural AVFs. The configuration of venous anatomy as reflected by both the Cognard and Borden classifications strongly predicts intracranial dural AVFs that will present with ICH or nonhemorrhagic neurological deficit.

C1-C2 transarticular screw fixation for treatment of C1-C2 instability.

C1-C2 instability has traditionally been treated by C1-C2 posterior wiring and bone grafting. However, this technique has an incidence of non-union which may exceed 10%. Transarticular screw fixation has developed as a technique of providing increased strength of fixation of C1-C2 arthrodesis, while at the same time avoiding the need for postoperative halo bracing and avoiding the risk of neurological injury associated with the passage of sublaminar wires. We present a retrospective review of 12 patients with C1-C2 instability treated by C1-C2 transarticular screw fixation. Eight patients underwent this procedure as primary treatment, and 4 after a failed Gallie fusion. Five patients had a cruciate ligament rupture, 5 had an odontoid process fracture, 1 had os odontoideum, and 1 had rheumatoid instability. There was no surgical morbidity or mortality and, at a mean follow up of 12.1 +/- 3 months (range 8-14 months), all patients had achieved solid fusion, and all neurological symptoms referable to the instability had resolved. C1-C2 transarticular screw fixation has been shown to be safe and effective and has a number of advantages when compared to traditional posterior wiring techniques. We recommend that this technique be considered as a primary treatment of C1-C2 instability.

Nutrition intervention program of the Modification of Diet in Renal Disease Study: a self-management approach.

OBJECTIVE: To characterize the Modification of Diet in Renal Disease (MDRD) Study nutrition intervention program by determining the frequency of intervention strategies used by the dietitians and the usefulness of program components as rated by participants. DESIGN: Dietitians recorded which of 32 intervention strategies they used at each monthly visit. Participants rated the usefulness of 19 program components. SUBJECTS: 840 adults with renal insufficiency. INTERVENTION: Participants were assigned randomly to usual-, low-, or very-low-protein diet groups. Each eating pattern also specified a phosphorus intake goal. Each participant met monthly with a dietitian for an average of 26 months. STATISTICAL ANALYSES: Analyses of variance and chi 2 analyses. RESULTS: Dietitians used the following intervention strategies most often in all groups: providing feedback based on self-monitoring and/or food records, reviewing adherence or biochemistry data, providing low-protein foods, and reviewing graphs of adherence progress. In general, the dietitians used feedback, modeling, and support strategies more often, and knowledge and skills strategies less often, with participants who had to make the greatest reductions in protein intake and those with more advanced disease. In all groups, the dietitians' use of knowledge and skills, feedback, and modeling strategies decreased over time (P < .001), whereas use of support strategies was maintained. The type and frequency of intervention strategies used by dietitians and the usefulness ratings of participants did not vary by educational level of the participant. Both self-monitoring and dietitian support were rated as "very useful" by 88% of the participants. CONCLUSIONS: Three features were central to the MDRD Study nutrition intervention program: feedback, particularly from self-monitoring and from measures of adherence; modeling, particularly by providing low-protein food products; and dietitian support. We recommend the self-management approach.

Factors associated with adherence to the dietary protein intervention in the Modification of Diet in Renal Disease Study.

OBJECTIVE: To determine the characteristics and behaviors associated with adherence to dietary protein interventions among participants with chronic renal disease in the Modification of Diet in Renal Disease (MDRD) Study. DESIGN: Participants were categorized as consistent adherers or nonadherers on the basis of urinary urea nitrogen excretion and dietary protein intake data from self-reports. Psychosocial and behavioral factors were compared between groups. SUBJECTS: Subgroups of consistently adherent and non-adherent participants in the MDRD Study. SETTING: 15 clinical centers in the United States. INTERVENTION: In the nutrition intervention program, participants were assigned randomly to a usual-, low-, or very-low-protein diet group. Each eating pattern also specified a phosphorus goal. STATISTICAL ANALYSIS: Analysis of variance. RESULT: Psychosocial factors significantly related to adherence included participant knowledge, attitude, support, satisfaction, and self-perception of success. Behavioral strategies including participant self-monitoring of protein intake and the provision of feedback by the dietitian were also significantly related to adherence. APPLICATION: Nutrition interventions for patients with renal disease should focus on psychosocial factors and behavioral approaches. Such approaches can be successfully incorporated into treatment programs and will assist the dietitian in promoting adherence to usual-, low-, and very-low-protein eating patterns.

Dietary satisfaction correlated with adherence in the Modification of Diet in Renal Disease Study.

OBJECTIVE: To measure satisfaction with modified protein eating patterns and the relationship of satisfaction to adherence and sociodemographic factors in a clinical trial. DESIGN: Participants completed the Dietary Satisfaction Questionnaire at baseline, at 6-month follow-up visits, at annual visits, and at the final visit. Satisfaction with diet was rated on a visual analog scale from 1 (dislike extremely) to 5 (like very much). Adherence to protein goals was assessed using urine urea nitrogen excretion from monthly 24-hour urine samples. SUBJECTS: 840 adults with chronic renal disease. INTERVENTION: Individual participants, randomly assigned to a usual-protein, low-protein, or very-low-protein group, received monthly counseling from a dietitian for an average of 26 months. STATISTICS: Analyses of variance and two-sample t tests compared, among study/diet groups, satisfaction with diet, its relationship to adherence and sociodemographic characteristics, and changes in satisfaction over time. Paired t tests compared changes within diet groups from baseline to final visit. RESULTS: From the baseline visit to the final visit, satisfaction with the prescribed eating pattern increased slightly in the usual-protein group, declined slightly in the low-protein group, and declined significantly in the very-low-protein group. Participants in all of the eating pattern groups who were more satisfied at the final visit had mean protein intakes closer to their assigned protein goals. This relationship was significant in the low-protein group (P < .05). In men, satisfaction with diet declined significantly from baseline to the final follow-up visit in the very-low-protein group. APPLICATIONS: The Modification of Diet in Renal Disease Study Dietary Satisfaction Questionnaire may be useful in other research and clinical settings to assess and enhance dietary adherence.

C1-C2 posterior cervical fusion: long-term evaluation of results and efficacy.

Posterior wiring techniques are the most commonly used methods of achieving C1-C2 arthrodesis. Recently, transarticular screw fixation and interlaminar clamping have been advocated to achieve more secure fixation. A retrospective review of patients undergoing C1-C2 fusion for nonneoplastic disease was undertaken at the University of Toronto Hospital, with the aim of determining the long-term outcome of the selected procedures. Thirty-two patients underwent 36 procedures from 1986 to 1992, with a mean follow-up of 4.7 +/- 2.2 years (range, 2.0-8.0 yr). The most common disease processes were odontoid fracture (18 patients), transverse atlantal ligament injury (5 patients), os odontoideum (5 patients), and rheumatoid C1-C2 instability (3 patients). Thirty-one Gallie fusions, one Brooks-Jenkins fusion, two transarticular screw fusions, and two Halifax clamp applications were performed. Six (19%) of Gallie/Brooks-Jenkins fusions failed. These occurred with os odontoideum (three patients), Type II odontoid fracture (two patients), and transverse atlantal ligament injury (one patient). All transarticular screw and Halifax clamp procedures resulted in successful fusions. Two procedures (6%) resulted in new neurological deficit; both of these patients underwent posterior wiring for os odontoideum. This study suggests that Type II odontoid fractures may be successfully managed by a posterior wiring technique alone. Rheumatoid C1-C2 instability may be managed by posterior wiring supplemented with halo immobilization. Transarticular screw fixation has several potential advantages as a technique for C1-C2 arthrodesis and, in particular, may be appropriate for os odontoideum that had a high failure rate (75%) with conventional posterior wiring, even when this was supplemented with halo bracing.